Breathing Scientific Research

 

Science is important; so we have included a selection of relevant scientific studies below that highlight the physical benefits of breathing. The low financial reward for offering breathing as a self healing tool is a barrier to further research, despite large numbers of the medical profession advocating the importance of doing so.

Frontiers in Psychology, 2012; 3 DOI: 10.3389/fpsyg.2012.00116
“Meditate to create: the impact of focused-attention and open-monitoring training on convergent and divergent thinking.”
Lorenza S. Colzato, Ayca Ozturk and Bernhard Hommel Institute for Psychological Research and Leiden Institute for Brain and Cognition, Leiden University, Leiden, Netherlands.
The practice of meditation has seen a tremendous increase in the western world since the 60s. Scientific interest in meditation has also significantly grown in the past years; however, so far, it has neglected the idea that different type of meditations may drive specific cognitive-control states. In this study we investigate the possible impact of meditation based on focused-attention (FA) and meditation based on open-monitoring (OM) on creativity tasks tapping into convergent and divergent thinking. We show that FA meditation and OM meditation exert specific effect on creativity. First, OM meditation induces a control state that promotes divergent thinking, a style of thinking that allows many new ideas of being generated. Second, FA meditation does not sustain convergent thinking, the process of generating one possible solution to a particular problem. We suggest that the enhancement of positive mood induced by meditating has boosted the effect in the first case and counteracted in the second case.
***NOTE: If you don’t want to peruse the entire study beyond the Abstract, co-author Ayca Szapora commented thusly on the use of Transformational Breath in this research:”The original premise was to find out the differences in the results between focused meditation vs. non focused (or open-monitoring meditation). We tested subjects who practiced both focused meditation and Transformational Breath. We found that Transformational Breath enhances divergent thinking. Divergent thinking is the most important ingredient of creativity. It refers to the process of generating new ideas, alternative solutions to an open-ended problem, thinking out-of-the-box, seeing connections and associations and coming up with unique ideas. A breath session of half an hour was enough to enhance performance significantly on creativity tasks, which is remarkable. After a vigorous peer-review, our findings have now become part of scientific literature.”Transformational Breath is an open monitoring system, vs. a focused meditation system. We have found that in a short amount of time with Transformational Breath such a brain state was reached which increased these performances. This has far reaching interest and applications, from the scientific world as well as spiritual groups.”
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Eur J Heart Fail. 1999 Aug;1(3):297-300.
“Effects of resistive breathing on exercise capacity and diaphragm function in patients with ischaemic heart disease.”
Darnley GM, Gray AC, McClure SJ, Neary P, Petrie M, McMurray JJ, MacFarlane NG. Institute of Biomedical and Life Sciences, Glasgow University, Scotland, UK.
BACKGROUND: Muscle weakness has been suggested to result from the deconditioning that accompanies decreased activity levels in chronic cardiopulmonary diseases. The benefits of standard exercise programmes on exercise capacity and muscular strength in disease and health are well documented and exercise capacity is a significant predictor of survival in patients with chronic heart failure (CHF). Selective respiratory muscle training has been shown to improve exercise tolerance in CHF and such observations have been cited to support the suggestion that respiratory muscle weakness contributes to a reduced exercise capacity (despite biopsies showing the metabolic profile of a well trained muscle). AIMS: This study aimed to determine the effects of selective inspiratory muscle training on patients with chronic coronary artery disease to establish if an improved exercise capacity can be obtained in patients that are not limited in their daily activities. METHODS: Nine male patients performed three exercise tests (with respiratory and diaphragm function assessed before the third test) then undertook a 4-week programme of inspiratory muscle training. Exercise tolerance, respiratory and diaphragmatic function were re-assessed after training. RESULTS: Exercise capacity improved from 812+/-42 to 864+/-49 s, P<0.05, and velocity of diaphragm shortening increased (during quiet breathing from 12.8+/-1.6 to 19.4+/-1.1 mm s(-1), P<0.005, and sniffing from 71.9+/-9.4 to 110.0+/-12.3 mm s(-1), P<0.005). In addition, five from nine patients were stopped by breathlessness before training; whereas only one patient was stopped by breathlessness after training. CONCLUSION: The major findings in this study were that a non-intensive 4-week training programme of resistive breathing in patients with chronic coronary artery disease led to an increase in exercise capacity and a decrease in dyspnoea when assessed by symptom limited exercise testing. These changes were associated with significant increases in the velocity of diaphragmatic excursions during quiet breathing and sniffing. Patients that exhibited small diaphragmatic excursions during quiet breathing were most likely to improve their exercise capacity after the training programme. However, the inspiratory muscle-training programme was not associated with any significant changes in respiratory mechanics when peak flow rate, forced expiratory volume and forced vital capacity were measured. The resistive breathing programme used here resulted in a significant increase in the velocity of diaphragm movement during quiet breathing and sniffing. In other skeletal muscles, speed of contraction can be determined by the relative proportion of fibre types and muscle length (Jones, Round, Skeletal Muscle in Health and Disease. Manchester: University Press, 1990). The intensity of the training programme used here, however, is unlikely to significantly alter muscle morphology or biochemistry. Short-term training studies have shown that there can be increases in strength and velocity of shortening that do not relate to changes in muscle biochemistry or morphology. These changes are attributed to the neural adaptations that occur early in training (Northridge et al., Br. Heart J. 1990; 64: 313-316). Independent of the mechanisms involved, this small, uncontrolled study suggests that inspiratory muscle training may improve exercise capacity, diaphragm function and symptoms of breathlessness in patients with chronic coronary artery disease even in the absence of heart failure.
