Showing papers in "Circulation Research in 1973"
TL;DR: It is concluded that E(t), represented by Emax and Tmax, explicitly reflects the ventricular contractility.
Abstract: As a means of assessing ventricular performance, we analyzed the time-varying ratio of instantaneous pressure, P(t), to instantaneous volume, V(t), in the canine left ventricle. Intraventricular volume was measured by plethysmography, while the right heart was totally bypassed. The cardiac nerves were sectioned, and an epinephrine infusion was used to alter the contractile state. The instantaneous pressure-volume ratio was defined as E(t) = P(t)/[V(t) - Vd], where Vd is an experimentally determined correction factor. We found that (1) all the E(t) curves thus defined were similar in their basic shape and attained their peak near the end of the ejection phase regardless of the mechanical load, the contractile state, or the heart rate, (2) under a constant heart rate and contractile state extensive changes in preload, afterload, or both did not alter the peak value of E(t), Emax, or the time to Emax from the onset of systole, Tmax, and (3) these parameters of E(t) markedly changed with epinephrine infusion ...
1,485 citations
TL;DR: The results show that even in a small area of atrial muscle containing no anatomical obstacle the impulse can be entrapped in a circus movement and was the underlying mechanism of the arrhythmia.
Abstract: The isolated left atrium of the rabbit, which showed no spontaneous activity, was electrically driven for 20 beats with a cycle length of 500 msec. Tachycardia could be repeatedly initiated by the application of a single adequately timed stimulus shortly after the refractory period of the last basic beat. After the termination of the tachycardia, either spontaneously or artificially by a properly timed stimulus, this procedure was repeated. The number of beats of these tachycardias varied from just one (coupled extrasystole) to many hundreds. Surface electrograms were recorded at about 300 different sites. From the moments of activation of these sites, the spread of activation during regular driving and during the premature beat and the subsequent tachycardia could be determined. In contrast to the radial spread of the activation during basic rhythm, the impulse of the premature beat was propagated in a circular pathway. This circus movement was maintained during tachycardia. These results show that even in a small area of atrial muscle containing no anatomical obstacle the impulse can be entrapped in a circus movement. This circus movement was the underlying mechanism of the arrhythmia.
778 citations
TL;DR: The primary function of the baroreceptor reflex is not to set the chronic level of arterial blood pressure but, instead, to minimize variations in systemic arterialBlood pressure, whether these variations are caused by postural changes of the animal, excitement, diurnal rhythm, or even spontaneous fluctuations of unknown origin.
Abstract: Normal and sinoaortic baroreceptor-denervated dogs were monitored continuously (24 hours a day) to quantify the role of the baroreceptors in determining the average level and the variability of arterial blood pressure, heart rate, cardiac output, and total peripheral resistance. The frequency of occurrence over 24-hour periods was obtained for each variable using a fiber optic curve-scanning system to read the variables from continuously recorded charts and a digital computer system to plot curves. The results indicate that the degree of hypertension previously reported for this preparation has been highly exaggerated, presumably due to the methods of study. The average 24-hour mean arterial blood pressure was 101.6 mm Hg in normal dogs and only 112.7 mm Hg in baroreceptor-denervated dogs. The normal dogs exhibited narrowly distributed 24-hour frequency distribution curves for blood pressure; in contrast the denervated dogs exhibited curves with twice the 24-hour standard deviation. Similar analysis indicated that the baroreceptors exerted less influence on the daily stabilization of heart rate than they did on arterial blood pressure and that they had very little if any influence on the daily stabilization of cardiac output and total peripheral resistance. Hemodynamic variables during postural changes were studied along with diurnal rhythms. We concluded that the primary function of the baroreceptor reflex is not to set the chronic level of arterial blood pressure but, instead, to minimize variations in systemic arterial blood pressure, whether these variations are caused by postural changes of the animal, excitement, diurnal rhythm, or even spontaneous fluctuations of unknown origin.
593 citations
498 citations
TL;DR: The results indicate that k is sensitive to stiffness changes due to infarction, hypertrophy causes an increase in the value of k although elastic stiffness remains within normal limits, and k for the intact human heart is lower than it is for isolated muscle.
Abstract: A sensitive method was developed for detecting stiffness changes in the left ventricle. Stress-strain relationships (σ--e) were obtained in the form dσ/de = kσ + c from published studies on eight normal canine hearts, five infarcted canine hearts, and seven isolated cat papillary muscles. Utilizing pressure-volume relationships, the elastic stiffness (dσ/de) and the stiffness constant ( k ) were also evaluated in patients with normal ventricles, inappropriate hypertrophy, and congestive cardiomyopathy. The k values were 35.0 ± 1.7 (isolated muscle, 30°C), 37.3 ± 1.9 (normal canine, 23°C), and 23.9 (infarcted). For the patient groups, k and the passive elastic stiffness were 15.8 ± 0.3 and 249 ± 22.4 g/cm 2 for 13 normal patients, 26.4 ± 1.7 and 286 ± 32.0 g/cm 2 for 7 patients with inappropriate hypertrophy, and 20.1 ± 1.2 and 1360 ± 209 g/cm 2 for 6 patients with congestive cardiomyopathy. The results indicate that (1) k is sensitive to stiffness changes due to infarction, (2) hypertrophy causes an increase in the value of k although elastic stiffness remains within normal limits, and (3) k for the intact human heart is lower than it is for isolated muscle.
