Flow-Limited Ischemia on Left Ventricular Function

We compared left ventricular (LV) myocardial blood flow and function accompanying severe demand ischemia (rapid atrial pacing in the presence of critical bilateral coronary stenoses) and supply ischemia (complete bilateral coronary occlusion) of the same ischemic regions in 14 pentobarbital-anesthetized dogs. Pacing-induced ischemia resulted in pronounced reductions in average regional epicardial blood flow (0.8±0.4 vs. control 1.2±0.4 [±SD] ml/g/min, p<0.05) and endocardial blood flow (0.4±0.1 vs. control 1.3+±0.3 ml/g/min, p<0.05). More severe reductions in average regional epicardial and endocardial blood flow were seen after bilateral coronary occlusion (BCO) (0.3+±0.3 and 0.1± 0.1 vs. control 1.3 ±0.3 ml/g/min,p <0.05, respectively). Hemodynamics of postpacing ischemia (PPi) were consistently characterized by systolic impairment including depressed systolic contractile performance [(+)dP/dtmax 1,281±442 vs. control 2,173+±775 mm Hg/sec, p<0.05], ventricular dilation (left ventricular [LV] end-diastolic dimension [EDDI 47.6±7.8 vs. control 44.7±8.6 mm, p<0.05), and an increase in LV end-diastolic pressure (EDP) (14.4+2.8 vs. control 4.2±2.8 mm Hg, p<0.05). Abnormalities in early and late diastolic function with PPi included increased time constant of isovolumic relaxation (78.0+40.4 vs. control 46.4±20.5 msec, p <0.05) and increased chamber stiffness (1.9±+0.77 vs. control 0.81±0.55 mm Hg/mm, p<0.05), respectively. The LV diastolic pressure-dimension relation, however, shifted upward and to the right in eight of nine animals, whereas an upward shift was observed in only one animal. Thus, in this model of postpacing ischemia, we observed contractile failure and passive changes in diastolic function. Alterations in ventricular function occurred consistently earlier and to a greater extent during BCO than PPi, including higher LVEDP (25.3+8.1 vs. 14.9±6.6 mm Hg, p<0.05), greater ventricular dilation (ALVEDD 4.9±2.5 vs. 3.5±2.8 mm, p<0.05), and reduced minor-axis dimension shortening (3.3±3.1% vs. 6.5+±3.6%, p<0.05). To detect potential qualitative differences in ventricular function between the two types of ischemia, we evaluated hemodynamics at comparable loading conditions (30 seconds to 1 minute of BCO). Impairment in systolic function was similar, and abnormalities in early and late diastolic function were qualitatively similar with PPi and the early phase of BCO, including equivalent prolongation of the time constant of isovolumic relaxation (78.0±40.4 and 72.2±30.6 msec, p=NS), elevation in minimal LV diastolic pressure (5.6+4.4 and 4.6±2.6 mm Hg, p=NS), and shifts in the LV diastolic pressure-dimension relation. Thus, although bilateral coronary occlusion produced quantitatively more extensive ischemia than a comparable duration of pacing-induced ischemia, abnormalities in systolic and diastolic function were qualitatively similar during a severe form of demand ischemia. Therefore, the ventricular response to ischemia does not simply depend on whether supply or demand ischemia is present but on a complex interaction between the duration, extent and severity, and type of ischemia elicited. (Circulation 1990;81:1380-1392)