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Biomedical subjects

R Lazzara

Publications and source records attributed to R Lazzara.

At least 19 recordsLinked to original sources
PubMed1992

High-performance liquid chromatographic determination of BRB-I-28, a novel antiarrhythmic agent, in dog plasma and urine.

A sensitive reversed-phase high-performance liquid chromatographic (HPLC) technique with ultraviolet detection has been developed to determine the concentration of BRB-I-28 (I), a novel antiarrhythmic agent, in dog plasma and urine. The mobile phase was acetonitrile-methanol-37.5 mM phosphate buffer, pH 6.8-triethylamine (50:50:75:0.1, v/v). The compound was extracted from dog plasma and urine with chloroform after alkalinization with sodium hydroxide. The extraction recovery was 83% from plasma and 84% from urine. Good linearity (r > 0.996) was observed throughout the ranges 0.1-12.0 micrograms/ml (plasma) and 0.1-8.0 micrograms/ml (urine). Intra- and inter-assay variabilities were less than 4%. The lower limit of quantitation was 0.08 microgram/ml in either plasma or urine. HPLC analysis of plasma and urine samples from a dog treated with I has demonstrated that the method was accurate and reproducible.

Animals↗
PubMed1992

Conversion of Mobitz type II AV block to 1:1 AV conduction by premature ventricular beats.

Preliminary experiments in a canine model of Mobitz type II atrioventricular (AV) block showed improvement of conduction after premature ventricular beats. In this investigation, the authors studied the mechanism(s) responsible for this response. In vivo studies were performed in 16 anesthetized dogs. Block was induced by ischemia after septal artery occlusion or by mechanical trauma. Two pairs of plunge electrodes were inserted in the proximal and distal His bundle. An electrode catheter was positioned at the level of the aortic root to provide an overall view of His bundle activation. Bipolar pacing was performed from the high right atrium, right ventricular outflow tract, and proximal and distal His bundle. Infra-nodal 2:1 AV block was consistently induced at an atrial rate of 238 +/- 21 beats/min. In 15 dogs a narrow time window (10-60 ms; mean, 32 +/- 6 ms) was found during which premature beats resulted in transient (2-11 beats; n = 9) or persistent (n = 8) restoration of 1:1 AV conduction. Retrograde penetration of the site of block, that is, Hb, was found even when the anterograde impulse was blocked, demonstrating the asymmetric nature of anterograde versus retrograde conduction. In vitro studies were performed in the same hearts. Intracellular recordings were obtained in the damaged His bundle and proximal right bundle. The site of block showed frequent displacements along the bundle. The introduction of a retrograde stimulus during 2:1 block restored 1:1 anterograde conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Mapping in the atrioventricular junction.

Ectopic conduction is defined as the premature exit of the cardiac impulse from the specialized conduction system across a damaged Purkinje-ventricular muscle interface. This anomalous form of atrioventricular (AV) conduction was induced in the dog heart by lidocaine injection of the His bundle-interventricular septum interface and by ischemic damage of the AV junction subsequent to anterior septal artery ligation in the dog heart. The electrocardiogram (ECG) manifestation of ectopic conduction is the loss of initial forces and replacement of the Q waves with delta waves. In order to verify these effects, the authors devised a multi-electrode, malleable plaque (63 electrode sites) that could be secured at the AV junction during venous occlusion in the open-chest, anesthetized dog. Preliminary maps indicated a dramatic change in activation that proceeded from apex to base of the heart in the control state and reversed after ischemic damage to the His bundle. In vitro, it was possible to induce ectopic conduction by lidocaine injection at the interface of the right bundle branch and septal muscle. Microelectrode studies demonstrated that foot potentials, for example, electrotonic, or subthreshold potentials mediated the connection from Purkinje to muscle in the damaged zone. In a recent set of experiments in vivo, subthreshold stimulation (STS) was delivered to simulate electrotonic potentials to the His bundle region, and right ventricular apex, using multipolar electrode catheters. In the normal heart, STS delivered as DC constant current or pulse trains (1000 Hz, 50 ms pulse duration) induced shortened P-R intervals and delta waves with or without bundle branch block patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The significance of electrocardiographic late potentials: predictors of ventricular tachycardia.

