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P Danilo

Publications and source records attributed to P Danilo.

At least 73 records · Page 4Linked to original sources

Electrophysiologic characteristics of human ventricular and Purkinje fibers.

We studied the electrophysiologic characteristics of ventricular muscle and Purkinje fibers from the hearts of five patients undergoing cardiac transplantation. All five patients had congestive failure and coronary artery disease before surgery and were receiving digitalis therapy. Ventricular muscle had a maximal diastolic potential (MDP) of -78 +/- 1 mV (mean +/- SEM), an action potential (AP) amplitude of 104 +/- 2 mV, a phase 0 upstroke velocity (Vmax) of 297 +/- 19 V/sec and an AP duration at 50% repolarization (APD50) of 190 +/- 4 msec. Purkinje fibers had an MDP of -80 +/- 2 mV, an AP amplitude of 107 +/- 2 mV, a Vmax of 388 +/- 25 V/sec and an APD50 of 195 +/- 9 msec. Fibers from infarcted sections of the heart had significantly longer APD than those from noninfarcted, which resulted in marked dispersion of APD in infarcted and adjacent zones. Both epinephrine and ouabain induced delayed after depolarizations in Purkinje fiber. This suggest that delayed after depolarizations and resultant triggered activity can occur in the human ventricle.

Action Potentials↗

The electrophysiological properties of normal neonatal and adult canine cardiac Purkinje fibers.

To determine the basis for age-related changes that occur in the transmembrane action potentials (AP) of canine cardiac Purkinje fibers (PF), we used standard microelectrode techniques to study PF from normal neonatal and adult beagles. As previously shown, neonatal PF AP have a less negative maximum diastolic potential (MDP), a lower AP amplitude (amp) and maximum upstroke velocity of phase 0 (Vmax), and shorter AP duration measured at 50% and 100% repolarization than have those of adults. Further, the termination of phase 1 and the peak of phase 2 occur at more positive levels of membrane potential in neonatal PF. The less negative MDP in neonatal PF is associated with a lower intracellular potassium activity (aKi) as demonstrated with a K+-sensitive microelectrode. Neonatal PF showed greater depression of AP amp and Vmax during superfusion with the rapid Na+ channel blocker, tetrodotoxin (TTX), than did adult PF. The attainment of more negative voltages at the termination of phase 1 in adult compared to neonatal PF was not attributable to age-related differences in response to changes in drive cycle length, temperature, or external Cl- concentration. However, 4-aminopyridine, a blocker of the early, repolarizing potassium current, altered this variable in adult and not in neonatal PF. The effects of verapamil and AHR-2666, both slow inward current blockers; of TTX, which blocks a background inward Na+ current; and of TEA+, which blocks repolarizing K+ current, were studied on AP repolarization. Adult PF AP were more sensitive to the effects of AHR-2666, verapamil, and TEA+ and less sensitive to the effects of TTX than neonates.

Action Potentials↗

Maternal and fetal effects of uterine stimulants and relaxants.

There are numerous pharmacologic agents available for either the stimulation or relaxation of the gravid uterus. Although these drugs have been in use for many years, recent advances have made their employment more desirable and therefore more frequent. While many of these drugs obtain the desired effect, all of them have side effects that may be either beneficial or adverse to the mother or fetus, or to both. It is important that those who are administering these drugs understand the complete range of effects they may evoke.

Abortifacient Agents↗

Effects of pirmenol HCl on electrophysiologic properties of cardiac Purkinje fibers.

We studied the effects of pirmenol hydrochloride (CI 845), cis-(+/-)-alpha-[3-(2,6-dimethyl-1-piperidinyl)propyl]-alpha-phenyl-2-pyridinemethanol monohydrochloride, on the electrophysiologic properties of canine cardiac Purkinje fibers having normal (fast response) action potentials. CI 845 greater than or equal to 1 X 10(-6) M depressed both maximum upstroke velocity of phase 0 and automaticity. CI 845 greater than or equal to 1 X 10(-5) M significantly decreased action potential amplitude and duration measured at 50% repolarization and prolonged action potential duration measured at full repolarization. In addition, this concentration depressed membrane responsiveness and prolonged the effective refractory period and conduction time. All changes were reversible following superfusion with drug-free Tyrode solution. Increasing extracellular potassium ([K+]0) from 4 mM to 6 mM did not potentiate the CI 845-induced changes. CI 845 1 X 10(-5) M decreased automaticity of slow response action potentials studied in a Na+-free solution but had no effect on the action potential characteristics of these spontaneously discharging fibers. In blood superfusion studies, plasma levels of 0.1--3.0 micrograms/ml CI 845 affected the action potential characteristics in a manner similar to concentrations ranging from 1 X 10(-6) to 1 X 10(-5) M CI 845 in Tyrode solution. At plasma levels greater than or equal to 1.1 micrograms/ml, CI 845 induced a significant prolongation of the electrocardiographic PR interval. These studies indicate that CI 845 has effects on the action potential and ECG similar but not identical to those of 'local anesthetic' antiarrhythmic agents.

Action Potentials↗

Effects of verapamil on electrophysiologic properties of blood superfused cardiac Purkinje fibers.

Blood superfusion techniques were used to study the effects of verapamil on the body surface electrocardiogram and blood pressure of intact, anesthetized dogs as well as transmembrane action potential characteristics of isolated Purkinje fibers. Verapamil, 100 to 600 microgram/kg, administered in sequential doses intravenously to the intact (donor) animal caused a dose-dependent increase in the P-R interval and a decrease in systemic arterial pressure while exerting no significant effect on the normal, fast response Purkinje fiber action potential. To study effects of verapamil in depolarized fibers, maintained stretch was applied to Purkinje fibers until resting potentials had decreased from approximately -91 mV to a stable level of approximately -55 mV. For these fibers, verapamil, 400 microgram/kg, given as a single injection almost totally suppressed the slow response action potential while prolonging the P-R interval by less than 30% above control. These experiments suggest that in the presence of normal sinus and atrioventricular nodal function, plasma concentrations of verapamil which abolish the slow response action potential should have no major effect on sinus rate and atrioventricular conduction.

Action Potentials↗

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↗

Tocainide.

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Administration, Oral↗

Mexiletine.

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Arrhythmias, Cardiac↗

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↗