416 citations
TL;DR: Transmembrane activity was recorded from canine false tendons bathed with Tyrode's solution at 37°C, resulting in sustained bigeminal rhythms with fixed coupling that may provide a mechanism for various clinically observed arrhythmias induced by cardiac glycosides.
Abstract: Transmembrane activity was recorded from canine false tendons bathed with Tyrode's solution at 37°C. Stimulus patterns provided a 3-second pause after every ten beats. Acetylstrophanthidin was infused at concentrations up to 2x10-7 g/ml. One or two transient depolarizations (TDs) followed the last driven response of each series. The appearance of TDs was associated with depression of normal phase-4 depolarization. The peak of the earliest TD (TD-1) occurred at an interval approximately equal to the basic cycle length. The later TD (TD-2) occurred at about twice the basic cycle length. Coupling intervals were determined primarily by the last cycle length. The amplitude of TD-1 was maximal when the basic cycle length was 600 msec, but TD-2 continued to increase as the basic cycle length diminished further. The amplitude of both TDs increased with the number of beats in the train. Either or both could reach threshold and induce single extrasystoles or trains of extrasystoles. TDs could be induced to reach th...
391 citations
TL;DR: The finding that cholesterol can enter the normal aortic wall as a constituent of lipoprotein, primarily beta-lipop Protein, suggests the possibility of a causal relationship between hypercholesterolemia and cholesterol in the arterial wall.
Abstract: • A high concentration of plasma cholesterol has been recognized as one of the principal risk factors in the development of coronary, peripheral, and, possibly, cerebral arteriosclerosis in man. Studies in experimental animals have shown a direct relationship between hypercholesterolemia and the accumulation of cholesterol in the arterial wall. It is usually assumed that cholesterol in blood plasma is transferred to the arterial wall as such or as part of a lipoprotein complex. Indeed, free or complexed beta-lipoprotein or apoprotein has been demonstrated in atheromatous plaques and fatty streaks (1-6). It is not known, however, whether the presence of lipoprotein in a diseased artery causes plaque formation or results from increased arterial permeability due to the disease. The finding that cholesterol can enter the normal aortic wall as a constituent of lipoprotein, primarily beta-lipoprotein (7, 8), suggests the possibility of a causal relationship. Various mechanisms proposed to explain the accumulation of lipids in the arterial wall have been summarized recently (9). Many of them include a high concentration of plasma cholesterol or a high concentration of low-density (beta) lipoproteins as a necessary condition for atherogenesis. More recently, clinical and epidemiological evidence (10-12) has implicated elevated plasma triglycerides or pre-beta-lipoproteins as an additional risk factor for clinical atherosclerosis. The mechanism by which the pre-beta-lipoproteins act as atherogenic
353 citations
TL;DR: The fulminating hypertension evoked by lesions of the nucleus tractus solitarii was due to the increased vasoconstriction caused by the augmented discharge of sympathetic nerves in response to central deafferentation of baroreceptor reflexes.
Abstract: Bilateral electrolytic lesions of the nucleus tractus solitarii in the rat at the level of the obex abolished baroreceptor reflexes and resulted in an immediate, marked elevation in systemic blood pressure without a change in heart rate. In unanesthetized rats the hypertension was associated with a marked increase in total peripheral resistance, a reduction in blood flow in the abdominal aorta, and an increase in central venous pressure. The cardiac output was reduced to 62% of control as a consequence of reduced stroke volume, which was reflected, in turn, by increased end-diastolic pressure. The hypertension was abolished and the end-diastolic pressure lowered by blockade of alpha receptors with phentolamine. The hypertension was not due to changes in blood gases or to release of agents from the kidneys or the adrenal glands; it was very sensitive to anesthetics and was abolished or aborted by midcollicular decerebration. Within hours after lesioning, the rats developed progressive congestive heart failure and died in shock, often in association with pulmonary edema. We concluded that the fulminating hypertension evoked by lesions of the nucleus tractus solitarii was due to the increased vasoconstriction caused by the augmented discharge of sympathetic nerves in response to central deafferentation of baroreceptor reflexes; the hypertension was mediated by alpha receptors and depended on the integrity of structures lying above the midbrain.
337 citations
TL;DR: Alterations in cardiac electrophysiology that accompany myocardial infarction were studied in dogs subjected to a two-stage ligation of the anterior descending coronary artery and subendocardial Purkinje fibers which survived in the infarct had reduced maximum diastolic potentials, action potential amplitudes, and maximum depolarization velocities.
