Effect of nitroprusside on local contractile performance after coronary ligation and reperfusion.

To study the effects of nitroprusside infusion on the regional contractile performance of the left ventricle after coronary occlusion, local tension and segment length of the ischemic, border and nonischemic zones were studied using Walton-Brodie strain gauge arches and mercury-in-Silastic tubing segment length gauges in open chest dogs. The effect of this intervention on the time period for functional reversibility of the affected areas after revascularization was also examined. Fifteen minutes after occlusion of the left anterior descending coronary artery, nitroprusside (4 to 11 mug/kg per min) was infused to keep systolic pressure 20 to 25% below control levels for 2 hours after occlusion and then 1 hour after reperfusion. The ischemic zone showed no change in either tension or length although there was a gradual continuing decrease in tension. However, in the border zone total tension which had decreased to 81.4 +/- 9.6 (standard error of the mean) percent of control level 15 minutes after coronary occlusion, increased to 87.5 +/- 11.3% immediately after nitroprusside infusion and continued at that level for 2 hours. Preejection tension rate of tension rise and ejection tension demonstrated parallel increases. Segment length, which had increased to 144.1 +/- 4.5% of control level after coronary occlusion, declined to 115 +/- 10.7% (P less than 0.02) immediately after the onset of infusion. The nonischemic zone showed a sustained increase in all tension variables (P less than 0.01) and a decrease in segment length during the period of nitroprusside infusion with a return to control value after discontinuation of the infusion. The immediate deterioration in tension in the ischemic zone caused by reperfusion after 2 hours of occlusion was prevented by nitroprusside. The border zone continued to maintain improved tension after reperfusion but exhibited an immediate decrease from 84.1 +/- 7.8% to 69.1 +/- 11.7% (P less than 0.05) after discontinuation of nitroprusside. In summary, nitroprusside infusion provides a sustained increase in tension and decrease in length of the border and the nonischemic zones after acute coronary occlusion whereas the ischemic zone remains unaffected. Although administration of nitroprusside fails to prolong the time period for functional reversibility of the affected zones with reperfusion, it appears to prevent further deterioration.     

Temporal relation of epicardial electrographic, contractile and biochemical changes after acute coronary occlusion and reperfusion.

The increasing use of changes in the S-T segment of local epicardial electrograms to quantitate myocardial infarct size has led to the need for a better understanding of this method. Accordingly, we studied the local electrographic, tension and biochemical changes that occurred after coronary occlusion and subsequent reperfusion in 44 dogs using epicardial electrograms from 10 to 12 sites, Walton-Brodie strain gauge arches and myocardial ratios of potassium ion to sodium ion (K+/Na+). After coronary occlusion for 1 hour, total S-T segment elevation increased from 10.2 +/- 2.4 to 78.3 +/- 13.7 mv (P less than 0.001) and tension development decreased to 63.6 +/- 7.0% of control value (P less than 0.001); occlusion for 3 hours resulted in a total S-T segment elevation increase from 5.8 +/- 3.4 to 56.7 +/- 8.7 mv (P less than 0.001) and a tension decrease to 61.4 +/- 5.3% (P less than 0.001) of control value. After reperfusion two types of response were observed. In nine experiments new local pathologic Q waves appeared in an average of 5.3 of 8.2 ischemic electrode sites within 5 to 10 minutes of reperfusion concomitant with a marked further decrease in total tension from 67.3 +/- 5.5% to 42.4 +/- 6.0% of control value (P less than 0.001). Simultaneously, total S-T elevation decreased from 66.1 +/- 8.2 to 25.3 +/- 3.4 mv (P less than 0.001). In seven experiments no Q waves appeared after reperfusion and there was no significant change in tension. Total S-T elevation again decreased from 58.3 +/- 12.7 to 27.1 +/- 5.7 mv (P less than 0.025). When normal saline solution was perfused distal to the coronary arterial occlusion total S-T elevation decreased from 68.0 +/- 3.6 to 36.3 +/- 5.2 mv (P less than 0.001). After 3 hours of coronary occlusion, myocardial K+ decreased and Na+ increased in the ischemic zone, resulting in a significant decrease in the K+/Na+ ratio (P less than 0.005). Reperfusion for 2 hours resulted in a further depletion of K+ and an increase in Na+ with a resultant complete reversal of the K+/Na+ ratio (P less than 0.001). In summary, after reperfusion the S-T segment abnormalities rapidly decreased in all experiments despite the appearance of new Q waves in more than half of these studies concomitant with either a decrease or no change in contractile ability and continuing myocardial K+ loss and Na+ accumulation. S-T segment mapping therefore appears to be of limited value in assessing the effect of reperfusion on infarct size. The decrease in S-T segments that occurred with perfusion of either blood or saline solution suggests a "washout" phenomenon.     

