Biomedical subjects

A H Kadish

Publications and source records attributed to A H Kadish.

At least 109 records · Page 6Linked to original sources

PubMed1988

Changes in myocardial repolarization in patients undergoing balloon valvuloplasty for congenital pulmonary stenosis: evidence for contraction-excitation feedback in humans.

Alterations in ventricular loading conditions lead to changes in action potential duration and arrhythmias via contraction-excitation feedback; a decrease in load leads to prolongation of repolarization. To determine whether changes in right ventricular load alter ventricular repolarization in man, the corrected QT interval, a measure of overall ventricular repolarization, was measured in 32 patients before and after valvuloplasty for pulmonary stenosis. Right ventricular systolic pressure decreased (82.5 +/- 30.7 to 40.5 +/- 9.5 mm Hg, p less than .001) and the QTc increased concurrently (409.1 +/- 24.3 to 440.7 +/- 28.0 msec, p less than .001) after successful valvuloplasty. The increase in QTc was most marked for those patients with a greater than 30 mm Hg decrease in right ventricular pressure (40.0 +/- 23.3 vs 16.3 +/- 21.3 msec, p = .006). In a subset of seven patients in whom monophasic action potentials were recorded, monophasic action potential duration, a measure of local repolarization, was prolonged (230.0 +/- 24.3 vs 216.9 +/- 21.9, p less than .001) after successful valvuloplasty, confirming that the QTc prolongation reflected changes in local ventricular repolarization. In addition, during nine acute right ventricular outflow tract occlusions in a subset of six patients, monophasic action potential duration shortened (206.6 +/- 17.6 vs 221.7 +/- 20.9 msec, p less than .01) and early afterdepolarizations developed consistent with contraction-excitation feedback. These data suggest that, in humans, changes in mechanical load are associated with changes in ventricular repolarization consistent with contraction-excitation feedback.

Action Potentials↗

PubMed1988

Accentuated antagonism between beta-adrenergic and vagal effects on ventricular refractoriness in humans.

The purpose of this study was to determine whether there is accentuated antagonism between sympathetic and vagal effects on ventricular refractory periods (VRPs) in humans. The effects of 0.04 mg/kg of atropine on the right ventricular effective and functional refractory periods were determined in the setting of beta-adrenergic blockade by propranolol (0.15 mg/kg loading dose, then 0.1 mg/min continuous infusion, group 1) and in the setting of beta-adrenergic stimulation by 25 or 50 ng/kg/min isoproterenol (groups 2 and 3, respectively). Groups 4 to 6 served as control groups. In group 4, VRPs were determined on three occasions separated by 10 min each in the absence of drug. VRPs also were determined on two occasions after infusion of propranolol (group 5) or 25 ng/kg/min of isoproterenol (group 6). Groups 1 to 4 consisted of 10 subjects each, and groups 5 and 6 consisted of five subjects each. VRPs were determined with the use of basic drive cycle lengths of 600, 500, 400, and 350 msec. Because of sinus tachycardia, sufficient data for comparison of groups 1 to 3 were available only at drive cycle lengths of 400 and 350 msec. Atropine significantly shortened the VRPs in groups 1 to 3, but the magnitude of atropine's effects in group 3 (5.3% to 5.8% shortening at drive cycle length of 350 msec) was significantly greater than in group 1 (2.6% to 3.0% shortening, p less than .05) Data from the control groups demonstrated that there was no effect of time on measurement of VRPs either in the drug-free state or in the presence of propranolol or isoproterenol. The results of this study indicate that cholinergic tone lengthens VRPs in the absence of background sympathetic activity and that this lengthening of VRPs may become accentuated during beta-adrenergic stimulation.

Adult↗

PubMed1988

Inducible sustained ventricular tachycardia 4 years after experimental canine myocardial infarction: electrophysiologic and anatomic comparisons with early healed infarcts.

