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Biomedical subjects

Q Timour

Publications and source records attributed to Q Timour.

At least 37 records · Page 2Linked to original sources
PubMed1993

Arrhythmogenicity of antiarrhythmic drugs and intraventricular conduction disorders: possible aggravation by myocardial ischemia--study in the porcine in situ heart.

The effects of three antiarrhythmic drugs were investigated in anesthetized, open-chest pigs, in a left ventricular area, under pacing at a constant high rate (180 beats/min), in the absence and presence of ischemia. Ischemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin. In addition to the surface electrocardiogram, conduction time and monophasic action potential were recorded in the contractile fibers. In the absence of ischemia, intravenous flecainide and propafenone 2.5 mg/kg, and intravenous cibenzoline 2.0 mg/kg considerably lengthened conduction time (by 50-90%) but had no significant effect on the monophasic action potential duration. Consequently, the cited antiarrhythmic drugs enhance the prolongation of conduction time by 60% but do not limit the 30% shortening of the monophasic action potential caused by ischemia. Contrary to what was expected, they largely reduced the time to onset of the fibrillation due to ischemia from about 120 to 25 seconds. Thus, they manifested profibrillatory properties (more pronounced than those of other antiarrhythmic drugs of class I), which might be explained by their potent action on depolarization.

Animals↗
PubMed1993

Enhancement by ischemia of the risk of cardiac disorders, especially fibrillation, in regional anesthesia with bupivacaine.

The impairment of intraventricular conduction by bupivacaine may result in reentrant arrhythmias including ventricular fibrillation. The concentrations responsible for serious accidents are high (5.0 to 8.0 micrograms/ml), but likely to be lowered by myocardial ischemia which gives rise to similar disorders. Therefore we did an electrophysiological study of bupivacaine's effects in an ischemic area of the myocardium. Monophasic action potential (MAP) of the ventricular myocardium was recorded in 30 anesthetized, open-chest pigs. Conduction time and effective refractory period were also measured. Data were obtained during short periods (10-15 s) of pacing at 180 beats/min, but ventricular beats remained governed by the sinus node in the intervals. Ischemia was produced by occluding the left anterior descending coronary artery completely but transiently (up to 8 min), not far from its origin. Comparison was made between the effects of bupivacaine i.v. (n = 10), ischemia (n = 10) and both factors (n = 10). Two min after injection of bupivacaine 2.0 mg/kg (plasma levels 2.0-3.0 micrograms/ml), the duration of MAP was only slightly (7.5-15%) prolonged and its ischemia-induced shortening only slightly attenuated by bupivacaine. At the same time, conduction time was considerably (75-150%) lengthened and its ischemia-induced lengthening enhanced, so that ventricular fibrillation induced by coronary occlusion occurred sooner (about 100 instead of 300 s) in the presence of bupivacaine. Consequently, bupivacaine should be used only with caution in individuals whose myocardium is ischemic or liable to ischemia episodes.

Action Potentials↗
PubMed1992

Role of asynchronous activation of the ventricular fibres by an ectopic pacemaker in the accidents, especially fibrillation, caused by Ic antiarrhythmic drugs.

Class Ic antiarrhythmic drugs, which are known to slow down conduction in the ventricular muscle, are likely to impair synchrony in activity of the ventricular fibres. Asynchronous activation was first investigated between an ischaemic and a normal area by the simultaneous recording in anaesthetized, open-chest pigs of two left ventricular monophasic action potentials (MAPs) under ventricular pacing at a high rate of 180 beats.min-1. Asynchronous activation was then investigated in the intact myocardium according to the distance separating the recording from the pacing electrode. Furthermore, mechanical effects of left ventricular systole were observed by recording dP/dt(max) and mean arterial blood pressure during the pacing periods. Ischaemia was produced by transient complete occlusion of the left anterior descending coronary artery near its origin; as a result, activation time reached 85 ms in the ischaemic area under flecainide administered iv in a 2.5 mg.kg-1 dose instead of approximately 60 ms in the normal area for fibres equi-distant from the pacing electrode. Similar delays in activation were observed in the intact myocardium, depending on whether the explored region was close to or far from the pacing electrode. In the latter case, the difference in activation time may become markedly greater if the distance or the dose of flecainide are increased. This difference, which possibly exceeds one-third of the MAP duration (practically unchanged by flecainide), may account for the occurrence of fibrillation or the sudden loss of systole mechanical efficacy.

Animals↗
PubMed1991

Class Ic antiarrhythmic drugs and myocardial ischaemia: study in the pig heart in situ.

