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Vasodilation and Vasoconstriction References: CO2 - (most) potent vasodilator

Coetzee A, Holland D, Fox P, Ryder A, Jones L, The effect of hypocapnia on coronary blood flow and myocardial function in the dog, Anesthesia and Analgesia 1984 Nov; 63(11): p. 991-997.

The effect of hypocapnia on global and regional myocardial function and coronary blood flow (CBF) was studied in dogs anesthetized with halothane before and after critical constriction of the left anterior descending (LAD) coronary artery. Coronary blood flow decreased 29% (P less than 0.05) when hypocapnia was induced in dogs with a normal LAD artery. Critical constriction reduced CBF by 42% (P less than 0.05)...


Dutton R, Levitzky M, Berkman R, Carbon dioxide and liver blood flow, Bull Eur Physiopathol Respir. 1976 Mar-Apr;12(2): p. 265-273.

... Thus, hypercapnia alone increases total liver blood flow, primarily by an increase in portal vein flow. Hypoxia results in a decrease in portal vein flow. The superimposition of hypercapnia on hypoxia restores blood flow to a level close to that found with hypercapnia alone. Hypercapnia in the range of 63 +/- 4 mmHg PCO2 overwhelms the tendency toward a reduction of portal vein blood flow induced by an arterial PO2 of 42 +/- 5 mmHg in the presence of mild hypocapnia (PCO2 : 30.2 +/- 1 mmHg).


Fox P, Ryder WA, Effect of CO2 on the systemic and coronary circulations and on coronary sinus blood gas tensions, Bull Eur Physiopathol Respir 1979 Jul-Aug; 15(4): p.625-638.
...The alterations of coronary blood flow (reduction following hypocapnia, augmentation following hypercapnia) were considerably larger than the changes of cardiac output and of myocardial oxygen consumption.


Fortune JB, Feustel PJ, deLuna C, Graca L, Hasselbarth J, Kupinski AM, Cerebral blood flow and blood volume in response to O2 and CO2 changes in normal humans, J Trauma. 1995 Sep; 39(3): p. 463-471.

Changes in cerebral blood volume (CBV) after head injury may be an important determinant of intracranial pressure (ICP). To determine the normal response of CBV to hypoxemia, hypercapnia, and hypocapnia, eight normal subjects (5 males and 3 females; ages 25 to 43) were studied under these conditions...  For conditions of hypocapnia, hypercapnia, and hypoxemia, the percentage of change in CBV was: -7.2 +/- 0.01, 12.8 +/- 0.01, and 5.2 +/- 0.03, respectively. The simultaneous percentage of change in CBF for the same conditions was -30.7 +/- 4.0, 29.5 +/- 9.2, and 18.4 +/- 6.9, respectively...


Fujita Y, Sakai T, Ohsumi A, Takaori M, Effects of hypocapnia and hypercapnia on splanchnic circulation and hepatic function in the beagle, Anesthesia and Analgesia 1989 Aug; 69(2): p. 152-157.

... Hypocapnia caused a decrease in HABF (hepatic artery blood flow) without affecting the systemic circulation. Hypercapnia, on the other hand, caused a significant increase in cardiac output without changing mean arterial pressure...


Karlsson T, Stjernstrom EL, Stjernstrom H, Norlon K, Wiklund L, Central and regional blood flow during hyperventilation. An experimental study in the pig, Acta Anaesthesiol Scand. 1994 Feb; 38(2): p.180-186.

Blood flow to the cerebellum decreased soon after the induction of hyperventilation, whereas the cerebral blood flow did not decrease until the second hour of hyperventilation. Cardiac output, splanchnic perfusion and portal vein blood flow all decreased. Myocardial perfusion and arterial blood flow to spleen and kidney decreased while pancreatic and liver arterial blood flows were unaffected...


Liem KD, Kollue LA, Hopman JC, De Haan AF, Oeseburg B, The influence of arterial carbon dioxide on cerebral oxygenation and haemodynamics during ECMO in normoxaemic and hypoxaemic piglets, Acta Anaesthesiol Scand Suppl. 1995; 107: p.157-164.

