Avian cerebral blood flow: influence of the Bohr effect on oxygen supply.

To clarify the problems of altitude tolerance in birds, we studied the combined effect of hypocapnia and hypoxia on cerebral blood flow (CBF) in ducks. CBF was measured by the xenon clearance method. Normocapnic hypoxia causes CBF to increase when the arterial O2 tension (PaO2) falls below 60--70 mmHg. Hypocapnic hypoxia significantly shifts the blood flow curve so that blood flow does not increase until a lower PaO2 (50--60 mmHg) is reached. This gives the appearance that hypocapnia suppresses the hypoxia-induced increase in CBF. However, due to the Bohr effect, the hypocapnic blood contains significantly more O2 than does the normocapnic blood at the same PaO2. Therefore, when CBF is expressed as a function of O2 content, rather than PO2, CBF in the hypocapnic group does not differ significantly from the CBF in the normocapnic group. We interpret this to mean that because of the significantly greater oxygen content of the hypocapnic blood at a given PaO2, the degree of hypoxia experienced by these brains is not as severe as that experienced by the normocapnic brains.     

The relationship between arterial po2 and cerebral blood flow in hypoxic hypoxia.

The relationship between arterial oxygen tension (PaO2) and cerebral blood flow (CBF) in hypoxic hypoxia was studied in artificially ventilated and normocapnic rats. Changes in CBF were evaluated from arteriovenous differences in oxygen content after 2, 5, 15 and 30 min exposure to PaO2 85, 75, 55, 45, 35, and 25 mm Hg. In separate experiments the PaO2 was decreased to 25 mm Hg for 1, 2, 5, 15 and 30 min in animals in which PaCO2 was allowed to fall by 5-10 mm Hg. There was a small, gradual increase in CBF when PaO2 was lowered in steps from 130 to 55 mm Hg, and a more pronounced increase at PO2 values below 50 mm Hg. At PaO2 25 mm Hg CBF increased to values of 500% of normal. Significant increased in CBF were recorded at PaO2 values of 85 and 75 mm Hg in spite of the fact that previous studies have failed to record an elevated tissue lactate content at these po2 levels, and in spite of an unchanged cerebral venous PO2. When the PaO2 was reduced to 25 mm Hg CBF increased markedly already at 1 and 2 min, and this increase in CBF occurred even if PaCO2 was allowed to fall by 5-10 mm Hg. Previous results have shown that in such short periods enough lactic acid is not formed to induce a net tissue acidosis. The results thus give no support to the hypothesis that cerebral hyperemia in hypoxia is coupled to accumulation of lactic acid in the tissue.     

The influence of acute normovolemic anemia on cerebral blood flow and oxygen consumption of anesthetized rats.

The influence of acute normovolemic anemia on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRo2) was studied in normocapnic rats under nitrous oxide anaesthesia. The arterial hemoglobin content was reduced to values of about 12, 9, 6 and 3 g.(100 ml)(-1) by arterial bleeding and substitution with equal volumes of homolgous plasma. The CBF increased in proportion to the reduction in hemoglobin content to reach values of 500-600 per cent of normal at extreme degrees of anemia, but CMR02 remained unchanged. Cerebral venous PO2 and oxygen saturation did not decrease below normal values, indicating that tissue hypoxia did not develop. However, since the increase in CBF at hemoglobin concentrations of below 9 g(100 ml)(-1) was far in excess of that expected from the decrease in viscosity the results indicate thatdilatation of cerebral resistance vessels occurred. This dilatation, which was obviously related to the fall in arterial oxygen content, cannot be explained by any of the current theories proposed to explain cerebral hyperemia in hypoxia.     

Intestinal O2 consumption and 86Rb extraction during arterial hypoxia

Earlier reports indicated that arterial hypoxia not only dilated intestinal resistance vessels but also increased capillary filtration coefficients. The latter finding was interpreted as reflecting an increased number of perfused capillaries. Because both increased blood flow and increased capillary density would tend to maintain tissue oxygenation in spite of arterial hypoxia, the main purpose of this paper was to determine how effectively intestinal O2 utilization is maintained during arterial hypoxia. Therefore, I perfused isolated loops of canine small bowel at constant arterial pressure. Under this condition, reducing arterial PO2 to a mean value of 46 +/- 2.4 mmHg caused blood flow to increase to 146% of control, and O2 consumption was kept within 26% of control. In gut loops perfused at constant blood flow, arterial hypoxia depressed O2 uptake still further, but measurements of 86Rb extraction confirmed that the density of the perfused capillary bed increased. Thus, the responses of both resistance and exchange vessels tend to maintain O2 delivery to intestinal tissue during arterial hypoxia.     

