Diving response and arterial oxygen saturation during apnea and exercise in breath-hold divers.

This study addressed the effects of apnea in air and apnea with face immersion in cold water (10 degrees C) on the diving response and arterial oxygen saturation during dynamic exercise. Eight trained breath-hold divers performed steady-state exercise on a cycle ergometer at 100 W. During exercise, each subject performed 30-s apneas in air and 30-s apneas with face immersion. The heart rate and arterial oxygen saturation decreased and blood pressure increased during the apneas. Compared with apneas in air, apneas with face immersion augmented the heart rate reduction from 21 to 33% (P < 0.001) and the blood pressure increase from 34 to 42% (P < 0.05). The reduction in arterial oxygen saturation from eupneic control was 6.8% during apneas in air and 5.2% during apneas with face immersion (P < 0.05). The results indicate that augmentation of the diving response slows down the depletion of the lung oxygen store, possibly associated with a larger reduction in peripheral venous oxygen stores and increased anaerobiosis. This mechanism delays the fall in alveolar and arterial PO(2) and, thereby, the development of hypoxia in vital organs. Accordingly, we conclude that the human diving response has an oxygen-conserving effect during exercise.     

Foetal circulatory responses to arrest of uterine blood flow in sheep: effects of chemical sympathectomy.

Acute foetal asphyxia, caused by arrest of uterine blood flow, increases both sympathetic activity and peripheral vascular resistance and decreases blood flow to peripheral organs (Jensen et al., J. Dev. Physiol., 9, 543-559). The rapidity and uniformity of this peripheral vasoconstriction suggest that the sympatho-neuronal system may reflexly cause these initial blood flow changes during acute asphyxia. To test this hypothesis, we studied 5 intact and 6 chemically sympathectomized (6-hydroxy-dopamine, 46.1 +/- 6 mg/kg foetal weight) chronically prepared normoxaemic foetal sheep in utero at 0.9 of gestation. Organ blood flows (microsphere method), plasma concentrations of catecholamines, vasopressin, and angiotensin II, acid-base balance and blood gases were measured before, during and after arrest of uterine blood flow for 2 min, i.e., at 0, 1, 2, 3, 4 & 30 min. In intact foetuses there was a progressive increase in arterial blood pressure and a rapid circulatory centralization in favour of the brain stem and heart and at the expense of most of the peripheral organs. The changes in peripheral blood flow during and after asphyxia were well reflected by those in the skin and scalp. In chemically sympathectomized foetuses, arterial blood pressure fell transiently at 1 min of asphyxia and cardiac output was redistributed towards the carcass and intestinal organs at the expense of the heart, spinal medulla, and placenta. We conclude that in foetal sheep at 0.9 of gestation, the short-term adaptation to arrest of uterine blood flow is a rapid and profound peripheral vasoconstriction to effect an increase in arterial blood pressure. This initial response during circulatory centralization, which is necessary to increase or maintain blood flow to the heart, brain stem, and placenta, is blunted by sympathectomy. Thus, the foetal sympatho-neuronal system is important for short-term adaptation to and intact survival of asphyxia.     

Arterial blood pressure during voluntary diving in the tufted duck,Aythya fuligula

Arterial blood pressure was monitored in voluntarily diving tufted ducks. Mean arterial blood pressure while diving increased during the pre-dive tachycardia, fell to resting levels on submersion, then gradually increased before peaking on surfacing. Estimated total peripheral resistance fell during the pre-dive and post-dive tachycardia, presumably to allow the oxygen stores to be loaded and replenished respectively and/or for carbon dioxide levels to be reduced. Changes in mean arterial blood pressure and total peripheral resistance suggest that peripheral vasoconstriction occurs in some vascular beds during a dive. An increase in arterial blood pressure (and therefore perfusion pressure) may be employed to increase blood flow and oxygen delivery to the active leg muscles.Abbreviations ecg Electrocardiogram, f _H, heart rate - MABP mean arterial blood pressure - P _b blood pressure(s) - TPR total peripheral resistance - V _b cardiac output     

Characteristics of the human cardiovascular system in the human diving response

Comparative-evolutional research of diving response showed that mechanisms of its expression had much in common in humans and in animals. Firstly, it involves a reflex bradycardia, vasoconstriction of peripheral vessels, and blood flow centralization. But, unlike animals whose diving response has some typical species peculiarities, human diving response is rather diverse. Four types of cardiovascular system response to face submersion were revealed: over-reactive, reactive, paradoxical, and nonreactive. These types were chosen according to the bradycardia character. It is also supposed that the occurrence of individual maximal R--R-interval, while serving as a signal to apnea stopping, is among the reasons of apnea activity limitation.     

Cardiovascular control during voluntary static exercise in humans with tetraplegia.

The purpose of the present study was 1) to investigate whether an increase in heart rate (HR) at the onset of voluntary static arm exercise in tetraplegic subjects was similar to that of normal subjects and 2) to identify how the cardiovascular adaptation during static exercise was disturbed by sympathetic decentralization. Mean arterial blood pressure (MAP) and HR were noninvasively recorded during static arm exercise at 35% of maximal voluntary contraction in six tetraplegic subjects who had complete cervical spinal cord injury (C(6)-C(7)). Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were estimated by using a Modelflow method simulating aortic input impedance from arterial blood pressure waveform. In tetraplegic subjects, the increase in HR at the onset of static exercise was blunted compared with age-matched control subjects, whereas the peak increase in HR at the end of exercise was similar between the two groups. CO increased during exercise with no or slight decrease in SV. MAP increased approximately one-third above the control pressor response but TPR did not rise at all throughout static exercise, indicating that the slight pressor response is determined by the increase in CO. We conclude that the cardiovascular adaptation during voluntary static arm exercise in tetraplegic subjects is mainly accomplished by increasing cardiac pump output according to the tachycardia, which is controlled by cardiac vagal outflow, and that sympathetic decentralization causes both absent peripheral vasoconstriction and a decreased capacity to increase HR, especially at the onset of exercise.     

The diving paradox: new insights into the role of the dive response in air-breathing vertebrates

When aquatic reptiles, birds and mammals submerge, they typically exhibit a dive response in which breathing ceases, heart rate slows, and blood flow to peripheral tissues is reduced. The profound dive response that occurs during forced submergence sequesters blood oxygen for the brain and heart while allowing peripheral tissues to become anaerobic, thus protecting the animal from immediate asphyxiation. However, the decrease in peripheral blood flow is in direct conflict with the exercise response necessary for supporting muscle metabolism during submerged swimming. In free diving animals, a dive response still occurs, but it is less intense than during forced submergence, and whole-body metabolism remains aerobic. If blood oxygen is not sequestered for brain and heart metabolism during normal diving, then what is the purpose of the dive response? Here, we show that its primary role may be to regulate the degree of hypoxia in skeletal muscle so that blood and muscle oxygen stores can be efficiently used. Paradoxically, the muscles of diving vertebrates must become hypoxic to maximize aerobic dive duration. At the same time, morphological and enzymatic adaptations enhance intracellular oxygen diffusion at low partial pressures of oxygen. Optimizing the use of blood and muscle oxygen stores allows aquatic, air-breathing vertebrates to exercise for prolonged periods while holding their breath.     

Altered baroreflex control of forearm vascular resistance during simulated microgravity

Reflex peripheral vasoconstriction induced by activation of cardiopulmonary baroreceptors in response to reduced central venous pressure (CVP) is a basic mechanism for elevating systemic vascular resistance and defending arterial blood pressure during orthostatically-induced reductions in cardiac filling and output. The sensitivity of the cardiopulmonary baroreflex response [defined as the slope of the relationship between changes in forearm vascular resistance (FVR) and CVP] and the resultant vasoconstriction are closely and inversely associated with the amount of circulating blood volume. Thus, a high-gain FVR response will be elicited by a hypovolemic state. Exposure to microgravity during spaceflight results in reduced plasma volume. It is therefore reasonable to expect that the FVR response to cardiopulmonary baroreceptor unloading would be accentuated following adaptation to microgravity. Such data could provide better insight about the physiological mechanisms underlying alterations in blood pressure control following spaceflight. We therefore exposed eleven men to 6 degrees head-down bedrest for 7 days and measured specific hemodynamic responses to low levels of the lower body negative pressure to determine if there are alterations in cardiopulmonary baroreceptor stimulus-FVR reflex response relationship during prolonged exposure to an analog of microgravity.     

Cardiovascular changes during deep breath-hold dives in a pressure chamber

Ferrigno, Massimo, Guido Ferretti, Avery Ellis, DanWarkander, Mario Costa, Paolo Cerretelli, and Claes E. G. Lundgren. Cardiovascular changes during deep breath-hold dives ina pressure chamber. J. Appl. Physiol.83(4): 1282-1290, 1997.Electrocardiogram, cardiac output, andblood lactate accumulation were recorded in three elite breath-holddivers diving to 40-55 m in a pressure chamber in thermoneutral(35°C) or cool (25°C) water. In two of the divers, invasiverecordings of arterial blood pressure were also obtained during divesto 50 m in cool water. Bradycardia during the dives was more pronouncedand developed more rapidly in the cool water, with heart rates droppingto 20-30 beats/min. Arrhythmias occurred, particularly during thedives in cool water, when they were often more frequent than sinusbeats. Because of bradycardia, cardiac output decreased during thedives, especially in cool water (to <3 l/min in 2 of the divers).Arterial blood pressure increased dramatically, reaching values as highas 280/200 and 290/150 mmHg in the two divers, respectively. Thishypertension was secondary to peripheral vasoconstriction, which alsoled to anaerobic metabolism, reflected in increased blood lactateconcentration. The diving response of these divers resembles the onedescribed for diving animals, although the presence of arrhythmias andlarge increases in blood pressure indicate a less perfect adaptation inhumans.

     

Differential antioxidant protection in tissues from marine mammals with distinct diving capacities. Shallow/short vs. deep/long divers

The diving response in marine mammals results in bradycardia and peripheral vasoconstriction, with blood flow redistributing preferentially to nervous and cardiac tissues. Therefore, some tissues are rendered ischemic during a dive; with the first breath after a dive, blood flow to all tissues is reestablished. In terrestrial mammals, reactive oxygen species (ROS) production increases in response to ischemia/reperfusion and oxidative damage can occur. The capacity of marine mammals to tolerate repeated ischemia/reperfusion cycles associated with diving appears to be due to an enhanced antioxidant system. However, it is not known if diving depth and/or duration elicit differences in tissue capacity to produce ROS and antioxidant defenses in marine mammals. The objective of this study was to analyze ROS production, antioxidant defenses and oxidative damage in marine mammal species that perform shallow/short vs. deep/long dives. We measured production of superoxide radical (O₂^??), oxidative damage to lipids and proteins, activity of antioxidant enzymes, and glutathione levels in tissues from shallow/short divers (Tursiops truncatus) and deep/long divers (Kogia spp.). We found that differences between the diving capacity of dolphins and Kogia spp. are reflected in O₂^?? production and antioxidant levels. These differences suggest that shallow/short and deep/long divers have distinct mechanisms to successfully maintain redox balance.     

Balancing conflicting metabolic demands of exercise and diving

During enforced diving, aquatic animals activate a set of physiological reflexes (apnea, bradycardia, peripheral vasoconstriction), which are termed the diving response and are in effect the first line of defense against hypoxia. At least in the Weddell seal, this strategy is now known also to be used in voluntary diving at sea, but the response is necessarily modified to accommodate potentially conflicting demands of diving and swimming exercise. The main modification appears to involve skeletal muscles used in swimming, which, because of their high energy requirements, must be powered by aerobic metabolism. Thus they must remain perfused at rates porportional to swimming velocity (which is why heart rates are adjusted to swimming velocity). The required regulation of O2 delivery is achieved at least in part by a well-paced release of oxygenated red blood cells, stored at the beginning of the dive apparently in the spleen. The main metabolic difference between laboratory and voluntary diving is that, in the latter, working muscles serve as a sink for lactate and thus the entry rates of lactate into the plasma can be balanced by exit rates from the plasma; the maintenance of this balance means that no excess lactate remains for a lactate washout in postdiving exercise except under long, exploratory diving. Even in the latter long dives, however, the amount of lactate formed is far less than would be expected if the energetic shortfall caused by hypoperfusion and O2 lack were made up by anaerobic glycolysis (Pasteur effect). Consequently, during diving, hypoperfused tissues necessarily sustain a metabolic arrest of variable degrees as a mechanism of defense against hypoxia.     

Decreased cardiac output at the onset of diabetes: renal mechanisms and peripheral vasoconstriction

Recently we reported that hindquarter blood flow, measured 24 h/day, decreased progressively over the first 6 days of type 1 diabetes in rats. That response, coupled with the tendency of mean arterial pressure to increase, suggested a vasoconstrictor response. The purpose of this study was to measure the changes in cardiac output together with the renal hemodynamic and excretory responses to allow integrative determination of whether vasoconstriction likely accompanies the onset of type 1 diabetes. Rats were instrumented with a Transonic flow probe on the ascending aorta and with artery and vein catheters, and cardiac output and mean arterial pressure were measured continuously, 24 h/day, throughout the study. The induction of diabetes, by withdrawing intravenous insulin-replacement therapy in streptozotocin-treated rats, caused a progressive decrease in cardiac output that was 85 +/- 5% of control levels by day 7. This was associated with significant increases in glomerular filtration rate, renal blood flow, and microalbuminuria as well as urinary fluid and sodium losses, with a negative cumulative sodium balance averaging 15.7 +/- 1.6 meq by day 7. Restoring insulin-replacement therapy reversed the renal excretory responses but did not correct the negative sodium balance, yet cardiac output returned rapidly to control values. Increasing sodium intake during the diabetic and recovery periods also did not significantly affect the cardiac output response during any period. These results indicate that cardiac output decreases significantly at the onset of type 1 diabetes without glycemic control, and although volume loss may contribute to this response, there also is a component that is not volume or sodium dependent. We suggest this may be due to vasoconstriction, but to what extent local blood flow autoregulation or active vasoconstriction may have mediated that response is not known.     

Cerebral blood flow response to isocapnic hypoxia during slow-wave sleep and wakefulness.

Nocturnal hypoxia is a major pathological factor associated with cardiorespiratory disease. During wakefulness, a decrease in arterial O2 tension results in a decrease in cerebral vascular tone and a consequent increase in cerebral blood flow; however, the cerebral vascular response to hypoxia during sleep is unknown. In the present study, we determined the cerebral vascular reactivity to isocapnic hypoxia during wakefulness and during stage 3/4 non-rapid eye movement (NREM) sleep. In 13 healthy individuals, left middle cerebral artery velocity (MCAV) was measured with the use of transcranial Doppler ultrasound as an index of cerebral blood flow. During wakefulness, in response to isocapnic hypoxia (arterial O2 saturation -10%), the mean (+/-SE) MCAV increased by 12.9 +/- 2.2% (P < 0.001); during NREM sleep, isocapnic hypoxia was associated with a -7.4 +/- 1.6% reduction in MCAV (P <0.001). Mean arterial blood pressure was unaffected by isocapnic hypoxia (P >0.05); R-R interval decreased similarly in response to isocapnic hypoxia during wakefulness (-21.9 +/- 10.4%; P <0.001) and sleep (-20.5 +/- 8.5%; P <0.001). The failure of the cerebral vasculature to react to hypoxia during sleep suggests a major state-dependent vulnerability associated with the control of the cerebral circulation and may contribute to the pathophysiologies of stroke and sleep apnea.     

Chemoreceptor reflexes and cardiovascular control

Evidence is presented which indicates that in the absence of other known inputs to the nervous system and during controlled pulmonary ventilation, stimulation of the carotid body chemoreceptors causes bradycardia and selective peripheral vasoconstriction. These responses may be attenuated, however, by concomitant changes in respiration and arterial blood pressure, and by activity of higher parts of the brain stem. Stimulation of the aortic bodies in mammals in which they are functionally active, causes bradycardia or tachycardia and selective peripheral vasoconstriction. The reflex vascular effects from the peripheral arterial chemoreceptors are mediated by alpha-adrenergic sympathetic fibres. A potential mechanism exists therefore whereby the peripheral arterial chemoreceptors could contribute to the neurogenic component of hypertension.     

Skin-surface cooling elicits peripheral and visceral vasoconstriction in humans.

Skin-surface cooling elicits a pronounced systemic pressor response, which has previously been reported to be associated with peripheral vasoconstriction and may not fully account for the decrease in systemic vascular conductance. To test the hypothesis that whole body skin-surface cooling would also induce renal and splanchnic vasoconstriction, 14 supine subjects performed 26 skin-surface cooling trials (15-18 degrees C water perfused through a tube-lined suit for 20 min). Oral and mean skin temperature, heart rate, stroke volume (Doppler ultrasound), mean arterial blood pressure (MAP), cutaneous blood velocity (laser-Doppler), and mean blood velocity of the brachial, celiac, renal, and superior mesenteric arteries (Doppler ultrasound) were measured during normothermia and skin-surface cooling. Cardiac output (heart rate x stroke volume) and indexes of vascular conductance (flux or blood velocity/MAP) were calculated. Skin-surface cooling increased MAP (n = 26; 78 +/- 5 to 88 +/- 5 mmHg; mean +/- SD) and decreased mean skin temperature (n = 26; 33.7 +/- 0.7 to 27.5 +/- 1.2 degrees C) and cutaneous (n = 12; 0.93 +/- 0.68 to 0.36 +/- 0.20 flux/mmHg), brachial (n = 10; 32 +/- 15 to 20 +/- 12), celiac (n = 8; 85 +/- 22 to 73 +/- 22 cm.s(-1).mmHg(-1)), superior mesenteric (n = 8; 55 +/- 16 to 48 +/- 10 cm.s(-1).mmHg(-1)), and renal (n = 8; 74 +/- 26 to 64 +/- 20 cm.s(-1).mmHg(-1); all P < 0.05) vascular conductance, without altering oral temperature, cardiac output, heart rate, or stroke volume. These data identify decreases in vascular conductance of skin and of brachial, celiac, superior mesenteric, and renal arteries. Thus it appears that vasoconstriction in both peripheral and visceral arteries contributes importantly to the pressor response produced during skin-surface cooling in humans.     

Changes in renal autacoids and hemodynamics associated with aging and isolated systolic hypertension

The aging kidney is characterized by a decrease in renal blood flow and glomerular filtration rate mainly due to glomerulosclerosis. Nevertheless, even in the presence of these changes, the kidney maintains its functionality until advanced age. However, there is a tendency towards greater renal vasoconstriction in the elderly as compared with young individuals. This occurs either in physiological circumstances such as physical exercise, or in disease manifestations, such as the effective circulatory volume depletion that develops, for example, in heart failure. This tendency may be secondary to the reduction of renal autacoid modulatory capacity, particularly at the vasodilating prostaglandin level. In an acute experimental model we could demonstrate that, in the healthy elderly, the renal response to adrenergic activation by mental stress is characterized by a prolonged and pronounced vasoconstriction. In addition to this, in elderly patients affected by isolated systolic hypertension, we demonstrated an impairment of renal hemodynamic and humoral adaptation capacity in response to adrenergic activation and blood pressure increase. In the presence of sudden blood pressure increase, the kidney of these patients responds with a passive vasodilation and a glomerular filtration rate increase without any activation of humoral modulatory substances. The impairment in renal adaptation capacity may predispose these patients to renal injury, particularly in the presence of the many hypertensive peaks which characterize everyday life of elderly individuals. In conclusion, these results show that renal adaptation capacity of elderly patients with isolated systolic hypertension is completely lost. Further studies will elucidate whether antihypertensive treatment per se, or specific classes of antihypertensive drugs, are able to revert this impairment.     

Dynamic changes in organ blood flow and oxygen consumption during acute asphyxia in fetal sheep

The effects of acute asphyxia on both the time course of blood flow changes in central and peripheral organs, including the skin, and the time course of changes in oxygen consumption were studied in 9 unanaesthetized fetal sheep in utero at 130 +/- 2 days of gestation during 4-min arrest of uterine blood flow. Blood flow distribution and total oxygen consumption were determined at 1-min intervals during asphyxia using isotope-labelled microspheres (15 micrograms diameter) and by calculating the decline of the arterial O2 content, respectively. During asphyxia peripheral blood flow including that to the skin, scalp, and choroid plexus decreased rapidly, whereas blood flow to the heart, brain stem and (in surviving fetuses only) adrenals increased slowly. Total oxygen consumption fell exponentially with time and was closely correlated with the fall in both arterial oxygen content and peripheral blood flow; the time courses of these changes were very similar to those of the decreasing blood flows to the skin and scalp. Blood flow within the brain was redistributed at the expense of the cerebrum and the choroid plexus; the total blood flow to the brain did not change. In the 5 fetuses that died during the recovery period adrenal blood flow failed to increase and, at the nadir of asphyxia, peripheral vessels dilated and central vessels constricted. We conclude that in fetal sheep near term during acute asphyxia the time course of changes in blood flow to central and peripheral organs is different; total oxygen consumption depends on arterial O2 content and peripheral blood flow; total blood flow to the brain does not change, but is redistributed towards the brain stem at the expense of the cerebrum and choroid plexus; fetal death is preceded by a failure of adrenal blood flow to increase, by peripheral vasodilatation, and by central vasoconstriction and skin blood flow validly indicates rapid changes in the distribution of blood flow and the changes in oxygen consumption that accompany it.     

