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This study was designed to examine the functional properties of myocardium subjected to acute coronary occlusion but surviving the ischemic insult. Ten conscious mongrel dogs underwent mild-circumflex coronary occlusion and were treated for 6 hours with prostacyclin, 540 ng/kg/min, and ibuprofen, 110 micrograms/kg/min, or dipyridamole (7-9.7 micrograms/kg/min). At 7 days, each dog was anesthetized, the chest was opened, and cross-sectional two-dimensional echocardiograms were obtained through the middle of the occluded vascular bed. A computer-aided contouring system was used to assess percent systolic thickening in 16 equally spaced segments around the left ventricle. Metal markers sewn to the epicardium permitted precise regional correlation of histology, percent systolic thickening, and flow, as measured by radioactive microspheres. Necrosis was minimal, averaging only 2.2 +/- 0.8% (+/- SEM) of the left ventricular ring corresponding to the echocardiographic cross section. Percent systolic thickening was 28.6 +/- 4.7 in the nonischemic anterior wall, but was reduced to -4.5 +/- 3.1 in the occluded bed (p less than 0.01). In individual echo segments, percent systolic thickening correlated with local flow (r = 0.69, p less than 0.001), but was still depressed even when flow was normal. In six segments within the occluded bed that had normal histology and flow, percent systolic thickening was 52% less than that in the nonischemic region (p less than 0.02). Thus, coronary artery occlusion combined with drug treatment results in myocardium that, although histologically normal and supplied by normal myocardial blood flow, remains functionally abnormal 7 days after occlusion.
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PMID:Impaired function of salvaged myocardium: two-dimensional echocardiographic quantification of regional wall thickening in the open-chest dog. 633 7

Previous studies investigating the effect of hypertonic mannitol infusion during coronary occlusion have yielded conflicting results. The present study investigated the effect of hypertonic mannitol infusion on regional myocardial blood flow (microsphere technique), a metabolic index of ischaemic severity (myocardial PCO2 (PmCO2] and myocardial water accumulation during a 2 h anterior descending coronary artery (LAD) occlusion in open chest anaesthetised dogs. In seven dogs studied without mannitol intervention, LAD ligation resulted in an initial fall in regional blood flow to 25% of control flow followed by no significant change thereafter. Myocardial PCO2 distal to the ligation rose to a peak of 34.0 +/- 4.4 kPa (256 +/- 89) (mean +/- SEM). At the completion of the 2 h ischaemia period, myocardial water content was 8.4% greater in ischaemic than non-ischaemic tissue (3.87 +/- 0.11 and 3.57 +/- 0.03 g X g-1 dry weight respectively). In seven additional dogs, mannitol infusion begun 12 min following occlusion resulted in an increase in plasma osmolarity from 304 +/- 5 to 346 +/- 8 mosmol X litre-1, but failed to influence regional flow, PmCO2, or water accumulation in the ischaemic tissue. The inability of mannitol to favourably influence the severity of myocardial ischaemia during prolonged coronary occlusion may be due to its inability to prevent myocardial cell swelling in this model.
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PMID:Effect of hypertonic mannitol infusion during prolonged coronary occlusion. 641 5

Open-chest dog preparations were used to determine divalent cation transport following acute myocardial infarction. Cardiac lymph flow, lymph and plasma protein, zinc, calcium, and magnesium content and hemodynamic measurements were recorded every 20 min before and after coronary artery occlusion in sham operated (N = 4), infarcted (N = 6), and lymph-ablated animals (N = 4). During the 4-hr occlusion period, with constant blood pressure, lymph flow increased from 1.53 +/- 0.25 to 2.15 +/- 0.44 mg/hr (SEM), P less than 0.01. Zinc decreased in plasma from 0.69 +/- 0.10 to 0.41 +/- 0.08 micrograms/ml, P less than 0.01, and in lymph from 0.69 +/- 0.08 to 0.40 +/- 0.02 micrograms/ml, P less than 0.01. Zinc to protein ratio decreased similarly to total zinc in plasma and lymph. Changes in calcium and magnesium were insignificant. Lymph to plasma concentration ratios increased for protein from 0.57 +/- 0.05 to 0.62 +/- 0.02, P less than 0.05, and for zinc from 1.10 +/- 0.26 to 1.21 +/- 0.14, P less than 0.05. Heart lymph clearance (lymph:plasma ratio X lymph flow) steadily rose for protein from 0.31 to 0.06 to 0.50 +/- 0.08, P less than 0.05, and for zinc from 0.59 +/- 0.18 to 0.92 +/- 0.15, P less than 0.05. Lymph and plasma measurements did not change significantly in sham-operated animals. Plasma zinc remained unchanged from baseline after coronary occlusion in all lymph-ablated animals. The increased clearance of protein and zinc suggests that plasma proteins are zinc carriers after acute myocardial infarction and that the reduction of plasma zinc is dependent upon an intact cardiac lymphatic circulation.
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PMID:Zinc transport by the heart lymphatic system after acute myocardial infarction. 662 Oct 29