Abstract: Alterations in cardiac electrophysiology that accompany myocardial infarction were studied in dogs subjected to a two-stage ligation of the anterior descending coronary artery. A multipolar transmural needle electrode was used to record electrical activity from the in situ infarcted heart 24 hours after coronary occlusion. Bipolar electrograms recorded from subendocardial regions of infarcted myocardium demonstrated the persistence of early, rapid deflections suggesting Purkinje fiber activity; evidence of ventricular muscle activity in the infarct was absent in both subendocardial and intramural electrograms. The infarcted myocardium and the adjacent non-infarcted tissue were then excised and studied with intracellular microelectrodes in vitro. Transmembrane action potentials could be recorded from one or two cell layers of subendocardial Purkinje fibers at all sites within the infarcted region, but no ventricular muscle action potentials were found. Subendocardial Purkinje fibers which survived in the infarct had reduced maximum diastolic potentials, action potential amplitudes, and maximum depolarization velocities compared with normal subendocardial Purkinje fibers; also, action potential durations in these surviving fibers were extraordinarily prolonged. Spontaneous diastolic depolarization was evident in some surviving fibers. Since subendocardial Purkinje fibers that generate abnormal action potentials survive in an infarct, these fibers may participate in the genesis of ventricular arrhythmias that accompany infarction.
319 citations
TL;DR: Findings illustrate several important differences between anoxia and ischemia and suggest that insulin may be more harmful than it is beneficial in severely ischemic tissue.
Abstract: The rates of utilization of glycogen and exogenous glucose by hearts perfused at low coronary flows and high perfusate oxygen tension (ischemia) and by hearts perfused at high coronary flows and low perfusate oxygen tension (anoxia) were studied in the isolated, working rat heart. Ischemic tissue had a glycolytic rate that was 25% of the anoxic rate and 50% of the control rate. Inhibition of carbohydrate utilization during ischemia was due to a lower flux through the glycolytic pathway and not to a lower rate of glucose transport or substrate availability. Insulin and elevated perfusate glucose increased glucose transport and caused accumulation of free intracellular glucose, but ischemia still inhibited glucose utilization. Insulin failed to maintain tissue levels of high-energy phosphates or to prevent mechanical failure in ischemic hearts. In the absence of insulin, tissue lactate increased tenfold during 20 minutes of ischemia, although it increased only threefold in anoxic tissue. The increased tissue lactate in ischemic hearts corresponded to the inhibition of glycolysis and to the failure of mechanical performance. Insulin caused a further increase in tissue lactate during ischemia. These findings illustrate several important differences between anoxia and ischemia and suggest that insulin may be more harmful than it is beneficial in severely ischemic tissue.
317 citations
TL;DR: The length-tension relationships for arterial smooth muscle were determined using vascular strips teased from the media of hog carotid arteries using potassium-induced depolarization and Norepinephrine and electric field stimulation.
Abstract: The length-tension relationships for arterial smooth muscle were determined using vascular strips teased from the media of hog carotid arteries. Histological examination revealed that the strips were (1) free of adventitia and (2) composed of smooth muscle cells oriented parallel to the long axis of the strips. Measurements from electron micrographs indicated that 60% of the cross-sectional area consisted of smooth muscle. At L 0 (the optimal length for tension development) the total cross-sectional area of the strips varied from 0.3 to 0.8 mm 2 . Potassium-induced depolarization was the most effective stimulus for force development. Norepinephrine and electric field stimulation elicited responses which were 70% and 30%, respectively, of that produced by potassium-induced depolarization. At L 0 the intrinsic load-bearing capacity (P 0 ) of the contractile system was 2.22 x 10 6 dynes/cm 2 . Tension development fell off gradually at lengths shorter than L 0 and more rapidly at lengths greater than L 0 . Passive length-tension curves were determined after quick releases from higher to lower lengths to avoid complications arising from tone. Passive tension was negligible at lengths below 0.9 L 0 . At L 0 the passive tension was 10% of P 0 .
TL;DR: The results suggest a postulate for the heart wall: in the beating heart, each muscle fiber changes direction and length uniquely as the wall changes shape.
Abstract: The relations between end-diastolic ( D ) and end-systolic ( S ) fiber angles (α) and sarcomere lengths ( s ) have been previously studied at different sites in canine left ventricular myocardium. However, no postulates have been advanced for predicting a and s in successive states of the ejection cycle ( D or S) or at different sites in one state when the semimajor ( Z ) and semiminor (R) axes of the wall surfaces for successive states and the fiber orientations and sarcomere lengths at one site in one state are known. In this study, the myocardial fibers were regarded as the matrix of a myocardial continuum: they are prisoners of the heart wall and must comply with the movements of the wall. Using the same values as in the preceding article, the wall was treated as a nested set of truncated ellipsoidal shells of revolution with shell volumes preserved from D to S. Both confocal and nonconfocal configurations were analyzed. In each shell, the fibers were assumed to follow a "helical" path with a constant advance in each turn about the Z axis (the simplest possible path). The results of this assumption were compatible with previously reported values of a and s measured at various sites in the left ventricular free wall in states D and S . These results suggest a postulate for the heart wall: in the beating heart, each muscle fiber changes direction and length uniquely as the wall changes shape.
