RESPONSES OF MYOCARDIAL HIGH-ENERGY PHOSPHATES AND WALL THICKENING TOPROLONGED REGIONAL HYPOPERFUSION INDUCED BY SUBTOTAL CORONARY STENOSIS

The response of the myocardium to prolonged or chronic ischemia may di ffer from the well documented changes that occur acutely subsequent to the onset of hypoperfusion. Therefore, we have examined in an instrum ented canine model and using spatially localized spectroscopy to achie ve transmural differentiation, the myocardial HEP and P(i) levels as w ell as wall thickening in situ during prolonged ischemia induced by su stained coronary artery stenosis. The results demonstrate that subtota l coronary artery occlusion causes immediate and transmurally inhomoge neous decreases in the myocardial HEP content and increase in the P(i) /CP ratio; however, during prolonged mild hypoperfusion, metabolic cha nges occur which lead to statistically significant recovery of CP (but not ATP) and disappearance of P(i) despite the persistence of reduced blood flow and oxygen supply. Upon release of the occlusion, the prev iously ischemic muscle recovered blood flow, and some (but not all) of its preischemic contractile function without parallel changes in the HEP levels. It is concluded that normal HEP and P(i) levels cannot be equated with either the absence of underperfusion or insensitivity of NMR spectroscopy to ischemia. Rather, it is imperative that both funct ional and spectroscopic measurements are performed simultaneously to d istinguish between ischemic myocardium which is adapted versus unadapt ed to the hypoperfusion.