Cardiac late potentials are observed by using a high-resolution, computer-processed ECG that can detect very low-level signals not seen with standard ECG techniques. Numerous clinical studies have demonstrated that patients with low-level signals after the QRS complexes (late potentials) are at much higher risk of ventricular tachycardia and sudden death following myocardial infarction. Other clinical populations have been studied, e.g. those with syncope, coronary reperfusion, and cardiomyopathy, with varying degrees of success in predicting ventricular tachycardia.

Death, Sudden↗
PubMed1992

Effects of BRB-I-28, a novel antiarrhythmic agent, and its derivatives on cardiac Na+,K(+)-ATPase, Mg(2+)-ATPase activities and contractile force.

The effects of BRB-I-28, SAZ-VII-22 and SAZ-VII-23, a novel class of antiarrhythmic agents and other 3,7-diheterobicyclo[3.3.1]nonane (DHBCN) derivatives on guinea pig myocardial Na+,K(+)-ATPase and Mg(2+)-activated ATPase activities were investigated in comparison with those of tedisamil, lidocaine and ouabain. BRB-I-28, SAZ-VII-22, SAZ-VII-23, tedisamil and their derivatives produced concentration-dependent inhibition on both Na+,K(+)-ATPase and Mg(2+)-activated ATPase. Ouabain had no effect on the Mg(2+)-activated ATPase activity and GLG-IV-44 had no significant inhibition on Na+,K(+)-ATPase. Molar refractivity, retention time in reverse-phase HPLC, and partition coefficients were determined and the influence of these three parameters on the inhibitory effects of DHBCN on ATPase was examined. It seems that inhibitory effects of DHBCN derivatives on Na+,K(+)-ATPase and Mg(2+)-activated ATPase increase with an increase in lipophilicity, while hydrophilic groups of the drugs may not be important for interaction between drugs and ATPases. The effects of BRB-I-28 on contractile force development in rabbit atrial and papillary muscles were studied. At paced rates of 0.5 and 1.0 Hz in atrial muscle, BRB-I-28 produced an apparent positive inotropic effect in isolated rabbit atrial muscle, which is consistent with its inhibitory effects on Na+,K(+)-ATPase and Mg(2+)-ATPase activities. Inhibitory effects on myocardial Na+,K(+)-ATPase and Mg(2+)-activated ATPase activities may be the basis of some electrophysiological effects of antiarrhythmic properties of BRB-I-28, SAZ-VII-22, SAZ-VII-23, and tedisamil.

Animals↗
PubMed1992

Electrophysiologic actions of clofilium and lidocaine in ischemically injured canine epicardium.

The electrophysiologic actions of the Class III antiarrhythmic drug, clofilium, and the Class IB antiarrhythmic drug, lidocaine, were examined in ischemically injured canine epicardium, 4 days after coronary artery occlusion. Experiments were performed utilizing 1) composite electrode recordings from the intact heart in the anesthetized dog and 2) intracellular and extracellular recordings from superfused canine epicardium. In intact hearts, both clofilium (2 mg/kg i.v.) and lidocaine (6 mg/kg i.v.) increased refractoriness (188 +/- 16 to 331 +/- 39 and 288 +/- 18 msec, respectively, P less than .01), and produced tachycardia-dependent conduction disorders in ischemically injured epicardium. For both drugs, slowing the sinus heart rate with vagus nerve stimulation (32 +/- 6/min) returned activation delays to predrug values. Unlike lidocaine, clofilium failed to increase maximal activation delays in ischemically injured epicardium preceding conduction block (116 +/- 14 msec vs. 71 +/- 7 msec and 147 +/- 16 msec for clofilium and lidocaine, respectively, P less than .01 for both drugs). In superfused epicardium, both clofilium (3 x 10(-7) M) and lidocaine (4 mg/l) prolonged refractoriness in ischemically injured epicardium (175 +/- 16 predrug vs. 273 +/- 33 msec, P less than .01) and (181 +/- 3 predrug vs. 216 +/- 10 msec, P less than .01), respectively, whereas only lidocaine reduced Vmax and prolonged local conduction times in the same tissue. The results demonstrate that 1) lidocaine increases refractoriness in ischemically injured tissue via a decrease in Vmax and conduction velocity and 2) clofilium increases refractoriness in ischemically injured tissue without altering action potential duration, Vmax or conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The monophasic action potential in clinical cardiology.

For more than 30 years, the monophasic action potential has been used as an experimental tool for the study of myocardial repolarization. With recent improvements in catheter design, the utility of the tool as a means to identify the bases for ventricular arrhythmias in humans has been greatly improved. Abnormalities of repolarization leading to ventricular arrhythmia formation can be identified and specific pharmacologic therapies may be evaluated. Further evaluation of the technique by cardiac electrophysiologists may improve both the diagnosis and the treatment of ventricular arrhythmias dependent upon afterdepolarization formation (acquired and familial long QT syndromes).

Action Potentials↗
PubMed1991

Transesophageal echocardiographic evaluation for mural thrombus following radiofrequency catheter ablation of accessory pathways.

BACKGROUND: Catheter ablation of accessory pathways (APs) provides a definitive therapy for patients with Wolff-Parkinson-White Syndrome. The reported incidence of thrombus formation on ablation-induced injuries with direct current shock varies from 0%-20% in animal studies. The purpose of this study was to determine the prevalence of mural thrombus following catheter ablation with radiofrequency current of accessory pathways in humans. METHODS AND RESULTS: Radiofrequency current (30-35 watts) was applied through a catheter electrode placed against the mitral or tricuspid annulus guided by catheter recordings of AP potentials. Transthoracic (TTE) and transesophageal echocardiography (TEE) were performed in 95 of 111 patients, at 18 +/- 6 hours following catheter ablation. After ablation, no thrombus was identified at or near the ablation site in any patient. Two out of 95 patients had a mural thrombus at a remote site that was detected by TEE but not by TTE. No new wall motion abnormality was detected in any patient. No significant regurgitant valvular lesion was found in any patient. CONCLUSION: Intracardiac thrombus was not identified at the site of catheter ablation, possibly owing to the small lesions produced by radiofrequency energy and high blood flow normally present in those areas. However, patients may be at small risk for mural thrombus at a remote site from prolonged placement of catheters.

Adult↗
PubMed1991

Factors associated with recurrence of accessory pathway conduction after radiofrequency catheter ablation.

Catheter ablation of 215 accessory pathways (APs) using radiofrequency current (RF) was attempted in 204 consecutive patients. Two hundred twelve of the 215 (99%) APs were successfully ablated. After a minimum of follow-up period of 1 month (mean 8.5 +/- 5.4 months), AP conduction had returned in 17 patients (8%). Recurrence of AP conduction was manifest by atrioventricular (AV) reentrant tachycardia in six patients, palpitations suggestive of AV reentrant tachycardia in five patients, ventricular preexcitation on electrocardiogram in five patients, and inducible AV reentrant tachycardia during a follow-up electrophysiological study in one asymptomatic patient. AP conduction returned as early as 12 hours and as late as 4.7 months, but was evident within 2 months of ablation in 15 of 17 (88%) patients. AP conduction recurred in 12%-14% of anteroseptal, right free-wall, and posteroseptal APs, but only 5% of left free-wall APs (P less than 0.01). Retrograde only conducting APs (concealed APs) had recurrence of AP conduction more frequently (16%) than APs that exhibited antegrade conduction (5.5%; P less than 0.01). Failure to record AP potentials from the ablation electrode, reflecting poor AP localization, was a strong predictor for recurrence of AP conduction. AP conduction returned in 19% of 48 APs when AP potentials were not recorded, compared to 5% of 164 APs where AP potentials were recorded from the ablation electrode (P less than 0.01). The time to block of AP conduction from the onset of RF current application was longer in APs with recurrence of conduction (4.9 +/- 6.1 sec vs 2.9 +/- 3.4 sec; P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Electrophysiological actions of BRB-I-28 in canine myocardial tissues.