TL;DR: To study selective changes in capacitive and resistive load under constant left atrial filling pressure, isolated cat hearts were loaded with a hydraulic model simulating the input impedance of the systemic arteries.
Abstract: To study selective changes in capacitive and resistive load under constant left atrial filling pressure, isolated cat hearts were loaded with a hydraulic model simulating the input impedance of the systemic arteries. The model was constructed so that resistive (peripheral resistance) and capacitive (total arterial compliance) characteristics could be changed independently. Aortic and left ventricular pressure and aortic flow, as generated by the left ventricle against the different impedances, were measured. An increase in resistance resulted in an increase in systolic, diastolic, and mean aortic pressure. A decrease in capacitance caused a small increase in systolic pressure and a decrease in diastolic and mean aortic pressure. Mean left ventricular pressure increased when resistance increased or capacitance decreased. Both peak flow and mean flow decreased when resistance increased or capacitance decreased. We attempted to explain these observations by the concept of source impedance. This concept had been, until now, incorrectly approached, because the nonlinearity arising from the aortic valves had been neglected. The correct computations met with difficulties, but it was shown that the isolated heart, with constant atrial filling pressure, behaved as neither a flow source nor a pressure source.
TL;DR: Purkinje cells in the infarcted zone showed distinctive alterations in electrophysiological properties which were probably related to deleterious factors that accumulated in that zone.
Abstract: Electrophysiological mechanisms which underlie the ectopic ventricular beats occurring 1 day after occlusion of the anterior descending coronary artery of dogs were explored. In intact dogs, bipolar electrograms were recorded in the infarcted and normal zones. Both Purkinje and ordinary myocardial potentials were recorded from the endocardial surface of the normal zone, but only Purkinje potentials were recorded from the infarcted zone. The Purkinje potentials in the infarcted zone were diminished in amplitude and rapidity. The threshold for endocardial pacing was higher in the infarcted zone than it was in the normal zone. The refractory periods of Purkinje cells were longer in the infarcted zone than they were in the normal zone. Excised specimens of endocardial surface containing the infarcted zone were superfused with Tyrode's solution. No ordinary myocardial cells were electrically active at the endocardial surface of the infarcted zone. Purkinje cells showed diminished resting and action potentials, reduced upstroke velocity, enhanced automaticity and phase 4 depolarization, and long action potentials with prolonged phase 3. Excitability was depressed within the infarcted zone. During superfusion, even with Tyrode's solution poor in oxygen and free of dextrose, Purkinje cells recovered toward normal with respect to amplitude of resting and action potentials, upstroke velocity, automaticity, and excitability. The prolonged action potentials persisted. Repetitive firing was easily elicited within the infarcted zone. Various types of pacemaker activity were detected within the infarcted zone. Thus Purkinje cells in the infarcted zone showed distinctive alterations in electrophysiological properties which were probably related to deleterious factors that accumulated in that zone. It is likely that the arrhythmia which occurred in the intact dogs at this time originated within the altered Purkinje cells of the infarcted zone.
TL;DR: The increased transcapillary escape rate and the outflux of albumin probably reflected an increase in arteriolar and capillary permeability to albumin, due to the high intra-arterial pressure.
Abstract: The transcapillary escape rate of albumin, the fraction of intravascular mass of albumin that passes to the extravascular space per unit time, was determined from the disappearance of intravenously injected 131I-labeled human serum albumin during the first 60 minutes after the injection in 10 normotensive and 18 hypertensive male subjects. The investigation was preceded by at least 12 hours of fasting and 30 minutes of rest in the supine position. The transcapillary escape rate of albumin was significantly increased in the hypertensive group: it averaged 7.6±1.2 (SD) %/hour compared with 5.6±1.1%/hour in the normotensive group (P<0.001). Similar results were obtained for the outflux of albumin, the mass of intravascular albumin that passes to the extravascular space per unit time, when identical intravascular albumin masses were compared (P<0.001). A highly significant correlation between the transcapillary escape rate of albumin and blood pressure was found in the hypertensive group (P<0.001). Therefore,...
TL;DR: Convergence of afferent fibers in the vagi and the cardiac sympathetic nerves on the same cardiac vagal and cardiac sympathetic postganglionic neurons was demonstrated and Convergence from carotid sinus baroreceptors was observed.
Abstract: The reflex changes in single cardiac vagal efferent fibers elicited by excitation of afferent cardiac sympathetic fibers were studied in cats anesthetized with chloralose and urethane. Efferent vagal and sympathetic units were dissected from the end of a cardiac nerve cut at its junction with the right atrium. In some cases, efferent vagal units were dissected from the cervical vagus. Excitation always evoked a clear reduction in the discharge of cardiac vagal units and a clear increase in the discharge of cardiac sympathetic fibers. The effects on cervical vagal efferents were variable. Hence, excitation of afferent cardiac sympathetic fibers could simultaneously elicit inhibition of the vagal outflow to the heart and excitation of the sympathetic outflow. By contrast, stimulation of the cut central end of the contralateral vagus produced the opposite effects. Convergence of afferent fibers in the vagi and the cardiac sympathetic nerves on the same cardiac vagal and cardiac sympathetic postganglionic neurons was demonstrated. Convergence from carotid sinus baroreceptors was also observed.
TL;DR: The results suggest that subendocardial Purkinje fibers which survive in an infarct may be the site of origin of some of the ventricular arrhythmias that accompany myocardial infarction.
Abstract: The cellular electrophysiological mechanisms underlying the ventricular arrhythmias that accompany myocardial infarction were studied in isolated, superfused infarcted myocardium excised from dogs previously subjected to a two-stage ligation of the anterior descending coronary artery Ventricular arrhythmias frequently occurred in the intact heart 24 hours after coronary occlusion Surviving subendocardial Purkinje fibers in infarcts excised at this time were highly arrhythmic when they were studied with intracellular microelectrodes in vitro These arrhythmias consisted of rapid, repetitive depolarizations and occurred spontaneously or could be induced by premature electrical stimulation Premature stimulation also resulted in single unstimulated responses In such instances, premature impulses conducted extremely slowly through the infarcted region where surviving Purkinje fiber action potential durations were extraordinarily prolonged Conduction block at some sites in the infarct caused phenomena which were interpreted as reentrant beats Some surviving subendocardial Purkinje fibers in the infarct demonstrated spontaneous diastolic depolarization and appeared to function as pacemakers in the absence of electrical stimulation In some instances, these fibers constituted typical parasystolic foci, demonstrating both entrance and exit block These results suggest that subendocardial Purkinje fibers which survive in an infarct may be the site of origin of some of the ventricular arrhythmias that accompany myocardial infarction
TL;DR: It is concluded that functional alterations observed in spontaneously hypertensive rats probably resulted from primary changes in ion transport by vascular smooth muscle rather than from secondary effects of altered regulatory systems.
Abstract: The interaction of vascular electrolytes and early spontaneous hypertension was studied in the rat aorta. Chemical composition (H2O, Na, K, Ca, Mg, Cl, collagen, and elastin), extracellular space, and cell water content were little changed. Only uronic acid and hexosamine contents were significantly elevated in the spontaneously hypertensive rat. Approximately 37% of the aortic weight was cellular. Functional changes in ion transport were observed in smooth muscle from hypertensive rats; the muscle exhibited decreased ability to accumulate K and extrude Na and increased turnover of 42K (0.0165 ± 0.0009 vs. 0.0086 ± 0.0002 min-1) and 36C1 (0.162 ± 0.011 vs. 0.118 ± 0.003 min-1). Spontaneously hypertensive rats maintained increased 42K exchange after adrenalectomy and reserpinization. The bioregulants, aldosterone, norepinephrine, and angiotensin had important actions on ion exchange. After adrenalectomy, aldosterone therapy reduced 42K exchange toward intact levels. Norepinephrine increased the rate of 42K...
TL;DR: It is concluded that PGE2 participates in maintaining renal vascular tone which heretofore has been ascribed to autonomous, intrinsic renal arteriolar activity.
Abstract: Inhibition of prostaglandin synthesis in chloralose-anesthetized dogs reduced renal blood flow, and this reduction closely correlated (r=0.92, P<0.01) with a decline in the renal efflux of a substance having the properties of PGE2. We used solvent extraction and thin-layer chromatography coupled with parallel bioassay to identify and assay the PGE- and PGF-like substances (expressed as PGE2 and PGF2α equivalents). Either of two antiinflammatory acids, indomethacin or meclofenamate, that inhibited conversion of 14C-arachidonic acid to prostaglandins in renal homogenates decreased the basal concentration of a PGE-like substance in renal venous blood to 0.06 ± 0.02 ng/ml from a mean control value of 0.34 ± 0.10 ng/ml (P<0.01). This change was associated with a mean reduction in renal blood flow of 45% in spite of increased renal perfusion pressure. Femoral blood flow and cardiac output were variably and insignificantly affected. Changes in the renal efflux of a PGF-like substance induced by indomethacin were...
TL;DR: Dogs treated with propranolol showed significantly less necrosis than did untreated controls, but the mechanism of the drug's action remains unknown.
