RELATION BETWEEN ACUTE MYOCARDIAL UPTAKE AND HEMODYNAMIC AND ELECTROCARDIOGRAPHIC EFFECTS OF METOPROLOL IN HUMANS

We studied myocardial disposition of meteprolol after a 4-mg intraveno us (i.v.) bolus in 12 patients undergoing cardiac catheterization for investigation of chest pain, using a paired transcoronary sampling tec hnique with simultaneous determination of coronary sinus blood flow (C SF). Myocardial metoprolol content (MMC) was then correlated with conc omitant effects on hemodynamic and ECG parameters. Peak myocardial met eprolol content (1.89+/-0.40% of injected dose) was attained rapidly ( 2.67+/-0.38 min), but time to peak content was significantly delayed i n the presence of extensive coronary artery disease. Residual MMC 17.5 min after injection was 49.1+/-8.7% of maximal MMC. Extent of coronar y artery disease or variability in left ventricular (LV) systolic func tion did not influence peak MMC. Metoprolol induced slowing of spontan eous heart rate (HR, p<0.05), reduction in LV +dP/dt (p<0.0005), and p rolongation of PR intervals (p<0.05) with maximal changes 5-10 min aft er injection. Thus, time of peak hemodynamic effects of metoprolol was consistently delayed relative to time of peak MMC. We conclude that a fter i.v. injection, myocardial metoprolol accumulation in humans is r apid, with marked hysteresis between peak MMC and subsequent hemodynam ic effects.