ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We compared the maximal upstroke velocity of action potentials in short rabbit Purkinje fibers with sodium currents measured with a two-microelecrrode voltage clamp. The number of sodium channels available to open during a sudden depolarization was varied either by blockade with tetrodotoxin or by inactivation with steady depolarizations. In both cases, the maximal upstroke velocity was found to be a very nonlinear measure of the number of available sodium channels. For example, 3 μM tetrodotoxin blocks 85% of the sodium channels, but reduces the maximal upstroke velocity by only 33%. Voltage clamp and upstroke velocity experiments were reconstructed with a computer model of the rabbit Purkinje fiber preparation that was closely based on experimental measurements of passive cable properties and sodium channel characteristics. The simulations indicate that our voltage clamp measurements of sodium current accurately report changes in channel availability, but they also show that the maximal upstroke velocity is a strongly nonlinear index of available sodium conductance. Most of the nonlinearity arises from the activation kinetics of the sodium channels: as the pool of available channels decreases, a greater percentage of those channels activate and contribute inward current at the time of the maximal upstroke velocity. Simulations predict that the maximal upstroke velocity-available sodium conductance relationship would still remain nonlinear at 37°C or under different stimulus conditions that give uniform or continuously propagated action potentials. The nonlin earity may invalidate inferences based on earlier maximal upstroke velocity experiments: the existence of two types of sodium channels with different tetrodotoxin sensitivity, steady state voltage dependence of tetrodotoxin block, voltage range over which sodium channels inactivate, and rapid, then slow recovery of sodium channel availability following a sudden repolarization. All of these conclusions need to be reevaluated.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The intracellular sodium ion activity was measured using liquid ion-exchange microelectrodes with rapid response times in sheep Purkinje fibers and ventricular muscle under voltage control. The mean sodium ion activity in quiescent Purkinje fibers was 8.5 mM at a holding potential of —80 mV. With maintained hyperpolarizing (—110 mV) or depolarizing (—40 and 0 mV) voltage steps, sodium ion activity increased or decreased, respectively. At 0 mV, the mean steady state value for the sodium ion activity was 3.8 HIM. Following a voltage step to 0 mV, or back to —80 mV, the time course of the sodium ion activity change could be fitted by single exponentials, with similar half-times. Increasing the extracellular potassium ion concentration from 5.4 to 15 ITIM did not alter the steady state value of the sodium ion activity at clamped voltages of —80 or 0 mV, which suggests that the external potassium ion activating site of the Na-K pump was saturated. With the extracellular potassium concentration 0 mM (holding potential —80 mV), the sodium ion activity increased. When maintained depolarizing steps to 0 mV were applied, the sodium ion activity decreased by up to 20 ITIM. This large fall in sodium ion activity is assumed to represent partial reactivation of the Na-K pump due to potassium ion accumulation in clefts. We also studied the stimulation-dependent change in sodium ion activity. Trains of action potentials or short duration depolarizing voltage damp steps caused a frequency dependent rise in sodium ion activity. The magnitude of the rise of sodium ion activity was not altered by lengthening the duration of each voltage clamp step, but was inhibited by tetrodotoxin or by holding the membrane potential at —50 mV between depolarizing steps. These results show that sodium ion activity is a complex function of membrane voltage, depolarization frequency, and time. The rise in sodium ion activity with stimulation appears to depend on sodium ion entry regulated by the sodium channel, and may be important in the modulation of intracellular calcium and tension through the Na-Ca exchange mechanism.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Input impedance of the pulmonary arterial system was determined in 10 subjects undergoing elective cardiac catheterization. No cardiovascular or pulmonary disease was found in these patients. In five of the subjects, systemic arterial input impedance was also obtained, so that both systems could be compared. Pulmonary and systemic peripheral resistances were 79 ± 9 dynes sec/cm5(mean ± SEM) and 1016 ± 50 dynes sec/cm5, respectively. Characteristic impedance of the pulmonary circulation was lower than the characteristic impedance of the systemic circulation: 20 ± 1 dynes sec/cm5vs. 47 ± 9 dynes sec/cm!, respectively. Pulmonary pressure and flow spectra for both systems are also presented. The amplitudes of the harmonics of pressure and flow are smaller for the pulmonary circulation, which is consistent with the lower pressures and more rounded waveforms of the normal pulmonary circulation. In all 10 subjects, input impedance of the pulmonary system was examined during both the inspiratory and expiratory phases of respiration. There was no difference between inspiration and expiration in either pulmonary vascular resistance (77± 10 dynes sec/cm!vs. 80 ± 9 dynes sec/cm5, respectively), characteristic impedance (20 ± 1 dynes sec/cm5vs. 20 ± 1 dynes sec/cm5) or in the overall impedance spectrum. Quiet respiration, thus, has no effect on the pulmonary arterial load, and changes in pressure and flow must result from alterations in right ventricular performance.