Abstract: The effect of propranolol on the severity of myocardial necrosis following 40 minutes of temporary coronary artery occlusion was assessed in dogs. The circumflex coronary artery was occluded 1-2 cm from the aorta in open-chest dogs anesthetized with sodium pentobarbital. One group of dogs was untreated and a second group received propranolol (5.0 mg/kg, iv) 10 minutes prior to the occlusion. After 40 minutes the clamp was removed and arterial perfusion was restored. Dogs which survived this procedure were killed 2-5 days later for gross and histologic assessment of the necrosis. The relative area of necrosis (percent of fibers involved) in the posterior papillary muscle of each heart was quantified from stained histologic sections prepared from serial longitudinal slices of each posterior papillary muscle. Dogs treated with propranolol showed significantly less necrosis than did untreated controls, but the mechanism of the drug's action remains unknown. During coronary artery occlusion, propranolol-treated dogs exhibited somewhat lower heart rates, systolic blood pressures, and S-T segment elevations than did untreated dogs. However, none of these latter differences between groups was significant.
TL;DR: The reflex controls the total systemic venous capacity to a degree that changes cardiac output potentially by 30–10% per 25-mm Hg change in ISP, which is consistent with quantitative understanding of carotid sinus baroreceptor reflex control of cardiac output.
Abstract: To attain a quantitative understanding of carotid sinus baroreceptor reflex control of cardiac output, we studied the reflex control of total systemic vascular capacity in vagotomized dogs. In experiments measuring blood volume shifts caused by the carotid sinus reflex (series 1), venous return was diverted into a reservoir while cardiac output and central venous pressure were maintained at constant levels. The pressure in the isolated carotid sinuses (ISP) was lowered or raised in 25-mm Hg steps between 75 and 200 mm Hg. This procedure mobilized blood into or out of the reservoir, indicating a decrease or an increase in total vascular capacity, respectively. The mean maximum volume shift, 3.6 ml/kg body weight, occurred in the same ISP region, 135 ± 12.5 mm Hg, where reflex control of total peripheral resistance was strongest. The total volume shift was approximately 7.5 ml/kg for ISP changes from 75 to 200 mm Hg. When mean arterial blood pressure was maintained constant during the ISP step changes, the ...
TL;DR: Microspheres of different sizes, 125I-labeled antipyrine (I-Ap), and 42KCl or 86RbCl were injected into the aortic inflow of isolated, Langendorff, perfused, nonworking dogs hearts, and the deposition of 42K and that of I-Ap were essentially similar in three hearts over a large range of regional variation.
Abstract: Microspheres of different sizes, '-"'I-labeled antipyrine (I-Ap), and 4 -KCl or 86 RbCl were injected into the aortic inflow of isolated, Langendorff, perfused, nonworking dogs hearts at blood flows of 1.3-4.8 ml/min g~'. After 15 seconds to 5 minutes, the left ventricle was sectioned into about 300 ordered pieces, and the amount of each tracer was determined. For all tracers, the relative density of deposition was generally higher in the endocardial region, except in one heart in which the aortic pressure and the total coronary flow were low. The deposition of ^-K and that of I-Ap were essentially similar in three hearts over a large range of regional variation. This finding suggests either that both tracers were distributed in proportion to flow or that a small diminution in relative density of deposition of 42 K in high-flow regions due to lower transcapillary extraction was quantitatively similar to a decrease in the residual fraction of I-Ap in these same regions due to faster washout in the first 15—30 seconds after injection. Large microspheres were deposited preferentially in regions of high flow, exaggerating the apparent heterogeneity of regional flows. The distribution of the smaller microspheres was closer to that for I-Ap or 42 K.
TL;DR: The results suggest a postulate for the heart wall: in the beating heart, each muscle fiber changes direction and length uniquely as the wall changes shape.
Abstract: The relations between end-diastolic ( D ) and end-systolic (S) cavitary volumes ( V c ), wall volumes ( V 10 ), and cavitary dimensions have been studied in the canine and human left ventricle. However, the models selected for left ventricular myocardium do not represent the real heart adequately for a fiber-by-fiber analysis of fiber orientation and sarcomere length during successive states of the ejection cycle. In this study, the endocardial and epicardial surfaces were postulated to be a nested set of truncated ellipsoidal shells of revolution where wall volumes were preserved from D to S. Shell dimensions on the semiminor and semimajor axes, R and Z , respectively, were related to V c and V w by two representations: confocal and nonconfocal. If the focal length C = ) 1/2 and C is the same for each shell, then the shells are confocal, otherwise they are nonconfocal. From measured V c , V w , and epicardial Z in D , shell dimensions were calculated for states D and S, using both confocal and nonconfocal representations, and compared with the measured dimensions. When no empirical corrections were made, the calculated endocardial R in S underestimated the measured R in S by 12%; moreover, the calculated epicardial R in S overestimated the measured R in S by 4%. Endocardial and epicardial C measured 3.73 ± 0.33 (SE) cm and 3.79 ±0.34 cm, respectively, in D and 3.77±0.11 cm and 3.71 ±0.10 cm, respectively, in S.