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Blood Press Monit. 2003 Oct;8(5):211-4.
“Effect of deep breathing test on finger blood pressure.”
Jagomägi K, Raamat R, Talts J, Länsimies E, Jurvelin J. Institute of Physiology, University of Tartu, 18 Ulikooli Street, 51014 Tartu, Estonia.
BACKGROUND: The deep breathing test (DB) is a simple method to measure heart rate variability. However, in most studies the amplitude of blood pressure oscillations has not been considered and little is known about the influence of the deep breathing test on the blood pressure level. DESIGN: The aim of this study is to investigate the effect of DB on finger blood pressure (FBP). METHODS: Continuous beat-to-beat FBP was recorded by the volume clamp method (Portapres model 2 monitor). RESULTS: Thirteen volunteers were studied before, during and after DB at a fixed rate of six breaths/min. After DB, systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) were lower than before DB by 9.1, 4.3 and 5.9 mmHg, respectively. There was no significant correlation between the reduction in the BP level and the amplitudes of induced oscillations in blood pressure and heart rate during the deep breathing test. CONCLUSIONS: Deep breathing might be used to reduce blood pressure.

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Hypertens Res. 2005 Jun;28(6):499-504.
“How does deep breathing affect office blood pressure and pulse rate?”
Mori H, Yamamoto H, Kuwashima M, Saito S, Ukai H, Hirao K, Yamauchi M, Umemura S. Japanese Medical and Dental Practitioners for the Improvement of Medical Care, Tokyo, Japan.
Japanese Medical and Dental Practitioners for the Improvement of Medical Care, Tokyo, Japan. Little is known about the relation between deep breathing (DB) and blood pressure (BP). We studied the relationship between DB and BP in a large Japanese population. The subjects were recruited from randomly selected clinics and hospitals that were members of a medical association, and divided into two groups. In one group, BP was measured before and after taking 6 DB over a period of 30 s, and in the other group BP was measured before and after a 30-s rest in a sitting position without DB. Before these measurements, all patients rested 10 min or more in the waiting room and another 2 min or more in the doctor’s office. Analyses were performed on data collected from 21,563 subjects. In both groups, systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were significantly reduced after DB or a 30-s rest compared with the baseline measurements (p < 0.001). SBP reductions were greater in the DB group than in the 30-s rest group (normotensives: -6.4 +/- 8.3 vs. -3.0 +/- 7.4 mmHg, p < 0.001; untreated hypertensives: -9.6 +/- 10.2 vs. -5.9 +/- 9.1 mmHg, p < 0.001; treated hypertensives: -8.3 +/- 9.6 vs. -4.4 +/- 8.3 mmHg, p < 0.001). Greater BP reductions were found in patients with a higher baseline BP in both the DB and 30-s rest groups. In conclusion, the present study showed a baseline BP-dependent BP reduction by DB, suggesting that BP measurement should be done without DB in the office because DB lowers BP
J Altern Complement Med. 2004 Oct;10(5):757-66.
“Hemodynamic observations on a yogic breathing technique claimed to help eliminate and prevent heart attacks: a pilot study.”
Shannahoff-Khalsa DS, Sramek BB, Kennel MB, Jamieson SW. The Research Group for Mind-Body Dynamics, Institute for Nonlinear Science, University of California, San Diego, La Jolla, CA 92093-0402, USA.
OBJECTIVE: This pilot study investigated the hemodynamics of a yogic breathing technique claimed “to help eliminate and prevent heart attacks due to abnormal electrical events to the heart” and to generally “enhance performance of the central nervous system (CNS) and to help eliminate the effects of traumatic shock and stress to the CNS.” DESIGN: Parameters for (4) subjects were recorded during a preexercise resting period, a 31-minute exercise period, and a postexercise resting period. SETTINGS/LOCATION: Parameters for subjects were recorded in a laboratory at the University of California, San Diego. SUBJECTS: Parameters for 3 males (ages 44, 45, 67) and 1 female (age 41) were recorded. One (1) subject (male age 45) had extensive training in this technique. Interventions: This yogic technique is a 1 breath per minute (BPM) respiratory exercise with slow inspiration for 20 seconds, breath retention for 20 seconds, and slow expiration for 20 seconds, for 31 consecutive minutes. OUTCOME MEASURES: Fourteen beat-to-beat parameters were measured noninvasively and calculated for body surface area to yield: stroke index (SI), heart rate (HR), cardiac index, end diastolic index, peak flow, ejection fraction, thoracic fluid index, index of contractility, ejection ratio, systolic time ratio, acceleration index, and systolic, diastolic, and mean arterial pressures (MAPs). Left stroke work index (LSWI) and stroke systemic vascular resistance index (SSVRI) were calculated. RESULTS: We report on SI, HR, MAP, LSWI, and SSVRI and how they can help to describe hemodynamicstate changes. This technique induces dramatic shifts in all hemodynamic variables during the 1 BPM exercise and can produce unique changes in the postexercise resting period after long-term practice that appears to have a unique effect on the brain stem cardiorespiratory center regulating the Mayer wave (0.1-0.01 Hz) patterns of the cardiovascular system. CONCLUSIONS: Preclinical studies are warranted to examine the possible long-term effects of this technique that appear to reset a cardiorespiratory brain-stem pacemaker. We postulate that this effect may be the basis for the purported yogic health claim.

