Inorganic phosphate and coronary perfusion pressure mediate contractile dysfunction during mild ischemia

During mild graded ischemia in perfused rat hearts, we (V. M. Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 1794-1802, 1992) previously found a relationship between decreased left ventricular developed pressure (LVDP) and increased P(i), in which intracellular pH, cytosolic Ca²⁺ concentration ([Ca²⁺]i), ATP, and free- energy change of ATP hydrolysis were not altered enough to affect contractility. However, the contribution of decreased coronary perfusion pressure (CPP) to decreased LVDP could not be determined. Thus, in the present study, graded hypoxia in perfused rat hearts (95-37.5% O₂) was used to increase P(i) to similar levels produced during mild ischemia without altering CPP and minimizing changes of other potential mediators of contractile dysfunction. ³¹P-magnetic resonance spectroscopy and indo 1 fluorescence were used to assess energy metabolites and [Ca²⁺]i, respectively. The relationship between LVDP and P(i) during graded hypoxia was fit to a monoexponential (LVDP = 105 X e(-0.04Pi)). These data were compared with the relationship of LVDP and P(i) during mild ischemia (LVDP = 106 x e(-0.08Pi)) (V. M. Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 17941802, 1992). The exponential constant, which describes the effect of P(i) on LVDP, was 50% lower during graded hypoxia relative to mild ischemia. This suggests that another mediator, which accounted for ~50% of the decrease of LVDP during mild ischemia, was not present during hypoxia. Because CPP decreased during ischemia but not hypoxia, these data suggest that CPP and P(i) contribute similarly in mediating contractile dysfunction during mild ischemia.