EFFECT OF HEART-RATE REDUCTION BY NYLAMINO)-1,2-DIMETHYL-6-(METHYLAMINO)PYRIMIDINIUM CHLORIDE ON INFARCT SIZE IN DOG

Heart rate (HR) reduction may reduce the severity of myocardial ischem ia. ZD7288 nylamino)-1,2-dimethyl-6-(methylamino)pyrimidinium chloride ) is a novel bradycardic agent with a specific effect on the sinoatria l node without having any other direct effects on the heart. In the pr esent study, the effect of ZD7288 on infarct size and regional myocard ial function during regional myocardial ischemia and reperfusion was i nvestigated. Seventeen anesthetized open chest dogs (control, n = 8, a nd ZD7288, n = 9) underwent I h of left anterior descendent artery (LA D) occlusion followed by 6 h of reperfusion. In one group, ZD7288 was given intravenously (0.7 mg/kg body weight) 45 min before LAD occlusio n. Regional myocardial function was assessed by sonomicrometry as syst olic wall thickening fraction (sWTF) in the anteroapical (interest reg ion, IR) and the posterobasal wall (control region, CR). Ischemic regi onal myocardial blood flow (RMBF) was determined by colored microspher es and infarct size (IS) by triphenyltetrazolium staining. ZD7288 inje ction decreased HR from 104 +/- 5 to 74 +/- 3 bpm (mean +/- SEM, p < 0 .001 vs control, vs baseline), but did not change sWTF. During reperfu sion, sWTF of the TR was significantly greater in the ZD7288 group (26 +/- 12 vs -14 +/- 13 %, 1 h reperfusion, p < 0.05), while sWTF of CR stayed equal (120 +/- 13 vs 111 +/- 16 %, p = ns. IS was markedly redu ced in the ZD7288 group (4.7 +/- 1.8 vs 18.0 +/- 5.2 % of LR, p < 0.05 ). There was no difference in ischemic endocardial RMBF (ZD7288 11.0 /- 4.3 vs control 12.3 +/- 6.5 ml/min/100 g, p = ns). ZD7288 reduces H R without having direct effects on regional myocardial function. This HR reduction leads to a smaller IS and to a better regional functional recovery.