 

Altern Ther Health Med. 2005 Jul-Aug;11(4):44-52.
“Randomized, controlled trial of breath therapy for patients with chronic low-back pain.”
Mehling WE, Hamel KA, Acree M, Byl N, Hecht FM. Osher Center for Integrative Medicine, Department of Family and Community Medicine, University of California, San Francisco, USA.
CONTEXT: Patients suffering from chronic low back pain (cLBP) are often unsatisfied with conventional medical care and seek alternative therapies. Many mind-body techniques are said to help patients with low back pain by enhancing body awareness, which includes proprioception deficit in cLBP, but have not been rigorously studied in cLBP. Breath therapy is a western mind-body therapy integrating body awareness, breathing, meditation, and movement. Preliminary data suggest benefits from breath therapy for proprioception and low back pain. OBJECTIVE: To assess the effect of breath therapy on cLBP. DESIGN: Randomized, controlled trial. SETTING: Academic medical center. PARTICIPANTS: Thirty-six patients with cLBP. INTERVENTIONS: Six to eight weeks (12 sessions) of breath therapy versus physical therapy. MAIN OUTCOME MEASURES: Pain by visual analog scale (VAS), function by Roland Scale, overall health by Short Form 36 (SF-36) at baseline, six to eight weeks, and six months. Balance as a potential surrogate for proprioception and body-awareness measured at the beginning and end of treatment. RESULTS: Pre- to post-intervention, patients in both groups improved in pain (VAS: -2.7 with breath therapy, -2.4 with physical therapy; SF-36: +14.9 with breath therapy and +21.0 with physical therapy). Breath therapy recipients improved in function (Roland: -4.8) and in the physical and emotional role (SF-36: +15.5 and 14.3). Physical therapy recipients improved in vitality (SF-36: +15.0). Average improvements were not different between groups. At six to eight weeks, results showed a trend favoring breath therapy; at six-months, a trend favoring physical therapy. Balance measures showed no improvements and no correlations with other outcomes. CONCLUSIONS: Patients suffering from cLBP improved significantly with breath therapy. Changes in standard low back pain measures of pain and disability were comparable to those resulting from high-quality, extended physical therapy. Breath therapy was safe. Qualitative data suggested improved coping skills and new insight into the effect of stress on the body as a result of breath therapy. Balance measures did not seem to be valid measures of clinical change in patients’ cLBP.
 
Complement Ther Med. 2005 Sep;13(3):165-74.
“Biofeedback assisted diaphragmatic breathing and systematic relaxation versus propranolol in long term prophylaxis of migraine.”
Kaushik R, Kaushik RM, Mahajan SK, Rajesh V. Department of Medicine, Himalayan Institute of Medical Sciences, Swami Rama Nagar, Dehradun 248140, Uttaranchal, India.
OBJECTIVES: To evaluate utility of biofeedback assisted diaphragmatic breathing and systematic relaxation in migraine and to compare their efficacy with propranolol in long term prophylaxis of migraine. METHODS: 192 migraine patients were randomly distributed into two groups. Propranolol group received propranolol 80 mg/day while biofeedback group received electromyogram (EMG) and temperature biofeedback assisted diaphragmatic breathing and systematic relaxation training accompanied by home practice for 6 months. RESULTS: Significant clinical response was seen with biofeedback in 66.66% and with propranolol in 64.58% of patients. Frequency, severity, duration of attacks and number of vomiting episodes were significantly reduced in both the groups at 6 months but inter-group differences were statistically insignificant. During 1 year post-treatment period, significantly lesser resurgence of migraine was seen in biofeedback group as whole (9.37%) and in biofeedback responders in biofeedback group (9.37%) in comparison to resurgence of migraine in propranolol group as whole (38.54%) and in propranolol responders in propranolol group (53.22%) respectively. CONCLUSIONS: Biofeedback assisted diaphragmatic breathing and systematic relaxation were very useful in migraine and had significantly better long-term prophylactic effects than propranolol in migraine.
Spinal Cord Injury helped by hyperpneic normocapnic breathing.
J Rehabil Med. 2008 Feb;40(2):119-25.
“Patients with acute spinal cord injury benefit from normocapnic hyperpnoea training.”
Van Houtte S, Vanlandewijck Y, Kiekens C, Spengler CM, Gosselink R. Department of Rehabilitation Sciences, Katholieke Universiteit Leuven, Faculty of Kinesiology and Rehabilitation Sciences, Leuven, Belgium.
