Changes in Coronary Perfusion after Occlusion of Coronary Arteries in Kawasaki Disease

Purpose

Myocardial infarction in children with total occlusion of a coronary artery after Kawasaki disease is rare due to multiple collateral vessels. We aimed to investigate the changes in coronary perfusion associated with coronary artery occlusion after Kawasaki disease.

Materials and Methods

Eleven patients with coronary artery occlusion after Kawasaki disease were investigated. Serial coronary angiographies after total occlusion of a coronary artery were reviewed and the changes were described in all patients with additive information collected.

Results

The median age at the occlusion was 5.9 years old. The interval to occlusion was 6.2±6.9 years. Four left anterior descending coronary artery total occlusions and 10 right coronary artery total occlusions were detected. Immediate coronary artery bypass graft for left anterior descending coronary artery total occlusion made right coronary total occlusion occurred in all except one patient and the intervals thereof were 1 year, 1.8 years, and 4 years. Collaterals to the left coronary artery regressed after recanalization, while new collaterals to the right coronary artery developed. In three, collaterals to the right coronary artery decreased without recanalization without clinical signs.

Conclusion

The right coronary artery should be followed up carefully because of possible occlusion of new onset or changes in collaterals.     

Experimental infarct size as a function of the amount of myocardium at risk.

Occlusion of the same coronary artery at the same anatomic site in a group of dogs results in significant variation in the size of the resultant infarcts. The present study shows that much of this variation can be explained by differences in the pattern of distribution of the occluded coronary artery. The relationship between the anatomic size of an occluded coronary bed and the the amount of necrosis resulting from 40 minutes of proximal circumflex coronary (LCC) occlusion and 3 days of reperfusion was determined in randomly selected dogs using an in vitro latex coronary injection technique. The amount of necrosis, calculated from serial histologic sections taken through the posterior papillary muscle (PP), correlated closely with the size of the occluded coronary bed: 5 dogs with small LCC beds (26 +/- 2%) had 10 +/- 3% PP necrosis; 5 dogs with medium-sized LCC beds (37 +/- 2%) had 33 +/- 1% necrosis; and 7 dogs with large LCC beds (42 +/- 1%) had 51 +/- 2% necrosis. The results show that much of the variability in infarct size among dogs subjected to coronary artery occlusion at the same anatomic site is a function of differences in ischemic bed size. Grouping dogs by occluded coronary bed size may improve the resolution of experimental studies testing the effect of various therapies on infarct size.     

Myocardial performance and collateral flow after transient coronary occlusion in exercising dogs.

Fourteen dogs with prior constriction of the left circumflex (LCf) coronary artery were studied at rest and during treadmill running. Hemodynamics were measured before and after a 1-min LCf occlusion. Coronary and collateral flows were quantitated during occlusion both at rest and during exercise. Group I consisted of 4 dogs with resting collateral flow exceeding one-half (average 78%) of normal flow, and group II consisted of 10 dogs with collateral flows less than one-half (average 30%) of normal. At rest LCf occlusion caused no hemodynamic changes in group I, but stroke volume fell significantly in group II. During running, collateral flow after LCf occlusion doubled in group I, and there was only a small rise in left atrial pressure to 18 mmHg. In group II, collateral flow increased by 50% during running and actually decreased in 4 dogs. Significant cardiac failure developed as stroke volume halved, and left atrial pressure rose to an average 30 mmHg. Therefore exercise-induced depression of left ventricular function in the ischemic heart can be correlated to the amount of coronary collateral flow.     

Coronary arteriographic findings soon after non-Q-wave myocardial infarction

Complete occlusion of the infarct-related coronary artery is a frequent finding soon after Q-wave (transmural) myocardial infarction. We performed coronary arteriography to study the frequency of total coronary occlusion and of angiographically visible collateral vessels in 341 patients within one week of non-Q-wave myocardial infarction. In this cross-sectional study, 192, 94, and 55 patients underwent coronary arteriography within 24 hours of peak symptoms, between 24 and 72 hours after peak symptoms, and between 72 hours and seven days after peak symptoms, respectively. In the three groups, total occlusion of the infarct-related vessel was found in 26 percent (49 of 192), 37 percent (35 of 94), and 42 percent (23 of 55) of the patients, respectively (P less than 0.05). The presence of visible collateral vessels increased in parallel: 27 percent (52 of 192), 34 percent (32 of 94), and 42 percent (23 of 55), respectively (P less than 0.05). The frequency of subtotal occlusion (i.e., greater than or equal to 90 percent stenosis) decreased inversely: 34 percent (65 of 192), 25.5 percent (24 of 94), and 18 percent (10 of 55), respectively (P less than 0.05). Thus, in contrast to Q-wave infarction, total coronary occlusion of the infarct-related vessel is infrequently observed in the early hours of non-Q-wave infarction, but it increases moderately in frequency over the next several days. These cross-sectional data suggest that non-Q-wave infarction may be related to a preserved but marginal blood supply, which sufficiently disrupts the relation between the supply of and the demand for myocardial oxygen to cause tissue necrosis.     

Distribution of cytosolic and mitochondrial aspartate aminotransferase in normal, ischemic, and necrotic myocardium. An immunohistochemical study

We utilized immunoperoxidase methods to study the distribution of both cytosolic or soluble(s) and mitochondrial (m) aspartate aminotransferase (AspAT) in normal, ischemic, and necrotic myocardium. Human myocardium was obtained from autopsy (n = 9) and surgery (n = 6). Cardiac tissue from 26 dogs with experimental myocardial infarction induced by closed-chest balloon occlusion and four dogs with myocardial ischemia without necrosis induced by a 50% reduction in left main coronary artery flow for 3 hours were studied. Duration of occlusion was 45 minutes (n = 1), 3 hours (n = 11), 5 to 6 hours (n = 10), or 15 to 24 hours (n = 4). Highly purified m- and s-AspAT and specific antibodies were prepared in our laboratory. In all cases, control experiments were performed. Microscopically normal human and dog myocardium uniformly stained for m- and s-AspAT. Necrotic myocardium from patients with infarcts showed markedly reduced immunostaining. In those dogs with myocardial necrosis, all dogs with coronary occlusion of 5 to 24 hours, and eight of 11 dogs with 3-hour occlusions, immunostaining was significantly reduced for both s- and m-AspAT in regions confirmed to be necrotic by triphenyl tetrazolium chloride and hematoxylin and eosin staining. Myocardial necrosis was confirmed in the 3-hour infarcts by electron microscopy. In the four dogs with a 50% reduction in left main flow for 3 hours, and one dog with a 45-minute coronary occlusion, ischemia was demonstrated by glycogen loss in period acid-Schiff-stained sections but there was no evidence of necrosis by electron microscopy or triphenyl tetrazolium chloride staining and there was no loss of immunostaining evident for s- or m-AspAT. Thus, s- and m-AspAT were visualized in normal and ischemic myocardium with decreased staining in necrotic tissue using immunoperoxidase techniques. Loss of both s- and m-AspAT can be demonstrated in human myocardium and in experimental canine myocardium as early as 3 hours after coronary occlusion and appears to be specific for irreversible myocardial injury. No depletion of isoenzyme can be detected by immunohistochemical techniques in tissue that is ischemic but not necrotic. Furthermore, by these immunoperoxidase techniques, loss of s- and m-AspAT from necrotic myocardium appears to be simultaneous.     

Verapamil in two reperfusion models of myocardial infarction. Temporary protection of severely ischemic myocardium without limitation of ultimate infarct size

The ability of verapamil to protect severely ischemic myocardium was assessed in dogs using 40 minutes of temporary coronary occlusion. Reperfusion was established for 4 days after which infarcts were sized histologically. Untreated dogs developed subendocardial infarcts (the more moderately ischemic subepicardial region being salvaged by reperfusion). Pretreatment with verapamil reduced the size of these subendocardial infarcts from 34 +/- 8 to 8 +/- 3% of the ischemic circumflex vascular bed at risk (identified by postmortem perfusion of the previously occluded and unoccluded arteries with different dyes). Thus, verapamil prevented cell death in the severely ischemic subendocardial region for the 40-minute test period. In a second study to establish whether verapamil could delay cell death for a longer period of time in the less severely ischemic subepicardial region, a 3-hour period of coronary occlusion was used. This period of occlusion caused infarcts averaging 60 +/- 6% of the ischemic area at risk in untreated dogs. Dogs treated with verapamil 15 minutes postocclusion and throughout the remaining 165 minutes of the 3-hour test period had no limitation of infarct size (53 +/- 3% of the area at risk). In this 3-hour study, the effect of variation in collateral blood flow on infarct size was evaluated by plotting infarct size versus subepicardial collateral flow. Verapamil neither improved collateral flow nor altered the relationship between infarct size and baseline collateral flow. Thus, pretreatment with verapamil prevented necrosis of severely ischemic myocytes, when reperfusion was established at 40 minutes, but failed to prevent necrosis of moderately ischemic myocardium and thus failed to limit infarct size when the period of coronary occlusion was prolonged to 3 hours and treatment was started 15 minutes after the onset of ischemia.     

Myocardial infarction in dogs with acute and gradual occlusion of the circumflex or right coronary arteries

This study was designed to quantitate and describe the incidence and magnitude of myocardial infarction in the canine heart following acute and gradual occlusion of the circumflex or right coronary arteries. In animals with acute occlusion, the circumflex artery was ligated just distal to the bifurcation of the left coronary artery for 4 hr (seven dogs). Gradual occlusion was produced by placing an Ameroid occluder on the circumflex artery for 1 month (nine dogs), 3 months (nine dogs), and 5 months (eight dogs) and on the right coronary artery for 3 months (nine dogs). Ten dogs served as controls. At the end of the experiments the dogs were sacrificed, and identification of myocardial infarction was made with an enzyme-mapping technique in dogs with acute occlusion and with histological methods in dogs with gradual occlusion. The volume of ventricular infarction was determined with the use of an Apple II Computer and graphics tablet. After 3 months, gradual occlusion of the right coronary artery produced a 22% incidence of infarction which was significantly less (P <.01, X²) than the 67% incidence observed with 3 months of gradual circumflex occlusion. The average infarct volume produced by gradual right coronary occlusion was 0.94 + 0.69%. The average volume of left ventricular infarction in animals with circumflex acute occlusion was 15.6% + 6.6 and the incidence of infarction was 100%. With gradual occlusion of the circumflex artery for 1, 3, and 5 months, average left ventricular infarction was 2.02 ± 1.01%, 3.13 ± 1.53%, and 2.96 ± 1.35%, respectively. There were no significant differences in the amount of damage observed among the three groups with gradual occlusion, and the average incidence of infarction for these three groups was 76%. In the 1-, 3- or 5- month animals with circumflex occlusion, no additional areas of necrosis subsequent to the original damage were found, indicating that infarction is a single event in this model of gradual occlusion. These results suggest that infarct size is determined primarily by factors at the time of total occlusion and that gradual occlusion allows sufficient time for collateral growth, thereby limiting the extent of myocardial injury.     

Myocardial infarction in the baboon: regional function and the collateral circulation.

Occlusion of the anterior descending coronary artery was produced in sedated baboons 7-15 days after implantation of a micromanometer and ultrasonic crystals for measurement of regional left ventricular dimensions in ischemic, marginal, and control segments. One minute after coronary occlusion (CO), ischemic segments exhibited a marked systolic bulge with wall thinning, and percent systolic shortening of marginal segments decreased. Over the ensuing weeks, there was a progressive increase of end-diastolic lengths in marginal and ischemic segments, whereas systolic shortening in these segments did not improve significantly. Control segments did not change. In control baboons, the coronary collateral index was 55 +/-25 (SE) compared to 560 +/- 74 in normal dogs. One month after CO, the collateral index was 543 +/- 144 in baboons compared to 6,685 +/- 716 in dogs, regions of normal tissue were seen in the infarct (14.2 +/- 2% of left ventricular mass). Minimal coronary collateral development in the baboon provides a likely explanation for differences from the dog in regional functional responses and in the character of the infarct.     

Effects of time on volume and distribution of coronary collateral flow.

Changes in the volume and distribution of collateral blood flow were studied during the 1st h after coronary occlusion in nine open-chest dogs. Labeled microspheres (7-10 mum) were injected into the left atrium prior to and 20 s, 5 min, and 60 min after acute occlusion of the midcircumflex coronary artery so that myocardial perfusion to small segments of the entire left ventricle could be measured. The segmental perfusions were classified as normally perfused, severely hypoperfused, moderately hypoperfused, and borderline hypoperfused. Standard hemodynamic measurements were obtained and relative coronary vascular resistance to the normally perfused and hypoperfused zones was calculated. The principal conclusions of the study are as follows: 1) during the 1st h after coronary occlusion the collateral flow to the hypoperfused myocardium increases substantially; 2) the increase in collateral flow is distributed fairly evenly to various hypoperfused zones and is associated with a marked decrease in coronary vascular resistance; and 3) as a result of this influx in collateral flow the size of the hypoperfused area decreases and the relative proportion of severely hypoperfused segments within the hypoperfused area decreases.     

Intramural PCO2: a reliable index of the severity of myocardial ischemic injury.

The present study was performed to evaluate the usefulness of changes in intramural oxygen (PmO2) and carbon dioxide (PmCO2) tensions shortly after coronary artery occlusion as indices of the severity of myocardial ischemic injury. In 14 open-chest, anesthetized dogs, a 60-min coronary artery occlusion was performed, during which PmO2 and PMCO2 were measured continuously with a mass spectrometer. Regional myocardial blood flow (RMBF) adjacent to the mass spectrometer probes was measured by the xenon-127 washout technique both before and 30 min after coronary artery occlusion. At the end of 60 min of occlusion, the dogs were killed, and biopsies for histological examination of 1-micron-thick sections were obtained from the tissue surrounding each mass spectometer probe. The decline in PmO2 during the 60-min occlusion bore no relationship either to the severity of ischemic injury as assessed by histological examination, or to the reduction of RMBF. In contrast, the magnitude of rise in PmCO2 during the 60 min of occlusion corresponded closely to both the severity of injury assessed histologically and the reduction of RMBF.     

The effect of chronic hypoxemia on regional myocardial blood flow in the conscious dog after acute coronary artery occlusion

Chronic hypoxemia was produced in 16 dogs by surgical transposition of the caudal vena cava to the left atrium to determine if chronic hypoxemia would alter the response of the myocardium to acute ischemia. An electromagnetic aortic flow probe, left atrial tube, and occlusive cuff on the left circumflex coronary artery were permanently implanted in 11 hypoxemic and 26 normal control dogs. The animals were studied in the conscious state after recovery from the surgery. Dogs with hypoxemia had a blood hematocrit value of 54.3 ± 1.0% (SE), arterial PO₂ of 43.2 ± 1.4 mm Hg, and 80.2 ± 1.6% oxygen saturation. There was no difference from control animals in the ratio of left ventricular weight to body weight, but the right ventricular weight was significantly decreased in the hypoxemic dogs. Cardiac output from the left ventricle was twice that of the right ventricle. Aortic blood flow was 3.68 ± 0.22 liters/min in hypoxemic animals and 2.64 ± 0.19 liters/min in normal dogs. Myocardial blood flow measured with 15-μ diameter tracer microspheres was increased from 79 ± 10 and 59 ± 8 ml/100 g/min in left ventricular endocardial and epicardial halves, respectively, in normal dogs to 212 ± 48 and 172 ± 39 in dogs with chronic hypoxemia. There were no deaths in 10 hypoxemic dogs within 24 hours after complete circumflex coronary artery occlusion; 7 of 26 (27%) normal dogs died after circumflex coronary artery occlusion during the conscious state. Gross infarct size was extremely variable in both groups. Median infarct size was smaller in dogs with hypoxemia and was directly correlated with arterial PO₂ in hypoxemic dogs. There was a mild, but statistically not significant, increase in the anastomotic index of hypoxemic dogs compared with that of normal animals, suggesting that a metabolic adaptive change rather than increased collateral circulation may have been responsible for the decreased mortality and smaller infarct size in hypoxemic dogs.     

Analog Electrical Model of the Coronary Circulation in Case of Multiple Revascularizations

In this work, we propose an analog electrical model of the coronary circulation for patients with obstructive disease undergoing revascularization. In this clinical situation, the collateral circulation to the occluded artery is difficult to ascertain via preoperative measurements and well-developed collaterals might induce long-term restenosis of the revascularized artery due to flow competition mechanisms. The proposed model allows an original biomechanical analysis of per-operative hemodynamic data in order to assess quantitative evaluation of pressures and flows inside the native stenosed arteries, the collateral network and the bypass grafts. Average cardiac cycle values are analysed. In the case of 3-vessel disease and chronic occlusion of the right coronary artery, the quantitative results confirm the protective effects of the collateral flows in the pathological situation, but also show that the revascularization of the occluded right artery is fully justified since the collateral flows remain low, even when the left territory is revascularized. The model thus provides a computational tool to evaluate therapeutic strategies for each patient.     

Dynamics of the sounds caused by partially occluded femoral arteries in dogs

Previous studies have indicated that partially occluded arteries produce sounds due to turbulence. If these sounds from the coronary arteries could be detected externally, they would provide a simple approach to the detection of coronary artery disease. To confirm the hypothesis that coronary stenosis produces detectable acoustic correlates, sounds caused by a controlled occlusion of the femoral artery of dogs were detected and analyzed using both the fast Fourier transform (FFT) and the autoregressive (AR) methods. The femoral artery was chosen, since its size and flow approximate those of coronary arteries in humans. The poles of the AR spectra and the power ratios of different sections of the FFT and AR spectra were used to differentiate the degree of the stenosis. The results showed that high frequency acoustical power between 200 and 800 Hz is associated with the turbulence produced by the partially occluded femoral arteries of the dogs. Using the AR method, high acoustic power above 200 Hz increased when the degree of the occlusions increased. The poles and power ratios of the AR spectra differed according to the degree of stenosis. However, the high frequency acoustical power above 200 Hz did not increase above the 85% occlusion.     

冠心病患者冠状动脉侧支循环的形成与PDGF mRNA水平的关系

目的:探讨冠心病患者单核细胞血小板源性生长因子(PDGF)与冠状动脉侧支循环的关系。方法:依据选择性冠状动脉造影结果将64例患者分为对照组(非冠心病患者,n=15)、冠心病不伴侧支循环组(n=31)、冠心病伴侧支循环组(n=18),采用RT-PCR技术检测3组患者主动脉根部血液及股动脉血液中单核细胞PDGFmRNA水平。结果:(1)冠心病患者有、无侧支循环组之间的冠状脉动病变程度、不稳定心绞痛及心肌梗死发生率无显著差异(P>0.05);但无侧支循环患者心功能不全、室壁瘤的发生率显著增加(P<0.01);(2)与对照组相比,冠心病患者主动脉根部血液单核细胞PDGFmRNA水平增加(P<0.01);有侧支循环患者增加更为显著(P<0.01);而冠心病患者股动脉血液中单核细胞PDGFmRNA水平显著增加(P<0.01),有无侧支循环者之间无显著差别(P>0.05)。结论:冠状动脉侧支循环的建立可显著降低心肌梗死后心功能不全、室壁瘤的发生;PDGFmRNA水平增加与冠状动脉侧支循环形成密切相关;侧支循环形成与否可能主要取决于病变冠状动脉局部单核细胞PDGF基因水平;单核细胞PDGF基因水平可作为评价冠心病患者预后好坏的指标之一。     

Anomalous branch of the left common carotid artery

A previously unreported anomalous branch of the left common carotid artery (LCCA) was observed during dissection at the Zagreb Medical School. The anomalous branch arose from the anterior surface of the LCCA approximately 2 cm superior to the aortic arch, and subsequently bifurcated into a right and left branch. We describe its anatomic features. Clinical implications are also discussed.     

Septal collateralization: Demonstration of canine intramyocardial collaterals

The anatomical distribution of intra-myocardial collateral arteries that develop from the septal to the other major coronary arteries was studied in dogs following gradual Ameroid occlusion of tftt circumflex artery. The septal artery was cannulated and injected with Batson's plastic compound resulting in a cast of the coronary circulation. Collateral vessels radiated from the septal vascular bed to both the circumflex and anterior descending arteries. The collaterals developed from the entire base-to-apex extent of the septal artery and were found on both the right and left sides of the septum. Collateral growth appeared to be more concentrated at the apex of the heart. The anatomical details of septal collateral circulation illustrate the importance of intramyocardial collateralization in the dog, which was thought to exhibit primarily epicar-dial collaterals.     

Ventricular arrhythmias parallel cardiac histamine efflux after coronary artery occlusion in the dog

Release of cardiac histamine by immunologic and pharmacologic stimuli is known to provoke ventricular arrhythmias. Augmented histamine efflux from ischemic myocardium has been proposed but remains controversial. The purpose of this study was to determine whether cardiac histamine efflux is precipitated by coronary artery occlusion and if so, whether histamine efflux is associated with the development of early ischemic ventricular arrhythmias. The left anterior descending coronary artery was occluded while recording a continuous electrocardiogram and coronary sinus blood was sampled frequently during the first 30 min of coronary artery occlusion in pentobarbital-anesthetized, openchest dogs. Coronary sinus histamine concentration rose from a mean baseline of 0.06±0.10 ng/ml (±SD) before coronary artery occlusion to a mean peak of 0.61±0.40 ng/ml after coronary artery occlusion (p<0.0001;n=14). The median peak coronary sinus histamine concentration was significantly greater in dogs that suffered ventricular fibrillation after coronary artery occlusion (n=4) than in those that did not (n=10) (0.86 ng/ml vs. 0.37 ng/ml;p=0.05). The area under the coronary sinus histamine concentration-vs.-time curve (total cardiac histamine efflux) correlated directly with the total number of ventricular premature contractions during the first 30 min after coronary artery occlusion (r=0.81;p<0.005;n=10), and with infarct size (r=0.91;p<0.01;n=6). Thus, during acute myocardial ischemia, the coronary sinus histamine concentration increases simultaneously with the development of early ischemic ventricular arrhythmias and in proportion to their severity.This work was supported by grants HL34215, HL37407 and HL18828 from the National Institutes of Health, Bethesda, Maryland; by a grant from the Eleanor Naylor Dana Charitable Trust, New York, New York and by General Research Funds from the Veterans Administration Medical Center, New York, New York.     

Changes in ultrasonic attenuation indicative of early myocardial ischemic injury.

This study was designed to determine whether quantitative alterations in ultrasonic attenuation are associated with myocardial changes occurring after acute ischemic injury. Five hundred seventeen regions of myocardium from 41 dogs were studied in vitro at five intervals after coronary occlusion: 15 min, 1 h, 6 h, 24 h, 3 days, and 6 wk. Quantitative indices of ultrasonic attenuation were determined from the measured frequency dependence of the ultrasonic attenuation coefficient characterizing each myocardial region over the range 2-10 MHz. Independent definition of regions of ischemic injury was provided by either creatine kinase depletion or colloidal carbon dye distribution. Results of this study indicate that ischemic myocardial regions investigated 15 min to 24 h after coronary occlusion demonstrated ultrasonic attenuation significantly decreased from nonischemic regions (P less than 0.05). In contrast, ultrasonic attenuation was significantly increased in zones of ischemia or infarction investigated at 3 days and 6 wk after coronary occlusion (P less than 0.05 and P less than 0.01, respectively). These results indicate that altered attenuation of transmitted ultrasound by myocardium in vitro is an early manifestation of ischemia.     

Mortality after high ligation of the anterior descending branch of the left coronary artery in dogs; effects of various pharmacological agents

Summary Over a period of seven years the anterior descending branch of the left coronary artery was acutely ligated in a total of 93 dogs. Two control series, 1963/1964 and 1969/1970, on 11 and 13 dogs respectively, produced essentially identical survival rates of 9.1% and 7.7% despite variations in the experimental team. Two experimental series performed at the same time with Intensain pretreatment show essentially the same survival rate (62.2%,p<0,05 and 66.7%,p<0.01, respectively.After pretreatment with Persantin the survival rate of 84.7% is likewise significantly higher than in the control animals (p<0.001). After prolonged administration of Carduben, 42.9% of the experimental animals survived coronary occlusion (p<0.05).If young animals of the age of 9 to 12 months are used in the control series, the survival rate of 58.3% is clearly higher than with adult ones (p<0.01). If young animals receive prophylactically Pteridinol (RE 102), the survival rate is increased after acute occlusion of the anterior descending artery to 91.1% (p<0.05). The higher survival rate in young animals may be explained by an improved collateral circulation of the myocardium.The good reproducibility of survical rates following acute coronary occlusion over several years with both controls and treated dogs proves the significance of comparative studies between treated and untreated animals. The experimental conditions, age and living conditions, however, must be comparable.     

The Effect of Glucose-Insulin-Potassium on Cardiac Ultrastructure Following Acute Experimental Coronary Occlusion

The effects of glucose-insulin-potassium (GIK) on cardiac ultrastructure following acute experimental coronary occlusion were studied in dogs. Epicardial ST segment elevations at multiple sites on the anterior surface of the left ventricle 15 minutes after ligation of the left anterior descending coronary artery were used to predict infarct development. Biopsies removed from sites of known ST segment elevation were examined with the electron microscope, and the degree of injury was correlated with the ST segment elevation. The animals receiving GIK showed significantly less necrosis than was seen in dogs with occlusion alone at corresponding levels of ST segment elevation. Other evidence suggesting a beneficial effect of GIK was the presence of a fibrillar material in several biopsies from the treated animals, which may indicate the regeneration of myofilaments.