References and abstracts with vasodilation-related quotes
Coetzee A, Holland D, Foëx 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). In the critically constricted LAD artery, hypocapnia did not reduce CBF. During hypocapnia and with a normal LAD artery, oxygen extraction by the myocardium increased 16% (P less than 0.01) and oxygen tension in the coronary sinus was reduced by 19% (P less than 0.001). After critical constriction of the LAD, hypocapnia was associated with an increase in oxygen extraction of 14% (P less than 0.01) and the coronary sinus oxygen tension was reduced by 21% (P less than 0.001). CBF of the left circumflex coronary artery (LC) increased 36% (P less than 0.05) after critical constriction to the LAD when compared with control values of the preconstriction phase. However, LC flow did not change during hypocapnia when critical stenosis had been applied to the LAD artery. Although oxygen supply (product of CBF and arterial oxygen content) to the myocardium was reduced during hypocapnia, regional myocardial function did not change from control values. Regional function was similarly maintained during hypocapnia and critical constriction of the LAD.
Dutton R, Levitzky M, Berkman R, Carbon dioxide and liver blood flow, Bull
Eur Physiopathol Respir. 1976 Mar-Apr;12(2): p. 265-273.
This study was designed to determine blood flow to the liver during hypercapnia
and combined hypercapnia-hypoxia with the portal vein and hepatic artery intact
except for placement of an electromagnetic flow probe around these vessels.
Twenty mongrel dogs weighing 30-45 kg were anesthetized with pentobarbital and
flow probes and occluders were surgically implanted. Ten of these dogs were
subjected to hypercapnia alone. During inspiration of 6% CO2 in room air, portal
vein flow increased from 588 +/- 73 ml/min to 731 +/- 113 ml/min (p less than
.05), while hepatic artery flow did not change significantly from its control
mean of 221 +/- 38 ml/min. In the remaining dogs, inhalation of 6% O2 resulted
in a reduction of portal blood flow within 30 min from 527 +/- 55 ml/min to 381
+/- 41 ml/min (p less than .01). Again, mean hepatic artery flow did not
increase significantly above its control of 273 +/- 43 ml/min. Subsequent
inhalation of 6% CO2 plus 6% O2 (combined hypercapniahypoxia) for 30 min in
these same animals resulted in a significant increase of portal vein blood flow
from 514 +/- 46 ml/min to 716 +/- 116 ml/min (p less than .05). 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).
Foëx 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 responses to hypocapnia and to hypercapnia of both the systemic and the
coronary circulations have been studied in the dog during intermittent positive
pressure ventilation under halothane anaesthesia. In the absence of significant
variations of myocardial contractility, the reduction of cardiac output, because
of hypocapnia, was determined by the increase of systemic vascular resistance,
while the increase of cardiac output because of hypercapnia was determined by an
increase of heart rate without change of stroke volume. 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. Such disparity between oxygen supply and demand,
together with the effect of pH and PCO2 on the oxyhaemoglobin dissociation curve
led to a marked reduction of coronary sinus PO2 in response to hypocapnia and a
marked increase of coronary sinus PO2 in response to hypercapnia. The data
suggests that PCO2 (or respiratory alterations of pH) may have a direct effect
on the regulation of coronary blood flow. The low coronary sinus PO2 observed at
hypocapnia may suggest the risk of myocardial ischaemia.
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.
Section of Trauma Surgery, Albany Medical College, New York, USA.
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. Cerebral
blood volume was measured using an external collimated gamma detector to
determine 99m-Tc-labeled red blood cell (RBC) activity in the intracranial
vascular pool, and cerebral blood flow (CBF) was determined by internal carotid
artery duplex scanning. Hypocapnia (Paco2 = 26.0 +/- 1.7 mm Hg, mean +/- SE) was
achieved by hyperventilation, hypercapnia (Paco2 = 47.8 +/- 1.5 mm Hg) was
achieved by inhalation of 6% CO2, and hypoxemia (Pao2 = 38.1 +/- 1.1 mm Hg, O2
saturation = 76.7 +/- 2.0%) was achieved by inhalation of 10% O2. Changes in CBF
and CBV were determined by comparing the values in each condition to the
immediately preceding period of normoxia and normocapnia. 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. For all conditions, changes in CBF were
greater than changes in CBV; however, this was most pronounced during hypocapnia
induced by hyperventilation. Because the change in CBV reflects the potential
change in ICP in response to treatment, therapeutic hyperventilation may impair
CBF to a greater degree than it reduces ICP.(ABSTRACT TRUNCATED AT 250 WORDS)
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.
Department of Anesthesiology, Kawasaki Medical School, Okayama, Japan.
The effects of mild hypocapnia (PaCO2 22 mm Hg) and hypercapnia (PaCO2 59 mm Hg) on the splanchnic circulation and hepatic function were studied in six pentobarbital anesthetized, laparotomized, mechanically ventilated beagles. Tidal volume and respiratory frequency were held constant throughout the measurements. Hepatic artery blood flow (HABF) and portal vein blood flow (PVBF) were measured by electromagnetic flowmeters. Hepatic function was assessed by indocyanine green (ICG) elimination kinetic analysis after intravenous injection of the dye. 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. There was a significant increase in PVBF and total hepatic blood flow (THBF = PVBF + HABF). Despite the increases in PVBF and THBF, the half-life of ICG was significantly longer during hypercapnia (9.09 +/- 0.79 min) than during hypocapnia (7.16 +/- 0.37 min), and plasma ICG clearance was smaller during hypercapnia (4.79 +/- 0.44 ml.min-1) than during hypocapnia (5.44 +/- 0.33 ml.min-1) or normocapnia (5.27 +/- 0.50 ml.min-1), indicating the depressed hepatic function during hypercapnia. We conclude that mild hypocapnia decreases HABF without affecting hepatic function and that mild hypercapnia is associated with a depression of hepatic function in spite of the increases in PVBF and THBF.
Karlsson T, Stjernström EL, Stjernström H, Norlén 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.
Department of Anaesthesiology and Intensive Care, Uppsala University Hospital,
Sweden.
Mechanical hyperventilation not only reduces brain oedema after neurotrauma but
also affects the central and systemic circulation. We have, in pigs, measured
blood flow in the pulmonary artery, the portal vein and in the femoral artery,
as well as estimated the splanchnic blood flow and studied the relative
perfusion using the microsphere technique in normo- and hypocarbia during
intermittent positive pressure ventilation. A normoventilated control group did
not change in cardiac output, portal vein blood flow, splanchnic blood flow and
femoral arterial blood flow. Hyperventilation was performed to a PCO2 of 3.0 +/-
0.1 kPa. We found that in pigs ventilated with high tidal volume skeletal muscle
blood flow did not change during the first 60 min of hyperventilation but
gradually decreased thereafter. 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. It is concluded that mechanical
hyperventilation with low frequency and large tidal volumes reduces the flow to
most tissues, where the relative decrease according to microsphere measurements
is most pronounced in skeletal muscles, heart muscle and cerebellum. However,
the changes in cardiac output and splanchnic blood flow were not observed when
hyperventilation was induced by increased frequency, keeping the tidal volume
constant.
Liem KD, Kollée 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.
Department of Pediatrics, University Hospital, University of Nijmegen, The
Netherlands.
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. No changes in LCaBF were
found. Hypocapnia resulted in decreased cO2Hb and increased cHHb except in group
3. LCaBF decreased in all groups except group 2. CBV decreased only in groups 2
and 4. No effect on ICP was observed in any of the groups. The other variables
showed no important changes either during hypercapnia or hypocapnia. ECMO after
hypoxaemia resulted in a greater response of cO2Hb and cO2Hb and cHHb during
hypocapnia. The effect of hypercapnia on CBV while on ECMO was greater than
without ECMO. CONCLUSION. Since cerebrovascular reactivity to CO2 remains intact
during ECMO in piglets, it is important to keep arterial CO2 tension stable and
in normal range during clinical ECMO.
Macey PM, Woo MA, Harper RM, Hyperoxic brain effects are normalized by
addition of CO2, PLoS Med. 2007 May; 4(5): e173.
Department of Neurobiology, David Geffen School of Medicine, University of
California Los Angeles, Los Angeles, California, United States of America.
BACKGROUND: Hyperoxic ventilation (>21% O2) is widely used in medical practice
for resuscitation, stroke intervention, and chronic supplementation. However,
despite the objective of improving tissue oxygen delivery, hyperoxic ventilation
can accentuate ischemia and impair that outcome. Hyperoxia results in,
paradoxically, increased ventilation, which leads to hypocapnia, diminishing
cerebral blood flow and hindering oxygen delivery. Hyperoxic delivery induces
other systemic changes, including increased plasma insulin and glucagon levels
and reduced myocardial contractility and relaxation, which may derive partially
from neurally mediated hormonal and sympathetic outflow. Several cortical,
limbic, and cerebellar brain areas regulate these autonomic processes. The aim
of this study was to assess recruitment of these regions in response to
hyperoxia and to determine whether any response would be countered by addition
of CO2 to the hyperoxic gas mixture. METHODS AND FINDINGS: We studied 14
children (mean age 11 y, range 8-15 y). We found, using functional magnetic
resonance imaging, that 2 min of hyperoxic ventilation (100% O2) following a
room air baseline elicited pronounced responses in autonomic and hormonal
control areas, including the hypothalamus, insula, and hippocampus, throughout
the challenge. The addition of 5% CO2 to 95% O2 abolished responses in the
hypothalamus and lingual gyrus, substantially reduced insular, hippocampal,
thalamic, and cerebellar patterns in the first 48 s, and abolished signals in
those sites thereafter. Only the dorsal midbrain responded to hypercapnia, but
not hyperoxia. 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.
Department of Anesthesiology, Yokohama City University School of Medicine,
Japan.
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). On the contrary, FABF and skeletal muscle surface PO2 increased by hypocapnia and decreased during hypercapnia. Neither PaCO2 or cardiac output showed any significant change during the entire experiment. Arterial PCO2 appears to exert significant effects on both splanchnic and skeletal muscle perfusion as well as corresponding changes in tissue oxygenations. It is possible that injudicious and prolonged hypocapnic hyperventilation may seriously compromise splanchnic organ perfusion and oxygenation.
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.
Department of Anesthesiology, Yokohama City University School of Medicine,
Japan.
We investigated the effects of arterial carbon dioxide tension on the myocardial tissue oxygen tensions of subepicardium and subendocardium in the anesthetized dogs. The study was done in fourteen open-chest mongrel dogs, weighing 13 +/- 1 kg, anesthetized with sodium pentobarbital (30 mg.kg-1 iv), and mechanically ventilated with 100% oxygen to maintain normocapnia. End tidal CO2 fraction (FECO2) was monitored continuously by capnograph. Regional myocardial tissue PO2 was measured using a monopolar polarographic needle electrode. Two pairs of combined needle sensors were carefully inserted, one in the epicardial and the other in the endocardial layer of the beating heart. Electromagnetic blood flow probe was applied on the left anterior descending artery (LAD). After a stable normocapnic ventilation, hypocapnia was induced by increasing the respiratory rate, and this mechanical hyperventilation was kept fixed throughout the experiments. To induce hypercapnia, exogenous carbon dioxide was added to the inspired gas step-wise until FECO2 reached 10%. 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.
Department of Anesthesiology, Yokohama City University School of Medicine.
Carbon dioxide (CO2) has been well documented to act as a potent vasodilator of coronary vessels under normal conditions. But there is little data available on the effect of CO2 on the collateral perfusion of patients with coronary insufficiency. We studied the effects of CO2 on the myocardial tissue PO2 in anesthetized dogs with critical coronary stenosis. Twelve mongrel dogs were anesthetized with pentobarbital and ventilated with 100% O2 to maintain normocapnia. Electromagnetic blood flow (BF) probe was applied on the left anterior descending artery (LAD). Regional myocardial PO2 was measured at two different sites using two pairs of monopolar polarographic needle electrodes; one inserted in the epicardial (EPI) layer, and the other in the endocardial (ENDO) layer. These were placed in the regions supplied by LAD and circumflex. Following the baseline recording, critical stenosis of LAD was produced by adjusting a copper-wire clamp occluder until LADBF was reduced by 50%. After a stable normocapnic ventilation, hypocapnia was produced by hyperventilation. To induce hypercapnia, exogenous CO2 was added to the inspired gas stepwise until end-tidal CO2 fraction reached 10%. Hypocapnia resulted in a significant reduction in myocardial PO2 in both EPI and ENDO non-stenotic areas, while hypercapnia increased these PO2 values dose-dependently. After coronary stenosis, hypocapnia resulted in a small but significant reduction of PO2 in endocardial ischemic area. Hypercapnia did not induce any sign of reduced regional myocardial PO2 or evidence of regional or intramural "steal" phenomenon. (ABSTRACT TRUNCATED AT 250 WORDS)
Wexels JC, Myhre ES, Mjøs 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.
The relative importance of pCO2 versus pH in regulating myocardial blood-flow (MBF)
is not settled. Therefore, the influence of hypocapnia, hypercapnia and sodium
carbonate infusion, on MBF and myocardial metabolism, has been investigated in
10 closed-chest pentobarbital anaesthetized dogs. The animals were
hyperventilated, and CO2 was added to the inspiratory gas to induce normocapnia
and hypercapnia. A mass spectrograph continuously measured the ventilatory gas
components, and MBF was measured by the hydrogen desaturation technique with a
catheter positioned in the coronary sinus. During the experiments, there were no
significant alterations in heart rate, mean aortic blood-pressure, myocardial
oxygen consumption or uptake of glucose and free fatty acids. During hypocapnia
MBF was insignificantly reduced, while myocardial oxygen extraction increased
significantly. During hypercapnia, however, MBF (myocardial blood-flow) increased more than 40%.