Baseline physiological state and the fMRI-BOLD signal response to apnea in anesthetized rats

To decipher the biophysical mechanism behind the fMRI-BOLD response to apnea and its dependence on the baseline cerebral blood flow and oxygenation, fMRI and laser Doppler flow (LDF) studies were carried out in anesthetized rats. Baseline cerebral blood flow (CBF) and PaO2 were modulated by ventilating with different gas mixtures namely, room air (21% O2), 100% O2, carbogen (95% O2+5% CO2), 2% CO2 in air or 5% CO2 in air, respectively. A decrease in BOLD signal intensity was observed after the onset of apnea with either room air, 2% CO2 or 5% CO2 ventilation. PaO2 and cerebral tissue PO2 decreased during apnea under these conditions. However, the apnea-induced BOLD signal intensity was unaffected with carbogen ventilation and increased with 100% O2 ventilation, during which PaO2 remained constant and cerebral tissue PO2 increased. When baseline CBF was high during hypercapnia, a faster decrease occurred in the apnea-induced BOLD signal. Apnea induced the largest increase in CBF of 85 +/- 25% when ventilated with 2% CO2 while a 44 +/- 8% increase was observed with room air. During the other ventilatory conditions, minimal or no significant change in CBF was observed during apnea. These results show a significant correlation between the BOLD signal change and tissue PO2 in response to apnea under different physiological conditions. Apnea-induced increase in CBF affects the magnitude of the BOLD signal response when PaO2 remains constant or changes minimally.     

Liver Hemodynamics and Liver Function in Cats during Graded Hypoxic Hypoxemia

In 15 cats, anesthetized with chloralose and curarized, liver hernodynamics and liver function were followed during graded hypoxic hypoxemia. Hepatic arterial and intrahepatic portal venous conductance were not influenced by hypoxia, whereas severe hypoxemia increased gastrointestinal conductance. Total liver blood flow remained constant and hypoxemia was compensated for by an increase in hepatic extraction of oxygen approaching 100% Only when the hepatic venous PO₂ fell below 5–10 mmHg did hypoxemia decrease liver function. The results indicate that the sinusoidal perfusion is homogeneous.     

The Influence of Acute Normovolemic Anemia on Cerebral Blood Flow and Oxygen Consumption of Anesthetized Rats

The influence of acute normovolemic anemia on cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMR_O2) was studied in normocapnic rats under nitrous oxide anaesthesia. The arterial hemoglobin content was reduced to values of about 12, 9, 6 and 3 g.(100 ml)^-1 by arterial bleeding and substitution with equal volumes of homologous plasma. The CBF increased in proportion to the reduction in hemoglobin content to reach values of 500–600 per cent of normal at extreme degrees of anemia, but CMR_O2 remained unchanged. Cerebral venous P_O2 and oxygen saturation did not decrease below normal values, indicating that tissue hypoxia did not develop. However, since the increase in CBF at hemoglobin concentrations of below 9 g ^. (100 ml)^-1 was far in excess of that expected from the decrease in viscosity the results indicate that dilatation of cerebral resistance vessels occurred. This dilatation, which was obviously related to the fall in arterial oxygen content, cannot be explained by any of the current theories proposed to explain cerebral hyperemia in hypoxia.     

Brain metabolism and blood flow in acute cerebral hypoxia studied by NMR spectroscopy and hydrogen clearance.

