Experimental QT interval prolongation.
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Adrenergic beta-Antagonists↗
Biomedical subjects
P Danilo
Publications and source records attributed to P Danilo.
Mechanical and electrophysiologic changes in rat cardiac allografts during immunologic rejection.
We studied the relationship between immunologic rejection and changes in contractility of isolated perfused papillary muscle, using heterotopically transplanted rat hearts. Rejection assessed by mononuclear cell infiltration was associated with depressed twitch amplitude and lower rates of tension development and relaxation. The relationship between maximum developed tension and [Ca2+]o was attenuated in muscle from the rejecting allografted heart, as compared with muscle of normal or isografted hearts. To determine the effects of rejection on ventricular electrophysiologic properties, we recorded transmembrane action potentials in isolated ventricular myocardium. We found that in rejecting allografted hearts the resting potential, action potential amplitude, and maximum upstroke velocity of phase zero were significantly reduced compared with normal and isografted hearts. The attenuation in the mechanical and electrophysiologic properties was largely prevented by treating the transplanted rat with anti-lymphocyte-globulin on days 0, 1, and 2 after transplantation. In summary, the present study demonstrates that immunologic rejection of the heterotopically allotransplanted rat heart is associated with marked attenuation of both mechanical and electrophysiologic properties of the ventricular myocardium.
Action Potentials↗
Beta-adrenergic receptor sensitivity and guanine nucleotide regulatory proteins in transplanted human hearts and autotransplanted baboons.
This study was conducted in human subjects and in baboons to assess elements of the beta-adrenergic receptor complex in vivo and in vitro following cardiac transplantation. In human subjects, the concentration at which administered isoproterenol increased heart rate by 25 beats per min was within the normal range (mean, 3.2 +/- 0.4 micrograms). Myocardial biopsies and lymphocytes were obtained from 14 transplant recipients undergoing routine right heart catheterization. The stimulatory guanine nucleotide regulatory protein, Gs, was significantly greater in the lymphocyte than in right ventricular myocardium (5.8 +/- 1.7 vs. 2.0 +/- 0.5 relative to standard rat heart membrane preparation, P less than 0.05). In contrast, Gi was significantly greater in the myocardium than in the lymphocyte (4.2 +/- 1.3 vs. 1.1 +/- 0.3, P less than 0.025). There was no correlation between lymphocyte and cardiac G protein determinations. In the autotransplanted baboon heart, beta-receptors were increased (73 +/- 4 vs. 36 +/- 10 fmol/mg, P less than 0.05). Gs was not significantly different in denervated myocardial tissue vs. control cardiac tissue (1.1 +/- 0.2 vs. 0.8 +/- 0.2, P greater than 0.05). However, the inhibitory G protein, Gi, was significantly greater in transplanted animals (0.4 +/- 0.1 vs. 0.2 +/- 0.04, P less than 0.05). Relative enrichment of a Gi-like protein in the autotransplanted baboon heart was associated with a non-statistically significant trend towards a uniform reduction in basal and Gs-mediated adrenergic effects on adenylate cyclase activity. Despite the lack of biochemical evidence of enhanced beta-adrenergic receptor-mediated adenylate cyclase coupling, denervation in the autotransplanted baboon was associated with in vitro evidence of chronotropic and inotropic supersensitivity to isoproterenol. The results call into question the notion of adrenergic hypersensitivity in human subjects following cardiac transplantation, indicate the potential role for guanine nucleotide regulatory proteins in mediating responses of the denervated heart, and distinguish between several characteristics of the chronically denervated, transplanted human heart compared with the acutely auto-denervated of the baboon heart.
Adenylyl Cyclases↗
Aprindine.
Aprindine is a long-acting antiarrhythmic agent, effective when administered orally or intravenously in the treatment of ventricular arrhythmias of varying etiologies. It may be especially useful in the treatment of the Wolff-Parkinson-White syndrome. To a lesser extent, it may be useful in the treatment of atrial arrhythmias. Side effects can be minimized by careful titration of the dose of aprindine. If the frequency of such serious side effects as cholestatic jaundice and agranulocytosis remains low enough, aprindine should prove to be a useful addition to currently available antiarrhythmic drugs.
Administration, Oral↗
Action of halothane on myocardial adenylate cyclase of rat and cat.
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Adenylyl Cyclases↗
Effects of acetylcholine on the ventricular specialized conducting system of neonatal and adult dogs.
We determined the effects of acetylcholine on automaticity of isolated cardiac Purkinje fibers from neonatal and adult dogs and on the idioventricular rhythm of adult dogs with complete atrioventricular block. Isolated Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. For both age groups, spontaneous rate was decreased by acetylcholine, an effect which was reduced by atropine. The magnitude of the effect is equal in both neonatal and adult dogs. The negative chronotropic effect of acetylcholine was not prevented by phentolamine, indicating that an alpha-adrenergic mechanism was not involved. The idioventricular rate of conscious dogs with formalin-induced heart block was decreased by administration of acetylcholine. The effect was augmented by propranolol and attenuated by atropine. Thus, for both the in vitro and in situ ventricular specialized conducting system, acetylcholine decreases automaticity presumably through combination with a muscarinic receptor.
