Experimental and clinical investigations for the time interval from onset of symptoms to the coronary reperfusion

To clarify the relationship between time interval from the onset of coronary occlusion to the reperfusion and reperfusion rates or left ventricular function, an experiment with 113 mongrel dogs was carried out. Coronary thrombi experimentally induced within 4 hours in 63 dogs were rapidly lysed by intracoronary thrombolytic agent (Experiment 1). Infarct size was investigated in 17 dogs. The infarct size (% of left ventricle) in 9 dogs with 4-hour reperfusion following 2-hour coronary occlusion was significantly smaller than that in 8 dogs with 6-hour occlusion (12.0 +/- 7.9 vs 19.1 +/- 8.7% respectively p less than 0.05) (Experiment 2). The infarct size in 8 dogs with 7-day reperfusion following 2-hour occlusion was also significantly reduced compared to that in 7 dogs with 7-day occlusion (16.3 +/- 7.4 vs 28.5 +/- 8.9%, respectively p less than 0.02) (Experiment 3). The infarct size in 11 dogs with 4-hour reperfusion with verapamil administration following 2-hour occlusion was significantly reduced compared to that in 7 dogs with 6-hour occlusion without verapamil (5.5 +/- 1.9 vs 20.3 +/- 3.3%, respectively p less than 0.01) (Experiment 4). In experiment 3, anterior wall motion also was assessed by contrast ventriculography and infarct related areas in reperfused group was found to be improved compared to non-reperfused group at 7 days after infarction. In clinical studies, 121 patients who were admitted within 12 hour of onset of symptoms, were investigated to evaluate reperfusion rates and left ventricular function. The reperfusion rate of young age thrombus within 3 hours was 89% of 18 patients with completely occluded coronary artery. It was 77% of the 52 patients with 3 to 6 hour occlusion and 72% of the 18 patients with over 6 hour occlusion. There was a tendency towards high reperfusion rates in younger thrombus. In patients who were recanalized within 3 hours from the onset of symptoms ejection fraction of left ventricle at the chronic stage had a significantly higher percentage when compared to the unsuccessful group. Wall motion of infarct-related areas in patients who were thrombolysed within 6 hours was improved compared to the unsuccessful group. Administration of verapamil during reperfusion in patients with acute myocardial infarction suppressed rapid CK release and sigma CK. Thus, young age thrombus can be lysed easily, earlier recanalization after coronary occlusion can reduce infarct size and improve left ventricular function. Reinforced administration of verapamil during reperfusion can also reduce infarct size.     

Serial nuclear magnetic resonance imaging of acute myocardial infarction with and without reperfusion

To compare nuclear magnetic resonance (NMR) image-derived T1 and T2 changes during evolving infarction, 14 dogs were studied serially: (1) 1 to 2 hours after left anterior descending coronary occlusion, (2) 2 to 3 hours after coronary occlusion (n = 7) or in the first hour after reperfusion following 2 hours of occlusion (n = 7), and (3) 5 days and (4) 21 days after occlusion/reperfusion. In addition, the extent of T1 and T2 abnormalities was compared to the extent of infarction as determined histologically for each set of images. With sustained coronary occlusion, an increase versus control values (T1 = 351 +/- 11 msec; T2 = 41 +/- 2 msec) was observed in the second hour after occlusion (T1 = 448 +/- 51 msec; T2 = 51 +/- 8 msec), gradually reaching a maximum by day 5 (T1 = 490 +/- 64 msec; T2 = 63 +/- 9 msec). By 21 days, T1 had decreased to 427 +/- 43 msec and T2 to 55 +/- 11 msec. However, with myocardial reperfusion, an abrupt increase in both T1 and T2 occurred compared to prereperfusion values in the first hour after release of occlusion, from 445 +/- 32 msec to 555 +/- 65 msec and from 52 +/- 5 msec to 65 +/- 8 msec, respectively. Subsequently, T1 remained elevated whereas T2 normalized. Only on day 21 images was there a good correlation between the extent of T1 and T2 abnormalities and infarct size, in both nonreperfused (r = 0.87; p less than 0.05), and reperfused (r = 0.89; p less than 0.01) dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Streptokinase improves reperfusion blood flow after coronary artery occlusion

Streptokinase is an effective thrombolytic agent which, with early restoration of coronary blood flow, has the potential for limiting infarct size. Distinct from thrombolysis, we studied the effects of streptokinase on reperfusion coronary blood flow and infarct size. Open-chest anesthetized canines underwent a 90 minute snare occlusion of the left circumflex coronary artery followed by release and reperfusion through a critical stenosis for 6 hours. The animals were assigned randomly to two groups. Intracoronary streptokinase [group 1 (n = 8): 6000 IU/kg in 3 ml of saline] or saline [group 2 (n = 8): 3 ml of saline] was infused at 0.05 ml/min for 60 minutes beginning 30 minutes before reperfusion. Coronary blood flow was stable in group 1 during reperfusion, while in group 2 it fell during 6 hours of reperfusion (30 +/- 4 ml/min to 18 +/- 2 ml/min, P = 0.05). The ST-segment elevation on the limb lead II electrocardiogram 15 minutes after coronary artery occlusion was similar in both groups (group 1: 3.9 +/- 0.6 mV, group 2: 2.3 +/- 0.5 mV), suggesting the extent of myocardial ischemia was also similar in both groups. The infarct sizes were similar when expressed both as a percent of the total left ventricular mass [(IZ/LV) group 1: 17 +/- 2.5%, group 2: 17.5 +/- 2.5%] or as a percent of the area at risk of infarction [(IZ/AR) group 1: 39 +/- 6%, group 2: 39 +/- 5%]. In both groups, the mass of left ventricle dependent on the blood flow distribution of the left circumflex coronary artery was similar when compared to total left ventricular mass [(AR/LV) group 1: 41 +/- 3%, group 2: 44 +/- 4%]. These results demonstrate that streptokinase maintains reperfusion coronary blood flow through a critical stenosis at a rate similar to baseline levels. Despite the fact that coronary blood flow remained stable with streptokinase during reperfusion, infarct size was not limited after 90 minutes of fixed coronary artery occlusion in this canine model of myocardial injury.     

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.     

Sustained beneficial effects of gallopamil (D600) on size of myocardial infarction 24 hours after coronary artery occlusion in dogs

To examine whether gallopamil (D600), a methoxy derivative of verapamil, has sustained beneficial effects on the ischemic myocardium, its effects on the size of myocardial infarction determined 6 hours (protocol 1) and 24 hours (protocol 2) after left anterior descending coronary artery occlusion were compared in anesthetized, open-chest dogs. To quantify the extent of the hypoperfused zone, Tc-99m- or In-111-albumin microspheres were injected into the left atrium 1 minute after occlusion. Fifteen minutes after occlusion, dogs were randomly assigned to a control group or a gallopamil-treated group that received immediately after assignment 0.08 mg/kg of gallopamil followed by a continuous infusion of 0.2 mg/kg/hr for 6 hours. Six or 24 hours after occlusion, the left ventricle was cut into 3 mm thick slices for triphenyltetrazolium chloride staining and autoradiography. There were no differences in the extent of the hypoperfused zone among the four groups. In both protocols 1 and 2 the ratio of the extent of myocardial necrosis to the extent of the hypoperfused zone was significantly smaller in the treated groups (56.7 +/- 6.7% [n = 8], p less than 0.01 and 72.3 +/- 5.3% [n = 6], p less than 0.05 for protocols 1 and 2, respectively) than in the control groups (100.7 +/- 6.0% [n = 7] and 95.2 +/- 4.3% [n = 5] for protocols I and II, respectively). Thus gallopamil administered early after coronary artery occlusion had beneficial effects on the ischemic myocardium, which were sustained for at least 24 hours after the onset of infarction.     