Brain Res. 2009 Dec 22; 1304: 90-5.
Carbogen inhalation increases oxygen transport to hypoperfused brain tissue in
patients with occlusive carotid artery disease: increased oxygen transport to
hypoperfused brain.
Ashkanian M, Gjedde A, Mouridsen K, Vafaee M, Hansen KV, Ostergaard L, Andersen
G.
Center of Functionally Integrative Neuroscience (CFIN), Aarhus University
Hospital, Norrebrogade 44, Bygn. 30, 8000 Aarhus C, Denmark. mahmoud@pet.auh.dk
Hyperoxic therapy for cerebral ischemia reduces cerebral blood flow (CBF)
principally from the vasoconstrictive effect of oxygen on cerebral arterioles.
Based on a recent study in normal volunteers, we now claim that the vasodilatory
effect of carbon dioxide predominates when 5% CO(2) is added to inhaled oxygen
(the mixture known as carbogen). In the present study, we measured CBF by
positron emission tomography (PET) during inhalation of test gases (O(2),
carbogen, and atmospheric air) in healthy volunteers (n = 10) and in patients
with occlusive carotid artery disease (n = 6). Statistical comparisons by an
additive ANOVA model showed that carbogen significantly increased CBF by 7.51 +
or - 1.62 ml/100 g/min while oxygen tended to reduce it by -3.22 + or - 1.62
ml/100 g/min. A separate analysis of the hemisphere contralateral to the
hypoperfused hemisphere showed that carbogen significantly increased CBF by 8.90
+ or - 2.81 ml/100 g/min whereas oxygen inhalation produced no reliable change
in CBF (-1.15 + or - 2.81 ml/100 g/min). In both patients and controls, carbogen
was as efficient as oxygen in increasing Sa(O2) or PaO(2) values. The study
demonstrates that concomitant increases of CBF and Sa(O2) are readily obtained
with carbogen, while oxygen increases only Sa(O2). Thus, carbogen improves
oxygen transport to brain tissue more efficiently than oxygen alone. Further
studies with more subjects are, however, needed to investigate the applicability
of carbogen for long-term inhalation and to assess its therapeutic benefits in
acute stroke patients.
Neuroscience. 2008 Oct 28;156(4):932-8. Epub 2008 Aug 22.
Improvement of brain tissue oxygenation by inhalation of carbogen.
Ashkanian M, Borghammer P, Gjedde A, Ostergaard L, Vafaee M.
Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus
University Hospital, Aarhus C, Denmark. mahmoud@pet.auh.dk
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). Therefore, we used positron emission tomography
(PET) to measure CBF and cerebral metabolic rate of oxygen (CMRO(2)) during
inhalation of test gases (O(2), CO(2), carbogen and atmospheric air) in 10
healthy volunteers. Arterial blood gases were recorded during administration of
each gas. The data were analyzed with volume-of-interest and voxel-based
statistical methods. Inhalation of CO(2) or carbogen significantly increased
global CBF, whereas pure oxygen decreased global CBF. The CMRO(2) generally
remained unchanged, except in white matter during oxygen inhalation relative to
condition of atmospheric air inhalation. The volume-of-interest results were
confirmed by statistical cluster analysis. 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).
Hear Res. 1991 Oct;55(2):255-62.
The effect of CO2- and O2-gas mixtures on laser Doppler measured cochlear and
skin blood flow in guinea pigs.
Kallinen J, Didier A, Miller JM, Nuttall A, Grénman R.
University Central Hospital Department of Otolaryngology, Turku, Finland.
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. BP was elevated with each gas. In freely
breathing animals, only 10% CO2-in-air caused a small increase in CBF; both
carbogen and O2 caused CBF to decrease. SPF changes were similar in form, but
larger than those seen in respirated subjects. No consistent change in BP was
seen during breathing of these mixtures. Arterial PO2 was increased by carbogen
and 10% CO2-in-air for both groups. PCO2 increased for both CO2 gas mixtures
during forced respiration; but in free-breathing animals PCO2 only increased for
10% CO2-in-air (normal PCO2 values were maintained with carbogen thorough
increased breathing rate). The observed changes in CBF were consistent with a
balance between a combined vasoconstrictive effect of PO2 and vasodilation
effect of PCO2 on cochlear vessels. Analysis of cochlear vascular conductivity (CBF/BP)
indicated that vasodilation was significant only with 10% CO2-in-air in
respirated animals. In all other conditions the increased CBF apparently
reflects the increase profusion pressure associated with respiration of each
gas. For clinical purposes, while carbogen does not appear to directly cause
vasodilation of cochlear vessels it does lead to an increased oxygenation of the
cochlea blood and would appear to avoid the cochlear vasoconstriction caused by
100% O2.
Acta Otolaryngol. 1985 Sep-Oct;100(3-4):218-28.
Reduction of acoustically induced auditory impairment by inhalation of carbogen
gas. II. Temporary pure-tone induced depression of cochlear action potentials.
Brown JJ, Meikle MB, Lee CA.
Guinea pigs were exposed to a 4.5 kHz pure-tone at 104 dB for 10 min during
artificial ventilation with either carbogen gas (95% O2/5% CO2) or normal air.
Mean N1 response amplitudes to tone bursts at 32 test frequencies extending from
2.1 kHz through 30 kHz were measured at standardized intervals before and after
the acoustic overstimulation. All animals received normal air during recovery.
Significant reduction of N1 response amplitude depression within a 3/8 to 1
octave frequency domain above the exposure frequency was found in the group
which received the carbogen gas. Those frequencies found to be maximally
depressed and the relative rate of recovery from the acoustic overstimulation
were not affected by carbogen inhalation. The invariance of the "half-octave
shift" following pure-tone acoustic overload was confirmed. Arterial blood gas
analysis of guinea pigs respiring carbogen revealed a marked rise in PO2 and
PCO2. Carbon dioxide is a potent stimulator of cerebral and cochlear
vasodilatation. Sound-induced vasoconstrictive ischemia has been implicated
in noise-induced cochlear pathology. The beneficial effects of elevated arterial
PCO2 are suggested to have been mediated by reduction of acoustically induced
vascular insufficiency within the inner ear.
Microvasc Res. 2008 Mar;75(2):263-8. Epub 2007 Aug 28.
Concentration-dependent vasoconstrictive effect of hyperoxia on hypercarbia-dilated
retinal arterioles.
Kisilevsky M, Hudson C, Mardimae A, Wong T, Fisher J.
Department of Ophthalmology and Vision Science, University of Toronto, Toronto,
ON, Canada.
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). At maximal hyperoxia (group mean PETO(2) of 556 mm
Hg) vessel diameter, blood velocity and flow were reduced by 9%, 22% and 36%,
respectively, relative to baseline (p<0.001). CONCLUSION: The
concentration-dependent vasoconstrictive effect of oxygen in retinal arterioles
was quantified for the first time by implementing precise control of end-tidal
concentrations of CO(2) and O(2). Oxygen-induced vasoconstriction is
sufficiently potent to offset and reverse hypercarbia-induced vasodilation.
J Neurosurg. 1975 Dec;43(6):689-705.
Central cholinergic control of cerebral blood flow in the baboon. Effect of
cholinesterase inhibition with neostigmine on autoregulation and CO2
responsiveness.
Aoyagi M, Meyer JS, Deshmukh VD, Ott EO, Tagashira Y, Kawamura Y, Matsuda M,
Achari AN, Chee AN.
Cerebral autoregulation and vastomotor responsiveness to carbon dioxide (CO2)
were measured quantitatively by the use of the autoregulation index and chemical
index, respectively, in normal baboons before and after intravertebral and
intracarotid infusion of the anticholinesterase agent, neostigmine methylsufate
(Prostigmin). Continuous measurements were made of cerebral blood flow (measured
as bilateral internal jugular venous outflow), arterial and cerebral venous pO2
and pCO2, cerebral arteriovenous oxygen differences, and endotracheal CO2. The
effect of intravertebral infusion of neostigmine (12.5 mug/kg body weight) was
compared to intravertebral infusion of neostigmine (25 mug/kg body weight) for
assessment of any specific action of the drug on a hypothetical cholinergic
vasomotor center, presumed to be located in the territory of the vertebrobasilar
supply. No significant or persistent changes in cerebral blood flow (CBF) and
cerebral metabolic rate for oxygen (CMRO2) followed either intravertebral or
intracarotid infusion of neostigmine. Cerebral vascular resistance (CVR) and
cerebral perfusion pressure (CPP), however, decreased significantly after
intravertebral infusion. Cerebral autoregulatory vasoconstriction during
increases of CCP was significantly reduced following both intravertebral and
intracarotid infusion. Cerebral autoregulatory vasodilatation was not altered as
CPP was lowered. Cerebral vasodilatory reactivity to CO2 inhalation was
significantly enhanced following intravertebral neostigime but not following
intracarotid neostigmine. Cerebral vasoconstrictive response to
hyperventilation was not influenced by neostigmine. These results support
the view that central cholinergic cerebrovascular influences exist, and are
vasodilatory in nature.
Retrobulbar haemodynamics and contrast sensitivity improvements after CO2
breathing.
Huber KK, Adams H, Remky A, Arend KO.
Department of Ophthalmology, Rheinisch Westfaelische Technische Hochschule
Aachen University, Germany. khuber@ukaachen.de
PURPOSE: Effects of gas mixtures have been widely studied. Carbon dioxide
(CO(2)) is known to act as a vasodilator, whereas oxygen (O(2)) acts as a
vasoconstrictor. Therefore, the interpretation of results is difficult. In this
study, only the effect of an elevated CO(2) level on retrobulbar hemodynamics
and contrast sensitivity was investigated. METHODS: Thirty adults (age 31 +/- 7)
were examined under normocapnic and hypercapnic conditions. Colour Doppler
imaging was used to measure the velocity in the ophthalmic and central retinal
artery. Moreover, contrast sensitivity using the CSV-1000 was investigated.
Blood pressure, heart rate and intraocular pressure (IOP) were measured and
ocular perfusion was calculated. RESULTS: Under hypercapnia, mean end tidal
CO(2) increased from 36.4 mmHg to 42.5 mmHg and blood oxygen saturation
increased from 98.3% to 98.6% (p < 0.0001). Hypercapnia significantly reduced
IOP by 0.94 mmHg (p < 0.0008). In the central retinal artery, the mean PSV
increased by 18% (p < 0.0001) and the mean EDV by 21% (p = 0.0054). In the
ophthalmic artery, the mean PSV increased by 13% (p < 0.0001) and the mean EDV
by 26% (p = 0.0002). Furthermore, there was a significant increase of contrast
sensitivity (spatial frequency: 3cpd: p = 0.0016; 6cpd: p = 0.005; 12cpd: p =
0.0012). Systolic blood pressure (p = 0.0225), mean arterial blood pressure (p =
0.0097) and ocular perfusion pressure (p = 0.0013) increased significantly.
CONCLUSION: This setting was able to detect an increase in blood flow
velocity in normal subjects under hypercapnia. Furthermore, hypercapnia results
in a functional improvement in contrast sensitivity, possible due to the
increased blood flow or the increase in blood oxygen levels.
J Endovasc Ther. 2004 Dec;11 Suppl 2: II140-50.
Development of vascular biology over the past 10 years: heme oxygenase-1 in
cardiovascular homeostasis.
Ohta K, Yachie A.
Department of Pediatrics, Angiogenesis, and Vascular Development, Graduate
School of Medical Science, Kanazawa, Japan. ohta_kunio@ped.m.kanazawa-u.ac.jp
The study of vascular biology has provided strong evidence for the role that
free radical attack plays in the pathogenesis of cardiovascular diseases. The
endothelial cell (EC) dysfunction that results from exposure to oxidative
stresses, such as oxidized LDL, influences vascular cell gene expression,
promoting smooth muscle cell (SMC) mitogenesis and apoptosis. These factors also
play an important role in atherogenesis, which is attenuated by antioxidants.
Thus, antioxidants are important to understanding the pathophysiology of
cardiovascular diseases and to constructing an effective treatment strategy for
these patients. Over the last decade, there has been a tremendous interest in
the biology of heme oxygenase-1 (HO-1), which exhibits antioxidant effects in
various forms of tissue injury. 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. Thus, HO-1-derived
products provide various mechanisms to maintain cardiovascular homeostasis. We
review recent work on the cellular and molecular biological aspects of the HO/CO
system in vascular pathophysiology.
J Thorac Cardiovasc Surg. 2004 Sep;128(3):354-6.
Effect of carbon dioxide insufflation on free internal thoracic artery flows: is
it a vasodilator?
Ozkan M, Koramaz I, Ulus AT, Tavil Y, Filizlioglu H, Baykan EC, Eryilmaz S, Inan
B, Katircioglu SF, Ozyurda U.
Department of Cardiovascular Surgery, Ozel Karadeniz Hospital, Trabzon, Turkey.
BACKGROUND: This study was conceived to evaluate the effect of carbon dioxide
insufflation on free internal thoracic artery flows. METHODS: We studied 56
consecutive patients who underwent coronary artery bypass grafting in which the
left internal thoracic artery was anastomosed to the left anterior descending
artery. The first 26 consecutive internal thoracic arteries were harvested as a
pedicled graft (group 1), and the next 30 consecutive internal thoracic arteries
were dissected by using the carbon dioxide insufflation technique (group 2). The
internal thoracic artery harvesting was performed by 2 experienced surgeons by
using the same instrumentation and technique. First, free flows of the internal
thoracic arteries were registered after distal cutting of the vessel in both
groups. After the first measurements, diluted papaverine was sprayed on the
internal thoracic artery pedicle only in group 1, and then second measurements
were registered after 15 minutes in both groups. Hemodynamic parameters were
recorded with each measurement. RESULTS: The first free flow measurement was
significantly higher in the carbon dioxide-insufflated internal thoracic
arteries (group 2, 60 +/- 32 mL/min; group 1, 28 +/- 19 mL/min; P <.05).
Although the second free flow measurement of the carbon dioxide-insufflated
group was higher than in group 1, the difference was not statistically
significant (68 +/- 46 mL/min vs 53 +/- 32 mL/min; P =.53). 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.
Neuroimage. 2004 Apr;21(4):1652-64.
Resting fluctuations in arterial carbon dioxide induce significant low frequency
variations in BOLD signal.
Wise RG, Ide K, Poulin MJ, Tracey I.
Centre for Functional Magnetic Resonance Imaging of the Brain, Department of
Clinical Neurology, John Radcliffe Hospital, University of Oxford, Oxford, UK.
wise@fmrib.ox.ac.uk
Carbon dioxide is a potent cerebral vasodilator. We have identified a
significant source of low-frequency variation in blood oxygen level-dependent
(BOLD) magnetic resonance imaging (MRI) signal at 3 T arising from spontaneous
fluctuations in arterial carbon dioxide level in volunteers at rest.
Fluctuations in the partial pressure of end-tidal carbon dioxide (Pet(CO(2))) of
+/-1.1 mm Hg in the frequency range 0-0.05 Hz were observed in a cohort of nine
volunteers. Correlating with these fluctuations were significant generalized
grey and white matter BOLD signal fluctuations. We observed a mean (+/-standard
error) regression coefficient across the group of 0.110 +/- 0.033% BOLD signal
change per mm Hg CO(2) for grey matter and 0.049 +/- 0.022% per mm Hg in white
matter. Pet(CO(2))-related BOLD signal fluctuations showed regional differences
across the grey matter, suggesting variability of the responsiveness to carbon
dioxide at rest. Functional magnetic resonance imaging (fMRI) results were
corroborated by transcranial Doppler (TCD) ultrasound measurements of the middle
cerebral artery (MCA) blood velocity in a cohort of four volunteers. Significant
Pet(CO(2))-correlated fluctuations in MCA blood velocity were observed with a
lag of 6.3 +/- 1.2 s (mean +/- standard error) with respect to Pet(CO(2))
changes. This haemodynamic lag was adopted in the analysis of the BOLD signal.
Doppler ultrasound suggests that a component of low-frequency BOLD signal
fluctuations is mediated by CO(2)-induced changes in cerebral blood flow (CBF).
These fluctuations are a source of physiological noise and a potentially
important confounding factor in fMRI paradigms that modify breathing. However,
they can also be used for mapping regional vascular responsiveness to CO(2).
Anesthesiology. 2003 Dec;99(6):1333-9.
Mild hypercapnia induces vasodilation via adenosine triphosphate-sensitive K+
channels in parenchymal microvessels of the rat cerebral cortex.
Nakahata K, Kinoshita H, Hirano Y, Kimoto Y, Iranami H, Hatano Y.
Department of Anesthesia, Japanese Red Cross Society, Wakayama Medical Center,
Japan.
BACKGROUND: Carbon dioxide is an important vasodilator of cerebral blood
vessels. Cerebral vasodilation mediated by adenosine triphosphate
(ATP)-sensitive K+ channels has not been demonstrated in precapillary
microvessel levels. Therefore, the current study was designed to examine whether
ATP-sensitive K+ channels play a role in vasodilation induced by mild
hypercapnia in precapillary arterioles of the rat cerebral cortex. METHODS:
Brain slices from rat cerebral cortex were prepared and superfused with
artificial cerebrospinal fluid, including normal (Pco2 = 40 mmHg; pH = 7.4),
hypercapnic (Pco2 = 50 mmHg; pH = 7.3), and hypercapnic normal pH (Pco2 = 50
mmHg; pH = 7.4) solutions. The ID of a cerebral parenchymal arteriole (5-9.5
microm) was monitored using computerized videomicroscopy. RESULTS: During
contraction to prostaglandin F2alpha (5 x 10(-7) m), hypercapnia, but not
hypercapnia under normal pH, induced marked vasodilation, which was completely
abolished by the selective ATP-sensitive K+ channel antagonist glibenclamide (5
x 10(-6) m). However, the selective Ca2+-dependent K+ channel antagonist
iberiotoxin (10(-7) m) as well as the nitric oxide synthase inhibitor
NG-nitro-L-arginine methyl ester (10(-4) m) did not alter vasodilation. A
selective ATP-sensitive K+ channel opener, levcromakalim (3 x 10(-8) to 3 x
10(-7) m), induced vasodilation, whereas this vasodilation was abolished by
glibenclamide. CONCLUSION: These results suggest that in parenchymal
microvessels of the rat cerebral cortex, decreased pH corresponding with
hypercapnia, but not hypercapnia itself, contributes to cerebral vasodilation
produced by carbon dioxide and that ATP-sensitive K+ channels play a major role
in vasodilator responses produced by mild hypercapnia.
Keio J Med. 2002 Mar;51(1):1-10.
From O2 to H2S: a landscape view of gas biology.
Kashiba M, Kajimura M, Goda N, Suematsu M.
Department of Biochemistry and Integrative Medical Biology, School of Medicine,
Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. kashiba@sc.itc.keio.ac.jp
The majority of molecular oxygen (O2) consumed in the body is used as a
substrate of cytochrome c oxidase to maintain oxidative phosphorylation for ATP
synthesis. Rest of the O2 is used for oxidative biosynthesis including synthesis
of vasoactive substances such as prostaglandins and secondary gaseous mediators
such as nitric oxide (NO) and carbon monoxide (CO). Thus, O2 is not only used
for maintenance of energy supply but also for regulating blood supply into
tissues. Nitrous oxide (N2O), laughing gas for anesthesia, is generated
endogenously through NO reductase in bacteria and fungi, and has recently been
shown to modulate N-methyl-D-aspartic acid (NMDA) receptor function. A number of
other biologically active gases could participate in regulation of cell and
tissue functions. Carbon dioxide (CO2) is generated mainly through the Krebs
cycle as a result of glucose oxidation and serves as a potent vasodilator,
and hydrogen sulfide (H2S) synthesized through degradation of cysteine has
recently been postulated to be a neuromodulator, although their receptor
proteins for signaling have not been verified as a discernible molecular entity.
Easy penetration allow these gases to access the inner space of receptor
proteins and to execute their biological actions. These gases are generated and
consumed in anaerobic bacteria through varied reactions distinct from those in
mammals. This review summarizes recent information on mechanisms for gas
generation and reception in biological systems.
Neuroradiology. 1998 Jul;40(7):466-8.
Enhanced catheter propagation with hypercapnia during superselective cerebral
catherisation.
Djurberg HG, Tjan GT, Al Moutaery KR.
Department of Anaesthesia, Armed Forces Hospital, Riyadh, Saudi Arabia.
During arterial catherisation of a cerebral arteriovenous malformation it may be
difficult or impossible to access the nidus of the malformation through its
small, tortuous feeding vessels due to microcatheter impaction. 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.
Nippon Ganka Gakkai Zasshi. 1998 Feb;102(2):130-4.
[The effect of carbon dioxide on intraorbital hemodynamics in glaucoma
determined by color Doppler imaging]
[Article in Japanese]
Niwa Y, Yamamoto T, Matsubara M, Takahashi D, Kitazawa Y.
Department of Ophthalmology, Gifu University School of Medicine, Japan.
We developed a new system to safely supply carbon dioxide (CO2) to man to
investigate the effect of the gas vasodilator on orbital blood flow in open
angle glaucoma (OAG) patients. Using the system, we determined orbital
hemodynamics in OAG by color Doppler imaging (CDI) at baseline conditions and
during CO2 supplementation sufficient to increase end-tidal CO2% by 10%. Seven
OAG patients (mean age, 60.9 +/- 16.4 years; normal-tension glaucoma/primary
open-angle glaucoma = 5/2) were included in the study. CDI was performed to
measure resistance index (RI), and peak-systolic and end-diastolic blood flow
velocities (PSV & EDV) of the ophthalmic artery (OA) and the central retinal
artery (CRA). Systemic conditions including oxygen saturation and blood pressure
were monitored throughout the period of the CO2 inhalation. CO2 significantly
increased PSV and EDV in the CRA (p = 0.0273, p = 0.0094, respectively; Wilcoxon
signed-rank test), but not in the OA. Other parameters were not altered. The
results suggest that CO2 inhalation increases blood flow velocities in distal
arteries in OAG patients without affecting proximal vessels. The new system
enables us to supply CO2 in a safe and controlled manner in glaucoma patients
and to modify orbital hemodynamics.