Renal hypertensive hypertrophy in the rat: a substrate for arrhythmogenicity.
We investigated the ability of ouabain to produce lethal arrhythmias in rats with myocardial hypertrophy resulting from chronic renal hypertension. A gradual pressure overload was produced in female Wistar rats by left renal artery stenosis (two kidney, one clip, Goldblatt hypertension). Hypertension (systolic blood pressure greater than 150 mm Hg) developed within three weeks after clipping of the left renal artery and blood pressure continued to increase for the next five weeks. At ten weeks after the onset of hypertension animals were anesthetized with sodium pentobarbital (40 mg/kg) and artificially ventilated with room air while ECG was continually monitored and recorded. Continuous infusion of ouabain was maintained (0.7 mg/kg/min) through the inferior vena cava. Body weight and heart rate of control animals (C) was not significantly different from hypertensive (H) values, while systolic blood pressure in animals hypertensive for ten weeks was considerably greater (187 +/- 8.4 mm Hg) than their age-matched normotensive counterparts (123 +/- 6.0 mm Hg). Heart weight in hypertensive animals was elevated by 69% +/- 2.5 by time of study. Serological evaluation of both groups of animals revealed no significant differences in electrolytes and blood gases while significant differences were noted in glucose, BUN and creatinine. The average time to the first premature ventricular contraction was significantly shorter in H animals (3.5 +/- 0.2 min) when compared to C rats (6.0 +/- 0.2 min). The average time to ventricular tachycardia, ventricular fibrillation and death were also significantly shorter in H rats when compared to C animals (7.5 +/- 0.6 vs. 13.5 +/- 0.3; 13.5 +/- 0.5 vs. 21.0 +/- 0.5; 15.6 +/- 0.4 vs. 24.0 +/- 0.6 min). Thus, the hypertensive hypertrophied myocardium displays an increased propensity for lethal cardiac arrhythmias due to ouabain.
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D001806:Blood Urea Nitrogen; D002312:Cardiomyopathy, Hypertrophic / Q000503:physiopathology*; D004562:Electrocardiography; D004573:Electrolytes / Q000097:blood; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D004573:Electrolytes; D010042:Ouabain