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We examined, in conscious dogs, the potential role of prejunctional a2-adrenergic receptors for the regulation of heart rate and contractility response to exercise through modulation of the neurotransmitter release. Changes in heart rate and left ventricular pressure with time during comparable exercise levels, together with changes in norepinephrine concentration in the coronary sinus, were compared before and after the intravenous administration of: prazosin (0.5 mg/kg), a preferential postjunctionalα1-adrenergic receptor blocking agent; phentolamine (1 mg/ kg), a nonselectiveα-adrenergic blocking agent; and yohimbine (0.3 mg/kg), a preferential prejunctional “2-adrenergic receptor blocking agent”. During exercise after phentolamine or yohimbine, changes in heart rate and left ventricular dP/dt were markedly potentiated compared to the control exercise, as well as to exercise after prazosin, whereas the norepinephrine concentration in the coronary sinus was substantially elevated. After intracoronary administration of phentolamine (0.1 mg/kg) or yohimbine (0.03 mg/kg)/ heart rate and contractility response to exercise were also potentiated, compared to the control exercise. These observations indicate that, in the intact conscious animal, prejunctionalα2-adrenoreceptors are stimulated during exercise, thereby modulating the norepinephrine release through a negative feedback inhibitory mechanism. Blocking these receptors by phentolamine or yohimbine results in an uncontrolled norepinephrine release dunng exercise associated with an augmented β-adrenergic receptor-mediated end organ response, i.e., a potentiation in heart rate and contractility response.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Two distinct myosin heavy chain isoforms, referred to asaand ft, were identified in the human heart with specific antimyosin antibodies. By indirect immunofluorescence, myosin heavy chainawas found to be a major component of atrial myosin and a minor component of ventricular myosin, while heavy chain β was found to be a major component of ventricular myosin and a minor component of atrial myosin. In the normal heart, there was marked individual variability in the proportion of ventricular myocytes reactive for heavy chain α. Atrial myocytes staining for heavy chain β were rare in the left atrium and more numerous in the right atrium, especially in the crista terminalis and in the interatrial septum. Surgical and autoptic specimens from hypertrophied left ventricles of patients with mitral regurgitation showed a myosin immu-noreactivity pattern similar to that of normal specimens. Very rare muscle cells reactive for heavy chainawere seen in the hypertrophied left ventricles of subjects with hypertension and in the hypertrophied right ventricles of subjects with tetralogy of Fallot. A dramatic transformation of myosin heavy chain composition was observed in hypertrophied left atria of patients with mitral stenosis, with a shift to heavy chain β in a large proportion of atrial myocytes. The findings indicate that chronic exposure to hemodynamic overload can induce marked changes in the myosin heavy chain composition of human atria, whereas it affects only slightly that of the ventricles.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We determined the effects of the timing of repetitive bursts of vagal stimulation on the positive chronotropic responses of the heart to trains of cardiac sympathetic nerve stimulation in open-chest anesthetized dogs. Trains of sympathetic stimulation alone, at frequencies of 2 and 4 Hz, decreased the cardiac cycle length by 176 ± 19 msec (mean ± SE) and 190 ± 22 msec, respectively. When bursts of vagal stimuli were given once each cardiac cycle and they were placed at their least effective time in the cycle, sympathetic stimulation at frequencies of 2 and 4 Hz decreased cardiac cycle length by only 107 ± 8 and 120 ± 8 msec, respectively. However, when the bursts of vagal stimuli were delivered at their most effective time in each cycle, the same levels of sympathetic stimulation elicited much larger reductions in cardiac cycle length (285 ± 32 and 330 ± 32 msec, respectively). Therefore, the effects of sympathetic stimulation were significantly attenuated by the vagal stimuli when the vagal bursts were relatively ineffective. Conversely, the chronotropic effects of the sympathetic stimulation were exaggerated substantially when the vagal stimulus bursts were initially positioned at their most effective time in the cardiac cycle. This latter response is contrary to the characteristic “accentuated antagonism,” wherein the effect of any given level of sympathetic stimulation is diminished as the level of vagal activity is increased. This vagally mediated enhancement of the positive chronotropic response to sympa thetic stimulation occurs because the phase dependency of the response of the automatic cells to the bursts of vagal stimulation is altered by the increased sympathetic activity.