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Biomedical subjects

Q Timour

Publications and source records attributed to Q Timour.

At least 19 recordsLinked to original sources
PubMed2000

Unsuspected cardiac lesions associated with sudden unexpected perioperative death.

The retrospective analysis of 1700 forensic autopsies over 17 years (1981-97) following unexpected sudden cardiac death revealed a group of 50 cases that could have been related to surgery and/or anaesthesia. Patients were young with no history of cardiac disease. Surgery was performed for uncomplicated disorders, all classified as ASA 1. Cardiac arrest took place at induction of anaesthesia in 16% of cases, during surgery in 64% and at the end of surgery in 20%. Investigation and expertise reports ordered by the public prosecutor revealed none of the typical causes of death usually associated with surgery or anaesthesia. Pathological examination showed cardiac lesions in 47 cases: arrhythmogenic right ventricular cardiomyopathy in 18 cases, coronary artery disease in 10 cases, cardiomyopathy in eight cases, structural abnormalities of the His bundle in nine cases, mitral valve prolapse in one case, and acute myocarditis in one case. Identification of the cause of death of patients at low risk may provide major relief to the family of the patient and the medical staff.

Adolescent↗
PubMed2000

Opposite change with ischaemia in the antifibrillatory effects of class I and class IV antiarrhythmic drugs resulting from the alteration in ion transmembrane exchanges related to depolarization.

It is known that class I antiarrhythmic drugs lose their antifibrillatory activity with severe ischaemia, whereas class IV antiarrhythmic drugs acquire such activity. Tachycardia, which is also a depolarizing factor, has recently been shown to give rise to an alteration of ion transmembrane exchanges which is particularly marked in the case of calcium. This leads one to wonder if the change in antifibrillatory activity of antiarrhythmic drugs caused by ischaemia depends on the same process. The change in antifibrillatory activity was studied in normal conditions ranging to those of severe ischaemia with a class I antiarrhythmic drug, flecainide (1.00 mg x kg(-1) plus 0.04 mg x kg(-1)x min(-1), a sodium channel blocker, and a class IV antiarrhythmic drug, verapamil (50 microg x kg(-1) plus 2 microg x kg(-1) x min(-1)), a calcium channel blocker. The experiments were performed in anaesthetized, open-chest pigs. The resulting blockade of each of these channels was assessed at the end of ischaemic periods of increasing duration (30, 60, 120, 180, 300, and 420 s) by determining the ventricular fibrillation threshold (VFT). VFT was determined by means of trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode introduced into the myocardium (heart rate 180 beats per min). Ischaemia was induced by completely occluding the left anterior descending coronary artery. The monophasic action potential was recorded concurrently for the measurement of ventricular conduction time (VCT). The monophasic action potential duration (MAPD) varied with membrane polarization of the fibres. The blockade of sodium channels by flecainide, which normally raises VFT (7.0 +/- 0.4 to 13.8 +/- 0.8 mA, p < 0.001) and lengthens VCT (28 +/- 3 to 44 +/- 5 ms, p < 0.001), lost its effects in the course of ischaemia. This resulted in decreased counteraction of the ischaemia-induced fall of VFT and decreased aggravation of the ischaemia-induced lengthening of VCT. The blockade of calcium channels, which normally does not alter VFT (between 7.2 +/- 0.6 and 8.4 +/- 0.7 mA, n.s.) or VCT (between 30 +/- 2 and 34 +/- 3 ms, n.s.), slowed the ischaemia-induced fall of VFT. VFT required more time to reach 0 mA, thus delaying the onset of fibrillation. Membrane depolarization itself was opposed as the shortening of MAPD and the lengthening of VCT were also delayed. Consequently there is a progressive decrease in the role played by sodium channels during ischaemia in the rhythmic systolic depolarization of the ventricular fibres. This reduces or suppresses the ability of sodium channel blockers to act on excitability or conduction, and increases the role of calcium channel blockers in attenuating ischaemia-induced disorders.

Action Potentials↗
PubMed1999

Thoracoscopic epicardial radiofrequency ablation for vagal atrial fibrillation in dogs.