BACKGROUND: Functional loss of respiratory muscles in persons with spinal cord injury leads to impaired pulmonary function and respiratory complications. In addition, respiratory complications are responsible for 50-67% of the morbidity in this population. OBJECTIVE: To investigate the effects of normocapnic hyperpnoea training in acute spinal cord injury. PATIENTS AND METHODS: Fourteen patients were randomized between control (sham) and an experimental normocapnic hyperpnoea training group. Vital capacity, maximal voluntary ventilation, respiratory muscle strength and endurance, respiratory complications and symptoms were evaluated before, after 4 and 8 weeks of training and after 8 weeks follow-up. RESULTS: Maximal voluntary ventilation, respiratory muscle strength and endurance improved significantly in the experimental group compared with the control group (p < 0.05). Improvements in vital capacity tended to be different from the control group at 8 weeks of training. The Index of Pulmonary Dysfunction decreased after 4 weeks of training and respiratory complications were reported less frequently in the experimental group compared with the control group. CONCLUSION: Normocapnic hyperpnoea training in patients with spinal cord injury improved respiratory muscle strength and endurance. Respiratory complications occurred less frequently after training.TBF Commentary: Hyperpneic breathing refers to breathing at a higher than normal level (i.e. increased depth but not necessarily with an increased rate of breathing.) Normocapnic refers to normal levels of CO2 in the blood. It has been erroneously put forth time and again that hyperpneic or hyperventilation (even voluntary) will lead to lower than normal levels of CO2 thus causing panic, cramping, and other symptoms. This association is not true as demonstrated by this study. These attributes (normocapnic hyperpnea) are precisely the technical basis of our work and have great positive effects even in cases of acute trauma. Wonderful study.
Exp Ther Med. Apr 2013; 5(4): 1194–1200.
“Breathing Exercises improve post-operative Pulmonary function and quality of life in patients with Lung Cancer: A meta-analysis”
Wei Liu et al.
Institute for Psychological Research and Leiden Institute for Brain and Cognition, Leiden University, Leiden, Netherlands.
Previous research has shown that breathing exercises may improve the prognosis and health status in patients with lung cancer by enhancing pulmonary function and quality of life (QOL). However, individually published results are inconclusive. The aim of the present meta-analysis was to evaluate the clinical value of breathing exercises on post-operative pulmonary function and QOL in patients with lung cancer. A literature search of Pubmed, Embase, the Web of Science and CBM databases was conducted from their inception through to October 2012. Crude standardized mean differences (SMDs) with 95% confidence intervals (CIs) were used to assess the effect of breathing exercises. A total of eight clinical studies were ultimately included with 398 lung cancer patients. When all the eligible studies were pooled into the meta-analysis, there was a significant difference between the pre-intervention and post-intervention results of breathing exercises on post-operative pulmonary function; forced expiratory volume in 1 sec (FEV1): SMD, 3.37; 95% CI, 1.97–4.77; P<0.001; FEV1/FVC: SMD, 1.77; 95% CI, 0.15–3.39; P=0.032). Furthermore, the QOL in patients with lung cancer was significantly improved following the intervention with breathing exercises; there were significant differences between the pre-intervention and post-intervention results on the ability of self-care in daily life (SMD, −1.00; 95% CI, −1.467 to −0.52; P<0.001), social activities (SMD, −0.94; 95% CI, −1.73 to −0.15; P=0.02), symptoms of depression (SMD, −0.91; 95% CI, −1.25 to −0.57; P<0.001) and symptoms of anxiety (SMD, −0.91; 95% CI, −1.20 to −0.63; P<0.001). Results from the present meta-analysis suggest that breathing exercises may significantly improve post-operative pulmonary function and QOL in patients with lung cancer.

Yoga Studies 

“Restorative yoga for women with ovarian or breast cancer: findings from a pilot study.”
Danhauer SC, Tooze JA, Farmer DF, Campbell CR, McQuellon RP, Barrett R, Miller BE.
J Soc Integr Oncol. 2008 Spring;6(2):47-58.
Yoga has demonstrated benefit in healthy individuals and those with various health conditions. There are, however, few systematic studies to support the development of yoga interventions for cancer patients. Restorative yoga (RY) is a gentle type of yoga that has been described as “active relaxation.” The specific aims of this pilot study were to determine the feasibility of implementing an RY intervention as a supportive therapy for women diagnosed with ovarian or breast cancer and to measure changes in self-reported fatigue, psychological distress and well-being, and quality of life. Fifty-one women with ovarian (n = 37) or breast cancer (n = 14) with a mean age of 58.9 years enrolled in this study; the majority (61%) were actively undergoing cancer treatment at the time of enrollment. All study participants participated in 10 weekly 75-minute RY classes that combined physical postures, breathing, and deep relaxation. Study participants completed questionnaires at baseline, immediately postintervention, and 2 months postintervention. Significant improvements were seen for depression, negative affect, state anxiety, mental health, and overall quality of life. Fatigue decreased between baseline and postintervention follow-up. Health-related quality of life improved between baseline and the 2-month follow-up. Qualitative feedback from participants was predominantly positive; relaxation and shared group experience were two common themes.
BMC Complement Altern Med. 2007 Dec 19;7:43.
“Wellness through a comprehensive Yogic Breathing program – a controlled pilot trial.”
Pullen PR, Nagamia SH, Mehta PK, Thompson WR, Benardot D, Hammoud R, Parrott JM, Sola S, Khan BV.
Department of Kinesiology and Health, Georgia State University, Atlanta, Georgia, USA.
