Showing papers in "Circulation Research in 1965"

Equations for Measuring Blood Flow by External Monitoring of Radioisotopes

Abstract: It is possible by external monitoring alone to measure blood flow per unit volume through any vascular bed accessible to external monitoring of the radioactive tracer if the tracer input function or if the quantity of tracer entering the system is known. The methods proposed exploit the fact that the mean transit time through the system is the flow per unit volume of distribution of tracer. The equations are free of assumptions that require solutions as exponentials or any other specified frequency function of transit times. If the input function is known, measurement of the concentration of tracer in blood leaving the part sensed by the external detector, combined with external detection of radioactivity, can lead to measurement of absolute blood flow.

Measurement of Pulmonary Edema

Abstract: Two methods for the measurement of pulmonary edema are compared. The first method, which permits serial measurements in vivo, depends on the difference in mean transit time of a water label and an intravascular label. The second method is a postmortem one in which total lung water is measured and allocated to the pulmonary blood or to pulmonary extravascular water. Three groups of six dogs each were studied: controls, a group with pulmonary edema produced by elevating pulmonary venous pressure, and a group with pulmonary edema produced by alloxan. The isotopic as compared with the postmortem method accounted for 71% of the pulmonary extravascular water found in the controls, 94% in high pressure edema and 57% in alloxan edema. Shunting, as measured by a large fall in PaO 2 despite 100% oxygen breathing, became marked in a second group of five alloxan dogs and only 31% of the postmortem pulmonary extravascular water was measured by the isotope method. It is concluded that the isotope transit time method is a useful one for the serial measurement of pulmonary edema in vivo. The edema water is determined more accurately when pulmonary edema is due to elevated pulmonary venous pressure than when due to increased vascular permeability.

Interstitial Fluid Pressure: II. Pressure-Volume Curves of Interstitial Space

Abstract: Pressure-volume curves of the interstitial fluid spaces were estimated using four different methods. Interstitial fluid pressure was measured from implanted perforated capsules while interstitial fluid volume was varied (a) by perfusing the isolated hind limb of the dog with several types of fluid and at different perfusion pressures, (b) by elevating the venous pressure so that fluid would transude into the interstitial compartment, (c) by infusing large quantities of Tyrode's solution into the whole animal, and (d) by intravenous infusion of concentrated dextran solution. In all these studies, the compliance of the interstitial fluid system was found to be very low when the interstitial fluid pressure was negative but very high when the pressure rose slightly above atmospheric pressure. A physical model of the interstitial spaces was also constructed. Pressure-volume curves recorded from this model demonstrated a pattern of compliance changes similar to that shown by the interstitial pressure-volume curves recorded from dogs. These experiments give further support to the concept that the interstitial fluid pressure is normally negative but becomes positive as edema fluid accumulates.

Responses of coronary smooth muscle to catecholamines.

Abstract: Responses to catecholamines were studied in isolated helical muscle strips of large and small coronary vessels and in isolated perfused coronary arteries from the dog. Epinephrine and norepinephrine in concentrations well below those normally present in the blood uniformly caused relaxation of small coronary vessels. Norepinephrine was much more potent than epinephrine. The relaxation was reversibly blocked by the beta adrenergic blocker, nethalide. During this blockade, catecholamines either were inactive or produced a slight contraction. Strips contracted by angiotensin, blood or KCl, as well as those completely depolarized by K2SO4, were relaxed by catecholamines. Strips taken from large coronary vessels, unlike those from small vessels, were, in some cases, contracted by catecholamines; in others, after a transient contraction, they were relaxed. Contraction was blocked by Dibenzyline. This difference in behavior of large and small vessels may account for some of the contradictions found in the litera...

Measurement of Renin Activity in Human Plasma

Abstract: A method is described for estimating plasma renin activity by using renin substrate present in plasma. This method differs from other indirect renin assay methods by (1) incubation in the absence of ions thus establishing conditions for zero order kinetics for the reaction between endogeneous renin and substrate and (2) the use of angiotensinase inhibitors di-sodium ethylenediamine tetraacetic acid (EDTA) and d-isopropylfluorophosphate (DFP). Recoveries of renin added to plasma in levels similar to those occurring in plasma are 85% SD±7%. The incubation was done at pH 5.5 which was shown to be the optimum for human renin reacting with human substrate. By incubating human plasma samples with known quantities of human renin, evidence was obtained suggesting that factors other than enzyme or total substrate concentrations affect the velocity of angiotensin formation. This variability of reaction rate may be explained by the existence of an inhibitor or activator in this system or by a variation in the type of substrate.

Relative Roles of the Sympathetic and Parasympathetic Nervous Systems in the Reflex Control of Heart Rate

Abstract: This study was designed to define the relative roles of the sympathetic and parasympathetic nervous systems in the reflex alterations of heart rate consequent to changes in arterial pressure. In 23 experiments carried out on 22 anesthetized dogs and in studies performed on four trained, unanesthetized dogs, acute changes in arterial pressure were produced by administering drugs acting on the peripheral vascular bed. The effects of acutely elevating systemic pressure were also investigated in four intact unanesthetized human subjects. Augmenting arterial pressure above control levels with graded doses of phenylephrine always slowed heart rate strikingly. Although complete sympathetic blockade with guanethidine or pronethalol did not significantly alter the degree of slowing, parasympathetic blockade with atropine or vagotomy essentially abolished this response. Conversely, lowering pressure with intravenous injections of nitroglycerin always raised heart rate in the control state, a response abolished by sympathetic blockade with guanethidine or nethalide, but not by parasympathetic blockade with vagotomy or atropine. Thus, when arterial pressure rises above control, the decrease in heart rate is mediated by the parasympathetic nervous system, withdrawal of sympathetic activity playing no detectable role; when pressure falls below control levels, the elevation of heart rate is mediated primarily by the sympathetic nervous system. These findings are not consonant with the traditional concept of control of heart rate which predicates simultaneous reciprocal changes in activity occurring in the two components of the autonomic nervous system.

Aberrant A-V Impulse Propagation in the Dog Heart: A Study of Functional Bundle Branch Block

Abstract: Excessive delay and configurational change of ventricular responses to atrial premature beats, previously attributed to dissociation within the A-V node, were shown to be due to functional block of the right bundle branch. It was found that the refractory period (RP) of the right bundle branch often exceeded the functional refractory period (FRP) of the A-V node at slow heart rates, permitting an early premature atrial response to reach the ventricles before recovery of the right bundle. Vagal stimulation and rapid driving frequencies, by delaying the intranodal transit of the premature response, prevented the exposure of bundle branch block. Epinephrine in low doses sometimes facilitated its occurrence. Premature responses initiated in the His bundle in open heart preparations were commonly blocked in the right bundle under conditions in which atrial premature responses were normally propagated to the ventricles. Evidence was obtained in such preparations that the portion of the right bundle system beyond the site of the block was activated retrogradely from the left side. Under certain conditions the retrograde activation process returned to the His bundle and the atrium as an echo.

Direct Renal Vasodilatation Produced by Dopamine in the Dog

Abstract: The effects on directly measured renal blood flow, mean blood pressure, and calculated renal vascular resistance of intravenous infusions of dopamine, isoproterenol, and norepinephrine were compared. Dopamine, at doses not affecting mean blood pressure, decreased renal vascular resistance and increased renal blood flow. In contrast, isoproterenol decreased both blood pressure and renal vascular resistance but did not consistently increase renal blood flow. Renal artery injection of dopamine produced vasodilatation at doses ranging from 0.75 to 12 µg and biphasic flow responses including transient vasoconstriction at higher doses. It is concluded that the probable basis for the effect of intravenous dopamine infusion on renal blood flow is its direct renal vasodilating action. The direct effect of dopamine on the femoral vascular bed is vasoconstriction. The combination of renal vasodilating, and femoral vasoconstricting, effects is unique and is interpreted as evidence for a renal vasodilating effect of dopamine distinct from the conventional beta-adrenergic mechanism. A possible physiological role for dopamine other than as a precursor to norepinephrine may be related to this property. It is also suggested that the ability of dopamine to alter the distribution of cardiac output in favor of visceral organs may find useful clinical applications.

Effect of Exercise on Cardiac Output, Left Coronary Flow and Myocardial Metabolism in the Unanesthetized Dog

Abstract: Cardiac output, left coronary artery flow, central aortic blood pressure and myocardial metabolism have been studied in the intact unanesthetized dog during exercise. Cardiac output and left coronary artery flow increase 350 to 400% during moderately severe exercise. The primary mechanical determinant of this increase appears to be cardio-acceleration; the stroke volume and stroke coronary flow contribution is relatively mild. Myocardial oxygen usage increases 300% or more with only a small elevation of the percentage of extraction of oxygen. The large increase of coronary flow in the dog and the significant elevation in hematocrit supply the extra oxygen.

Action of Driving Stimuli from Intrinsic and Extrinsic Sources on in Situ Cardiac Pacemaker Tissues

Abstract: The interactions between pacemakers, and the effects on pacemakers, of terminating imposed driving were studied in the in situ heart of anesthetized dogs. Following atrial fibrillation or termination of a fast drive imposed through an artificial pacemaker, pacemaker action in intrinsic pacemakers is suppressed. Pacemakers tend to accelerate and compete with imposed drives which exceed control rates by only a small percentage (10 to 15%). Arrhythmias may result if imposed drive is slower than or identical with intrinsic pacemaker rate. Post-drive depression of pacemakers and the resulting deceleration of the heart is followed normally by an overshoot or supranormal acceleration. The magnitudes and durations of depression and late acceleration are proportional, within limits, to the rate and duration of drive. Atrioventricular and ectopic atrial pacemakers are much more readily depressed than is the sinoatrial pacemaker. Furthermore, beats of ectopic origin are much more likely to occur while subsidiary pacemakers are recovering from post-drive depression. Augmentation of depression by Prostigmin, its diminution by atropine, and the potentiation of late acceleration by cocaine and its absence after reserpine or guanethidine pretreatment, indicate that acetylcholine and catecholamines are liberated by driving stimuli. Placement of the pacemaker over the sinoatrial node, or near to regions where nerve terminals are concentrated, results in the greatest post-drive effects. The fact that propagated action potentials cause depressions and accelerations subject to drug block or potentiation indicates that mediators are also released in the course of propagated activity. Since atropine does not completely block post-drive depression, it is thought that a potassium ion shift may be involved.

Pulmonary Vascular Impedance in the Dog

Abstract: Pulmonary vascular hydraulic input impedance was measured in 13 anesthetized openchest dogs with normal sinus rhythm, and 2 dogs with surgically induced atrioventricular block, by means of electromagnetic flowmeters and strain gauge manometers of known frequency response. The linearity of the pulmonary bed was evaluated by measuring impedance while the heart rate, and hence the pulsatile input to the bed, was varied. The pulmonary bed behaved as a quasilinear system, within the limits of accuracy of the methods employed and the range of frequencies tested. The use of input impedance, or oscillatory pressure/flow ratio, to describe some characteristics of the bed is therefore justifiable, and analogies with linear models like the simple transmission line are not unreasonable. The characteristic input impedance averaged 3,094 dyne sec cm-5 kg, or about one-third the magnitude of the pulmonary vascular resistance, and was therefore a significant part of the total opposition that must be overcome in moving bl...

