Superoxide dismutase (SOD) and catalase (CAT), enzymes that degrade superoxide anion and hydrogen peroxide, respectively, reduce size of infarction in anesthetized, open-chest dogs subjected to coronary occlusion followed by reperfusion. To evaluate potential protective effects of these enzymes in conscious animals, three groups of dogs were instrumented at sterile surgery with a hydraulic occluder on the left circumflex (LCX) coronary artery, sonomicrometers to measure regional wall thickness, and catheters to monitor arterial and left ventricular pressures. Ten to 14 days after surgery, the animals were sedated with morphine sulfate (0.5 mg/kg). The LCX artery was occluded for 3 hr by inflation of the hydraulic cuff. Infusions of SOD (n = 7), CAT (n = 6), or saline (control group, n = 7) were begun 15 min before reperfusion and lasted for 45 min of reperfusion. The doses of SOD and CAT were 5 mg/kg, dissolved in 60 ml of saline, and infused at a rate of 1 ml/min. Myocardial blood flow was measured with tracer-labeled microspheres (15 gm diameter) before occlusion, after 5 to 10 min of occlusion, after 150 min of occlusion, and 5 to 10 min after reperfusion. Size of infarction was measured 24 hr later by dual-perfusion staining with Evans blue and triphenyl tetrazolium. Size of infarction (expressed as a percentage of area at risk) did not differ significantly among the three groups: control, 32 + 17% (mean ± SD); SOD, 38 + 17%; CAT, 27+ 17%. Hemodynamic parameters and myocardial blood flows (measured before infusion of any agents) were not significantly different among the three groups. Serum SOD levels in SOD-treated dogs were 19 ± 2 gg/ml at the onset of reperfusion and 29 ± 3 gg/ml at the end of the infusion. Blood assays collected after infusion showed a monoexponential decay of SOD levels with a half-life of 22 ± 6 min. We conclude that myocardial protection by SOD or CAT is model dependent. In conscious dogs subjected to 3 hr of coronary occlusion followed by reperfusion, SOD and CAT failed to alter size of infarction.

Previous 2DE studies have suggested that left ventricular wall thickening determinants of regional left ventricular function may be more precise than left ventricular wall motion parameters in the assessment of myocardial ischemia and infarction. To study the relationship between regional wall motion and regional wall thickening abnormalities relative to myocardial ischemia, we performed 2DE in 27 dogs at baseline and following 1 hour of circumflex coronary occlusion. A 2DE circumferential map of regional wall motion and regional wall thickening was generated at 22.5-degree intervals over 360 degrees using a fixed centroid. With the use of three consecutive beats, 95% normal tolerance levels were derived for each individual left ventricular function map. The circumferential extent of left ventricular dysfunction was measured at the curve intercepts of the occluded and normal maps. The left ventricular ischemic area at risk for the corresponding 2DE slice was determined by technetium-99 autoradiography. Following coronary occlusion, left ventricular end-diastolic area increased (p less than 0.0005), left ventricular end-systolic area increased (p less than 0.0005), and left ventricular area ejection fraction decreased (50 +/- 2% to 30 +/- 2%, p less than 0.0005). The circumferential extent of regional wall motion overestimated the area at risk by 77% (226 +/- 11 degrees vs 128 +/- 7 degrees, p less than 0.0005), whereas the circumferential extent of regional wall thickening corresponded to the area at risk (147 +/- 9 degrees vs 128 +/- 7 degrees, p = NS). In addition, the circumferential extent of regional wall motion overestimated regional wall thickening by 54% (p less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Immediate percutaneous transluminal coronary angioplasty has been advocated for patients with a residual stenosis after coronary thrombolysis because of the possibility that the residual stenosis may restrict reflow and thereby increase infarct size. Because there are few experimental data bearing on this issue, we measured left ventricular function, myocardial blood flow, and infarct size in 20 anesthetized open-chest dogs during 2 hr of left circumflex occlusion and 4 hr of reperfusion. Ten animals were reperfused through a critical stenosis of the left circumflex artery (critical stenosis group) and the remaining 10 animals underwent full reperfusion without stenosis (control group). In both groups, a comparable degree of echocardiographic systolic wall thinning was present during occlusion and partial recovery of global and regional left ventricular function was seen after reperfusion. There were no significant differences in global or regional left ventricular function in the two groups. Subendocardial blood flow was decreased in the critical stenosis group relative to the control group at 5 min after reperfusion (0.52 + 0.16 ml/min/g in the critical stenosis group vs 1.55 + 0.32 ml/min/g in the control group, p < .05) but not at 4 hr after reperfusion, when a reduced reflow response was seen in both groups. No differences in subepicardial blood flow were seen in the two groups of animals. Infarct size was slightly greater in the critical stenosis group than the control group, but this difference was not statistically significant (infarct/risk area ratio: 55.5 + 7.8% in the critical stenosis group vs 39.4 + 9.7% in the control group, p = .21). A close inverse exponential relationship was seen between infarct size/risk area ratio and subendocardial blood flow during occlusion (r = .89, p = .001). Two control animals had high levels of subendocardial collateral flow (> 0.2 ml/min/g); when these animals were excluded from analysis, differences in the infarct size/risk area ratio in the control and critical stenosis groups were less striking: (55.5 + 7.8% in the critical stenosis group vs 48.4 + 9.6% in the control group). Thus, the presence of a critical stenosis results in restriction of hyperemic blood flow to the subendocardium after reperfusion but does not

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The immediate and early effects of coronary artery reperfusion initiated 1 and 3 hours after coronary artery occlusion were evaluated by two-dimensional echocardiographic measurements of overall and regional left ventricular function. A total of 29 anesthetized open chest dogs underwent one of the following: 1 hour occlusion followed by reperfusion (Group I, n = 9), 3 hour occlusion followed by reperfusion (Group II, n = 12) or 5 hour occlusion without reperfusion (Group III, n = 8). Serial two-dimensional echocardiography was performed at baseline; at 1, 3 and 5 hours of coronary occlusion; within 5 minutes of reperfusion; and at 2 hours of reperfusion. After occlusion, all groups manifested significant (p less than 0.01) increases in left ventricular diastolic and systolic area and decreases in left ventricular area ejection fraction. With coronary reperfusion, there was no improvement in these global variables in Groups I and II. However, immediately after reperfusion, there was improvement in the regional extent of dysfunction (Group I, 138 +/- 35 to 66 +/- 62 degrees, p less than 0.05; Group II, 156 +/- 51 to 85 +/- 77 degrees, p less than 0.05) as well as improvement in the regional degree of dyskinesia (p less than 0.05). These regional improvements were transient and resolved by 2 hours of coronary reperfusion. This immediate rebound of function was not associated with the duration of coronary occlusion, hemodynamic variables or ultimate infarct size. Thus, in the anesthetized open chest dog model, coronary artery reperfusion at 1 or 3 hours produces an immediate but transient improvement in regional systolic myocardial function.