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E Vanoli

Publications and source records attributed to E Vanoli.

44 records · Page 3Linked to original sources

Efficacy of diltiazem in two experimental feline models of sudden cardiac death.

The potential role of calcium entry blockers in the prevention of life-threatening arrhythmias associated with acute myocardial ischemia and reperfusion is still controversial. In 98 anesthetized cats, the effect of diltiazem was examined in two experimental models. In protocol I, ventricular tachycardia or fibrillation was consistently induced by the interaction between a 2 minute coronary artery occlusion and a 30 second left stellate ganglion stimulation. After three trials under control conditions, if the same pattern of arrhythmia was induced, the drug under study was administered and three additional trials were performed. In 16 animals the administration of saline solution did not modify the pattern of arrhythmias. In contrast, diltiazem (0.1 mg/kg body weight plus 0.2 mg/kg per h) abolished both ventricular tachycardia and fibrillation that had occurred in 64 and 36%, respectively, of the cats in the control state. In protocol II, a 20 minute coronary artery occlusion was released in three groups; one served as the control group, one received diltiazem 15 minutes before occlusion and one received diltiazem 3 minutes before reperfusion. The incidence of reperfusion ventricular fibrillation was 62% (16 of 26) in the control group. It was significantly (p less than 0.05) reduced by diltiazem administered before the occlusion to 25% (4 of 16), whereas it was not affected when diltiazem was administered just before reperfusion (7 [47%] of 15). These results indicate that diltiazem exerts a striking protective effect against the malignant arrhythmias induced by the combination of acute myocardial ischemia and sympathetic hyperactivity. Diltiazem was also effective in reducing the incidence of life-threatening reperfusion arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)

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Lack of correlation between occlusion and reperfusion arrhythmias in the cat.

Recently it has been stated that in dogs absence of arrhythmias during coronary artery occlusion identifies a subgroup at almost no risk for developing ventricular fibrillation (VF) during reperfusion. A potential implication would be that prevention of ischemic arrhythmias may also prevent the most severe reperfusion arrhythmias. This concept is at variance with available clinical evidence. In order to reexamine this problem the left anterior descending coronary artery was occluded for 20 minutes in 41 anesthetized cats; the incidence and type of arrhythmias during occlusion and during the first minute of reperfusion were analyzed. Five animals had VF during occlusion and were not resuscitated. Twenty animals had ischemic arrhythmias, and among them the incidence of reperfusion VF was 50%. Sixteen animals did not have ischemic arrhythmias, but they did have a very similar incidence of reperfusion VF (44%). Thus, in this feline preparation, absence of ischemic arrhythmias did not help to predict a favorable outcome at the moment of reperfusion. This disparity with previous studies does not depend on the protocol used, but it may be partly due to species difference. These results demonstrate a lack of correlation between reperfusion VF and ischemic arrhythmias and provide further support for the concept of different mechanisms involved in occlusion and reperfusion arrhythmias.

Animals↗

The effect of antiarrhythmic drugs on life-threatening arrhythmias induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity.

Transient myocardial ischemia, with attendant sympathetic hyperactivity, seems to play a major role in sudden cardiac death among patients with ischemic heart disease. Ventricular tachycardia (VT) and fibrillation (VF) are consistently and repeatedly elicited in cats by the interaction between a 2-minute occlusion of the left descending coronary artery and a 30-second stimulation of the left stellate ganglion. When three consecutive trials yield almost identical results, time alone will not modify the response and a given drug can be injected to test its efficacy with an internal control analysis. In 90 cats the efficacy of the following drugs was assessed: lidocaine (n = 11), mexiletine (n = 12), propafenone (n = 12), propranolol (n = 19), prazosin (n = 10), amiodarone (n = 14), and verapamil (n = 12). Class I antiarrhythmic drugs completely failed to afford protection and worsening of arrhythmia was observed in several instances. Propranolol and prazosin showed efficacy in approximately 80% and 60% of the animals, respectively. Amiodarone and verapamil completely prevented the onset of VT and VF. Protection from arrhythmias seems to be related to the combined presence of a noncompetitive adrenergic blockade associated with salutary effects on coronary circulation. These findings correlate with and help to explain the results of clinical trials in postmyocardial infarction patients. This model may help to provide a rational choice of antiarrhythmic drugs to be tested in clinical trials.

Amiodarone↗

Cardiac arrhythmias elicited by interaction between acute myocardial ischemia and sympathetic hyperactivity: a new experimental model for the study of antiarrhythmic drugs.

The choice of an adequate model for the study of antiarrhythmic drugs, relevant to the clinical problem of life-threatening arrhythmia, is a difficult and important task for contemporary cardiovascular pharmacology. Guided by pathophysiological considerations, we have designed an arrhythmia model in which ventricular tachyarrhythmias can be reproducibly elicited by combining the two clinically relevant stimuli of acute myocardial ischemia and augmented sympathetic activity. In anesthetized cats, following ablation of the right stellate ganglion, the left anterior descending coronary artery is occluded for 2 min. After 1 min of occlusion the left stellate ganglion is electrically stimulated for 30 s. In most experiments ventricular tachyarrhythmias, usually ventricular tachycardia or fibrillation, can be regularly elicited for six to eight trials. The consistency of the arrhythmic response allows an internally controlled study, since a drug may be administered after three trials under control conditions. This avoids the limitations due to individual variability of comparisons between groups. This model seems to be particularly well suited for preliminary evaluation, before final study in conscious animals, of drugs thought to have a protective effect against malignant arrhythmias associated with acute myocardial ischemia.

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