Acetylcholine↗
Age-related changes in Purkinje fiber action potentials of adult dogs.
To determine the effects of age on electrophysiological properties of Purkinje fibers (PF), we used standard microelectrode techniques to study PF from normal beagles of five age groups: 19.1 +/- 0.8, 63.7 +/- 2.6, 88.3 +/- 1.9, 107.2 +/- 1.6, and 132.3 +/- 4.3 months (mean +/- SE). Maximum diastolic potential (MDP) did not change over this age range. Action potential (AP) amplitude and maximum upstroke velocity of phase 0 (Vmax) attained peak values at 63.7 months and then declined. As age increased there was an increase in phase 1 repolarization, a prolongation in the time to the peak of the plateau, and a decrease in plateau height. AP duration reached a maximum at 63.7 months and thereafter remained unchanged. Fibers were superfused with the slow channel blocker, AHR-2666, and the fast channel blocker, tetrodotoxin (TTX). AHR-2666 had age-related effects on AP duration, phase 1 repolarization, plateau height, and time to the peak of the plateau. There were no age-related changes in TTX effects on phases 0--2. In another series of experiments, Purkinje fibers from dogs 23 +/- 1.2 to 106 +/- 1.4 months old were superfused with a calcium-rich solution in which Na+ was replaced by tetraethylammonium (TEA+). The resultant slow response action potentials, which are calcium dependent, showed an age-related decrease in AP amplitude, Vmax, and time to peak amplitude. When these fibers were superfused with the slow channel blocker, verapamil, there was an age-related effect on AP amplitude. Our studies indicate that in the normal aging heart, major changes occur in repolarization that appear, in the main, to result from change in the slow inward current carried by Ca2+.
Action Potentials↗
Epinephrine-induced automaticity of canine cardiac Purkinje fibers and its relationship to the adenylate cyclase-adenosine 3',5'-monophosphate system.
We studied the relationship between epinephrine-induced increases in automaticity and in the adenylate cyclase-adenosine 3',5'-monophosphate (cAMP) system in canine cardiac Purkinje fibers. In intact Purkinje fiber bundles superfused with Tyrode's solution, epinephrine induced a concentration-dependent increase in automaticity and in cAMP content. Both of these effects were reduced by propranolol. Decreasing the temperature of the superfusate from 37 degrees to 25 degrees C blocked the epinephrine-induced increase in automaticity, but not the increase in cAMP content. Addition of the metabolic blocking agent, iodoacetate, to the superfusate did not block the effect on Purkinje fiber automaticity, but the cAMP content did not increase. In Purkinje fiber bundle whole homogenates adenylate cyclase was stimulated more by isoproterenol than by epinephrine. Low concentrations of phenylephrine decreased adenylate cyclase activity; higher concentrations induced an increase toward control values. Iodoacetate did not significantly alter cyclase activity and did not affect its response to epinephrine. These students have shown that although intact Purkinje fiber bundles respond to epinephrine with increases in automaticity and cAMP content, these two events can be dissociated under appropriate conditions.
Action Potentials↗
Effects of the phenothiazine analog, EN-313, on ventricular arrhythmias in the dog.
Effects of the phenothiazine analog, EN-313, on ventricular electrical activity were studied using isolated blood-superfused canine Purkinje fibers and conscious dogs with sustained ventricular arrhythmias following a 2-stage ligation of the left anterior descending coronary artery, EN-313, less than 3 mg/kg, i.v., had no significant effect on transmembrane potentials of Purkinje fibers. At 3 mg/kg, EN-313 significantly decreased maximum upstroke velocity of phase 0 depolarization and action potential duration. In conscious dogs, EN-313 (1-3 mg/kg i.v.; 10-20 mg/kg p.o.) reduced arrhythmias that occured larger than or equal to 24 h after coronary artery ligation. No excessive changes in electrocardiographic parameters were observed following EN-313. These studies demonstrate that EN-313 suppresses ventricular arrhythmias in doses which have little effect on cellular electrophysiologic properties of normal Purkinje fibers and suggest that EN-313 should be useful in treating cardiac arrhythmias arising as a result of coronary occlusion.
Animals↗
Effects of adrenergic amines on electrophysiological properties and automaticity of neonatal and adult canine Purkinje fibers: evidence for alpha- and beta-adrenergic actions.
We determined age-related differences in automaticity and responsiveness of cardiac Purkinje fibers from adult and neonatal dogs to graded concentrations of epinephrine, isoproterenol, and phenylephrine. Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 37 degrees C. Control spontaneous rates for adults and neonates did not differ significantly. There was a biphasic response to all agonists such that rate decreased at low and increased at high concentrations. The decrease was greater with phenylephrine and epinephrine than with isoproterenol. The increase in rate was greater with isoproterenol and epinephrine than with phenylephrine. Propranolol shifted the dose-response curves downward and to the right for all agonists; phentolamine, shifter the curves upward and to the left. Epinephrine and isoproterenol dose-response curves for the neonates were upward and to the left of those for adults. Phenylephrine curves were identical for adults and neonates. Thus there are alpha- and beta-adrenergic effects on Purkinje fiber automaticity; the former decrease and the latter increase rate. Furthermore, the effects on automiticity of beta-adrenergic amines are greater in the neonates than in the adult.
