ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Calcium channel blockers suppress early ischemic arrhythmias, possibly by diminishing intracellular calcium overload and its effects on the ventricular action potential. To explore this, we compared the effects of diltiazem on ischemic injury potentials and ventricular fibrillation during serial coronary artery occlusions in dogs. Injury potentials and ventricular fibrillation were elicited every 15–25 minutes by simultaneous occlusion of the left anterior descending and circumflex arteries during rapid atrial pacing. DC epicardial electrograms were recorded differentially between the ischemic region and a small nonischemic region supplied by a proximal branch of the left anterior descending artery. Injury potentials developed with a uniform time course during five control occlusions, but were reduced by diltiazem infusion (0.5 mg/kg over 25 minutes) in each of eight dogs. The mean diastolic injury potential (T-Q depression) at 150 seconds of ischemia was 9.1 ± 2.7 mV before diltiazem and 6.1 ± 1.6 mV afterward (P ± 0.001). Diltiazem increased the mean time between coronary occlusion and ventricular fibrillation from 186 to 366 seconds (P ± 10–5), but did not change the magnitude of the diastolic injury potential at onset of ventricular fibrillation. Diltiazem also delayed ischemia-induced conduction impairment to the same extent that it delayed injury potential development. In five dogs, the effect of diltiazem on regional blood flow near the epicardial electrodes was measured by infusion of radionuclide-labeled microspheres. Coronary occlusion reduced flow to the ischemic zone from 0.86 to 0.05 ml/min per g (P = 0.001). Diltiazem increased preocdusion flow by 11% (P = 0.03), but did not significantly alter flow during occlusion. Hemodynamic measurements show that diltiazem did not diminish cardiac work. Diltiazem therefore produced a flow-independent reduction of cellular depolarization during ischemia, which may be due to relief of calcium overload, and which may explain the antifibrillatory effect.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The early adaptation to aortic stenosis was studied in eight conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular minor equator, left ventricular major axis, and ventricular wall thickness. Data were compared during control, acute inflation of a supravalvular aortic cuff occluder and 24 hours after aortic stenosis with and without β-blockade. Acute aortic stenosis increased peak systolic pressure and end-systolic pressure with a decrease of percent systolic shortening of minor diameter (%±L). Twenty-four hours after aortic constriction for heart rates, end-diastolic dimensions, and systolic pressures similar to those measured during acute aortic stenosis, %±L was significantly increased, compared with acute aortic constriction, and was close to control values. End-systolic diameter was not significantly different from control during sustained pressure overload, although end-systolic stress was increased by 26.7 ± 6.1% (P ± 0.01 with control), representing a leftward shift of the end-systolic stress-diameter relation. Similar results were obtained under β-blockade. We conclude that there is, in this model of moderate pressure overload, a nonsympathetic increased inotropic state very early after aortic constriction.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The antihypertensive action of central GABA-ergic stimulation was investigated in conscious stroke prone spontaneously hypertensive rats. Injection of the potent GABA agonist musrimol (0.01–1 μg) into the lateral brain ventricle (icv) lowered mean arterial blood pressure (192.1 ± 8.4 mm Hg) dose-dependently in stroke prone spontaneously hypertensive rats with a maximal fall of −52.7 ± 5 mm Hg lasting for about 90 minutes. This was accompanied by bradycardia and sedation. Pretreatrnent with atropine (2 mg/kg, ip, or 15 μg/kg, icv) did not significantly influence the muscimol-induced fall in mean arterial pressure. In normotensive (109.3 ± 1.9 mm Hg) Wistar-Kyoto controls, the maximal decrease in mean arterial pressure was −12.1 ± 1.6 mm Hg from 109.3 ± 1.9 mm Hg, and the duration of the effect was much less than in stroke prone spontaneously hypertensive rats. Following 1 jig muscimol, icv, plasma noradren- aline did not fall significantly in stroke prone spontaneously hypertensive and Wistar-Kyoto rats, but in stroke prone spontaneously hypertensive rats, plasma adrenaline was fully suppressed (from 118.1 ± 24.2 to 22.8 ± 5.7 pg/ml) throughout the depressor response. The efferent sympathetic nervous activity as directly recorded from the n. splanchnicus was similar in conscious stroke prone spontaneously hypertensive and Wistar-Kyoto rats, and was moderately reduced in both strains by 1 μg muscimol, icv. Basal adrenal nerve activity was higher in stroke prone spontaneously hypertensive than in Wistar-Kyoto rats (14.8 ± 3.7 vs. 10.6 ± 1.7 μV, P ± 0.02); it was reduced by 44% in stroke prone spontaneously hypertensive rats and only by 24% in Wistar- Kyoto rats after central muscimol administration. In contrast to muscimol, the central antihypertensive action of the α2-adrenoceptor agonist donidine in conscious stroke prone spontaneously hypertensive rats was accompanied by similar reductions of splanchnic nerve activity (28%) and adrenal activity (25%). Our results demonstrate for the first time an increased efferent adrenal nerve activity in conscious stroke prone spontaneously hypertensive rats and a selective inhibition of the sympathoadrenal pathway by central GABA-ergic stimulation. The antihypertensive action of central GABA receptor stimulation in stroke prone spontaneously hypertensive rats is not mediated by an increase in vagal tone or a generalized reduction in sympathetic tone, but is associated with the selective suppression of sympathoadrenal activity.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