OBJECTIVE. To investigate the cerebrovascular response to changes in arterial CO2 tension during extracorporeal membrane oxygenation (ECMO) in normoxaemic and hypoxaemic piglets. METHODS. Four groups of six anaesthetized, paralysed and mechanically ventilated piglets: group 1-normoxaemia without ECMO, group 2-ECMO after normoxaemia, group 3-hypoxaemia without ECMO, and group 4-ECMO after hypoxaemia, were exposed successively to hypercapnia and hypocapnia. Changes in cerebral concentrations of oxyhaemoglobin (cO2Hb), deoxyhaemoglobin (cHHb), (oxidized-reduced) cytochrome aa3 (cCyt.aa3) and blood volume (CBV) were continuously measured using near infrared spectrophotometry. Heart rate, arterial O2 saturation, arterial blood pressure, central venous pressure, intracranial pressure (ICP) and left common carotid artery blood flow (LCaBF) were measured simultaneously. RESULTS. Hypercapnia resulted in increased CBV, cO2Hb and ICP in all groups, while cHHb was decreased...


Macey PM, Woo MA, Harper RM, Hyperoxic brain effects are normalized by addition of CO2, PLoS Med. 2007 May; 4(5): e173.

... CONCLUSIONS: In this group of children, hyperoxic ventilation led to responses in brain areas that modify hypothalamus-mediated sympathetic and hormonal outflow; these responses were diminished by addition of CO2 to the gas mixture. This study in healthy children suggests that supplementing hyperoxic administration with CO2 may mitigate central and peripheral consequences of hyperoxia.


Okazaki K, Okutsu Y, Fukunaga A, Effects of carbon dioxide (hypocapnia and hypercapnia) on tissue blood flow and oxygenation of liver, kidney and skeletal muscle in the dog  [Article in Japanese], Masui 1989 Apr, 38 (4); p. 457-464.

We investigated the effects of carbon dioxide on the splanchnic visceral organs (liver and kidney) as well as skeletal muscle in the anesthetized dog. Thirty two adult mongrel dogs were anesthetized with sodium pentobarbital, intubated and ventilated mechanically with 100% oxygen to maintain normocapnia. After laparotomy, miniature Clark-type polarographic oxygen electrodes were placed on the surfaces of liver, kidney and rectus femoris muscle. Electromagnetic blood flow (BF) probes were also applied to hepatic artery (HA), portal vein (PV), left renal artery (RA) and left femoral artery (FA). After a stable normocapnic ventilation, the hypocapnia was produced by increasing respiratory rate, and the hypercapnia was induced by adding the exogenous carbon dioxide. Results: Hyperventilation resulted in a significant decrease in HABF, PVBF, liver surface PO2 and kidney surface PO2 in parallel with the decreased PaCO2, but these parameters increased dose dependently when the carbon dioxide was added to the inspired gas (hypercapnic hyperventilation)...


Okazaki K, Hashimoto K, Okutsu Y, Okumura F, Effect of arterial carbon dioxide tension on regional myocardial tissue oxygen tension in the dog [Article in Japanese], Masui 1991 Nov; 40(11): p. 1620-1624.

... Hypocapnic hyperventilation (PaCO2: 22 mmHg) invariably resulted in a significant reduction of coronary blood flow (LADBF) and left ventricular myocardial tissue PO2 in both epicardial and endocardial layers, while addition of carbon dioxide to the inspired gas (hypercapnic hyperventilation) reversed the change by increased LADBF and arterial PaCO2 in a dose-dependent manner. These results indicate that injudicious and severe hypocapnic hyperventilation may induce impaired myocardial tissue perfusion and oxygenation although normal cardiac output and arterial blood oxygenation are maintained.


Okazaki K, Hashimoto K, Okutsu Y, Okumura F, Effect of carbon dioxide (hypocapnia and hypercapnia) on regional myocardial tissue oxygen tension in dogs with coronary stenosis [Article in Japanese], Masui 1992 Feb; 41(2): p. 221-224.

Carbon dioxide (CO2) has been well documented to act as a potent vasodilator of coronary vessels under normal conditions...