Action Potentials↗
Effects of disopyramide on electrophysiologic properties of canine cardiac purkinje fibers.
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Action Potentials↗
Cardiac effects of disopyramide.
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Action Potentials↗
Effects of therapeutic concentrations of diphenylhydantoin on transmembrane potentials of normal and depressed Purkinje fibers.
Standard intracellular microelectrode techniques were used to study canine Purkinje fibers (PF) which had been superfused with blood or Tyrode's solution to determine the cardiac cellular electrophysiologic changes induced by antiarrhythmic concentrations of diphenylhydantoin (DPH). Some PF were normal whereas others were depressed by stretch, exposure to ouabain (125 mug/1) or superfusion with a solution in which all Na+ was replaced by tetraethylammonium. For normal fibers, therapeutic concentrations of DPH (DPH) induced slight decreases in action potential (AP) amplitude, maximum upstroke velocity of phase O (Vmax) and membrane responsiveness and somewhat greater decreases in AP duration. For fibers moderately depressed by ouabain or stretch, with reduced AP amplitude, maximum diastolic potential and Vmax, therapeutic [DPH] increased these variables. Fibers markedly depressed by Na-free solution or stretch developed slow response AP. The amplitude and Vmax of the AP were decreased by therapeutic [DPH]. Therapeutic [DPH] also suppressed automaticity and ouabain-induced delayed afterdepolarizations. Our studies suggest that the slight depression of normal PF AP characteristics induced by therapeutic [DPH] probably is of little significance with respect to antiarrhythmic effect. In contrast, both the improvement of AP characteristics of moderately depressed fibers and further depression of severely depressed fibers caused by [DPH] might modify arrhythmias. Effects of DPH on automaticity and delayed afterdepolarizations also would contribute to its antiarrhythmic effect.
Action Potentials↗
The effects of dimethyl quaternary propranolol on the electrophysiologic properties of canine cardiac Purkinje fibers.
The effects of dimethyl quaternary propranolol (UM-272) on electrophysiologic properties of canine cardiac Purkinje fibers (PF) were studied using standard microelectrode techniques. In PF superfused with Tyrode's solution, the effects of UM-272, 10- minus 7 to 10- minus 5 M, were studied. In other experiments, UM-272, 3 mg/kg, was injected into donor animals whose blood was used to superfuse isolated PF. Antiarrhythmic concentrations of UM-272 decreased action potential (AP) amplitude, phase 0 upstroke velocity, membrane responsiveness, AP duration and the effective refractory period (the decrease in the effective refractory period was less than that in AP duration). Automaticity of spontaneously firing PF was suppressed. As perfusate potassium concentration was increased, the magnitude of UM-272 effect was accentuated. When the actions of equimolar concentrations of UM-272 and propranolol on PF AP were compared, propranolol attained a steady-state effect more rapidly and tended to depress the AP more markedly. UM-272 did not block epinephrine-induced increases in PF automaticity or the adenylate cyclase activation of PG homogenates induced by epinephrine. These studies indicate that UM-272 has direct effects on the PF AP similar to those of propranolol, but lacks the beta blocking properties of the latter.
Action Potentials↗
Is preoperative fasting necessary?
The effects of fasting and of histamine (H2) antagonists on gastric volume and acidity were studied in 56 baboons undergoing various surgical procedures under general anesthesia and randomly allocated into 4 groups; group A--fasted for 14 hours; group B--given 100-120 ml of water 3 hours before surgery; groups C and D--also given 100-120 ml of water 3 hours before surgery; in addition, the former received cimetidine 10 mg/kg IM and the latter ranitidine 1.5 mg/kg IM 30-40 minutes before anesthesia. There were no significant differences between groups A and B with respect to the gastric volume and pH. Both ranitidine and cimetidine significantly (P < 0.02) reduced gastric volume and increased gastric pH. Thus, prolonged withholding of oral fluids does not reduce the gastric volume or increase gastric pH. H2-antagonists are effective in reducing both gastric residual volume and pH.
Animals↗
[High, asymptomatic and persistent thrombocytosis in splenectomized subjects].
The Authors illustrate clinicals evaluations of tree splenectomised patients, whose platelets' counts were normal in the pre-operatory period. The patients had shown, after splenectomy, high (platelets' count upper than 10(6)/mmc), asymptomatic (without hemorrhage and thromboembolism), persistent father four months, spontaneously and progressively decreasing thrombocytosis. Clinical evaluations and blood analysis concern respectively periods of four years and six months, two years and two months, three years and six months after splenectomy. Furthermore the Authors examine the splenectomy's role into thrombocytosis, and remark, on the contrary of inherent literature, that, in some occurrences, the splenectomy produces high, persistent and asymptomatic thrombocytosis.
Adult↗