It has been established that glucocorticoids and several nonsteroidal antiinflammatory drugs, when administered early after coronary occlusion, interfere with myocardial scar formation. To determine whether this action is associated with expansion of myocardial infarct during the first week of coronary occlusion and whether expansion affects ventricular function, the effects of indomethacin on the left ventricle in the early phase of infarction were studied. In a blinded randomized study, experimental myocardial infarction was produced in 17 open-chest dogs by ligation of the proximal left anterior descending coronary artery; the treated group (n = 8) received 10 mg/kg iv indomethacin at 15 min and 3 hr after occlusion, and the control group (n = 9) received saline. After 7 days, regional function expressed as percent change of area (% delta A) of the left ventricular cavity was calculated from short-axis two-dimensional echocardiograms at the level of the infarct, the animals were killed, and their hearts were examined. The ratio of infarct thickness to noninfarcted wall thickness was 1.20 +/- 0.08 (mean +/- SEM) in the control group, and the ratio was lower in the indomethacin group, 0.96 +/- 0.04 (p less than .025). An expansion index of myocardial infarction was calculated as previously described and was 1.02 +/- 0.04 in the control group vs 1.29 +/- 0.06 in the indomethacin group (p less than .005). In eight dogs (six control and two treated) without expansion (expansion index less than 1.09), regional function expressed as % delta A was 46.8 +/- 2.6% (SEM), and in nine dogs (six treated and three control) with expansion, % delta A was significantly lower, 28.7 +/- 4.0% (p less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Drug-induced expansion of infarct: morphologic and functional correlations. 669 21

The authors used an in vitro myocardial tissue slice technique to quantitate the transmural distribution of alterations in cell volume regulation and membrane integrity following early ischemic injury and to evaluate directly the effects of therapeutic interventions in a system not subjects to influences of coronary blood flow. Left circumflex coronary occlusion was produced in 57 dogs for 30 or 60 minutes. After in vitro incubation in Krebs-Ringer-phosphate-succinate medium containing trace 14C-inulin, typical values (ml H2O/g dry weight) for control nonischemic myocardial slices were 3.68 +/- 0.07 (SEM) for total tissue water, 2.67 +/- 0.07 for inulin impermeable space, and 1.01 +/- 0.04 for inulin diffusible space. Ischemic myocardial slices exhibited an impaired response to cold shock (0 C for 60 minutes) and rewarming (37 C for 60 minutes). After 60 minutes coronary occlusion, respective increases in total tissue water, inulin-impermeable space and inulin-diffusible space of ischemic slices were 25.5 +/- 2.6%, 6.2 +/- 4.9% and 84.4 +/- 12.5% for papillary muscle, 22.2 +/- 2.1%, 10.4 +/- 4.2% and 52.5 %/- 10.3% for subendocardium and 9.1 +/- 1.5%, 7.2 +/- 2.3% and 15.8 +/- 5.5% for subepicardium. Significant but usually less marked alterations occurred after 30 minutes of coronary occlusion. Propranolol treatment in vivo (2 mg/kg) and/or in vitro (0.01 mg/ml medium) produced no significant changes in tissue water or inulin spaces of ischemic slices, compared with saline controls. Incubation in hyperosmolar mediums resulted in significant reductions in total tissue water and inulin-impermeable space with little change in inulin-diffusible space of both ischemic and control slices. Fifty milliosmolar polyethylene glycol (MW 6000) produced a greater reduction in tissue water and ultrastructural evidence of cell swelling than did either 40 or 100 milliosmolar mannitol (MW 182). The major effect of hyperosmolar incubation appeared to be a selective reduction in edema of cells with structurally intact membranes. Thus, in vitro studies, with myocardial tissue slices provide evidence of widespread alterations of membrane integrity after 30--60 minutes of in vivo coronary artery occlusion. In vitro abnormalities of cell volume regulation can be partially reversed by direct osmotic effects on myocardial cells.
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PMID:Abnormalities of volume regulation and membrane integrity in myocardial tissue slices after early ischemic injury in the dog: effects of mannitol, polyethylene glycol, and propranolol. 678 78

Changes in myocardial purine metabolism were studied after temporary coronary artery occlusion and subsequent reperfusion in the dog. Sequential myocardial biopsies were performed to allow for measurements of ATP, adenine nucleotide, nucleoside, and base concentrations after 15 min of ischemia, and after 90 min and 72 hr of reperfusion following this period of ischemia. Control, nonischemic sites were also sampled. After 15 min of coronary occlusion, subendocardial ATP concentrations (reported in nmol/mg of protein; mean +/- SEM) were depressed in the ischemic zone at 19.9 +/- 3.5 compared to 38.1 +/- 2.8 in the nonischemic zone (P < 0.001). Subepicardial ATP concentrations also were depressed at 27.0 +/- 2.2 in ischemic sites compared to subepicardial nonischemic sites (40.0 +/- 4.0, P < 0.005). After 90 min of reperfusion ATP concentrations remained depressed in the previously ischemic subendocardium 26.8 +/- 4.2 (P < 0.025 vs. nonischemic sites). After 72 hr of reperfusion, ATP was still depressed in the previously ischemic subendocardium at 29.2 +/- 2.5 (P < 0.025 vs. nonischemic) and subepicardium (27.9 +/- 3.3, P < 0.05 vs. nonischemic). Total purines were determined as the sum of ATP, ADP, AMP, adenosine, inosine, and hypoxanthine. After 15 min of occlusion, the total purine pool in the ischemic subendocardium tended towards being lower than in the nonischemic zone (42.0 +/- 5.9 vs. 53.8 +/- 5.2, not significant) but in the ischemic subepicardium the total purine pool was similar to that in the nonischemic zone. After 90 min of reperfusion the previously ischemic subendocardial purine pool was reduced compared to the nonischemic zone (39.0 +/- 4.8, P < 0.025). Total purines were also depleted in both the subendocardium and subepicardium of previously ischemic zones after 72 hr of reperfusion (44.5 +/- 2.9 and 40.0 +/- 4.4, respectively, P < 0.05). Histologic analysis of the previously ischemic tissue revealed no evidence of necrosis. Therefore, brief temporary coronary artery occlusions not associated with anatomic evidence of necrosis may result in prolonged abnormalities of ATP concentration and significant depletion of the total purine pool.
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PMID:Prolonged derangements of canine myocardial purine metabolism after a brief coronary artery occlusion not associated with anatomic evidence of necrosis. 693 66

The purpose of this study was to determine whether or not the biochemical, functional, and ultrastructural abnormalities produced by brief temporary coronary occlusions (unassociated with necrosis) ever resolve and, if so, when they do. Anesthetized open-chest dogs were subjected to 15 min of coronary artery occlusion followed by 72 hr, 7 days, or 14 days of reperfusion. Serial in vivo myocardial biopsies were performed for measurement of ATP and for ultrastructural analysis. Regional function was evaluated by sonomicrometry. Mean (+/- SEM) myocardial ATP concentration was 36.6 +/- 1.2 nmol/mg of cardiac protein in nonischemic subendocardium and 18.9 +/- 1.5 in ischemic subendocardium after 15 min of ischemia. ATP remainede performed for measurement of ATP and for ultrastructural analysis. Regional function was evaluated by sonomicrometry. Mean (+/- SEM) myocardial ATP concentration was 36.6 +/- 1.2 nmol/mg of cardiac protein in nonischemic subendocardium and 18.9 +/- 1.5 in ischemic subendocardium after 15 min of ischemia. ATP remainede performed for measurement of ATP and for ultrastructural analysis. Regional function was evaluated by sonomicrometry. Mean (+/- SEM) myocardial ATP concentration was 36.6 +/- 1.2 nmol/mg of cardiac protein in nonischemic subendocardium and 18.9 +/- 1.5 in ischemic subendocardium after 15 min of ischemia. ATP remained depressed in the reperfused previously ischemic subendocardium at both 90 min (68% of nonischemic value) and 72 hr (78% of nonischemic value) but returned to normal at 7 days. Regional systolic function and cardiac ultrastructural abnormalities required 7 days for full recovery. Histologic and histochemical analysis did not reveal necrosis at any time. Therefore, biochemical, functional, and ultrastructural abnormalities induced by brief periods of transient coronary occlusion not associated with necrosis do resolve completely but the recovery period is prolonged.
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PMID:Recovery from prolonged abnormalities of canine myocardium salvaged from ischemic necrosis by coronary reperfusion. 676 71

We studied the effect of the pericardium on the end-diastolic pressure-segment length (P-L) relation in volume loading (Experiment I) and in acute ischemia (Experiment II). Experiment I: In 6 open chest dogs, segment length of left and right ventricles were measured using ultrasonic crystals during blood infusion. Drawing end-diastolic pressure (P, on ordinate) against segment length (L, on abscissa), the P-L curve with pericardium positioned upward compared to that without pericardium. The slopes (b) of the exponential curve (P = aebL) with pericardium were steeper than those without pericardium in both ventricles. The difference between the slopes with and without pericardium was significantly larger in the right ventricle (RV, 0.30 +/- 0.10, mean +/- SEM) than in the left ventricle (LV, 0.05 +/- 0.02, p less than 0.05). These results show that the pericardium inhibits the distensibility of the free wall more in RV than in LV, and enhances a mechanical coupling of both ventricles during volume over-load. Experiment II: In 8 open chest dogs, segment lengths of ischemic and non-ischemic regions in LV were measured after left circumflex coronary occlusion. When the segment lengths and LV pressure became stable, a pericardiectomy was performed. After the pericardiectomy, whereas heart rate and LV systolic pressure did not change, end-diastolic segment length in the ischemic region further lengthened (12.0 +/- 0.2 to 12.5 +/- 0.2 mm, p less than 0.01) and that in the non-ischemic region did not change despite the concomitant fall in LV end-diastolic pressure (EDP, 11.9 +/- 0.6 to 9.8 +/- 0.6 mmHg, p less than 0.01). These results suggest that the pericardium alters the LV end-diastolic pressure-volume relation and is one of the factors contributing to an increase in LVEDP during acute ischemia.
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PMID:The effect of pericardium on the diastolic properties of the heart--experimental studies on volume load and on acute ischemia in open chest dogs. 705 73

We studied the difference in effect of sympathetic stimulation on refractory periods of ischemic and non ischemic myocardium in eight dogs, and the effect of sympathetic stimulation on dispersion of refractory periods in ischemic myocardium in seven additional dogs. In the first group of dogs, refractory periods of ischemic sites averaged 164 +/- 2.2 msec (M +/- SEM) and those at non ischemic sites averaged 193 +/- 1.8 msec. Sympathetic stimulation shortened refractory periods at non ischemic sites to an average of 183 +/- 2.0 msec and prolonged refractory periods at ischemic sites to an average of 171 +/- 2.2 msec. As a result of the different effects of sympathetic stimulation on refractory periods of ischemic and non ischemic myocardium, refractory periods between ischemic and non ischemic areas were more uniform during sympathetic stimulation than during coronary occlusion alone. In the second group of dogs in which the effects of sympathetic stimulation on dispersion of refractory periods were studied, pooled variances in refractory periods were calculated. There was no statistically significant difference in the pooled variance of refractory periods during control periods and during sympathetic stimulation alone. Coronary occlusion alone significantly increased the variance in refractory periods, but there was no statistically significant difference in the variance of refractory periods during coronary occlusion alone and during coronary occlusion and sympathetic stimulation. Our findings suggest that at some times during the course of myocardial infarction the effects of high sympathetic tone may be partially protective with respect to arrhythmias by reducing inequalities of recovery between ischemic and non ischemic tissue.
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PMID:Effects of sympathetic stimulation on refractory periods of ischemic canine ventricular myocardium. 706 15

Coronary reserve in patients with supravalvular aortic stenosis may be limited by coronary artery ostial obstruction or left ventricular hypertrophy. To assess the relative effect of these two factors on coronary reserve, seven patients with supravalvular aortic stenosis were studied intraoperatively before and after repair. Six patients who underwent elective cardiac surgery for conditions that did not involve the left ventricle or the left anterior ascending coronary artery served as controls (control group 1). Four patients were studied before and after cardiopulmonary bypass to determine if cardiopulmonary bypass altered coronary reserve in normal vessels perfusing normal ventricle (control group 2). Using a pulsed Doppler probe to determine coronary velocity, coronary reactive hyperemia was induced in the left anterior descending coronary artery (patients with supravalvular aortic stenosis and group 1 controls) or right ventricular branches of the right coronary artery (group 2 controls) during maximal coronary dilation produced by a 20-second coronary occlusion. All patients with supravalvular aortic stenosis underwent patch aortoplasty to relieve left coronary artery ostial obstruction and outflow tract obstruction; three patients also underwent aortic valvotomy and one patient also underwent valve replacement. Coronary reactive hyperemia was calculated as the ratio of peak to resting velocity. This ratio was 5.0 +/- 0.6 (mean +/- SEM) preoperatively and 3.6 +/- 0.3 postoperatively in control group 2. Thus, coronary reserve was only modestly reduced after cardiopulmonary bypass. Before repair, the ratio of peak to resting velocity was markedly reduced in patients with supravalvular aortic stenosis compared with control group 1 (1.8 +/- 0.3 vs 4.9 +/- 0.5, p less than 0.05) and did not change after repair (1.7 +/- 0.2), even though the aortic gradient was reduced (80 +/- 14 vs 38 +/- 6 mm Hg, p less than 0.05) and real or potential coronary ostial obstruction was eliminated by the operation. Because coronary reserve did not improve after surgery in patients with supravalvular aortic stenosis, we conclude that left ventricular hypertrophy is probably the primary determinant of decreased coronary reserve in these patients.
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PMID:Determination of coronary reserve in patients with supravalvular aortic stenosis. 708 41


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