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We examined effects of hypercholesterolemia and atherosclerosis on vasoconstrictor responses to norepinephrine and serotonin. Responses were compared in normal, atherosclerotic, and hypercholesterolemic but non-atherosclerotic cynomolgus monkeys. The hindlimb was per fused at constant flow so that changes in perfusion pressure indicated changes in vascular resistance. We measured the pressure gradient from the iliac to the dorsal pedal artery so that responses of the large artery segment could be determined. Serotonin decreased total hindlimb resistance in normal and hypercholesterolemic monkeys, but increased total resistance in athero sclerotic monkeys. There was a greater than 10-fold increase in constrictor responses of large arteries to serotonin in atherosclerotic monkeys, compared with normal and hypercholesterolemic monkeys. In contrast, we found that vasoconstrictor responses tc norepinephrine are normal in atherosclerotic monkeys and increased in hypercholesterolemic monkeys prior to development of atherosclerosis. Hypercholesterolemia augmented responses of small vessels to norepinephrine. We conclude that, during early stages of hypercholesterolemia in cynomolgus monkeys, vasocon strictor responses to norepinephrine are increased in small vessels. At a later stage, as atheroscle rosis develops, responses to norepinephrine return to normal, but vasoconstrictor effects of large arteries to serotonin are greatly potentiated.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

We studied the effect of chronic right ventricular pressure overload on diastolic ventricular interdependence in dogs without pericardia, instrumented to measure left ventricular pressure, right ventricular pressure, and 3 left ventricular dimensions. We studied 12 dogs before (control) and nine dogs after 6 weeks of pulmonary artery constriction producing systolic right ventricular pressure ≥270 mm Hg. Compared to control, following pulmonary artery band there was greater (P < 0.01) interventricular septal mass (53 ± 15 vs. 35 ± 7 mg, mean ± SD), thickness (15 ± 2 vs. 10 ± 1 mm), and ratio of the surface area of the interventricular septal to total left ventricular surface area (0.38 ± 0.03 vs. 0.33 ± 0.02), but unchanged left ventricular free wall mass (81 ± 12 vs. 84 ± 14 mg) and thickness (11 ± 2 vs. 11 ± 2 mm). End-diastolic right and left ventricular pressures and left ventricular volume were varied by vena cava and pulmonary artery occlusions and releases. Volume was calculated as an ellipsoid and the data in each dog fit to: left ventricular pressure = a0+ a]V + a2V2+ a3V3+ a4V4+ bPRV, r > 0.91 in each dog. During control, b was similar, whether calculated from both pulmonary artery and vena cava occlusions (0.47 ± 0.09) or from vena cava occlusions alone (0.43 ± 0.11), and was greater than the ratio of the interventricular septal surface area to left ventricular surface area (0.33 ± 0.02,P< 0.05). Following the pulmonary artery band, b decreased to 0.21 ± 0.10 (P< 0.05) and was less than the ratio of interventricular septal surface area to the left ventricular surface area which increased to 0.38 ± 0.03 (P < 0.05). We conclude that the effect of alterations in right ventricular pressure on the end-diastolic left ventricular pressure volume relationship, independent of the pericardium, is reduced following the pulmonary artery band that produces interventricular septal hypertrophy. These results are consistent with the hypothesis that the effect of alterations of right ventricular pressure on the diastolic left ventricular pressure-volume relationship depends on the relative elastance of the interventricular septum and left ventricular free wall, and not simply on the ratio of the interventricular septal surface area to the left ventricular surface area.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The relationship between left ventricular end-systolic pressure and volume has been proposed as a model of left ventricular contraction which may be useful for quantifying inotropic state independent of preload and afterload. Although the model has been well-validated in isolated hearts, systematic evaluation in conscious animals with an intact peripheral circulation has been limited. Accordingly, we derived end-systolic pressure-volume relationships in twelve conscious dogs, chronically instrumented to measure left ventricular pressure and dimensions from endocardial ultrasonic crystals in three orthogonal axes. We examined the linearity of the end-systolic pressure-volume relationship, its response to alterations of inotropic state and the peripheral circulation, and the influence of β-adrenergic reflexes. End-systolic pressure-volume relationships were constructed by linear regression of end-systolic pressure-volume coordinates produced by transient inferior vena caval occlusions during atrial pacing. The relations were highly linear; of 127 inferior vena caval occlusions, the correlation coefficient was 0.96 ± 0.05 (mean ± SD). The slope of the end-systolic pressure-volume relationship was not significantly altered either by a moderate resistive afterload induced by angiotensin II infusion, or by a moderate increase in preload produced by dextran, but was increased from 4.7 ± 2.3 to 6.5 ± 2.2 mm Hg/ml (P > 0.05) in response to the positive inotropic stimulus of dobutamine. The volume intercept at zero end-systolic pressure was unaffected by dextran or dobutamine, but was decreased from 12 ± 8 to 5 ± 11 ml (P > 0.01) by angiotensin II infusion, indicating a leftward shift of the end-systolic pressure-volume relationship. Pretreatment with propranolol to blockfi-mediated adrenergic reflexes did not affect the response to angiotensin or dextran. We conclude that linear end-systolic pressure-volume relationships can be derived in conscious dogs with intact sympathetic reflexes. The slope appears to reflect left ventricular contractile function and is indepednent of the level of afterload and preload. However, the relation is shifted leftward by high levels of arterial resistance, indicating that end-systolic pressure is a function, not only of end-systolic volume and inotropic state, but also of the peripheral circulation, in this intact animal model.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID