Intestinal capillary blood flow during metabolic hyperemia

It has been postulated that local circulatory control mechanisms regulate the O2 flux to parenchymal cells by two vascular mechanisms: changes in blood flow that minimize capillary PO2 variations and changes in the density of the perfused capillary bed through which O2 extraction is regulated. To test this prediction, isolated loops of canine jejenum and ileum were perfused at either constant blood flow or constant pressure, and intraluminal glucose was used to increase metabolic rate. In the constant-flow series, glucose increased O2 extraction, O2 uptake, and rubidium extraction. Resistance fell when the metabolic rate was elevated. In the constant-pressure series, glucose increased blood flow, O2 extraction, O2 uptake, and capillary filtration coefficients. These results show that vascular resistance falls and that capillary density increases following an increase in oxygen demand. Thus, the glucose-stimulated gut loop seems to be a valid model of metabolic hyperemia, and its behavior would be difficult to reconcile with a purely myogenic theory of intestinal blood flow autoregulation.     

Intestinal O2 uptake during sympathetic stimulation and partial arterial occlusion.

In isolated loops of canine small bowel perfused at constant blood flow, stimulating perivascular sympathetic nerves (8--10 Hz) depressed O2 extraction and O2 uptake. Because sympathetic stimulation also decreased 86Rb extraction, the results confirmed earlier studies indicating that sympathetic stimulation closes "precapillary sphincters" and through diffusion limitations reduces the capillary-to-cell flux of oxygen. To determine if sympathetic stimulation could lower O2 uptake under more physiologic circumstances, a second series of experiments was performed during constant arterial pressure perfusion. Sympathetic stimulation reduced blood flow by about 30% in the steady phase. Oxygen extraction did not increase appreciably, so O2 uptake was also reduced. When partial arterial occlusion was used to lower the blood flow to the level that it reached during sympathetic stimulation, large increases (37%) in O2 extraction occurred so that O2 uptake remained near control levels. The results indicate that after arterial occlusion local mechanisms maintain O2 uptake by increasing O2 extraction through capillary density increases, but that this mechanism is impaired by sympathetic stimulation.     

Effects of arterial hypoxia on the cutaneous circulation of the rabbit

1. Changes in blood flow of the skin of the rabbit's ear and hind limb have been studied during arterial hypoxia by a calibrated heat conductivity method, together with changes in arterial pressure and aortic blood temperature.

2. There is little change in the blood flow of the hind-limb skin during the early phase of arterial hypoxia, reflecting a balance between the local dilator effects of hypoxia and the increased constrictor activity mediated through the sympathetic nerves as a result of arterial chemoreceptor excitation. During more prolonged arterial hypoxia there is a small gradual dilatation of the vessels of the hind-limb skin as a result of some diminution in the initial intensity of vasoconstrictor activity.

3. There is much more extensive vasodilatation in the ear than in the hind-limb skin during arterial hypoxia. Vasoconstrictor activity is slight in this region. Comparison of the ear responses to arterial and to primary tissue hypoxia suggests that in the former type of hypoxia stimulation of the arterial chemoreceptors inhibits thermoregulatory vasoconstriction to the ear, whilst in the latter type of hypoxia baroreceptor reflexes maintain or intensify it.

     

The control of the circulation in skeletal muscle during arterial hypoxia in the rabbit

1. The effects of arterial hypoxia on muscle blood flow were examined in normal unanaesthetized rabbits in relation to simultaneously determined changes in cardiac output, arterial pressure and heart rate. Muscle blood flow was estimated from the difference between total limb flow (local thermodilution) and the estimated skin flow (using a calibrated heat conductivity method). The role of the arterial chemoreceptors and baro-receptors in the control of muscle blood flow was examined and the nature of the sympathetic efferent discharge analysed.2. In mild hypoxia (P(O2) > 35 mm Hg) in the rabbit, muscle blood flow did not change, although cardiac output increased. During moderate hypoxia (P(O2) 30-35 mm Hg) there was initial vasoconstriction in muscle, followed by a return to control values paralleling the changes in cardiac output. In severe arterial hypoxia (P(O2) < 30 mm Hg) the initial vasoconstriction was less marked, and during the ;steady state' there was a large vasodilatation and increase in muscle blood flow, at a time when the cardiac output was not elevated.3. The early vasoconstriction in arterial hypoxia is mediated mainly through sympathetic vasoconstrictor nerves as a result of strong arterial chemoreceptor stimulation.4. Increased secretion of adrenaline is an important factor in restoring muscle blood flow to control values during moderate arterial hypoxia, and in elevating the muscle blood flow above these values in severe hypoxia. The peripheral dilator (beta-) effects of adrenaline oppose the peripheral constrictor (alpha-) effects resulting from increased activation of sympathetic constrictor nerves during arterial hypoxia.     

