Correlation of electrocardiologic and pathologic findings in 100 cases of Q wave and non-Q wave myocardial infarction

Of 100 cases of acute myocardial infarction as shown on autopsy, 55 cases were transmural infarcts and 45 were subendocardial. Pathologic Q waves appeared in 67% of the cases of transmural infarct and in 30% of subendocardial infarct. In transmural infarcts, Q wave infarcts occurred twice as frequently as non-Q wave infarcts. In the cases of subendocardial infarcts just the opposite was observed: non-Q wave infarcts had double the frequency of Q wave infarcts. In spite of this, when a myocardial infarct is characterized strictly by electrocardiology, it should be described by only the accurate terminology of Q wave infarct or non-Q wave infarct. To distinguish with certitude between subendocardial infarct and transmural myocardial infarct on the basis of the ECG does not seem possible. Q wave infarct as "transmural" and non-Q wave infarct as "subendocardial" does not correspond to the pathologic evidence.     

Lateral border zone: quantitation of lateral extension of subendocardial infarction in the dog

This study was undertaken to quantitate the lateral extension that occurs concomitantly with the transmural extension of a subendocardial infarction. A subendocardial infarct was produced in 12 dogs by a 40 minute temporary coronary artery occlusion. Infarct extension was induced 7 days later by permanent occlusion of the same vessel. Regional myocardial blood flows confirmed that ischemia had been produced with both coronary artery occlusions. The vascular boundaries between the normally perfused and ischemic beds were defined by perfusion with different-colored Microfil solutions. The extent of subendocardial infarction and subsequent transmural and lateral extensions were assessed by point counting of histologic specimens. The initial temporary occlusion produced a 30.0 +/- 4.2% transmural infarct and the subsequent permanent occlusion a 29.2 +/- 3.5% transmural extension in a risk region of 39 +/- 4 g. Lateral extension was not measured in four dogs because the initial subendocardial infarct was patchy with markedly irregular lateral borders. In eight dogs the size of the measured lateral infarct extension from each lateral margin from two histologic sections was 0.63 +/- 0.013 cm2. The area of both lateral extensions was 1.7 +/- 0.1% of the cross-sectional area of its risk region as determined by planimetry. Using a model of the risk region, the mass of the lateral extension was estimated to be 1.4 +/- 0.3 g or 3.5 +/- 0.6% of the region at risk. Thus, at the lateral margin of a subendocardial infarct there is a border zone that is small relative to the size of the region at risk and infarcted myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of collateral blood flow and of variations in MVO2 on tissue-ATP content in ischemic and infarcted myocardium

The left anterior descending coronary artery was occluded for 22.5, 45, 90, 180, and 360 mins in anesthesized open-chest dogs and pigs and thereafter reperfused for 30 min. Myocardial oxygen consumption was varied in dogs by cholinergic stimulation (bradycardia) and by cutting of the right and left vagus nerve (tachycardia). Regional myocardial blood flow was measured with radioactive tracer microspheres at the end of the occlusion period and 5 and 30 min after reflow. Tissue content of adenine nucleotides and of phosphocreatine were determined in the subendo- and subepicardium of transmural biopsies at the end of reflow. Infarct size was determined with nitrobluetetrazolium and compared with risk region size. Porcine hearts developed infarcts sooner. Those canines with a high MVO2 due to tachycardia had larger infarcts than those with bradycardia and resembled infarct development in the pig. The evolution of infarcts with time depended strongly on collateral flow which was significantly higher in canine hearts. Higher collateral flow and lower MVO2 in one group of canine hearts also resulted in better preserved tissue ATP. The fall in tissue ATP with time after coronary occlusion was compared with the O2-supply via collateral flow during occlusion. Assuming that the oxygen entering ischemic myocardium was used for ADP phosphorylation, we could estimate the degree of ATP-"overspending". Overspending was highest in low-flow ischemia and it correlated well with the speed of infarction. The ATP-data are best explained by the phosphocreatine energy shuttle model and by assuming slow access of cytosolic ATP to the ATP-splitting sites at the myofibrils. In conclusion, we postulate that both collateral flow as well as myocardial oxygen consumption before and during occlusion determine infarct size.     

Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging.

AIMS: Global angiographic scores have been developed to determine the extent of myocardium jeopardized by significant coronary stenosis. We adapted these scores to quantify the anatomic area at risk during acute myocardial infarction. We used contrast-enhanced magnetic resonance (CMR) infarct imaging to measure the portion of myocardium that developed necrosis within the so defined angiographic area at risk. METHODS AND RESULTS: In 83 subjects presenting for primary percutaneous intervention, the myocardium at risk was estimated angiographically using the Myocardial Jeopardy Index (BARI) and a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores. CMR was performed within a week to measure infarct size, infarct endocardial surface area (infarct-ESA), and infarct transmurality. As infarct transmurality increased, the infarct size closely approximated the myocardium at risk by angiography. In 35 subjects with transmural infarcts, the area at risk by BARI and APPROACH scores matched the infarct size (r = 0.90 and r = 0.92, P < 0.001). Additionally, BARI and APPROACH scores matched the infarct-ESA in all subjects independently of collateral flow and time to reperfusion (r = 0.90 and r = 0.87, P < 0.001). The presence of early reperfusion, collaterals, or both was associated with a progressive decrease in infarct transmurality (P < 0.001 for trend) with no difference in the infarct-ESA. CONCLUSION: The myocardium at risk of infarction can be determined angiographically as validated in subjects with transmural myocardial infarcts. Salvage provided by early reperfusion or collaterals occurs by limiting infarct transmurality, thereby the extent of endocardial infarct involved also allows estimation of the myocardium at risk in patients presenting with STEMI.     

Pathological changes after intravenous streptokinase treatment in eight patients with acute myocardial infarction

At necropsy five of eight patients (mean age 57 years) who died after intravenous streptokinase treatment for severe acute myocardial infarction (mean Peel index = 18) were found to have a patent infarct related coronary artery. Coronary artery stenoses were caused by fibrofatty atheromatous plaques; there were no residual thrombi in the lumen or acute intimal lesions. Three of these infarcts were of partial thickness (less than two thirds wall width) with sparing of the outer third of the myocardium and subendocardial zones. In the other three patients the infarct related coronary arteries remained histologically closed with residual lumen thrombi and underlying intimal lesions. Two infarcts were transmural. Six of the eight infarcts were noticeably haemorrhagic. Myocardial haemorrhage was confined to areas of necrotic myocardium and did not affect viable regions. These findings suggest that thrombus overlying a complex lesion may be more difficult to lyse than thrombus overlying a simple fibrofatty plaque. They also suggest that myocardial haemorrhage outside the infarct area, which might lead to cardiac rupture or delayed healing, does not usually occur.     

Pathological changes after intravenous streptokinase treatment in eight patients with acute myocardial infarction.

At necropsy five of eight patients (mean age 57 years) who died after intravenous streptokinase treatment for severe acute myocardial infarction (mean Peel index = 18) were found to have a patent infarct related coronary artery. Coronary artery stenoses were caused by fibrofatty atheromatous plaques; there were no residual thrombi in the lumen or acute intimal lesions. Three of these infarcts were of partial thickness (less than two thirds wall width) with sparing of the outer third of the myocardium and subendocardial zones. In the other three patients the infarct related coronary arteries remained histologically closed with residual lumen thrombi and underlying intimal lesions. Two infarcts were transmural. Six of the eight infarcts were noticeably haemorrhagic. Myocardial haemorrhage was confined to areas of necrotic myocardium and did not affect viable regions. These findings suggest that thrombus overlying a complex lesion may be more difficult to lyse than thrombus overlying a simple fibrofatty plaque. They also suggest that myocardial haemorrhage outside the infarct area, which might lead to cardiac rupture or delayed healing, does not usually occur.     

Strain rate imaging differentiates transmural from non-transmural myocardial infarction: a validation study using delayed-enhancement magnetic resonance imaging

OBJECTIVES: The aim of this study was to determine if strain rate imaging (SRI) correlates with the transmural extent of myocardial infarction (MI) measured by contrast-enhanced magnetic resonance imaging (Ce-MRI). BACKGROUND: Identification of the transmural extent of myocardial necrosis and degree of non-viability after acute MI is clinically important. METHODS: Tissue Doppler echocardiography with SRI and Ce-MRI were performed in 47 consecutive patients with a first acute MI between days 2 and 6 and compared to 60 age-matched healthy volunteers. Peak myocardial velocities and peak myocardial deformation strain rates were measured. Location and size of the infarct zone was confirmed by Ce-MRI using the delayed enhancement technique with a 16-segment model. RESULTS: Contrast-enhanced MRI identified transmural infarction in 21 patients, non-transmural infarction in 15 (mean transmurality of infarct 72.3 +/- 10.6%), and another 11 patients with subendocardial infarction (<50% transmural extent of the left ventricular wall). Peak systolic strain rate (SRs) of the transmural infarction segments was significantly lower compared to normal myocardium or with non-transmural infarction segments (both p < 0.0005). A cutoff value of SRs >-0.59 s(-1) detected a transmural infarction with high sensitivity (90.9%) and high specificity (96.4%), and -0.98 s(-1) >SRs >-1.26 s(-1) distinguished subendocardial infarction from normal myocardium with a sensitivity of 81.3% and a specificity of 83.3%. CONCLUSIONS: Peak myocardial deformation by SRI can differentiate transmural from non-transmural MI, and it allows noninvasive determination of transmurality of the scar after MI and thereby the extent of non-viable myocardium.     

Effects of calcium-channel blockers on myocardial preservation during experimental acute myocardial infarction

Calcium antagonists have become accepted agents for the attenuation of myocardial ischemia when it becomes manifest as angina pectoris. However, it is not known whether these agents can protect ischemic myocardium during the early evolution of an acute myocardial infarct. Calcium antagonists could potentially improve myocardial perfusion, by relieving coronary spasm or improving collateral blood flow, and reduce the energy demands of the ischemic myocardium either directly or by reducing heart rate or contractility. In some studies, calcium antagonists have decreased the rate of adenosine triphosphate depletion in ischemia and reduced functional or structural indexes of ischemic injury after relatively brief periods (up to 2 hours) of injury. We have assessed the ability of verapamil to protect severely ischemic myocardium in dogs with a 40-minute test period of circumflex occlusion followed by reperfusion. After 4 days of recovery, infarcts were sized by histologic methods. Untreated dogs had 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 (anatomic area at risk). Thus, verapamil prevented cell death in a substantial proportion of the severely ischemic subendocardial region that otherwise would have died as a result of the 40-minute test period of ischemia. To establish whether verapamil could prevent cell death for a longer period of time in the less severely ischemic subepicardial region, a 3-hour period of coronary occlusion with reperfusion was studied. This period of occlusion caused infarcts averaging 60 ± 6 % of the ischemic area at risk in untreated dogs. Dogs treated with verapamil 15 minutes after occlusion 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 untreated dogs, infarct size was related inversely to baseline subepicardial collateral flow. Verapamil neither improved collateral flow nor altered the regression of infarct size versus blood flow. Thus, the early protective effect of pretreatment with verapamil was not sustained when ischemia was prolonged to 3 hours and when verapamil was given 15 minutes after the onset of ischemia. In experimental studies from other laboratories, calcium antagonists have had either a protective effect or no effect when infarct size was evaluated after ≥3 hours of coronary occlusion. Preliminary results of clinical trials with calcium antagonists in acute myocardial infarction have not been encouraging. The available experimental data indicate that calcium antagonists can prevent ischemic cell death during relatively brief periods of ischemia if reperfusion is established, but it is uncertain whether these agents can limit infarct size when ischemia is maintained for longer periods.     