To examine the influence of the sex hormones on mechanical properties and biochemistry of the adult heart, we studied left ventricular function and cardiac contractile proteins in hearts from 20-week-old male and female rats that had been gonadectomized at 18 days of age, compared with hearts from sham-operated animals. Testosterone and estradiol were not detectable in serum from male and female gonadectomized rats, respectively. The male rats had lower body and heart weights than male sham operated rats, whereas these values were higher in female gonadectomized than in female sham-operated rats. Left ventricular function was studied in a working heart apparatus at similar heart rate and at controlled levels of aortic diastolic pressure and left atrial pressure. At moderate left atrial pressure, end-diastolic pressure and volume per gram dry left ventricle were the same in all groups, but at high left atrial pressure, end-diastolic pressure, and volume per gram dry left ventricle were lower in male and female gonadectomized than in the respective sham-operated rats. Further increases in left atrial pressure were associated with mechanical alternans in male and female gonadectomized rats. Significantly (P± 0.05) lower values for cardiac output, peak systolic pressure, ejection fraction, and myocardial oxygen consumption occurred in male gonadectomized compared with sham-operated rats at moderate and high left atrial pressure at higher levels of aortic diastolic pressure. Decreases in these values for female gonadectomized compared with sham-operated rats occurred only at high left atrial pressure. A significant downward shift in the mean force-velocity relationship was observed in all gonadectomized rats at both moderate and high left atrial pressure. In a followup study, when end-diastolic pressure was kept the same at both moderate and high left atrial pressure in female sham-operated and gonadectomized rats by reducing heart rate, decreases in contractile function in gonadectomized rats were observed at all preloads. Ca++-myosin ATP ase activity was significantly reduced by 34% in male and by 19% in female gonadectomized rats when compared to respective sham-operated control hearts. These alterations in myosin ATPase activity were associated with a reduction in the V, myosin isoenzyme and an increase in the V3isoenzyme. Thus, left ventricular filling and left ventricular function were impaired in hearts of gonadectomized rats. Alterations in function were associated with depressed cardiac myosin ATPase activity in male and female gonadectomized rats. These findings suggest that the sex hormones have cardioregulatory properties, but it remains uncertain whether their effect is exerted during or after maturation.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