Spread of Excitation from the Sinus Node

Abstract: Microelectrodes were employed to determine the mode of propagation of excitation from the sinus node in the rabbit heart. The excitation starts from the sinus node radially, at first, but then proceeds to the crista terminalis, often obliquely. This is because some special tissue having a slow conduction velocity lies behind the sinus node, and also because there is a zone of relatively faster conduction at the basal wall of the superior vena cava. Once the excitation wave enters the crista terminalis, it travels rapidly in two opposite directions through two branches of the ring-like structure which is formed by the crista terminalis and its extension. The excitation wave traveling through the branch encircling the inferior vena cava reached the atrioventricular node earlier in most instances. In the caval region inside the ring-like structure there is a zone of relatively faster conduction. The conduction to the atrioventricular node through this route is latent in the normal state, because conduction through the ring-like structure takes place beforehand. In the caval region near the sinus node, the conduction velocity of the excitation wave from the spontaneously beating sinus node was greater than that from the electrically driven atrium. The spontaneous action potential showed also a steeper rise than that produced by electrical stimulation. The mechanism responsible for this is discussed.

Factors Controlling Pacemaker Action in Cells of the Sinoatrial Node

Abstract: Rapid drive of isolated pacemaker tissues from cats resulted in a post-drive depression followed by a late acceleration to supernormal rates of pacemaker activity. These effects were similar to those occurring after drive of the pacemaker in situ. Lower SA nodal pacemakers discharged more slowly and irregularly than did upper SA nodal pacemaker cells. They were more readily depressed by rapid imposed drive. The balance between depression and acceleration varied in different preparations. Drive at only slightly above the intrinsic rate resulted frequently in acceleration not preceded by depression. Within limits, the greater the frequency and duration of drive, the greater the intensity and duration of both the depression and the late acceleration. Prostigmin augmented and atropine reduced post-drive depression. Cocaine potentiated the late acceleration. Excess potassium reduced post-drive depression and, in concentrations used, caused some acceleration. Pacemaker cells could be driven less rapidly than co...

Renomedullary vasodepressor substance, medullin: isolation, chemical characterization and physiological properties.

Abstract: The chemical and physiological properties of renomedullary depressor substances were investigated utilizing the normotensive, vagotomized, pentolinium-treated rat for assay. By a combination of solvent extraction, column chromatography, and thin-layer chromatography, three biologically active acidic lipids were isolated from rabbit renal medulla. The first compound, called medullin, is an acidic lipid with potent vasodepressor and relatively weak nonvascular smooth muscle-stimulating properties. Ultraviolet analysis revealed spectra closely resembling that of prostaglandin E-1 (PGE-1). Infrared analysis showed the presence of carbonyl, methylene, and hydroxyl groups in addition to trans ethylene bonds. Although closely resembling PGE-1, medullin appears to be a more unsaturated carboxylic lipid with less polar (hydroxyl) groups. The hypotensive action of medullin is attributable to a direct effect on peripheral arteriolar beds without cardiac depression, because intra-arterial and intravenous injections of medullin reduced peripheral resistance markedly and increased cardiac output simultaneously. In addition, no effect on cardiac rate or contractility was observed in the isolated rabbit heart preparation. Comparative studies of medullin and PGE-1 indicated that the hypotensive activity of these compounds is similar with respect to potency and mechanism of action. The only biological difference between crystalline PGE-1 and medullin was a fiftyfold greater stimulation of nonvascular smooth muscle by PGE-1 in comparison to medullin. A second biologically active acidic lipid isolated from rabbit medulla was tentatively identified as PGE-1, and was found to possess both vasodepressor and nonvascular smooth muscle-stimulating properties. The third isolate from rabbit medulla possessed potent intestinal stimulating activity but weak to absent vasodepressor effects, properties similar to those of prostaglandin F compounds.

Increased Pulmonary Vascular Resistance in the Dependent Zone of the Isolated Dog Lung Caused by Perivascular Edema

Abstract: Measurements of the distribution of blood flow in an isolated dog lung made with radioactive xenon showed a great increase in vascular resistance in the dependent zone of the lung in the presence of a raised pulmonary venous pressure in some preparations. Evidence that this increased vascular resistance was caused by perivascular edema consisted of the general correlation with interstitial edema, the regional distribution of the effect, the sensitivity to the arteriovenous pressure difference, the effect of certain infusions particularly hypertonic urea, and the demonstration of edema around the small arteries and veins in rapidly frozen sections. The mechanism of the increased resistance is postulated as an interference with the tethering effect of the lung parenchyma which normally holds the vessels open. The possible role of this mechanism in the increased pulmonary vascular resistance of patients with pulmonary venous hypertension is discussed.

