Biomedical subjects

J Loufoua

Publications and source records attributed to J Loufoua.

5 recordsLinked to original sources

PubMed1996

Cardiac beta-adrenoreceptor activation and ventricular fibrillation under normal and ischemic conditions.

OBJECTIVES: To investigate the role of ventricular and atrial beta-adrenoceptor activation by isoprenaline in the genesis of rhythm disorders and risk of fibrillation in the healthy or ischaemic heart. METHODS: The study was performed in anaesthetized, open-chest pigs. Electrical fibrillation threshold (EFT) of the ventricles was measured with trains of diastolic stimuli of 100 ms duration synchronized with respect to the R-waves and delivered to the myocardium by a subepicardial electrode introduced into the area which could be subjected to ischaemia. Monophasic action potential (MAP) and effective refractory period (ERP) were recorded in the same area. Ischaemia was obtained by complete occlusion of the left anterior descending coronary artery near its origin during increasing periods (30, 60, 90, 120, 150, 180, 240 s). RESULTS: At a rate varying according to the action exerted by isoprenaline on the sinus rate, EFT decreased by about 30% in the healthy heart during the infusion of 0.5 micrograms/kg/min isoprenaline under the influence of the acceleration of cardiac beats. In the ischaemic heart, sinus tachycardia accelerated the fall in EFT and the reduction in MAP duration and resulted sooner in spontaneous ventricular fibrillation. During ventricular pacing at a constant rate of 200 beats/min, isoprenaline raised EFT by nearly 80% in the absence of ischaemia, but this rise was abolished by ischaemia, at least of no-flow type. CONCLUSION: Tachycardia produced by activation of atrial adrenoceptors decreases EFT in the healthy heart and aggravates its fall in the ischaemic heart. Ventricular adrenoceptor activation counteracts the EFT fall related to tachycardia in the healthy heart, but not in the ischaemic heart. Therefore, the protection against ischaemic fibrillation due to beta-blockers would be essentially attributable to their action on the sinus nodes.

Action Potentials↗

PubMed1996

[Value of calcium channel blockers in the prevention of ventricular fibrillation of ischemic etiology: experimental arguments].

The prevention of ventricular fibrillation raises a special problem when related to myocardial ischaemia, since class I antiarrhythmic drugs are then ineffective and may even behave as profibrillatory agents: the usual antifibrillatory properties of these drugs which are inhibitors of sodium channel, activated at high potentials, disappear with the disappearance of the role of sodium channel caused by ischaemic depolarization. Calcium channel then replacing sodium channel, calcium channel inhibitors should tend to prevent ischaemic ventricular fibrillation. Therefore, vulnerability to ventricular fibrillation was assessed in open-chest pigs by the threshold for fibrillation electrically induced with impulses of 100 ms duration at the rate of 180 beats/min. Ischaemia was produced by total occlusion of the left anterior descending coronary artery near its origin. Electrical fibrillation threshold was measured at the end of ischaemic period of increasing duration (30, 60, 120, 180, 240, 360 s) under control conditions and after i.v. administration of verapamil (50 micrograms/kg loading dose and 2 micrograms/kg/min infusion). Unaffected by verapamil when coronary circulation was normal, fibrillation threshold was raised by the drug when lowered by ischaemia, increasingly with the prolongation of ischaemia responsible for depolarization of the fibres, up to 500%. The rise of fibrillation threshold resulted in a delay in the triggering of fibrillation which occurs when the fibrillation threshold (6-8 mA) falls down to the pacing threshold (0.3-0.4 mA). These experiments tend to confirm the positive results recently obtained in man with verapamil in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, in these experiments, left ventricular dP/dt max was not reduced by more than 15%, even just after the loading dose and returned to its control values within a few minutes.

Animals↗

PubMed1995

Bupivacaine hastens the ischemia-induced decrease of the electrical ventricular fibrillation threshold.