Epicardial radiofrequency catheter ablation of the atria in the open-chest dog has been shown to reduce inducibility of atrial fibrillation. Video-assisted endoscopic techniques decrease the operative trauma in adult thoracic surgery. We report our results of video-assisted thoracoscopic radiofrequency catheter ablation of the atria for the prevention of atrial fibrillation induction in canines. In 12 consecutive anesthetized dogs, induction of sustained atrial fibrillation was reproducibly obtained by burst pacing and cervical vagal stimulation. In six dogs, biatrial ablation was performed through right and left minithoracotomies and guided by video-assisted endoscopic techniques. The remaining six dogs underwent a video-guided left atrial procedure. Long continuous and transmural lesions were produced using epicardial temperature controlled radiofrequency energy delivery according to a simplified maze approach. Transmural lesions were demonstrated at the end of the study by examination of the heart. Sustained atrial fibrillation was still inducible after the right atrial ablation but sustained atrial fibrillation could not be induced following left atrial ablation. In acute canine studies: (1) epicardial radiofrequency catheter ablation of the atria is feasible using video-assisted endoscopic techniques; (2) ablation extended or confined to the left atrium appears to be effective in preventing the inducibility of sustained vagal atrial fibrillation; and (3) ablation of the right atrium alone had no antiarrhythmic effect.

Animals↗
PubMed1998

Efficacy of a beta-adrenergic receptor antagonist, propranolol, in preventing ischaemic ventricular fibrillation: dependence on heart rate and ischaemia duration.

OBJECTIVES: To investigate the prevention of ventricular fibrillation with a beta-adrenergic receptor (beta-AR) antagonist in anaesthetized, open-chest pigs in a model of ischaemia, intended to reproduce what happens either in anginal attack or in the first hour of infarction. METHODS: Ventricular fibrillation threshold (VFT) was determined with trains of diastolic stimuli of 100 ms duration delivered by a subepicardial electrode inserted in the area subjected to ischaemia. Ischaemia was obtained by the complete occlusion of the left anterior descending coronary artery, either near its origin during brief but increasing periods (30, 60, 90, 120, 150, 180, 240, 300 s), or half-way from its origin for a much longer time (more than 60 min). RESULTS: During transient proximal occlusion and isoprenaline infusion (0.25 microgram/kg/min), propranolol (50 micrograms/kg plus 2 micrograms/kg/min) attenuated both tachycardia and the fall in VFT to 0 mA. The shortening of MAP duration accompanying depolarization of the fibres was concurrently slowed down, and time to fibrillation prolonged (122 +/- 15 to 262 +/- 14 s, p < 0.001). In the absence of isoprenaline infusion, propranolol exerted similar effects, but to a lesser degree, in proportion to heart rate dependent on sympathetic activity. In contrast, it became unable to raise VFT before and during ischaemia, when heart rate was kept constant by pacing. After persistent midportion occlusion, significant differences in VFT were found only at the 5th min, depending on whether heart rate was accelerated by isoprenaline (0.8 +/- 0.2 mA), left normal (1.8 +/- 0.3 mA) or slowed down by propranolol (1.6 +/- 0.3 mA). Later on, especially after 15 and 25 min of ischaemia, VFT, which was below 1.0 mA, did not appear to be influenced by the activation or blockade of beta-ARs: spontaneous fibrillations were observed in the same number in this period with or without the administration of propranolol. Beyond 30 min after occlusion, the rise in VFT, subsequent to the first irreversible cell damage, also occurred in the same way. CONCLUSIONS: The prevention of ischaemic ventricular fibrillation by a beta-AR antagonist, judged from VFT, is easily checked experimentally when ischaemia is only transitory, especially if sympathetic activity is high. The maintenance of VFT at a relatively high level is essentially related to the depressant effect on the sinus rate. The same animal model does not give support to an effective protection in the first hour of infarction. However, the control of heart rate may also be beneficial in these circumstances by attenuating systemic haemodynamic disorders.

Adrenergic beta-Agonists↗
PubMed1998

[Cardiac accidents of locoregional anesthesia: experimental study of risk factors with bupivacaine].

