Beneficial effects of the Ca2+ sensitizer EMD 57033 in exercising pigs with infarction‐induced chronic left ventricular dysfunction

It is unknown how cardiac stimulation by Ca2+ sensitization modulates the cardiovascular response to exercise when left ventricular (LV) function is chronically depressed following a myocardial infarction. We therefore investigated the effects of EMD 57033 at rest and during exercise and compared these to those of the mixed Ca2+‐sensitizer/phosphodiesterase‐III inhibitor pimobendan. Pigs were chronically instrumented for measurement of cardiovascular performance. At the time of instrumentation, infarction was produced by coronary artery ligation (MI, n=12). Studies in MI were performed in the awake state, 2 – 3 weeks after infarction. MI were characterized by a lower resting cardiac output (18%), stroke volume (30%) and LVdP/dtmax (18%), and a doubling of LV end‐diastolic pressure, compared to normal pigs (N, n=13). In 11 resting MI, intravenous EMD 57033 (0.2 – 0.8 mg kg−1 min−1) increased LVdP/dtmax (57±5%) and stroke volume (26±6%) with no effect on heart rate, LV filling pressure, and myocardial O2‐consumption, similar to N. In MI, the effects of EMD 57033 (0.4 mg kg−1 min−1, IV) on stroke volume and LVdP/dtmax were maintained during treadmill exercise up to 85% of maximal heart rate, while heart rate was lower compared to control exercise (all P