An analysis of the reflex systemic vasodilator response elicited by lung inflation in the dog

1. A maintained inflation of the lungs caused a reflex reduction in total systemic vascular resistance in anaesthetized dogs under conditions in which the systemic circulation was perfused at constant blood flow and the arterial blood P(O2) and P(CO2) were maintained constant.2. The fall in systemic arterial perfusion pressure evoked by inflation of the lungs was accompanied by an increase in blood flow to the lower limbs and a reduction in their calculated vascular resistance. Since the fall in resistance occurred when the limb was perfused either at constant pressure or at constant blood flow, it must be due to vasodilatation.3. Lung inflation caused vasodilatation in skin, muscle, and in the splanchnic vascular bed. The responses in vertebral circulation were, however, small and variable.4. The vasodilator responses in the vascular territories studied were reflex in nature, being abolished by cutting the cervical vagosympathetic nerves, in which run the afferent fibres, or by interrupting the sympathetic pathways to the blood vessels.5. In the intact limb, muscle, skin and splanchnic vascular bed, the vasodilator responses to lung inflation were unaffected by atropine or propranolol, but were abolished by hexamethonium, dibenyline and bretylium tosylate, indicating that they were due predominantly to a reduction in the activity in sympathetic adrenergic vasoconstrictor fibres.     

Diminution of the hypoxic effect of conjugate functions in skeletal muscles under the action of gamma-oxybutyric acid

The resistive, capacitive, and exchange function of vessels in hypoxia (8% O2) was studied on cat shank muscles isolated in relation to hemodynamics. The perfusion pressure reduced by 28%, the pre- and postcapillary resistance by 32 and 35%, the capillary hydrostatic pressure by 12%. The venous flow increased by 0.13 ml/100 g, the capillary filtration coefficient by 58%. Infusion of sodium salt of gamma-oxybutyric acid (GOBA) (10 mg/min) into the region caused lesser changes of parameters while the venous flow increased by 0.63/100 g. Combination of hypoxia and infusion of the agent stabilized precapillary resistance, capillary hydrostatic pressure, and venous flow within ranges close to the initial background, while the capillary filtration coefficient increased by 25%. Changes of perfusion pressure and postcapillary resistance were similar to those recorded under conditions of control hypoxia. The mechanisms of the effect of GOBA sodium salt on conjugate functions of vessels of the skeletal muscles in hypoxia are discussed.     

The influence of the position of the oxygen dissociation curve on oxygen-dependent functions of the isolated perfused rat liver

The influence of a 2,3-diphosphoglycerate (2,3-DPG)-induced displacement of the oxygen dissociation curve (O.D.C.) on the isolated perfused rat liver was studied at different levels of anaemic hypoxia. Rat livers were perfused either with fresh or with 2,3-DPG-depleted human erythrocytes at different haematocrit values (from 30% to 2.5%) at constant Po2 of the inflowing perfusate and at constant blood flow rate. The 2,3-DPG-induced difference in oxygen affinity of the red cells did not cause a significant difference in perfusion pressure during the perfusion experiments. Therefore, there is no evidence that 2,3-DPG did alter the vascular resistance of the liver, since blood flow rate could be adusted at equal values. The decrease in oxygen supply brought about by decrease of haematocrit caused a decrease of O2 consumption, of bile flow rate and of venous Po2 and an increase of lactate/pyruvate (L/P) ratio and of beta-hydroxybutyrate/acetoacetate (betaOH/Acac) ratio. There was no influence of a difference in 2,3-DPG content of the erythrocytes on the above-metioned parameters during severe anaemic hypoxia. At moderate anaemic hypoxia the venous Po2 was higher during perfusion with fresh erythrocytes than during perfusion with 2,3-DPG-depleted erythrocytes. Thus, although 2,3-DPG may play a compensatory role during conditions of mild anaemia, no such effects can be observed during conditions of severe hypoxia.     

