Effect of chronic colchicine administration on the myocardium of the aging spontaneously hypertensive rat

Colchicine has been demonstrated to suppress the release of fibroblast growth factors, retard collagen formation and augment collagenase activity. Trials with colchicine in patients with hepatic fibrosis have suggested clinical benefit. The development of impaired myocardial function in the spontaneously hypertensive rat (SHR) is associated with a marked increase in myocardial fibrosis. The present study was carried out to test the hypothesis that chronic colchicine administration to the SHR would prevent the development of fibrosis and impaired myocardial performance. Colchicine (1 mg/l drinking water) was administered to male SHR and WKY rats from at age 13 months until 24 months or until evidence of heart failure was observed. Age-matched untreated SHR and colchicine treated and untreated WKY served as controls. At study, active and passive properties of isolated left ventricular muscle preparations were determined. Myocardial fibrosis was assessed by measuring hydroxyproline and histologic determination of interstitial cross-sectional area. Increases in LV hydroxyproline and interstitial area were found in untreated SHR relative to WKY; passive myocardial stiffness was increased and active muscle properties were depressed. In comparing colchicine treated vs untreated SHR, no differences in hydroxyproline, interstitial area or intrinsic myocardial function were found. In the WKY, colchicine increased myocardial interstitium and passive stiffness without changing hydroxyproline. Active myocardial function was not depressed. Thus, chronic colchicine administration neither attenuated the development of interstitial fibrosis nor prevented impaired myocardial function in the SHR. Colchicine treatment was associated with increased interstitium in WKY with increased passive myocardial stiffness.