Scientific Research on CO2 Therapy and Breathing

Scientific Research on CO2 Therapy and Breathing

Dive into the science behind CO2 therapy and breathing with evidence-based research across key areas like Heart & Circulation, Performance & Recovery, Brain & Nervous System, and more. Explore how optimizing CO2 levels and breathing techniques can enhance health, improve recovery, and support overall well-being. Discover the latest findings and references to unlock the full potential of your breath.
Blood Pressure, Heart Rate, Circulation, Wound Healing, Diabetes Foot

Title: Effect of leg immersion in mild warm carbonated water on skin and muscle blood flow

Authors: Ogoh S, Washio T, Suzuki K, Ikeda K, Hori T, Olesen ND, Muraoka Y.

Journal: Physiol Rep. 2018 Sep;6(18):e13859. doi: 10.14814/phy2.13859. PMID: 30221833; PMCID: PMC6139710.

Link to full text: Effect of leg immersion in mild warm carbonated water on skin and muscle blood flow

Abstract: Leg immersion in carbonated water improves endothelial-mediated vasodilator function and decreases arterial stiffness but the mechanism underlying this effect remains poorly defined. We hypothesized that carbonated water immersion increases muscle blood flow. To test this hypothesis, 10 men (age 21 ± 0 years; mean ± SD) underwent lower leg immersion in tap or carbonated water at 38°C. We evaluated gastrocnemius muscle oxyhemoglobin concentration and tissue oxygenation index using near-infrared spectroscopy, skin blood flow by laser Doppler flowmetry, and popliteal artery (PA) blood flow by duplex ultrasound. Immersion in carbonated, but not tap water elevated PA (from 38 ± 14 to 83 ± 31 mL/min; P < 0.001) and skin blood flow (by 779 ± 312%, P < 0.001). In contrast, lower leg immersion elevated oxyhemoglobin concentration and tissue oxygenation index with no effect of carbonation (P = 0.529 and P = 0.495). In addition, the change in PA blood flow in response to immersion in carbonated water correlated with those of skin blood flow (P = 0.005) but not oxyhemoglobin concentration (P = 0.765) and tissue oxygenation index (P = 0.136) while no relations was found for tap water immersion. These findings indicate that water carbonation has minimal effect on muscle blood flow. Furthermore, PA blood flow increases in response to lower leg immersion in carbonated water likely due to a large increase in skin blood flow.

Title: Carbonate Ion-Enriched Hot Spring Water Promotes Skin Wound Healing in Nude Rats

Authors: Liang J, Kang D, Wang Y, Yu Y, Fan J, Takashi E.

Journal: PLoS One. 2015 Feb 11;10(2):e0117106. doi: 10.1371/journal.pone.0117106. PMID: 25671581; PMCID: PMC4324962.

Link to full text: Carbonate Ion-Enriched Hot Spring Water Promotes Skin Wound Healing in Nude Rats

Abstract: Hot spring or hot spa bathing (Onsen) is a traditional therapy for the treatment of certain ailments. There is a common belief that hot spring bathing has therapeutic effects for wound healing, yet the underlying molecular mechanisms remain unclear. To examine this hypothesis, we investigated the effects of Nagano hot spring water (rich in carbonate ion, 42°C) on the healing process of the skin using a nude rat skin wound model. We found that hot spring bathing led to an enhanced healing speed compared to both the unbathed and hot-water (42°C) control groups. Histologically, the hot spring water group showed increased vessel density and reduced inflammatory cells in the granulation tissue of the wound area. Real-time RT-PCR analysis along with zymography revealed that the wound area of the hot spring water group exhibited a higher expression of matrix metalloproteinases-2 and -9 compared to the two other control groups. Furthermore, we found that the enhanced wound healing process induced by the carbonate ion-enriched hot spring water was mediated by thermal insulation and moisture maintenance. Our results provide the evidence that carbonate ion-enriched hot spring water is beneficial for the treatment of skin wounds.

Title: A Novel Bathing Therapeutic Approach for Diabetic Foot Ulcers

Authors: Tappia PS, Hiebert B, Sanjanwala R, Komenda P, Sathianathan C, Arneja AS, Ramjiawan B.

Journal: Applied Sciences. 2021; 11(18):8402. https://doi.org/10.3390/app11188402

Link to full text: A Novel Bathing Therapeutic Approach for Diabetic Foot Ulcers

Abstract: Ineffective healing and treatment of foot ulcers can lead to an infection and gangrene of the wound area that ultimately results in the loss of the limb. The incidence of foot ulcers is higher in patients with diabetes, peripheral vascular disease and kidney disease. Accordingly, this study was undertaken to assess the ability of foot bathing in CO2-enriched water to heal foot ulcers. The design was a double-blinded, randomized, placebo-controlled study. Patients with at least one foot ulcer were randomized to receive either a treatment with bath therapy at 37 ± 0.5 °C containing either 1000–1200 ppm CO2-enriched tap water (the intervention) or non-carbonated tap water at 37 ± 0.5 °C (the control group). Treatment was conducted three times/week for 15 min per session for up to 16 weeks for a total of 48 treatment sessions. Before and at the end of every treatment month, wound size, wound area oxygenation and the ankle brachial index were measured. In addition, the McGill pain questionnaire was conducted. Blood was also collected at these time points (for a total of five collections) for the measurement of different biomarkers. While no significant differences (p < 0.05) in the group/time interaction effect were observed, a clear separation within the wound area reduction/wound area/oxygenated Hb outcomes was seen between placebo (control) and treatment (CO2) group. This pilot study is suggestive that bathing in CO2-enriched water may accelerate the healing of foot ulcers.

Title: Effect of Carbon Dioxide Therapy on Diabetic Foot Ulcer

Authors: Shalan, N. , Al-Bazzaz, A. , Al-Ani, I. , Najem, F. and Al-Masri, M.

Journal: Journal of Diabetes Mellitus, 5, 284-289. doi: 10.4236/jdm.2015.54035.

Link to full text: Effect of Carbon Dioxide Therapy on Diabetic Foot Ulcer

Abstract: Ulceration of diabetic foot represents one of the most concerning complications associated with uncontrolled blood sugar in diabetes mellitus. The aim of this study is to evaluate the condition of twenty-two diabetic patients with different degrees of ulceration in their feet after daily secessions of carbon dioxide therapy. Blood flow to the affected foot was measured by Doppler; also the size, color, degree of ulceration and sensation of the ulcerative area were all evaluated. Results showed improvement of blood flow to the affected foot as well as improvement in the sensation and color of the ulcerative area. It was concluded that carbon dioxide therapy of diabetic foot was promising and needed thorough investigation to be brought widely into application.

Title: Cognitive factors in carbon dioxide therapy

Authors: van den Hout MA, Griez E.

Journal: J Psychosom Res. 1982;26(2):209-14. doi: 10.1016/0022-3999(82)90038-1. PMID: 6804625.

Link to PubMed: Cognitive factors in carbon dioxide therapy

Abstract: The effects of CO2 inhalation on subjective state, heart rate and blood pressure were studied in two differently instructed groups, with use of air for placebo. Participants who were told that inhalation would produce a state of pleasant relaxation reported a statistically significant, confirming change when administered CO2, whereas air was found not to alter the subjective state appreciably. Those who had expected unpleasant feelings of tension did show a non-significant change in this respect after CO2 inhalation and no such reaction at all to the placebo. Heart rate and diastolic blood pressure dropped significantly after CO2 intake. Surprisingly, participants were subject to a significant decrease in heart rate upon inhalation of air when relaxation was expected. Finally, a number of theoretical inferences are made and the role of cognitive processes in the clinical use of CO2 therapy is underscored.

Title: Cardiovascular and subjective responses to inhalation of carbon dioxide. A controlled test with anxious patients

Authors: van den Hout MA, Griez E.

Journal: Psychother Psychosom. 1982;37(2):75-82. doi: 10.1159/000287556. PMID: 6812154.

Link to PubMed: Cardiovascular and subjective responses to inhalation of carbon dioxide. A controlled test with anxious patients

Abstract: Cardiovascular and subjective responses to inhalation of a 35% CO2 mixture were studied in a sample of anxious neurotics. Inhalation of air was used as a placebo control treatment. In comparison with the inhalation of air, CO2 produced a significant drop in diastolic blood pressure. A drop in heart rate frequency was observed both after inhalation of CO2 and air. CO2 inhalation did not produce an average decline in subjective feelings of distress. Explanations of these data are offered and they are compared with earlier findings. Some speculations are made on the clinical usefulness of CO2 inhalation in the treatment of anxious neurotics.

Title: Effect of carbon dioxide-enriched water and fresh water on the cutaneous microcirculation and oxygen tension in the skin of the foot.

Authors: Hartmann BR, Bassenge E, Pittler M.

Journal: Angiology. 1997 Apr;48(4):337-43. doi: 10.1177/000331979704800406. PMID: 9112881.

Link to PubMed: Effect of carbon dioxide-enriched water and fresh water on the cutaneous microcirculation and oxygen tension in the skin of the foot.

Abstract: The effects of immersion of the lower leg and foot in fresh water and in carbon dioxide (CO2)-enriched water (1200 mg CO2 per kg water; succinate+sodium bicarbonate: Actibath, KAO Tokyo) on cutaneous circulation, vasomotion and oxygen tension (PO2) were measured by laser Doppler flowmetry and transcutaneous oximetry. On the first of two consecutive days patients were randomly assigned to have the lower extremities immersed in either fresh water or CO2-enriched water under standardized conditions (temperature, 34 degrees C; depth, 35 cm; immersion time, twenty minutes) with concurrent measurement. On the second day patients were switched to the other bath type. For both sets of measurements probes were attached symmetrically to the dorsum of each foot. Included in the study were 18 patients with mild, bilateral, peripheral, occlusive arterial disease (intermittent claudication, femoral or iliac type). During immersion in CO2-enriched water the Doppler laser signal and vasomotion amplitude rose by 300%, while PO2 increased by 10%. These increases were still apparent during the latter part of the measurement period, following withdrawal of the limbs from the bath, while patients were seated and supine. During immersion in fresh water and thereafter the Doppler laser signal was unchanged and the PO2 increase was considerably less marked. The authors were thus able to demonstrate vasodilation and increased oxygen utilization (Bohr effect) resulting from topical CO2 application, and hence, that the use of topical CO2 has an objective basis.

Title: Effects of serial percutaneous application of carbon dioxide in intermittent claudication: results of a controlled trial

Authors: Hartmann BR, Bassenge E, Hartmann M.

Journal: Angiology. 1997 Nov;48(11):957-63. doi: 10.1177/000331979704801104. PMID: 9373047.

Link to full text: Effects of serial percutaneous application of carbon dioxide in intermittent claudication: results of a controlled trial

Abstract: In a prospective, controlled clinical trial, serial application of carbon-dioxide-enriched water was compared with fresh water. Twenty-four patients with peripheral arterial occlusive disease (stable claudication) were randomly allocated to one of two serial intervention groups, lower extremities immersed in either fresh water or in CO2-enriched water (1000 mg CO2/kg) water under standardized conditions (temperature, 33 degrees C; depth, 40 cm; immersion time, 30 min; five times a week over 4 weeks). The serial application of carbon-dioxide-enriched water increased arterial peak flow (reactive hyperemia), transcutaneous oxygen tension (basal value and half-recovery-time), and pain-free walking distance. The serial fresh water application did not change these values. The authors conclude that serial carbon dioxide application can be clinically effective in patients with arterial obstructions in the lower extremities.

Title: Vasomotor effects of transcutaneous CO2 in stage II peripheral occlusive arterial disease

Authors: Savin E, Bailliart O, Bonnin P, Bedu M, Cheynel J, Coudert J, Martineaud JP.

Journal: Angiology. 1995 Sep;46(9):785-91. doi: 10.1177/000331979504600904. PMID: 7661381.

Link to full text: Vasomotor effects of transcutaneous CO2 in stage II peripheral occlusive arterial disease

Abstract: Vasomotor effects of skin exposure to carbon dioxide (CO2) have been described in normal subjects. It was of interest, therefore, to determine whether percutaneous CO2 is of therapeutic benefit. In a randomized, double-blind study, 10 patients with lower limb arteriopathy (stage II) were investigated before and after local exposure for twenty minutes to CO2-rich spa gas or to water-vapor-saturated air at the same temperature as that CO2-rich spa gas. Brachial and femoral blood flows, brachial and posterior tibial artery pressures, heart rate, and chest and foot transcutaneous oxygen tensions (tcPO2) were determined. Femoral blood flow, tibial pressure, and foot tcPO2 were significantly increased after exposure of the skin to CO2-rich spa gas. This effect was not accompanied with systemic hemodynamic modifications. Water-vapor-saturated air had no effect. These results suggest that transfer of CO2 across the skin can have beneficial local vasomotor effects in patients with lower limb stage II arteriopathy.

Title: The effect of carbonated mineral water and mofette treatment in Baile Tusnad after ischemic stroke – a case report

Authors: Dogaru, G., Marieta, M., Bulboacă, A.E., Ciumărnean, L., & Stanescu, I.C.