BACKGROUND:
Increasing rates of psychosocial disturbances give rise to increased risks and vulnerability for a wide variety of stress-related chronic pain and other illnesses. Relaxation exercises aim at reducing stress and thereby help prevent these unwanted outcomes. One of the widely used relaxation practices is yoga and yogic breathing exercises. One specific form of these exercises is Sudarshan Kriya and related practices (SK&P) which are understood to have favourable effects on the mind-body system. The goal of this pilot study was to design a protocol that can investigate whether SK&P can lead to increased feeling of wellness in healthy volunteers.METHODS:
Participants were recruited in a small university city in Sweden and were instructed in a 6-day intensive program of SK&P which they practiced daily for six weeks. The control group was instructed to relax in an armchair each day during the same period. Subjects included a total of 103 adults, 55 in the intervention (SK&P) group and 48 in the control group. Various instruments were administered before and after the intervention. Hospital Anxiety Depression Scale measured the degree of anxiety and depression, Life Orientation Test measured dispositional optimism, Stress and Energy Test measured individual’s energy and stress experiences. Experienced Deviation from Normal State measured the experience of altered state of consciousness.RESULTS:There were no safety issues. Compliance was high (only 1 dropout in the SK&P group, and 5 in the control group). Outcome measures appeared to be appropriate for assessing the differences between the groups. Subjective reports generally correlated with the findings from the instruments. The data suggest that participants in the SK&P group, but not the control group, lowered their degree of anxiety, depression and stress, and also increased their degree of optimism (ANOVA; p < 0.001). The participants in the yoga group experienced the practices as a positive event that induced beneficial effects.CONCLUSION:
These data indicate that the experimental protocol that is developed here is safe, compliance level is good, and a full scale trial is feasible. The data obtained suggest that adult participants may improve their wellness by learning and applying a program based on yoga and yogic breathing exercises; this can be conclusively assessed in a large-scale trial.TRIAL REGISTRATION:
Australian Clinical Trial Registry ACTRN012607000175471.
J Altern Complement Med. 2004 Oct;10(5):757-66.
“Hemodynamic observations on a yogic breathing technique claimed to help eliminate and prevent heart attacks: a pilot study.”
Shannahoff-Khalsa DS, Sramek BB, Kennel MB, Jamieson SW. The Research Group for Mind-Body Dynamics, Institute for Nonlinear Science, University of California, San Diego, La Jolla, CA 92093-0402, USA.
OBJECTIVE: This pilot study investigated the hemodynamics of a yogic breathing technique claimed “to help eliminate and prevent heart attacks due to abnormal electrical events to the heart” and to generally “enhance performance of the central nervous system (CNS) and to help eliminate the effects of traumatic shock and stress to the CNS.” DESIGN: Parameters for (4) subjects were recorded during a preexercise resting period, a 31-minute exercise period, and a postexercise resting period. SETTINGS/LOCATION: Parameters for subjects were recorded in a laboratory at the University of California, San Diego. SUBJECTS: Parameters for 3 males (ages 44, 45, 67) and 1 female (age 41) were recorded. One (1) subject (male age 45) had extensive training in this technique. Interventions: This yogic technique is a 1 breath per minute (BPM) respiratory exercise with slow inspiration for 20 seconds, breath retention for 20 seconds, and slow expiration for 20 seconds, for 31 consecutive minutes. OUTCOME MEASURES: Fourteen beat-to-beat parameters were measured noninvasively and calculated for body surface area to yield: stroke index (SI), heart rate (HR), cardiac index, end diastolic index, peak flow, ejection fraction, thoracic fluid index, index of contractility, ejection ratio, systolic time ratio, acceleration index, and systolic, diastolic, and mean arterial pressures (MAPs). Left stroke work index (LSWI) and stroke systemic vascular resistance index (SSVRI) were calculated. RESULTS: We report on SI, HR, MAP, LSWI, and SSVRI and how they can help to describe hemodynamicstate changes. This technique induces dramatic shifts in all hemodynamic variables during the 1 BPM exercise and can produce unique changes in the postexercise resting period after long-term practice that appears to have a unique effect on the brain stem cardiorespiratory center regulating the Mayer wave (0.1-0.01 Hz) patterns of the cardiovascular system. CONCLUSIONS: Preclinical studies are warranted to examine the possible long-term effects of this technique that appear to reset a cardiorespiratory brain-stem pacemaker. We postulate that this effect may be the basis for the purported yogic health claim.

Oxygen Studies 

Brain Res Bull. 2006 Mar 31;69(2):109-16. Epub 2005 Dec 15.
“Involvement of the mitochondrial ATP-sensitive potassium channel in the neuroprotective effect of hyperbaric oxygenation after cerebral ischemia.”
Lou M, Chen Y, Ding M, Eschenfelder CC, Deuschl G.
Department of Neurology, The Second Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou 310009, PR China.
In the present study, we investigated whether activation of mitochondrial ATP-sensitive potassium channel is involved in the neuroprotective effect offered by early hyperbaric oxygenation after cerebral ischemia. The selective mitochondrial ATP-sensitive potassium channel antagonist 5-hydroxydecanoate was infused intracerebroventricularly before hyperbaric oxygenation treatment initiated 3 h after middle cerebral artery occlusion for 90 min. Neurological status was evaluated and brains were removed for the measurement of infarct size and immunohistochemical evaluation of apoptosis 24 h after middle cerebral artery occlusion. Early hyperbaric oxygenation treatment improved neurologic deficits and reduced infarct volume, while these effects were reversed by the administration of 5-hydroxydecanoate. Furthermore, early hyperbaric oxygenation significantly decreased the number of apoptotic cells in the peri-infarct cortex 24 h after ischemic insult and this effect was also blocked by 5-hydroxydecanoate. The present findings suggest that early hyperbaric oxygenation therapy prevents apoptosis and promotes neurologic functional recovery after focal cerebral ischemia, and the opening of mitochondrial ATP-sensitive potassium channel plays a role in this antiapoptotic effect of early hyperbaric oxygenation
Neuroscience. 2007 May 11;146(2):555-61. Epub 2007 Mar 23.
