Dynamics of human cardiovascular responses in different periods of long-term exposure to weightlessness

The purpose of this work was to determine the dynamics of changes in the state of the human cardiovascular system at rest and upon exposure to lower body negative pressure (LBNP) in different periods of short-term (8?C25 days) and long-term (126?C438 days) space flights (SFs) using the data of ultrasonic examinations and leg occlusive plethysmography. It was established that the changes caused by blood redistribution and hypovolemia development??a decreased left-ventricular filling and stroke volume without an impairment of myocardial contractility, a decreased renal artery resistance, and an increased maximal capacity of leg veins??occurred in the first week of an SF. Over 30?C40 days of SF, these changes increased and were followed by the relative stabilization of hemodynamics at rest. Arterial cerebral blood flow was stable; however, the phenomena of venous congestion in this region increased with the SF??s duration. The most dramatic changes were observed in leg vessels, both in arteries (decreased resistance) and veins (increase in maximum capacity). Changes in the venous part of the cardiovascular system were more marked than in the arterial one. Despite the relative stabilization of the hemodynamics at rest, exposure to LBNP revealed a deterioration of gravity-dependent reactions, which changed as a function of the SF duration. In the first month of FS, the downward trend of the femoral artery vasoconstriction was not detrimental to cerebral blood flow. SF extension impaired the regulation of the vascular tone and caused increased blood flow deficiency on exposure to LBNP. In some cases, the hemodynamic response was affected to the extent that could be regarded as a failure to adapt to orthostatic effects.     

The venous circulation: a piscine perspective

Vascular capacitance describes the pressure–volume relationship of the circulatory system. The venous vasculature, which is the main capacitive region in the circulation, is actively controlled by various neurohumoral systems. In terrestrial animals, vascular capacitance control is crucial to prevent orthostatic blood pooling in dependent limbs, while in aquatic animals like fish, the effects of gravity are cancelled out by hydrostatic forces making orthostatic blood pooling an unlikely concern for these animals. Nevertheless, changes in venous capacitance have important implications on cardiovascular homeostasis in fish since it affects venous return and cardiac filling pressure (i.e. central venous blood pressure), which in turn may affect cardiac output. The mean circulatory filling pressure is used to estimate vascular capacitance. In unanaesthetized animals, it is measured as the central venous plateau pressure during a transient stoppage of cardiac output. So far, most studies of venous function in fish have addressed the situation in teleosts (notably the rainbow trout, Oncorhynchus mykiss), while any information on elasmobranchs, cyclostomes and air-breathing fishes is more limited. This review describes venous haemodynamic concepts and neurohumoral control systems in fish. Particular emphasis is placed on venous responses to natural cardiovascular challenges such as exercise, environmental hypoxia and temperature changes.     

Effects of freshwater and saltwater adaptation and dietary salt on fluid compartments, blood pressure, and venous capacitance in trout

Trout are of interest in defining the relationship between fluid and salt balance on cardiovascular function because they thrive in freshwater (FW; volume loading, salt depleting), saltwater (SW; volume depleting, salt loading), and FW while fed a high-salt diet (FW-HS; volume and salt loading). The effects of chronic (>2 wk) adaptation to these three protocols on blood volume (51Cr red cell space), extracellular fluid volume (99mTc-diethylene triaminepenta-acetic acid space), arterial (dorsal aortic; P(DA)) and venous (ductus Cuvier; Pven) blood pressure, mean circulatory filling pressure (zero-flow Pven), and vascular capacitance were examined in the present study on unanesthetized rainbow trout. Blood volume, extracellular fluid volume, P(DA), Pven, and mean circulatory filling pressure progressively increased in the order SW < FW < FW-HS. Vascular capacitance in SW fish appeared to be continuous with the capacitance curve of FW fish and reflect a passive volume-dependent unloading of the venous system of FW fish. Vascular capacitance curves for FW-HS fish were displaced upward and parallel to those of FW fish, indicative of an active increase in unstressed blood volume without any change in vascular compliance. These studies are the first in any vertebrate to measure the relationship between fluid compartments and cardiovascular function during independent manipulation of volume and salt balance, and they show that volume, but not salt, balance is the primary determinant of blood pressure in trout. They also present a new paradigm with which to investigate the relative contributions of water and salt balance in cardiovascular homeostasis.     

The venous circulation: a piscine perspective.

Vascular capacitance describes the pressure-volume relationship of the circulatory system. The venous vasculature, which is the main capacitive region in the circulation, is actively controlled by various neurohumoral systems. In terrestrial animals, vascular capacitance control is crucial to prevent orthostatic blood pooling in dependent limbs, while in aquatic animals like fish, the effects of gravity are cancelled out by hydrostatic forces making orthostatic blood pooling an unlikely concern for these animals. Nevertheless, changes in venous capacitance have important implications on cardiovascular homeostasis in fish since it affects venous return and cardiac filling pressure (i.e. central venous blood pressure), which in turn may affect cardiac output. The mean circulatory filling pressure is used to estimate vascular capacitance. In unanaesthetized animals, it is measured as the central venous plateau pressure during a transient stoppage of cardiac output. So far, most studies of venous function in fish have addressed the situation in teleosts (notably the rainbow trout, Oncorhynchus mykiss), while any information on elasmobranchs, cyclostomes and air-breathing fishes is more limited. This review describes venous haemodynamic concepts and neurohumoral control systems in fish. Particular emphasis is placed on venous responses to natural cardiovascular challenges such as exercise, environmental hypoxia and temperature changes.     

Cardiovascular Function in Humans Using Thigh Cuffs during Seven Days of Simulated Microgravity

Data are summarized on changes in the human cardiovascular system associated with the use of cuffs during seven days of antiorthostatic hypokinesia simulating weightlessness. Eight subjects participated in two series of experiments, of which one was carried out with and the other (the control) without cuffs wrapped snugly around the upper third of the thighs. The parameters of the systemic hemodynamics, the cardiac function, and the hemodynamics of the cervicocephalic region and the lower limbs recorded under control and experimental conditions were analyzed. Without cuffs, changes in the hemodynamics during antiorthostatic hypokinesia were caused by displacement of body fluids in the cranial direction. The subjects responded favorably to the use of cuffs during antiorthostatic hypokinesia: most of their hemodynamic parameters remained at the baseline level, and signs of venous stasis in the cervicocephalic region were alleviated. Although the leg veins were distended in subjects wearing thigh cuffs during antiorthostatic hypokinesia, no pathological changes in the veins were detected during or after the experiment. Cuff usage during antiorthostatic hypokinesia lasting for seven days did not produce a cumulative effect on the cardiovascular system. These results justify the use of thigh cuffs in the initial period of adaptation to simulated or real weightlessness.     

Effects of LBNP + specific physical exercises on leg venous hemodynamics during a 28-days -6 degrees head-down bedrest

The mechanisms underlying increased venous distensibility during exposure to microgravity are not well known yet. However, there seems to be evidence indicating that skeletal muscle changes resulting from exposure to microgravity play a very important role. The purpose of this experiment was to test the hypothesis that leg muscles could play an important role in the changes of leg venous distensibility observed in simulated microgravity. Twelve subjects were submitted for 28 days to a -6 degrees head-down bedrest. Changes in leg vein hemodynamics (filling and emptying) have been measured by mercury strain gauge plethysmography with venous occlusion. Six of these subjects trained their lower limbs with isometric and isokinetic exercises during bedrest (group CM), while the other 6 subjects (control group, C) had no training.     

Effect of Passive Leg Raising on Systemic Hemodynamics of Pregnant Women: A Dynamic Assessment of Maternal Cardiovascular Function at 22–24 Weeks of Gestation

Objective

To investigate functional hemodynamic response to passive leg raising in healthy pregnant women and compare it with non-pregnant controls.

Materials and Methods

This was a prospective cross-sectional study with a case-control design. A total of 108 healthy pregnant women at 22–24 weeks of gestation and 54 non-pregnant women were included. Cardiac function and systemic hemodynamics were studied at baseline and 90 seconds after passive leg raising using non-invasive impedance cardiography.

Main outcome measures

Trends and magnitudes of changes in impedance cardiography derived parameters of cardiac function and systemic hemodynamics caused by passive leg raising, and preload responsiveness defined as >10% increase in stroke volume or cardiac output after passive leg raising compared to baseline.

Results

The hemodynamic parameters in both pregnant and non-pregnant women changed significantly during passive leg raising compared to baseline, but the magnitude and trend of change was similar in both groups. The stroke volume increased both in pregnant (p = 0.042) and non-pregnant (p = 0.018) women, whereas the blood pressure and systemic vascular resistance decreased (p<0.001) following passive leg raising in both groups. Only 14.8% of pregnant women and 18.5% of non-pregnant women were preload responsive and the difference between groups was not significant (p = 0.705).

Conclusion

Static measures of cardiovascular status are different between healthy pregnant and non-pregnant women, but the physiological response to passive leg raising is similar and not modified by pregnancy at 22–24 weeks of gestation. Whether physiological response to passive leg raising is different in earlier and later stages of pregnancy merit further investigation.     

Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model.

It recently has been demonstrated that magnetic resonance imaging can be used to map changes in brain hemodynamics produced by human mental operations. One method under development relies on blood oxygenation level-dependent (BOLD) contrast: a change in the signal strength of brain water protons produced by the paramagnetic effects of venous blood deoxyhemoglobin. Here we discuss the basic quantitative features of the observed BOLD-based signal changes, including the signal amplitude and its magnetic field dependence and dynamic effects such as a pronounced oscillatory pattern that is induced in the signal from primary visual cortex during photic stimulation experiments. The observed features are compared with the results of Monte Carlo simulations of water proton intravoxel phase dispersion produced by local field gradients generated by paramagnetic deoxyhemoglobin in nearby venous blood vessels. The simulations suggest that the effect of water molecule diffusion is strong for the case of blood capillaries, but, for larger venous blood vessels, water diffusion is not an important determinant of deoxyhemoglobin-induced signal dephasing. We provide an expression for the apparent in-plane relaxation rate constant (R2*) in terms of the main magnetic field strength, the degree of the oxygenation of the venous blood, the venous blood volume fraction in the tissue, and the size of the blood vessel.     

Effect of Hydroxyethylrutosides on Blood Oxygen Levels and Venous Insufficiency Symptoms in Varicose Veins

Oxygen levels (tension, saturation, and content) in blood from varicose leg veins were found to be significantly lower than those in blood from normal leg veins at the same site on the limb under the same laboratory conditions. Treatment with hydroxyethylrutosides significantly increased the oxygen levels in blood from varicose veins, and this was associated with an improvement in leg symptoms attributable to venous insufficiency. Hydroxyethylrutosides have been shown to have a beneficial effect on capillary dysfunction in venous stasis.     

Role of mechanosignaling on pathology of varicose vein

Varicose veins are the most common vascular disease in humans. Veins have valves that help the blood return gradually to the heart without leaking blood. When these valves become weak, blood and fluid collect and pool by pressing against the walls of the veins, causing varicose veins. In the cardiovascular system, mechanical forces are important determinants of vascular homeostasis and pathological processes. Blood vessels are constantly exposed to a variety of hemodynamic forces, including shear stress and environmental strains caused by the blood flow. In varicose veins within the leg, venous blood pressure rises in the vein of the lower extremities due to prolonged standing, creating a peripheral tension in the vessel wall thereby causing mechanical stimulation of endothelial cells and vascular smooth muscle. Studies have shown that long-term increased exposure to vascular wall tension is associated with the overexpression of HIF-1α and HIF-2α and increased levels of MMP-2 and MMP-9, thereby reducing venous contraction and progressive venous dilatation, which is involved in the development of varicose veins. Following the expression of metalloproteinase, the expression of type 1 collagen increases, and the amount of type 3 collagen decreases. Therefore, collagen imbalance will cause the varicose veins to not stretch. Loss of structural proteins (type 3 collagen and elastin) in the vessel wall causes the loss of the biophysical properties of the varicose vein wall. This review article tries to elaborate on the effect of mechanical forces and sensors of these forces on the vascular wall in creating the mechanism of mechanosignaling, as well as the role of the onset of molecular signaling cascades in the pathology of varicose veins.     

The study of cerebral venous blood flow disturbance peculiarity in the norm and under the extravasal compression of brachiocephalic veins with the use of magnetic resonance venography and ultrasound duplex scanning

The MR-venography of the veins and brain venous sinuses, brachiocephalic veins an internal jugular veins duplex scanning have been performed in order to study the distinctions of cerebral venous hemodynamics of healthy people and the patients with venous encephalopathy caused by the extravasal compression of the brachiocephalic veins at the neck level and the superior sections of mediastinum. It has been revealed that the blood flow reducing in transverse brain sinuses occurs not only in the case of outflow disorder in the distal sections of the venous system, but also in norm. This reducing depends on anatomic constitution of confluens sinuum and the venous angle type of brachiocephalic veins. The three venous angle types of brachiocephalic veins have been distinguished: y-type, mu-type and Y-type. It has been registered that in case of the mu-type angle the blood flow can be reduced in norm due to peripheral resistance increase at the physiological bends of nearly a right angle type. The distinctions of hemodynamics in case of venous obstruction in contrast to arterial obstruction have been described. It has been registered that in case of outflow trouble in one of the internal jugular veins the speed and the volume of the blood flow in it are progressively reduced depending on the duration and the manifestation of compression. All this results in narrowing of the vein diameter from the affected side, and in compensatory distention of the diameter and increase of blood flow volume in the contralateral internal jugular vein, vertebral and external jugular veins, in succession.     

Venous distensibility and venous emptying in the legs during a 42-day -6 degrees head-down bedrest

Exposure to actual or simulated microgravity is known to result in changes in lower limb venous compliance or distensibility which may play a role in post-bedrest or postflight orthostatic intolerance. Venous deconditioning has only been described in terms of changes in vascular compliance or distensibility. But a complete understanding of changes in venous hemodynamics and cardiovascular regulation occurring under these conditions has to take into account changes in emptying capacities of the veins which influence venous return, cardiac filling, and cardiac output regulation. Moreover, few data are available about the course of changes in venous hemodynamics for periods of simulated microgravity longer than 4 weeks. The purpose of this investigation was to measure parameters of venous compliance and venous emptying before, during, and after a 42-day period of bedrest at -6 degrees head-down tilt for a better understanding of long term venous physiological adaptation to microgravity.     

Adrenergic control of venous capacitance during moderate hypoxia in the rainbow trout (Oncorhynchus mykiss): role of neural and circulating catecholamines

Central venous blood pressure (P(ven)) increases in response to hypoxia in rainbow trout (Oncorhynchus mykiss), but details on the control mechanisms of the venous vasculature during hypoxia have not been studied in fish. Basic cardiovascular variables including P(ven), dorsal aortic blood pressure, cardiac output, and heart rate were monitored in vivo during normoxia and moderate hypoxia (P(W)O(2) = approximately 9 kPa), where P(W)O(2) is water oxygen partial pressure. Venous capacitance curves for normoxia and hypoxia were constructed at 80-100, 90-110, and 100-120% of total blood volume by transiently (8 s) occluding the ventral aorta and measure P(ven) during circulatory arrest to estimate the mean circulatory filling pressure (MCFP). This allowed for estimates of hypoxia-induced changes in unstressed blood volume (USBV) and venous compliance. MCFP increased due to a decreased USBV at all blood volumes during hypoxia. These venous responses were blocked by alpha-adrenoceptor blockade with prazosin (1 mg/kg body mass). MCFP still increased during hypoxia after pretreatment with the adrenergic nerve-blocking agent bretylium (10 mg/kg body mass), but the decrease in USBV only persisted at 80-100% blood volume, whereas vascular capacitance decreased significantly at 90-110% blood volume. In all treatments, hypoxia typically reduced heart rate while cardiac output was maintained through a compensatory increase in stroke volume. Despite the markedly reduced response in venous capacitance after adrenergic blockade, P(ven) always increased in response to hypoxia. This study reveals that venous capacitance in rainbow trout is actively modulated in response to hypoxia by an alpha-adrenergic mechanism with both humoral and neural components.     

Mathematical model for the estimation of hemodynamic and oxygenation variables by tissue spectroscopy

This article presents a quasistatic, compartmental model of tissue-level hemodynamics and oxygenation that leads to a set of formulas, which is suitable to calculate important physiological variables from the mean tissue concentration and saturation of hemoglobin, measured by tissue spectroscopy. Dimensioned quantities are represented relative to their baseline value in the equations (relative value = perturbed/baseline). All model parameters are non-dimensional. The model is based and extends on a number of previous works: previous models of similar aim and scope are consolidated, and every critical assumptions and approximations are treated explicitly; extensions include for example the incorporation of the Fahraeus-effect and the separate estimation of the volume changes of the arterial and the venous compartments. The information content of spectroscopic data alone is shown to be valuable, but limited: the relative venous volume, the oxygen extraction fraction and the relative cellulovascular coupling (defined as the ratio of blood flow and oxygen consumption) can be calculated from these data, if the alterations in arterial blood volume are negligible. The number of variables estimated by the derived formulas can be increased if local blood flow is measured simultaneously: in this case, the relative arterial and venous volume and resistance, the oxygen extraction fraction, and the relative oxygen consumption can be determined. Given that this model considers arterial blood pressure, saturation and hematocrit as its inputs, when measured, the model becomes applicable in such conditions as hyper- or hypotension, hypoxic hypoxia, hemodilution and hemorrhage, where these variables do change. The estimation of the changes in arterial resistance can be applied to estimate the extent of an autoregulatory response.     

Cardiac homeostasis is independent of calf venous compliance in subjects with paraplegia

The purpose of this study was to examine cardiac hemodynamics during acute head-up tilt (HUT) and calf venous function during acute head-down tilt (HDT) in subjects with paraplegia compared with sedentary nondisabled controls. Nineteen paraplegic males (below T6) and nine age-, height-, and weight-matched control subjects participated. Heart rate, stroke volume, and cardiac output were assessed using the noninvasive acetylene uptake method. Venous vascular function of the calf was assessed using venous occlusion plethysmography. After supine measurements were collected, the table was moved to 10 degrees HDT followed by the three levels of HUT (10, 35, and 75 degrees ) in random order. Cardiac hemodynamics were similar between the groups at all positions. Calf circumference was significantly reduced in the paraplegic group compared with the control group (P < 0.001). Venous capacitance and compliance were significantly reduced in the paraplegic compared with control group at supine and HDT. Neither venous capacitance (P = 0.37) nor compliance (P = 0.19) increased from supine with 10 degrees HDT in the paraplegic group. A significant linear relationship was established between supine venous compliance and supine cardiac output in the control group (r = 0.80, P < 0.02) but not in the paraplegic group. The findings of reduced calf circumference and similar venous capacitance at supine rest and 10 degrees HDT in the paraplegic group imply that structural changes may have limited venous dispensability in individuals with chronic paraplegia. Furthermore, the lack of a relationship between supine venous compliance and supine cardiac output suggests that cardiac homeostasis does not rely on venous compliance in subjects with paraplegia.     

Partial hepatectomy hemodynamics changes: Experimental data explained by closed-loop lumped modeling

The liver function may be degraded after partial liver ablation surgery. Adverse liver hemodynamics have been shown to be associated to liver failure. The link between these hemodynamics changes and ablation size is however poorly understood. This article proposes to explain with a closed-loop lumped model the hemodynamics changes observed during twelve surgeries in pigs. The portal venous tree is modeled with a pressure-dependent variable resistor. The variables measured, before liver ablation, are used to tune the model parameters. Then, the liver partial ablation is simulated with the model and the simulated pressures and flows are compared with post-operative measurements. Fluid infusion and blood losses occur during the surgery. The closed-loop model presented accounts for these blood volume changes. Moreover, the impact of blood volume changes and the liver lobe mass estimations on the simulated variables is studied. The typical increase of portal pressure, increase of liver pressure loss, slight decrease of portal flow and major decrease in arterial flow are quantitatively captured by the model for a 75% hepatectomy. It appears that the 75% decrease in hepatic arterial flow can be explained by the resistance increase induced by the surgery, and that no hepatic arterial buffer response (HABR) mechanism is needed to account for this change. The different post-operative states, observed in experiments, are reproduced with the proposed model. Thus, an explanation for inter-subjects post-operative variability is proposed. The presented framework can easily be adapted to other species circulations and to different pathologies for clinical hepatic applications.     

Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

Administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla.     

Dry immersion effects on the mechanisms of metaboreflex regulation of hemodynamics during exercise

The effects of four-day dry immersion on metaboreflex regulation of hemodynamics were evaluated during local static exercise (30% of the maximum voluntary contraction) of the calf plantar flexors. One group of immersed subjects received low-frequency electrostimulation of their leg muscles to decrease the immersion effect on the EMG of exercising muscles. Metaboreflex regulation was evaluated by comparison of cardiovascular responses to physical loads with and without post-exercise circulatory occlusion. Immersion slightly increased the heart rate (HR) and reduced the systolic blood pressure in resting subjects; however, it did not have a distinct effect on blood pressure (BP) and HR during exercise or metaboreflex potentiation of hemodynamic shifts.     

Simulation of pulmonary O2 uptake during exercise transients in humans

Computer simulation of blood flow and O2 consumption (QO2) of leg muscles and of blood flow through other vascular compartments was made to estimate the potential effects of circulatory adjustments to moderate leg exercise on pulmonary O2 uptake (VO2) kinetics in humans. The model revealed a biphasic rise in pulmonary VO2 after the onset of constant-load exercise. The length of the first phase represented a circulatory transit time from the contracting muscles to the lung. The duration and magnitude of rise in VO2 during phase 1 were determined solely by the rate of rise in venous return and by the venous volume separating the muscle from the lung gas exchange sites. The second phase of VO2 represented increased muscle metabolism (QO2) of exercise. With the use of a single-exponential model for muscle QO2 and physiological estimates of other model parameters, phase 2 VO2 could be well described as a first-order exponential whose time constant was within 2 s of that for muscle QO2. The use of unphysiological estimates for certain parameters led to responses for VO2 during phase 2 that were qualitatively different from QO2. It is concluded that 1) the normal response of VO2 in humans to step increases in muscle work contains two components or phases, the first determined by cardiovascular phenomena and the second primarily reflecting muscle metabolism and 2) the kinetics of VO2 during phase 2 can be used to estimate the kinetics of muscle QO2. The simulation results are consistent with previously published profiles of VO2 kinetics for square-wave transients.     

Effects of asphyxia on arterial blood pressure, formation of nitric oxide in medulla and blood parameters in the cat

The rostral ventrolateral medulla (RVLM) plays an important role in the integration of cardiovascular functions. We examined the effect of asphyxia on cardiovascular responses, on sympathetic vertebral nerve activity (VNA) and nitric oxide (NO) formation in the RVLM, on hemodynamics, and on plasma concentrations of catecholamines, blood gas partial pressures and carbohydrate metabolites. Using 16 anesthetized cats we found that the systemic arterial pressure (SAP), VNA, NO formation and the release of plasma catecholamine components of norepinephrine and epinephrine were increased during asphyxia. The onset of NO production was significantly earlier than that of SAP and VNA. The venous partial pressure of O2 decreased, while the partial pressure of CO2 increased. Furthermore, metabolism of glucose and lactate increased, as did the blood concentrations of white and red blood cells, hemoglobin and platelets. Thus, asphyxia increased SAP, VNA and NO formation. It increased the plasma catecholamines, blood gases, carbohydrate metabolites and blood cells.