Quadiri Timour

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 delivered 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.

5‐Fluorouracil—Induced Tako‐Tsubo—Like Syndrome

Tako‐Tsubo cardiomyopathy (also known as apical ballooning syndrome) is a relatively new clinical entity characterized by reversible left ventricular dysfunction. Its clinical presentation and electrocardiographic findings are similar to acute myocardial infarction but without significant coronary artery disease. Cardiotoxicity is a major complication of various anticancer drugs; however, only a few cases of Tako‐Tsubo cardiomyopathy associated with anticancer drugs, including 5–fluorouracil, have been reported. We describe a 48–year‐old man who developed acute coronary syndrome, thought to be similar to Tako‐Tsubo syndrome, after receiving a chemotherapy regimen consisting of 5–fluorouracil, oxaliplatin, and calcium folinate (FOLFOX protocol) for colic adenocarcinoma. Approximately 24 hours after receiving his first cycle of chemotherapy, the patient, who did not have a history of cardiovascular disease, developed chest pain, with abnormal electrocardiographic results and a mildly increased troponin T level. Coronary angiography did not show any significant coronary lesions. Echocardiography revealed marked left ventricular dysfunction (left ventricular ejection fraction [LVEF] 15%) with severe hypokinesia in all apical and median segments. The patient was stabilized with the introduction of an intraaortic balloon pump and pressor therapy. One month later, myocardial magnetic resonance imaging confirmed total recovery of left ventricular systolic function. Thus, the second chemotherapy cycle was administered at half the dose‐intensity along with ramipril and diltiazem. The chemotherapy regimen was well tolerated. Two weeks later, at the end of the third chemotherapy cycle, administered using the full‐dose regimen, the patient experienced cardiac arrest, necessitating cardiopulmonary resuscitation. After transfer to the cardiology intensive care unit, acute heart failure recurred (LVEF 35%). Normal recovery of left ventricular function occurred a few days later. Chemotherapy was discontinued, and treatment with bisoprolol was started. Four months later, the patient remained completely asymptomatic of any cardiac manifestations. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 8) between the patients development of acute coronary Tako‐Tsubo‐like syndrome and 5–fluorouracil. Clinicians should be aware of this potential adverse effect when monitoring patients receiving chemotherapy with 5–fluorouracil.

Efficacy of a β-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.

Ivabradine induces an increase in ventricular fibrillation threshold during acute myocardial ischemia: an experimental study.

Background: Tachycardia often facilitates ischemic ventricular fibrillation (VF). Objective: This study assessed the impact of ivabradine (IVA), a selective inhibitor of the cardiac pacemaker If current, on ventricular fibrillation threshold (VFT) during acute myocardial ischemia. Methods: The experiments were conducted on a total of 54 domestic pigs. Myocardial ischemia was induced in anesthetized pigs by total 1-minute coronary occlusion at baseline and then on 2 occasions after intravenous administration of saline or 0.5 mg/kg of IVA. VF was triggered by electrical stimuli of increasing intensity at a fixed rate. Heart rate (HR), VFT, monophasic action potential duration, and peak of the time derivative of left ventricular pressure (LV dP/dtmax) were monitored on each occasion. The activity of mitochondrial succinodehydrogenase was measured on heart sections. Results: Compared with controls, IVA induced a 31% reduction in HR, a 2.9-fold increase in VFT, and prevented ischemia-induced monophasic action potential duration shortening (+1 ± 12 vs. −14 ± 11 milliseconds) without affecting peak LV dP/dt. This beneficial effect on VFT was mainly due to HR reduction and was accompanied by a significant reduction in the hypoxic area (26% ± 1% vs. 38% ± 1%, P < 0.0001). Conclusion: HR reduction and the decrease in myocardial damage induced by IVA protected against primary ischemic VF without altering myocardial contractility.

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.

Sudden death of cardiac origin and psychotropic drugs.

Mortality rate is high in psychiatric patients versus general population. An important cause of this increased mortality is sudden cardiac death (SCD) as a major side-effect of psychotropic drugs. These SCDs generally result from arrhythmias occurring when the posology is high and may attain a toxic threshold but also at dosages within therapeutic range, in the presence of risk factors. There are three kinds of risk factors: physiological (e.g., low cardiac rate of sportsmen), physiopathological (e.g., hepatic insufficiency, hypothyroidism) and “therapeutic” (due to interactions between psychotropic drugs and other medicines). Association of pharmacological agents may increase the likelihood of SCDs either by (i) a pharmacokinetic mechanism (e.g., increased torsadogenic potential of a psychotropic drug when its destruction and/or elimination are compromised) or (ii) a pharmacodynamical mechanism (e.g., mutual potentiation of proarrhythmic properties of two drugs). In addition, some psychotropic drugs may induce sudden death in cases of pre-existing congenital cardiopathies such as (i) congenital long QT syndrome, predisposing to torsade de pointes that eventually cause syncope and sudden death. (ii) A Brugada syndrome, that may directly cause ventricular fibrillation due to reduced sodium current through Nav1.5 channels. Moreover, psychotropic drugs may be a direct cause of cardiac lesions also leading to SCD. This is the case, for example, of phenothiazines responsible for ischemic coronaropathies and of clozapine that is involved in the occurrence of myocarditis. The aims of this work are to delineate: (i) the risk of SCD related to the use of psychotropic drugs; (ii) mechanisms involved in the occurrence of such SCD; (iii) preventive actions of psychotropic drugs side effects, on the basis of the knowledge of patient-specific risk factors, documented from clinical history, ionic balance, and ECG investigation by the psychiatrist.

Hidden Cardiac Lesions and Psychotropic Drugs as a Possible Cause of Sudden Death in Psychiatric Patients: A Report of 14 Cases and Review of the Literature

Objective: To confirm the hypothesis that psychotropic drugs, especially neuroleptics, lithium, and antidepressants, are implicated as a cause of unexpected sudden death in psychiatric patients because of their cardiotoxicity, especially when hidden cardiac lesions are present. Method: We performed a full pathological examination of 14 psychiatric patients who unexpectedly and suddenly died between 1980 and 1999. Results: Neuroleptics were involved in 13 instances, antidepressants in 9, and anxiolytics in 5. Psychotropic drugs were combined in all but a single patient. In all 14 patients, toxicological analyses discarded drug overdose as cause of death. At postmortem examination, the brain and abdominal organs were normal. In 13 patients, the following lesions were found in the heart and lungs: dilated cardiomyopathy (6 patients), left ventricular hypertrophy (2 patients, 1 of which was associated with mitral prolapse and anomalies of His bundle), arrhythmogenic cardiopathy of the right ventricle (1 patient), pericarditis (1 patient), mitral prolapse (1 patient), muscular bridge on the anterior interventricular artery (1 patient), and Mendelsons syndrome (1 patient). In 1 case, no changes were seen. Most of the drugs that were taken immediately prior to death can induce arrhythmias either by prolonging the QT interval, potentially resulting in torsades de pointes, or by widening QRS complexes, possibly leading to reentry and ventricular fibrillation. Conclusion: Our findings suggest that the arrhythmogenic effects of psychotropic drugs can be exacerbated when preexisting hidden cardiac lesions are present and can result in sudden death. Patients should be systematically evaluated for cardiac lesions prior to starting any treatment with psychotropic drugs; the minimal effective dosage should be used.

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

SummaryThe 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.

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

SummaryCalcium 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.

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.