Myocardial oxygen tension determines the degree and pressure range of coronary autoregulation

Abstract

Experiments were designed to separate effects of myocardial oxygen tension and oxygen consumption on coronary autoregulation. The approach was to measure coronary hemodynamic and metabolic responses to decreases in perfusion pressure during interventions that altered the balance between myocardial oxygen supply and demand. Studies were conducted in anesthetized heart-blocked dogs with the left coronary artery perfused from a pressure-controlled blood reservoir. Decreasing oxygen consumption by lowering heart rate from 120 to 40 bpm increased coronary venous oxygen tension and reduced the degree of flow autoregulation between 120 and 80 mm Hg by threefold. In contrast to effects of bradycardia, coronary constriction with vasopressin or indomethacin (heart rate 120 bpm), which produced comparable increases in baseline vascular resistance, decreased coronary venous oxygen tension, and augmented flow autoregulation by nearly twofold. Initial coronary venous oxygen tension but not oxygen consumption was strongly correlated with a quantitative index of autoregulation (-0.052 PO2 + 2.01, R2 = 0.86) over the pressure range of 120 to 80 mm Hg. When heart rate was lowered to 40 bpm and coronary venous oxygen tension subsequently reduced with vasopressin to control values (120 bpm), autoregulation was completely restored. Parallel studies examined the effects of metabolic and pharmacologic interventions on coronary pressure-flow relations over a wide range of pressures. For each 20 mm Hg decrement in pressure between 160 and 80 mm Hg, lowering heart rate attenuated autoregulation whereas pharmacologic coronary constriction augmented autoregulation. The observed variations in the autoregulation index were largely explained by differences in the prevailing venous oxygen tension. Furthermore, the upper pressure limit for autoregulation was dependent on venous oxygen tension with a threshold oxygen tension for autoregulation of 32 mm Hg. These results indicate that coronary autoregulation is closely coupled to the prevailing venous oxygen tension but not oxygen consumption and is facilitated at low venous oxygen tension.