To study the response of large coronary arteries to short periods of myocardial ischemia a pair of ultrasonic dimension transducers, a flow probe and a hydraulic occluder were implanted around the left circumflex coronary artery for the instantaneous and continuous measurement of external coronary artery dimensions and coronary blood flow, respectively. At 6.1 ± 0.4 seconds after release of a 15-second occlusion, mean coronary blood flow increased by 255 ± 30% from a preocclusion flow of 32 ± 4.1 ml/min. At this time, large coronary arterial cross-sectional area was unchanged but increased slowly, reaching a peak 28 ± 4.4% above preocclusion levels 61 ± 3.2 seconds after occlusion, i.e., reactive dilation. During maximal reactive dilation, coronary blood flow had already returned to control levels, and heart rate, mean arterial pressure, left ventricular systolic pressure, and left ventricular dP/dt were not different from control. The reactive dilation was not affected if the occlusion occurred proximal or distal to where diameter was measured, or by combined ã-and β-adrenergic receptor blockade, ganglionic blockade, inhibition of prostaglandin synthesis, or by aminophylline. When the reactive hyperemia was prevented by constricting the coronary artery upon release of the coronary occlusion, the reactive dilation was not observed. Thus, large coronary arteries respond to brief periods of occlusion with reactive dilation. The time course of this response is distinctly different from the accompanying reactive hyperemia, and could be eliminated by preventing the marked increase in coronary blood flow following release from the brief period of coronary artery occlusion.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The effects of stretches and releases on the contractile performance of isolated single frog atrial cells (Rana catesbeiana) were investigated. A stretch or release was imposed on the cell-either during a contraction (test) or before the onset of contraction (control)-and the contractile performance (length, velocity and force) of the test contraction was compared with that of the control contraction to determine whether the stretch or release imposed on the contracting cell altered the contractility of the cell. We found that the velocity of cell (and sarcomere) shortening for the remainder of the test contraction following either a stretch or release was markedly less than that occurring at the same time in the control contraction. This decreased velocity occurred even though the force in the test contraction was less than that in the control contraction and the sarcomere length was longer in the test contraction than in the control contraction. These results indicate that after a stretch or release imposed on the contracting cell, the force-velocity relationship at any given length and time is depressed than had the stretch or release not been imposed on the contracting cell. Thus, stretches and releases applied to the contracting single cardiac cell either produce a long-term depression in the contractility of the cell, or that the contractility at any given time and sarcomere length depends markedly on the history of the contraction.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Intracellular potassium activity in guinea pig left atria was measured using potassium ion-selective microelectrodes and conventional microelectrodes. The effects of extracellular potassium concentration and acetylcholine on both intracellular potassium activity and the relationship between the resting membrane potential and the potassium equilibrium potential were investigated. Intracellular potassium activity was 102.1 mM in bathing media with a potassium concentration of 5 mM. Neither increasing extracellular potassium concentration to 10 mM nor exposure to acetylcholine (2 ± 10−6to 10−3M) significantly altered intracellular potassium activity. In contrast, intracellular potassium activity decreased to 92.9 mw in 2.5 mM potassium concentration solutions. Resting membrane potential was 18.6, 9.6, and 7.3 mV positive to the potassium equilibrium potential in 2.5, 5, and 10 mM potassium, respectively. Acetylcholine caused a significant hyperpolarization at each extracellular potassium activity, confirming that resting membrane potential was positive to the potassium equilibrium potential. Even after exposure to 10−3M acetylcholine, the resting membrane potential apparently remained positive to the potassium equilibrium potential. If potassium accumulates in extracellular clefts during acetylcholine exposure, the calculated potassium equilibrium potentials are too negative, and the resting membrane potential might closely approximate the potassium equilibrium potential under these conditions. Fading of the acetylcholine-induced hyperpolarization and overshoot of the resting membrane potential on washout of acetylcholine were observed and are consistent with an accumulation of potassium during exposure to acetylcholine. In 5.0 mM potassium bathing solution, preparation-to-preparation variability of resting membrane potential can largely be explained by variability of intracellular potassium activity. The resting membrane potential is dependent on the logarithm of the intracellular potassium activity with a slope of −54.2 mV/10- fold increase in the intracellular potassium activity (r= −0.869). For fibers suprafused with 2.5 mM extracellular potassium, this relationship has a slope of −28.5 mV/10-fold increase in intracellular potassium activity (r= −0.454), and other factors must be invoked to explain the variability of the resting membrane potential.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Microspheres approximately 25 or 50 μm in diameter were systemically embolized from the left ventricular cavity. The number of microspheres given was empirically chosen to minimize the possibility of more than one microsphere lodging in an arteriole (3 mg/kg), yet was sufficient to allow for adequate histological assessment. The dogs were sacrificed after 24 hours, and focal areas of myocytolytic necrosis were noted in the myocardium. Groups of dogs were given prerreatment with drugs 10 minutes before embolization. Dogs pretreated with phentolamine (n = 8) and prazosin (n= 2) did not reveal any areas of myocardial necrosis after embolization with 25 -μmmicrospheres. Cardiac lesions were also prevented in four of five dogs pretreated with verapamil. In contrast, cardiac lesions were not prevented by prerreatment with yohimbine (n = 2), dipyridamole (n = 3), propranolol (n= 2), or atropine (n = 2). Drug prerreatment with phentolamine or verapamil was not able to prevent cardiac lesions after embolization with 50-μm microspheres. Furthermore, despite a greater number of microspheres physically present in the subendocardial layer, the necrotic lesions were more frequent in the mid-wall and epicardial layers. Lesions produced by 25- or 50-jtm emboli were also significantly smaller in the endocardium. Systemic embolization with microspheres excluding the coronary circulation did not produce cardiac lesions. We conclude that mechanical interruption of the coronary circulation with a 25-μm microsphere may be a necessary but not sufficient condition to produce cardiac necrosis. An ai-adrenergic mechanism is also involved in the production of these lesions. The distinct transmural differences in distribution and size of the embolic lesions suggest the possibilities of a nonuniform transmural ã-adrehergic tonic influence on the coronary microtirculation and/or a nonuniform transmural arteriolar hierarchy within the left ventricular myocardium.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Recent evidence indicates that contraction of vascular smooth muscle may be regulated by two calcium-dependent mechanisms: activation of myosin kinase, and calcium binding to a second, unknown regulatory site. This hypothesis implies that vasodilators could modify vascular tone by several mechanisms, including inactivarion of myosin kinase. Since relaxation of the carotid artery following agonist removal may occur when myosin phosphorylation is at resting levels, we could determine whether dephosphorylation of myosin is necessarily involved in the molecular mechanisms mediating relaxation in response to vasodilators. The relaxant effects of adenosine, 3-isobutyl-l-methylxanthine, forskolin, sodium nitroprusside, and 8-bromo-cGMP were tested under conditions where myosin phosphorylation was at basal levels (0.08 ± 0.02 mol P1/mol light chain). All of these agents increased the rate of relaxation in non-steady state experiments where relaxation was induced by stimulus washout. Steady state dose-response curves were obtained for forskolin and 8-bromo-cGMP in the presence of basal myosin phosphorylation. Forskolin caused a dose-dependent increase in cAMP levels at a rate consistent with a cause and effect relationship between relaxation and total tissue cAMP content. Both drugs relaxed the muscles, with no detectable change in myosin phosphorylation. Therefore, dephosphorylation of myosin is not a necessary event in the molecular mechanism of several vasodilators, including some which presumably act via cyclic nucleotides.

ISSN:0009-7330    

出版商:OVID    

年代:1984

数据来源: OVID