Experimental study on myocardial salvage by coronary thrombolysis and mechanical recanalization

Salvage of the ischemic myocardium by coronary thrombolysis and mechanical recanalization (simulated angioplasty) was studied in a canine experimental model of acute myocardial infarction induced by coronary occlusive thrombus at the left anterior descending coronary artery. Forty-four open-chest dogs divided into three groups were studied. Group I (n = 15, control group) was observed for 6 hours following the onset of infarct. In group II (n = 14, thrombolysis group), thrombolysis was obtained by intravenous administration of urokinase 2 hours after the onset of infarct. In group III (n = 15, mechanical recanalization group), simulated angioplasty was performed 2 hours after infarct. Coronary reperfusion was continued for 4 hours in groups II and III. The areas of left ventricular risk and infarct were measured by double staining methods with Evans blue dye and triphenyl tetrazolium hydrochloride. There were no significant differences in control blood flow and risk area in the three groups. Myocardial infarct area/risk area was 65 +/- 3% in group I, 45 +/- 1% in group II, and 35 +/- 2% in group III (group I vs II, p less than 0.001; group II vs III, p less than 0.001). Restored coronary blood flow in the left anterior descending artery was 8 +/- 1 ml/min in group II and 14 +/- 1 ml/min in group III (p less than 0.001). The data suggest that coronary mechanical recanalization is more effective than thrombolysis in salvaging the ischemic myocardium in the early phase of myocardial infarction, most probably because coronary blood flow is better restored by mechanical recanalization.     

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)     

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.     

福辛普利对猪急性心肌梗死再灌注后无再流的影响

目的评价福辛普利防治猪急性心肌梗死再灌注后无再流的作用。方法中华小型猪24只随机分成对照组、福辛普利组(1mg·kg-1·d-1)和假手术组,每组8只。冠状动脉结扎3h,松解1h制备急性心肌梗死再灌注模型。梗死前、后和再灌注后均行血液动力学测定和心肌声学造影检查,最终行病理学分析。结果心肌声学造影和病理染色所测的冠状动脉结扎区心肌范围(LA)差异无统计学意义。与对照组相比,福辛普利可促进急性心肌梗死后心功能的恢复,增加再灌注后1h冠状动脉血流量(对照组50·6%,福辛普利组72·1%,P<0·01),减少无再流面积(对照组心肌声学造影和病理:78·5%和82·3%LA;福辛普利组心肌声学造影和病理:24·5%和25·2%LA,P均<0·01),减少心肌坏死面积(对照组98·5%,福辛普利组88·9%LA,P<0·05)。结论福辛普利能有效地防治心肌梗死再灌注后无再流。     

Reduction in reperfusion injury by blood-free reperfusion after experimental myocardial infarction

Because myocardial reperfusion injury may be caused by various blood constituents, a transient period of blood-free reperfusion was evaluated in closed chest dogs subjected to a 90 min angioplasty balloon occlusion of the left anterior descending coronary artery. In the treated group (n = 13), the balloon remained inflated for an additional 15 min while the infarct vessel was perfused with an acellular oxygenated perfluorochemical emulsion (Fluosol). The balloon was then deflated, permitting blood reperfusion. In the control group (n = 13), the balloon was deflated after 90 min of coronary occlusion. One week after infarction, the area at risk was defined in vivo by monastral blue dye staining, and the area of myocardial necrosis was assessed using triphenyltetrazolium chloride staining with histologic confirmation. Major determinants of infarct size, including rate-pressure product, area at risk and severity of myocardial ischemia (assessed by the extent of ST segment elevation during coronary occlusion), were not significantly different in the two groups. Treated dogs demonstrated a 47% reduction in infarct size expressed as a percent of the area at risk compared with control dogs (27.0 +/- 4.4% versus 50.8 +/- 4.4%, p less than 0.01). Treated dogs also demonstrated a superior global left ventricular ejection fraction (57.5 +/- 2.5% versus 51.0 +/- 2.2%, p less than 0.05) and anterolateral (regional) ejection fraction (32.6 +/- 3.6% versus 19.8 +/- 3.9%, p less than 0.05) compared with values in control dogs assessed by contrast ventriculography after 1 week of reperfusion. It is concluded that a transient period of blood-free reperfusion with an oxygenated perfluorochemical reduces reperfusion injury in a canine model of myocardial infarction.     

Effects of intermittent coronary sinus occlusion on experimental myocardial infarction and reperfusion hemorrhage

The effects of intermittent coronary sinus occlusion (ICSO) on the size of myocardial infarction and reperfusion hemorrhage was evaluated. In Protocol 1, 8 dogs with ICSO and 8 controls underwent 4h of occlusion of the left anterior descending coronary artery. The same number of dogs underwent 4h of occlusion followed by 1h reperfusion in Protocal 2. The ICSO was started 1h after the ligation and continued through the occlusion period. There was no difference between the ICSO and the control group in hemodynamics and regional myocardial blood flow using hydrogen clearance method. However, ICSO did accelerate the rate of decline in intramyocardial CO2 tension. The half life of CO2 tension was 256 +/- 106 min in the control group but 139 +/- 34 min in the ICSO group (p less than 0.01). Lactate extraction rate showed the improving tendency during ICSO period. The ICSO resulted in a 50% and 80% reduction on an average in the size of infarct and reperfusion hemorrhage, respectively. We conclude that ICSO has prospective effects on myocardial ischemia with promise for clinical application.     

Short-term treatment with synchronized coronary venous retroperfusion before full reperfusion significantly reduces myocardial infarct size.

The efficacy of short-term synchronized coronary venous retroperfusion (SRP) before full arterial reperfusion was studied in a canine model. A control group (n = 6) was subjected to 90 minutes of occlusion of the left anterior descending coronary artery, which was followed by 6 hours of reperfusion. In another group (n = 6) the left anterior descending coronary artery was occluded for 2 hours followed by 5.5 hours of reperfusion. In this group SRP was applied for 30 minutes before full reperfusion. Myocardial regional blood flow was measured with the use of colored microspheres. During occlusion of the left anterior descending coronary artery, there was severe myocardial ischemia in both groups. Blood flow in the subendocardial area was, however, significantly better in the SRP group (0.51 +/- 0.17 ml/min/gm after 3.5 hours of reperfusion) than in the control group (0.29 +/- 0.16 ml/min/gm) after 4 hours of reperfusion (p less than 0.05). Left ventricular function was assessed as global ejection fraction from a left ventriculogram. Ejection fraction was reduced during ischemia in both groups (control = 38% +/- 3%, SRP = 32% +/- 8%). This dysfunction remained after 4 hours of reperfusion. Infarct size was assessed by means of triphenyltetrazolium chloride staining. The myocardial area at risk was similar in the two groups (control = 33.1% +/- 5.3%, SRP = 30.6% +/- 6.5%). Infarct size, which was expressed as the percent of the area at risk, was significantly smaller in the SRP group (17.2% +/- 14.6%) than in the control group (36.0% +/- 8.1%; p = 0.0197).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of cytochrome C on the extent of myocardial infarction and regional function of the ischemic myocardium

The effects of cytochrome C, an electron carrier in the process of oxidative phosphorylation, on infarct size and regional left ventricular function after a coronary artery occlusion were investigated. Thus, in 30 dogs, 1 minute after left anterior descending coronary artery occlusion, 99mTc-labeled albumin microspheres (8 mCi) were injected into the left atrium for subsequent assessment of the hypoperfused zone, that is, the area at risk of infarction. Fifteen minutes after coronary artery occlusion, dogs were randomized into a control group (n = 15) and a cytochrome C-treated group (n = 15). The latter immediately received cytochrome C, 2.5 mg/kg intravenously. Six hours after coronary artery occlusion the dogs were sacrificed and their left ventricles were cut into 3 mm thick slices. Infarct size was determined by triphenyltetrazolium chloride staining and measured by planimetry. The same slices were then submitted to autoradiography and the hypoperfused zone was then measured by planimetry. The hypoperfused zone was 22 +/- 2% and 23 +/- 2% of the left ventricle in the control and treated groups, respectively (NS), indicating that the extent of myocardium at risk before treatment was similar. The extent of the hypoperfused zone which evolved to necrosis was 90 +/- 3% in the control group but only 50 +/- 7% in the treated group (p less than 0.001). Myocardial salvage in the treated group was paralleled by improvement in systolic wall thickness of the ischemic segment as measured by two-dimensional echocardiography. Thus, cytochrome C reduced the extent of myocardial necrosis by 44% and improved systolic function of the ischemic myocardium.     

Assessment of myocardial perfusion by myocardial contrast echocardiography using harmonic power and the transvenous contrast agent SHU 563A in acute coronary occlusion and after reperfusion

BACKGROUND: Harmonic power Doppler imaging is a novel technique for the assessment of myocardial perfusion by contrast echocardiography. In this study, we examined whether myocardial contrast echocardiography using harmonic power Doppler and the new transvenous contrast agent SHU 563A can identify myocardial perfusion defects during coronary occlusion and reperfusion. METHODS: To assess the potential of this technique, we occluded either the left anterior descending coronary artery or the circumflex coronary artery for 2 to 3 h followed by 1 h reperfusion in 10 dogs in an open chest model. After transvenous administration of SHU 563A, an air-filled, polymeric contrast agent, myocardial contrast echocardiography was performed in short and long axis views with triggered harmonic power Doppler imaging after coronary occlusion and reperfusion. Post-mortem triphenyl tetrazolium chloride staining was performed to verify infarction. Harmonic power Doppler and anatomic data were analyzed by independent observers. RESULTS: During coronary occlusion, harmonic power Doppler showed perfusion defects in all 10 dogs. The defect size in the short axis view at papillary muscle level ranged 4-51% (14+/-13%) and 3-43% (16+/-10%) in the long axis view (% total LV slice area). After reperfusion (1 h) and infusion of dipyridamole (0.56 mg/kg), power Doppler demonstrated perfusion defects in seven dogs: 0-20% (9+/-8%) (short axis view) and 0-48% (13+/-14%) (long axis view). Five dogs showed anatomic infarction. The anatomic infarct area was 0-18% (6+/-8%) (slices corresponding to the echocardiographic short axis images). Perfusion defect size by harmonic power Doppler correlated well with residual infarct size (r=0.82, P<0.01). CONCLUSIONS: Myocardial contrast echocardiography using harmonic power Doppler and the new contrast agent SHU 563A accurately displays perfusion defects during acute coronary occlusion and after reperfusion. The site and size of residual myocardial infarction is reliably identified on line, in color. This approach has excellent potential for clinical application.     

Limitations of fluorocarbons in reducing myocardial infarct size

The effects of the oxygen-carrier fluorocarbons on myocardial infarct size were assessed in non-exchange-transfused dogs subjected either to a 3-hour occlusion of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion (protocol I) or to a 5-hour permanent LAD occlusion (protocol II). Fluorocarbon administration was begun 30 minutes after LAD occlusion and was continued over the entire period of ischemia. After 5 hours, the hearts were excised and areas of necrosis were visualized by triphenyl tetrazolium chloride staining while risk regions were assessed by radiolabeled microspheres injected after coronary occlusion just before the onset of therapy, and further, in protocol I, by thallium-201 perfusion imaging performed at the end of fluorocarbon administration. In protocol I experiments, the ratio of necrotic area to area at risk was 81 +/- 35% (mean +/- standard deviation) in control saline-treated dogs (n = 6) and 67 +/- 27% in fluorocarbon-treated dogs (n = 6) (difference not significant). There was no significant difference between risk regions measured after and before fluorocarbon treatment. In protocol II, the ratio of necrotic area to area at risk was 47 +/- 30% in control dogs (n = 5) and 63 +/- 29% in fluorocarbon-treated dogs (n = 5) (difference not significant). However, in control dogs, the ratio of necrotic area to area at risk increased from 47 +/- 30% in the dogs that underwent permanent occlusion to 81 +/- 35% in the group that underwent reperfusion (p less than 0.001) while this ratio was similar in the corresponding subsets of fluorocarbon-treated animals.(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.     