Reflex pressor response to gastric mechanical stimulation in rats

Neural and humoral mechanisms involved in the reflex pressor response during mechanical stimulation of the stomach of rats were investigated. The arterial blood pressure response was prevented by inhibition of alpha-adrenergic vasoconstriction using either an alpha-adrenergic blocker or a ganglionic blocker. In addition, there was a small decrease in the response after nephrectomy. However, there were no alterations in the response after beta-adrenergic blockade, bilateral adrenalectomy, inhibition of converting enzyme activity with enalapril or bilateral cervical vagus nerve transection. The heart rate was not modified after either intervention. After vagotomy the time of recovery of the basal blood pressure was significantly prolonged. It can be concluded that the blood pressure response to mechanical stimulation of the stomach wall is of neural rather than of humoral origin and mainly involves activation of alpha-adrenergic receptors. Vagal efferent pathways could be also involved.     

Vascular response to infusions of a nonextravasating hemoglobin polymer.

The clinical utility of cross-linked tetrameric hemoglobin solutions is limited by peripheral vasoconstriction thought to be due to scavenging of nitric oxide. In addition, transfusion of crude preparations of hemoglobin polymers can cause arterial hypertension. We tested the hypothesis that eliminating low-molecular-weight components from the polymer solution would prevent extravasation and its associated pressor response. A zero-link polymer of bovine hemoglobin was developed without chemical linkers left between the tetramers. Transfusion of unprocessed preparations of these polymers in rats resulted in appearance of the polymer in the renal hilar lymph. However, eliminating the low-molecular-weight components with a 300-kDa diafiltration resulted in an average hydrodynamic radius of 250 A and in undetectable levels of polymer in hilar lymph. Exchange transfusion in anesthetized rats and cats and in awake cats produced no increase in arterial pressure. In anesthetized cats, exchange transfusion with an albumin solution reduced hematocrit from 30 to 18%, increased cerebral blood flow, and dilated pial arterioles. In contrast, reducing hematocrit by transfusing the diafiltered polymer did not increase cerebral blood flow as pial arterioles constricted. These results are consistent with the hypothesis that the increase in arterial pressure associated with cell-free hemoglobin transfusion depends on hemoglobin extravasation. Constriction observed in the cerebrovascular bed with a nonextravasating hemoglobin polymer at low hematocrit is presumably a regulatory response to prevent overoxygenation at low blood viscosity.     

The mechanism of beta-adrenergic receptor blockade-induced elevation of arterial blood pressure in rats

Beta-adrenergic blockade increases peripheral vascular resistances acutely and paradoxically lowers arterial blood pressure in most species but not in the rat. In this study the hypothesis has been tested of a significant participation of unopposed alpha-adrenergic mediated vasoconstriction following beta-adrenergic blockade in blood pressure regulation of conscious rats. Alpha-adrenergic blockade in propranolol-pretreated rats significantly decreased mean arterial blood pressure by 22%, heart rate by 20%, and total peripheral resistance by 14% when compared to rats treated only with propranolol, whereas cardiac output was similar in the two groups. A significant 28% reduction of coronary blood flow in rats treated with alpha- and beta-adrenergic blockers, when compared to rats treated only with propranolol, is most likely related to phentolamine's indirect effects on the coronary vasculature. Cerebrovascular and renovascular resistances were similar in these groups. All changes reported were significant at the 95% confidence level. It is concluded that the mechanism of increased blood pressure following beta-adrenergic blockade in rats is related at least in part to unmasking of unopposed alpha-receptor tone, which, however, is minimal in the coronary, cerebral and renal circulations.