Journal:

Link to full text: The effect of carbonated mineral water and mofette treatment in Baile Tusnad after ischemic stroke – a case report

Abstract: Carbon dioxide baths might represent an effective therapeutic method in the rehabilitation of coronary heart disease, myocardial infarction and stroke, as well as in the treatment of chronic venous insufficiency, inflammatory diseases and functional disorders. According to the World Health Organization, 5.5 million deaths from stroke were recorded in 2001, and about 15 million people survive stroke every year. Mortality from stroke is 11% for women and 8.4% for men. According to the European Association for Cardiovascular Prevention Rehabilitation, phase II and III cardiovascular rehabilitation is performed in Romania only in a proportion of 10%. The therapeutic effects of carbonated mineral waters are due to the action of carbon dioxide. This induces cutaneous vasodilation, with a decrease in blood pressure values. It also causes an increase of cardiac output, while reducing blood pressure and heart rate. Mofettes are natural emanations along the Harghita volcanic massif, which contain CO2 in concentrations of 90-98% with cutaneous vasodilator effects, increasing cerebral and muscle blood flow. The natural therapeutic factors in Baile Tusnad, consisting of carbonated mineral water baths, mofettes, climate therapy, along with medical physical culture, indicated in the rehabilitation treatment of post-stroke patients had a beneficial effect on clinical and functional symptomatology, improving the quality of gait and balance, functionality and exercise capacity in a patient who suffered stroke five years before and was followed up for three years, while she attended an annual medical rehabilitation program in Baile Tusnad. Continuing medical rehabilitation programs, in the absence of contraindications, in Romanian spa resorts for cardiovascular treatment, as well as conducting randomized clinical studies on the efficiency of these treatments is important.

Title: Effects of inhaled carbon dioxide and oxygen on cheyne-stokes respiration in patients with heart failure

Authors: Lorenzi-Filho G, Rankin F, Bies I, Douglas Bradley T.

Journal: Am J Respir Crit Care Med. 1999 May;159(5 Pt 1):1490-8. doi: 10.1164/ajrccm.159.5.9810040. PMID: 10228116.

Link to full text: Effects of inhaled carbon dioxide and oxygen on cheyne-stokes respiration in patients with heart failure

Abstract: We hypothesized that in patients with congestive heart failure (CHF), reductions in PaCO2 sensed at the peripheral chemoreceptors trigger central apneas during Cheyne-Stokes respiration (CSR-CSA), and that raising PaCO2 by inhalation of a CO2 would eliminate these events. The effects of CO2 inhalation on the frequency of apneas and hypopneas during stage 2 (S2) sleep were studied in 10 CHF patients with CSR-CSA. The time from the breath with the minimal end tidal fraction of CO2 (FETCO2) during hyperpnea until the onset of apnea correlated strongly with the lung to ear circulation time (LECT) (r2 = 0.90, p < 0.0001), a measure of lung to carotid body circulatory delay. Among the six patients who also inhaled O2, CO2 inhalation increased transcutaneous PCO2 (PtcCO2) (36.4 +/- 4.6 mm Hg versus 38 +/- 4.4 mm Hg, p < 0.002), abolished central apneas and hypopneas (43.0 +/- 8.4 per hour on air versus 1.6 +/- 2.6 per hour on CO2, p < 0.0001), and increased SaO2. In contrast, O2 inhalation causing a similar rise in SaO2 had no significant impact on either PtcCO2 or the frequency of central events. We conclude that central apneas in patients with CHF are triggered by a low PaCO2 most likely sensed at the peripheral chemoreceptors, and that inhalation of CO2 reverses central apneas by raising PaCO2.

Title: Acute effects on cardiovascular oscillations during controlled slow yogic breathing

Authors: Bhagat OL, Kharya C, Jaryal A, Deepak KK.

Journal: Indian J Med Res. 2017 Apr;145(4):503-512. doi: 10.4103/ijmr.IJMR_830_15. PMID: 28862183; PMCID: PMC5663165.

