Acceleration of the wavefront of myocardial necrosis by chronic hypertension and left ventricular hypertrophy in dogs

Previous studies have shown that hypertension and left ventricular hypertrophy (HT-LVH) increase completed infarct size. Myocardial infarction progresses in a wavefront of myocardial necrosis from the subendocardium to the subepicardium. We tested two hypotheses: First, HT-LVH accelerates the wavefront of myocardial necrosis when compared with normotensive animals; and second, lowering of arterial pressure by infusing nitroprusside 1 hour after coronary artery occlusion exerts a salutary effect on infarct size. To test these hypotheses, systemic hypertension (mean aortic pressure = 141 +/- 3 mm Hg) and left ventricular hypertrophy (18% increase in left ventricular mass) were induced in dogs using a single-kidney, single-clip model. Seventeen adult mongrel dogs were used as controls. We measured mean aortic pressure, heart rate, left atrial pressure, and myocardial perfusion (microspheres) in several groups of normal and HT-LVH awake dogs. In two groups (normal and HT-LVH), 1 hour of circumflex coronary artery occlusion was followed by 4 hours of reperfusion. In two additional groups (normal and HT-LVH), 3 hours of circumflex coronary artery occlusion was followed by 90 minutes of reperfusion. In another group with HT-LVH, nitroprusside was infused to reduce mean arterial pressure to 100 mm Hg beginning 1 hour after occlusion and was continued for the duration of reperfusion period (HT-LVH + N). Infarct size was assessed using triphenyltetrazolium chloride stain and risk area was determined using postmortem barium angiography. Fifteen of 17 (88%) control animals survived coronary artery occlusion, whereas only 17 of 42 (40%) dogs with HT-LVH survived coronary occlusion (p less than 0.05). Infarct-to-risk ratios in the various layers of the left ventricular wall were determined for survivors in all groups. After 1 hour of coronary occlusion more than twice as much mid-wall and epicardium was infarcted in the HT-LVH group compared with the control group. After 3 hours of coronary occlusion significantly more endocardium, mid-wall, and epicardium was infarcted in the dogs with HT-LVH. In the nitroprusside-treated HT-LVH dogs, the infarct sizes were similar to control animals. From these data we conclude: 1) the rate of infarction is accelerated in animals with HT-LVH; 2) nitroprusside infused 1 hour after coronary artery occlusion and continued throughout the reperfusion period exerts beneficial effect on infarct size when compared with control animals; and 3) acute coronary artery occlusion in animals with HT-LVH is associated with significantly greater mortality when compared with control animals.     

Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion

Dilatation of infarcted segments (infarct expansion) may occur during recovery from myocardial infarction, but the fate of noninfarcted segments is uncertain. Accordingly, left ventricular geometric changes were assessed by left ventricular angiography and M mode echocardiography on admission and 2 weeks later in 30 patients with their first acute transmural myocardial infarction. All patients demonstrated chest pain, ST segment elevation with subsequent development of Q waves (15 anterior, 15 inferior), and elevation of cardiac enzymes. Sequential left ventricular angiographic and hemodynamic findings were available in these patients by virtue of their participation in a study of thrombolysis in acute myocardial infarction. By that study design, all patients treated successfully with thrombolytic therapy and demonstrating improvement of flow in an occluded coronary artery underwent repeat cardiac catheterization. At 2 weeks there was a significant decrease in left ventricular and pulmonary capillary wedge pressures (p less than .01), whereas both left ventricular end-diastolic (LVEDV) and end-systolic (LVESV) volume indexes increased (p less than .01). The increase in LVEDV correlated directly with the percentage of the ventriculographic silhouette that was akinetic or dyskinetic at the initial catheterization (r = .71, p less than .001). To assess regional changes in both infarcted and noninfarcted segments, serial endocardial perimeter lengths of both the akinetic-dyskinetic segments (infarction zone) and of the remainder of the cardiac silhouette (noninfarction zone) were measured in all patients who demonstrated at least a 20% increase in their LVEDV at 2 weeks after myocardial infarction. Notably, there was a mean increase of 13% in the endocardial perimeter length of infarcted segments and a 19% increase in the endocardial perimeter length of noninfarcted segments. Serial M mode echocardiographic studies showed no significant change in the wall thickness of noninfarcted myocardial segments. Hemodynamic changes that occurred in this subgroup of patients included significant decreases in left ventricular end-diastolic and pulmonary capillary wedge pressures (p less than .05) and significant increases in angiographic cardiac index (p less than .01) and LVESV index (p less than .01). We conclude that in patients who manifest cardiac dilatation in the early convalescent period after myocardial infarction, there is remodeling of the entire left ventricle including infarct expansion of akinetic-dyskinetic segments and volume-overload hypertrophy of noninfarcted segments.(ABSTRACT TRUNCATED AT 400 WORDS)     

Epicardial, endocardial and transmural mapping in assessing electrophysiological effects of 14-C lidocaine and 14-C propafenone on activation times in experimental chronic myocardial infarction. Correlations with myocardial drugs concentrations

The electrophysiological effects of lidocaine (L) and propafenone (P) in chronic myocardial infarction in relation to tissue drug concentrations (TDC) are unknown. Thus of 16 dogs with one week old myocardial infarction, 8 received propafenone 2 mg/kg and 8 lidocaine 5 mg/kg followed by 0.2 mg/kg/min of either drug for 60 min. Epicardial (EPI) mapping (greater than 30 points) was performed with a bipolar electrode. Endocardial (ENDO) and transmural (TRANS) mapping (greater than 20 points) were performed with 4 pairs of needle mounted bipolar electrodes. The % change in activation times (% delta AT) in EPI, ENDO and TRANS was evaluated in normal (N) and infarcted (I) zones at control and 60 min after drugs. Ventricular arrhythmias (VA) were studied with programmed extra stimulation. Results (P less than 0.01 to L, P less than 0.01 to N zone, # P less than 0.05 to ENDO): (Table: see text) At 60' ventricular tachycardia and ventricular fibrillation were both still inducible in 50% in the lidocaine group (37% in control), while only in 16% in the propafenone group (62% in control). Despite lower drug concentrations in the infarct, the effects on AT are comparable to normal zones for both drugs. In conclusion lidocaine reduces and propafenone increases AT, affecting in opposite directions the inducibility of reentrant ventricular arrhythmias.     

Ultrasonic tissue characterization of acute canine myocardial infarction

This study assessed changes in left ventricular texture on two-dimensional (2-D) echocardiography after experimental myocardial infarction. In 13 dogs, the left anterior descending coronary artery (LAD) was occluded for 3 h, followed by 1 h of reperfusion and sacrifice. Two-dimensional echocardiography was performed pre-LAD occlusion, 3 h post occlusion and 1 h after reperfusion by placing a 5 MHz transducer on the chest wall. After sacrifice, triphenyltetrazolium chloride staining was performed on 1 cm thick left ventricular cross-sectional slices. Five dogs served as controls (shams). Two-dimensional echocardiograms were digitized and in the region of left ventricular asynergy (area of myocardial infarction), and adjacent normal area, the mean pixel intensities (+/- SD) were calculated. There was no significant change in the mean pixel intensity from 0 through 4 h in the lateral (22.8 +/- 1.3 and 23.4 +/- 1.8) and anteroseptal (23.2 +/- 1.9 and 22.6 +/- 1.9) regions in sham operated dogs. In dogs undergoing LAD occlusion, the mean pixel intensity from the pre- to post occlusion period showed no significant change in the lateral (normal) area, 24.4 +/- 2.7 versus 24.7 +/- 2.9. In the area of wall motion abnormality (area of myocardial infarction) the mean pixel intensity increased from 25.4 +/- 2.7 to 33.7 +/- 4.5, P less than 0.01. There was no significant change in the mean pixel intensity between the 3 h post occlusion and post reperfusion period in either the lateral (normal) or anteroseptal areas of the left ventricle. The area of left ventricular asynergy corresponded to the area of myocardial infarction on triphenyltetrazolium chloride stain.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of mannitol in the prevention of evolving myocardial infarction

The ability of hyperosmolar mannitol to salvage evolving myocardial infarction was studied in 50 open-chest dogs subjected to 3 hours occlusion of the left anterior descending coronary artery. In 28 dogs, 20% hyperosmolar mannitol was infused into the distal half of the infarcted portion after commencement of reperfusion, leaving the proximal half mannitol free. In the other 22 dogs, physiological saline was infused instead of mannitol. The wall thickness at the distal half of the infarcted portion was increased 2 hours after reperfusion in both the saline and the mannitol groups. After 2 hours reperfusion the chest was closed. Thirteen out of 28 dogs in the mannitol group and 12 out of 22 dogs in the saline group died over one week. Seven days later, myocardial samples were measured for myocardial water content and creatine phosphokinase activity (CPK). Myocardial water content was increased in the infarcted portion in both the saline and the mannitol groups. In the saline group, myocardial CPK was reduced markedly in the proximal half (54.8 +/- 7.8% at the inner layer and 53.1 +/- 4.7% at the outer layer). These depletions were even more marked in the distal half (47.9 +/- 5.8 and 48.3 +/- 3.3%). In the mannitol groups, although the CPK was similarly depressed in the proximal half (44.8 +/- 5.8 and 41.1 +/- 5.4%), the CPK depletion in the distal half was less (48.1 +/- 6.1 and 58.1 +/- 6.7%) than the proximal half, suggesting mannitol preserved CPK depletion in the infarcted portion. It was concluded that intracoronary infusion of mannitol after reperfusion may salvage the infarcted myocardium.     

Measurement of infarct size and percentage myocardium infarcted in a dog preparation with single photon-emission computed tomography, thallium-201, and indium 111-monoclonal antimyosin Fab

Single photon-emission tomography (SPECT) and indium 111-labeled monoclonal antimyosin Fab fragments were used to measure myocardial infarct size in 12 dogs, six subjected to balloon catheter-induced coronary artery occlusion for 6 hr (late reperfusion) and six subjected to occlusion with reperfusion at 2 hr (early reperfusion). Tomographic imaging was performed 24 hr after the intravenous injection of labeled Fab fragments with the use of a dual-head SPECT camera with medium-energy collimators. Immediately after the first tomographic scan, thallium-201 was injected into nine of 12 dogs and imaging was repeated. Estimated infarct size in grams was calculated from transaxially reconstructed, normalized, and background-corrected indium SPECT images with the use of a threshold technique for edge detection. Estimated noninfarcted myocardium in grams was calculated from obliquely reconstructed thallium SPECT images by a similar method. The animals were killed and infarct size in grams and true infarct size as a percentage of total left ventricular myocardial volume were measured by triphenyl tetrazolium chloride staining. Estimated infarct size from indium SPECT images showed an excellent correlation with true infarct size (r = .95, SEE = 4.1 g). Estimated percentage myocardium infarcted was calculated by dividing estimated infarct size from indium images by the sum of estimated infarct size plus estimated noninfarcted myocardium obtained from thallium images. Correlation between the estimated percentage of myocardium infarcted and true percentage of myocardium infarcted was excellent (r = .93, SEE = 4.4%). We conclude that dual-isotope SPECT with indium 111-monoclonal antimyosin antibodies and thallium-201 can accurately estimate infarct size and percentage myocardium infarcted.     

Electrocardiographic effects of experimental nontransmural myocardial infarction

Clinical and experimental data have documented the ability of nontransmural myocardial infarction to produce abnormal Q waves on both the epicardial and body surfaces. We undertook this study to define the anatomic determinants of such Q wave development. Thirty dogs were studied before and after occlusion-reperfusion (26 dogs) or latex embolization (four dogs) of the left circumflex coronary artery. Occlusion was maintained for 60 to 240 min before reperfusion to produce nontransmural lesions of various sizes. Electrocardiographic data were registered from 84 torso electrodes by body surface mapping techniques before and 1 week after infarction. Infarct size was quantitated by computer analysis of heart slices stained with triphenyl tetrazolium chloride. Six dogs did not develop infarction. Of the remaining 24, 10 did and 14 did not develop significant changes in body surface Q wave duration and width. The incidence of Q wave changes was not different in dogs with nontransmural and those with transmural lesions. Infarct size (expressed as a percentage of the left ventricle infarcted), the percentage of endocardium subjacent to infarction, the average depth of necrosis, the percent of the four outer fifths of the ventricular wall infarcted, and the duration of occlusion were significantly (p less than .05) greater in dogs with than in those without Q wave changes. Logistic regression modeling demonstrated that only two anatomic parameters--percentage of left ventricle infarcted and average lesion depth--significantly and independently predicted Q wave development. A model including only these two variables accurately classified all 24 cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of beta-adrenergic blockade on the natural progression of myocardial infarct size and compensatory hypertrophy

Using contrast-enhanced computed tomography, the effects of beta-adrenergic blockade were assessed on experimentally produced myocardial infarcts in dogs evaluated serially over the course of approximately 1 month. Infarct size, initial perfusion defect (jeopardized segment) and noninfarcted muscle mass were studied in two groups of conditioned mongrel dogs. Group 1 (n = 11) served as the control group and Group 2 (n = 10) was pretreated with propranolol (2 mg/kg). Each animal in the propranolol-treated group was given identical amounts of the agent twice daily for 7 days after coronary occlusion. Both groups developed increases in the noninfarcted muscle mass of the left ventricle (compensatory hypertrophy). The mean increase averaged 19.8% over 30 days when the two groups were included together. Infarct size was smaller in the propranolol-treated group, and averaged 28% less (p less than 0.05) than that of the control group 30 days after initial myocardial infarction. Thus, pharmacologic interventions were shown by computed tomography to alter the size of an acute experimental myocardial infarct, particularly when examined over the time course of infarct healing. Moreover, compensatory hypertrophy occurred in both the control and propranolol-treated groups.     

Functional significance of post-myocardial infarction left ventricular hypertrophy: a beneficial response.

Hypertrophy of noninfarcted myocardium occurs as a chronic response to myocardial infarction, but no previous study has related the changes in wall thickness to serial changes in left ventricular function. Thus the functional significance of postinfarction hypertrophy is unknown. The purpose of this study was to determine the relationship between the development of postinfarction hypertrophy and the resting left ventricular ejection fraction measured by two-dimensional echocardiography. After occlusion of the proximal left anterior descending coronary artery in 11 dogs, the ejection fraction fell acutely (0.63 +/- 0.08 to 0.33 +/- 0.10, p less than 0.001) and rose at 3.5 months to 0.62 +/- 0.12. End-diastolic thickness of the noninfarcted left ventricle increased (11 +/- 1.0 mm to 13 +/- 1.4 mm, p less than 0.01) as did left ventricular mass (101 +/- 18 gm to 134 +/- 21 gm, p less than 0.0001). Restoration of the ejection fraction toward the baseline value correlated with the increases in left ventricular mass (r = 0.79, p = 0.007) and wall thickness (r = 0.71, p = 0.025). Hypertrophy of the noninfarcted myocardium correlated with the magnitude and approximately paralleled the time course of the improvement in the ejection fraction and therefore may have had a beneficial effect on resting left ventricular function as a chronic adaptation to myocardial infarction.     

Histochemical studies of monoamine oxidase in experimental myocardial infarctions.

Sequential histochemical studies were conducted to determine the level of monoamine oxidase (MAO) activity in the infarcted tissue of the experimental myocardial infarction in dog. MAO activity was not found in the normal heart muscle, but the activities were present in the wall of the coronary artery histochemically. Fibroblasts and collagen fibers began to take the place of the destroyed heart muscles in the infarcted area from 10 days after the coronary occlusion in dogs, and MAO activities were noted sporadically in the fibroblasts and the interstices of the collagen fibers in the infarcted area. MAO activities increased histochemically in the fibroblasts and the fiber interstices in the infarcted area 10 days or more after the coronary occlusion. These findings suggested the presence of the active collagen metabolism outside the myocardial cells in the infarcted area in the recovery stage of the experimental myocardial infarction. It was also suggested that the interstices of the collagen fibers in the myocardial wall constituted the lymphatic ducts outside the blood vessels and that the MAO activity in serum determined by the method in which tryptamine hydrochloride was used as substrate might indicate the grade of fibrosis of the myocardial tissue in the infarcted areas.     

Extension of Hemorrhage After Reperfusion of Occluded Coronary Artery: Contrast Echocardiographic Assessment in Dogs

Objectives. The aim of this study was to elucidate the progression of intramural hemorrhage complicated by reperfusion with the use of myocardial contrast echocardiography.Background. Although hemorrhagic infarction is known to occur in ischemia followed by reperfusion, its onset and sequence have not been well characterized.Methods. In 20 anesthetized dogs, 3-h occlusion of the left circumflex coronary artery was followed by reperfusion. The area at risk during coronary occlusion was ∼25%. Myocardial contrast echocardiogram was examined, and the time-intensity curves for both ischemic and nonischemic areas were obtained at baseline, at 3 min after reperfusion and then at 15-min intervals until 90 min after reperfusion. The wall thickness of both areas was also measured.Results. Gross hemorrhage in the reperfused areas was observed in five dogs (Group H) but not in seven dogs (Group NH). All wall segments were opacified at 3 min after reperfusion in both groups. However, the contrast defect spread significantly with time after reperfusion in Group H but not in Group NH (18.7 ± 3.4% and 3.3 ± 1.8%, respectively, at 90 min after reperfusion p < 0.005). The wall of the risk area at 90 min after reperfusion had thickened to 1.3 times baseline thickness in Group H but was unchanged in Group NH. The other eight dogs were excluded from study because of fatal arrhythmias or the existence of collateral circulation during coronary occlusion.Conclusions. Both progression of the contrast defect area on myocardial contrast echocardiography and a gradual thickening of the wall with reperfusion are characteristic of hemorrhagic infarction.     

Kinetics and imaging of indium-11-labeled autologous platelets in experimental myocardial infarction

The kinetics of accumulation and the external imaging patterns of indium-111-labeled platelets infused in a dog model of left anterior descending coronary artery occlusion with reperfusion were studied. The effects of infarct age and regional residual myocardial blood flow upon platelet accumulation were quantified, and the capacity of indium-111 platelets to image the experimental infarction was evaluated qualitatively. The endocardial accumulation of indium-111 platelets occurred primarily in infarct zones with residual blood flow less than 0.6 times normal and was maximal (24.98 +/- 2.76 times normal) in the lowest blood flow zone (less than 0.1 times normal). Indium-111 platelet accumulation in the epicardium occurred in the regions with blood flow less than 0.6 times normal and was maximal (17.83 +/- 1.20 times normal) in the lowest blood flow zone (less than 0.1 times normal). The maximal endocardial and epicardial platelet accumulation occurred 24 hours after reperfusion and was significantly decreased at 48 hours. In vivo cardiac images revealed discrete areas of increased myocardial radioactivity uptake in the anterior wall of dogs 24 hours after reperfusion. All images 48 hours after reperfusion were negative. Thus, in the experimental setting, indium-111 platelets allow quantification of platelet accumulation after myocardial infarction at a tissue level and provide a noninvasive means of in vivo imaging of reperfused infarcted myocardium.     

Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog

Accumulation of polymorphonuclear neutrophils during the acute inflammatory response may exacerbate tissue injury through the release of activated oxygen products or proteolytic enzymes or both. To assess the role of neutrophils in acute myocardial infarction, circulating neutrophil levels in dogs were reduced by 77 +/- 2% (mean +/- SEM) by administering rabbit antiserum to dog neutrophils. Acute myocardial infarction was induced in open-chest anesthetized dogs by 90 minutes of left circumflex coronary artery occlusion followed by 6 hours of reperfusion. Dogs treated with neutrophil antiserum (n = 8) developed myocardial infarcts that were an average of 43% smaller than infarcts in dogs treated with nonimmune rabbit serum (n = 7) (27.0 +/- 4.5% vs 47.1% +/- 7.5% of the area at risk, p less than 0.05). In a saline-treated control group (n = 8), infarct size was 48.0 +/- 4.7% of the area at risk, a value not significantly different from that of the nonimmune serum group but significantly greater than that in the neutrophil antiserum dogs (p less than 0.05). There were no major hemodynamic differences between groups. Histopathologic examination revealed that infarcted myocardium from dogs given saline or treated with nonimmune serum had a substantial neutrophilic infiltrate, which was virtually absent in infarcted tissue from dogs treated with neutrophil antiserum. These observations suggest that neutrophil accumulation in response to myocardial ischemia may be responsible for a substantial portion of the irreversible myocardial injury resulting from temporary coronary artery occlusion.     

犬心肌梗死后血管紧张素受体的异常分布及缬沙坦对其的调节作用

目的 探讨心肌梗死(MI)后心脏局部不同部位血管紧张素受体的分布情况及其对局部心室功能的影响,评价缬沙坦对其的调节作用,进一步阐明缬沙坦对心脏的保护机制.方法 将21只犬随机分为假手术组、MI组与缬沙坦组(MI后每天给予缬沙坦10 mg/kg),后两组建立左心室前侧壁MI模型.术后4周应用组织多普勒超声检测梗死区近端心底部及远端心尖部梗死比邻的非梗死区各部位心室功能;应用免疫组织化学技术及定量逆转录-聚合酶链反应检测上述部位血管紧张素Ⅱ(AngⅡ)1型受体(AT1)和2型受体(AT2)蛋白及mRNA表达情况,假手术组在MI组对应部位取材.结果 MI组心底及心尖部AT1受体蛋白和mRNA表达量均高于假手术组(P<0.05),缬沙坦组AT1受体蛋白和mRNA表达量均低于MI组(P<0.05),心尖部低得明显.MI组心底及心尖AT2受体蛋白及mRNA表达量高于假手术组(P<0.05),缬沙坦组AT2受体蛋白和mRNA表达量均高于MI组(P<0.05).MI组心尖侧心肌收缩峰值速度(Sm)、舒张早期峰值速度(Em)和舒张晚期峰值速度(Am)较心底侧降低的比率[(心底侧-心尖侧)/心底侧](分别为79.5%±3.3%,77.3%±5.3%,86.3%±2.5%)明显大于假手术组(分别为46.7%±8.5%,36.5%±5.2%,40.7%±7.8%,均P<0.01)和缬沙坦组(分别为63.5%±5.8%,53.9%±6.6%,55.5±6.1%,均P<0.01),缬沙坦组较MI组局部心肌收缩速度明显恢复.结论 MI后压力负荷促使AT1、AT2受体蛋白及mRNA表达量增加,缬沙坦能够抑制AT1受体上调,促进AT2受体上调,对心脏起保护作用.     

Early assessment of tissue viability with radioiodinated heptadecanoic acid in reperfused canine myocardium: comparison with thallium-201.

Myocardial scintigraphy with heptadecanoic acid labeled with iodine-123 (123I-HDA) may allow early noninvasive delineation of viable myocardium after reperfusion. In this study myocardial uptake of 123I-HDA was compared with that of thallium-201 in six closed-chest dogs after 5 hours of occlusion followed by 1 hour of reperfusion of the left anterior descending coronary artery. Myocardial blood flow was measured with microspheres, and myocardial viability was assessed by means of triphenyltetrazolium chloride staining. In viable areas of the reperfused region, 123I-HDA uptake, thallium-201 uptake, and myocardial blood flow were similar to those measured in the control circumflex region. However, in infarcted areas they were reduced to 48 +/- 2% (mean +/- SEM; p less than 0.001), 59 +/- 3% (p less than 0.001), and 74 +/- 5% (p less than 0.001) of control values, respectively. Results of multiple regression analysis showed that thallium-201 uptake primarily reflected the level of flow during reperfusion, whereas 123I-HDA uptake was dependent on both myocardial blood flow and viability. At each level of flow, 123I-HDA uptake was significantly lower in infarcted than in viable myocardium. By means of discriminant analysis, 123I-HDA uptake was found to be the single most important predictor of viability, whereas thallium-201 was only of limited importance. Myocardial 123I-HDA uptake greater than or equal to 71% or myocardial thallium-201 uptake greater than or equal to 73% best differentiated viable from infarcted myocardium. According to these criteria, 123I-HDA predicted myocardial viability with a sensitivity of 77%, a specificity of 84% and a predictive accuracy of 81%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distinguishing viable from infarcted myocardium after experimental ischemia and reperfusion by using nuclear magnetic resonance imaging

Early reperfusion has the potential for salvaging ischemic myocardium at risk for infarction. To test the ability of nuclear magnetic resonance (NMR) imaging to differentiate between stunned and infarcted myocardium early after reperfusion, 16 mongrel dogs underwent transient occlusion of the left anterior descending artery or a diagonal branch for 30, 60 or 180 min followed by reperfusion. To identify the area at risk for infarction and to assess the extent of hypoperfusion and reperfusion, two-dimensional and contrast echocardiography were performed at baseline study, during coronary occlusion and at three separate times during reperfusion (before NMR imaging, immediately after NMR imaging and 12 to 14 h later). Wall thickening in the control and ischemic zones and the circumferential extent of abnormal wall motion were analyzed at each time point using short-axis echocardiograms. Nuclear magnetic resonance imaging at 1.5 tesla was performed 2 to 3.5 h (mean 2.7 +/- 0.5) after reperfusion. Short-axis, multislice spin-echo images (TE 26 and TE 60) were obtained. Signal intensity was measured in the control and ischemic areas and expressed as a percent difference compared with normal myocardium. All dogs demonstrated a significant decrease in wall thickening and abnormal wall motion before and after NMR imaging. Seven of the eight dogs with infarction had an area of increased signal intensity on TE 60 images. The mean percent difference in signal intensity compared with adjacent normal myocardium was 127 +/- 68% (p = 0.002). None of the eight dogs without infarction had a visually apparent change in signal intensity on TE 60 images (mean percent difference versus control area 13 +/- 11%), despite regional systolic dysfunction documented by echocardiography at the time of imaging. The area of increased signal intensity correlated with infarct size (r = 0.69), although overestimation by NMR imaging occurred. The area of increased signal intensity did not correlate with the extent of echocardiographic contrast defect during coronary occlusion (risk area). This study demonstrates that NMR imaging can be applied early after coronary reperfusion to assess the potential for recovery of dysfunctional myocardium. In addition, by using a TE 60 multislice spin-echo imaging sequence at 1.5 tesla, quantification of the extent of infarction also may be possible.     

Detection of early myocardial tissue changes in acute canine myocardial infarction by ultrasonic tissue characterization methods

To determine the time after left anterior descending (LAD) artery occlusion in which myocardial texture changes first occur, two-dimensional echocardiograms on five sham operated dogs and eight dogs before and after proximal LAD occlusion were performed. Serial two-dimensional echocardiograms were performed every 15 mins by placing a 5 MHz transducer directly on the chest wall. The dogs were sacrificed at the end of the study and the area of myocardial infarction was confirmed by triphenyltetrazolium chloride staining. The two-dimensional echocardiogram images were digitized. The mean pixel intensity +/- SD in the area of myocardial infarction (region of asynergy) and a normally moving area (control region) equidistant from the transducer were calculated; thus, each dog served as its own control. In sham operated dogs, no significant changes in mean pixel intensity, skewness or kurtosis were observed. There was a significant increase (P less than 0.01) in mean pixel intensity in the infarcted regions (anteroseptal) compared to values obtained in the normally moving (lateral) regions at 30 mins (mean pixel intensity 25.2 +/- 2.1 versus 23.0 +/- 0.7, P less than 0.05); this difference persisted at 45 mins (mean pixel intensity 25.8 +/- 0.9 versus 22.6 +/- 0.5, P less than 0.01), 60 mins (mean pixel intensity 27.2 +/- 1.4 versus 22.8 +/- 0.8, P less than 0.01), 90 mins (mean pixel intensity 28.6 +/- 1.6 versus 22.5 +/- 0.9, P less than 0.01) and 180 mins (mean pixel intensity 28.7 +/- 1.8 versus 21.3 +/- 1.4, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of ischemic injury and early reperfusion derangements by hypothermic retroperfusion

Hypothermic synchronized retroperfusion was applied during coronary artery occlusion to determine its ability to alleviate junctional derangements of reperfusion and to reduce infarct size. The proximal left anterior descending coronary artery was occluded in 25 closed chest dogs for 3 hours and then reperfused for 7 days. Thirteen dogs with no reperfusion pretreatment served as a control group (Group A). In 12 dogs, hypothermic retroperfusion was applied from 30 minutes up to 3 hours of the occlusion period (Group B). Sequential two-dimensional echocardiographic and hemodynamic as well as metabolic measurements were performed. Compared with untreated control dogs, dogs with hypothermic synchronized retroperfusion had significantly reduced heart rate and rate-pressure product, decreased left ventricular volumes and improved ejection fraction during the occlusion period. Two-dimensional echocardiographically-derived ischemic zone systolic fractional area change and systolic wall thickening indicated significantly improved function as a result of retroperfusion. During the reperfusion period, untreated control dogs (group A) had more severe derangements in hemodynamics and wall motion than dogs treated by hypothermic retroperfusion (group B). Mortality was 30.7% in group A, 16.7% in group B and 7th day infarct size as percent of the left ventricle was 12.0 +/- 6.5 (mean +/- standard deviation) and 4.2 +/- 5.9, respectively (p less than 0.02). It is concluded that hypothermic synchronized retroperfusion applied after coronary occlusion and before reperfusion significantly improves cardiac function during occlusion, minimizes complications of reperfusion and reduces the ultimate infarct size. Because this form of circulatory assistance helps maintain cardiac function and delays the evolution of myocardial necrosis, its application may be beneficial during an evolving acute myocardial infarction before achievement of surgical or nonsurgical reperfusion.     

Kinetics of thallium-201 in reperfused canine myocardium after coronary artery occlusion

To study the kinetics of thallium-201 in nonsalvaged acutely infarcted myocardium and salvaged myocardium, the tracer was administered after experimental left anterior descending coronary artery reperfusion 2 hours after occlusion. In 19 dogs, thallium activity was then monitored for 4 hours in the reperfused anterior wall and normal posterior wall using miniature cadmium telluride radiation detectors. After sacrifice, 13 of the dogs were found to have an infarcted anterior wall by triphenyltetrazolium-chloride staining. In these dogs, mean (+/- standard deviation) fractional 4 hour thallium clearance was 0.33 +/- 0.08 for the infarct zone and 0.15 +/- 0.06 for the normal control zone (p less than 0.001). When computer-modeled, the clearance curve from the infarct zone was biexponential. The second exponential clearance curve from the infarct zone began 19.1 +/- 3.2 minutes after tracer administration, and was indistinguishable from the monoexponential clearance curve from the normal control zone. Thallium clearance from the blood pool was triexponential, the final exponential clearance curve being indistinguishable from the normal control zone clearance curve. Six dogs were found to have a salvaged noninfarcted anterior wall by triphenyltetrazolium-chloride staining. In these dogs, mean fractional 4 hour thallium clearance was 0.20 +/- 0.07 for the reperfused zone, and 0.19 +/- 0.08 for the normal control zone (p = NS). When computer-modeled, clearance curves for the reperfused and control zones were monoexponential. The monoexponential clearance curve for the salvaged reperfused zone was indistinguishable from the monoexponential clearance curve for normal myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determinants of myocardial hemorrhage after coronary reperfusion in the anesthetized dog

Intramyocardial hemorrhage often occurs with reperfusion in experimental acute myocardial infarction and is thought to be associated with extension of necrosis. To determine if hemorrhage was associated with extension of necrosis, 20 anesthetized dogs were reperfused after 6 hours of circumflex coronary artery occlusion and 10 others had control occlusion with no reperfusion. Fifteen of the 20 reperfused dogs had gross hemorrhage and none of the control dogs did. In 12 reperfused and 10 control dogs, radioactive microspheres were injected after coronary occlusion to quantitate collateral flow and in the reperfusion group microspheres were injected to quantitative reflow. Complete flow data were available in eight reperfused and 10 control dogs. Twenty-four hours after coronary occlusion, 1-g segments of infarct and control regions were analyzed for hemorrhage, collateral flow and creatine kinase activity. Serial microscopic examination was performed in eight additional dogs reperfused after 6 hours to determine if hemorrhage occurs into otherwise microscopically normal myocardium. Pathologic examination indicated that hemorrhage did not occur into otherwise microscopically normal myocardium. In dogs with hemorrhage, the extent of hemorrhage was inversely related to myocardial creatine kinase concentration and collateral flow. Mean collateral flow in 47 hemorrhagic segments was 4.5 ml/100 g (4.2% of control). Mean creatine kinase in 36 hemorrhagic segments was 233 mIU/g (21% of control). No hemorrhage was found in areas with collateral flow more than 21% of control or creatine kinase more than 37% of control. Mean reflow in hemorrhagic segments was 78.5% of control flow. These studies indicate that hemorrhage on reperfusion is associated with severe myocardial necrosis and markedly depressed flow before reperfusion and thus occurs only into myocardium already markedly compromised at the time of reperfusion. There is no evidence for hemorrhage into areas that had normal or even moderately depressed flows before reperfusion.