Changes in regional myocardial cross-sectional area during brief coronary occlusion and reperfusion in conscious dogs

The effect of a brief period of coronary occlusion on a regional myocardial cross-sectional area was studied in 6 conscious dogs. Subendocardial segment length and wall thickness were continuously measured with a sonomicrometer in the central ischemic area perfused by the left circumflex coronary artery during a 2-min circumflex occlusion and subsequent reperfusion. Measurements were repeated before and after collateral development induced by 180 +/- 30 (SEM) 2-min circumflex occlusions (20 +/- 3 days). In order to evaluate the changes in regional myocardial volume, end-diastolic regional cross-sectional area was calculated as a product of end-diastolic segment length and wall thickness. Before collateral development, end-diastolic regional cross-sectional area transiently decreased 1.4 +/- 0.6% (NS) at 10 sec following sudden coronary occlusion, thereafter gradually increased to 3.7 +/- 1.0% (P less than 0.05) at the end of a 2-min occlusion. At 10 sec of reperfusion, end-diastolic regional cross-sectional area further increased to 7.0 +/- 1.1% (P less than 0.05) probably due to increased intravascular volume. Increase in end-diastolic regional cross-sectional area was still 2.5 +/- 0.6% (NS) at 3 min after the release of occlusion. After collateral development, the changes in end-diastolic regional cross-sectional area were 0.1 +/- 0.1% (NS), 0.4 +/- 0.3% (NS), 1.0 +/- 0.6% (NS) and 0.2 +/- 0.4% (NS), respectively. Thus, a significant increase in the regional myocardial cross-sectional area occurs during a brief period of coronary occlusion and reperfusion.     

Response of reperfusion-salvaged, stunned myocardium to inotropic stimulation

The purpose of this study was to determine whether myocardium salvaged by reperfusion following coronary occlusion could respond to inotropic stimulation by dopamine. Mongrel dogs underwent a 2-hour occlusion of the proximal left anterior descending coronary artery, followed by reperfusion for 5 or 28 hours. Dopamine (5 to 10 micrograms/kg/min) or dextrose was administered 1 hour or 24 hours after the onset of reperfusion. Serial, computer-assisted, two-dimensional echocardiographic determination of percentage of systolic wall thickening (%SWT) and cross-sectional ejection fraction (% delta area) were used to evaluate the response to treatment. Myocardium in the region of central ischemia contracted poorly after 1 hour of reperfusion (mean %SWT = 1.3 +/- 13.3% [mean +/- SD] compared to preocclusion value of 43.6 +/- 18.5%, p less than 0.001) and tended to thin at 24 hours of reperfusion (mean %SWT = -6.0 +/- 12.3%, p less than 0.001). After 1 hour of reperfusion, dopamine produced a greater than fourfold improvement in %SWT within the reperfused zone (to 15.3 +/- 7.3%, p less than 0.05). After 24 hours of reperfusion, dopamine again produced an improvement in %SWT (to 5.8 +/- 12.5%, p less than 0.05). There were no significant changes in %SWT with dextrose infusion. Thus, dopamine stimulates the reperfusion-salvaged but noncontracting (stunned) myocardium to contract as early as 1 hour after reperfusion.     

Limitations of myocardial revascularization in restoration of regional contraction abnormalities produced by coronary occlusion

The effect of reperfusion instituted from 30 minutes to 3 hours after coronary occlusion on the contractile characteristics of the ischemic zone, border zone and nonischemic myocardium was studied in 29 dogs using Walton-Brodle strain gauge arches and mercury-in-Silastic^® tubing segment length gauges. After 30 and 45 minutes of coronary occlusion, reperfusion resulted in an immediate reversal of abnormalities in segment length and tension of the ischemic zone to near normal. Preejection tension Increased from 32.3 ± 5.1 to 95.2 ± 4.7 percent of control level, ejection tension from zero to 71.7 ± 7.0 percent, total tension from 27.5 ± 2.5 to 87.1 ± 6.2 percent and $\text{dT}\text{dt}$ from 42.1 ± 4.1 to 100.0 ± 4.5 percent. Phasic segment length decreased from 150.2 ± 5.1 percent to 100.0 ± 5.0 percent of control value. Aneurysmal bulging disappeared completely. However, after 1 hour of coronary occlusion, reperfusion resulted In a significant (P < 0.01) further decrease in all contraction variables In the ischemic zone. Preejection tension decreased from 58.7 ± 7.9 to 31.2 ± 5.5 percent, ejection tension decreased initially but recovered to prereperfusion levels, total tension decreased from 48.5 ± 5.9 to 24.0 ± 4.0 percent and $\text{dT}\text{dt}$ declined from 60.7 ± 7.2 to 30.9 ± 5.7 percent of control levels. Phasic segment length gradually decreased from 162.5 ± 6.0 to 137.5 ± 12.5 percent of control value. The border zone exhibited similar decreases in function In four studies, and improved in two. After 2 and 3 hours of coronary occlusion, reperfusion was uniformly followed by further decreases In function of both ischemic and border zones.In conclusion, contraction abnormalities produced by 45 minutes of coronary occlusion are reversible with reperfusion. However, when reperfusion is instituted after 1 hour of occlusion, the abnormalities are often accentuated and this becomes invariable after 2 hours of occlusion. Thus, the myocardial impairment appears to be functionally irreversible after this time period.     

Immediate rebound followed by deterioration of regional left ventricular function with coronary reperfusion

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.     

Effects of regional myocardial ischaemia on coronary artery calibre in the rabbit

Microangiographic and electron microscopic studies were undertaken in isolated, perfused rabbit hearts to examine the effects of acute regional myocardial ischaemia on coronary artery calibre, vascular resistance and ultrastructure. Selective left coronary angiograms were recorded prior to, after 90 min of acute regional myocardial ischaemia induced by occlusion of the marginal left ventricular branch of the circumflex artery, and after reperfusion for 5 min. Vasodilation occurred in the proximal left anterior descending artery (9 +/- 1%, P less than 0.01) and the unoccluded part of the marginal branch (21 +/- 1%, P less than 0.001) during ischaemia which reversed on reperfusion. During reperfusion, coronary vascular resistance increased by 43 +/- 10% (P less than 0.001) despite mild vasodilation of vessels in the ischaemic zone (up to 10 +/- 1%, P less than 0.01). Failure of reperfusion occurred in vessels smaller than 30 microns in diameter (terminal arterioles) and was associated with ultrastructural damage in the ischaemic zone which was particularly prominent at the apex. These findings suggest that failure of reperfusion following 90 min of acute regional myocardial ischaemia in the rabbit is associated with damage to terminal arterioles and capillaries and that the calibre of the larger coronary vessels is maintained. Failure of reperfusion after prolonged myocardial ischaemia may occur despite arterial dilatation in the ischaemic zone.     

'Early' ischemia and reperfusion-induced arrhythmias: antiarrhythmic effects of diltiazem in the conscious rat

The ability of diltiazem to prevent early ischemia and reperfusion-induced arrhythmias was investigated in conscious rats with coronary artery occlusion. During a 30-min period of occlusion of the left coronary artery, 100% of placebo-treated animals exhibited ventricular tachycardia, 65% exhibited ventricular fibrillation and the mean total number of premature ventricular complexes was 1076 +/- 254. Diltiazem (0.5 or 2.0 mg/kg body weight, given intravenously 10 mins prior to coronary occlusion), reduced the incidence of ventricular tachycardia to 62% (P less than 0.01) and 54% (P less than 0.001), respectively and the incidence of ventricular fibrillation to 31% (P = NS) and 15% (P less than 0.01), respectively. The total number of premature ventricular complexes was also reduced to 248 +/- 78 (P = NS) and 156 +/- 55 (P less than 0.02). The development of ST segment elevation, induced by coronary artery occlusion, was delayed in both drug-treated groups. Similarly, diltiazem, at the same doses, reduced the incidence of ventricular fibrillation induced by reperfusion after 5 mins of coronary artery occlusion from 100% to 50% (P less than 0.01) and 25% (P less than 0.001) and mortality from 87% to 42% (P less than 0.02) and 25% (P less than 0.01), respectively. The anti-arrhythmic effects of diltiazem were not related to changes in heart rate and all groups showed similar occluded zone sizes, as measured by a fluorescent microsphere technique. Thus, diltiazem affords substantial protection against both early ischemia-induced ventricular arrhythmias and reperfusion-induced arrhythmias and this action may be associated with the beneficial effects on ischemia-induced ST segment elevation.     

