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The lateral borders of an infarcted area are sharply delineated in terms of perfusion, but functional impairment extends a limited distance into adjacent nonischemic myocardium. To determine the distribution of functional impairment we arrayed three ultrasonic dimension gauges to measure two subendocardial segment lengths in series. The center crystal, placed at the perfusion boundary (PB) between left anterior descending and circumflex arteries, radiated ultrasound to receiver crystals 7-17 mm to either side of the PB. The locations of the functional measurements relative to the PB were determined with myocardial blood flow (microsphere) "maps" constructed from multiple small tissue samples obtained circumferentially. On the nonischemic side of the PB, segment shortening (dL) increased from 2.00 +/- 0.37 mm during control conditions to 2.20 +/- 0.43 mm (P less than 0.05) after left circumflex coronary occlusion. Similar results were obtained in four conscious chronically instrumented dogs, supporting the conclusion that segment function adjacent to the ischemic margin is well preserved after coronary occlusion. On the ischemic side of the PB, dL decreased from 2.24 +/- 0.54 to 0.42 +/- 0.39 mm (P less than 0.01). By adding the data from the two segments in series, a combined measurement of dL across heterogeneously perfused myocardium was derived that decreased by 38% from control. The level of shortening represented an integral of normal and abnormal motion that was proportional to the mean reduction in blood flow (-44%) in all of the muscle spanned by the crystals. We conclude that subendocardial segment lengths "average" shortening in the muscle they subtend when arrayed across the perfusion boundary.

To evaluate the degree and lateral extent of dysfunction in nonischemic myocardium adjacent to ischemic muscle, we measured systolic wall thickening with sonomicrometers during circumflex coronary occlusion in 12 anesthetized, open-chest dogs. The locations of the wall thickness measurements relative to the perfusion boundary were determined with myocardial blood flow (microspheres) maps constructed from multiple, small tissue samples. Five minutes after circumflex occlusion, systolic wall thickening in the central ischemic zone decreased from 3.00 +/- 0.61 (mean +/- SD) mm to -0.61 +/- 0.36 mm (P less than 0.01). In nonischemic myocardium greater than 10 mm from the perfusion boundary, systolic wall thickening increased from 2.56 +/- 0.57 to 3.24 +/- 0.72 mm (P less than 0.01). In nonischemic myocardium within 10 mm of the perfusion boundary, systolic wall thickening was slightly but significantly reduced compared with control (2.72 +/- 0.80 to 2.44 +/- 0.79 mm, P less than 0.05), supporting the concept of regional dysfunction in nonischemic myocardium at the lateral borders of an ischemic area. Sigmoid curves were fitted to the data to model changes in wall thickening as a continuous function of distance from the perfusion boundary. This allowed estimation of the extent of dysfunction into nonischemic myocardium which averaged less than 8 mm (approximately 30 degrees of endocardial circumference) at one border. The level of functional impairment in this zone was relatively modest, and systolic wall thickening in the immediate border area was reduced more than 50% from control only in tissue characterized by a blood supply of mixed ischemic and nonischemic origin. We conclude that a functional border zone exists lateral to an acutely ischemic area, but measurement of regional function produces relatively small exaggeration of the size of the acutely ischemic zone if severe reduction in mechanical performance is used to define the extent of the ischemic area.

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 micron 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 micrograms/ml at the onset of reperfusion and 29 +/- 3 micrograms/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.

Studies focusing on the functional border zone have been performed largely with anesthetized, open-chest preparations. Therefore, we instrumented 14 dogs at sterile surgery with sonomicrometers arrayed to measure systolic wall thickening across the perfusion boundary produced by circumflex coronary occlusion. We fitted sigmoid curves to the data to model the distribution of wall thickening impairment as a function of distance from the perfusion boundary, which was delineated with myocardial blood flow (15 micron diameter microspheres) maps. Using this approach, we defined the functional border zone as the distance from the perfusion boundary to 97.5% of the sigmoid curve's nonischemic asymptote. The lateral extent of the functional border zone, measured 10 min and 3 hr after occlusion, was 32 and 28 degrees of circumference, respectively. To evaluate the severity of nonischemic dysfunction, we measured average systolic wall thickening within the functional border zone. It was reduced from 3.69 +/- 1.10 (mean +/- SD) mm to 2.98 +/- 1.07 mm (p less than .01) and 2.74 +/- 1.12 mm (p less than .01) early and late after coronary occlusion. Thus, a narrow functional border zone was evident during circumflex coronary occlusion in conscious dogs. Its lateral extent was limited to approximately 30 degrees (similar to findings in open-chest, anesthetized dogs), severe dysfunction was restricted to the immediate vicinity of the perfusion boundary, and the average severity of nonischemic dysfunction within the functional border zone was mild.

The functional border zone is nonischemic myocardium that exhibits reduced function adjacent to an ischemic area. To determine if the functional border zone can be modified by pharmacologic interventions that alter contractility, we infused isoproterenol (0.04-0.10 micrograms/kg/min) or administered propranolol (2 mg/kg) during circumflex coronary occlusion in nine anesthetized, open-chest dogs. We measured systolic wall thickening on both sides of the perfusion boundary, which was delineated with myocardial blood flow (microsphere) maps constructed from small tissue samples. By fitting sigmoid curves to the composite systolic wall thickening data after coronary occlusion, we modeled the distribution of functional impairment across the perfusion boundary. Defined as the distance from the perfusion boundary to 97.5% of the nonischemic asymptote of the sigmoid fits, the functional border zone was 31 degrees of circumference after coronary occlusion alone. Isoproterenol increased +dP/dt by 58% and augmented nonischemic systolic wall thickening without changing the lateral extent of the functional border zone (32 degrees). Propranolol reduced +dP/dt by 24% and depressed nonischemic systolic wall thickening, but the size of the functional border zone remained limited to 28 degrees. Within the functional border zone, wall thickening was significantly but only moderately reduced (-28%) compared with thickening in nonischemic myocardium more than 10 mm away from the perfusion boundary. The ratio of nonischemic border zone to central nonischemic area wall thickening remained the same with each intervention. We conclude that the dimensions of the functional border zone are fixed early after coronary occlusion and that inotropic interventions do not modify the extent or relative severity of nonischemic regional dysfunction.

To evaluate how aortic constriction affects nonischemic myocardium adjacent to the perfusion boundary (the "functional border zone"), we measured systolic wall thickening (dWT) with sonomicrometers in eight anesthetized, open-chest dogs. The locations of the wall thickening measurements relative to the perfusion boundary (PB) were determined with myocardial blood flow (microspheres) maps constructed from multiple, small tissue samples. In nonischemic myocardium more than 10 mm from the PB produced by circumflex coronary occlusion, dWT increased significantly from 2.57 +/- 0.62 (mean +/- SD) to 3.24 +/- 0.73 mm (P less than 0.01). Within 10 mm of the PB, however, dWT did not change significantly (2.48 +/- 0.79 to 2.38 +/- 0.66 mm, NS). When the aorta was mechanically constricted, peak systolic pressure increased approximately 50%. Wall thickening decreased to the same relative degree in nonischemic muscle less than 10 mm and more than 10 mm from the perfusion boundary. By fitting sigmoid curves to the data, we estimated the extent of nonischemic dysfunction. It averaged 26 +/- 6 degrees (6-8 mm of endocardial circumference) during coronary occlusion alone and it was not significantly different (29 +/- 11 degrees) after aortic constriction. Thus elevated afterload affects nonischemic myocardium uniformly and does not increase the size or relative severity of the functional border zone.

The relationship between epicardial and transmural function (measured with sonomicrometers) was examined in 13 anesthetized open-chest dogs. Systolic wall thickening was used as a standard of integrated transmural function to compare with epicardial function measured as segment shortening parallel to surface fibers. Three levels of coronary inflow restriction were produced by using decrements in systolic wall thickening as an index of changes in the transmural distribution of myocardial blood flow (microspheres) in myocardium perfused by the left anterior descending artery (anterior-apical group, n = 7) or circumflex artery (posterior-basal group, n = 6). Levels 1 and 2 were characterized by reductions in systolic wall thickening of 35% and 80%, respectively, and marked decreases in deep myocardial blood flow. In the subepicardium, myocardial blood flow was minimally affected at levels 1 and 2 and there was no change in posterior-basal epicardial segment shortening, but anterior segment shortening decreased significantly (by 21% and 37%, respectively). At level 3 myocardial blood flow was reduced transmurally, producing systolic wall thinning and marked epicardial dysfunction in both groups. Parallel epicardial segment shortening underestimated the extent of transmural dysfunction in both groups at levels 1 and 2 but the degree of underestimation was greatest in the posterior-basal group. Anterior-apical segment shortening was impaired at levels 1 and 2, whereas posterior-basal segment shortening was unaffected, suggesting that significant regional variability exists in the epicardial response to nontransmural ischemia.

To determine the lateral extent of dysfunction in nonischemic myocardium adjacent to ischemic muscle, we measured systolic wall thickening during circumflex coronary occlusion in two groups of anesthetized, open-chest dogs. In one group (n = 12), wall thickening was measured with sonomicrometers arrayed on both sides of the perfusion boundary (PB) between ischemic and nonischemic myocardium. The location of the PB and the distances of the sonomicrometers from the PB were determined from full circumference maps of myocardial blood flow (microspheres) distribution constructed from multiple, small tissue samples. Sigmoid curves were fitted to the data to model changes in wall thickening as a continuous function of distance from the PB. Using this approach, the average extent of dysfunction (defined as wall thickening less than control condition values) was approximately 4–5 mm (or 15–18 degrees) of endocardial circumference. In the second group (n = 18), cross-sectional two-dimensional echocardiograms were obtained to measure regional function. Wall thickening was measured at 22.5 degree intervals around cross-sections of the left ventricle and myocardial blood flow distribution in the corresponding 16 sectors was measured with microspheres or autoradiography. Circumferential maps of wall thickening and blood flow distribution during circumflex coronary occlusion were constructed. By superimposing the maps, the difference between the size of the hypofunctional zone (174 ± 4 degrees) and ischemic zone (125 ± 26 degrees) was estimated. Consistent with the results obtained with sonomicrometry, the extent of nonischemic dysfunction averaged approximately 25 degrees (or 8–9 mm of endocardial circumference) at each lateral border of the ischemic area. We conclude that a ‘functional border zone’ (defined as nonischemic muscle exhibiting abnormal function) exists adjacent to acutely ischemic myocardium. Because its lateral extent is relatively limited, however, it is possible to estimate the size of the ischemic zone with reasonable accuracy using functional measurements alone.

The envelope‐weighted average of instantaneous frequency (EWAIF) model of auditory perception has been successfully applied to simple, two‐component signals, simultaneously amplitude‐ and frequency‐modulated tones, and even to the complex signals used in the early “profile analysis” work. The EWAIF model predicts performance from a calculation of the envelope‐weighted average of the instantaneous frequency fluctuations inherent in almost every complex periodic sound. When the model is in error, it generally predicts better performance than our listeners achieve. A revised version of the EWAIF model incorporates a temporal processing window. The revised model was tested by comparing its predictions with listeners' performance in a frequency‐change discrimination task. The experiment requires the listener to distinguish a smooth frequency glide from a discrete, multistep transition over the same trajectory. The listeners' ability to distinguish the glide from the multistep transition, in a 2IFC task, decreased to chance as the number of steps increased. The EWAIF model performance follows that of the listeners, given the appropriate choice of temporal window parameters. [Work supported by AFOSR and NIH.]