Mechanism of Norepinephrine Depletion in Experimental Heart Failure Produced by Aortic Constriction in the Guinea Pig

Abstract: The present study was undertaken to evaluate the influence of heart failure on the cardiac stores of norepinephrine, and to elucidate the mechanisms responsible for the changes observed. Congestive heart failure was produced in the guinea pig by supravalvular aortic constriction. Significant reductions in both the concentration and content of norepinephrine in the ventricles were observed, the magnitude of changes being related to the severity of the constriction. The renal concentration of norepinephrine was not usually affected. Infusions of large quantities of norepinephrine produced elevations of ventricular norepinephrine concentrations which were significantly less in guinea pigs with heart failure than in normal animals. Injections of lesser quantities of radioactive norepinephrine also resulted in smaller amounts of this material in the hearts of animals with failure. Measurement of the decay of specific activity indicated that heart failure did not alter the net turnover of norepinephrine in the ...

Permeability of the Alveolar Membrane to Solutes

Abstract: The lower lobe of the left lung of 54 dogs was isolated and perfused with a dextran-Tyrode9s solution. The alveoli were filled with Tyrode9s solution, and permeability coefficients were measured for diffusion of several substances across the alveolar membrane. The permeability coefficients of the pulmonary membrane for K 42 , urea, Na 24 , glucose, D 2 O, and dinitrophenal(DNP) were 56.5 ± 3.5, 22.9±9.2, 7.5±2.1, 3.1±0.7, 400, and 400x10 -7 cm/sec, respectively. The effect of varying the flow rate on the permeability coefficient of Na 24 was investigated, and the data failed to show any significant correlation between the flow limits of 3.8 to 12. 8 cm/min/g lung tissue. The effect of two different procedures for filling the alveoli with fluid on the permeability coefficients was also investigated and no difference could be discerned in the results. The data support the thesis that the alveolar membrane has permeability characteristics similar to those of the usual cell membrane. The interstitial fluid volume of the lung (extravascular sodium space) was measured and yielded a value in normal lungs of 0.250 ± 0.129 cc/g lung tissiue. In three edematous lungs, this space averaged three times the normal value.

Depression of ventricular contractility by stimulation of the vagus nerves.

Abstract: In three different types of canine heart preparations, it was demonstrated that efferent vagal stimulation exerts a potent, negative inotropic influence upon the ventricular myocardium. In the paced, isovolumetric, left ventricle preparation, vagal stimulation evoked a reduction of left ventricular systolic pressure which, within limits, varied directly with the magnitude of the stimulus. Supramaximal stimulation elicited a mean reduction of 23% in the peak pressure generated by the left ventricle. No differences could be detected between the effects of the right and left vagi upon ventricular contractility. The percentage changes induced by vagal stimulation upon ventricular contractility in the paced heart were less than the percentage changes in heart rate induced in the spontaneously beating heart. In a pumping heart preparation in which a constant rate of venous return was delivered to the left atrium, vagal stimulation consistently elicited an appreciable elevation of left ventricular end diastolic ...

Nature of the inotropic action of angiotensin on ventricular myocardium.

Abstract: The effect of changes in various chemical and physical factors on the positive inotropic action of angiotensin was studied in isolated papillary muscles of kittens. Pretreatment of the animals with reserpine did not diminish the positive inotropic effect of angiotensin. Concentrations of nethalide which strongly antagonize the response of the papillary muscle to levarterenol or tyramine had no effect on the inotropic concentration-effect curve for angiotensin. It is concluded that angiotensin does not release significant amounts of cate-cholamines from the cardiac stores and that its inotropic action on ventricular myocardium does not result from stimulation of adrenergic β-receptors. Increases in external calcium concentration, decreases in sodium concentration, and shortening of the interval between contractions diminish both the absolute and the relative inotropic effect of angiotensin. All these maneuvers and angiotensin itself raise myocardial contractility by increasing the degree of activation of the contractile element. Cooling of papillary muscles does not decrease the absolute inotropic effect of the drug. Angiotensin and increases in external calcium concentration affect the mechanical properties of papillary muscles in a similar fashion. Angiotensin may raise contractility by augmenting the entry of Ca ++ into the myocardial fiber.

