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Attenuation of the Negative Inotropic Effects of Metoprolol at Short Cycle Lengths in Humans

Comparison With Sotalol and Verapamil

Rebecca H. Ritchie, BSc(Hons), PhD^_*,,1, Christopher J. Zeitz, MBBS, PhD, FRACP^_*,2, Ronald D. Wuttke, BSc^_*, John T.Y. Hii, BMBS, FRACP^_* and John D. Horowitz, MBBS, PhD, FRACP^_*,_*

^_* Cardiology Unit, The Queen Elizabeth Hospital, University of Adelaide, Adelaide, Australia
Baker Heart Research Institute, Melbourne, Australia.

View larger version (13K): [in a new window]   Figure 1 A theoretical mechanical restitution curve (MRC): a (units are percent baseline LV+dP/dtmax) and d (units are percent baseline R-R interval) represent the horizontal and vertical asymptotes, respectively; the parameter c (units are percent baseline LV+dP/dtmax) represents the reduction in LV+dP/dtmax with a 40% reduction in R-R interval (13). LV+dP/dtmax = maximal rate of increase of left ventricular pressures.

View larger version (19K): [in a new window]   Figure 2 Time course of changes in LV+dP/dtmax (percent baseline) induced by metoprolol, sotalol, or verapamil during baseline pacing before (open bars), 5 min after (hatched bars), and 10 min after (solid bars) injection. Asterisks indicate statistical significance compared with baseline (analysis of variance with repeated measures). Abbreviations as in Figure 1.

View larger version (18K): [in a new window]   Figure 3 Mechanical restitution curve (MRC) curve-fitting analysis for (A) metoprolol, (B) sotalol, and (C) verapamil. The left-hand panel shows representative raw and fitted data obtained from one patient in each group, before (closed circles, solid curve) and 10 min after (open circles, dashed curve) drug administration. The right-hand panel shows mean data from the fitted MRC before (closed circles) and after (open circles) drug administration. Abbreviations as in Figure 1.

View larger version (17K): [in a new window]   Figure 4 Time course of changes in the parameter c from mechanical restitution curve (MRC) curve-fitting analysis (the decrease in LV+dP/dtmax with a 40% reduction in R-R interval from the fitted MRC model) for each of (A) metoprolol, (B) sotalol, and (C) verapamil. Asterisks indicate statistical significance compared with baseline (analysis of variance with repeated measures). (D) The increment in parameter c after drug treatment. Verapamil induces a significantly different response to metoprolol (analysis of variance). Abbreviations as in Figure 1.

View larger version (16K): [in a new window]   Figure 5 Influence of negatively inotropic agents on frequency potentiation for each of (A) metoprolol, (B) sotalol, and (C) verapamil. Time course of LV+dP/dtmax during rapid pacing before (closed circles) and after (open circles) drug injection. Results are expressed as a percent of LV+dP/dtmax observed immediately before the onset of rapid pacing. (D) The relative frequency potentiation (FP) response after drug treatment (the increase in LV+dP/dtmax after 10-s rapid pacing, observed 10 min after treatment as a ratio of the response observed previously). Both sotalol and verapamil (but not metoprolol) significantly attenuated the frequency potentiation response (analysis of variance). Abbreviations as in Figure 1.