摘要:

Studies were performed on the dog heart in situ to determine the effects of diphenylhydantoin (DPH) on excitability and automaticity. DPH decreased automaticity in the His-Purkinje system, evidenced by an increase in the ventricular escape time both during vagal stimulation in intact dogs and after ventricular overdrive in dogs with heart block. The spontaneous ventricular rate of dogs with heart block was unaffected by doses up to 20 mg/kg. DPH had no significant effect on either atrial or ventricular diastolic threshold when this variable was tested with bipolar stimuli or with stigmatic anodal or cathodal stimuli. The effective refractory period of atrial and particularly of ventricular muscle was shortened by DPH (10 mg/kg); a leftward shift in the strength-interval curve occurred consistently. Multiple response threshold and fibrillation thresholds were elevated by DPH in both the ventricle and atrium (20 of 24 experiments). In anesthetized dogs, intraventricular conduction velocity increased minimally after DPH administration. DPH increased transmembrane threshold voltage and reduced the current required to stimulate isolated Purkinje fibers. The commercial solvent used clinically as a diluent for DPH was found to increase diastolic threshold and prolong the effective refractory period.

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

摘要:

Isolated rabbit left atrial preparations were perfused with Tyrode's solutions containing 1 to 10 μg/ml (4 × 10−6−4 × 10−5M) diphenylhydantoin (DPH), 2.6−5.6 mM K+, and 154−308 mM Na+. Steady-state transmembrane resting and action potentials were recorded from these preparations with glass microelectrodes at stimulation rates ranging from 0.2 to 3/sec. DPH had little or no effect on the relationship between extracellular [K+] and membrane resting potential. Action potential overshoot was generally decreased by 5 and 10 μg/ml DPH and increased by 1 μg/ml DPH at stimulation rates of 2 and 3/sec in the presence of increased [K+]. DPH and increased [K+] acted synergistically to shorten action potential duration (measured at 50% repolarization). The effect of DPH on phase 0 of the action potential (measured as action potential rise time between 10 and 50% and 50 and 90% depolarization) was markedly dependent upon drug concentration, extracellular [K+] and stimulation rate. The lowest concentration of DPH (1 μg/ml) usually shortened action potential rise time, particularly when it had been prolonged by increasing extracellular [K+]. Conversely, the highest concentration of DPH (10 μg/ml) and increased [K+] acted synergistically to prolong action potential rise time (i.e., decrease depolarization rate). When present, the depressant effect of DPH on membrane depolarization was rapidly antagonized by increasing extracellular [Na+]. It is proposed that DPH may either enhance or depress (like quinidine) membrane activity in atrial tissue, and that both the direction and magnitude of effect are strongly dependent upon drug concentration, ionic milieu, and heart rate.

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

摘要:

Glucagon decreases peripheral vascular resistance by direct action on the arterioles. The present experiments were performed to study the effect of glucagon on the coronary resistance vessels. In isolated hearts from eight dogs the coronary arteries were perfused at a constant rate and the change in coronary pressure was used as an index of change in resistance after the intracoronary injections of glucagon (50 μg/kg). In the beating heart, glucagon caused a 22% decrease in the average coronary pressure (from 102 to 80 mm Hg); however, with this decrease in coronary resistance, myocardial contractility rose an average of 45% (from 11 to 16 units), the average heart rate increased 38% (from 156 to 213 beats/min), and the average coronary venous oxygen saturation decreased from 79.7% to 63.7%. However, when similar intracoronary injections of glucagon were made after cardiac arrest by potassium there was no change in coronary venous oxygen saturation and no significant decrease in coronary pressure. We conclude that the decrease in coronary resistance in the beating heart after glucagon injection is secondary to the metabolic effects of the increased myocardial contractility and heart rate, and that there is no significant direct vasodilating effect on the coronary resistance vessels.

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

摘要:

The positive inotropic effects of catecholamines have been postulated to result from an increase in the intracellular level of cyclic AMP (adenosine 3′,5′-monophosphate) produced by activation of adenyl cyclase. Although lack of an inotropic effect by exogenously administered cyclic AMP has cast doubt on this hypothesis, cardiac cells are not readily permeable to cyclic AMP. The N6-2′-O-dibutyryl derivative of cyclic AMP is thought to enter cells more readily and is resistant to enzymatic degradation by phosphodiesterase. We examined the effects of cyclic AMP and its dibutyryl derivative on the contractile performance of isolated cat right ventricular papillary muscles. Cyclic AMP (1 × 10−4to 5 × 10−3M) had no effect on papillary muscle function. However, dibutyryl cyclic AMP caused a concentration-dependent increase in isometric tension and rate of tension development, the threshold concentration being 5 × 10−4M. The increments in tension (4.5 ± 0.4 g/mm2) and rate of tension development (58.4 ± 5.4 g/mm2/sec) at peak concentration (3 × 10−3M) were similar to those found at peak norepinephrine concentration (10−5M). Dibutyryl cyclic AMP (10−3M) also caused a marked shift of the force-velocity curve upward and to the right. Although 10−6M propranolol depressed the inotropic effects of norepinephrine, it did not alter the contractile response to dibutyryl cyclic AMP. These findings are consistent with the hypothesis that the positive inotropic effects of catecholamines are mediated by cyclic AMP.

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

摘要:

Rat ventricles, ranging from 306 to 1999 mg, were obtained from normal animals of different ages and from animals subjected to chronic aortic constriction. The concentration of DNA in the paired ventricles (right and left) was found to be closely related to the concentration of nuclei in the left ventricular papillary muscles. Muscle nuclei represented only 10 to 15% of this population of nuclei. In young animals (phase 1), the total ventricular content of muscle nuclei, nonmuscle nuclei, and of DNA were increasing with ventricular growth. In the adult rat (phase 2), the total ventricular content of DNA and of both muscle and nonmuscle nuclei remained relatively constant with ventricular growth. In the enlarged hearts (phase 3), there was a further increase in total ventricular DNA but there was no further increase in the total number of muscle nuclei. Spectrophotometric studies (Feulgen stain), showed that 88% of the muscle nuclei belonged to a single ploidy class (probably diploid). No relation could be demonstrated between the extent of nuclear polyploidy and the weight of the ventricles. It was concluded that polyploidy was not a significant factor in the increased total DNA of phase 3. The increased ventricular DNA of phase 3 was explained by the proliferation of the nonmuscle nuclei.

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

摘要:

A sensitive and specific double-isotope dilution method for assaying norepinephrine and epinephrine separately is described. The method is based on enzymatic conversion of these two catecholamines to their respective metanephrines and was applied successfully to measurement of resting plasma concentrations of norepinephrine and epinephrine in normal subjects with the finding that norepinephrine (0.20 ± 0.08 μg/liter) normally constitutes approximately 80% of the plasma catecholamine content and epinephrine (0.05 ± 0.03 μg/liter) 20%.

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID

ISSN:0009-7330    

出版商:OVID    

年代:1970

数据来源: OVID