Myocardial ischemia sensitizes the cardiotoxic effects of bupivacaine, especially the propensity to ventricular fibrillation. To investigate this sensitization and to elucidate its mechanism, the influence of bupivacaine alone, or associated with ischemia, was studied on electrical fibrillation threshold in anesthetized, open chest pigs. Determination of fibrillation threshold was performed with impulses of 100 ms duration at the rate of 180 bpm, in the absence of ischemia and at the end of increasing periods of ischemia (30, 60, 120, 180 s) obtained by complete occlusion of the left anterior descending coronary artery close to its origin. The effect of bupivacaine (1.00 mg/kg initial dose plus 0.04 mg.kg-1.min-1 over 25 min) was compared to the control in the same animals. This effect corresponded to 1.4-1.8 micrograms/mL plasma concentrations likely to be observed in humans after regional anesthesia. Bupivacaine significantly increased the fibrillation threshold before coronary occlusion from approximately 7.0 to 9.5 mA. In contrast, during ischemia the fibrillation threshold was shifted to the left and down, with a hastening of spontaneous fibrillation. Recording of monophasic action potentials in the ischemic area revealed that conduction time was prolonged by more than 100% under the combined influence of ischemia and bupivacaine, whereas the major enhancement of excitability due to ischemia was not attenuated by bupivacine. Therefore, bupivacaine should be used with caution in the condition of ischemia, especially if heart rate is rapid. In the present experiments, tachycardia is another factor in the enhancement of bupivacaine effects on conduction.

Action Potentials↗

PubMed1995

Preconditioning reduces infarct size but accelerates time to ventricular fibrillation in ischemic pig heart.

Preconditioning protects the rat heart from ventricular arrhythmias. However, the mechanism of this beneficial effect and its existence in large animal models remain unknown. We submitted 49 pigs to 40 min of left anterior descending coronary occlusion and 2 h of reperfusion and assessed the incidence of ventricular fibrillation (VF) and time to VF. Monophasic action potential duration (MAPD) and ventricular fibrillation threshold (VFT) were measured throughout the experiment. Preconditioning significantly reduced infarct size but failed to reduce the incidence of VF either during the 40-min ischemic insult or the following reperfusion. Moreover, preconditioning accelerated the onset of VF during the prolonged ischemia; time to VF averaged 8 +/- 2 min in the preconditioned group vs. 18 +/- 2 min in the control group (P < 0.05). This premature peak of VF in preconditioned hearts was associated with a significant decrease of VFT and shortening of MAPD. This suggests that preconditioning does not limit the incidence of VF in the pig model. Rather, preconditioning decreases the time to VF in this species, likely through lowering of the VFT and shortening of the action potential duration.

Action Potentials↗

PubMedDate not supplied

Possible role of drug interactions in bupivacaine-induced problems related to intraventricular conduction disorders.

Clinically, bupivacaine has depressant effects on intraventricular conduction that may lead to serious atrioventricular blocks or reentrant arrhythmias at plasma levels below those required to produce these effects experimentally (2-3 micrograms/ml instead of 8-10 micrograms/ml). The difference could be due to drugs present in the blood at the time of regional anesthesia that similarly inhibit conduction. This hypothesis was examined in 30 anesthesized, closed-chest dogs by measuring conduction time in the ventricular contractile fibers as well as effective refractory period under pacing at a constant, relatively high (180 beats/minute) rate. Changes in sinus rate were limited, as well as changes in ventricular effective refractory period and blood pressure regardless of the drug tested. In contrast, cibenzoline, disopyramide, and propranolol increased conduction time and lengthened QRS duration. Clomipramine appeared to prolong conduction time and widen QRS only moderately in therapeutic doses, whereas verapamil did not manifest noticeable effects on conduction. Caution is therefore recommended in regional anesthesia with bupivacaine in subjects being treated with cardiovascular drugs, such as cibenzoline, disopyramide, and propranolol and their congeners, or even by tricyclic antidepressants.

Animals↗