Cardiac disorders are observed when excessive plasma concentrations of local anaesthetics are reached, following for instance intravascular accidental injection for epidural anaesthesia or brachial plexus block. Bupivacaine particularly, which is one of the most used local anaesthetics, adversely affects intraventricular conduction and cardiac contractile strength from the 3.0-4.0 micrograms/ml blood levels. Depression of conduction is especially to be feared, for it can result in reentrant arrhythmias likely to degenerate into often fatal ventricular fibrillation. Such accidents may sometimes occur at far lower concentrations, subsequent to diffusion into systemic circulation from the injection site (0.4-1.2 micrograms/ml). These accidents were probably due to various factors which concomitantly intervene during the anaesthesia. We could identify a number of these factors by associating them to an intravenous infusion of bupivacaine (0.04 mg/kg/min after a loading dose of 1.00 mg/kg) in animals (dogs and pigs) under electrocardiographic monitoring, in which conduction time, monophasic action potential duration, effective refractory period and electrical fibrillation threshold were determined in the ventricular fibres. The electrophysiological changes due to bupivacaine may be enhanced by 1) dilution hyponatremia (115-110 mmol/l) induced by a short (5 min) intravenous 10 ml/kg/min infusion of hypotonic solution and/or hyperkalemia (7-8 mmol/l) induced by 0.05 mmol/kg/min infusion of potassium chloride; 2) the acceleration of cardiac contractions (180-210 beats/min) induced by ventricular pacing; 3) mild hypothermia (35-34 degrees C) induced by blood cooling in an extracorporeal circuit; 4) myocardial ischaemia induced by complete temporary occlusion of the left anterior descending coronary artery near its origin. The risk of cardiac accidents, possibly severe, is therefore enhanced by each of these factors capable of lowering the concentration required for their triggering and, of course, the combination of two or several of them. On the contrary, the knowledge of these factors should allow to prevent most of cardiac accidents of locoregional anaesthesia.

Accidents↗
PubMed1997

Ischaemia-induced loss or reversal of the effects of the class I antiarrhythmic drugs on vulnerability to fibrillation.

1. In the last decade, a number of clinical observations have questioned the efficacy of certain class I antiarrhythmic drugs against ischaemia-induced ventricular fibrillation. The effects of three drugs of this class, disopyramide (Ia), lignocaine (Ib) and flecainide (Ic) on the vulnerability to fibrillation during experimental ischaemia were investigated. 2. The study was carried out in anaesthetized, open-chest pigs (n = 8 for each of the drugs, in addition to the control group, n = 6). Vulnerability to fibrillation was evaluated by measuring electrical fibrillation threshold (EFT) by means of stepwise increased intensity of wide (100 ms) diastolic impulses applied to the ischaemic tissue at a 180 beats min-1 rate. Monophasic action potential (MAP) duration and conduction time in the ischaemic region were also measured. 3. EFT determinations were performed before and during periods of ischaemia induced by complete occlusion of the left anterior descending coronary artery near its origin. Ischaemic periods of increasing duration (30, 60, 90, 120, 150 s) were induced to determine the electrophysiological changes, of EFT especially, leading to fibrillation. 4. In the absence of ischaemia, all three drugs, administered by intravenous route (1 mg kg-1 plus 0.04 mg kg-1 min-1) increased EFT to a similar extent (from approximately 7 to 10 mA), despite a 25% prolongation of conduction time. 5. During ischaemia, none of the drugs prevented the fall in EFT towards 0 mA, resulting in spontaneous fibrillation. After 30 s of ischaemia, they no longer had any capacity for raising EFT and, after 60, 90 and 120 s of ischaemia, the decrease in EFT was exacerbated. This accelerated reduction in EFT shortened the time to onset of fibrillation (after 120 s of ischaemia, 62.5% of fibrillations with flecainide instead of 12.5 under control conditions, 75% instead of 25 with lignocaine and 50% instead of 25 with disopyramide). The reduction in MAP duration due to ischaemia was also significantly accelerated (at 60 s, 178 +/- 5 ms instead of 192 +/- 4 with flecainide, 175 +/- 3 ms instead of 194 +/- 5 with lignocaine and 180 +/- 5 ms instead of 196 +/- 3 with disopyramide) and the slowing of conduction was made worse (prolongation of conduction time by 70% instead of 50). 6. In conclusion, the antifibrillatory properties normally manifested by these drugs are first suppressed, then inverted by ischaemia, depending on oxygen debt varying with severity and duration of ischaemia.

Animals↗
PubMed1997

Magnesium--a profibrillatory or antifibrillatory drug depending on plasma concentration, heart rate and myocardial perfusion.

