Biomedical subjects

M Freysz

Publications and source records attributed to M Freysz.

112 records · Page 7Linked to original sources

PubMedDate not supplied

[Demonstration of the fibrillatory effect of class I anti-arrhythmia agents based on the time of fibrillation onset and electrical threshold in myocardial ischemia].

In recent clinical studies, certain class I antiarrhythmic drugs (flecaïnide, lidocaïne) appeared to be responsible for an increase in mortality, when used to treat ventricular arrhythmias occurring after or during infarction. Experimentally, in pigs whose rate of ventricular beats was kept constant by pacing, all the studied class I antiarrhythmic drugs, disopyramide, lidocaïne and flecaïnide, proved to be to a variable degree capable of shortening time to onset of fibrillation (TOF) elicited by controlled myocardial ischemia. Fibrillation occurred at the end of the decline, under the influence of ischemia, of electrical fibrillation threshold (EFT) down to near 0 mA. The fall of EFT to this level was checked by ischemias of increasing duration to be hastened by the cited antiarrhythmic drugs. In other words, these drugs exert a profibrillatory effect in the ischemic heart.

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PubMedDate not supplied

Vulnerability to ventricular fibrillation related to ischaemia: comparison of the acute effects of beta-blockers and calcium antagonists.

A comparative evaluation of beta-blockers and calcium antagonists as protective agents against ventricular fibrillation related to myocardial ischaemia, was attempted in the pig heart in situ of anaesthetized, open-chest animals, subjected to a temporary complete occlusion of the left anterior descending coronary artery near its origin. This occlusion resulted in fibrillation occurring after a time depending on the vulnerability to the fibrillatory process. As this time to onset of fibrillation does normally not exceed a few minutes, its determination could be achieved repeatedly in the course of an experiment, in the absence and presence of drugs such as beta-blockers and calcium antagonists. When propranolol (0.05 mg/kg, i.v.) and verapamil (0.05 mg/kg, i.v.) abolished tachycardia produced by isoproterenol (0.25 micrograms/kg/min), the triggering of fibrillation was delayed in either case: in animals under atrial pacing at a rate close to the sinus rate on each determination, time to fibrillation was prolonged from about 160 to 400 sec by propranolol and from 160 to 640 sec by verapamil, with a return to control values within 60 min. Under ventricular pacing at a constant high rate (180 beats/min), no change was observed in time to fibrillation after propranolol (0.025 or 0.050 mg/kg), whereas verapamil, in the same conditions and in the same doses, multiplied this time by about 4 and 6, respectively. Consequently, propranolol and verapamil are likely to protect against fibrillation immediately after i.v. injection, but the protection due to propranolol is only indirect and a consequence of bradycardia which tends to increase the polarization of the muscular fibres, whereas verapamil adds to the same influence a direct preventive action by avoiding a cellular calcium overload in these fibres, which is responsible for the depolarization and fluctuations of their membrane potential.

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PubMedDate not supplied

Disappearance with ischaemic depolarization of the antifibrillatory activity in a sodium channel blocker and appearance in calcium channel blocker.

Results obtained in the prevention of ventricular fibrillation secondary to myocardial ischaemia are unexpected. Profibrillatory properties might be manifested by Class I antiarrhythmic drugs, normally antifibrillatory. Clear antifibrillatory properties might be manifested by calcium channel blockers, the antifibrillatory effects of which are normally questionable. Therefore, the action of a Class I antiarrhythmic drug, flecainide, and of a calcium channel blocker, verapamil, on the vulnerability to ischaemic ventricular fibrillation was assessed in anaesthetized, open-chest pigs by ventricular fibrillation threshold. Ventricular fibrillation threshold was determined with trains of diastolic stimuli of 100 msec duration, delivered at a rate of 180 beats/min (near that of the ventricular tachycardia), by a subepicardial electrode inserted into the area that could be subjected to ischaemia. Before determining this threshold, ventricles were paced at the same rate, particularly during the ischaemic periods. Ischaemia was produced by complete occlusion of the left anterior descending coronary artery, either at its origin or half-way from it, over increasing periods. The monophasic action potential and conduction time were recorded in the ischaemic area. Before ischaemia, flecainide was adapted to rais the ventricular fibrillation threshold, in spite of a lengthening of the conduction time. Verapamil was devoid of any influence on these parameters. The antifibrillatory effect of flecainide disappeared with ischaemia, which reduced the ventricular fibrillation threshold down to near 0 mA, with triggering of the spontaneous fibrillation at this level: this reduction was no longer counteracted and even hastened by flecainide, becomes finally profibrillatory. Verapamil, on the contrary, delayed the fall in ventricular fibrillation threshold, maintained far from 0 mA, with prevention of fibrillation, unless the occlusion was maintained over a much longer period. Verapamil similarly delayed the shortening of the monophasic action potential duration and the lengthening of the conduction time, preceding fibrillation and leading to it. Consequently, ischaemic depolarization is apparently responsible for the loss of antifibrillatory activity in a sodium blocker, such as flecainide, and the development of antifibrillatory activity in a calcium blocker, since the sodium channel is activated only at high potentials, whereas the calcium channel is activated at lower potentials.

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PubMedDate not supplied

Prevention by calcium antagonists of profibrillatory effects of class I antiarrhythmic drugs in acute myocardial ischemia: study in pig heart in situ.

Class I antiarrhythmic drugs do not decrease, but increase, the risk of ventricular fibrillation in the ischemic myocardium. On the contrary, vulnerability to fibrillation related to ischemia appears to be substantially reduced by calcium antagonists. We assessed whether the calcium antagonist diltiazem (0.50 mg/kg bolus plus 0.02 mg/kg/min infusion) could prevent the profibrillatory effect or even partially restore the antifibrillatory effect of a class I antiarrhythmic drug, flecainide (1 mg/kg bolus plus 0.04 mg/kg/min infusion) in the ischemic myocardium of anesthetized, open-chest pigs. Ischemia was obtained by completely occluding the left anterior descending coronary artery near its origin. Vulnerability to fibrillation was assessed by electrical fibrillation threshold (EFT), measured with diastolic impulses of 100 msec duration delivered at a rate of 180 beats/minute. Diltiazem did not oppose the rise in EFT induced by flecainide in the absence of ischemia (6.8 +/- 1.2 to 9.9 +/- 0.9 mA, p<0.001). It limited the fall in EFT observed under the dual influence of ischemia and flecainide (4.2 +/- 0.9 vs 1.3 +/- 0.6 mA, p<0.001). By reducing calcium entry into myocardial fibers, diltiazem delayed ischemic depolarization, as evidenced by reduced shortening of the monophasic action potential duration from 215 +/- 7 to 200 +/- 4 msec, instead of 178 +/- 6 (p<0.001), and reduced lengthening of intraventricular conduction time from 33 +/- 5 to 43 +/- 4 msec, instead of 53 +/- 4 (p<0.01). Therefore, diltiazem is likely to prevent the loss and even the reversal of the antifibrillatory properties of flecainide due to myocardial ischemia in dosages that do not adversely affect myocardial contractility or atrioventricular conduction to a large extent.

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