Nontransmural versus transmural myocardial infarction: A morphologic study

Although “nontransmural” and “transmural” are morphologic terms used widely to distinguish patients with myocardial infarction, controversy exists as to their meaning regarding clinical course. For this study, a transmural infarct was defined as one that involves essentially the full thickness of the ventricular wall, and nontransmural was defined as something less. The purpose of this study was to identify true morphologic nontransmural acute (less than 21 days old) infarcts at autopsy and compare them with transmural (full-thickness) infarcts in age-matched subjects, for clinical and pathologic similarities and differences. Among the autopsy subjects, comparing 35 nontransmural and 35 transmural infarcts, there was no significant difference with regard to subjects' race or sex, chest pain, arrhythmias, heart block, or cause of death; transmural myocardial infarctions did have a higher frequency of new Q waves (30 of 35 versus six of 35, p < 0.001) and presented more often with increasing dyspnea. At autopsy, there were no significant differences regarding heart weight, location of infarcts, severity of coronary disease, age of acute infarct, or total size of infarct (18 percent of left ventricle for nontransmural versus 22 percent for transmural). There was, however, a significantly greater tendency for those with nontransmural infarct to have evidence of prior infarction at autopsy (27 of 35 versus 19 of 35, p < 0.05). Acute coronary thrombi in the distribution of the infarct were significantly more common among transmural myocardial infarcts (32 of 35 versus 18 of 35, p < 0.001). Morphologically, the nontransmural infarcts showed mural involvement ranging from 20 to 90 percent of the left ventricle, and histologically showed more contraction band (i.e., reflow) injury (57 percent with more than 30 percent contraction band necrosis) compared with transmural infarcts (32 percent with more than 30 percent contraction band necrosis) (p < 0.05). Fatal nontransmural and transmural infarcts have major clinical and pathologic similarities, but differences in number of prior infarcts, type of necrosis, and occurrence of coronary thrombi suggest differing pathophysiology. The heterogeneity of both transmural and nontransmural infarcts likely accounts for existing differences among clinical studies regarding prognosis. Although this classification system has value in the clinical setting, that at times it represents an imprecise oversimplification of infarct type should be recognized in assessing individual patients.     

Myocardial infarct expansion, infarct extension, and reinfarction: pathophysiologic concepts

Infarct expansion and infarct extension are events early in the course of myocardial infarction with serious short- and long-term consequences. Infarct expansion, disproportionate thinning, and dilatation of the infarct segment probably begin within hours of acute infarction and usually reach peak extent within seven to 14 days. Clinical data suggest that infarct expansion occurs in approximately 35% to 45% of anterior transmural myocardial infarctions and to a lesser extent in infarctions at other sites. Although expansion usually develops in large infarcts, the extent of transmural necrosis rather than absolute infarct size predicts its occurrence. Expansion has an adverse effect on infarct structure and function for several reasons. Functional infarct size is increased because of infarct segment lengthening, and expansion results in over-all ventricular dilatation. Thus, patients with expansion of an infarct have poorer exercise tolerance, more congestive heart failure symptoms, and greater early and late mortality than those without expansion. Infarct rupture and late aneurysm formation are two additional structural consequences of infarct expansion. Experimental and clinical data suggest that the incidence and severity of expansion can be modified by interventions. Increased ventricular loading conditions and steroidal and nonsteroidal antiinflammatory agents make expansion more severe. Reperfusion of the infarct segment and pharmacologic interventions that decrease ventricular afterload lessen the severity of expansion. Previous myocardial infarction and preexisting ventricular hypertrophy may also limit the development of infarct expansion. Infarct extension is defined clinically as early in-hospital reinfarction after a myocardial infarction. The pathologic finding of infarct extension is necrotic and healing myocardium of several different recent ages within the same vascular territory. Although this pathologic criterion usually cannot be verified, studies employing invasive and noninvasive assessment of patients with early reinfarction provide evidence that the new myocardial injury is usually in the same vascular risk region as the original infarction. A variety of different criteria have been applied in the clinical diagnosis of infarct extension, and this has resulted in a large range of estimated frequencies from under 10% to as high as 86%. High estimates are found in studies using one or two nonspecific criteria such as ST segment shift or reelevation of total CK. The lowest rates have been found when combinations of criteria are used.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical and electrocardiographic features of cardiac rupture following acute myocardial infarction

Characteristic clinical and electrocardiographic findings are reported in six autopsy cases of cardiac rupture following acute myocardial infarction. These patients were generally elderly with an acute, transmural myocardial infarction uncomplicated by “pump failure.” They had hypertension and/or a “stressful episode” prior to cardiac rupture. Delay in diagnosis of myocardial infarction, absence of previous history of coronary artery disease and new or protracted chest pain were frequent accompanying findings. At the time of cardiac rupture the electrocardiogram showed persistent electrical activity when apparent mechanical activity was absent (electromechanical dissociation), preceded or accompanied by S-T segment elevation or depression.     

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.     