BACKGROUND: The opinions on the efficacy of magnesium as an antiarrhythmic drug vary considerably. The action of magnesium on vulnerability to fibrillation was therefore investigated in anaesthetized, open-chest pigs under different conditions as regards plasma concentration, heart rate and myocardial perfusion. METHODS: Vulnerability to fibrillation was assessed by electrical fibrillation threshold (EFT), measured with 100-ms duration diastolic impulses. These stimuli were delivered to the heart normally perfused, at a usual (90 and 120 beats/min) or accelerated (180 beats/min) rate. Vulnerability to fibrillation was also assessed at the high rate (180 beats/min) in the heart made ischaemic by complete occlusion of the left anterior descending coronary artery near its origin. EFT was then measured at the end of occlusion periods which were of increasing duration (30, 60, 90, 120 s). Monophasic action potential (MAP) duration, intraventricular conduction time, left ventricular dP/dt max (LVdP/dt max) and mean blood pressure were concurrently measured. RESULTS: In the absence of ischaemia, 5 mumol.kg-1.min-1 magnesium i.v. infusion, which raised plasma concentration to 1.78 +/- 0.14 mmol/L, lowered EFT, measured at the rate of 116 beats/min, from 14.0 +/- 1.1 to 6.8 +/- 1.0 mA (P < 0.001), without significant variation of the other parameters. Administered as previously or in a markedly higher dose (400 mumol.kg-1 loading dose and 10 mumol.kg-1.min-1 infusion) which raised plasma concentration up to 4.84 +/- 0.52 mmol/L, magnesium significantly influenced neither EFT nor MAP duration, reduced by the high rate (180 beats/min) to 6.2-6.7 mA and 212-220 ms respectively. Under the same conditions, at the same 180 beats/min rate, ischaemia brings about a fall of EFT, from 6.9 down to nearly 0 mA, with occurrence of fibrillation, in approximately 120 s. Magnesium failed to slow this fall and to delay the onset of fibrillation. In contrast, within the minutes following the end of occlusion, magnesium increased EFT to a great extent (from 7.1 +/- 0.4 to 13.5 +/- 0.7 mA, P < 0.001), with a significant prolongation of MAP duration (212 +/- 6 to 234 +/- 8 ms, P < 0.01). CONCLUSION: Magnesium may develop profibrillatory or antifibrillatory effects depending on plasma concentration, heart rate and myocardial perfusion.

Animals↗
PubMed1997

Calcium antagonists and prevention of ventricular fibrillation induced by transient or persistent ischemia.

Experimental studies have shown the limitation by calcium antagonists of the propensity to fibrillation secondary to the occlusion of a large coronary artery. However, this capacity, studied in the acute phase of infarction, is less obvious and still under debate. Ischemia was therefore produced in anesthetized, open-chest pigs by complete occlusion of the left anterior descending coronary artery according to two modes, either near its origin during brief but increasing periods (30, 60, 120, 180 s, etc) or half-way from this origin for a much longer time (60 min). The time course of vulnerability to fibrillation was monitored by ventricular fibrillation threshold (VFT), measured by trains of diastolic stimuli of 100 ms. Verapamil was administered in a 50 micrograms/kg dose followed by 2 micrograms/kg/min infusion. 1) In the case of brief proximal occlusions under pacing at a constant high rate (180 beats/min), verapamil slowed the decline of VFT from 6-8 mA to nearly 0 mA. VFT was 4.4 +/- 0.4 mA after 60 s ischemia, whereas it had already fallen to 1.8 +/- 0.3 mA (p < 0.001) in the absence of the drug. Accordingly, the onset of spontaneous fibrillation which depends on the decrease in VFT to about 0 mA was prolonged from 2-3 to 6-9 min. Bradycardia, concurrently produced by verapamil, is a factor which enhances these alterations. 2) In the case of a persistent midportion occlusion of the artery under sinus rate, fibrillations were similarly delayed by verapamil from 14-25 to 23-49 min after occlusion, but they were more numerous. VFT was lowered to critical values later, but also for a longer time. The period propitious to fibrillation was prolonged because the return of VFT to higher values reflecting hypoexcitability subsequent to the first cell injury was substantially delayed. Consequently, calcium antagonists should often prevent ventricular fibrillation when transient ischemia disappears before VFT falls to the vicinity of 0 mA. In contrast, a real benefit could not be expected from these drugs when ischemia is persistent since they then only delay fibrillations, the number of which is increased.

Analysis of Variance↗
PubMed1996

Delay by a calcium antagonist, amlodipine, of the onset of primary ventricular fibrillation in myocardial ischemia.

Calcium antagonists have been reported to counteract the increase by ischemia of vulnerability to ventricular fibrillation. This ability might be especially of interest in the prevention of sudden death subsequent to a major, but transitory, inadequacy between myocardial oxygen requirements and available coronary blood flow produced by exercise, emotion, etc., because death is then not related to irreversible damage of myocardial fibers. This study has been undertaken to examine the protective effect of a calcium antagonist on an animal model of this type of ischemia. This model used complete, but transient occlusion of the left anterior descending coronary artery near its origin during pacing at a constant high rate (180 beats/min) in anesthetized, open-chest pigs, most often resulting in fibrillation within 1-2 minutes after a progressive fall of the electrical fibrillation threshold. Amlodipine was the preferred calcium antagonist for this study because it is only moderately negatively inotropic. The results of the preventive administration of amlodipine was assessed by the time to onset of fibrillation. Amlodipine 0.30 mg/kg prolonged this time by 50-100% (p < 0.05) without appreciable impairment of blood pressure or myocardial contractility. Concurrently, amlodipine delayed the shortening of the monophasic action potential duration, the lengthening of conduction time, and the alterations of ST segments and T waves linked to ischemic depolarization. Consequently, when given experimentally before the occurrence of major, but transitory ischemia, amlodipine protected against fibrillation. Similarly, in clinical settings it ought to delay sudden death that may occur as a result of a major but transitory inadequacy between myocardial oxygen requirements and available coronary blood flow.

Action Potentials↗
PubMed1996

Cardiac implications of amlodipine-dantrolene combinations.

PURPOSE: Cardiac disorders, cardiac arrest and ventricular fibrillation in the most severe cases, have been observed after the administration of dantrolene to patients treated by verapamil for coronary artery disease. This study was designed to examine the interaction of dantrolene with amlodipine, a dihydropyridine. METHODS: In 12 anaesthetized, open-chest pigs, the effects of the interaction have been studied on heart rate, atrioventricular conduction, monophasic action potential duration, intraventricular conduction time, left ventricular dP/dt max and mean blood pressure. The study was performed with normal coronary circulation and ischaemia of a large area of the left ventricule, obtained by complete occlusion of the left anterior descending coronary artery near its origin, under pacing at a constant high rate, 180 beats.min-1. The drugs were injected iv, amlodipine 0.4 mg.kg-1 first and dantrolene 3.0 mg.kg-1 20 min later in six animals and the order was reversed in the other animals. RESULTS: Sinus rate and atrioventricular conduction were not affected by amlodipine, but were slowed by dantrolene added (145 +/- 9 to 131 +/- 7 beats.min-1, P < 0.01 and 150 +/- 15 to 180 +/- 20 msec, P < 0.01). In contrast, amlodipine or amlodipine plus dantrolene did not change MAP duration or conduction time in the normal heart. Similarly, they did not alter the maximal variations due to ischaemia, but delayed them, while prolonging the time to onset of fibrillation (111 +/- 8 to 343 +/- 33 sec. P < 0.001 with amlodipine alone, 289 +/- 11 to 323 +/- 16 sec, P < 0.05 with dantrolene). Left ventricular dP/dt max was lowered from 1670 +/- 86 to 1532 +/- 50 mmHg.sec-1 (P < 0.001) and mean blood pressure from 79 +/- 4 to 70 +/- 3 mmHg (P < 0.01) by amlodipine, but dantrolene did not enhance and even counteracted these effects. Finally, potassium plasma concentration did not increase above 5.1 +/- 0.2 mmol.L-1 under the dual influence of amlodipine and dantrolene. CONCLUSION: In usual clinical doses, dantrolene may be safely administered concurrently with amlodipine.

Amlodipine↗
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↗
PubMed1996

Possible prevention by amlodipine of ventricular fibrillation related to brief ischemia episodes.