Topographic changes in the left ventricle after experimentally induced myocardial infarction in the rat

The factors that determine the thickness of transmural myocardial infarcts are unknown. Therefore, the relation between the size and thickness of transmural infarcts in 67 rats 21 days after occlusion of the left main coronary artery was studied. On examination of histologic sections, infarct size was determined by planimetry and expressed as a percentage of the left ventricular (LV) area, and thickness was expressed as a percentage of noninfarcted ventricular septal wall thickness. The circumferential length of the infarcted ventricle was measured in millimeters, as well as the circumferential length of the noninfarcted ventricular septum. Septal wall thickness was similar in rats with transmural infarcts and in sham-operated rats. No significant correlation was observed between infarct size and thickness (r = 0.10) or between circumferential length of the infarct and infarct thickness (r = 0.17). However, large (greater than or equal to 20% of the left ventricle, n = 37) and small (less than 20% of the left ventricle, n = 30) infarcts which were similarly thin (37 +/- 1% and 34 +/- 2% of septal wall thickness, respectively) affected LV topography differently. Large infarcts resulted in a 23% greater loss of myocardium (p less than 0.001), greater expansion of the LV cavity (18 +/- 9 mm2 compared with 14 +/- 1 mm2 in small infarcts, p less than 0.005), and lengthening of the septal wall (7.2 +/- 1.1 mm and 6.7 +/- 1.0 mm in large and small infarcts, respectively [p less than 0.05], and 6.3 +/- 0.1 mm in shams). Increase in cavity area and septal length in infarcted ventricles suggested a volume overload hypertrophy, which at 3 weeks was nonetheless inadequate to provide as much normal muscle as was present in sham-operated rats. In an additional 9 rats with subendocardial infarctions (involving less than 75% of the LV wall from endocardium to epicardium), the LV walls were thicker (94 +/- 5% of septal wall thickness, compared with 35 +/- 1% for transmural infarcts, p less than 0.001) and an inverse correlation was observed between infarct size and thickness. In conclusion, neither the size of a transmural infarct in rat nor the circumferential length of infarction determines the thickness of the infarct; however, infarct size does affect LV topography by increasing LV cavity area and the length of the noninfarcted septal wall. Subendocardial infarcts result in less myocardial thinning than do transmural infarcts.     

Temporal and spatial development of myocardial infarcts in porcine hearts without significant collateral blood flow

To evaluate the time-dependent beneficial effect of reperfusion on infarct size, we investigated the temporal and spatial development of infarcts in porcine hearts. The left anterior descending coronary artery was occluded in 17 pigs for different periods of time. Ischemia was always followed by 4 hours of reperfusion. After 60 minutes of ischemia, transmural needle biopsies subdivided into subendocardial and subepicardial halves were removed from the ischemic apex to determine the tissue concentrations of adenosine triphosphate and nicotinamide adenine dinucleotide. The myocardium at risk was determined with a fluorescent dye, and the infarcted tissue with nitroblue tetrazolium stain. Infarct size was expressed as the ratio of the infarcted myocardium over the risk region. Ischemic cell death began in the jeopardized left ventricular subendocardial septum after about 30 minutes of ischemia. Further progress involved the right subendocardial septum and the subendocardium of the left anterior free wall. After 75 minutes of ischemia, most of the myocytes were already irreversibly injured. Tissue damage from the infarctions was complete after 90 to 120 minutes of ischemia. These results indicate that in hearts without a significant collateral blood flow, reperfusion can only reduce infarct size if initiated within 60 to 75 minutes of ischemia. As in canine hearts, infarctions in porcine hearts progress from the ischemic subendocardium toward the outer layers.     

Assessment of fibrosis in infarcted human hearts by analysis of ultrasonic backscatter

In animal hearts, the magnitude of integrated ultrasonic backscatter is increased in fibrotic myocardium. Our purpose in this study was to quantitate the relationship between ultrasonic backscatter and collagen deposition in 10 excised human hearts with old infarcts. A 2.25 MHz, 50% fractional bandwidth transducer was positioned at the transducer focal distance from the epicardium of each specimen. The radio frequency backscatter signal was digitized, squared, and integrated to yield the integrated ultrasonic backscatter, which was referenced to the backscatter from a water/steel interface. The interrogated myocardium was then excised and divided into two portions. One portion was assayed for hydroxyproline, a marker for collagen. A second portion was sectioned, stained with Masson's trichrome, and studied with the use of a computer-assisted image analysis system. There was a linear correlation between the magnitude of integrated backscatter and myocardial collagen content estimated by hydroxyproline assay (r = .78). Quantitative histologic analysis revealed a variable relationship between the transmural distribution of collagen and the corresponding transmural pattern of the backscatter signal. In two specimens exhibiting a discrete layer of subendocardial fibrosis, the backscatter amplitude was also increased in the subendocardial region. In specimens with other patterns of fibrosis, the local backscatter amplitude did not correspond to the transmural pattern of collagen distribution. We conclude that the quantitative analysis of ultrasonic backscatter shows promise for the noninvasive evaluation of myocardial fibrosis after infarction.     

Regional redistribution of myocardial blood flow after coronary occlusion and reperfusion in the conscious dog

Early and late changes in regional myocardial blood flow distribution within the left circumflex coronary arterial bed after occlusion and after occlusion and reperfusion were compared with the extent of myocardial tissue necrosis. Radiolabeled microspheres, 15 μm, were used to study regional myocardial blood flow in conscious dogs at 5 minutes, 2 and 6 hours and 1 month after coronary occlusion. Blood flow was measured in conscious dogs whose hearts were reperfused for 72 hours after 2, 6 and 24 hours of occlusion. Blood flow was measured in four distinct transmural myocardial zones dellneated by dye injections and gross infarct features of the occluded left circumflex coronary bed. After occlusion, myocardial flow was redistributed from deep layers to outer layers, and within 6 hours after occlusion collateral flow was increased to the outer zones in excess of redlstributed flow. After reperfusion, blood flow greatly increased to regions containing predominantly normal tissue, and flow was redlstrlbuted away from the necrotic zones. The indigenous collateral circulation was a major determinant of infarct size in the occluded and reperfused myocardium. The concept of a migrating and narrowing marginal zone is discussed.     

Correlation of electrocardiographic and pathologic findings in healed myocardial infarction

A correlative study in 50 cases of healed myocardial infarction compared the 12 lead electrocardiogram with pathologic observations. The electrocardiogram was interpreted according to established Minnesota codes with some modifications. The following conclusions were reached: (1) The electrocardiogram underestimates the extent of myocardial infarction. (2) When a healed myocardial infarct at a specific location is recognized with electrocardiographic criteria, it is likely that there are unrecognized infarcts involving other areas of the left ventricle. (3) Infarctions involving the lateral and inferobasal areas are frequently unrecognized. (4) The electrocardiogram is more likely to miss myocardial infarcts in patients with multiple, than in those with single, electrocardiographically diagnosed infarcts. (5) Apical myocardial infarction does not appear to have specific electrocardiographic findings, other than those related to general infarct localization by electrocardiogram, particularly in patients with anteroseptal or anterolateral infarction. (6) Abnormal Q waves, generally thought to indicate transmural myocardial infarction, are frequently found in subendocardial infarction. (7) The simplified electrocardiographic classification of myocardial infarct site (anteroseptal, inferior, anterolateral) used in this study is preferable to more detailed classifications previously suggested by others.     

The healing of myocardial infarcts in man.

One hundred and fifty hearts of patients who died within 25 days of the onset of a clinically proven myocardial infarct were examined. Three morphologically distinct forms of myocardial necrosis were recognized. In the central and median zones of an infarct the muscle showed coagulation necrosis. Subsequently the dead tissue was obsorbed by macrophages with the preservation of sarcolemmal sheaths. Then fibroblastic collagenization of the preserved stroma occurred. Repair was not achieved by granulation tissue. Coagulative myocytolysis occurred in the outer zone of an infarct and in the non-infarcted myocardium. The dead cells were acidophilic and showed myofibrillary damage characterized by anomalous cytoplasmic band formation. Breakdown of the fibres was followed by macrophage absorption and healing as in the central area of coagulation necrosis. Colliquative myocytolysis was seen in big infarcts. It affected a narrow band of myocardial cells in the subendocardial zone or surrounding blood vessels. The fibres became oedematous and seemed to liquefy.     

Global cardiac remodeling after acute myocardial infarction: a study in the rat model

Infarct expansion, regional dilation and thinning of the infarct zone, occurs within 1 day after myocardial infarction. Whether the early change in regional shape of infarct expansion affects the architecture of remote normal regions is unknown. To study this question, 45 rats with a transmural infarct were killed at 1, 2 and 3 days after infarction and their hearts were examined for infarct size and extent of expansion. Wall thickness and radius of curvature were measured within, adjacent to and remote from the infarct zone. Equivalent regions were analyzed in eight control hearts. The extent of disproportionate wall thinning and increased radius of curvature within the infarct zone of hearts with expansion was not dependent on infarct size. Significant wall thinning and increased regional radius of curvature were also seen in adjacent and remote regions of the hearts with expansion (p less than 0.001). These structural changes outside of the infarct occurred independent of infarct age and size, and were not seen in hearts without infarct expansion. Thus, when disproportionate thinning and dilation occur in the infarct region, they are accompanied by a distortion in shape of the entire heart including remote normal myocardium. This remote remodeling of noninfarcted myocardium correlates with extent of expansion, but not with age or size of the infarct.     

Morphometric mapping of regional myocyte diameters after healing of myocardial infarction in cats.

Myocyte diameters were measured in two models of healed myocardial infarction to test the hypothesis that myocyte hypertrophy is a function of proximity to the infarct. Left ventricular transmural and non-transmural myocardial infarctions were produced in cats by multiple ligatures of the distal tributaries of the left coronary artery system. Thirteen to twenty months after surgery the left ventricular free wall was cut longitudinally, embedded in plastic and stained for reticulum with modified silver stain. Myocardial cell diameters were measured from apex to base through the infarct. No regional differences were found in non-operated control hearts. In the transmural infarct hearts, all cell diameters were significantly increased in comparison to controls (P less than or equal to 0.05). In the hearts with non-transmural infarcts, cell diameters were significantly increased in tissues adjacent to the infarct, but as distance from the infarct increased the cell diameters were not different from controls. Cells from the transmural infarctions had a greater percent increase in diameter, compared to controls, than did cells from the non-transmural infarctions. There is a gradient increase in myocyte diameters in transmural and non-transmural healed myocardial infarctions; this increase is greatest in the tissues adjacent to the infarct. We conclude that cells close to a healed myocardial infarction hypertrophy because they are contracting against a non-compliant scar.     

Scintigraphic assessment of sympathetic innervation after transmural versus nontransmural myocardial infarction

To evaluate the feasibility of detecting denervated myocardium in the infarcted canine heart, the distribution of sympathetic nerve endings using I-123 metaiodobenzylguanidine (MIBG) was compared with the distribution of perfusion using thallium-201, with the aid of color-coded computer functional map in 16 dogs. Twelve dogs underwent myocardial infarction by injection of vinyl latex into the left anterior descending coronary artery (transmural myocardial infarction, n = 6), or ligation of the left anterior descending coronary artery (nontransmural myocardial infarction, n = 6). Four dogs served as sham-operated controls. Image patterns were compared with tissue norepinephrine content and with histofluorescence microscopic findings in biopsy specimens. Hearts with transmural infarction showed zones of absent MIBG and thallium, indicating scar. Adjacent and distal regions showed reduced MIBG but normal thallium uptake, indicating viable but denervated myocardium. Denervation distal to infarction was confirmed by reduced norepinephrine content and absence of nerve fluorescence. Nontransmural myocardial infarction showed zones of wall thinning with decreased thallium uptake and a greater reduction or absence of MIBG localized to the region of the infarct, with minimal extension of denervation beyond the infarct. Norepinephrine content was significantly reduced in the infarct zone, and nerve fluorescence was absent. These findings suggest that 1) MIBG imaging can detect viable and perfused but denervated myocardium after infarction; and 2) as opposed to the distal denervation produced by transmural infarction, nontransmural infarction may lead to regional ischemic damage of sympathetic nerves, but may spare subepicardial nerve trunks that course through the region of infarction to provide a source of innervation to distal areas of myocardium.     