We studied a group of 17 dogs 4 to 6 years after infarction produced by 2 hr occlusion of the anterior descending coronary artery followed by reperfusion. Dogs in this "late" infarct group were compared with a group of 24 dogs with "early" healed infarcts (2 to 24 weeks old). With signal-averaging techniques body surface potentials were recorded during sinus rhythm. After thoracotomy epicardial electrograms were recorded from 45 standardized sites within the infarcted region and characteristics of selected electrograms were compared with anatomic features of underlying myocardium. Epicardial recordings from the late infarct group demonstrated earlier local activation (p less than .001) and shorter electrogram duration (p less than .001) when compared with recordings from the early infarct group. There was less temporal dispersion of activation and electrogram duration among the 45 sites in dogs with late infarcts as measured by respective coefficients of variance (p = .007 and less than .001). With programmed stimulation six dogs in the late and eight in the early infarct group exhibited inducible sustained ventricular tachycardia. Mean cycle length of the tachycardia in dogs with late infarcts was significantly shorter (p = .035). Late potentials were notably less prominent in dogs in the late infarct group with ventricular tachycardia than in dogs in the early infarct group. Fewer abnormal electrophysiologic characteristics of late infarcts coincided with relatively less scar in the underlying myocardium. Moreover, the strength of electrophysiologic-anatomic correlations differed in late as opposed to early infarcts. The latter findings suggest long-term evolution of infarct anatomy. We conclude that a substrate for reentrant tachycardia is present in dogs 4 to 6 years after reperfused infarction. Conduction characteristics are less abnormal in these late healed infarcts and are associated with a shorter ventricular tachycardia cycle length and less pronounced late potentials on the body surface.

Animals↗

PubMed1988

Effects of lidocaine and procainamide on normal and abnormal intraventricular electrograms during sinus rhythm.

The effect of lidocaine (n = 6) and procainamide (n = 12) on electrogram characteristics from electrically normal right ventricular and electrically abnormal left ventricular endocardial sites was determined in 18 patients with prior myocardial infarction. Bipolar electrograms were recorded during sinus rhythm with No. 6F catheters positioned at a left ventricular abnormal site (electrograms fulfilling two of the following criteria: amplitude less than 3 mV, duration greater than 70 msec, or an amplitude to duration ratio less than .046) and normal sites at the right ventricular apex (RVA) and right ventricular outflow tract (RVOT). All electrograms were recorded from the same location before and after intravenous lidocaine or procainamide administered to obtain mean serum concentrations of 4.2 +/- 0.6 and 9.42 +/- 2 micrograms/ml respectively. Lidocaine and procainamide had no significant effect on sinus cycle length or electrogram amplitude. After lidocaine, no significant change in QRS width (112 +/- 23 vs 114 +/- 24 msec), left ventricular electrogram duration (76 +/- 21 vs 78 +/- 15 msec), or right ventricular electrogram duration (RVA 33 +/- 9 vs 33 +/- 10 msec, RVOT 31 +/- 9 vs 33 +/- 11 msec) was noted during sinus rhythm. At a paced cycle length of 600 msec, there was also no change in the paced QRS duration (197 vs 198 msec), the RVA electrogram duration (30 vs 32 msec), the RVOT electrogram duration (49 vs 52 msec), or the left ventricular electrogram duration (102 vs 108 msec).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Catheterization↗

PubMed1988

Mechanisms of depressed conduction from long-term amiodarone therapy in canine myocardium.

Amiodarone therapy leads to a significant impairment in myocardial conduction, yet it causes only a modest decrease in the maximum rate of depolarization of the action potential (dV/dT). To determine whether the decrease in dV/dT solely accounts for the impaired myocardial conduction or whether passive membrane properties may also be involved, we studied 21 ventricular epicardial tissues from 14 beagles; six dogs received long-term treatment (3-6 weeks) of amiodarone orally, and the remaining dogs served as controls. Amiodarone therapy was associated with a decrease in conduction velocity (0.41 +/- 0.15 vs. 0.56 +/- 0.05 m/sec; p less than 0.01). There was a trend toward a decrease in dV/dT and a significant decrease in the space constant (0.69 +/- 0.27 vs. 1.05 +/- 0.25 mm; p = 0.01), of which the latter correlated closely with the decrease in conduction velocity measured in the amiodarone-treated tissues (r = 0.85, p less than 0.05). These data indicate that the decrease in myocardial conduction velocity caused by amiodarone is primarily due to effects on overall resistance to passive current flow rather than effects on the inward sodium current.

Action Potentials↗

PubMed1987

Usefulness of electrophysiologic study to determine the clinical tolerance of arrhythmia recurrences during amiodarone therapy.

The relation of clinical and electrophysiologic variables to outcome was evaluated in 121 patients treated with amiodarone for sustained ventricular tachyarrhythmias. Electrophysiologic study was performed in all patients a mean of 14 days after beginning amiodarone therapy. Forty-six patients who were given oral amiodarone therapy experienced arrhythmia recurrence. Multivariate analysis was performed using 16 clinical and electrophysiologic variables to determine which factors were associated with 1) arrhythmia recurrence and 2) a poorly tolerated arrhythmia recurrence (that is, cardiac arrest or sudden cardiac death) during oral amiodarone therapy. No variable predicted arrhythmia recurrence. Five variables correlated significantly with a poorly tolerated arrhythmia recurrence. Hemodynamic stability of the arrhythmia induced on electrophysiologic testing during amiodarone therapy had the best predictive value (p less than 0.001). Younger age, lower ejection fraction, a poorly tolerated rhythm at clinical presentation and absence of left ventricular aneurysm were also associated with a poorly tolerated arrhythmia recurrence. Only 3 of 57 patients who had a well tolerated arrhythmia induced on electrophysiologic testing during amiodarone therapy had recurrence of a poorly tolerated arrhythmia versus 19 of 47 who had hemodynamically unstable arrhythmias induced during amiodarone therapy (p less than 0.001). Thus, electrophysiologic testing during amiodarone therapy appears useful in identifying patients who are prone to have catastrophic arrhythmia recurrences and could allow for the institution of additional or alternative modes of therapy.

Amiodarone↗

PubMed1987

The cellular electrophysiologic changes induced by ablation: comparison between argon laser photoablation and high-energy electrical ablation.

The cellular electrophysiologic effects of myocardial ablation performed in vitro with argon laser energy were compared with those of high-energy electrical shocks. A border zone of injured but nonnecrotic tissue surrounding the site of energy delivery was present after tissue ablation by both energy modalities. A decrease in resting membrane potential, action potential amplitude, and maximum rate of upstroke velocity was noted in each tissue sample, was greatest nearest the site of energy delivery, and was of graded severity at increasing distances from the crater edge. The extent of injury, as indexed by changes in action potential variables and necrosis, histologically determined, was greater for tissues exposed to high-energy shocks. The relatively focal injury after argon laser photoablation may explain the lower incidence of arrhythmias and hemodynamic dysfunction noted with the use of this method of ablation in vivo.

Action Potentials↗

PubMed1987

Depression of action potential characteristics and a decreased space constant are present in postischemic, reperfused myocardium.

Brief periods of ischemia and reperfusion may lead to arrhythmias and delayed epicardial activation. To determine the nature of the electrophysiologic substrate and to gain insight into potential mechanisms underlying the electrophysiologic and hemodynamic abnormalities that develop in this setting, standard microelectrode techniques were used to measure action potential characteristics, conduction velocity, and space constants in canine isolated epicardial preparations removed after a 15-min anterior descending artery occlusion and 20-min reflow period in vivo. Our results demonstrate a significant reduction in conduction velocity (0.78 +/- 0.38 vs. 0.31 +/- 0.12 m/s, P less than 0.001), space constant (1.05 +/- 0.42 vs. 0.45 +/- 0.12 mm, P = 0.004), resting membrane potential (81.3 +/- 2.5 vs. 61.7 +/- 7.8 mV, P less than 0.001), action potential amplitude (94.1 +/- 4.2 vs. 64.1 +/- 1.5 mV, P less than 0.001), and dV/dT (164.7 +/- 37.3 vs. 52.6 +/- 19.7 V/s, P less than 0.001) in postischemic reperfused myocardium. The space constant and dV/dT each correlated with conduction velocity; in addition, the space constant was an independent predictor of conduction velocity in these tissues. These electrophysiologic abnormalities may play a role in the arrhythmias and abnormalities of contraction present in postischemic, reperfused myocardium.

Action Potentials↗

PubMed1986

Amiodarone: correlation of early and late electrophysiologic studies with outcome.

