Wall stress-induced arrhythmias in the working rat heart as left ventricular hypertrophy regresses during captopril treatment.
OBJECTIVE
(1) To determine whether regression of left ventricular hypertrophy (LVH) leads to a reduction in wall stress induced arrhythmia. (2) To determine the relationship between the time course of LVH regression and changes in arrhythmias in the spontaneously hypertensive rat heart.


METHODS
67 male spontaneously hypertensive rats (SHR) and 67 normotensive Wistar Kyoto rats (WKY) rats were studied at 100 days of age. 39 of each were treated with the ACE inhibitor captopril 2 mg/ml in drinking water, and the remaining 28 were controls. At 0, 2, 4, 8 and 16 weeks hearts were removed and perfused in the working heart mode. Control afterload was 80 mm Hg and perfusate K+ was 2.4 mM. Step increases in afterload (20, 40 and 80 mm Hg rises; 20 s duration; 2 min between each) were applied in random order to increase ventricular wall stress and induce arrhythmias.


RESULTS
Total number of ventricular premature beats (VPBs) elicited by each afterload step were counted. The ratio of left ventricular weight to body weight in the SHR (an index of LVH) showed a rapid and marked decline with captopril treatment (2.65 +/- s.e.m. 0.07 mg/g after 2 weeks treatment compared to 3.38 +/- 0.08 before treatment; P < 0.01), indicating that captopril produced rapid regression of LVH. In contrast, the number of wall stress-induced arrhythmias in SHR did not show a significant decline over the 16 week treatment period. However, when the effect of regression of LVH on wall thickness was taken into account, and compensation was made for differences in wall stress applied, there did appear to be a slow reduction in arrhythmias in SHR. This decline in VPBs was significant after 16 weeks treatment for 40 and 80 mm Hg rises in afterload (P < 0.05).


CONCLUSIONS
Treatment with captopril produced a rapid regression of LVH in the SHR. In contrast, arrhythmias declined more slowly over the 16 week period. There did not appear to be a direct relationship between the degree of regression of LVH and wall stress-induced arrhythmias in this model.
Dalton
G R
GR
Department of Physiology, School of Medical Sciences, University of Bristol, UK.
Jones
J V
JV
Evans
S J
SJ
Levi
A J
AJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D002216:Captopril / Q000627:therapeutic use*; D006321:Heart / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril