Francis L. Abel

Respiratory and cardiac effects on venous return

Abstract Cardiac activity and respiration markedly alter the venous flow patterns in the major thoracic systemic veins. Cardiac activity ( vis a fronte ) is associated with two periods of increased and two periods of decreased venous flow, corresponding to changes in atrial pressure. Respiratory activity predominates in most instances, however, producing a large increase in venous return during inspiration. Alterations in respiratory activity produced by procedures such as positive pressure ventilation, airway occlusion, whining, etc., cause much greater changes in venous return and cardiac output than do changes in posture or passive tilting. Excitement, exercise, and pentobarbital anesthesia can produce marked changes in venous return. Pentobarbital can increase the percentage of blood returning to the right heart via the inferior vena cava. Gravity apparently is relatively unimportant in returning blood to the heart.

An Analysis of the Left Ventricle as a Pressure and Flow Generator in the Intact Systemic Circulation

The effects of increasing and decreasing peripheral resistance on the relationship between aortic pressure and left heart output were investigated in 41 experiments in the dog. The data were analyzed in terms of the slope of the aortic pressure-cardiac output graphs. The results indicate a finite variable internal resistance for the left ventricle. In general it acts as a low resistance generator (constant pressure source) for situations of low peripheral resistance and as a higher resistance generator for situations of high peripheral resistance, although its constant pressure attributes were much more consistent and pronounced than its constant flow characteristics.

Myocardial Performance in Hemorrhagic Shock in the Dog and Primate

Myocardial performance was investigated in nine dogs and six monkeys during experimental hemorrhagic shock under conditions of constant afterload. Left ventricular function curves were obtained by opening an aorta to left atrial bypass, and simultaneous recordings of stroke volume, peak stroke power, maximal dP/dt, maximal dF/dt, heart rate, atrial pressure and end-diastolic pressure were made. Total plasma catecholamine content was also measured in the monkeys during the control period and at death. The dogs showed a marked increase in performance, in contrast to the control group, 0–2 hours after reinfusion. Performance then deteriorated significantly by 2–4 hours, although it was still comparable to control levels. However, higher atrial and end-diastolic pressures were obtained, and in most cases cardiac failure developed soon thereafter. Two additional dogs were subjected to all stresses except the hypotension for 10 hours without evidence of deterioration. The monkeys did not withstand the surgical procedure as well as the dogs did and survived a maximum of 136 minutes after reinfusion. Catecholamine levels decreased in five of the six monkeys but not below normal levels, which indicates that failure was not due to depletion of myocardial stores. The data are interpreted as direct evidence for a factor(s) seriously depressing myocardial performance during the postinfusion period of experimental hemorrhagic shock in the dog and the monkey despite the high levels of performance in the early postinfusion period and the maintenance of coronary driving pressure and arterial oxygen content.

Effects of Acetylstrophanthidin on Coronary Vascular Resistance and Myocardial Oxygen Consumption

The effects of acetylstrophanthidin on coronary circulation were studied in 31 dogs. Coronary blood flow was measured in empty beating hearts or in fibrillating hearts by collecting coronary venous return during perfusion of the systemic circulation (cardiopul-monary bypass). In 14 animals with ventricular fibrillation, acetylstrophanthidin caused an initial coronary constriction and fall in coronary blood flow. This was followed, after approximately 10 minutes, by a significant drop in resistance and a rise in coronary blood flow which persisted for the remainder of the experiment. Associated with the increase of blood flow was an increase of myocardial oxygen consumption. This effect was not abolished by ganglionic blockade, cardiac denervation or bilateral adrenalectomy. In nine dogs with beating but empty hearts, after the initial constriction of the coronary vessels, there was only a small change in coronary blood flow and resistance, although myocardial oxygen consumption was increased. The lack of coronary vasodilatation was attributed to increased mechanical resistance due to the augmented force of contraction produced by the drug.

Peripheral Vascular Response to Simulated Hemorrhagic Shock during Cardiopulmonary Bypass in Dogs

The peripheral vascular response to hemorrhagic hypotension was examined in thirteen anesthetized dogs on cardiopulmonary bypass. Nine animals were subjected to 2 or 4 hours of hypotension by decreasing pump output (30ml/kg/min), thereby controlling mean arterial blood pressure at 40 mm Hg. Systemic flow was then returned to prehypotensive levels (100 ml/kg/min), and the animals were observed for 6 more hours. Dynamic venous compliance was determined by occluding the venous outflow catheters and recording the venous pressure rise at a known rate of inflow. Venous compliance, changes in reservoir fluid volume, total peripheral resistance, and mean arterial blood pressure were measured at 30-minute intervals. During the first hour of hypotension there was a marked increase in venous compliance, a decrease in reservoir fluid volume, and an increase in total peripheral resistance. Fluid uptake increased during the first hour after returning flow to control values, although mean arterial blood pressure, venous compliance, and total peripheral resistance were similar to the controls during the posthypotensive period. Three dogs were subjected to the same procedure, but without hypotension, to determine the influence of extracorporeal circulation on dynamic compliance when flow is constant. The results indicate that the dog on cardiopulmonary bypass responds to hypotension by arterial constriction and an increase in venous compliance. There was no evidence to indicate a loss of venous or arterial tone within 6 hours following the period of hypotension, although the gross changes in the gut at autopsy were similar to those seen in dogs dying in hemorrhagic shock.

Problems with use of the end systolic pressure-volume slope as an indicator of left ventricular contractility: an alternate method.

ABSTRACT The use of end-systolic elastance as a parameter of left ventricular contractility is based on a theory put forward by Sagawa (1) and is limited by an assumed linearity of the model for a time varying compliance. A major problem is the contractility-dependent curvilinearity of the end-systolic pressure-volume relationship (ESPVR), which may result in intercept volumes that are below a passive unstretched volume. Based on the experimental data of Burkhoff et al. (2), we demonstrate the reasons for the lack of correlation of the slope (k) of the end-systolic pressure (Pes)-volume (Ves) relationship with ventricular contractility. A parabolic relation, Pes = a ± Ves2 + b ± Ves + c, was used for approximation of the ESPVRs, as proposed by Burkhoff et al., and the slope (k = 2 ± a ± Ves + b), together with the volume axis intercepts (Vo), calculated for the tangents for all Pes/Ves points of the ESPVRs. The results demonstrate the volume range dependence of the slope and Vo of linear regression lines. However, intercepts of the ESPVRs tangents with a midrange constant pressure line (e.g., 80 mmHg or 100 mmHg) justify the use of the shift of the end-systolic pressure-volume relationship as a parameter of left ventricular contractility. This method appears to be valid over a much wider range of end-systolic volumes than is the use of the slope alone.

Beat-to-beat evaluation of cardiac function in low-dose endotoxemia using a conscious sheep model.

The effects of very low doses of endotoxin (20 ng/kg/h for 8 h) were evaluated in a conscious sheep model in which introducers for catheters for monitoring pressure and ventricular dimensions had been previously inserted so that the studies could be performed without anesthesia and without a previous thoracotomy. Analog data was obtained at hourly intervals for 10 h and again at 24 h and was used to construct a beat-to-beat analysis of left ventricular performance. Only minimal effects were observed on heart rate, end diastolic pressure, arterial pressure, cardiac output, or cardiac work, although there was a significant rise in pulmonary artery pressure at 1 h of infusion. Despite the absence of changes in heart rate, preload, or afterload, maximal dp/dt decreased significantly by 4 h and remained decreased for the 10-h observation period; it returned to normal at 24 h. End systolic elastance decreased at 6 h and Pmax/EDV, a new indicator of performance, also decreased at 6 and 9 h. Thus, systolic performance decreased. Negative dp/dt did not change, but time for relaxation from 80% to 20% of peak ventricular pressure increased significantly at 5, 6, and 8 h. Plasma TNF-alpha was also measured and showed a significant rise at 2 h, but rapidly decreased thereafter. These results indicate an early depression of myocardial contractility and distensibility at doses of endotoxin insufficient to produce measurable effects on arterial pressure or cardiac output.

Comparative measurements of left-ventricular performance produced by rapid changes in blood volume in dogs

Left-ventricular function was evaluated in 11 open-chest dogs under pentobarbital anesthesia. Ventricular performance was altered by infusing or withdrawing crossmatched blood, and simultaneous recordings obtained of left-atrial pressure, leftventricular pressure, aortic flow, and aortic pressure. From these recording were obtained the stroke volume, stroke work, peak ventricular power, and the maximal rate of change of aortic flow and ventricular pressure. The derived variables were plotted versus end diastolic pressure to provide ventricular-function curves. The curves were obtained during a control state, during norepinephrine infusion, and subsequent to aortic constriction at the level of the coronary ostia. Studies were done in the heart-rate paced and nonpaced animal; the data were presented in terms of per cent change from control values. Peak power and stroke work provided the more classical type of ventricular-function curves and it is suggested that these provide the most useful information. Pressure-derivative curves were the most widely separated. Similar studies were repeated in seven animals in which afterload was controlled at 100 mm Hg. Curve shape was somewhat altered but overall changes were comparable.

Effects of Alterations in Peripheral Resistance on Left Ventricular Function.

Summary The effects of increasing or decreasing peripheral resistance on heart rate, left ventricular stroke volume, cardiac output, stroke work, cardiac work and aortic pressure were investigated in 51 open-chest acute experiments. The results show a decrease in cardiac output, heart rate, and cardiac work with an increase in systemic resistance. Aortic pressure increased, but stroke work showed no consistent relationship to an increase in resistance. Stroke volume increased in approximately one-half of the animals when resistance was increased, accompanied by a decrease in heart rate. Cardiac output, stroke volume, cardiac work and stroke work all increased in response to a decrease in systemic resistance, accompanied by smaller changes in heart rate and aortic pressure. Right atrial pressure also increased significantly when resistance was decreased.

Renal Function in Dogs with Hypertension Induced by Immunologic Nephritis

Summary Development of hypertension in unanesthetized dogs in response to rabbit anti-canine kidney glomerular antiserum (IgG) was examined over periods of time totalling 7.5–9 mo. The dosage of IgG was such as to cause minimal renal functional alterations, and BUN remained normal. Two of three dogs studied developed hypertension. Plasma renin and aldosterone value were not increased. Tentative mechanisms for the observed hypertension are discussed in the light of possible failure of the kidney medulla to produce and release depressor material. We are indebted to Chris Amneus and Carol Van Ermen for valuable technical assistance; to Dr. Myron Weinberger, Department of Medicine, for the radioimmune assays of renin and aldosterone, and to Dr. Roger P. Maickel, Department of Pharmacology, Bloomington, for the catecholamine assays.