Link to full text: Acute effects on cardiovascular oscillations during controlled slow yogic breathing

Abstract: Background & objectives: Breathing exercises are believed to modulate the cardiovascular oscillations in the body. To assess the validity of the assumption and understand the underlying mechanism, the key autonomic regulatory parameters such as heart rate variability (HRV), blood pressure variability (BPV) and baroreflex sensitivity (BRS) were recorded during controlled slow yogic breathing. Alternate nostril breathing (ANB) was selected as the yogic manoeuvre. Methods: Twelve healthy volunteers (age 30±3.8 yr) participated in the study. ANB was performed at a breathing frequency of 5 breaths per minute (bpm). In each participant, the electrocardiogram, respiratory movements, beat-to-beat BP and end-tidal carbon dioxide were recorded for five minutes each: before, during and after ANB. The records were analyzed for HRV, BPV and BRS. Results: During ANB, HRV analysis showed significant increase in the standard deviation of all NN intervals, low-frequency (LF) component, LF/HF (low frequency/high frequency) ratio and significant decrease in the HF component. BPV analysis showed a significant increase in total power in systolic BPV (SBPV), diastolic BPV (DBPV) and mean BPV. BRS analysis showed a significant increase in the total number of sequences in SBPV and DBPV and significant augmentation of α-LF and reduction in α-HF. The power spectrum showed a dominant peak in HRV at 0.08 Hz (LF component) similar to the respiratory frequency. The acute short-term change in circulatory control system declined immediately after the cessation of slow yogic breathing (ANB) and remained elevated in post-ANB stage as compared to the pre-ANB. Interpretation & conclusions: Significant increase in cardiovascular oscillations and baroreflex recruitments during-ANB suggested a dynamic interaction between respiratory and cardiovascular system. Enhanced phasic relationship with some delay indicated the complexity of the system. It indicated that respiratory and cardiovascular oscillations were coupled through multiple regulatory mechanisms, such as mechanical coupling, baroreflex and central cardiovascular control.

Title: Effect of slow abdominal breathing combined with biofeedback on blood pressure and heart rate variability in prehypertension

Authors: Wang SZ, Li S, Xu XY, Lin GP, Shao L, Zhao Y, Wang TH.

Journal: J Altern Complement Med. 2010 Oct;16(10):1039-45. doi: 10.1089/acm.2009.0577. PMID: 20954960.

Link to PubMed: Effect of slow abdominal breathing combined with biofeedback on blood pressure and heart rate variability in prehypertension

Abstract: Objective: Prehypertension is a new category designated by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) in 2003. Managing prehypertension with nonpharmacological intervention is possibly beneficial to the prevention of hypertension. In this study, we observed the effect of slow abdominal breathing combined with electromyographic (EMG) biofeedback training on blood pressure (BP) in prehypertensives and assessed the changes of heart rate variability (HRV) in order to find an optional intervention to prevent hypertension and acquire some experimental data to clarify the underlying neural mechanism. Methods: Twenty-two (22) postmenopausal women with prehypertension were randomly assigned to either the experiment group or the control group. The experiment group performed 10 sessions of slow abdominal breathing (six cycles/min) combined with frontal electromyographic (EMG) biofeedback training and daily home practice, while the control group only performed slow abdominal breathing and daily home practice. BP and HRV (including R-R interval and standard deviation of the normal-normal intervals [SDNN]) were measured. Results: Participants with prehypertension could lower their systolic blood pressure (SBP) 8.4 mm Hg (p < 0.001) and diastolic blood pressure (DBP) 3.9 mm Hg (p < 0.05) using slow abdominal breathing combined with EMG biofeedback. The slow abdominal breathing also significantly decreased the SBP 4.3 mm Hg (p < 0.05), while it had no effect on the DBP (p > 0.05). Repeated-measures analyses showed that the biofeedback group + abdominal respiratory group (AB+BF) training was more effective in lowering the BP than the slow breathing (p < 0.05). Compared with the control group, the R-R interval increased significantly during the training in the AB+BF group (p < 0.05). The SDNN increased remarkably in both groups during the training (p < 0.05). Conclusions: Slow abdominal breathing combined with EMG biofeedback is an effective intervention to manage prehypertension. The possible mechanism is that slow abdominal breathing combined with EMG biofeedback could reduce sympathetic activity and meanwhile could enhance vagal activity.

Title: Hyperventilation-induced changes of blood cell counts depend on hypocapnia

Authors: Stäubli M, Vogel F, Bärtsch P, Flückiger G, Ziegler WH.

Journal: Eur J Appl Physiol Occup Physiol. 1994;69(5):402-7. doi: 10.1007/BF00865403. PMID: 7875136.

Link to PubMed: Hyperventilation-induced changes of blood cell counts depend on hypocapnia

Abstract: Voluntary hyperventilation for 20 min causes haemoconcentration and an increase of white blood cell and thrombocyte numbers. In this study, we investigated whether these changes depend on the changes of blood gases or on the muscle work of breathing. A group of 12 healthy medical students breathed 36 l.min-1 of air, or air with 5% CO2 for a period of 20 min. The partial pressure of CO2 decreased by 21.4 mmHg (2.85 kPa; P < 0.001) with air and by 4.1 mmHg (0.55 kPa; P < 0.005) with CO2 enriched air. This was accompanied by haemoconcentration of 8.9% with air (P < 0.01) and of 1.6% with CO2 enriched air (P < 0.05), an increase in the lymphocyte count of 42% with air (P < 0.001) and no change with CO2 enriched air, and an increase of the platelet number of 8.4% with air (P < 0.01) and no change with CO2 enriched air. The number of neutrophil granulocytes did not change during the experiments, but 75 min after deep breathing of air, band-formed neutrophils had increased by 82% (P < 0.025), whereas they were unchanged 75 min after the experiment with CO2 enriched air. Adrenaline and noradrenaline increased by 360% and 151% during the experiment with air, but remained unchanged with CO2 enriched air. It was concluded that the changes in the white blood cell and platelet counts and of the plasma catecholamine concentrations during and after voluntary hyperventilation for 20 min were consequences of marked hypocapnic alkalosis.

Title: Reversal of Hypoxia in Murine Atherosclerosis Prevents Necrotic Core Expansion by Enhancing Efferocytosis

Authors: Marsch E, Theelen TL, Demandt JA, Jeurissen M, van Gink M, Verjans R, Janssen A, Cleutjens JP, Meex SJ, Donners MM, Haenen GR, Schalkwijk CG, Dubois LJ, Lambin P, Mallat Z, Gijbels MJ, Heemskerk JW, Fisher EA, Biessen EA, Janssen BJ, Daemen MJ, Sluimer JC.

Journal: Arterioscler Thromb Vasc Biol. 2014 Dec;34(12):2545-53. doi: 10.1161/ATVBAHA.114.304023. Epub 2014 Sep 25. PMID: 25256233.

Link to full text: Reversal of Hypoxia in Murine Atherosclerosis Prevents Necrotic Core Expansion by Enhancing Efferocytosis

Abstract: Objective: Advanced murine and human plaques are hypoxic, but it remains unclear whether plaque hypoxia is causally related to atherogenesis. Here, we test the hypothesis that reversal of hypoxia in atherosclerotic plaques by breathing hyperoxic carbogen gas will prevent atherosclerosis. Approach and results: Low-density lipoprotein receptor-deficient mice (LDLR(-/-)) were fed a Western-type diet, exposed to carbogen (95% O2, 5% CO2) or air, and the effect on plaque hypoxia, size, and phenotype was studied. First, the hypoxic marker pimonidazole was detected in murine LDLR(-/-)) plaque macrophages from plaque initiation onwards. Second, the efficacy of breathing carbogen (90 minutes, single exposure) was studied. Compared with air, carbogen increased arterial blood pO2 5-fold in LDLR(-/-)) mice and reduced plaque hypoxia in advanced plaques of the aortic root (-32%) and arch (-84%). Finally, the effect of repeated carbogen exposure on progression of atherosclerosis was studied in LDLR(-/-)) mice fed a Western-type diet for an initial 4 weeks, followed by 4 weeks of diet and carbogen or air (both 90 min/d). Carbogen reduced plaque hypoxia (-40%), necrotic core size (-37%), and TUNEL(+) (terminal uridine nick-end labeling positive) apoptotic cell content (-50%) and increased efferocytosis of apoptotic cells by cluster of differentiation 107b(+) (CD107b, MAC3) macrophages (+36%) in advanced plaques of the aortic root. Plaque size, plasma cholesterol, hematopoiesis, and systemic inflammation were unchanged. In vitro, hypoxia hampered efferocytosis by bone marrow-derived macrophages, which was dependent on the receptor Mer tyrosine kinase. Conclusions: Carbogen restored murine plaque oxygenation and prevented necrotic core expansion by enhancing efferocytosis, likely via Mer tyrosine kinase. Thus, plaque hypoxia is causally related to necrotic core expansion. Keywords: atherosclerosis; carbogen; hypoxia; macrophages.

Title: The Effect of Dry Carbon Dioxide Bathing on Peripheral Blood Circulation Measured by Thermal Imaging among Patients with Risk Factors of PAD

Authors: Zbroja H, Kowalski M, Lubkowska A.

Journal: Int J Environ Res Public Health. 2021 Feb 4;18(4):1490. doi: 10.3390/ijerph18041490. PMID: 33557430; PMCID: PMC7916006.

Link to full text: The Effect of Dry Carbon Dioxide Bathing on Peripheral Blood Circulation Measured by Thermal Imaging among Patients with Risk Factors of PAD

Abstract: Peripheral artery disease (PAD) is becoming a serious health problem of present times. It appears crucial to explore therapies that might help to restore blood flow or increase tissue oxygenation. The most effective methods of detecting early-stage changes in blood circulation in the extremities need to be identified. The aim of this study was to identify the effect of carbon dioxide (CO2) bathing on peripheral blood circulation measured by thermal imaging among patients with risk factors of PAD and ankle-brachial index (ABI) in the normal range or ABI indicating some or moderate arterial disease (ABI > 0.5). The correlation between surface temperature change and PAD-relevant characteristics was also examined. Forty-six patients who were over 65 years old who had a minimum of two additional PAD risk factors were recruited. A series of ten dry CO2 baths was performed. Thermal images were taken before and after the intervention. The CO2 therapy caused a significant change in the body surface temperature of many body areas. Numerous moderate correlations between temperature change and health-related characteristics were identified. Therefore, patients with PAD risk factors could benefit from CO2 therapy. Improvements in blood flow change the body surface temperature, and these changes could be successfully detected by thermal imaging. Keywords: carbon dioxide; cardiovascular disease; peripheral artery disease; therapy; thermography.

Title: Carboxytherapy - an innovative trend in resort medicine

Authors: Bunyatyan ND, Drogovoz SM, Kononenko AV, Prokofiev AB.

Journal: Vopr Kurortol Fizioter Lech Fiz Kult. 2018;95(5):72-76. Russian. doi: 10.17116/kurort20189505172. PMID: 30412151.

Link to PubMed: Carboxytherapy - an innovative trend in resort medicine

Abstract: Carboxytherapy (the treatment based on carbon dioxide injections) is a multipurpose and widely used medical technology. The use of CO2 injections (intracutaneous, subcutaneous, and pneumopuncture) have substantially supplemented and increased the practical relevance of carboxytherapy as a method for the treatment of many diseases. Thanks to it physiological properties, CO2 has antihypoxic, antioxidant, vasodilatory, anti-inflammatory, analgesic, and spasmolytic activities; moreover, it improves blood viscosity, stimulates neoangiogenesis, and regenerative processes. Carbon dioxide is a sort of biochemical 'peacemaker' in tissue oxygenation: when blood cells are exposed to high CO2 concentrations (Bohr effect), the rate of gas exchange (CO2 and O2) increases. The human organism interprets carboxytherapy (local hypercapnia) as oxygen deficiency and responses to it by boosting not only the blood flow, but also the vascular endothelial growth factor which stimulates neoangiogenesis and in the long run improves blood supply and tissue trophism. The multiple mechanisms of action, polymodal efficacy, a tool kit with a wide range of detectors and various modes of treatment make carboxytherapy a popular medical technology all over the world, namely in cosmetology, dermatology, aesthetic medicine, angiology, orthopaedics, cardiology, neurology, pulmonology, gynaecology, urology, proctology, plastic and general surgery, and other areas. Carboxytherapy provides a perfect example of the off-label usage in medicine that made it one of the most extensively applied medical technology for the treatment of various diseases despite the lack of the preclinical data and scarce relevant information available in textbooks, reference books and booklets. Keywords: carboxytherapy; carbon dioxide; injectable; pharmacological effect; indication.

Title: Effect of Artificial Carbon Dioxide-Rich Water Immersion on Peripheral Blood Flow in Healthy Volunteers: Preliminary Study about Artificial Carbon Dioxide-Rich Water

Authors: Hasyar, A.R.A., Rasyid, H., Idris, I. and Yusuf, I.

Journal: Open Access Macedonian Journal of Medical Sciences 9.A (2021): 527-531.

Link to full text: Effect of Artificial Carbon Dioxide-Rich Water Immersion on Peripheral Blood Flow in Healthy Volunteers: Preliminary Study about Artificial Carbon Dioxide-Rich Water

Abstract: BACKGROUND: Peripheral blood circulation disorder is one of the global health problems. Balneotherapy that uses CO2 springs may be one of the complementary treatment options. The device to produce artificial CO2-rich water is needed to achieve an improvement effect, at least almost like the improvement effect of natural balneotherapy.AIM: This study aims to investigate the effect of artificial CO2-rich water immersion on peripheral blood flow using Bicarbonated JesC CREA BC-2000.METHODS AND MATERIALS: Thirty-nine healthy volunteers participated in this study. Each subject immersed both of their legs in a mixed solution from water and CO2 at temperature 38°C. This solution was mixed using a device, namely, "Bicarbonated JesC CREA BC-2000". Peripheral blood flow was measured for 5 min before immersion (in this study, we denoted it as the mean basal blood flow), 10 min during immersion, and 5 min after immersion using pocket JMS laser Doppler flowmetry MBF-IIA. Repeated analysis of variance was used for statistical analysis.RESULTS: There is the difference in peripheral blood flow among before, during, and after immersing the legs into artificial CO2-rich water using Bicarbonated JesC CREA BC-2000 (p < 0.001).CONCLUSION: Bicarbonated JesC CREA BC-2000 may be used as the device to produce an artificial CO2-rich water bath that may affect peripheral blood flow in healthy volunteers.

Title: Neonatal encephalopathy therapy optimization for better neuroprotection with inhalation of CO2: the HENRIC feasibility and safety trial

Authors: Szakmar E, Kovacs K, Meder U, Bokodi G, Andorka C, Lakatos A, Szabo AJ, Belteki G, Szabo M, Jermendy A.

Journal: Vopr Kurortol Fizioter Lech Fiz Kult. 2018;95(5):72-76. Russian. doi: 10.17116/kurort20189505172. PMID: 30412151.

Link to full text: Neonatal encephalopathy therapy optimization for better neuroprotection with inhalation of CO2: the HENRIC feasibility and safety trial

Abstract: Background: There is an association between hypocapnia and adverse neurodevelopmental outcome in infants with neonatal encephalopathy (NE). Our aim was to test the safety and feasibility of 5% CO2 and 95% air inhalation to correct hypocapnia in mechanically ventilated infants with NE undergoing therapeutic hypothermia. Methods: Ten infants were assigned to this open-label, single-center trial. The gas mixture of 5% CO2 and 95% air was administered through patient circuits if the temperature-corrected PCO2 ≤40 mm Hg. The CO2 inhalation was continued for 12 h or was stopped earlier if the base deficit (BD) level decreased <5 mmol/L. Follow-up was performed using Bayley Scales of Infant Development II. Results: The patients spent a median 95.1% (range 44.6-98.5%) of time in the desired PCO2 range (40-60 mm Hg) during the inhalation. All PCO2 values were >40 mm Hg, the lower value of the target range. Regression modeling revealed that BD and lactate had a tendency to decrease during the intervention (by 0.61 and 0.55 mmol/L/h, respectively), whereas pH remained stable. The rate of moderate disabilities and normal outcome was 50%. Conclusions: Our results suggest that inhaled 5% CO2 administration is a feasible and safe intervention for correcting hypocapnia.

Title: Carboxytherapy as an alternative off lable method for diabetes mellitus treatment: a review

Authors: Drogovoz, S. M., K. O. Kalko, I. A. Hailat, L. B. Ivantsyk, and I. V. Kireyev.

Journal: (2021).

Link to full text: Carboxytherapy as an alternative off lable method for diabetes mellitus treatment: a review

Abstract: Diabetes mellitus (DM) is one of the global medical and social problems of the XXI century. It was found that patients with diabetes mellitus showed an increased severity of coronavirus disease (COVID19) caused by infection with coronavirus 2 (SARS-CoV-2). At the same time, the development of new modern technologies allows the use of innovative methods for the treatment of diabetes. The purpose of this literature review was to analyze the possibilities of using carboxytherapy in the treatment of diabetes mellitus. Materials and research methods. Scientific publications in foreign and domestic journals on relevant topics over the past 5 years, Internet resources. Research results and their discussion. In the course of the literature review, the mechanisms of realization of the pharmacological effects of carboxytherapy have been summarized with the substantiation of the effect on individual links of pathogenesis in the body of patients with diabetes mellitus or with its complications. The scientific understanding of the role of carboxytherapy as an effective alternative method for treating diabetes mellitus and its complications has been expanded. Conclusions. Thus, the analyzed data indicate the rationality of the use of carboxytherapy as an alternative method for the treatment of diabetes mellitus and its complications. Keywords: diabetes mellitus (DM).