Twenty-nine patients with recurrent sustained ventricular tachycardia (VT) or cardiac arrest underwent baseline, early (after 2 weeks of therapy) and late (after 5 months, mean) electrophysiologic studies during oral amiodarone therapy. Inducible sustained VT was present in all patients at baseline study, in 21 of 22 at early and in 26 of 29 at late study. The cycle length of induced VT increased from 263 +/- 60 msec at baseline study to 305 +/- 58 msec at early follow-up study and to 318 +/- 64 msec at late study (p less than .05 = baseline vs late study). The ventricular effective refractory period increased from 237 +/- 22 msec at the baseline study to 253 +/- 26 msec at early and to 268 +/- 24 msec at late study (p less than 0.05 baseline vs early, baseline vs late and early vs late study). Twenty-four patients had no recurrent VT or cardiac arrest on amiodarone (group 1). Five patients had recurrent arrhythmia (group 2). In group 1, the ventricular effective refractory period increased by 39 +/- 19 msec, but in group 2 decreased by 4 +/- 27 from baseline to late follow-up study (p less than 0.05). Similarly, in group 1 the cycle length of induced VT increased by a mean of 75 +/- 56 msec but decreased in group 2 by a mean of 11 +/- 81 msec from baseline to late follow-up study (p less than 0.05). From the above findings we conclude: Chronic electrophysiologic effects of amiodarone are not completely manifest after 2 weeks of oral therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1986

Swallowing syncope: observations in the absence of conduction system or esophageal disease.

A patient is described with the clinical syndrome of "swallowing syncope" who reproducibly demonstrated sinus bradycardia, A-H prolongation, and intranodal atrioventricular block in response to swallowing during electrophysiologic study. Baseline electrophysiologic and esophageal manometric results were normal, as was his response to other vagal maneuvers. Demand ventricular pacing alleviated his symptoms. These findings suggest that "swallowing syncope" is mediated via an esophageocardiac reflex and can occur in the absence of cardiac conduction system or esophageal disease.

Bradycardia↗

PubMed1986

The cellular electrophysiologic changes induced by high-energy electrical ablation in canine myocardium.

High-energy electrical ablation is a new experimental approach to control arrhythmias. In this study, the cellular electrophysiologic effects of high-energy shocks (5 to 40 J) delivered in vitro to 14 epicardial tissues from 11 dogs were studied in an attempt to understand the nature and extent of injury as well as potential arrhythmogenic mechanisms. In addition, this preparation was used to test the importance of cathode-anode configuration, current density, and fiber orientation in the induction of tissue injury in vitro. Electrophysiologic abnormalities were noted up to 10 mm from the electrode wall, and their extent was determined in part by current density and the cathode-anode orientation. A decrease in resting membrane potential, action potential amplitude, and dV/dT occurred in all tissues after high-energy shocks, which was worst nearest the cathode and of graded severity at increasing distances from the cathode. The most severe effects were noted with high current densities and in tissues located between the cathode and anode. In addition, impaired impulse conduction and abnormal repolarization were documented. Histologic study demonstrated contraction band necrosis immediately after delivery of high-energy shocks. The extent and distribution of the contraction bands was in part dependent on the energy delivered and the cathode-anode configuration. These findings suggest potential mechanisms for arrhythmogenesis and altered regional hemodynamic abnormalities that occur in vivo.

Action Potentials↗

PubMed1986

Vector mapping of myocardial activation.

A custom-made probe, consisting of four electrodes arranged so that two orthogonal bipolar electrograms could be recorded from a single site, was used to record epicardial activity during atrial and ventricular pacing in five normal and five anesthetized open-chest mongrel dogs with myocardial infarction. Unfiltered bipolar electrograms recorded with a 2 mm interelectrode distance averaged 36 +/- 15 mV in amplitude and 16 +/- 5 msec in duration in normal areas and 14 +/- 11 mV and 23 +/- 12 msec in infarcted areas (p less than .01 infarct vs normal). The bipolar electrograms were vector summed so that a vector loop could be generated at each site. The direction of epicardial impulse propagation as determined by multipoint isochronal activation mapping was compared with that indicated by maximum x,y deflection of the vector loop. At 203 sites (141 normal and 62 infarcted) there was a median error of only 13 degrees and an excellent correlation by linear regression (r2 = .95). In normal myocardium vector loops were straight (60%), open (21%), or hooked (19%). In infarcted myocardium, notched and irregular loops were occasionally seen. However, a clear maximum x,y deflection was still obtained from 98% of infarcted sites. During ventricular pacing in normal dogs, uniform epicardial conduction was observed for up to 4 cm longitudinal to fiber orientation but only 1 cm transverse to it. At selected sites longitudinal to fiber orientation conduction velocity was 0.618 m/sec, electrogram duration 12 msec, and vector amplitude 76 mV compared with 0.304 m/sec, 18 msec, and 38 mV during conduction transverse to fiber orientation (p less than .05 for all comparisons). Vector mapping of epicardial activation was performed during ventricular tachycardia induced by programmed stimulation in two of five 2-week-old canine myocardial infarcts. Aside from minor irregularities caused by impulse spread around areas of block, vector loops indicated when impulses were spreading away from the area of early epicardial activity and thus directed mapping to the region of earliest activation. We conclude that vector loops generated by summing orthogonal local bipolar electrograms accurately represent the direction of epicardial activation in both normal and infarcted myocardium. Such loops may prove useful in mapping tachycardias and in clarifying details about cardiac activation processes.

Animals↗

PubMed1986

The effects of procainamide on conduction in anisotropic canine ventricular myocardium.

Although conduction velocity in cardiac tissue is dependent on fiber orientation, the influence of commonly used antiarrhythmic agents on conduction longitudinal and transverse to such fibers is unknown. We evaluated the effects of procainamide on conduction velocity and intracellular potentials in vitro during conduction longitudinal and transverse to fiber orientation in epicardial strips obtained from areas of uniform fiber orientation from 15 adult mongrel dogs. Ventricular epicardial strips demonstrated marked anisotropy. At a pacing cycle length of 1000 msec, mean conduction velocity longitudinal to fiber orientation averaged 0.602 +/- 0.051 m/sec and mean conduction velocity transverse to fiber orientation was 0.186 +/- 0.024 m/sec, resulting in a ratio of longitudinal to transverse conduction velocities of (theta L/T) 3.27 +/- 0.38. After the addition of procainamide, conduction velocity decreased to 0.532 +/- 0.062 m/sec longitudinal to fiber orientation and to 0.174 +/- 0.023 m/sec transverse to fiber orientation resulting in a decrease of theta L/T to 3.09 +/- 0.37 (p less than .05 vs control). Before the addition of procainamide, when pacing at progressively shorter cycle lengths, conduction velocity longitudinal to fiber orientation was relatively unchanged, whereas conduction velocity transverse to fiber orientation decreased resulting in an increase in theta L/T. After the addition of procainamide, conduction velocity at shorter pacing cycle lengths decreased both longitudinal and transverse to fiber orientation demonstrating the well-known use-dependent effect of procainamide. However, in contrast to control conditions, conduction velocity longitudinal to fiber orientation was slowed by a greater extent than the conduction transverse to fiber orientation, resulting in an even greater decrease in theta L/T. To investigate the effect of differences in drug binding during propagation in different directions, we examined conduction velocity during alternations in pacing direction and compared it with velocity during steady-state pacing. At a pacing cycle length of 1000 msec, no difference was observed between the initial conduction velocity after changing pacing directions and the steady-state conduction velocity. At pacing cycle lengths shorter than 1000 msec, when changing from transverse to longitudinal conduction, there was an initial drop in normalized conduction velocity that was present on the first beat of longitudinal conduction; however, with continued pacing in a longitudinal direction there was a further decrease in conduction velocity.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1986

The monophasic action potential upstroke: a means of characterizing local conduction.

The upstrokes of monophasic action potentials (MAPs) recorded with an extracellular pressure electrode were characterized in isolated canine tissue preparations in vitro. The characteristics of the MAP upstroke were compared with those of the local action potential foot as well as with the characteristics of approaching electrical activation during uniform and asynchronous conduction. The upstroke of the MAP was exponential during uniform conduction. The time constant of rise of the MAP upstroke (TMAP) correlated with that of the action potential foot (Tfoot): TMAP + 1.01 Tfoot + 0.50; r2 = .80. Furthermore, changes in Tfoot with alterations in cycle length were associated with similar changes in TMAP: Tfoot = 1.06 TMAP - 0.11; r2 = .78. In addition, TMAP and Tfoot both deviated from exponential during asynchronous activation; the inflections that developed in the MAP upstroke correlated in time with intracellular action potential upstrokes that were asynchronous in onset in these tissues. Finally, the field of view of the MAP was determined and was found to be dependent in part on tissue architecture and the space constant. Specifically, the field of view of the MAP was found to be greater parallel compared with transverse to fiber orientation (6.02 +/- 1.74 vs 3.03 +/- 1.10 mm; p less than .01). These data suggest that the MAP upstroke may be used to define and characterize local electrical activation. The relatively large field of view of the MAP suggests that this technique may be a sensitive means to record focal membrane phenomena in vivo.

Action Potentials↗

PubMed1977