Myocardial release of inosine, hypoxanthine and lactate during pacing-induced angina in humans with coronary artery disease.
The applicability of the adenosine triphosphate (ATP) catabolites, inosine and hypoxanthine as markers of myocardial ischemia in humans with coronary artery disease has been investigated. Inosine and hypoxanthine were assayed enzymatically after separation by a new column chromatographic method. The myocardial lactate extraction at rest (17 +/- 13%) changed to production values (-23 +/- 28%) during pacing-induced angina (P less than 0.0005). Coronary venous inosine values increased from 535 +/- 185 nmol/l at rest to 1030 +/- 740 nmol/l during angina (P less than 0.005), the arterial values amounted to 770 +/- 325 nmol/l and 805 +/- 515 nmol/l respectively (P, NS). The calculated myocardial uptake of inosine at rest (27 +/- 16%) changed to production values (-25 +/- 29%) during angina (P less than 0.0005). Coronary venous hypoxanthine increased from 1000 +/- 760 nmol/l at rest to 1235 +/- 800 nmol/l during angina (P, NS), the arterial values amounted to 1300 +/- 1040 nmol/l and 1235 +/- 800 nmol/l respectively (P, NS). The myocardial extraction changed from 20 +/- 18% at rest to -5.4 +/- 29% during angina (P less than 0.0025). The significant positive correlation (r = 0.61, P less than 0.0025) between myocardial release and uptake of inosine and lactate during severe angina demonstrates that anaerobic glycolysis is accompanied by ATP breakdown. During a second pacing period at less increased pressure--rate product after nitroglycerin, lactate production (-1.7 +/- 22%) already occurred whereas extraction of inosine (19 +/- 19%) and hypoxanthine (24 +/- 15%) did not change. In conclusion, lactate functions as a sensitive marker of myocardial ischemia and inosine is useful in detecting ischemic myocardial energy deficiency by the indication of insufficient glycolytic ATP supply.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000787:Angina Pectoris / Q000097:blood / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D002845:Chromatography / Q000379:methods; D003327:Coronary Disease / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007042:Hypoxanthines / Q000097:blood*; D007288:Inosine / Q000097:blood*; D007773:Lactates / Q000097:blood*; D009206:Myocardium / Q000378:metabolism*
D007042:Hypoxanthines; D007773:Lactates; D007288:Inosine; D000255:Adenosine Triphosphate