“Hyperbaric oxygen treatment attenuated the decrease in regional glucose metabolism of rats subjected to focal cerebral ischemia: a high resolution positron emission tomography study.”
Lou M, Zhang H, Wang J, Wen SQ, Tang ZQ, Chen YZ, Yan WQ, Ding MP.
Department of Neurology, The Second Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou, 310009, People’s Republic of China.
Cerebral hypoxia may be the main component of cell damage caused by ischemia. Previous studies demonstrated a neuroprotective effect of early hyperbaric oxygen (HBO) treatment in various animal models of focal cerebral ischemia. Neuropathologic study showed that exposure of HBO may prevent cell death in ischemic cortex. In the present study, we aimed to assess cellular function of ischemic rat brain after HBO treatment by means of a high-resolution positron emission tomography scanner (microPET) used specifically for small animal imaging. The male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO), with the regional cerebral blood flow monitored in vivo by laser Doppler flowmetry. One hour after ischemia, HBO therapy (3 atm absolute, 1 h) was initiated. Local cerebral glucose utilization in the ischemic area was measured before, 1 h and 3 h after ischemia, with 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) as a tracer. Neurological deficits and infarct volumes were assessed at 24 h after ischemia. Our study showed that early HBO therapy significantly reduced infarct volume of brain 24 h after ischemia. Moreover, glucose utilization in the ischemic area underwent a severe decrease during 1-3 h after MCAO, while the early HBO treatment significantly attenuated the decrease in cerebral metabolic rate of glucose in the ischemic core of the cortex compared with controls. We report for the first time the application of microPET to quantify the rates of glucose metabolism in the ischemic core of rats exposed to HBO. Our results suggest that the early exposure of HBO can partially reverse the downward trend for glucose utilization in the ischemic core, which might contribute to the reported beneficial effects of early HBO therapy on permanent cerebral ischemia.
J Cereb Blood Flow Metab. 2003 Jul;23(7):855-64.
“Inhibition of apoptosis by hyperbaric oxygen in a rat focal cerebral ischemic model.”
Yin D, Zhou C, Kusaka I, Calvert JW, Parent AD, Nanda A, Zhang JH.
Department of Neurosurgery, University of Mississippi Medical Center, Jackson, Mississippi, USA.
The hypothesis was tested that hyperbaric oxygen therapy (HBO) reduced brain infarction by preventing apoptotic death in ischemic cortex in a rat model of focal cerebral ischemia. Male Sprague-Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and subsequently were exposed to HBO (2.5 atmospheres absolute) for 2 h, at 6 h after reperfusion. Rats were killed and brain samples were collected at 24, 48, 72 h, and 7 days after reperfusion. Neurologic deficits, infarction area, and apoptotic changes were evaluated by clinical scores, 2,3,7-triphenyltetrazolium chloride staining, caspase-3 expression, DNA fragmentation assay, and terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate-biotin nick end labeling (TUNEL)-hematoxylin and eosin (H&E) costaining. In MCAO/R without HBO treatment animals, DNA fragmentation was observed in injured cortex at 24, 48, and 72 h but not in samples at 7 days after reperfusion. Double labeling of brain slides with NeuN and caspase-3 demonstrated neurons in the injured cortex labeled with caspase-3. TUNEL+H&E costaining revealed morphologic apoptotic changes at 24, 48, and 72 h after reperfusion. Hyperbaric oxygen therapy abolished DNA fragmentation and reduced the number of TUNEL-positive cells. Hyperbaric oxygen therapy reduced infarct area and improved neurologic scores at 7 days after reperfusion. One of the molecular mechanisms of HBO-induced brain protection is to prevent apoptosis, and this effect of HBO might preserve more brain tissues and promote neurologic functional recovery.
Hyperbaric oxygen helps heal Fournier’s disease – a rare form of gangrene.
J Urol. 1997 Sep;158(3 Pt 1):837-40.
“Hyperbaric oxygen therapy in the treatment of Fournier’s disease in 11 male patients.”
Pizzorno R, Bonini F, Donelli A, Stubinski R, Medica M, Carmignani G.
Department of Urology, University of Genoa, Italy.
PURPOSE: Optimal tissue oxygenation, as obtained by hyperbaric oxygen therapy, potentiates or restores the host’s bactericidal mechanisms and wound healing activity in patients afflicted by serious synergeic aerobic and anaerobic infections of the cutaneous and subcutaneous tissues. Furthermore, hyperbaric oxygen therapy has a direct toxic effect on anaerobic bacteria. We describe our experience with hyperbaric oxygen therapy in the treatment of 11 patients with Fournier’s syndrome. MATERIALS AND METHODS: The average age of our patients was 59.5 years; the most common predisponsing condition was diabetes. All patients were treated with antibiotic therapy and hyperbaric oxygen therapy (minimum 5 and maximum 24 cycles, consisting of 90 minutes 2.5 atmosphere absolute pressure). Furthermore, 6 of these patients underwent surgical debridement of the wounds and 3 patients underwent delayed reconstructive surgery. RESULTS: The results we obtained with hyperbaric oxygen therapy as an adjunctive measure for the treatment of these infections were excellent; our mortality rate for Fournier’s disease was 0. Moreover, no complications whatsoever were observed. Furthermore, the 3 patients who underwent delayed corrective surgery presented with well healed tissues and their operations were not complicated by infections or other pathological conditions. CONCLUSIONS: We believe that our findings, although limited in number, underline the excellent results that can be obtained with hyperbaric oxygen therapy as an adjunct treatment in Fournier’s disease.
