CLENTIAZEM AND DILTIAZEM PRESERVE ENDOTHELIUM-DEPENDENT RELAXATION FOLLOWING GLOBAL RAT-HEART ISCHEMIA

OBJECTIVE: To evaluate the effects of the calcium channel blockers dil tiazem and its chloride derivative clentiazem on coronary vasoregulati on of isolated rat hearts exposed to ischemia-reperfusion. Diltiazem h as been reported to prevent postreperfusion myocardial damage but its beneficial effects on coronary blood-flow regulation remain uncertain. METHODS: Two groups of hearts were pretreated with a 10 min infusion of either diltiazem (10(-9) and 10(-6) mol/L) or clentiazem (10(-9) to 10(-7) mol/L) (n=6 for each concentration) and exposed to 30 mins of no-flow ischemia. Another group (n=6) received no pretreatment and was used as control. Endothelium-dependent and -independent relaxation we re tested by assessing coronary flow increase to 5-hydroxytriptamine ( 10(-6) mol/L) and sodium nitroprusside (10(-5) mol/L) infusions, respe ctively, and were assessed before and after ischemia-reperfusion. Left ventricular pressure, dP/dt and coronary basal flow were also recorde d. Postreperfusion results are expressed as a percentage of pre-ischem ic value. Dunnet variance analysis was used to compare means of pretre ated groups with the control group. RESULTS: Endothelium-dependent rel axation was significantly improved with both drugs. Optimal preservati on was obtained with diltiazem 10(-6) mol/L (66+/-4%) and clentiazem 1 0(-7) mol/L (83+/-4%), whereas endothelial response was almost abolish ed in control hearts (6+/-11%), P<0.01). Clentiazem was found to be mo re potent than diltiazem at low concentration 10(-9) mol/L, clentiazem 89+/-13% versus diltiazem 3+/-16%, P<0.05). Optimal endothelium-indep endent relaxation preservation was achieved at 10(-8) mol/L in both gr oups (diltiazem 86+/-4%, clentiazem 82+/-8%, control 47+/-10%, P<0.05) . Left ventricular pressure and dP/dt were not affected by any pretrea tment. However, postreperfusion coronary basal flow was significantly increased in control hearts. CONCLUSION: This study indicates that pre -ischemic infusion of diltiazem and clentiazem enhances endothelium-de pendent and -independent coronary artery relaxation following reperfus ion in the isolated rat heart model, without affecting ventricular hem odynamics, and contributes to preservation of coronary artery autoregu lation.