To obtain a better understanding of the possible electrophysiological bases of the antiarrhythmic actions of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate (BRB-I-28), microelectrode recordings of myocardial electrical activity were obtained in canine Purkinje and ventricular tissue, and in isolated canine ventricular myocytes. BRB-I-28 (1.0 and 3.2 mg/l) reduced Vmax, action potential amplitude, overshoot potential and conduction velocity in Purkinje tissues without altering action potential duration or spontaneous automaticity. Vmax and conduction velocity were reduced only at paced cycle lengths of 500 msec or less. BRB-I-28 (3.2 and 10 mg/l) also reduced Vmax, action potential amplitude and overshoot potential in subendocardial and epicardial ventricular muscle, with Vmax reduced only at cycle lengths of 500 msec or less. Recovery half-times for Vmax estimated in canine subendocardium were 330 +/- 28 and 336 +/- 25 msec at BRB-I-28 concentrations of 3.2 and 10 mg/l, respectively. In epicardium, conduction velocity longitudinal to fiber orientation was depressed more than conduction velocity transverse to fiber orientation, despite similar changes in Vmax. In both epicardial and subendocardial ventricular muscle, a reduction in Vmax is observed in the absence of alterations in action potential duration. Experiments using myocytes isolated from canine epicardial tissue demonstrated similar rate-dependent changes in Vmax as ventricular epicardium. The data demonstrate a rate-dependent depression of Vmax by BRB-I-28 in canine ventricular tissues. The depression of conduction occurs only at rapid paced rates and occurs in the absence of changes in Purkinje cell automaticity or action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Seasonal variation in sudden cardiac death after experimental myocardial infarction.

The authors studied the incidence of sudden death by monitoring the ECG after ligation of the left anterior descending coronary artery in 184 dogs. A significant number of sudden deaths (46 dogs) occurred in the cold weather months, November-February (42%), compared to the summer months, July and August (6%). All deaths resulted from ventricular tachyarrhythmias (greater than or equal to 300/min) and occurred between 13 and 22 hours after coronary artery ligation. The survivors (138 dogs) were subjected to electrophysiological study, during which a significantly higher number showed induced sustained monomorphic ventricular tachycardia (VT) (heart rate greater than or equal to 300/min) during the winter months than during the summer months. Heart weight and infarct mass were not significantly different throughout the year. Higher sympathetic tone or catecholamine levels may account for the seasonal variation in sudden death during evolving myocardial infarction.

Animals↗
PubMed1990

Early and delayed afterdepolarizations associated with cesium chloride-induced arrhythmias in the dog.

Monophasic action potentials (MAPs) were utilized to examine the basis for cesium-induced arrhythmia in the dog. Cesium chloride (1 mmol/kg i.v.) produced an immediate prolongation of MAP (250 +/- 11 to 396 +/- 34 ms, p less than 0.05). Coupled premature ventricular beats (345 +/- 46 ms) and polymorphic ventricular tachycardia developed in association with early afterdepolarizations during the first 1-3 min after cesium administration. A slowing of the sinus heart rate with vagus nerve stimulation exacerbated the arrhythmia. During the subsequent 7 min, the MAP duration decreased from 396 +/- 34 to 316 +/- 19 ms. At 8-10 min, the premature ventricular beats were associated with delayed afterdepolarizations in the MAP recordings. However, there was no change in the coupling intervals of the premature ventricular beats (351 +/- 29 ms). Ventricular arrhythmias and delayed afterdepolarizations during this phase were exacerbated by increasing the heart rate with atrial pacing. T wave alternans and U wave formation in the ECG were associated with early or delayed afterdepolarizations in MAP. Cesium chloride (1 mmol) injected into the left anterior descending coronary artery produced local MAP prolongation and ventricular bigeminy. Although the MAP duration returned to predrug values after intracoronary cesium injection, the severity of ventricular arrhythmia increased with succeeding doses. These data suggest that early and delayed afterdepolarizations, T wave alterations, and ventricular beats can be dissociated from the initial action potential prolongation with cesium and closely resemble altered calcium transients observed in vitro.

Action Potentials↗