Ann Chir Gynaecol. 2000;89 Suppl 214:7-36.
“Hyperbaric oxygen therapy in acute necrotizing infections. With a special reference to the effects on tissue gas tensions.”
Korhonen K.
Department of Surgery, University of Turku, Finland.
Clostridial gas gangrene and perineal necrotizing fasciitis or Fournier’s gangrene are rare but serious infections with an acute onset, rapid progression, systemic toxemia and a high mortality rate. The aim of this study was to investigate the efficacy of surgery, antibiotic treatment, surgical intensive care and in particular the role of hyperbaric oxygen (HBO) in the management of these infections. An experimental rat model was used to investigate the possibilities for measuring tissue oxygen and carbon dioxide tensions during hyperbaric oxygen treatment. In addition to this preliminary experimental study, Silastic tube tonometer and capillary sampling techniques were tested to measure the effect of hyperbaric oxygen treatment on subcutaneous oxygen and carbon dioxide tensions in patients with necrotizing fasciitis and healthy controls. Between January 1971 and April 1997, 53 patients with Clostridial gas gangrene were treated in the Department of Surgery, University of Turku. The patients underwent surgical debridement, broad spectrum antibiotic therapy and a series of hyperbaric oxygen treatments at 2.5 atmospheres absolute pressure (ATA). Twelve patients died (22.6%). Hyperbaric oxygen therapy in gas gangrene seems to be life-, limb- and tissue saving. Early diagnosis remains essential. Patient survival can be improved if the disease is recognized early and appropriate therapy instituted promptly. Between February 1971 and September 1996, 33 patients with perineal necrotizing fasciitis were treated in the Department of Surgery, University of Turku. The management included surgical debridement of the necrotic tissue with incisions and drainage of the involved areas, antibiotic therapy, hyperbaric oxygen treatment at 2.5 ATA pressure and surgical intensive care. Three patients died giving a mortality rate of 9.1%. The survivors received hyperbaric oxygen therapy for 2-12 times. Our results indicate that hyperbaric oxygenation is an important therapeutic adjunct in the treatment of Fournier’s gangrene. Electrical equipment should not be used unsheltered in a hyperbaric chamber due to the increased risk of fire. The subcutaneous tissue gas tensions of rats were therefore measured using a subcutaneously implanted Silastic tube tonometer and a capillary sampling technique. The method was succesfully adapted to hyperbaric conditions. The subcutaneous oxygen tension levels increased five fold and the carbon dioxide tension levels two fold compared to intial levels. The PO2 and PCO2 of subcutaneous tissue and arterial blood were measured directly in six patients with necrotizing fasciitis and three healthy volunteers in normobaric conditions and during hyperbaric oxygen exposure at 2.5 ATA pressure. The measurements were carried out in healthy tissue and at the same time in the vicinity of the infected area of the patients. During HBO at 2.5 ATA subcutaneous oxygen tensions increased several fold from baseline values and carbon dioxide tensions also increased, but to a lesser degree in both healthy and infected tissues. When examining the subcutaneous PO2 levels measured from patients with necrotizing fasciitis, the PO2 was regularly higher in the vicinity of the infected area than in healthy tissue. In general, HBO treatment resulted in a marked increase in tissue oxygenation in both healthy tissue and in the vicinity of infected tissue. The hyperoxygenated tissue zone surrounding the infected area may be of significance in preventing the extension of invading microorganisms.
Brain Res. 2008 May 11.
“Neuroprotective effect of hyperbaric oxygen therapy in brain injury is mediated by preservation of mitochondrial membrane properties.”
Palzur E, Zaaroor M, Vlodavsky E, Milman F, Soustiel JF.
Acute Brain Injury Research Laboratory, Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel.
Recent experimental data have shown that hyperbaric oxygen therapy (HBOT) was associated increased Bcl-2 expression at the injury site that correlated with reduced apoptosis. We hypothesized that HBOT mediated enhancement of Bcl-2 expression and increased intracellular oxygen bio-availability may both contribute to preserve mitochondrial integrity and reduce the activation of the mitochondrial pathway of apoptosis. For this purpose, a cortical lesion was created in the parietal cortex of Sprague-Dawley rats by dynamic cortical deformation (DCD) and outcome measures in non-treated animals were compared with that of HBOT treated rats. Morphological analysis showed a profound reduction in neuronal counts in the perilesional area and a marked rarefaction of the density of the axonal-dentritic network. In treated animals, however, there was a significant attenuation of the impact of DCD over perilesional neurons, characterized by significantly higher cell counts and denser axonal network. In mitochondria isolated from injured brain tissue, there was a profound loss of mitochondrial transmembrane potential (Deltapsi(M)) that proved to be substantially reversed by HBOT. This finding correlated with a significant reduction of caspases 3 and 9 activation in HBOT treated animals but not of caspase 8, indicating a selective effect over the intrinsic pathway of apoptosis. All together, our results indicate that the neuroprotective effect of HBOT may represent the consequence of preserved mitochondrial integrity and subsequent inhibition of the mPTP and reduction of the mitochondrial pathway of apoptosis.
Life Sci. 2008 Jul 4;83(1-2):65-73. Epub 2008 May 23.
“Hyperbaric oxygen induces placental growth factor expression in bone marrow-derived mesenchymal stem cells.”
Shyu KG, Hung HF, Wang BW, Chang H.
Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
The bone marrow is home to mesenchymal stem cells (MSCs) that are able to differentiate into many different cell types. The effect of hyperbaric oxygen (HBO) on MSCs is poorly understood. Placental growth factor (PlGF) is an attractive therapeutic agent for stimulating revascularization of ischemic tissue. HBO has been shown to improve diabetic wound healing by increase circulating stem cells. We hypothesized that HBO induces PlGF expression in bone marrow-derived MSCs. The MSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of MSCs were identified by flow cytometry and immunophenotyping. HBO at 2.5 ATA (atmosphere absolute) significantly increased PlGF protein and mRNA expression. The induction of PlGF protein by HBO was significantly blocked by the addition of N-acetylcysteine, while wortmannin, PD98059, SP600125 and SB203580 had no effect on PlGF protein expression. However, the specific inhibitor of nitric oxide synthase, L-NAME did not alter the PlGF protein expression induced by HBO. HBO significantly increased the reactive oxygen species production and pretreatment with N-acetylcysteine significantly blocked the induction of reactive oxygen species by HBO. HBO significantly increased the migration and tube formation of MSCs and pretreatment with N-acetylcysteine and PlGF siRNA significantly blocked the induction of migration and tube formation by HBO. In conclusion, HBO induced the expression of PlGF in human bone marrow-derived MSCs at least through the oxidative stress-related pathways, which may play an important role in HBO-induced vasculogenesis.
Urology. 2008 Jun 23.
“Effects of Hyperbaric Oxygen Therapy on Tumor Growth in Murine Model of PC-3 Prostate Cancer Cell Line.”
Tang H, Sun Y, Xu C, Zhou T, Gao X, Wang L.
Department of Urology, Shanghai Changhai Hospital, Shanghai, China.
OBJECTIVES: To test the hypothesis that hyperbaric oxygen (HBO) has no effect on tumor growth in a murine model of indolent in vivo prostate cancer. HBO means breathing pure (100%) oxygen under increased atmospheric pressure. METHODS: Human prostate PC-3 cells were injected into 40 severe combined-immunodeficient mice. They were randomized to undergo 20 sessions of either HBO or normobaric air in standardized conditions and observed for 4 weeks before histologic assessment of any palpable tumors that had developed. The analysis of the developed PC-3 tumors included tumor volume, microvessel density, apoptosis-associated markers (ie, p53, p27), and the proliferative index (Ki-67). RESULTS: The exposure to HBO at 2 atm for 20 treatment sessions, which comprised a daily 90-minute session, 5 d/wk, had no effect on the prostate cancer volume (P > .05). No differences were observed in tumor microvessel density, proliferative index, or apoptosis markers compared with the non-HBO group (P > .05). CONCLUSIONS: HBO did not have a tumor stimulatory effect on prostate cancer and could potentially be used safely in conjunction with other therapeutic modalities.
Tohoku J Exp Med. 2004 Aug;203(4):253-65.
“The effects of hyperbaric oxygen treatment on oxidant and antioxidants levels during liver regeneration in rats.”
Ozden TA, Uzun H, Bohloli M, Toklu AS, Paksoy M, Simsek G, Durak H, Issever H, Ipek T.
Institute of Child Health, Trace Element Unit, Istanbul University, Capa, Turkey.
The effects of hyperbaric oxygen (HBO) therapy on oxidant/antioxidant metabolism are controversial and its effects on hepatic regeneration are not known. In this study, we investigated a possible beneficial effect of HBO therapy on oxidant and antioxidants levels during liver regeneration. To conduct this study, seventy percent hepatectomy was performed on forty-eight Spraggue-Dawley rats and the rats were divided into two equal groups: HBO-treated group and untreated group (non-HBO group). We determined the levels of malondialdehyde (MDA), an oxidative stress marker, and the levels of antioxidant enzymes/reagents, including glutathione (GSH), superoxide dismutase (SOD) activity, copper (Cu) and zinc (Zn), in the remnant liver samples. We also measured mitotic index (MI) and proliferating cell nuclear antigen (PCNA) levels to assess the degree of liver regeneration. HBO treatment significantly decreased MDA levels, whereas it increased SOD activity, GSH and Zn levels. In contrast, Cu levels were lower in the HBO-treated livers than the levels in the untreated remnant livers. The effect of HBO treatment may be mediated by the suppression of certain enzymes that are responsible for lipid peroxidation. In addition, HBO treatment may induce the production of antioxidant enzymes/reagents by remnant liver tissues. The HBO-treated rats maintained their body weights but the untreated rats lost body weights. HBO treatment also increased MI and PCNA levels, indicating HBO treatment enhances liver regeneration. These results indicate that HBO treatment has beneficial effects on liver regeneration by decreasing MDA and by increasing antioxidant activities. We therefore suggest that HBO therapy may be useful after liver resection.


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