Infarct expansion: pathologic analysis of 204 patients with a single myocardial infarct

The reasons for the marked variability in expansion of myocardial infarcts are unknown. To examine this question, the hearts in 204 patients with a single myocardial infarct, autopsied at The Johns Hopkins Hospital and studied after coronary arteriography and fixation in distension, were reviewed. There were 58 (28%) hearts with marked infarct expansion, 34 (17%) with moderate expansion and 112 (55%) with no or minimal expansion. The degree of expansion was greater in larger, more transmural infarcts (p less than 0.001). Infarcts with greater expansion had significantly more endocardial thrombus (p less than 0.001) and endocardial fibroelastosis (p less than 0.01). Larger heart weight and degree of left ventricular hypertrophy had a significant negative correlation with infarct expansion (p less than 0.05). A markedly greater degree of expansion was noted in the 101 infarcts (50%) caused by lesions in the distribution of the left anterior descending coronary artery as compared with the 57 infarcts (28%) secondary to right coronary lesions and the 46 infarcts (23%) in the distribution of the left circumflex coronary artery (p less than 0.001). The results show that expansion is associated with large infarcts but is less marked in hearts with ventricular hypertrophy. Expansion occurs predominantly in infarcts in the left anterior descending coronary artery distribution, that is, regions of the left ventricular myocardium with the greatest curvature. These results suggest that the degree to which an infarct expands may be influenced by the preinfarction thickness of the ventricular wall.     

Histopathological study on myocardial hypertrophy associated with ischemic heart disease

The mode and causes of myocardial hypertrophy occurring in association with ischemic heart disease were studied. The investigation involved autopsied hearts (15 cases of subendocardial infarction, 27 of transmural infarction, 20 of non-infarcted three vessel disease and 17 controls) and biopsied materials obtained during coronary-aorta bypass graft surgery (23 patients with angina pectoris and 46 with myocardial infarction). The subendocardial infarction group showed most marked myocardial hypertrophy that reflected extensive infarction and fibrosis, dilatation of the left ventricular cavity and the loss of myocytes. Despite a marked decrease in the number of myocyte layers, the residual myocardium of the left ventricle was uniformly hypertrophic, accompanied by an increase in the heart weight. The larger the area of fibrosis, the more marked was myocardial hypertrophy irrespective of the luminal diameter of the responsible coronary artery. These findings indicate that myocardial hypertrophy associated with ischemic heart disease is enhanced by the compensatory mechanisms for a decrease in the contractile myocardium due to fibrosis.     

Studies of autonomic properties after healing of experimental myocardial infarction.

The link between healed myocardial infarction, sympathetic activation, and sudden death has led to a series of studies in a specifically designed animal model. Transmural and non-transmural infarcts were produced in cat hearts and the studies were performed few months later. Using direct stimulation of cardiac sympathetic nerves and measuring local refractory periods it was found that there was an exaggerated response in the border zone. Competitive binding studies revealed that there was a modest reduction in the number of beta-adrenergic receptors in tissue adjacent to the scar. In similar preparations the norepinephrine content, in hearts with healed transmural infarcts, was significantly reduced in areas adjacent to scars. In contrast, in hearts with non-transmural infarcts, the norepinephrine content was not different from normal controls. Phenylephrine and isoproterenol induced afterdepolarizations, blocked respectively by phentolamine and propranolol, in 34% of Purkinje fibers of the preparations with a healed infarct. Thus, afterdepolarizations and triggered activity may be mediated by both alpha- and beta-adrenergic activity in hearts with healed myocardial infarction. These data suggest the persistence, after healing of myocardial infarction, of regional abnormalities in autonomic function at a myocardial level. These regional disparities are likely to influence propensity to arrhythmias.