Physiological development of the embryonic and larval crayfish heart

The cardiovascular system is the first system to become functional in a developing animal and must perform key physiological functions even as it develops and grows. The ontogeny of cardiac physiology was studied throughout embryonic and larval developmental stages in the red swamp crayfish Procambarus clarkii using videomicroscopic dimensional analysis. The heart begins to contract by day 13 of development (at 25 degrees C, 20 kPa O(2)). Cardiac output is primarily regulated by changes in heart rate because stroke volume remains relatively constant throughout embryogenesis. Prior to eclosion, heart rate and cardiac output decreased significantly. Previous data suggest that the decrease in cardiac parameters prior to hatching may be due to an oxygen limitation to the embryo. Throughout development, metabolizing mass and embryonic oxygen consumption increased, while egg surface area remained constant. The surface area of the egg membrane is a constraint on gas exchange; this limitation, in combination with the increasing oxygen demand of the embryo, results in an inadequate diffusive supply of oxygen to developing tissues. To determine if the decrease in cardiac function was the result of an internal hypoxia experienced during late embryonic development, early and late-stage embryos were exposed to hyperoxic water (PO(2) = 40 kPa O(2)). Heart rate in late-stage embryos exposed to hyperoxic water increased significantly over control values, which suggests that the suppression in cardiac function observed in late-stage embryos is due to a limited oxygen supply.     

Continuous negative extrathoracic pressure combined with high-frequency oscillation improves oxygenation with less impact on blood pressure than high-frequency oscillation alone in a rabbit model of surfactant depletion

Background  

Negative air pressure ventilation has been used to maintain adequate functional residual capacity in patients with chronic muscular disease and to decrease transpulmonary pressure and improve cardiac output during right heart surgery. High-frequency oscillation (HFO) exerts beneficial effects on gas exchange in neonates with acute respiratory failure. We examined whether continuous negative extrathoracic pressure (CNEP) combined with HFO would be effective for treating acute respiratory failure in an animal model.     

Effects of hemodilution on O2 transport in high-altitude polycythemia

A native of the Peruvian Andes (4,250 m) was studied before and after isovolemic hemodilution of the hematocrit from 62 to 42%. O2 transport was studied with newly developed catheters in the radial and pulmonary arteries. These catheters allowed continuous measurement of arteriovenous O2 content and intermittent cardiac output by thermodilution. During exercise tests, breath-by-breath gas exchange measurements also allowed cardiac output to be calculated by the O2-Fick technique. A complex series of interrelated physiological changes occurred in response to hemodilution. These included increased ventilation, increased arterial and mixed venous PO2, increased cardiac output (both heart rate and stroke volume), and improved ventilation-flow match. The general improvement in symptoms that followed hemodilution correlated well with increased anaerobic threshold and mixed venous PO2 during exercise.     

Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

Background  

Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow.     

Decreased O2 consumption and cardiac output during normobaric hyperoxia in conscious dogs

Recent reports indicate that under certain restricted conditions hyperoxia may decrease tissue O2 consumption. However, this effect has not been established for whole body O2 consumption in the intact healthy conscious state. The goal of the present study was to document the effect of hyperoxia on resting whole body O2 consumption and hemodynamics under these latter more general physiological conditions. The inspired gas was delivered by mask to six fasted resting conscious dogs and alternated hourly between air and O2-enriched air (hyperoxia) for 5 h, while hemodynamics and blood gas data were obtained every 20 min. Compared with air breathing, hyperoxia increased the mean arterial O2 tension from 95 to 475 Torr and decreased heart rate, cardiac output, pulmonary vascular resistance, and right and left ventricular work rates and thus, presumably, myocardial O2 consumption. Hyperoxia also increased systemic vascular resistance and right atrial pressure but did not change stroke volume or systemic arterial pressure. The increase in arterial O2 content during hyperoxia was counterbalanced by the decrease in cardiac output, so that O2 delivery was unchanged by hyperoxia. Surprisingly, hyperoxia decreased the arterial-to-mixed venous difference in O2 content; this decrease together with the decrease in cardiac output produced a decrease in resting whole body O2 consumption from 5.88 +/- 0.68 to 4.80 +/- 0.62 ml O2.min-1.kg-1 (P = 0.0002). It is concluded that under physiological conditions normobaric hyperoxia may decrease metabolic rate in addition to cardiac output, which may have important implications for the metabolic regulation of O2 utilization as well as for the medical and nonmedical uses of O2.     

Effects of digoxin on chemoreflex in patients with chronic heart failure.

The effects of digitalis on the baroreflexes in human chronic heart failure have been well studied. Similarly, since it has been recently shown that chemoregulation remains generally effective during cardiac failure, the goal of this study was to evaluate the effects of a chronic administration of digoxin on the chemoreflexes. Hemodynamic and blood gas parameters were assessed in 7 patients with chronic congestive heart failure before and after chronic administration for 10 days of digoxin therapy (0.25 mg daily). In both situations measurements were performed 1/ in baseline conditions at room air and, 2/ after inhalation of pure O2 for 30 min, in order to inhibit the activation of the chemoreflexes. At room air, acute O2 inhalation resulted in a significant decrease in heart rate and cardiac output. After digoxin therapy, comparatively to pre-treatment values, cardiac output, stroke volume and PaO2 were significantly higher while heart rate, systemic resistance and pulmonary wedge pressure were lower. Furthermore, acute O2 inhalation did not modify heart rate or any hemodynamic variables. These results suggest that after digoxin therapy chemoreflex was no more activated in these patients. This effect may be related to the sympatho-inhibitory and to the positive inotropic effects of digoxin: improving hemodynamic and blood gas parameters may result in the inactivation of the reflex.     

Dependence of the functional capacity of the cardiorespiratory system on the body mass in patients with coronary heart disease

The influence of excessive body mass on the development of cardiorespiratory deficiency was studied in patients with coronary heart disease (CHD). Basic parameters of hemodynamics and gas exchange were measured during a graded exercise test. In the CHD patients with excessive body mass, mean blood pressure, cardiac output, left ventricular power output, and left ventricular posterior wall thickness were significantly increased even at rest. During exercise, these patients displayed an increase in myocardial energy consumption and peripheral vascular resistance. It was concluded that an excess in body mass is critical when the increase in the body mass index (Quetelet’s index) exceeds the norm by 20%.     

Determinants of maximal oxygen uptake in severe acute hypoxia

To unravel the mechanisms by which maximal oxygen uptake (VO2 max) is reduced with severe acute hypoxia in humans, nine Danish lowlanders performed incremental cycle ergometer exercise to exhaustion, while breathing room air (normoxia) or 10.5% O2 in N2 (hypoxia, approximately 5,300 m above sea level). With hypoxia, exercise PaO2 dropped to 31-34 mmHg and arterial O2 content (CaO2) was reduced by 35% (P < 0.001). Forty-one percent of the reduction in CaO2 was explained by the lower inspired O2 pressure (PiO2) in hypoxia, whereas the rest was due to the impairment of the pulmonary gas exchange, as reflected by the higher alveolar-arterial O2 difference in hypoxia (P < 0.05). Hypoxia caused a 47% decrease in VO2 max (a greater fall than accountable by reduced CaO2). Peak cardiac output decreased by 17% (P < 0.01), due to equal reductions in both peak heart rate and stroke VOlume (P < 0.05). Peak leg blood flow was also lower (by 22%, P < 0.01). Consequently, systemic and leg O2 delivery were reduced by 43 and 47%, respectively, with hypoxia (P < 0.001) correlating closely with VO2 max (r = 0.98, P < 0.001). Therefore, three main mechanisms account for the reduction of VO2 max in severe acute hypoxia: 1) reduction of PiO2, 2) impairment of pulmonary gas exchange, and 3) reduction of maximal cardiac output and peak leg blood flow, each explaining about one-third of the loss in VO2 max.     

Estimation of cardiac output by analysis of respiratory gas exchange.

Cardiac output is estimated by least squares fitting of a model of pulmonary gas exchange to measurements of respiratory gas composition obtained with a mass spectrometer during a rebreathing maneuver. This new technique estimates cardiac output on spontaneously breathing subjects at rest and requires neither central venous nor arterial blood samples. Principal features of the technique are the use of multiple gases simultaneously in the analysis, the use of a mathematical model for breath-to-breath evaluation of gas exchange, and simultaneous estimation of gas exchange and alveolar gas tensions with the same instrumentation. The technique is compared with thermal dilution estimates in dogs before and during hemorrhagic shock. Two-thirds of these estimates were within 20% of one another. The standard deviation of replication was 15%. Shortcomings, possibilities for improvement, and possible applications are discussed.     

Relationship among cardiac output, shunt, and inspired O2 concentration.

In comparing gas exchange responses of the methacholine- (MCh) challenged mongrel dog with leukotriene receptor blockers and placebo at different inspiratory O2 fractions (FIO2), we previously noted systematically different values of cardiac output as a function of drug administration and/or FIO2. This confounds identification of the effects of FIO2 and/or drugs on gas exchange, because shunt is well known to vary directly with cardiac output when other factors are equal. Accordingly, in six dogs we examined the dependence of combined shunt and low ventilation-perfusion (VA/Q) blood flow ("shunt") on cardiac output in the MCh-challenged mongrel dog. Two dogs breathed 100% O2, another two breathed room air, and the final pair breathed 12% O2 while cardiac output was altered several times by sequentially opening and closing arteriovenous fistulas every 10 min for approximately 90 min after a standard MCh challenge. On 100% O2, shunt increased by 11.0% of the cardiac output per 1-l/min increase in cardiac output. On room air, the value was 7.4%. With 12% O2 breathing shunt rose by only 2.2% per 1-l/min rise in blood flow. This FIO2 -dependent behavior of the shunt-cardiac output relationship was highly reproducible, both within and between animals. It suggests that the increase in shunt with cardiac output depends more on vascular tone of noninjured areas than on tone of the low VA/Q regions (which are hypoxic at all FIO2 values).     

Contribution of cardiogenic oscillations to gas exchange in constant-flow ventilation

The contribution of cardiogenic oscillations to gas exchange during constant-flow ventilation was examined in 11 dogs. With the use of two variations of cardiopulmonary bypass to maintain the systemic and pulmonary circulation, the influence of cardiogenic oscillations was removed by arresting the heart. Cardiac arrest by ventricular fibrillation was associated with a mean decrease in alveolar ventilation of 43% in five dogs on right and left heart bypass. However, successful defibrillation and return of the prearrest level of alveolar ventilation could not be achieved; thus we studied six dogs on left heart bypass. Alveolar ventilation decreased an average of 37% with cardiac arrest, and defibrillation resulted in a return of alveolar ventilation to 81% of the prearrest value. These results are consistent with previous predictions that cardiogenic oscillations are an important mechanism of gas transport during constant-flow ventilation.     

Intrinsic and extrinsic influences on cardiac rhythms in crustaceans

Several factors cause predictable changes in heart rate of crustaceans thus affecting basic heart rhythms. In decapod crustaceans these consist of: many internal factors including influences from neural and neurohormonal systems and chemosensory influences; many external factors including startling stimuli and other disturbance; ventilatory (scaphognathite) reversals; tail flips and other postural movements including locomotor activity; and variations in environmental factors such as oxygen level, temperature and air-exposure. In many cases the initial response involves temporary bradycardia or cardiac arrest. These responses may quickly facilitate to sustained low level stimuli although maintained strong stimulation will eventually be associated with cardio-acceleration and escape responses. Measurement of change in heart rate alone is rarely a sensible monitor of cardiac performance in crustaceans since simultaneous changes in cardiac stroke volume occur which may confound diagnosis. Hypoxia for instance causes decrease in heart rate of adult crustaceans but the apparent decrease in cardiac output is offset or reversed by increase in stroke volume. Concomitant changes occur in cardiac output and in the proportion of cardiac output which is delivered to particular tissues. In fact change in heart rhythm is only one factor in a complex suite of responses involving several physiological systems which compensate uniquely for changes in environmental or other stimuli. Both neural and neuro-hormonal factors are known to play a role in control of these complex responses.     

Cardio- and hemodynamics of dogs in exposure of the heart to immune complexes

The cardiovascular effects induced by in-vitro obtained immune complexes (horse serum antigens--rabbit specific antibodies) were studied in dogs. Intracoronary administration of immune complexes was followed by the development of a hypotensive reaction, with a marked decrease in the cardiac output, left ventricle performance, and impairment of pump heart function. After administering immune complexes no marked injuries to the myocardium or depression of its contractility were recorded in the acute period of the reaction. A substantial decrease of venous blood return to the heart caused by blood pooling in the venous peripheral vascular bed underlies pump heart function impairment and the decreased cardiac output.     

Environmental influences on the development of the cardiac system in fish and amphibians

In poikilothermic animals body temperature varies with environmental temperature, and this results in a change in metabolic activity (Q10 of enzymatic reactions typically is around 2-3). Temperature changes also modify gas transport in body fluids. While the diffusion coefficient increases with increasing temperatures, physical solubility and also hemoglobin oxygen affinity decrease. Therefore, an increase in temperature typically requires adjustments in cardiac activity because ventilatory and convectional transport of respiratory gases usually are tightly coupled in adults in order to meet the oxygen demand of body tissues. Hypoxic conditions also provoke adaptations in the central circulatory system, like the hypoxic bradycardia, which has been described for many adult lower vertebrates, combined with an increase in stroke volume and peripheral resistance. In embryos and larvae the situation is much more complicated, because nervous control of the heart is established only late during development, and because the site of gas exchange changes from mainly cutaneous gas exchange during early development to mainly pulmonary or branchial gas exchange in late stages. In addition, recent studies in amphibian and fish embryos and larvae reveal, that at least in very early stages convectional gas transport of the hemoglobin is not essential, which means that in these early stages ventilatory and convectional gas transport are not yet coupled. Accordingly, in early stages of fish and amphibians the central cardiac system often does not respond to hypoxia, although in some species behavioral adaptations indicate that oxygen sensors are functional. If a depression of cardiac activity is observed, it most likely is a direct effect of oxygen deficiency on the cardiac myocytes. Regulated cardiovascular responses to hypoxia appear only in late stages and are similar to those found in adult species.     

The effects of dobutamine and dopamine on intrapulmonary shunt and gas exchange in healthy humans

The development of intrapulmonary shunts with increased cardiac output during exercise in healthy humans has been reported in several recent studies, but mechanisms governing their recruitment remain unclear. Dobutamine and dopamine are inotropes commonly used to augment cardiac output; however, both can increase venous admixture/shunt fraction (Qs/Qt). It is possible that, as with exercise, intrapulmonary shunts are recruited with increased cardiac output during dobutamine and/or dopamine infusion that may contribute to the observed increase in Qs/Qt. The purpose of this study was to examine how dobutamine and dopamine affect intrapulmonary shunt and gas exchange. Nine resting healthy subjects received serial infusions of dobutamine and dopamine at incremental doses under normoxic and hyperoxic (inspired O(2) fraction = 1.0) conditions. At each step, alveolar-to-arterial Po(2) difference (A-aDo(2)) and Qs/Qt were calculated from arterial blood gas samples, intrapulmonary shunt was evaluated using contrast echocardiography, and cardiac output was calculated by Doppler echocardiography. Both dobutamine and dopamine increased cardiac output and Qs/Qt. Intrapulmonary shunt developed in most subjects with both drugs and paralleled the increase in Qs/Qt. A-aDo(2) was unchanged due to a concurrent rise in mixed venous oxygen content. Hyperoxia consistently eliminated intrapulmonary shunt. These findings contribute to our present understanding of the mechanisms governing recruitment of these intrapulmonary shunts as well as their impact on gas exchange. In addition, given the deleterious effect on Qs/Qt and the risk of neurological complications with intrapulmonary shunts, these findings could have important implications for use of dobutamine and dopamine in the clinical setting.     

Induction of oscillatory ventilation pattern using dynamic modulation of heart rate through a pacemaker

For disease states characterized by oscillatory ventilation, an ideal dynamic therapy would apply a counteracting oscillation in ventilation. Modulating respiratory gas transport through the circulation might allow this. We explore the ability of repetitive alternations in heart rate, using a cardiac pacemaker, to elicit oscillations in respiratory variables and discuss the potential for therapeutic exploitation. By incorporating acute cardiac output manipulations into an integrated mathematical model, we observed that a rise in cardiac output should yield a gradual rise in end-tidal CO2 and, subsequently, ventilation. An alternating pattern of cardiac output might, therefore, create oscillations in CO2 and ventilation. We studied the effect of repeated alternations in heart rate of 30 beats/min with periodicity of 60 s, on cardiac output, respiratory gases, and ventilation in 22 subjects with implanted cardiac pacemakers and stable breathing patterns. End-tidal CO2 and ventilation developed consistent oscillations with a period of 60 s during the heart rate alternations, with mean peak-to-trough relative excursions of 8.4 +/- 5.0% (P < 0.0001) and 24.4 +/- 18.8% (P < 0.0001), respectively. Furthermore, we verified the mathematical prediction that the amplitude of these oscillations would depend on those in cardiac output (r = 0.59, P = 0.001). Repetitive alternations in heart rate can elicit reproducible oscillations in end-tidal CO2 and ventilation. The size of this effect depends on the magnitude of the cardiac output response. Harnessed and timed appropriately, this cardiorespiratory mechanism might be exploited to create an active dynamic responsive pacing algorithm to counteract spontaneous respiratory oscillations, such as those causing apneic breathing disorders.     

Comparison of Cardiorespiratory Effects of Isoprenaline and Salbutamol in Patients with Bronchial Asthma

The effects of isoprenaline and salbutamol administered orally, by inhalation, or by intravenous infusion were compared in 13 asthmatic patients. Bronchodilator activity was assessed by serial measurement of specific airways conductance (SGaw). Log-dose response curves were obtained for both drugs and showed them to be equipotent as bronchodilators. Cardiovascular effects were variable, but in general, isopenaline caused greater rise in pulse rate and a greater change in blood pressure than the same dose of salbutamol.Cardiorespiratory measurements during continuous intravenous infusion of increasing doses of both drugs suggested a greater effect of isoprenaline than the same dose of salbutamol on metabolic rate, pulmonary ventilation, pulmonary gas exchange, cardiac output, and heart rate. The effect of salbutamol on the heart rate was about 10 times less than that of isoprenaline but lasted longer.     

Reducing lung strain after pneumonectomy impairs oxygen diffusing capacity but not ventilation-perfusion matching.

After pneumonectomy (Pnx), mechanical strain on the remaining lung is an important signal for adaptation. To examine how mechanical lung strain alters gas exchange adaptation after Pnx, we replaced the right lung of adult dogs with a custom-shaped inflatable silicone prosthesis. The prosthesis was kept 1) inflated (Inf) to reduce mechanical strain of the remaining lung and maintain the mediastinum in the midline, or 2) deflated (Def) to allow lung strain and mediastinal shift. Gas exchange was studied 4-7 mo later at rest and during treadmill exercise by the multiple inert gas elimination technique while animals breathed 21 and 14% O2 in balanced order. In the Inf group compared with Def group during hypoxic exercise, arterial O2 saturation was lower and alveolar-arterial O2 tension difference higher, whereas O2 diffusing capacity was lower at any given cardiac output. Dispersion of the perfusion distribution was similar between groups at rest and during exercise. Dispersion of the ventilation distribution was lower in the Inf group at rest, associated with a much higher respiratory rate, but rose to similar levels in both groups during hypoxic exercise. Mean pulmonary arterial pressure at a given cardiac output was higher in the Inf group, whereas peak cardiac output was similar between groups. Thus creating lung strain by post-Pnx mediastinal shift primarily enhances diffusive gas exchange with only minor effects on ventilation-perfusion matching, consistent with the generation of additional alveolar-capillary surfaces but not conducting airways and blood vessels.     

Haemodynamic effects of beta-adrenergic blockade in hyperthyroid patients with and without heart failure.

Haemodynamic studies were performed in 10 patients with uncomplicated thyrotoxicosis and seven with thyrotoxic cardiac failure. The cardiac output of those with uncomplicated hyperthyroidism was higher than normal at rest. After 2 mg of intravenous propranolol there was a 13% fall but the level was still higher than normal. In patients with thyrotoxic cardiac failure the resting cardiac output was normal, but it fell after propranolol by 30% to subnormal levels. In both groups there was an increase in right heart pressures and fall in the rate of increase in arterial pressure, which indicated a decrease in myocardial contractility. These results indicate that increased autonomic activity is a compensatory phenomenon in hyperthyroid heart failure and that its abolition by beta-blocking drugs has a deleterious effect on cardiac function. They are therefore contraindicated in patients with thyrotoxic heart failure.     

心力衰竭状态下的动脉压力感受器反射

心力衰竭是以心脏泵血功能降低（心输出量减少）为始动因素的临床综合征。心输出量降低首先引起动脉压力感受性反射失负荷,进而通过迷走-交感机制加快心率;同时,支配血管床的交感传出活动增强,进而增加总外周阻力。本文主要论述在心力衰竭状态下压力感受性反射在循环功能异常调控中的作用机制。本综述及我们近年的研究表明：（1）在心力衰竭状态下压力感受性反射功能明显减弱;（2）中枢血管紧张素Ⅱ和活性氧在压力感受性反射功能失调中发挥关键作用;（3）心交感传入刺激和化学感受性反射能抑制压力感受性反射;（4）适当的运动可以部分纠正异常的心血管反射活动。