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Biomedical subjects

R Lazzara

Publications and source records attributed to R Lazzara.

At least 145 records · Page 8Linked to original sources
PubMed1984

Electrophysiologic basis for arrhythmias in ischemic heart disease.

Substantial gains have been made toward clarifying the mechanisms of arrhythmia in ischemia in animal models. After coronary occlusion in the dog, ischemic myocardial cells have reduced resting potential and slowed and diminished upstrokes of action potentials due to depression of fast channels. As a result, conduction is slow and irregular, especially at shorter cycle lengths, because refractoriness is altered by a delay in recovery of the fast channels beyond the completion of repolarization. These abnormalities occur during the acute phase of arrhythmia in the first half hour after occlusion and persist in surviving the subepicardial layers of myocardial cells for days to weeks. Reentry has been mapped in these surviving layers. Reentrant circuits form around regions of functional block formed by interfaces between responding and refractory myocardium. Standard antiarrhythmic agents generally are fast-channel blockers that further depress conduction and prolong refractoriness in ischemic tissue, causing block in slow conducting segments of the reentry circuits. However, antiarrhythmic agents may cause or accentuate reentrant arrhythmias by virtue of the same depressant actions. The greater likelihood of antiarrhythmic agents suppressing rather than producing reentrant arrhythmias may be due to enhanced depressant effects of antiarrhythmic agents on very slowly conducting tissues that are involved in reentry circuits. After the acute phase, arrhythmias occurring 1 to 4 days after coronary occlusion are probably largely automatic, although the potential for reentry remains if the cycle length is shortened. Abnormally enhanced automaticity and triggered activity are demonstrable in the surviving Purkinje network in regions of infarction, but the role of these phenomena in vivo has not been clarified.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1984

Mechanisms of ventricular arrhythmias in multivessel coronary disease: the effects of collateral zone ischemia.

We studied 15 anesthetized dogs with 4-day-old anterior wall infarctions caused by previous ligation of the left anterior descending coronary artery. Left circumflex artery (LCA) stenosis induced an average 41% decrease in collateral-dependent flow to the surviving anterior wall (epicardium) and only a 10% decrease to the normal posterior epicardial wall. Electrogram changes in 12 dogs consisted of fractionation and delay of anterior wall electrograms leading to bridging electrical activity between sinus beats and ventricular ectopic beats in five dogs. No similar electrogram changes were noted in posterior wall recordings. Ventricular paced beats induced ventricular tachycardia arising from the anterior wall in four dogs only after LCA stenosis. LCA stenosis in anterior myocardial infarction may be arrhythmogenic because of increased sensitivity of the surviving tissues, which have been electrically deranged by the ischemic/infarction process.

Angina Pectoris↗
PubMed1984

Ventricular tachyarrhythmias in the long QT syndromes.

Marked prolongation of the electrocardiographic QT interval often is associated with a distinctive form of ventricular tachycardia characterized by the gradual oscillation around the baseline of the peaks of successive QRS complexes. This was named torsades de pointes, or "twisting of the points." This form of ventricular tachycardia tends to be rapid and self-terminating and often occurs in clusters, leading afflicted patients to present with recurrent dizziness and syncope. Ventricular fibrillation and sudden death are common.

Adrenergic beta-Agonists↗
PubMed1984

Afterdepolarizations as a mechanism for the long QT syndrome: electrophysiologic studies of a case.

A young woman with palpitation and syncope was found to have ventricular tachyarrhythmia and a congenital long QT interval. The QT interval was shortened and the arrhythmia suppressed by propranolol. Electrograms recorded at various sites in both ventricles revealed a distinct diastolic slow wave that followed the T wave and measured 1.1 mV. Epinephrine infusion and emotion augumented this diastolic wave and induced ventricular ectopic complexes arising from this potential. Similar endocardial recordings in eight patients without a long QT interval showed diastolic slow waves that never exceeded 0.28 mV. In normal canine myocardium, afterdepolarizations can be induced by norepinephrine and blocked by propranolol. These findings suggest that the long QT syndrome is associated with abnormally large afterdepolarizations in ventricular myocardial cells, which are enhanced by beta-adrenergic stimulation to attain threshold and produce firing.

Adult↗
PubMed1984

Synthesis, conformational analysis, and antiarrhythmic properties of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonan-9-one, 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate, and 7-benzyl-9-phenyl-3-thia-7-azabicyclo[3.3.1]nonan-9-ol hydroperchlorate and derivatives: single-crystal X-ray diffraction analysis and evidence for chair-chair and chair-boat conformers in the solid state.

The synthesis of the title ketone has been completed via a type of Mannich reaction starting from 4- thianone . An X-ray diffraction analysis has revealed that the solid system is a chair-boat conformer with the sulfur atom in the boat portion of the bicyclic ring compound. Wolff- Kishner reduction of the ketone group gave 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane, which was isolated as the hydroperchlorate . However, X-ray diffraction analysis of the salt showed this solid to be a chair-chair conformer. Addition of phenylmagnesium bromide to the ketone gave a tertiary alcohol with the C-C6H5 bond being equatorial with respect to the thiane ring and axial with respect to the piperidine ring. The reaction of the Grignard reagent with the ketone to give this alcohol seems to be very stereospecific. An X-ray analysis of the hydroperchlorate of the alcohol confirmed the system to be a chair-chair form in the solid. The title compounds were screened for antiarrhythmic activity in anesthetized mongrel dogs in which myocardial infarctions had been created when the left anterior descending coronary artery was ligated. Vagal-induced slowing of the sinus mode firing rate was used to determine the underlying ventricular automaticity in the dogs, which averaged 164 +/- 27 beats/min. Ventricular pacing was initiated to rates between 240 and 390/min. This technique resulted in the induction of rapid and sustained ventricular tachycardia. At doses of 3 and 6 mg/kg of body weight, 7-benzyl-3-thia-7-azabicyclo [3.3.1]nonane hydroperchlorate in alcohol (the solution was administered intravenously) was able to suppress markedly the induced ventricular tachycardia in five of six dogs. The compound also caused a 10-15% increase in blood pressure within a few minutes. The antiarrhythmic properties of this compound and others of related structure are discussed, and some comparison is made with the action of lidocaine in similar dog preparations.

Animals↗
PubMed1983

Mechanisms of spontaneous and induced ventricular arrhythmias in the 24-hour infarcted dog heart.

The incidence and types of ventricular arrhythmias were evaluated in 14 dogs, 24 hours after occlusion of the left anterior descending coronary artery. After induction of anesthesia and left thoracotomy, standard electrocardiographic leads and electrograms from the His bundle and the left ventricular endocardium and epicardium (both infarct and normal zones) were recorded. Spontaneous ventricular tachycardia presumably due to abnormal automaticity was consistently observed (average rate 154 +/- 26 beats/min). These arrhythmias were irregular and multiform. In this same group of dogs 3 ventricular paced beats at rates above 300 beats/min induced rapid and uniform reentrant ventricular tachycardias (average rate 345 +/- 17 beats/min) that were difficult to terminate by premature beats or overdrive pacing. During this sustained ventricular tachycardia, continuous electrical activity was recorded from composite electrodes on the epicardial surface overlying the infarcted zone. Such interectopic activity was not observed during the spontaneous, automatic arrhythmias. Two of the 14 dogs showed only ventricular fibrillation in response to the provocative stimuli. These data confirm previous findings that 24 hours after acute myocardial infarction in the dog heart multiform ventricular rhythms can result from enhanced automaticity. In addition, it was found that ventricular tachycardia can be induced in the same dog heart by a standard ventricular pacing procedure. Continuous electrical activity bridging the interectopic intervals only during the latter tachycardia provides strong evidence for the reentrant basis of these induced arrhythmias. These experimental findings are comparable to the 2 different forms of ventricular arrhythmias described clinically, at the same stage of myocardial infarction. The direct myocardial recordings also provide new insights into the phenomenon of entrainment of tachyarrhythmias by overdrive pacing.

Animals↗
PubMed1983

Bradycardia-dependent triggered activity: relevance to drug-induced multiform ventricular tachycardia.

We used cesium chloride (CsCl) for electrophysiologic studies in canine hearts in vivo and in vitro to examine the mechanisms underlying ventricular arrhythmias that are related to prolonged repolarization. Cesium is known to depress normal ventricular automaticity and some experimental arrhythmias by blocking delayed outward currents and prolonging action potential duration. In 10 dogs in normal sinus rhythm, 1 to 1.5 mM/kg iv CsCl prolonged the QT (QU) interval and induced ventricular ectopy in all, including multiform ventricular tachycardia. In 12 dogs with atrioventricular block, 1 to 1.5 mM/kg iv CsCl produced marked suppression of idioventricular rates (from 45 +/- 6 to 8 +/- 4 beats/min). These low rates were then associated with bigeminy or bursts of multiform ventricular arrhythmia. Pacing at rates of 60 beats/min or more suppressed these arrhythmias. Low doses of tetrodotoxin (1 microgram/kg) also abolished these bradycardia-dependent arrhythmias without affecting the amplitude of ventricular electrograms. Tissue concentrations of cesium were determined by anatomic absorption spectroscopy in five dogs after injection of 1 mM/kg CsCl. Thirty minutes after the injection, cesium levels in Purkinje fibers were 5.3 +/- 1.0 mM/kg, levels in ventricular muscle were 4.6 +/- 0.9 mM/kg, and levels in atrial muscle were 4.1 +/- 0.8 mM/kg. In eight isolated endocardial preparations from canine ventricles, standard microelectrode techniques were used to study the effects of superfusion with 5 mM cesium. After 30 min, we observed early afterdepolarizations interrupting phase 3 of Purkinje fiber action potentials that already showed prolonged repolarization. Slowing the rate generated single or multiple action potentials arising from partially repolarized levels of membrane potentials (-80 to -65 mV). Pacing rates of 30 to 60 beats/min diminished the afterdepolarizations and suppressed the spontaneous beats. Tetrodotoxin at a concentration of 10(-8) g/ml, which did not affect upstroke velocity, abolished the afterpotentials. We conclude that cesium induced bradycardia-dependent ventricular arrhythmias caused by early afterdepolarizations. These data suggest that an inward current, probably carried by sodium ions, appears to be essential for the occurrence of this phenomenon. The association of delayed repolarization, afterdepolarizations, and triggered activity has similarities to the phenomenon of drug-induced prolongation of the QTU interval associated with multiform ventricular tachycardia in humans, i.e. "torsades de pointes."

Action Potentials↗
PubMed1983

Direct endocardial recording from an accessory atrioventricular pathway: localization of the site of block, effect of antiarrhythmic drugs, and attempt at nonsurgical ablation.

We recorded a discrete 0.95 mV potential consistent with accessory atrioventricular pathway (AP) activation during serial electrophysiologic studies in a patient with Ebstein's anomaly and Wolff-Parkinson-White syndrome. Bipolar pacing from the catheter electrode in which the AP potential was recorded resulted in a stimulus-ventricle interval identical to the AP-ventricle interval during antegrade conduction, and a stimulus-atrium interval identical to the AP-atrium interval during retrograde conduction. With the patient in the drug-free state, antegrade AP block during atrial pacing and retrograde AP block during ventricular pacing occurred distal to the AP potential (AP-ventricle junction and AP-atrium junction, respectively), supporting the "impedance mismatch" hypothesis. Procainamide and disopyramide each lengthened the antegrade AP effective refractory period by affecting the AP-ventricle junction (possibly by decreasing the current generated by the AP). Both drugs also lengthened the retrograde AP effective refractory period but produced a greater effect on the ventricle-AP junction than on the AP-atrium junction, suggesting marginal geometry of the former. R wave synchronous shocks of 160 and 320 W-sec delivered between the catheter electrode recording the largest unipolar AP potential and a skin electrode produced transient, complete, antegrade block over the AP, suggesting the feasibility of this new nonsurgical technique for AP ablation.

Adult↗
PubMed1982

Regional myocardial blood flow and ventricular arrhythmias following one-stage and two-stage coronary artery occlusion in anesthetized dogs.

Experiments were performed in 29 anesthetized dogs to compare effects of one-stage and two-stage coronary artery occlusion on ventricular arrhythmias and regional myocardial blood flow (MBF). Two periods of arrhythmias were observed and both were associated with evidence suggesting reentry; i.e., activity in ischemic zone electrograms which bridged the diastolic intervals preceding ventricular ectopic beats. Early ventricular arrhythmias followed progressive deterioration of conduction in the ischemic zone, whereas later arrhythmias occurred unexpectedly with the sudden appearance of bridging activity. One-stage occlusion produced a higher incidence of ventricular arrhythmias and ventricular fibrillation than two-stage occlusion. However, there was no difference in central ischemic zone blood flow, indicating that the protective effect of two-stage occlusion was not due to greater blood flow in this region. There results suggest that factors other than the degree of MBF reduction are important determinants of the incidence and severity of ventricular arrhythmias following coronary artery occlusion.

Anesthesia, General↗
PubMed1982

Mechanisms of bradycardia-induced ventricular arrhythmias in myocardial ischemia and infarction.

Experimental and clinical cases have been described in which bradycardia, i.e., heart rates below 60 beats/min or slowing of the heart rate, resulted in lethal ventricular arrhythmias during various stages of myocardial ischemia and infarction. The present study was designed to determine the relationship of lethal ventricular arrhythmias and slow heart rates. In 18 dogs anesthetized with sodium pentobarbital, the left anterior descending (LAD) coronary artery was ligated. Standard ECGs, His bundle electrograms and composite electrograms from intramural and epicardial areas in ischemic and normal zones were recorded during the first 3 hours of ischemia. Vagosympathetic trunk stimulation caused varying degrees of slowing and bradycardia. Of the 18 dogs, slowing of the heart rate or marked bradycardia induced ventricular ectopic beats coupled to the sinus beats in two, sustained ventricular tachycardia in two, and ventricular fibrillation in two. In another group of six dogs studied 17-25 days after LAD ligation, one dog showed sustained ventricular tachycardia in response to vagal-induced bradycardia. In all acute or chronic cases of arrhythmias after LAD ligation, continuous electrical activity was recorded on one or more of the electrograms within or overlying the ischemic or infarcted zones. This bridging electrical activation, which is indicative of slow conduction, provided strong presumptive evidence for reentry as the mechanism of lethal or potentially lethal ventricular arrhythmias triggered by bradycardia in the setting of myocardial infarction.

Animals↗
PubMed1979

Ventricular pacing from the middle cardiac vein mimicking supraventricular morphology.

A case is described in which ventricular pacing from the middle cardiac vein produced an electrocardiographic pattern which mimicked the morphology of the normally conducted beats. The possible etiologies of this unusual phenomenon and its implications concerning the functional anatomy of the normal conduction system in the human heart are discussed.

Aged↗
PubMed1979

Reentrant ventricular arrhythmias in the late myocardial infarction period. 7. Effect of verapamil and D-600 and the role of the "slow channel".

Reentrant ventricular arrhythmias (RVA) were analyzed in dogs 3--7 days after ligation of the anterior descending coronary artery using averaged "composite" recordings of electrical activity of reentrant pathways (RP) from the epicardial surface of the infarction zone (IZ). Verapamil (V) and D-600 (D) (0.2--0.5 mg/kg i.v.) resulted in slight-to-moderate improvement of conduction in RP with abolition of spontaneous RVA and RVA initiated by premature depolarizations. The effect of V was not blocked by pretreatment with propranolol (0.5 mg/kg i.v.). Using a standard microelectrode technique and strips of epicardial muscle from the IZ, D (0.5--1 X 10(-6) g/ml) slightly improved the upstroke velocity and membrane responses of depressed ischemic cells. In contrast, tetrodotoxin (5 X 10(-7) g/ml) further depressed or abolished action potentials of ischemic cells. We conclude: 1) the moderate antiarrhythmic effect of V and D on RVA is the result of improved conduction in RP; 2) this action is partly explained by improvement of a depressed sodium channel and is not related to catecholamine release; 3) slow-response action potentials play no significant role in the genesis of ischemia-related RVA, which probably results from depression of the fast response.

Action Potentials↗