Wexels JC, Myhre ES, Mjos OD, Effects of carbon dioxide and pH on myocardial blood-flow and metabolism in the dog, Clin Physiol. 1985 Dec; 5(6): p.575-588.

... During hypercapnia, however, MBF (myocardial blood-flow) increased more than 40%.


Ashkanian M, Gjedde A, Mouridsen K, Vafaee M, Hansen KV, Ostergaard L, Andersen G, Carbogen inhalation increases oxygen transport to hypoperfused brain tissue in patients with occlusive carotid artery disease: increased oxygen transport to hypoperfused brain, Brain Res. 2009 Dec 22; 1304: 90-5.

... Thus, carbogen improves oxygen transport to brain tissue more efficiently than oxygen alone.


Ashkanian M, Borghammer P, Gjedde A, Ostergaard L, Vafaee M, Improvement of brain body oxygen level by inhalation of carbogen, Neuroscience. 2008 Oct 28;156(4):932-8. Epub 2008 Aug 22.

Hyperoxic therapy for cerebral ischemia is suspected to reduce cerebral blood flow (CBF), due to the vasoconstrictive effect of oxygen on cerebral arterioles. We hypothesized that vasodilation predominates when 5% CO(2) is added to the inhaled oxygen (carbogen)... Oxygen and carbogen were equally potent in increasing oxygen saturation of arterial blood (Sa(O2)). The present data demonstrate that inhalation of carbogen increases both CBF and Sa(O2) in healthy adults. In conclusion we speculate that carbogen inhalation is sufficient for optimal oxygenation of healthy brain tissue, whereas carbogen induces concomitant increases of CBF and Sa(O2).


Kallinen J, Didier A, Miller JM, Nuttall A, Grunman R, The effect of CO2- and O2-gas mixtures on laser Doppler measured cochlear and skin blood flow in guinea pigs, Hear Res. 1991 Oct;55(2):255-62.

The effects of carbogen (5% CO2: 95% O2) 10% CO2-in-air and 100% O2 on cochlear blood flow (CBF), skin blood flow (SBP), blood pressure (BP) and arterial blood gases were investigated in the anesthetized, respired or self-respiring guinea pig. In respired animals, CBF and SBF were increased with carbogen and 10% CO2-in-air and decreased with O2...


Brown JJ, Meikle MB, Lee CA, Reduction of acoustically induced auditory impairment by inhalation of carbogen gas. II. Temporary pure-tone induced depression of cochlear action potentials, Acta Otolaryngol. 1985 Sep-Oct;100(3-4):218-28.

... Carbon dioxide is a potent stimulator of cerebral and cochlear vasodilatation...


Kisilevsky M, Hudson C, Mardimae A, Wong T, Fisher J, Concentration-dependent vasoconstrictive effect of hyperoxia on hypercarbia-dilated retinal arterioles, Microvasc Res. 2008 Mar;75(2):263-8. Epub 2007 Aug 28.

BACKGROUND/AIMS: The relative effects of simultaneously administered oxygen and carbon dioxide on vascular resistance are unknown. The purpose of the study was to investigate the independent effect of oxygen partial pressure on hypercarbia-induced vasodilation in the retinal arterioles. METHODS: Twelve young healthy volunteers participated in the study. End-tidal partial pressure of carbon dioxide was raised 23% from the baseline (i.e. air) at normoxia and then maintained constant while end-tidal partial pressure of oxygen (PETO(2)) was raised in a stepwise incremental fashion. Retinal vessel diameter and blood velocity were measured in the superior-temporal arteriole using the Canon Laser Blood Flowmeter. RESULTS: Hypercarbia resulted in a 16% increase in blood velocity and a 22% increase in blood flow (p<0.05)...


Ohta K, Yachie A, Development of vascular biology over the past 10 years: heme oxygenase-1 in cardiovascular homeostasis, J Endovasc Ther. 2004 Dec;11 Suppl 2: II140-50.

... Moreover, the reaction is also the major source of carbon dioxide (CO2) in the body, which is a physiologically important gaseous vasodilator that inhibits SMC proliferation.