Effect of postextrasystolic potentiation on systolic bulging of ischemic myocardium

Because the extent of myocardial bulging after acute coronary occlusion is primarily dependent on wall tension, this study examined whether the decrease in systolic bulging with postextrasystolic potentiation was due to contractile reserve or to changes in loading conditions. Seven dogs were atrially paced at 100 beats/min after the sinus node was crushed and atrial extrasystoles were generated. The left ventricular minor axis diameter and segment lengths in the ischemic and nonischemic zones were measured with sonomicrometers. Wall tension was estimated using Laplace's law, and regional tension-length loops were determined. By 5 min after the left anterior descending coronary artery was occluded, there was regional bulging. Postextrasystolic potentiation diminished the extent of bulging by increasing both isovolumic and ejection percent systolic shortening (isovolumic -9.1 +/- 2.0% to -5.9 +/- 1.7%, p less than 0.008; ejection 2.2 +/- 0.7% to 4.3 +/- 2.0%, p less than 0.008). The tension-length loops after coronary occlusion showed an exponential upstroke and almost superimposed downstroke consistent with passive movement. The loops were unchanged by postextrasystolic potentiation. Wall tension data showed that bulging was reduced because of a shift down the tension-length curve as end-systolic wall tension was reduced by augmented nonischemic contraction. Similar results were seen at 60 min of coronary occlusion. This study demonstrates that the decrease in bulging seen with postextrasystolic potentiation is due to changes in loading conditions and not to contractile reserve.     

Electrophysiologic effects of coronary occlusion and reperfusion. Observations of dispersion of refractoriness and ventricular automaticity.

In order to determine the electrophysiological changes that occur during coronary occlusion and following reperfusion, 19 mongrel dogs were studied. Refractory periods were determined by the extrastimulus method in nonischemic and ischemic zones prior to and after variable periods of left anterior descending artery occlusion and reperfusion. After 15-30 minutes of occlusion, refractory periods in the nonischemic zones remained unchanged while in the ischemic zone they shortened by 17%, resulting in a dispersion of refractoriness. Within three minutes of reperfusion, arrhythmias appeared together with a marked directional change of refractory periods to a prolongation by 34% (P less than 0.001) in the ischemic zone and by 3% (P less than 0.02) in the nonischemic zone. Refractory periods returned to baseline values after 60 minutes of reperfusion. After 60-90 minutes of occlusion, refractory periods in the nonischemic zones were unchanged whereas in the ischemic zone they demonstrated a decrease by 28% (P less than 0.01), again resulting in a dispersion of refractoriness. Within five minutes of reperfusion, refractory periods in the ischemic zone prolonged by 44% (P less than 0.001). Similar but smaller directional changes were also seen in nonischemic zones. Concomitant with the observed prolongation in refractory periods frequent ventricular ectopic activity was again documented. In addition, refractory periods did not return to control values after periods of observation up to 120 minutes in this group. In seven dogs, complete heart block was induced to ascertain the rate of idioventricular pacemaker and the effect of ventricular overdrive on the escape interval. Control ventricular rates (53.3 +/- 5.7 beats/min) remained unchanged (52.3 +/- 5.6) following coronary occlusion, but decreased to 48.0 +/- 4.4 (P less than 0.05) during reperfusion. Mean control escape intervals (1.8 +/- 0.2 sec) did not change after occlusion (1.7 +/- 0.2 sec) but prolonged to 2.1 +/- 0.2 sec (P less than 0.05) following reperfusion. In conclusion: 1) sudden prolongation in refractory periods following reperfusion leads to an overshoot resulting in a dispersion of refractoriness temporally related to the onset of ventricular arrhythmias and 2) re-entry, and not enhanced automaticity, appears to be the mechanism for postperfusion arrhythmias.     

Lactate metabolism in acute myocardial infarction and its relation to regional ventricular performance

Myocardial metabolism was assessed in 20 patients with acute anterior myocardial infarction using lactate uptake (defined as (aortic lactate - great cardiac venous lactate)/aortic lactate X 100) as an index. The regional ejection fraction of the anterior wall was obtained from left ventriculography. There was a linear relation between lactate uptake and regional ejection fraction (r = 0.79, p less than 0.001). Four patients without total occlusion in the infarct vessel had a higher lactate uptake (19.6 +/- 6.7 versus 4.2 +/- 13.4%, p less than 0.05) and regional ejection fraction (26.3 +/- 7.9 versus 14.9 +/- 7.0%, p less than 0.05) than did 16 patients with total occlusion. The latter group of patients underwent intracoronary infusion of urokinase, which resulted in reperfusion in 13 patients. Lactate uptake before urokinase infusion (sample I), just after reperfusion (sample II), 30 minutes after reperfusion (sample III) and 4 weeks after reperfusion (sample IV) was 5.7 +/- 13.2, -13.9 +/- 14.7, 2.9 +/- 15.2 and 20.2 +/- 11.0%, respectively (sample I versus II and II versus III, p less than 0.01; sample I versus IV and III versus IV, p less than 0.05). The decrease in lactate uptake immediately after reperfusion, which was accompanied by an increase in creatine kinase-MB isoenzyme release into the blood, was considered to be the result of a "washout" effect. Lactate uptake was ameliorated 4 weeks later, accompanied by an improvement (from 15.1 +/- 7.1 to 23.4 +/- 7.2%, p less than 0.01) in the regional ejection fraction. It is concluded that the degree of asynergy was closely related to the extent of metabolic deterioration in myocardial infarction.     

Regional differences in postischemic recovery in the stunned canine myocardium

To determine if differences exist in the degree of ischemic damage and in postischemic recovery when different coronary arteries are occluded and reperfused, 40 barbital-anesthetized dogs were subjected to brief 15-minute periods of coronary artery occlusion followed by 3 hours of reperfusion ("stunned" myocardium) of the left anterior descending (LAD) or the left circumflex (LCX) coronary arteries. Myocardial segment shortening (%SS) in the subendocardium of nonischemic and ischemic reperfused areas was measured by sonomicrometry, and regional myocardial blood flow was measured by radioactive microspheres. Transmural tissue biopsies were taken at the end of reperfusion for the measurement of adenine nucleotides and total tissue water content. Arterial and local coronary venous blood samples were collected during preocclusion, during occlusion, and at 30 and 180 minutes of reperfusion for determination of blood oxygen content and oxygen consumption in the ischemic area. During occlusion, subendocardial blood flow (LAD flow = 0.11 +/- 0.02; LCX flow = 0.15 +/- 0.04 ml/min/gm), myocardial oxygen consumption (LAD = 2.4 +/- 0.7; LCX = 2.7 +/- 0.7 ml/min/100 gm), and areas of the left ventricle at risk (LAD = 27.4 +/- 2.3%; LCX = 32.4 +/- 2.4) were similar in both groups, thus indicating equivalent degrees of ischemia. There were no differences between groups in hemodynamics throughout the experiment or in the loss of myocardial high-energy phosphates or increase in total tissue water in the ischemic reperfused area at 3 hours of reperfusion. There was a significantly greater loss (p less than 0.05) of systolic wall function during LAD versus LCX occlusion and a greater recovery of segment function from 5 minutes throughout 1 hour of reperfusion after LCX occlusion (p less than 0.05), with no difference in %SS at 2 and 3 hours following reperfusion. Thus, although similar changes occurred in blood flow, metabolite parameters, tissue edema, wall function, and overall hemodynamics when either the LAD or LCX perfusion territories were occluded and reperfused, the loss of systolic wall function and recovery of segment shortening were more variable after regional stunning of the LCX perfusion bed. These data suggest that evaluation of pharmacologic or surgical interventions to improve postischemic functional recovery may be more reliably performed when the LAD coronary artery is the vessel occluded.     

Reversal of dyskinesis by increased end diastolic segment length in ischaemic-reperfused myocardium

Persistent dyskinesis is universally observed after reperfusion of a severely ischaemic segment. Although inotropic stimulation shows a latent contractile reserve, it is not known whether this reserve can be recruited by increasing end diastolic segment length (local length-tension relation). To investigate this, six anaesthetised open chest dogs were placed on right heart bypass to increase end diastolic segment length independently of mean arterial pressure. Instantaneous left ventricular pressure-segment length relations and fractional systolic shortening were determined by sonomicrometry in the centre of the region perfused by the left anterior descending coronary artery during sequential increases in end diastolic segment length. Measurements were made before occlusion of the left anterior descending coronary artery, during 1 h of occlusion, and after 2 h of reperfusion. Before ischaemia, segmental shortening increased from 11.0(SEM 1.6)% to 23.5(1.5)% (p less than 0.05) as end diastolic segment length increased. Dyskinesis developed during occlusion of the left anterior descending coronary artery [12.1(2.6)% control v -7.2(1.6)% occlusion, p less than 0.05] and was present over the entire range of end diastolic segment lengths. Following reperfusion, segmental dyskinesis [-2.5(2.4)%] persisted at the lower end of the range of end diastolic segment length, but was progressively replaced by active shortening, averaging 7.3(3.2)% (p less than 0.05) as end diastolic segment length was sequentially increased. We conclude that segmental function following reperfusion is sensitive to changes in end diastolic segment length, and that active shortening is recruited from an apparently dyskinetic segment as end diastolic segment length progressively increases.     

Two-dimensional contrast echocardiographic assessment of the time course of regional ischemic myocardial function

The time course of percent fractional area change (%FAC) of the ischemic left ventricular wall as identified by myocardial contrast echocardiography was assessed. Two-dimensional echocardiograms of the left ventricular short axis at the level of the chordae tendineae were recorded in 16 anesthetized open-chest dogs. Myocardial ischemia was produced by occluding the left circumflex coronary artery (LCX) for 30 min, and identified by myocardial contrast echocardiography using aortic root contrast injection. The left ventricular wall in the short-axis view was divided into eight segments. The experiments were completed in nine dogs. The %FAC of the segment which includes the center of the ischemic area was normal before LCX occlusion (35 +/- 6%: mean +/- S.D.), markedly decreased during 30 min of LCX occlusion (-3 +/- 4%) and gradually recovered after coronary reperfusion. However, it was significantly decreased 150 min after reperfusion (8 +/- 9%) (p less than 0.001) compared to that before LCX occlusion. The %FAC of the segment which includes the center of the non-ischemic area was not significantly changed throughout the experiment. In conclusion, 1) the time course of regional ischemic myocardial function could be assessed by the analysis of the %FAC of the ischemic area determined by myocardial contrast echocardiography, 2) the %FAC is significantly decreased 150 min after coronary reperfusion following 30 min occlusion compared to that before coronary occlusion.     

Ischemic expansion during acute myocardial infarction and reversal by coronary reperfusion.

Previous studies have shown that infarct expansion occurs at least 1 day after a large transmural infarction. To assess whether regional left ventricular expansion is evident within hours of an acute myocardial infarction, 25 adult mongrel dogs underwent left circumflex coronary artery occlusion for 2 hours and 22 of these were subsequently reperfused. Two-dimensional echocardiography was used to record left ventricular topography and function at baseline, at 2 hours of occlusion, and following reperfusion. Short-axis midpapillary echocardiograms were analyzed using a microcomputer digitizing routine by establishing a 360-degree circumferential map of the left ventricle. The central ischemic zone was defined as that region with the most depressed contractility after 2 hours of occlusion, and the normal zone was set at 180 degree away from the central ischemic zone. Endocardial and epicardial segment lengths and wall thickness were measured for both the normal zone and the central ischemic zone at end diastole. After 2 hours of occlusion, diastolic central ischemic endocardial (1.3 +/- 0.05 to 1.42 +/- 0.04 cm, p less than 0.01) and central ischemic epicardial (1.84 +/- 0.06 to 1.93 +/- 0.06 cm, p less than 0.05) segment lengths were significantly increased. There were no significant changes in segment lengths or wall thickness in the normal zone. After 2 hours of occlusion, there was significant diastolic left ventricular (LV) dilatation (LV area increased from 18.2 +/- 1.3 to 21.0 +/- 1.3 cm2, p less than 0.01). Furthermore, central ischemic endocardial and epicardial segment length changes from baseline to occlusion correlated significantly with LV dilatation (r = 0.56, p less than 0.003; r = 0.55, p less than 0.004 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Early differentiation of infarcted and noninfarcted reperfused myocardium in dogs by quantitative analysis of regional myocardial echo amplitudes

This study tests the hypothesis that ischemic but viable reperfused myocardium can be differentiated from infarcted reperfused myocardium by regional analysis of myocardial echo amplitudes. In eight closed-chest, anesthetized dogs, the left anterior descending coronary artery was occluded for 3 hours, followed by 1 hour of reperfusion, and sacrifice. Infarct size was measured by the triphenyl tetrazolium chloride technique in a 1-cm-thick mid-left ventricular transverse slice, and matched with a corresponding end-diastolic two-dimensional echo short-axis cross-section. Outlining of epi- and endocardial surfaces, along with construction of a mid-myocardial outline, allowed measurements of regional myocardial echo intensities and grey-level histograms in subendo- and subepicardial regions. In 36 eventually infarcted subendocardial segments (greater than 20% wall necrosis), average pixel intensity (arbitrary units) was 73.7 +/- 33.1 (SD) in control, 75.8 +/- 33.0 at 3 hours of occlusion, and 107.8 +/- 40.9 at 5 minutes, 105.5 +/- 38.9 at 15 minutes, and 101.1 +/- 37.6 at 60 minutes postreperfusion P less than 0.05 vs. control or occlusion); intensity in normal segments (no or less than 20% wall necrosis) was 60.0 +/- 18.6 in control, 57.4 +/- 20.3 at 3 hours of occlusion, and 63.5 +/- 14.8, 68.0 +/- 27.9, and 64.2 +/- 22.3 at 5, 15, and 60 minutes postreperfusion, respectively (no significant change). The skew of the grey-level distribution in infarcted subendocardial segments did not change from control (0.49 +/- 0.72) to 3 hours of occlusion (0.41 +/- 0.52), but decreased (shift to higher echo amplitude) significantly at 5 minutes (-0.31 +/- 0.53), 15 minutes (-0.22 +/- 0.50), and 60 minutes (-0.28 +/- 0.45) after reperfusion (P less than 0.05 vs. control or occlusion); in normal subendocardial segments, there was no significant change throughout the study. In 31 partly infarcted subepicardial segments (greater than 50% wall necrosis), changes in postreperfusion echo amplitudes were less significant. Average pixel intensity was 71.3 +/- 28.6 in control, 71.8 +/- 29.2 after coronary occlusion, and 89.2 +/- 35.3, 83.7 +/- 37.5, and 85.6 +/- 34.9 at 5, 15, and 60 minutes after reperfusion, respectively. It is concluded that reperfusion of irreversibly injured myocardium is associated with consistent early increase in regional myocardial echo intensities and changes in the grey-level distribution. Such alterations might be used to detect the extent of tissue necrosis within minutes after reperfusion.     

The relationships of high energy phosphates, tissue pH, and regional blood flow to diastolic distensibility in the ischemic dog myocardium

Myocardial ischemia due to increased oxygen demand (pacing tachycardia plus critical coronary stenoses) alters diastolic distensibility and relaxation more than ischemia of comparable duration due to coronary occlusion. To investigate the relationship between myocardial diastolic function and metabolism, we compared myocardial high energy phosphate content, tissue pH, and regional blood flow for these two types of ischemia in anesthetized open-chest dogs. Myocardial biopsies were done with a high-speed air-turbine biopsy drill, permitting rapid (less than 1-second) freezing of tissue samples from both nonischemic and ischemic areas, while myocardial pH was measured with a hydrogen ion-selective polymer membrane implanted in the subendocardium. After 3 minutes of pacing tachycardia in dogs with critical coronary stenoses (demand-type ischemia, n = 14), regional systolic function (% segment shortening by ultrasonic crystals) was mildly depressed (from 19 +/- 2% control to 13 +/- 2% post-pacing, P less than 0.01), while left ventricular diastolic pressure-segment length relations shifted upward, indicating decreased distensibility of the ischemic myocardial segment. Associated with these changes in function, subendocardial adenosine triphosphate decreased (from 31.3 +/- 1.5 to 27.9 +/- 1.0 nmol/mg protein, P less than 0.01), as did creatine phosphate (53.8 +/- 2.1 to 39.6 +/- 2.5 nmol/mg protein, P less than 0.01), while myocardial pH declined slightly (delta pH = -0.14 +/- 0.02, P less than 0.01). In contrast, at 3 minutes of coronary artery occlusion (primary ischemia, n = 14), regional segment shortening was replaced by systolic bulging (% shortening decreased from 17 +/- 2% to -2 +/- 1% during occlusion, P less than 0.01), while left ventricular pressure-segment length relations were not shifted upward, and there was no decrease in diastolic distensibility of the ischemic segment. With coronary artery occlusion, subendocardial adenosine triphosphate declined slightly (33.2 +/- 0.5 to 29.2 +/- 2.0 nmol/mg, P less than 0.05), while creatine phosphate decreased substantially (51.1 +/- 2.3 to 7.8 +/- 1.4 nmol/mg protein, P less than 0.01). Myocardial pH fell strikingly (delta pH = -0.33 +/- 0.03, P less than 0.01), and the decline was 236% of that seen with demand-type ischemia. Regional myocardial blood flow (microsphere technique) showed a decreased endocardial:epicardial (endo:epi) ratio (1.04 +/- 0.04 control vs. 0.40 +/- 0.05 during pacing, P less than 0.01) and absolute subendocardial flow (1.02 +/- 0.47 to 0.47 +/- 0.05 ml/min per g, P less than 0.01) with demand-type ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Augmentation of regional function in nonischemic myocardium during coronary occlusion measured with two-dimensional echocardiography

Increased regional left ventricular function frequently occurs in the nonischemic myocardium after acute coronary occlusion. To further define the regional and global effects of this increased remote function in the ischemic left ventricle, 22 dogs were studied with two-dimensional echocardiography before and 1 h after left circumflex coronary artery occlusion. Two groups of dogs were identified with and without compensatory increased regional left ventricular function, defined as regional wall thickening in the nonischemic zone greater than 2 SD above baseline. After coronary occlusion, nonischemic wall thickening was 76 +/- 15% in the hyperfunction group (n = 11) and 45 +/- 14% in the nonhyperfunction group (n = 11) (p less than 0.001). Despite similar left ventricular end-diastolic cavity areas and equivalent degrees of ischemic wall thinning, dogs with increased left ventricular function in the nonischemic myocardium had a smaller extent of circumferential left ventricular dysfunction (136 +/- 33 versus 170 +/- 43 degrees, p less than 0.001) and a higher area ejection fraction (38 +/- 9% versus 27 +/- 6%, p less than 0.001). These functional differences occurred despite similar myocardial areas at risk by autoradiography (41 +/- 6% versus 37 +/- 12%, p = NS). The data suggest that increased left ventricular function in the nonischemic myocardium determines the global functional impact of acute coronary occlusion and, through interaction with adjacent myocardium, modifies the extent of circumferential left ventricular dysfunction.     

Steroid-induced enhancement of functional recovery of postischemic, reperfused myocardium in conscious dogs

The effects of methylprednisolone sodium succinate (20 mg/kg, intravenously administered) on the time course of functional recovery of myocardium following a 15-minute coronary artery occlusion period and subsequent 5 hour reperfusion period were studied in chronically instrumented, conscious dogs. In comparison to a control group, animals receiving methylprednisolone 90 minutes prior to coronary occlusion demonstrated less depression of regional segment shortening following 15 minutes of reperfusion (52 +/- 13% vs control levels of 23 +/- 7% of preocclusion values) and improved recovery at 5 hours postreperfusion (106 +/- 6% vs control levels of 54 +/- 4% of preocclusion values). In animals receiving methylprednisolone immediately prior to reperfusion, there was also similar recovery of segment shortening at 5 hours (97 +/- 3%). In contrast, dogs receiving methylprednisolone 15 minutes after the onset of reperfusion or sodium succinate (5.5 mg/kg, intravenously administered) 90 minutes prior to occlusion demonstrated no improvement in recovery of function. Experiments in dogs not subjected to coronary occlusion documented that methylprednisolone sodium succinate lacked inotropic and vasodilator properties. The results suggest that methylprednisolone administered prior to or during coronary artery occlusion but not after reperfusion enhances the functional recovery of hypokinetic, postischemic, reperfused myocardium. These effects are unrelated to any direct hemodynamic action of steroids or to the sodium succinate salt.     

Effects of reperfusion after coronary artery occlusion on post-infarction scar tissue

Early reperfusion after a coronary occlusion may reduce myocardial infarct size, but late reperfusion into necrotic myocardium may alter post-infarction healing. In rabbits, we compared 1- or 3-week-old scars resulting from permanent coronary occlusion to those resulting from a 1- or 3-hour occlusion followed by reperfusion. Reperfusion at 1 hour post-occlusion did not affect scar mechanical properties assessed at 1 week post-infarction, but at 3 weeks post-infarction, these scars had a tensile strength significantly lower than those not reperfused (78 +/- 11 vs. 158 +/- 15 g/mm2, P less than 0.001). They also were composed of a mixture of fibrous tissue (58 +/- 8%) and myocytes (43 +/- 8%) with a hydroxyproline content of 23 +/- 2.5 mg/g dry weight. The nonreperfused scars had a higher proportion of fibrous tissue (73 +/- 3%) by histological evaluation and a 35% higher hydroxyproline content (31 +/- 2 mg/g dry weight, P less than 0.001) than the scars reperfused after 1 hour. In contrast, 3-week-old scars resulting from "late" reperfusion at 3 hours post-occlusion were similar to nonreperfused scars in fibrous tissue composition and hydroxyproline content. Nonetheless, the tensile strength of these scars reperfused 3 hours post-occlusion was significantly less than that of the nonreperfused scars (72 +/- 5 vs. 158 +/- 15 g/mm2, P less than 0.001). The lower tensile strength was associated with a lower collagen cross-link density in this reperfused group of scars. At physiological stress levels (approximately 3 g/mm2), all groups of reperfused and nonreperfused scars had similar mechanical properties in terms of natural strain, stiffness, creep, and stress relaxation. Thus, although the reperfused scars ruptured more easily at high stresses, when assessed at physiological stresses their mechanical properties were not significantly different from those of nonreperfused scars.