Functional and metabolic responses of the isolated rat heart to changes in circulating inorganic phosphate concentration.

Abstract

Normoxic isolated rat hearts were perfused for 30 or 60 min with Krebs-Henseleit bicarbonate buffer (KHB) (in which the Pi concentration was adjusted to 0, 1.2, 2.4, or 10 mM) in both the presence and the absence of glucose as exogenous substrate. Functional performance and coronary flow were monitored throughout the perfusion period, and at its conclusion tissue high-energy phosphates (HEP), glycogen, Pi, and calcium were determined. In the presence of glucose, both developed pressure and coronary flow were significantly (P less than 0.05) reduced by perfusion with 10 mM Pi, while heart rate and energy status were unchanged. Tissue Pi levels were directly related to perfusate concentrations, with an apparent loss of 34% from hearts perfused with 0 mM Pi and a gain of 27% in hearts perfused with 10 mM Pi (which also caused a highly significant [P less than 0.01] uptake of calcium). HEP (ATP and creatine phosphate [CP]) were decreased after 60 min of perfusion with 0 mM Pi. In the absence of glucose, coronary flow was again significantly reduced by perfusion with 10 mM Pi. HEP were significantly (P less than 0.05) conserved and uptake of Pi and calcium was greater than in the presence of glucose. Equivalent free-Ca2+/normal Pi controls for the 10 mM Pi showed that the observed functional effects were not due to a lowering of perfusate free-Ca2+ by the raised Pi level. The effect on coronary flow appears to involve, primarily, a vasomotor mechanism.