Comparative cardioprotective effects of cromakalim and diltiazem in ischemic hypertrophied and non-hypertrophied rat hearts. Grover, Gary J., Steven Dzwonczyk, and Thomas M. Monticello. Departments of Pharmacology and Experimental Pathology, Bristol -Myers Squibb Pharmaceutical Research Institute, Princeton, N.J. 08543-4000
APStracts 2:0324H, 1995.
Previous studies have indicated that alterations in cardiac ATP -sensitive potassium channels (KATP) can occur with cardiac hypertrophy. The goal of this study was to determine the effect of cardiac hypertrophy in spontaneously hypertensive rats (SHR) on the response to the cardioprotective agents diltiazem and cromakalim. Isolated rat hearts from 14 week old SHR, normotensive heterozygote (WKY), and Sprague-Dawley (S-D) strains were subjected to 25 min global ischemia and 30 min reperfusion in the presence of vehicle, 3 -30 [mu]M cromakalim, or 0.1-1.0 [mu]M diltiazem. SHR animals had heart weight/body weight ratios 40-50% greater than age matched S-D or WKY rats. Both diltiazem and cromakalim increased reperfusion contractile function in a concentration-dependent manner in S-D rats as previously reported. Cromakalim and diltiazem caused similar improvements in reperfusion function in WKY rats and SHR. Cumulative LDH release during reperfusion was similar for vehicle-treated S-D, WKY or SHR hearts. LDH release was significantly attenuated by cromakalim and diltiazem at all concentrations tested in S-D and WKY hearts, whereas LDH release was not attenuated in SHR hearts by any concentration of cromakalim or diltiazem tested. Morphologic assessment of hearts by light microscopy indicated that the severity and distribution of myocardial lesions were not affected by cromakalim in SHR hearts, as compared to vehicle-treated SHR, supporting the LDH data. These results suggest that in SHR hearts, cromakalim and dilitiazan may exert much of their cardioprotective effects on the population of myocytes that are not irreversibly damaged. 

Received 12 December 1994; accepted in final form 27 June 1995.
APS Manuscript Number H1090-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 August 1995.