Cellular mechanism of the modulation of contractile function by coronary perfusion pressure in ferret hearts

Isovolumic left ventricular pressure was measured at various coronary arterial pressures in Langendorff-perfused ferret hearts. The concentrations of phosphorus-containing metabolites were measured using ³¹P nuclear magnetic resonance (NMR). Intracellular free calcium concentration ([Ca²⁺](i)), was measured with ¹⁹F NMR in a group of hearts that were loaded with the calcium indicator 5F-BAPTA. Developed pressure increased when coronary arterial pressure was raised from the control value of 80 to 100-160 mmHg and decreased when coronary pressure was lowered to 40-70 mmHg. The changes were reversible. Coronary flow varied directly with coronary pressure over the entire range from 40 to 160 mmHg. The concentrations of phosphorus-containing metabolites and the efflux of lactate from the heart remained unchanged at coronary pressures of 60 mmHg or higher. Below 60 mmHg, intracellular pH decreased, while inorganic phosphate concentration and lactate efflux increased. In contrast to the developed pressure during twitch contractions, maximal Ca²⁺-activated pressure remained constant at coronary pressures of 60-160 mmHg. Only below a coronary pressure of 60 mmHg did maximal Ca²⁺-activated pressure decline. An increase in coronary pressure produced an increase in developed pressure even in hearts stretched to the peak of the Frank-Starling relation. When coronary pressure was lowered from 80 to 60 mmHg, [Ca²⁺](i) decreased during systole; the opposite effect was apparent when coronary pressure was raised from 80 to 120 mmHg. We conclude that coronary perfusion (pressure or flow) modulates intracellular calcium and, consequently, contractile force. Ischaemia cannot fully explain this phenomenon, nor can changes in sarcomere length.