Cardioversion and Digitalis Drugs: Changed Threshold to Electric Shock in Digitalized Animals

Abstract: The relationships between the action of digitalis drugs and the effects of cardioversion were studied in 44 dogs. Ventricular tachycardia provoked by either acetyl strophanthidin (AS) or ouabain could not be reverted to sinus rhythm by DC shock. When ventricular fibrillation was induced electrically during digitalis toxicity, defibrillation could be accomplished readily but the toxic arrhythmia due to digitalis remained unaltered. When ventricular fibrillation was induced by AS, it was also unaffected by repeated high energy discharges. In control animals the median energy to produce ventricular tachycardia by electrical discharge was 400 watt-seconds. Repeated electrical shocks did not change the level of energy required to produce ventricular tachycardia. However, following recovery from ouabain-induced ventricular tachycardia, the electrical threshold for ventricular tachycardia was 0.2 watt-second. A similar but less consistent response was noted after AS-induced ventricular tachycardia. The sensitiza...

Use of radioiodinated fatty acid for photoscans of the heart

Abstract: Radioiodinated fatty acid bound to albumin (RIFA) was given by intravenous injection to dogs and moribund human subjects in order to label heart muscle. Photoscans of the thorax of dogs given RIFA revealed concentration of radioactivity in the ventricular region of the heart due to incorporation of the labeled fatty acid into myocardial triglyceride and phospholipid. Photoscans of the thorax following intravenous injection of radioiodinated serum albumin or NaI131 showed a different density pattern in the region of the heart due to radioactivity in blood within the cardiac chambers. Areas of myocardial infarction were detected in photoscans of the thorax in 11 of 14 dogs in which one coronary artery was ligated. At necropsy the concentration of radioactivity was much higher in healthy myocardium than in infarcted muscle. The same distribution of radioactivity was observed in hearts from three human subjects with myocardial infarction given RIFA shortly before death. It is proposed that areas of myocardial infarction might be demonstrated during life by photoscans of the thorax following intravenous injection of RIFA.

Durations of Transmembrane Action Potentials and Functional Refractory Periods of Canine False Tendon and Ventricular Myocardium: Comparisons in Single Fibers

Abstract: In vitro studies have shown that alterations in the ionic composition of the perfusion fluid, substitution of blood or plasma for Tyrode's solution, time lapse following removal of the cardiac preparation from the animal, and addition of varying amounts of acetylcholine and/or epinephrine, do not change differentially the functional refractory period and action potential duration of false tendon and papillary muscle fibers; false tendon values exceeded those of papillary muscle in all of the above conditions. Cycle length was the only variable found to influence differentially false tendon and papillary muscle functional refractory periods and action potential durations. At very short cycle lengths, produced by premature responses, the functional refractory period and action potential duration of false tendon and papillary muscle cells approached each other. In some experiments the functional refractory periods of premature false tendon responses were less than corresponding values for papillary muscle. The relationship between the action potential durations and functional refractory periods of canine epicardial and endocardial cells was investigated also. It was found that the epicardial cells had a shorter functional refractory period and action potential duration than endocardial units when studied at physiological rates.

Systemic and Coronary Energetics in the Resting Unanesthetized Dog

Abstract: This report is an initial attempt to study the coronary circulation in the chronic unanesthetized dog. A standardized preparation has been developed in which phasic aortic pressure and flow, phasic left coronary inflow, and myocardial metabolism have been studied for many weeks in the unanesthetized dog under resting conditions. The flow patterns in the main left coronary artery and in its major branches are very similar. In the resting dog, the left coronary inflow during systole is 7 to 45% of that during diastole. We believe that much of this flow into the epicardial arteries penetrates into the myocardium. Stroke coronary flow can change considerably without significant alterations of blood pressure and heart rate. Despite this, the coronary flow values (37 to 58 cc) and oxygen usage values (4.4 cc to 8.6 cc) per 100 grams left ventricle per minute are low. Since, however, these measurements can vary considerably not only in different dogs but also in the same dog on the same day, and from day to day, it is suggested that these animals were in a semiresting state and probably not in a basal state.