The effects of three Ic antiarrhythmic drugs, flecainide, propafenone and cibenzoline, were investigated in anaesthetized, open-chest pigs, in a left ventricular area, during pacing at a constant high rate (180 beats min-1), in the absence and the presence of ischaemia. Ischaemia was produced by transient complete occlusion of the left anterior descending coronary artery 1-1.5 cm from its origin. In addition to surface electrocardiogram, conduction time and monophasic action potential were recorded in the contractile fibres. Measurement of the effective refractory period was added in the absence of ischaemia. In this event, flecainide and propafenone, each in a dose of 2.5 mg kg-1 i.v. and cibenzoline, 2.0 mg kg-1, i.v., considerably lengthened (by 50-90%) conduction time, but did not affect or hardly affected the duration of the monophasic action potential or the effective refractory period. Thus, it seems that these Ic antiarrhythmic drugs enhance the prolongation of conduction time by 60% and do not prevent the 30% shortening of monophasic action potential caused by ischaemia: contrary to expectation, they produced a large reduction (from about 120 to 25 s) in the onset time of fibrillation due to ischaemia. Thus, they manifested profibrillatory properties (more pronounced than those of other class I antiarrhythmic drugs), which might be explained by their potent action on depolarization with almost total absence of action on repolarization.

Action Potentials↗
PubMed1991

Adverse interaction between bupivacaine and halothane on ventricular contractile force and intraventricular conduction in the dog.

Regional anesthesia with bupivacaine in pediatric patients is often accompanied by light levels of halothane general anesthesia. To determine the potential cardiotoxicity of these two drugs when used together, we defined the interaction between moderate plasma bupivacaine concentrations (1270-1760 ng/mL) and halothane (end-tidal concentrations, 0.5%-1.0%) on ventricular contractility and conduction in 22 closed-chest dogs anesthetized with chloralose. Bupivacaine alone (1-mg/kg intravenous bolus plus a 0.1-mg.kg-1.min-1 constant rate infusion) resulted in significant increases in ventricular conduction time (VCT) and effective refractory period (VERP) and nonsignificant decreases in dP/dtmax and blood pressure. The addition of halothane resulted in hypotension and in progressively increasing plasma bupivacaine levels secondary to reduced hepatic clearance, which led to further dose-related significant increases in VCT and VERP and to significant decreases in dP/dtmax and blood pressure. In other dogs given halothane but in which bupivacaine levels were held constant (1400 ng/mL), VCT remained constant and VERP lengthened slightly, whereas dP/dtmax decreased. We conclude that the combination of bupivacaine and halothane can cause adverse effects on ventricular contractility and intraventricular conduction.

Anesthesia↗
PubMed1991

[Arrhythmogenic risk of antiarrhythmic drugs: study with class Ic drugs during myocardial ischemia].

The effects of three Ic antiarrhythmic drugs were investigated in anaesthetized, open-chest pigs, in a left ventricular area under pacing at constant high (180/min) rate, outside and during an ischaemia produced by temporary complete occlusion of the left anterior descending coronary artery, 1-1.5 cm from its origin. In addition to surface ECG, conduction time and monophasic action potential were recorded in the contractile fibres. Measurement of effective refractory period was added outside the periods of ischaemia. In this event, flecainide and propafenone, in 2.5 mg/kg dose, and cibenzoline, in 2.0 mg/kg dose, i.v. injected, lengthened considerably (50 to 90%) conduction time, but did not affect or hardly affected monophasic action potential and effective refractory period. During ischaemia, they did not hinder the abbreviation of monophasic action potential (30%) and reduced to a large extent (about 120 to 25 s) the onset time of fibrillation. The profibrillatory effect of Ic antiarrhythmic drugs, certainly more pronounced than those of other antiarrhythmic drugs, might be explained by their potent action on depolarization of the contractile fibres coincident with an almost total absence of action on repolarization.

Animals↗
PubMed1990

Enhancement by hyponatremia and hyperkalemia of ventricular conduction and rhythm disorders caused by bupivacaine.

Intraventricular conduction disorders and reentrant arrhythmias in dogs can be produced by high plasma bupivacaine concentrations. The authors' aim was to determine if these conduction disturbances also occurred at moderate plasma bupivacaine concentrations (2.2-3.7 micrograms/ml) when in association with other factors which affect intracardiac conduction, such as hyponatremia and hyperkalemia. Thus, duration of the QRS complex, ventricular conduction time, and effective refractory period (ERP) was measured during ventricular pacing at 180 beats per min in 46 anesthetized, closed-chest dogs separated into five treatment groups as follows: group I, an iv bolus of 4 mg/kg of bupivacaine plus an infusion of 0.1 mg.kg-1.min-1 of bupivacaine followed in 50-60 min by 10 ml.kg-1.min-1 of 1.5% glycine iv to produce dilutional hyponatremia; group II, 1.5% glycine alone, as above; group III, bupivacaine, as above, followed in 50-60 min by 0.05 mmol.kg-1.min-1 of KCl iv to produce hyperkalemia; group IV, KCl alone, as above; and group V, bupivacaine, as above, except that the duration of infusion was 90 min. QRS duration and ventricular conduction time, which were prolonged approximately 33% and 61%, respectively, by bupivacaine alone were additionally prolonged 29% and 44%, respectively, when serum sodium concentration was lowered to 114 mmol/l and potassium concentration was raised to 7.7 mmol/l. The combinations of bupivacaine and hyponatremia, and bupivacaine and hyperkalemia tended to increase ERP more than did bupivacaine alone, although these changes were not statistically significant. Wave burst arrhythmias and episodes of ventricular tachycardia occurred spontaneously or were triggered by pacing in those dogs in which conduction time was most prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Ventricular and atrial electrophysiological effects of a IC antiarrhythmic drug, cibenzoline, in the innervated dog heart. Role of sodium and calcium channels.

The effects of cibenzoline, rightly known as a sodium channel inhibitor (class IC antiarrhythmic drug), were investigated in anaesthetized, closed-chest dogs, on conduction in the contractile fibres, ventricular and atrial, the His-Purkinje system and the atrioventricular node. In ventricular muscle, conduction time was measured between base and apex by two endocavitary electrodes. The other conduction times were obtained from the recording of the His bundle potentials. In addition, effective refractory period was determined by the extrastimulus method in ventricular and atrial muscle and in the atrioventricular node, and sinus rate monitored in the intervals of pacing periods. In the absence of vagal tone, cibenzoline in 4 mg.kg-1 dose prolonged conduction times in the ventricular contractile tissue, His-Purkinje system and atrial contractile tissue to a large extent, but decreasingly from the former to the latter. This prolongation was antagonized by hypernatremia (174 mmol.l-1). In contrast, conduction time in the atrioventricular node, effective refractory periods and sinus rate were very little influenced. In the presence of vagal tone, the prolongation of conduction times in the ventricular contractile tissue. His-Purkinje system and atrial contractile tissue did not differ substantially from previously. It was the same for ventricular effective refractory period. But atrial effective refractory period was then considerably lengthened, while conduction time and effective refractory period in the atrioventricular node were greatly shortened and sinus rate notably accelerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Potentiation by mild hypothermia of ventricular conduction disturbances and reentrant arrhythmias induced by bupivacaine in dogs.

High concentrations of bupivacaine and profound hypothermia individually cause intraventricular conduction disturbances and reentrant arrhythmias. The effects of the combination of relatively low concentrations of bupivacaine and mild hypothermia are unknown and are the subject of this study. Three groups (n = 10-12) of dogs anesthetized with thiopental-chloralose were treated as follows: group 1, bupivacaine + hypothermia; group 2, bupivacaine alone; group 3, hypothermia alone. Bupivacaine was administered as a 4 mg/kg iv bolus followed by an iv infusion of 0.1 mg.kg-1.min-1. Hypothermia, i.e., a 4 degrees C reduction in core temperature, was produced by cooling the blood with an extracorporeal circuit. The peripheral ECG was recorded to determine the duration of QRS complexes and the QT interval. Conduction time and effective refractory period (ERP) of ventricular contractile tissue were measured with right ventricular endocavitary electrodes. Measurements were made with the heart paced at 180 beats/min and without pacing. In group 1 dogs, bupivacaine (plasma level, 2.8 +/- 0.3 microgram/ml) initially caused a prolongation of conduction time and QRS duration, which were further lengthened (approximately doubled) by a temperature decrease of 4 degrees C from baseline. The QT interval and ERP also were increased but to a lesser degree. In dogs in which the effects were most pronounced, rhythm disorders, such as wave burst arrhythmias (most common), premature systoles, ventricular tachycardia, and even ventricular fibrillation, occurred either spontaneously or during pacing. Bupivacaine alone (group 2) increased QRS duration and conduction time significantly, whereas hypothermia alone (Group 3) did not cause changes in any conduction variables. In neither group were dysrhythmias observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of isoproterenol and propranolol on pharmacologically induced depression of intraventricular conduction.