TL;DR: From a cast of a human pulmonary arterial tree, the diameter, length, order, and end branches of all intact branches down to those 0.8 mm in diameter were measured and corrections for broken branches made and calculations of cross-sectional area, volume, and flow were made.
Abstract: From a cast of a human pulmonary arterial tree, the diameter, length, order, and end branches of all intact branches down to those 0.8 mm in diameter were measured and corrections for broken branches were made. A sample of structures smaller than these (0.8-0.1 mm) was similarly measured. The values for branches less than 0.1 mm in diameter were found by extrapolation and comparison with known data for the precapillary vessels. Therefore, data or estimates for each order of branching in the pulmonary tree were obtained and calculations of cross-sectional area, volume, and flow were made.
TL;DR: A brief review of the rapidly developing research on vascular smooth muscle presents the state of the art as I see it from within my own frame of reference.
Abstract: • This brief review of the rapidly developing research on vascular smooth muscle presents the state of the art as I see it from within my own frame of reference. For a more objective, detailed insight into the workings of vascular smooth muscle, several substantial reviews and compendiums may be read (1-7). CONTRACTILE PROTEINS The mechanical events responsible for the contraction of vascular smooth muscle are associated with its contractile proteins. These proteins not only develop the mechanical force responsible for the contraction but also act as the enzyme that catalyzes the release of energy by which this force is developed. They are both the spark plug and the piston of the contractile machine. The contractile proteins of vascular smooth muscle are arranged in well-organized thick and thin filaments (8-10). The thick filaments, presumably bundles of myosin molecules, average 15.5 nm in diameter and have lateral projections suggestive of cross-bridges extending toward adjacent thin filaments. The thin filaments, presumably fibrous actin, average 5-8 nm in diameter and appear to be attached to dense bodies that are usually connected to the cell membrane. Contraction of vascular smooth muscle most probably is effected by some version of the Huxley sliding filament mechanism. The most easily interpretable studies of the functions of the contractile proteins are those performed in isolation with the determinants of the enzymatic and physical responses tightly controlled. There is a qualitative similarity between the actomyosin of vascular smooth muscle and the actomyosin of skeletal muscle (11) evidenced by the observation that a hybrid actomyosin can be prepared by combining myosin from one of these types of muscle with actin from the other; this
TL;DR: The results suggest that the cell membrane of the vascular smooth muscle in the hypertensive rat is more labile than that in the normal rat and delineates individuality in vascular smooth Muscle reactivity in different types of experimental hypertension.
Abstract: The reactivity of vascular smooth muscle in helical strips from femoral arteries of normotensive, spontaneously hypertensive, renal hypertensive, and deoxycorticosterone acetate-- (DCA-) hypertensive rats was studied. Spontaneous rhythmic contractions occurred in 25 of the 30 strips from the three groups of hypertensive rats and in only 2 of the 10 strips from normotensive rats. Strips from renal and DCA hypertensive rats had lower thresholds to epinephrine and potassium chloride (KCl) than did strips from spontaneously hypertensive and normotensive rats. Lanthanum (2.5 mM) caused contraction of all 10 strips from spontaneously hypertensive rats but failed to cause contraction of any strip from the other three groups of rats. Strontium (5 mM) caused contraction in 8 of 10 strips from spontaneously hypertensive rats but caused contraction in only 7 of the 30 strips from the other three groups. The optimal calcium concentration for tension development in response to a KCl stimulus was approximately twice as high for strips from hypertensive rats as it was for strips from normotensive rats. Strips from DCA-hypertensive rats showed less tachyphylaxis to angiotensin II than did strips from the other three groups of rats. These results quantify our earlier observation that the reactivity of vascular smooth muscle from hypertensive rats is importantly different from that of normotensive rats. In addition, the study delineates individuality in vascular smooth muscle reactivity in different types of experimental hypertension. The results suggest that the cell membrane of the vascular smooth muscle in the hypertensive rat is more labile than that in the normal rat.
TL;DR: De novo synthesis of adenine nucleotides increased almost 100% in the heart in situ and in the isolated perfused heart during the first hour of recovery from asphyxia or ischemia, and this acceleration is regarded as an adaptive process contributing to the postanoxic restoration of normal adenines nucleotide levels.
Abstract: De novo synthesis of adenine nucleotides was measured in rat hearts in situ and in isolated perfused rat hearts under normal conditions and during recovery from asphyxia or ischemia. Using l- 14 C-glycine as the precursor substrate, rates of de novo synthesis were determined from the total radioactivity of adenine nucleotides and from the mean specific activity of intracellular glycine. The rate of de novo synthesis of adenine nucleotides was 8.4±1.42 nmoles/g hour -1 in the heart in situ and 1.3±0.12 nmoles/g hour -1 in the isolated perfused heart. De novo synthesis of adenine nucleotides increased almost 100% in the heart in situ and about 580% in the isolated perfused heart during the first hour of recovery from asphyxia or ischemia. This acceleration is regarded as an adaptive process contributing to the postanoxic restoration of normal adenine nucleotide levels. Possible biochemical mechanisms that might be involved in the stimulation of the de novo pathway are a release of feedback inhibition of 5-phosphoribosyl-1-pyrophosphate amidotransferase, an enhanced synthesis of 5-phosphoribosyl-1-pyrophosphate, and an alternate way of 5-phosphoribosyl-amine formation.