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.     

Effect of regional hypoxia and blood flow on capillary permeability in canine myocardium

The effect of hypoxia and blood flow on the capillary permeability-surface area product (PS) of ⁵¹Cr-EDTA was investigated in canine myocardium of open chest anesthetized dogs at constant aortic pressure, heart rate, and cardiac output. PS was determined by bolus injection of ⁵¹Cr-EDTA into the left anterior descending coronary artery (LAD) and external registration of the response curve. Vascular conductance (G) and PS were measured: (1) during pump perfusion of LAD with arterial blood (control state), and (2) during vasodilation obtained by LAD perfusion with deoxygenated blood at same blood flow as in control state, and (3) during increased blood flow with deoxygenated blood. Mean value of G in control state was 1.31 ml. min^-l. (100 g)^-1 (mmHg)^-1. The ratio G-hypoxialG-control used to assess the extent of vasodilation was 2.42 (range 1.67–3.56) during hypoxia and unchanged flow and 2.82 (range 1.81447) during hypoxia and increased flow. Mean value of PS in control state was 36 ml. (100 g)^-1. min^-1. With maximum vasodilation and constant blood flow PS increased to 47.3 ml.(100 g)-¹.min-¹ (37%) and during increased blood flow to 69.0 ml.(100 g)^-1. min^-1 (96%). The increase in PS most likely reflects an increase in capillary surface area available for exchange of ⁵¹Cr-EDTA indicating a 1.4– to 2-fold recruitment of capillaries.     

Effects of Low Tissue Temperature on Peripheral Vascular Control Mechanisms

Influence of low temperatures on vascular effects produced by adrenaline, noradrenaline and vasoconstrictor nerve stimulation was studied in the feet of ducks. Observations were made on isolated preparations as well as on intact ducks with one or both feet immersed in ice-water. Isolated preparations were perfused with physiological solution and information on changes in vascular resistance obtained by direct measurement of flow changes during perfusion at constant pressure or by measuring changes in perfusion pressure during perfusion at constant flow. In intact ducks changes in blood flow were recorded as changes in digital subcutaneous tissue temperature. The study revealed that in the duck foot a relatively large fraction of the resistance to blood flow is found in the arteries of the proximal part of the foot. During cooling of the foot the influence of vasoconstrictor nerve stimulation and low doses of adrenaline and noradrenaline on vascular resistance is gradually lost, and it is negligible at temperatures below 8°C. At these low temperatures the blood vessels stay dilated and blood flow through the web seems to be determined by the digital arterial blood pressure.     

Increased cardiovascular and metabolic tolerance to acute hypoxia in the rat with increased hemoglobin-O(2) affinity induced by Na-cyanate treatment.

Cyanate derivatives such as NaOCN have been known to increase the hypoxia tolerance of animals by increasing the affinity of hemoglobin (Hb) to O(2). To clarify the mechanism of this increase in hypoxia tolerance, we examined changes in metabolic rate and cardiovascular parameters during a hypoxia test in halothane-anesthetized, NaOCN-treated and spontaneously breathing rats (50 mg/kg/d S.C., 10 d). Control animals received saline. The capillary density in the skeletal muscle (sternocleidomastoid muscle), cardiac papillary muscle and medulla oblongata was also examined histologically. The Hb-O(2) affinity index, P(50), decreased from 38 (control rat) to 24 mmHg in NaOCN-treated rats. During hyperoxic gas breathing, the rat treated with NaOCN showed a significantly lower metabolic rate (V(.)O(2), V(.)CO(2)), higher cardiac stroke volume, slower heart rate, lower PvO(2), and lower O(2) extraction ratio than those in control rats. The NaOCN-treated rats exhibited well-maintained arterial blood pressure and a larger cardiac output response to reduction in FIO(2) to 0.10-0.08. The increase in O(2) extraction ratio with reduction in FIO(2) was larger in NaOCN-treated than in control rats. The circulatory and metabolic depressions at FIO(2) 0.05 were effectively attenuated in NaOCN-treated rats. The capillary density of the cardiac muscle and medulla oblongata but not the skeletal muscle was significantly higher in NaOCN-treated rats than in control rats. The greater hypoxia tolerance in NaOCN-treated rats is ascribed to the combined effects of left shift of Hb-O(2) dissociation curve, lower basal V(. )O(2), higher capillary density in the heart, and brain, and other adaptive mechanisms induced probably by prolonged tissue hypoxia.     

Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation.

Adenosine is a possible mediator of myocardial and skeletal muscle blood flow regulation. Whether adenosine plays a similar role in modulating the pulmonary pressor response to acute alveolar hypoxia is not known. Adenosine levels (nmol/g tissue) in lung in six dogs ventilated with 95% N2, and 5% CO2 for a period of 3 min increased nearly 10-fold. Inosine and hypoxanthine, adenosine enzymatic degradation products, sustained a 10- and 7-fold increase, respectively. These degradative products are mainly formed in the capillary endothelial cells that contain the degradative enzyme nucleoside phosphorylase as demonstrated by histochemical techniques. To determine the effect of ATP, ADP, AMP, and adenosine on the pulmonary circulation, the in situ left lower lobe of 10 dogs was perfused at either free flow or constant flow via its pulmonary artery. ATP and ADP increased lobar vascular resistance; AMP and adenosine decreased the resistance. During hypoxic ventilation, adenosine infusions (100 nmol/ml blood) entirely abolished the increase in vascular resistance that was due solely to hypoxia. Dipyridamole produced similar responses. These data indicate that adenosine is a pulmonary vasodilator and that it may modulate the pulmonary pressor response to acute alveolar hypoxia. The findings suggest that the use of adenosine or dipyridamole may be beneficial in patients with pathologic elevations of the pulmonary vascular resistance which are a result of an exaggerated pulmonary pressor response to hypoxia, as seen in high-altitude pulmonary edema or that following cerebral injury.     

Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction.

To delineate the mechanism through which vasoactive compounds alter intestinal oxygen consumption and to determine the pharmacological nature of the receptors involved, we quantitated the effects of vasoconstrictors on arteriovenous oxygen difference and on vascular resistance in isolated constant-flow perfused canine small bowel. Norepinephrine (NE) and sympathetic stimulation (SS) increased vascular resistance and depressed O2 extraction. These effects were not altered by beta-blockade, but were abolished by alpha-blockade. Since capillary filtration coefficients at constant-pressure perfusion and 86Rb extraction at constant flow are reported to diminish during NE and SS, it follows that these agents reduce O2 extraction by an alpha-adrenergic closure of precapillary sphincters. Vasopressin had similar effects which were not affected by adrenergic blocking agents. Epinephrine (Epi) in high doses or after propranolol produced the same effects as NE and SS. By contrast, Epi in low doses increased O2 and 86Rb extraction. This response to low doses of Epi was not affected by phentolamine, but was reversed by propranolol. We conclude that Epi in high doses or after propranolol depresses intestinal O2 extraction by the same mechanism as NE and SS, but the mechanism through which Epi increases intestinal O2 extraction is unclear.     

A compartmental model for oxygen transport in brain microcirculation

A compartmental model is formulated for oxygen transport in the cerebrovascular bed of the brain. The model considers the arteriolar, capillary and venular vessels. The vascular bed is represented as a series of compartments on the basis of blood vessel diameter. The formulation takes into account such parameters as hematocrit, vascular diameter, blood viscosity, blood flow, metabolic rate, the nonlinear oxygen dissociation curve, arterial PO₂, P₅₀ (oxygen tension at 50% hemoglobin saturation with O₂) and carbon monoxide concentration. The countercurrent diffusional exchange between paired arterioles and venules is incorporated into the model. The model predicts significant longitudinal PO₂ gradients in the precapillary vessels. However, gradients of hemoglobin saturation with oxygen remain fairly small. The longitudinal PO₂ gradients in the postcapillary vessels are found to be very small. The effect of the following variables on tissue PO₂ is studied: blood flow, PO₂ in the arterial blood, hematocrit, P₅₀, concentration of carbon monoxide, metabolic rate, arterial diameter, and the number of perfused capillaries. The qualitative features of PO₂ distrbution in the vascular network are not altered with moderate variation of these parameters. Finally, the various types of hypoxia, namely hypoxic, anemic and carbon monoxide hypoxia, are discussed in light of the above sensitivity analysis.     

Dilatory humoral adrenergic reactions of regional veins and arteries during systemic hypoxia and hypothermia

In experiments on anesthetized cats, perfusion of neurally decentralized vessels in the gastrocnemius muscle and small intestine with constant flow of autoblood containing isoproterenol induced dilator reactions in arteries and veins. Against the background of hypoxic hypoxia, the reactions of arteries and veins in the gastrocnemius muscles and veins in small intestine attenuated, although the arterial reactions in the latter region did not change. Total hypothermia (30°C) attenuated the dilator reactions in regional vessels. Under the combined action of hypoxia and hypothermia, the amplitudes of dilator reactions of muscle vessels and intestine veins were equal to the baseline values, although the responses of intestinal arteries were pronouncedly weakened. It is concluded that blood vessels in the gastrocnemius muscle and veins in the small intestine possess positive resistance to whole-body hypoxia and hypothermia.     

A model of dual circulation in liver acini with hypoxia regulated adenosine secretion

It was postulated by W.W. Lautt that the hepatic artery flow compensation for changes in portal vein flow (the 'hepatic arterial buffer response') is regulated through the portal blood washout of adenosine from the small fluid compartment that surrounds the hepatic arterial resistance vessels. It is presumed that the adenosine secretion there is constant and independent of oxygen supply or liver demand. It was reported by others that liver secretes variable quantities of adenosine and that secretion is related to the level of liver hypoxia. This paper is an attempt to describe a model of acinar circulation without sources of constant adenosine secretion. The presented model is based on the fact that portal blood enters acinar space near the vascular stalk in the zone 1, while most of the arterial branches empty one-third from the interlobular septa, at the beginning of the zone 2, just downstream from the zone 1. Another important characteristic of liver architecture is that near 5/9 of lobular volume is in the zone 1. Liver cells in zone 1 are well oxygenated by the portal blood and they have low adenosine secretion that might seem almost constant. Since most arterial branches empty more peripherally, the zone 1 normally does not depend on the arterial circuit and most of arterial branches are governed by the adenosine secretion from the upstream zone 1. Low portal flow, would increase adenosine secretion from the zone 1 and thus dilate numerous downstream arterial resistance vessels. An increased flow from these arterial vessels would compensate any decrease in the portal flow. Zones 2 and 3 probably have higher adenosine secretion rates since the oxygenation depends on the amount of added arterial blood and on the liver cell metabolism. Some of the arterial branches in those zones are probably open all the time, preserving them zones from hypoxic injury. Since the main point for arterial inflow is concentrated downstream from the zone 1, in cases of low portal pressures, or elevated upstream resistance, some of the arterial blood might leave the acinus in retrograde direction via the portal branch and enter some other acinus as a part of portal blood. These arterio-portal communications might be important in cases of low or none portal flow when zone 1 is in hypoxia. In the 3D liver space with tightly packed acini, very complex and ever-changing patterns of combined antegrade and retrograde flows can be expected.     

Influence of carotid baroreceptors on different components of the vascular system

1. Reflex changes in wall tension of the lateral saphenous vein of one hind limb, the splenic veins and capsule, and the resistance vessels of the other hind limb caused by changes in baroreceptor activity were measured in vagotomized dogs under thiopentone-chloralose anaesthesia.2. Three different methods were used to alter pressure in one or both carotid sinuses. (1) Both carotid sinuses were vascularly isolated and filled with fully oxygenated Krebs-Ringer bicarbonate solution (pH 7.4) from a reservoir in which the pressure could be altered at will. (2) One sinus was denervated, and the contralateral sinus was perfused with arterial blood at different flow rates. (3) One sinus was denervated, and the innervated sinus was perfused with arterial blood at constant flow, the pressure being altered by changing the outflow resistance.3. The left saphenous vein was perfused at constant flow with autologous blood; changes in perfusion pressure were used as a measure of changes in veno-motor activity. The right common iliac artery was perfused at constant flow to measure changes in resistance vessel activity. Blood flow through the spleen was temporarily arrested, trapping a fixed volume of blood in the organ. Under these conditions, changes in splenic vein pressure were a measure of changes in smooth-muscle tension in the splenic capsule and veins.4. In order to assess the responses to baroreceptor stimulation in terms of alterations in sympathetic nerve traffic to different components of the peripheral vascular system, ;frequency-response curves' were constructed for spleen, saphenous vein, and limb resistance vessels by electrical stimulation of the splenic nerves and lumbar sympathetic chains.5. The saphenous vein showed no consistent response to changes in baroreceptor activity. Reduction in carotid sinus pressure from 180 to 100 mm Hg caused an increase in venous pressure in the isovolumetric spleen and in the iliac artery perfusion pressure. These results were confirmed by electrical stimulation of the carotid sinus nerve. Whereas the peak responses of the limb resistance vessels corresponded to an increase in lumbar sympathetic nerve traffic of 6-10 c/s, the maximal splenic responses were equivalent to an increase in splenic nerve traffic of 1-4 c/s. These results are consistent with selective autonomic nervous control of different components of the peripheral vascular system.     

Cardiovascular responses in apnoeic asphyxia: role of arterial chemoreceptors and the modification of their effects by a pulmonary vagal inflation reflex

1. In the spontaneously breathing anaesthetized dog, the systemic circulation was perfused at constant blood flow; there was no pulmonary blood flow and the systemic arterial blood P(O2) and P(CO2) were controlled independently by an extracorporeal isolated pump-perfused donor lung preparation. The carotid and aortic bodies were separately perfused at constant pressure with blood of the same composition as perfused the systemic circulation.2. Apnoeic asphyxia, produced by stopping the recipient animal's lung movements and, at the same time, making the blood perfusing the systemic circulation and the arterial chemoreceptors hypoxic and hypercapnic by reducing the ventilation of the isolated perfused donor lungs, caused an increase in systemic vascular resistance.3. While the systemic arterial blood was still hypoxic and hypercapnic, withdrawal of the carotid and aortic body ;drive' resulted in a striking reduction in systemic vascular resistance. Re-establishing the chemoreceptor ;drive' immediately increased the vascular resistance again.4. Apnoeic asphyxia carried out while the carotid and aortic bodies were continuously perfused with oxygenated blood of normal P(CO2) had little or no effect on systemic vascular resistance.5. The systemic vasoconstrictor response produced by apnoeic asphyxia was reduced or abolished by re-establishing the recipient animal's lung movements, and this effect occurred in the absence of changes in the composition of the blood perfusing the systemic circulation and arterial chemoreceptors. This abolition of the vasoconstriction was due to a pulmonary reflex.6. Apnoeic asphyxia slowed the rate of the beating atria due to excitation of the carotid and aortic body chemoreceptors. This response can be over-ridden by an inflation reflex arising from the lungs.7. It is concluded that the cardiovascular responses observed in apnoeic asphyxia are due, at least in part, to primary reflexes from the carotid and aortic body chemoreceptors engendered by arterial hypoxia and hypercapnia. The appearance of these responses is, however, dependent upon there being no excitation of a pulmonary (inflation) vagal reflex.     

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.     

Effects of coronary flow reduction on capillary-myocardial exchange in dogs

The effects of coronary flow reduction on tracer capillary permeability surface area (PS) and distribution volumes were studied in open-chest dog preparations. A mixture of 51Cr-labeled red blood cells, 125I-labeled albumin, [14C]sucrose, and tritiated water (3H2O) was introduced into a shunt connecting the carotid and left anterior descending coronary arteries. Sampling from the coronary sinus produced a multiple indicator curve from which [14C]sucrose PS and 3H2O volumes were computed. Curves were observed in control situations and after the cannula was partially clamped. In six dogs, cardiac lymph was collected and analyzed for total protein. Paired comparison of control and flow-restricted indicator curves showed that flow reduction decreased the absolute values of PS and tracer volumes. The ratio of sucrose volume to weight of perfused tissue increased with flow reduction. The ratio of sucrose PS to weight of perfused tissue increased with moderate flow reduction and decreased with severe flow reduction. The results suggest that flow reduction has two effects which competively affect exchange: 1) flow restriction reduces surface area by capillary derecruitment, and 2) the remaining functional capillaries appear to undergo an increase in permeability to small molecules.