Anterior transmural myocardial infarction: effects of surgical coronary reperfusion on global and regional left ventricular function

Global and regional left ventricular function were assessed before and after surgical coronary reperfusion in 54 patients surviving anterior transmural myocardial infarction. Two groups were identified. Group I (n = 34) was treated within 4.8 +/- 0.7 (mean +/- standard deviation) hours of onset of symptoms of anterior transmural myocardial infarction, and Group II (n = 20) was treated 9.2 +/- 4.8 hours from the onset of symptoms (p less than 0.01). On study entry, the two groups were similar in all characteristics except global left ventricular ejection fraction (48 +/- 9 versus 42 +/- 13%, p less than 0.05). Regional ejection fraction was obtained by computer-assisted planimetry from ventriculographic tracings at end-systole and end-diastole. The anterior wall was divided into four equal segments from the apex (area 1) to base (area 4). Areas 2 and 3 defined the midportion of the anterior wall of the left ventricle. This yielded four fractional changes expressed as ejection fraction in percent. Global and regional ejection fractions (from apex to base) of the anterior wall significantly improved in Group I (from 48 +/- 9 to 55 +/- 11%; 7 +/- 17 to 18 +/- 20%; 12 +/- 14 to 25 +/- 18%; 25 +/- 15 to 38 +/- 17%; and 39 +/- 13 to 41 +/- 12%) (p less than 0.05, except for the basal area), but only to a minor degree in Group II (from 42 +/- 13 to 45 +/- 16%; 9 +/- 10 to 13 +/- 15%; 10 +/- 10 to 17 +/- 10%; 27 +/- 16 to 32 +/- 14%; and 37 +/- 10 to 36 +/- 13%) (all p values were not significant [NS] except for region 2). These data suggest significant enhancement of global function and regional wall motion in selected patients if surgical reperfusion is performed within 6 hours from the onset of symptoms of anterior infarction. Little improvement can be expected when the procedure is instituted later than 6 hours from peak symptoms, although improvement in some patients occurs if adequate collateral perfusion or nontotal left anterior descending coronary occlusion is present. In spite of functional improvements, some contractile deficit persisted throughout the period studied even when successful reperfusion was achieved early during evolving anterior transmural myocardial infarction.     

Left ventricular unloading during reperfusion does not limit myocardial infarct size

To determine whether venting the left ventricle during coronary reperfusion limits myocardial infarct size, we studied paced (200 beats/min) Langendorff rabbit hearts, perfused with blood from a support rabbit. A left coronary artery was occluded for 60 minutes, followed by 2 hours of reperfusion. Four experimental conditions, as follows, were used: In group 1 (control), the hearts contracted isovolumetrically on a fluid-filled balloon in the left ventricle during both occlusion and reperfusion. In group 2, the balloon was present only during occlusion, and the heart was vented during reperfusion. Hearts in group 3 were vented during occlusion and developed pressure during reperfusion. In group 4, the left ventricle was vented during occlusion and reperfusion. Perfusion pressure (91.2 +/- 0.9 mm Hg) and coronary flow (0.88 +/- 0.03 ml/min/g) were not different between groups. Left ventricular pressures (mean of all groups) were 87.3 +/- 1.5 mm Hg systolic and 6.5 +/- 0.6 mm Hg diastolic. Infarcted myocardium was assessed by triphenyl tetrazolium staining and expressed as a percentage of the area at risk, as measured by fluorescent particles. Venting during both ischemia and reperfusion (n = 10) did result in significantly smaller infarcts than in the unvented controls (n = 10), that is, 13 +/- 5% vs. 41 +/- 6%, respectively. Venting only during reperfusion (n = 10) or occlusion (n = 11) did not significantly limit infarct size (57 +/- 6% and 32 +/- 5%, respectively), as compared with controls. Thus, the clinically feasible intervention of left ventricular venting during reperfusion was not cardioprotective.     

Myocardial thallium-201 kinetics and regional flow alterations with 3 hours of coronary occlusion and either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis

Myocardial thallium-201 kinetics and regional blood flow alterations were examined in a canine model using 3 hours of coronary occlusion and different methods of reperfusion. Group I comprised 10 dogs undergoing a 3 hour left anterior descending artery occlusion and no reperfusion. Group II comprised seven dogs undergoing 3 hours of left anterior descending artery occlusion and rapid reperfusion through a totally patent vessel. Group III comprised 10 dogs undergoing 3 hours of left anterior descending artery occlusion and slow reperfusion through a residual stenosis. All dogs received 1.5 mCi of thallium-201 after 40 minutes of coronary occlusion. During occlusion and 2 hours of reperfusion, serial hemodynamic, blood flow and myocardial thallium-201 activity measurements were made. The relative thallium-201 gradient (normal zone minus ischemic zone activity when initial normal activity is expressed as 100%) during left anterior descending coronary occlusion was similar in all groups. Group I, 87 +/- 3%; Group II, 78 +/- 6%; Group III, 83 +/- 6% (p = NS). After 2 hours of either method of reperfusion, the final relative gradient had decreased to a similar level (Group II, 51 +/- 9%; Group III, 42 +/- 6%). These values were not significantly different from the final relative thallium-201 gradient seen in dogs undergoing a sustained 3 hour occlusion (Group I, 55 +/- 5%). After 2 hours of reperfusion, both methods of reflow were associated with similar degrees of "no reflow." Transmural flows in the central ischemic zone were 89 +/- 10% of normal in Group II and 71 +/- 6% of normal in Group III after reperfusion, with both flows substantially higher than the relative thallium-201 activities in these dogs. Infarct size (percent of left ventricle) determined with triphenyltetrazolium chloride was similar in all groups (Group I, 24 +/- 4%; Group II, 29 +/- 4%; Group III, 25 +/- 4%). Thus, in this experimental canine model, 3 hours of coronary occlusion followed by either rapid reperfusion through a totally patent vessel or slow reperfusion through a critical stenosis resulted in little delayed thallium-201 redistribution or myocardial salvage as assessed histologically, despite significant recovery of regional flow.     

Effects of previous myocardial infarction on measurements of reactive hyperemia and the coronary vascular reserve

The measurement of coronary vascular reserve by the reactive hyperemic response to ischemia has been advocated as a practical method of assessing the physiologic significance of coronary stenoses. Because the concept of measuring coronary blood flow during maximal vasodilation assumes a normal arteriolar network and viable myocardium, the presence of previous myocardial infarction may cause a significant decrease in the coronary reserve unrelated to the severity of a coronary stenosis itself. To determine the potential importance of this effect, rest and hyperemic coronary blood flow were measured in 14 dogs in the regions subtended by the left anterior descending and left circumflex coronary arteries. One hour occlusion of the left anterior descending artery followed by reperfusion was performed in 10 dogs; the 4 remaining dogs in which no occlusion was performed served as control animals (group 3). One week later, rest and hyperemic blood flow measurements were repeated in all 14 dogs. Of the 10 dogs undergoing left anterior descending artery occlusion, 5 had a large infarct (group 1) and 5 had a small infarct (group 2). In group 1 in the 1 week study, both the coronary reserve in the left anterior descending artery zone and the ratio of the coronary reserve in this zone and the left circumflex artery zone decreased compared with values before occlusion (from 425 +/- 134 to 150 +/- 34% and from 1.56 +/- 0.40 to 0.68 +/- 0.31, respectively; both p = 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)