Oscillatory Flow Impedance in Electrical Analog of Arterial System: Representation of Sleeve Effect and Non-Newtonian Properties of Blood

Abstract: In the analog computer for the human systemic circulatory system, the electrical equivalents of a segment of artery as designed up till now are not satisfactory, because they lack representation of the sleeve effect, which results from the interaction between viscous and inertial forces during pulsatile blood flow. First, a network which accounts for this effect was derived, starting out from entirely different equations. It was surprising to find that this does not alter the circuit completely, but only requires adding to the former circuit a corrective network which, however, may have considerable influence. Second, the effect of the anomalous viscosity of blood was taken into account. Its influence on oscillatory flow has been investigated by Taylor, who derived an expression for the relation between pressure-gradient and flow under the assumption that there exists a small boundary layer of lower viscosity at the wall, and found a similar formula for the case in which the blood is assumed to slip at the wall. The modifications of the electrical circuit, necessary to represent these conditions, are given in this paper and turn out to be remarkably simple.

Influence of atrial systole on effective ventricular stroke volume.

Abstract: The influence of atrial systole on forward or effective ventricular stroke volume at different heart rates and at constant cardiac output was investigated in an open chest dog preparation. The procedure employed allowed a ventricular ejection preceded by an atrial systole to be followed by one which was not. A comparison was made between the effective ventricular stroke volumes of these two ejections. The observations support the view that atrial systole plays a significant role in determining effective ventricular stroke volume and that its influence is greater at higher heart rates when cardiac output is kept constant and stroke volume decreases. The data indicate further that the decrease in effective ventricular stroke volume is due to both a decreased ventricular filling and initial atrioventricular regurgitation.

Electroaugmentation of ventricular performance and oxygen consumption by repetitive application of paired electrical stimuli.

Abstract: When a depolarizing stimulus is delivered to the ventricle immediately following the refractory period, little extrasystolic contraction occurs and repetitive paired stimulation then results in a marked and sustained improvement of ventricular performance which has been termed electroaugmentation. The present study characterizes this augmentation and its effects on myocardial oxygen consumption (MVOO2). In 45 experiments on 14 dogs in which mean aortic pressure and stroke volume were held constant by right heart bypass, a change from single to paired stimulation at identical contraction rates markedly increased the performance of the left ventricle as evidenced by shortening of ejection time increase in left ventricular dp/dt, stroke power, and peak ejection rate, and sometimes a fall in end diastolic pressure. Similar resul were obtained after administration of resepine or nethalide. In 15 experiments on 11 dogs the stroke volume of the left ventricle was varied during single and paired stimulation. Impr...

The Spread of Sinus Activation During Potassium Administration

Abstract: Electrodes were chronically implanted in intact dogs at several locations on the atria and ventricles, and studies made of the effect of an elevated extracellular K+ concentration on the spread of the sinus impulse throughout the atria. It was found that sinus activity propagates to the coronary sinus and ventricles at a time when the atrial muscle fibers have been rendered inexcitable. The finding of such a sino-ventricular rhythm supports the existence of a specialized conducting path between the sinus and the atrio-ventricular node; this path is particularly resistant to depolarization by potassium. Potassium-induced 2:1 sino-atrial block was described. In vitro experiments provided a demonstration that such block is frequency-dependent and due to marked prolongation of the refractory period provoked by high [K]0. It appears that the lengthened refractory period may be due to a marked reduction of the reactivation rate of the "sodium carrying system."