Ozkan M, Koramaz I, Ulus AT, Tavil Y, Filizlioglu H, Baykan EC, Eryilmaz S, Inan B, Katircioglu SF, Ozyurda U, Effect of carbon dioxide insufflation on free internal thoracic artery flows: is it a vasodilator? J Thorac Cardiovasc Surg. 2004 Sep;128(3):354-6.

...CONCLUSIONS: Carbon dioxide insufflation of the internal thoracic artery is an efficient technique to increase the flow and seems to be safe, simple, and reliable. When the internal thoracic artery is harvested in a carbon dioxide-insufflated fashion, arterial spasm and reduced early flow may be avoided, even without vasodilator agents such as papaverine.


Wise RG, Ide K, Poulin MJ, Tracey I, Resting fluctuations in arterial carbon dioxide induce significant low frequency variations in BOLD signal, Neuroimage. 2004 Apr;21(4):1652-64.

... Carbon dioxide is a potent cerebral vasodilator...


Nakahata K, Kinoshita H, Hirano Y, Kimoto Y, Iranami H, Hatano Y, Mild hypercapnia induces vasodilation via adenosine triphosphate-sensitive K+ channels in parenchymal microvessels of the rat cerebral cortex, Anesthesiology. 2003 Dec;99(6):1333-9.

BACKGROUND: Carbon dioxide is an important vasodilator of cerebral blood vessels...


Kashiba M, Kajimura M, Goda N, Suematsu M, From O2 to H2S: a landscape view of gas biology, Keio J Med. 2002 Mar;51(1):1-10.

... Carbon dioxide (CO2) is generated mainly through the Krebs cycle as a result of glucose oxidation and serves as a potent vasodilator...


Djurberg HG, Tjan GT, Al Moutaery KR, Enhanced catheter propagation with hypercapnia during superselective cerebral catherisation, Neuroradiology. 1998 Jul;40(7):466-8.

... Carbon dioxide, a most potent cerebral vasodilator, was temporarily added to the inspired gases of two anaesthetised patients undergoing superselective embolisation of an arteriovenous malformation, when the microcatheter had been impacted for a considerable time. Successful propagation of the microcatheter into the malformation was achieved in both patients after a relatively short period of hypercapnia.


References for CO2 vasodilation effect

Buteyko KP, Odintsova MP, Dyomin DV, Hyper- and Hypoxemia Effects on the Peripheral Vascular Tone, Materials of the Second Siberian Research Conference of Therapists, Irkutsk, 1964a.

Buteyko KP, Dyomin DV, Odintsova MP, Regressive Analysis in Differentiating Aerated Blood Gas Component Effects on Peripheral Arteriole Functional Conditions, Materials of the Second Siberian Research Conference of Therapists, Irkutsk, 1964b.

Buteyko KP, Zhuk EA, MIkaelyan AL, Electrocardiogram for Isolated Aortal Stenosis, Cardiologiya (Cardiology, USSR), 1964c, N 2, p. 67.

Buteyko KP, Dyomin DV, Odintsova MP, Ventilation of the Lungs and Arterial Vascular Tone Interconnection in Patients with High Blood Pressure and Angina Pectoris, Phyziologichny Zhurnal (Physiological Magazine, Ukrainian SSR) 1965. V. 11, N 5 (in Ukrainian).

Buteyko KP, Odintsova MP, Dyomin DV, Hyper- and Hypoxemia Effects on the Arterial Vascular Tone. Sovetskaya Meditsina (Soviet Medicine), 1967, N3, p.44-49.

Coetzee A, Holland D, Fox P, Ryder A, Jones L, The effect of hypocapnia on coronary blood flow and myocardial function in the dog, Anesthesia and Analgesia 1984 Nov; 63(11): p. 991-997.

Dutton R, Levitzky M, Berkman R, Carbon dioxide and liver blood flow, Bull Eur Physiopathol Respir. 1976 Mar-Apr; 12(2): p. 265-273.

Gilmour DG, Douglas IH, Aitkenhead AR, Hothersall AP, Horton PW, Ledingham IM, Colon blood flow in the dog: effects of changes in arterial carbon dioxide tension, Cardiovasc Res 1980 Jan; 14(1): 11-20.

