INTEGRATION OF VASCULAR, CONTRACTILE, AND METABOLIC RESPONSES TO HYPOXIA - EFFECTS OF MATURATION AND ADENOSINE

We examined myocardial responses to reduced arterial PO2 and the role of endogenous adenosine in constant-pressure perfused hearts from imma ture (Imm) and mature (Mat) rabbits. During normoxia, coronary flow an d myocardial O-2 consumption were similar in both groups. With moderat e hypoxia, coronary perfusate flow increased by 125 +/- 16% in Imm but by only 68 +/- 12% in Mat hearts. Imm hearts displayed better mainten ance of contractile function (87 vs. 67% in Mat hearts) and metabolic state. Blockade of cardiac adenosine receptors with 25 mu M 8-p-sulfop henyltheophylline attenuated vasodilation during hypoxia, reduced cont ractile function, and abolished age-related differences in one respons e to hypoxia. Myocardial purine release and extracellular purine level s were threefold higher in Mat compared with Imm hearts and was associ ated with higher cytosolic 5'-AMP concentration (and lower [ATP]/[ADP] .[P-i], where [ATP], [ADP], and [P-i] are concentrations of ATP, ADP, and P-i, respectively) in Mat hearts. In summary, I) Imm hearts are fu nctionally and metabolically more tolerant of hypoxic perfusion, large ly because of improved hypoxia-induced coronary vasodilation; 2) endog enous adenosine mediates this beneficial vasodilation, enhancing hypox ic tolerance; and 3) improved vascular sensitivity to adenosine allows for enhanced vasodilatory responses in the face of lower adenosine le vels and higher energy state in immature hearts.