The cardiac adrenergic system is known to have practically no influence on conduction velocity in the ventricles under normal conditions. The effects of isoproterenol and propranolol were investigated on depression of intraventricular conduction induced by a class IC antiarrhythmic drug, cibenzoline, in anaesthetized, closed-chest dogs. In addition to electrocardiogram for measurement of QRS duration in sinus rhythm, conduction time was measured in the ventricular contractile tissue between an electrode advanced to the apex and a pacing electrode near the base, at 400- and 200-ms pacing periods. Effective refractory period (ERP) was measured concurrently according to the extrastimulus method. After intraventricular conduction had been slowed down by cibenzoline IV administered (loading dose of 3 mg/kg plus infusion of 0.2 mg/kg/min over 15 min), isoproterenol was infused or propranolol injected by the intravenous route also (0.5 mn/micrograms/kg/min over 5 min and 0.4 mg/kg, respectively). When conduction time has been raised by 75/150% (depending on the pacing rate), isoproterenol appears to attenuate and propranolol to aggravate substantially the impairment of conduction, whereas the reduction undergone by ERP does not differ from usual. Thus, reentrant arrhythmias might be prevented by isoproterenol and triggered by propranolol. Intraventricular conduction, when depressed, therefore, is sensitive to adrenergic drugs, probably because of the enhanced influence of polarization of the fibres in the presence of a sodium conductance impairment.

Animals↗
PubMed1988

Biphasic dose-response relationship observed with Bay k 8644 on atrioventricular nodal conduction inhibited by verapamil.

The effects of a calcium channel blocker, verapamil, on the atrioventricular (AV) node, are antagonized by calcium, intravenously infused, so long as plasma calcium concentration does not reach 5.0 or 5.5 mmol.l-1, as previously shown. Beyond this, the antagonistic effects decrease progressively, so that there is a bell-shaped relationship between dose (or concentration) and response. The purpose of the present experiments has been to investigate a possible similar dose-response curve with a calcium channel activator, Bay k 8644. The study was carried out in anaesthetized, atropinized dogs, with cardiac pacing. The His bundle potentials were recorded by endocavitary electrodes and the AV nodal effective refractory period was measured by the extrastimulus method. Verapamil impaired AV nodal conduction and additional infusion of Bay k 8644 at a rate of 1 microgram.kg-1.min-1 partly antagonized this effect. Increasing the infusion rate of Bay k 8644 to 5 micrograms.kg-1.min-1 did not further increase but reduced the antagonism. In other experiments where infusion of calcium had partly antagonized the effect of verapamil, Bay k 8644 infused after cessation of calcium infusion did not further antagonize the effect of verapamil which even became again increasingly marked. Consequently, in the AV node depressed by a calcium channel blocker, Bay k 8644 gives rise to a bell-shaped dose-response relationship of its verapamil-antagonistic action and the reversal of this action by high doses of Bay k 8644 can be observed after both administration of either calcium or Bay k 8644 in moderate doses.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1988

Doxorubicin concentrations in plasma and myocardium and their respective roles in cardiotoxicity.

Three hours after the intravenous infusion of doxorubicin (3 mg/kg over 15 min) to anesthetized dogs, the drug concentration was found much higher in the myocardium than in the plasma (about 4,000 ng/g, i.e., 50 times higher). After the intravenous infusion of doxorubicin (1.5 mg/kg over 15 min) to conscious dogs, the drug concentration appeared to decline very slowly in the myocardium, since it was close to 200 ng/g at the 7th day, whereas the plasma concentration had fallen to zero, and the drug was still detected in the cardiac tissue 21 days after the administration. As myocardial concentrations of doxorubicin persist long after plasma clearance is complete, the hazards of repeated administration, based on plasma kinetic patterns, must be emphasized.

Animals↗
PubMed1988

[Systemic toxicity of local anesthetics. Pharmacokinetic and pharmacodynamic factors].

Local anaesthetics can have systemic adverse effects, mostly affecting the central nervous system and the heart. The physicochemical characteristics of the different local anaesthetics are recalled, for they determine the relationship between structure, activity and toxicity. The pharmacokinetic factors involved in the toxic effects of local anaesthetics, whether the drug is given in a single extravascular dose or, accidentally, within a blood vessel, are discussed. The toxic effects of repeated administrations of local anaesthetics depend on the metabolism of the drug as well as on pharmacokinetic factors. Possible maximal doses and drug interactions are also discussed. The mechanism of action of local anaesthetics, which block the sodium channel, explains their tissue toxicity and, more specifically, their central nervous and cardiovascular toxicities, which are more pronounced for the more potent local anaesthetic agents (bupivacaine, etidocaine). Systemic maternal effects and transplacental passage probably explain their foetal toxicity. Specific toxic effects are seen with some drugs, such as methaemoglobinaemia and allergic reactions (rarely for amide agents). Overall, local anaesthetic accidents are rare, but they must be prevented.

Anesthesia, Intravenous↗