Calcium antagonists may reduce propensity to ventricular fibrillation, by altering the balance between coronary blood flow and metabolic demand, and thus may substantially prolong time to occurrence of fibrillations. This delay in the onset of fibrillation should be sufficient to prevent sudden death in the case of transitory episodes of myocardial ischemia. Therefore, this study was based on the determination of time to onset of fibrillation in an animal model of transitory ischemia. This model was achieved by the complete, but transitory occlusion of the left anterior descending coronary artery near its origin under ventricular pacing at a constant high rate (180 beats/min), in anesthetized, open-chest pigs. Amlodipine was preferred to another calcium antagonist for this study because it is among the least negatively inotropic of these drugs. It was intravenously infused at 0.02 mg.kg-1.min-1. Time to fibrillation was prolonged from 87 +/- 10 to 146 +/- 16 s (p < 0.05) with the 0.30 mg/kg dose and to 201 +/- 22 s (p < 0.05) with the 0.60 mg/kg dose, without serious impairment of blood pressure or left ventricular dP/dtmax in the absence of ischemia. Concurrently, amlodipine significantly limited the shortening of monophasic action potential duration (200 +/- 4 vs. 172 +/- 6 ms), the lengthening of conduction time (43 +/- 2 vs. 53 +/- 2 ms), and the alterations of ST segments and T waves induced by 60 s ischemic depolarization. Consequently, amlodipine might reduce the incidence of sudden death by lengthening time to onset of fibrillation beyond the duration of the ischemia, when transitory.

Amlodipine↗
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

Profibrillatory effects of lidocaine in the acutely ischemic porcine heart.

Because recent clinical studies have failed to show evidence of the benefit of lidocaine in the arrhythmias occurring in the early stage of myocardial infarction and have even shown an increased mortality in patients thus treated, we investigated the value of lidocaine as a protective agent against ventricular fibrillation related to myocardial ischemia in the in situ heart of anesthetized open-chest pigs subjected to transient total occlusion of the proximal left anterior descending coronary artery (LAD) under ventricular pacing at a constant high rate. Vulnerability to the fibrillatory process induced by coronary occlusion was assessed both by time to onset of ventricular fibrillation (TF) and by electrical ventricular fibrillation threshold (EFT) determined after coronary occlusions of increasing duration (30, 60, 120, 180 s). Monophasic action potential (MAP) was recorded concurrently in the nonischemic and ischemic areas. Lidocaine, even in relatively high doses (2-4 mg.kg-1), did not prolong TF, nor did it increase EFT. On the contrary, TF was significantly shortened and EFT was significantly decreased (15-30%) at the maximal concentrations of lidocaine, with return to control values in 40-60 min. Therefore, lidocaine tends to increase the risk of ischemic ventricular fibrillation (VF): It fails to control the extreme enhancement of excitability and worsens conduction disorders, even though it decreases normal conduction only slightly. Use of lidocaine against rhythm disorders in acute myocardial infarction (AMI), is at least debatable and probably contraindicated.

Action Potentials↗
PubMed1993

Attenuation of the ischaemia-induced fall of electrical ventricular fibrillation threshold by a calcium antagonist, diltiazem.

Calcium antagonists have been reported to decrease the incidence of sudden death in postinfarction management and vulnerability to fibrillation secondary to experimental coronary occlusion. In order to confirm such beneficial results regarding ischaemic ventricular fibrillation, the threshold intensity for fibrillation electrically induced with impulses of 100 ms and 180 beats.min-1 was measured during the course of ischaemias obtained by total occlusion of the left anterior descending coronary artery near its origin in open-chest pigs. The variations of electrical fibrillation threshold with ischaemia duration (30, 60, 120, 180, 240, 360 s) were compared under control conditions and after i.v. diltiazem (0.50 mg.kg-1 plus 0.02 mg.kg-1.min-1 over 25 min). Electrical fibrillation threshold was not influenced by diltiazem before, but raised during ischaemia, particularly from the 60th s (1.7 to 4.0 mA), with delay in the triggering of fibrillation which occurs when the fibrillation threshold falls down to the pacing threshold (0.2 to 0.3 mA). In 6 pigs out of 8, fibrillation was even avoided in the longest of the ischaemic periods considered (360 s), for fibrillation threshold ceased falling before reaching the critical level. These experimental results obtained with diltiazem are consistent with the clinical effectiveness of calcium antagonists recently observed in the prevention of postinfarction sudden death, provided that myocardial contractility is not too much adversely affected. But, left ventricular dP/dtmax was not reduced by more than 6.8% in the present experiments.

Animals↗