Effects of hydrochlorothiazide, amiloride, and lisinopril on the metabolic, hemodynamic, and electrocardiographs responses to increased plasma epinephrine

Abstract

I n the treatment of cardiovascular disease, such as hypertension and heart failure, minor metabolic side effects of the long-term pharmacologic treatment might be of importance. Thus, diuretics may jnduce a potentially’arrhythmogenic hypokalemial and have negative effects on the glucose metabolism, and both diuretics and l3 blockers may have adverse effects on blood lipid levels2 that might increase the risk of coronary artery disease, despite the benefits provided by these drugs’ antihypertensive actions. In experimental settings, an infusion of epinephrine given at a rate to obtain serum concentrations comparable to those seen in acute myocardial infarction has profound metabolic and electrocardiographic effects that are known to facilitate the development of malignant ventricular arrhythmias.3 These effects of epinephrine may be aggravated by some drugs commonly prescribed in cardiovascular disorders.” This study investigated the effects of pretreatment with hydrochlorothiazide, amiloride, and lisinopril on the response to an epinephrine infusion. were analyzed: potassium, magnesium, calcium, phosphate, urate, albumin, creatinine, and blood glucose. An electrocardiographic recording was made during the infusion and for the following 30 minutes. The recordjng was analyzed for heart rate, T-wave amplitude, QRS duration, and QT interval. Systolic and diastolic (phase V) blood pressures were also determined. Prior to the epinephrine infusion, the volunteers were pretreated in random order for 14 days with: (1) placebo, (2) hydrochlorothiazide (HCTZ) 50 mg daily, (3) amiloride 10 mg daily, and (4) lisinopril 20 mg daily. Each volunteer received all of the pretreatments (Latin square design). The results were expressed as mean +: standard deviation. For statistical analysis, a multivariate analysis of variance for repeated measurements (MANOVA) was used with time during epinephrine infusion and the various pretreatments as within-subject factors.