TL;DR: These studies demonstrate that a gradual transition occurs from characteristic responses seen in mesenteric arteries to those seen in cerebral arteries (high sensitivity to serotonin, low sensitivity to norepinephrine), which appears that sympathetic nerves cannot play an important role in the regulation of vascular tone in large cerebral arteries.
Abstract: Spirally cut strips of cerebral and peripheral arteries from dogs were used for comparing the vasoconstricting effect of serotonin, norepinephrine, K + , and transmural electrical stimulation. Sensitivity of cerebral (basilar, posterior cerebral, and middle cerebral) arterial strips to serotonin was markedly greater than that to norepinephrine with respect to the median effective concentration (ED30) and the maximum response. Contractile responses of isolated human cerebral arteries to serotonin and norepinephrine were similar to those observed in the dog arteries. In contrast, proximal and distal strips from superior mesenteric arteries and strips from renal arteries were more sensitive to norepinephrine than they were to serotonin. Mean values of contractions caused by 5 X 10~ C M serotonin relative to those caused by 30 mM K + in cerebral, internal carotid, external carotid, common carotid, and superior mesenteric arteries were in a descending order, whereas those for norepinephrine were in an ascending order. These studies demonstrate that a gradual transition occurs from characteristic responses seen in mesenteric arteries (high sensitivity to norepinephrine, low sensitivity to serotonin) to those seen in cerebral arteries (high sensitivity to serotonin, low sensitivity to norepinephrine). Transmural stimulation did not produce contractions of cerebral and internal carotid arteries, but contractions were produced in external carotid, common carotid, and superior mesenteric arteries. It appears that sympathetic nerves cannot play an important role in the regulation of vascular tone in large cerebral arteries.
TL;DR: The results suggest that TDs and arrhythmias produced by acetylstrophanthidin may be caused by a transient Ca2+ influx.
Abstract: The role of calcium ions (Ca2+) in the generation of transient depolarizations (TDs) by acetylstrophanthidin was examined. Transmembrane activity was recorded from isolated canine false tendons exposed to acetylstrophanthidin; concentrations from 7.5 x 10-8 to 2 x 10-7 g/ml caused TDs coupled to driven action potentials and depressed slow diastolic depolarization. TDs could reach threshold and induce extrasystoles. Elevation of the Ca2+ concentration increased the amplitude of TDs induced by acetylstrophanthidin. High Ca2+ concentration (12.5 mM) caused TDs and depression of slow diastolic depolarization in the absence of acetylstrophanthidin. Elevation of potassium (K+) concentration depressed and reduction of K+ concentration potentiated TDs caused by either acetylstrophanthidin or high Ca2+ concentration. The production of TDs and the depression of slow diastolic depolarization by acetylstrophanthidin were reversed by reduction of the Ca2+ concentration or addition of manganese (2 mM) to the superfusing Tyrode's solution. The results suggest that TDs and arrhythmias produced by acetylstrophanthidin may be caused by a transient Ca2+ influx.
TL;DR: The mechanisms by which some commonly used antiarrhythmic drugs modify cardiac rhythm and conduction are reviewed, to emphasize the limitations in the understanding, and to indicate some of the types of experiments needed to minimize these limitations.
Abstract: • An understanding of the manner in which drugs used to treat arrhythmias modify the initiation and the spread of the cardiac impulse must be based in part on an understanding of their effects on the electrical activity of the normal heart and its constituent fibers. However, since these drugs are used to modify abnormalities of impulse initiation and conduction, it is equally important to understand their effects on the abnormal fibers responsible for arrhythmias and conduction disturbances. Although it is possible to study drug action on a variety of preparations of cardiac tissue from normal hearts that have been experimentally modified to produce conduction disturbances or abnormalities of rhythm (1-5), whether the mechanisms responsible for the experimental disturbances of rhythm and conduction are identical to the mechanisms which cause arrhythmias and conduction abnormalities in the diseased human heart is for the most part unknown. Furthermore, the electrocardiographic identification and the classification of arrhythmias and conduction disturbances contribute little if anything to an understanding o'\" the changes in electrical activity of the cardiac cell membrane which may be responsible for the electrocardiographic abnormalities. In the following pages, we shall attempt to review the mechanisms by which some commonly used antiarrhythmic drugs modify cardiac rhythm and conduction, to emphasize the limitations in our understanding, and to indicate some of the types of experiments needed to minimize these limitations.