Systolic time intervals in evaluation of the negative inotropic effect after single oral doses of mexiletine and disopyramide

Rousson, D.; Piolat, C.; Galleyrand, Jacques; Ferry, Serge; Boissel, Jean-Pièrre

doi:10.1007/bf00541525

Cited by 7 publications

(2 citation statements)

References 21 publications

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“…Although the underlying mechanism(s) responsible for disopyramide-induced depression of myocardial contractility remain to be elucidated, disopyramide appears to reduce the inotropic state of the myocardium such that the level of ventricular performance at a given ventricular end-diastolic volume is reduced (2,31,33,40). This was manifested in the present study by a dose-related decrease in CO and increase in LVEDP prior to hemodilution.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular effects of acute normovolemic hemodilution in rats with disopyramide-induced myocardial depression

et al. 1990

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The effect of myocardial depression on the circulatory response to acute normovolemic hemodilution (hematocrit 23%) with hetastarch was evaluated in 28 anesthetized Sprague-Dawley rats. Cardiac output was recorded using an electromagnetic flow probe. Mild, moderate, and severe myocardial depression were achieved by infusing disopyramide 50, 75, and 85 mg/kg. This resulted in a dose-dependent decrease in cardiac output (r = -0.73, p less than 0.05) and mean arterial pressure (r = -0.65, p less than 0.05), and an increase in left ventricular end-diastolic pressure (r = 0.77, p less than 0.05) and total peripheral resistance (r = 0.46, p less than 0.05). Following hemodilution, cardiac output and mean arterial pressure were significantly lower and total peripheral resistance significantly higher in animals with myocardial depression compared with saline anemic controls. These differences were dose-dependent for cardiac output (r = -0.83, p less than 0.05), mean arterial pressure (r = -0.68, p less than 0.05), and total peripheral resistance (r = 0.51, p less than 0.05). Although control animals were able to significantly increase their cardiac output and stroke volume after hemodilution compared with baseline, animals with severe myocardial depression were unable to do so. This resulted in marked hypotension after hemodilution in controls compared with severely depressed animals. The results suggest a diminished ability of the pharmacologically depressed heart to tolerate acute normovolemic hemodilution.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular effects of acute normovolemic hemodilution in rats with disopyramide-induced myocardial depression

et al. 1990

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“…So the results show varia tions in quantitative and qualitative obser vations. Nevertheless most papers show a drop in cardiac function which is greater for disopyramide than for mexiletine [1,3,5,17,19]. Both drugs are class I antiarrhyth mics according to the classification of Vaugham and Williams.…”

Section: Introductionmentioning

confidence: 99%

Hemodynamic Effects of Mexiletine and Disopyramide after Cardioplegic Arrest

Moritz¹,

Eckersberger²,

Losert³

et al. 1989

Eur Surg Res

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To study the hemodynamic side effects of mexiletine and disopyramide when administered before cardioplegic arrest 15 dogs underwent sham cardiac surgery with a 90-min period of aortic cross-clamping. 5 dogs served as control, 5 were given 8 mg/kg/day mexiletine and another five 11 mg/kg/day disopyramide for 1 week before surgery. On the day of surgery a continuous infusion was started. After reperfusion treated animals exceeded their preischemic blood pressure and regained their preoperative cardiac output. Compared to control animals left ventricular work was higher in the treated animals after reperfusion. The two tested type I antiarrhythmics tend to add to myocardial protection when given before cardioplegic arrest and do not exhibit negative inotropic side effects.

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Uncorrected pre-ejection period: A simple non-invasive measurement for pharmacodynamic screening of inotropic activity

Rousson

Galleyrand

Silie

et al. 1987

Eur J Clin Pharmacol

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Since heart rate (HR) is an important determinant of the duration of systole, systolic time intervals (STI) from 8 healthy subjects were examined after infusion of atropine. As no overall correlation was found between HR and pre-ejection period (PEP), the results confirm the need for individual estimates of the correction of the left ventricular ejection time (LVET) and the total electromechanical systole (OS2). In the same subjects the sensitivity of PEP to minor negative inotropic effects of mexiletine and disopyramide measured at Cmax was confirmed. Thus, in addition to its simplicity and reliability, the sensitivity of the uncorrected PEP should encourage use of this technique as part of any screening system for the early detection of an inotropic effect of new chemical entities.

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Systolic time intervals in evaluation of the negative inotropic effect after single oral doses of mexiletine and disopyramide

Cited by 7 publications

References 21 publications

Cardiovascular effects of acute normovolemic hemodilution in rats with disopyramide-induced myocardial depression

Cardiovascular effects of acute normovolemic hemodilution in rats with disopyramide-induced myocardial depression

Hemodynamic Effects of Mexiletine and Disopyramide after Cardioplegic Arrest

Uncorrected pre-ejection period: A simple non-invasive measurement for pharmacodynamic screening of inotropic activity

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