We have developed a reliable, reproducible model of hypoxia in the gerbil. 1H and 31P NMR spectroscopy demonstrates that cerebral energy metabolism is very resistant to hypoxia. Cerebral blood flow (measured by hydrogen clearance) began to increase when the arterial oxygen tension (paO2) was reduced to 40-50 mm Hg, and there was no change in phosphorus metabolites or lactate until paO2 was below 40 mm Hg. In 50% of the animals lactate increased prior to any change in the phosphorus metabolites or intracellular pH, suggesting that 1H NMR may be more sensitive than 31P NMR at detecting hypoxic or ischaemic changes. The calculated rate of oxygen delivery at a time when phosphorus energy metabolism becomes impaired is similar in both hypoxia and ischaemia (ca 4mL/100 g/min). We suggest that the critical factor in ischaemia is the reduction in oxygen supply, rather than the accumulation of toxic metabolites, such as lactate.     

Modelling study of the acute cardiovascular response to hypocapnic hypoxia in healthy and anaemic subjects

The present study analyses the cardiovascular response to acute hypocapnic hypoxia (simulating the effect of respiration at high altitude) both in healthy, unacclimatised subjects and in subjects with moderate anaemia, by means of a mathematical model of short-term cardiovascular regulation. During severe hypoxia, cardiac output and heart rate (HR) exhibit a significant increase compared with the basal level (cardiac output: +90%; HR: +64%). Systemic arterial pressure remains quite constant or shows a mild increase. Coronary blood flow increases dramatically (+200%), thus maintaining a constant oxygen delivery to the heart. However, blood oxygen utilisation in the heart augments, to fulfil the increased power of the cardiac pump during hypoxia. Cerebral blood flow rises only at very severe hypoxia but, owing to the vasoconstrictory effect of hypocapnia, its increase (+80%) is insufficient to maintain oxygen delivery to the brain. The model suggests that a critical level for the aerobic metabolism in these organs (heart and brain) is reached at an oxygen partial pressure in arterial blood (PaO₂) of approximately 25 mmHg. Moderate anaemia during normoxia is compensated by an increase in cardiac output (+22%), a decrease in total peripheral resistance (−30%) and an increase in O₂ extraction from blood (+40%). As cardiovascular regulation mechanisms are already recruited in anaemic subjects at rest, their action soon becomes exhausted during hypocapnic hypoxia. Critical levels for vital functions are already reached at a PaO₂ of approximately 45 mmHg.     

Relationship between arterial and cisternal CSF oxygen tension in rabbits.

Oxygen tension was measured in samples of blood and cisternal cerebrospinal fluid taken from anesthetized, paralyzed, and mechanically ventilated rabbits at various levels of arterial PO2. Cerebrospinal fluid oxygen tension (CSF PO2) was correlated with arterial PO2 (linear regression equation PCSFO2 = 0.2472 Pao2 + 42.34). During hypoxia CSF PO2 was higher than arterial PO2 in most experiments. These data can be attributed to the Bohr effect, which would increase the PO2 of the blood in choroid plexus capillaries as a result of its acidification. The acidification was suggested by Maren (Am. J. Physiol. 222: 885-889, 1972) to be a part of the ionic exchanges involved in cerebrospinal fluid formation. Such a mechanism may be of importance for supporting choroid plexus metabolism and function during hypoxia. This mechanism is most clearly seen in the rabbit.     

Physiologic effects of normal-or low-oxygen-affinity red cells in hypoxic baboons.

Baboons were bled one-third their red cell mass and were given homologous transfusions of red blood cells to restore the red cell volume. One group of baboons received red blood cells with a normal 2,3-diphosphoglycerate 2,3-DPG) level and normal affinity for oxygen, and in this group the 2,3-DPG level after transfusion was normal. The other group received red blood cells with a 160% of normal 2,3-DPG level and decreased affinity for oxygen, and in this group the 2,3-DPG level after transfusion was 125% of normal. In both groups of baboons, the inspired oxygen concentration was lowered and arterial PO2 tension was maintained at 55-60 mmHg for 2 h after transfusion. During the hypoxic state, systemic oxygen extraction was similar in the two groups, whereas oxygen saturation was lower in the high 2,3-DPG group than in the control animals. Cardiac output was significantly reduced 30 min after the arterial PO2 was restored to normal. These data indicate that red blood cells with decreased affinity for oxygen maintained satisfactory oxygen delivery to tissue during hypoxia.     

Intravenous oxygenation with lactated Ringer's solution

This experimental work was performed on 4 rabbits to demonstrate that administrations of oxygenated Ringer's lactate through the central venous infusion could be used as a means of oxygenation. The oxygen tensions of Ringer's lactate were determined upon changing the amount of oxygen being bubbled and the solutions with the mean PO2 and pH of 575.5 mmHg and 6.34 were used in this study. We did not use the solutions having the values below 416.6 mmHg PO2 and pH 6.08. After the infusion of the oxygenated solution through central vein, PaO2 values throughout the 1 hour experimental procedure were significantly increased above the control value. Other parameters such as pH, PaCOs, HCO3-, BE, O2 saturation did not show any statistically significant changes. Some degree of oxygenation could be obtained by infusing the oxygenated Ringer's solution. This suggested that oxygenation by infusion through the central venous line could used clinically in the treatment of some forms of hypoxia with hypovolemia.     

Adrenal and pancreatic endocrine responses to hypoxia in the conscious calf.

1. Pancreatic and adrenal responses to intense hypoxia have been examined in conscious unrestrained calves 3-5 weeks after birth. 2. The outputs of both cortisol and corticosterone from the right adrenal gland rose steadily in response to hypoxia and this cortical secretory response was accompanied by a pronounced increase in blood flow through the gland. The changes in both steroid output and adrenal blood flow corresponded with those which occur in response to supramaximal doses of corticotrophin in calves of the same age. 3. Neither adrenaline nor noradrenaline were released in significant amounts from the adrenal medulla until the arterial PO2 had fallen below 15 mmHg. Such severe hypoxia caused secretion of catecholamines at rates comparable with those recorded during maximal stimulation of the sympathetic innervation to the gland in anaesthetized calves. The response to intense hypoxia in these conscious calves differed from that which occurs under anaesthesia in that the amount of adrenaline released was invariably greater than that of noradrenaline. 4. Severe hypoxia produced a rapid but transient increase in plasma glucagon concentration, followed by a pronounced rise in plasma glucose concentration in animals with abundant liver glycogen. No change in plasma insulin concentration was observed during hypoxia although it rose subsequently in response to hyperglycaemia. 5. Bilateral section of the splanchnic nerves virtually abolished the release of catecholamines in response to hypoxia but the adrenal cortical and pancreatic responses did not appear to be affected.     

Adenosine and cyclic AMP in cerebral cortex of rats in hypoxia, status epilepticus and hypercapnia.

The influence of hypercapnia, hypoxia and status epilepticus on cerebral cortex concentrations of adenosine, adenine nucleotides and cyclic AMP was studied on lightly anaesthetized (70% N2O) and artificially ventilated rats. Neither hypercapnia (arterial PCO2 about 80 and about 300 mmHg) nor hypoxia (minimal values of 19 mmHg) altered tissue concentrations of AMP, cyclic AMP or adenosine. Bicuculline-induced status epilepticus was accompanied by increased concentrations of cyclic AMP but adenosine concentration did not change. Experiments with ischemia, and those in which tissue hypoxia was exaggerated by unilateral carotid artery ligation, showed that tissue adenosine concentrations were elevated only when AMP concentration rose. It is concluded that the marked increase in cerebral blood flow which occurs in hypoxia and status epilepticus is unrelated to changes in tissue adenosine concentration and that the increase in cyclic AMP during neuronal hyperactivity is triggered by other mechanisms than adenosine accumulation.     

Effect of hypoxia on vascular responses to the carotid baroreflex.

The effect of systemic hypoxia on the vascular responses to the carotid baroreflex was studied in anesthetized, vagotomized, artificially ventilated dogs. One hindlimb, kidney, gracilis muscle, and paw were perfused at constant flow, and neurograms were obtained from renal sympathetic fibers. Bilateral carotid occlusions were performed while the animal was breathing a mixture of air and O2 (mean arterial PO2 = 106 mmHg) and again during ventilation with 10% O2 (PO2 = 40 mmHg). With occlusion, the average increase in mean aortic pressure was 36 mmHg greater during hypoxia than during normoxia and the increase in renal perfusion pressure was 87 mmHg greater; the increase in hindlimb perfusion pressure was identical in both situations. Hypoxia did not change the reflex response of the paw to carotid occlusion and increased that of the muscle vessels by only 10%; the increase in renal sympathetic activity averaged 56 plus or minus 10% more with hypoxia than with normoxia. When the carotid chemoreceptors were destroyed, the greater increase in aortic and renal pressure response to carotid occlusion during hypoxia as compared to normoxia was abolished. Thus systemic hypoxia markedly potentiates the reflex renal constriction caused by the baroreflex, and this effect is due to the carotid chemoreceptor afferent input.     

不同疾病状态下新生儿脑组织氧合变化的对照研究

目的采用近红外光谱测定技术（NIRS）检测新生儿脑组织氧饱和度（rSO2）,探讨不同疾病状态下新生儿脑rSO2的变化规律,为临床应用提供依据。方法2007年4月至2008年10月以无特殊疾病的223名足月儿作为正常组足月儿亚组,于生后3d内测定脑rSO2;以196例患有可能影响脑氧合疾病的新生儿作为疾病组,在疾病急性期测定脑rSO2。疾病组分为呼吸系统疾病亚组（97例）,分析脑rSO2与PaO2的关系;循环系统疾病亚组（44例）,分析脑rSO2与心率的关系;脑损伤亚组（55例）,分析脑rSO2与脑血流的关系。结果①疾病组脑rSO2为（56±6）%,显著低于正常组足月儿亚组（P〈0.05）。②轻度与重度呼吸系统疾病亚组脑rSO2分别为（60±3）%和（54±6）%,轻度和重度循环系统疾病亚组脑rSO2分别为（59±3）%和（53±6）%,轻度和重度脑损伤亚组脑rSO2分别为（59±3）%和（54±4）%。3个疾病亚组中轻度与重度间脑rSO2差异均有统计学意义（P〈0.01）。③呼吸系统疾病亚组脑rSO2与PaO2呈三次方程曲线（y=-62.93＋4.75x-0.059x2＋0.00024x3）。PaO2≥60mmHg时,脑rSO2约为62%,脑氧合正常;PaO2〈50mmHg时,脑rSO2〈57%,脑组织缺氧。循环系统疾病亚组脑rSO2与心率呈二次方程曲线（y=1.11＋0.8241x-0.0027x2）。心率在105～200.min-1时,脑rSO2〉58%,脑氧合正常;心率低于105.min-1或高于200.min-1时,脑rSO2〈58%,脑组织缺氧。脑损伤亚组脑rSO2〈58%时,大脑前动脉血流平均速度代偿性增高,阻力指数偏低,脑损伤较重。结论严重疾病状态下可同时伴有脑组织缺氧。脑rSO2的变化与PaO2、心率及脑血流的变化密切相关。NIRS技术为临床提供了一种可靠的、有价值的脑氧合检测方法,有助于临床直观量化地发现脑组织的缺氧。     

Effects of hypotension induced by adenosine on brain surface oxygen pressure and cortical cerebral blood flow in the pig

Six pigs were anaesthetized with ketamine in combination with fentanyl and droperidol and paralysed with pancuronium. The pigs were tracheotomized and ventilated mechanically. Mean arterial blood pressure, MABP, was lowered from 97 +/- 21 mmHg stepwise to 58 +/- 2, 33 +/- 4 and 22 +/- 4 mmHg by intravenous infusion of adenosine (4-8 mg kg-1 min-1). Regional cerebral blood flow (rCBF) was measured directly onto the cortex of the brain by local atraumatic application of 133xenon. Brain surface oxygen pressure (PtO2) was obtained using a multiwire oxygen surface electrode. At the level of 60 mmHg, rCBF showed a significant increase, while flow values were not changed from initial values with further hypotension. Ten minutes after adenosine was discontinued, rCBF showed a rebound effect with higher values than initially. During normotension mean cortical PtO2 varied between 2.1 KPa and 3.9 kPa. During adenosine infusion PtO2 was increased at MABP-levels of 60 and 30 mmHg, while at 20 mmHg a decrease was seen in all animals. After discontinuation of the adenosine infusion, PtO2 values were higher than those measured at the initial normotension, a similar rebound phenomenon as seen with rCBF. During the experiments all hypotensive levels could be maintained at constant level without progressively increasing infusion rates, indicating no tachyphylaxis during these time periods. After discontinuation of the drug, blood pressure did not fully reach pre-hypotensive level within 10 min. Thus, hypotension induced by adenosine down to a MABP of 30 mmHg in animal experiments does not cause deterioration in either cerebral blood flow or oxygen pressure.     

The effect of O2 and CO2 on the dive behavior and heart rate of lesser scaup ducks (Aythya affinis): quantification of the critical PaO2 that initiates a diving bradycardia

Lesser scaup ducks were trained to dive for short and long durations following exposure to various gas concentrations to determine the influence of oxygen (O2) and carbon dioxide (CO2) on diving behavior and heart rate. Compared with normoxia, hyperoxia (50% O2) significantly increased the duration of long dives, whereas severe hypoxia (9% O2) significantly decreased the duration of both short and long dives. Hypercapnia (5% CO2) had no effect on dive duration. Surface intervals were not significantly altered by the oxygen treatments, but significantly increased following CO2 exposure. Heart rate during diving was unaffected by hyperoxia and hypercapnia, but gradually declined in long dives after severe hypoxia. Thus, our results suggest that during the majority of dives, O2 and CO2 levels in lesser scaup ducks are managed through changes in diving behavior without any major cardiovascular adjustments, but below a threshold PaO2, a bradycardia is evoked to conserve the remaining oxygen for hypoxia sensitive tissues. A model of oxygen store utilization during voluntary diving was developed to estimate the critical PaO2 below which bradycardia is initiated (approximately 26 mmHg) and predicted that this critical PaO2 would be reached 19s into a dive after exposure to severe hypoxia, which corresponded exactly with the time of initiation of bradycardia in the severe hypoxia trials.     

Reference values for gas exchange during exercise in healthy nonsmoking and smoking men

The gas exchange at rest and during exercise was measured in 50 healthy men, 25 lifelong nonsmokers and 25 smokers, between 20 and 65 years of age. Arterial blood samples were taken and expired air was collected at rest, supine and sitting, and during graded exercise. Prediction formulas for various gas exchange variables were obtained by multiple regression. Optimal conditions for gas transfer were present at light exercise. The arterial oxygen tension (PaO2) remained approximately constant during exercise, although in individual smokers and nonsmokers it decreased by up to 1.8 kPa (13.5 mmHg) between a workload of 50 W and the maximal workload. The lower limit for PaO2 at maximal exercise was about 10.7 kPa (80 mmHg). The alveolo-arterial difference in oxygen tension (PA-aO2) increased considerably with increased workload, from 1.09 +/- 1.05 kPa at 50 W to 3.1 +/- 0.9 kPa at maximal exercise. Ageing and tobacco smoking were associated with a decrease in PaO2 and an increase in PA-aO2 at rest in the supine position, but at maximal exercise neither PaO2 nor PA-aO2 was significantly influenced by age or tobacco smoking. In contrast, the dead space and total ventilation were increased during exercise by ageing and tobacco smoking.     

ANP decreases arterial oxygen partial pressure by increasing shunt flow in pulmonary circulation.

This study was designed to clarify the decreased arterial oxygen partial pressure (PaO2) mechanism induced by atrial natriuretic peptide (ANP) infusion. In order to examine the effects of ANP on gas exchange across the normal lungs, ANP was infused to eight anesthetized dogs, ventilated with mixed gases of oxygen and nitrogen. PaO2 and venous oxygen partial pressure (PvO2), ventilation-perfusion ratio (VA/Q), shunt-total blood flow ratio (QS/QT) were measured before and during ANP infusion under ventilation with 10, 20, 30% oxygen. In this study ANP decreased PaO2 from 89.0 +/- 4.2 to 85.4 +/- 5.4 mmHg during 20% oxygen ventilation, and from 138.1 +/- 3.6 to 132.5 +/- 4.1 mmHg during 30% oxygen ventilation. ANP increased VA/Q and QS/QT. We conclude that the decrease in PaO2 caused by ANP infusion was mainly due to the increased venous admixture.