Some Characteristics of Ventricular Echoes

Abstract: Reciprocal responses (ventricular "echoes") were initiated by premature stimuli applied directly to the bundle of His in dog hearts perfused from donor animals. The time relations of the responses in the His bundle and at the atrial margin of the exposed A-V node were studied under a number of conditions. It was found that: 1. The earliest premature response that can be induced in the His bundle is not propagated back to the atrium and does not lead to an echo. 2. There is, in most hearts, a continuous range of H1H2 intervals (the echo "zone") within which reciprocal responses of the His bundle occur. 3. The earliest effective H2 propagates slowly to the atrium, and the echo returns quickly. 4. The latest effective H2 responses propagate more quickly to the atria, but return more slowly. 5. The atrium is an essential link in the echo pathway; i.e., the H2 response must reach and activate the atrium before a return is possible. 6. Direct stimulation of the atrium in advance of the expected arrival of the A2 response propagated from the His bundle can initiate a response which propagates to the bundle; i.e., two responses can travel in opposite directions on a collision course, yet one of them can complete its journey. 7. The limiting parameter of the return pathway is the refractory period of that portion of the lower node which must fire twice in the echo circuit. 8. The limiting element is not the bundle of His. 9. The limiting element can be discharged by early H2 responses which fail to reach the atrium. 10. The refractory period of the limiting element is a function of the preceding cycle length. It was also demonstrated that the echo "zone" is shifted to a range of longer H1H2 intervals when the basic driving frequency is increased, or when the vagi are stimulated. Epinephrine shifts the echo zone to a range of briefer H1H2 intervals. It is suggested that echo responses occur when a retrograde impulse is arrested at one site within the node and continues to propagate to the atrium through collateral pathways. If the retrograde propagation time is long enough to permit the recovery of the lower elements of the node, an echo response reaches the His bundle. It was concluded that a self-sustained repetitive circuit may be possible when the round-trip conduction time exceeds the refractory period of the limiting tissue in the node.

Biphasic Action of Acetylcholine on Ventricular Myocardium

Abstract: Intracoronary infusions of acetylcholine have demonstrated two actions of this neurohumoral agent on ventricular myocardium: 1) an antagonism to the more forceful contractions evoked by adrenergic stimuli (sympathomimetic drugs or stellate stimulation), and 2) a sympathomimetic or positive inotropic effect (? release of a positive inotropic substance from the myocardium). The increased contractility ("rebound") was observed only after the infusion of acetylcholine was stopped; in the presence of physostigmine the "rebound" was absent. Atropine blocked both the cardio-inhibitory and cardio-excitatory actions of acetylcholine. Failure of hexamethonium and bretylium to block the "rebound" suggests that acetylcholine acts at a peripheral site. The possible catecholamine nature of the agent could not be established by direct analysis of coronary venous blood, by the use of an adrenergic beta receptor blocking agent or by pretreatment of the animals with reserpine; neither drug blocked the "rebound."

Hemodynamic Determinants of the Amplitude of the First Heart Sound

Abstract: The relationships between the amplitude of the first heart sound and various hemodynamic parameters and their analog functions were systematically investigated in 51 dogs under morphine and pentobarbital anesthesia. Simultaneous hemodynamic and phonocardiographic tracings were obtained by cardiac catheterization, high speed recording, and analog computers. Changes in cardiodynamics were induced by: l -epinephrine, levarterenol, phenylephrine, isoproterenol, methoxamine, veratrine, vasopressin, histamine, atropine, saline infusion, mechanical obstruction of the aorta, pulmonary artery, or both venae cavae, embolization of the coronary arteries with plastic microspheres, mechanical rupture of aortic valve leaflets, or hemorrhage. In this way, the relationships were examined over a wide range of pressures, volumes, and cardiodynamics. The results showed that the amplitude of the first sound is not directly related to stroke output, P-R interval, heart rate, end diastolic, or systolic ventricular or aortic pressures. Only the peak rate of rise of left ventricular systolic pressure (first derivative maximum) had a consistent relationship to first sound amplitude. The right ventricle seems to contribute very little to the external first sound. These observations suggest that the amplitude of the first sound is related to left ventricular contractility.