Fox P, Ryder WA, Effect of CO2 on the systemic and coronary circulations and on coronary sinus blood gas tensions, Bull Eur Physiopathol Respir 1979 Jul-Aug; 15(4): p.625-638.

Fortune JB, Feustel PJ, deLuna C, Graca L, Hasselbarth J, Kupinski AM, Cerebral blood flow and blood volume in response to O2 and CO2 changes in normal humans, J Trauma. 1995 Sep; 39(3): p. 463-471.

Fujita Y, Sakai T, Ohsumi A, Takaori M, Effects of hypocapnia and hypercapnia on splanchnic circulation and hepatic function in the beagle, Anesthesia and Analgesia 1989 Aug; 69(2): p. 152-157.

Hashimoto K, Okazaki K, Okutsu Y, The effects of hypocapnia and hypercapnia on tissue surface PO2 in hemorrhaged dogs [Article in Japanese], Masui 1989 Oct; 38(10): p. 1271-1274.

Henderson Y, Acapnia and shock. - I. Carbon dioxide as a factor in the regulation of the heart rate, American Journal of Physiology 1908, 21: p. 126-156.

Hughes RL, Mathie RT, Fitch W, Campbell D, Liver blood flow and oxygen consumption during hypocapnia and IPPV in the greyhound , J Appl Physiol. 1979 Aug; 47(2): p. 290-295.

Karlsson T, Stjernstrom EL, Stjernstrom H, Norlon K, Wiklund L, Central and regional blood flow during hyperventilation. An experimental study in the pig, Acta Anaesthesiol Scand. 1994 Feb; 38(2): p.180-186.

Liem KD, Kollue LA, Hopman JC, De Haan AF, Oeseburg B, The influence of arterial carbon dioxide on cerebral oxygenation and haemodynamics during ECMO in normoxaemic and hypoxaemic piglets, Acta Anaesthesiol Scand Suppl. 1995; 107: p.157-164.

Litchfield PM, A brief overview of the chemistry of respiration and the breathing heart wave, California Biofeedback, 2003 Spring, 19(1).

Macey PM, Woo MA, Harper RM, Hyperoxic brain effects are normalized by addition of CO2, PLoS Med. 2007 May; 4(5): p. e173.

McArdle WD, Katch FI, Katch VL, Essentials of exercise physiology (2nd edition); Lippincott, Williams and Wilkins, London 2000.

Okazaki K, Okutsu Y, Fukunaga A, Effect of carbon dioxide (hypocapnia and hypercapnia) on tissue blood flow and oxygenation of liver, kidneys and skeletal muscle in the dog, Masui 1989 Apr, 38 (4): p. 457-464.

Okazaki K, Hashimoto K, Okutsu Y, Okumura F, Effect of arterial carbon dioxide tension on regional myocardial tissue oxygen tension in the dog [Article in Japanese], Masui 1991 Nov; 40(11): p. 1620-1624.

Okazaki K, Hashimoto K, Okutsu Y, Okumura F, Effect of carbon dioxide (hypocapnia and hypercapnia) on regional myocardial tissue oxygen tension in dogs with coronary stenosis [Article in Japanese], Masui 1992 Feb; 41(2): p. 221-224.

Santiago TV & Edelman NH, Brain blood flow and control of breathing, in Handbook of Physiology, Section 3: The respiratory system, vol. II, ed. by AP Fishman. American Physiological Society, Betheda, Maryland, 1986, p. 163-179.

Starling E & Lovatt EC, Principles of human physiology, 14-th ed., 1968, Lea & Febiger, Philadelphia.

Tsuda Y, Kimura K, Yoneda S, Hartmann A, Etani H, Hashikawa K, Kamada T, Effect of hypocapnia on cerebral oxygen metabolism and blood flow in ischemic cerebrovascular disorders, Eur Neurol. 1987; 27(3): p.155-163.

Wexels JC, Myhre ES, Mjos OD, Effects of carbon dioxide and pH on myocardial blood-flow and metabolism in the dog, Clin Physiol. 1985 Dec; 5(6): p.575-588.

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