Cardiovascular profile of the calcium sensitizer EMD 57033 in open‐chest anaesthetized pigs with regionally stunned myocardium

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Abstract
Ca2+ sensitizers enhance systolic function, but may impair relaxation in vitro; these effects may differ in stunned and normal myocardium. We therefore studied the effect of EMD 57033 on systolic and diastolic function of normal and stunned porcine myocardium in vivo. Myocardial stunning by 15 min coronary occlusion and 30 min reperfusion abolished systolic shortening (SS) (baseline 13±1%) and decreased end‐systolic elastance (Ees) from 67±7 to 47±5 mmHg mm−1 (both Pmin) decreased from −850±100 to −320±30 mmHg mm−1 s−1, while the time constant τe of the decay of elastance increased from 58±3 to 68±6 ms (both Ped) was unchanged although the zero pressure intercept (L0,ed) had increased. In the stunned region, EMD 57033 (0.2 mg kg−1 min−1 for 60 min, i.v., n=7) increased SS to 19±2%, Ees to 287±40 mmHg mm−1, dE/dtmin to −3630±640 mmHg mm−1 s−1 and decreased τe to 50±3 ms, while Eed remained unchanged. In the normal region, EMD 57033 increased SS from 14±2 to 18±3%, Ees from 59±4 to 263±23 mmHg mm−1, dE/dtmin from −480±70 to −2280±700 mmHg mm−1 s−1 and decreased τe from 91±12 to 61±3 ms (all Ped remained unchanged. These responses were minimally affected by adrenoceptor blockade (n=7). Vehicle (n=7) had no effect on either region. EMD 57033 increased cardiac output (up to 27±8%) and LVdP/dtmax (86±19%). Mean aortic pressure decreased (19±7%) due to systemic vasodilation that was not amenable to blockade of adrenoceptors or NO synthesis. In conclusion, EMD 57033 restored systolic and diastolic function of stunned myocardium, and produced similar improvements in systolic and diastolic function in normal myocardium. British Journal of Pharmacology (2000) 129, 1413–1422; doi:10.1038/sj.bjp.0703231

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