Enhanced coronary flow following experimental androgen deprivation by orchidectomy

ABSTRACT

Androgen deprivation is an effective treatment for patients with advanced prostate cancer. The present work was conducted to study the impact of testosterone deprivation on cardiac functions and coronary flow. Experimental androgen deprivation was induced in rats by orchidectomy, compared to sham-operated controls. Two weeks after operation, rats were subjected to measurements of body weight, plasma testosterone and ECG recording. Cardiac functions were studied on isolated perfused hearts in a Langendorff preparation, under basal conditions and following exposure to 30 minutes of global ischemia followed by another 30 minutes of reperfusion. The following parameters were assessed heart rate [HR], peak tension [PT], time to peak tension [TPT], half relaxation time [HRT], and myocardial flow rate [MFR]. Absolute weights of different cardiac chambers and their relative weights were also determined. The orchidectoimzed [ORX] rats exhibited non significant changes in ECG parameters, significant increase in absolute weights of whole heart and left ventricle, associated with significant body weight gain. Hearts isolated from ORX rats displayed a significant increase in basal preischemic MFR compared to their matching controls. Upon isehemia reperfusion [I/R], MFR of hearts isolated from ORX rats was still higher compared to controls, After 30 minutes of reperfusion, hearts of control rats displayed non significant change in HR associated with significant decrease in MFR as compared to preisehemie values; while in hearts of ORX rats, HR was significantly decreased, and accompanied with non significant changes in MFR. The augmented MFR in response to I/R, in ORX rats,, was however associated with significant increase in TPT and HRT, indicating impaired ventricular contractility and delayed relaxation, respectively when compared to controls. Upon I/R, PT was preserved in ORX group, while it was deteriorated in the controls, as compared to the preischemia values. Expenmental androgen deprivation induced marked increase in coronary flow, possibly due to lack of the predominant vasoconstrietor effect of testosterone hormone