Detection of acute right ventricular infarction by right precordial electrocardiography

The value of 0.1 mV or greater of S-T segment elevation in at least one right precordial lead (V₄R to V₆R) in defining right ventricular myocardial infarction was assessed prospectively in 43 subjects (33 consecutive patients with enzymatically confirmed infarction of varying type and location, 4 patients with unstable angina and 6 healthy volunteers). Patients with acute myocardial infarction were studied with radionuclide ventriculography and technetium-99m stannous pyrophosphate myocardial scintigraphy 18.2 ± 14.3 (mean ± standard deviation) and 85.1 ± 18.0 hours after the onset of symptoms, respectively. Eleven patients (Group A: 9 patients with transmural inferior infarction, 1 with transmural inferolateral infarction and 1 with transmural anteroseptal infarction) demonstrated right precordial S-T segment elevation and 22 patients (Group B: 6 patients with transmural inferior infarction, 2 with transmural posterior infarction, 3 with transmural inferolateral infarction, 3 with transmural anteroseptal infarction, 3 with transmural extensive anterior infarction, 4 with subendocardial anterior infarction and 1 with unclassified infarction) did not. Right ventricular ejection fraction was significantly lower in Group A (0.47 ± 0.11) than in Group B (0.60 ± 0.12) (p < 0.01). Right ventricular total wall motion score was 63.8 ± 15.6 percent of normal in Group A versus 94.3 ± 8.5 percent in Group B (p < 0.001). Technetium-99m pyrophosphate uptake (2+ or greater) over the right ventricle occurred in nine patients (81.8 percent) in Group A and in one patient (4.5 percent) in Group B (p < 0.001). No patient with unstable angina and no healthy volunteer had S-T segment elevation in a right precordial lead. S-T segment elevation of 0.1 mV or greater in one or more of leads V₄R to V₆R is both highly sensitive (90 percent) and specific (91 percent) in identifying acute right ventricular infarction.     

Late effects of acute infarct dilation on heart size: a two dimensional echocardiographic study

Dilation of the infarct zone (infarct expansion) has been shown to be a cause of regional left ventricular dilation within days of transmural anterior myocardial infarction. Whether this process stabilizes, continues or regresses thereafter, and whether uninfarcted myocardium is affected is unknown. To explore this, two to six (mean four) serial two dimensional echocardiographic studies were obtained over a 3 to 30 month period (mean 13) in 13 patients beginning 10 to 21 days after anterior transmural myocardial infarction. With use of the papillary muscles as internal left ventricular landmarks, anterior and posterior segmental dilation in each patient was assessed from the slope of the regression line of segment length versus time. Study patients were classified into those with (seven patients) and those without (six patients) infarct expansion. Infarct expansion was defined as an anterior segment length 10 to 21 days after infarction that exceeded the upper limit of normal determined from 13 age-and sex-matched normal control subjects. Ten to 21 days after infarction, the average anterior segment length in the seven patients with expansion was 65 percent greater than that in normal control subjects. The seven patients with infarct expansion showed significant and continuing dilation during long-term observation of both the infarcted anterior (p < 0.01) and the uninfarcted posterior (p < 0.05) segments. The average increase in anterior segment length was 1.1 cm (8 percent) and in posterior segment length 0.9 cm (19 percent). This represents an average increase in overall left ventricular circumference of 11 percent during the observation period. The six patients without infarct expansion showed no significant change in anterior or posterior segment length (mean ± standard error of the mean [SEM] ?0.7 ± 0.3 and 0.2 ± 0.3 mm/mo, respectively). Six of the seven patients with infarct expansion were functionally limited by dyspnea or angina, or both; no patient without infarct expansion had functional cardiac limitation.Thus, infarct expansion occurring within 3 weeks of transmural myocardial infarction appears to be the main contributor to left ventricular dilation, and is associated with impaired functional status. Moreover, a significant increase in ventricular size due to infarct expansion appears to predict chronic progressive ventricular enlargement due to lengthening of both the infarcted zone and the uninfarcted segment.     

Factors presaging early recurrent myocardial infarction (“Extension”)

A prospective study of 200 consecutive patients with acute myocardial infarction was undertaken to characterize the frequency and severity of early recurrent infarction (extension), manifested by secondary plasma MB creatine kinase (CK) and myoglobin peaks, and to identify patients at particularly high risk. Serial MB CK and myoglobin determinations and continuous electrocardiographic recordings were obtained in all patients for 14 days, and serial radioventriculograms were obtained in selected patients. Chest pain and S-T segment changes occurred often, in 57 and 43 percent, respectively, of the entire group of patients. However, a secondary rise in plasma MB CK levels indicative of recurrent infarction, occurring an average of 10 ± 4 days after the initial infarct, was evident in only 17 percent of patients. Forty-three percent (25 of 58) of patients with initial subendocardial infarction exhibited recurrent infarction compared with only 8 percent of those with initial transmural infarction. The mortality rate was 7 percent in patients with subendocardial infarction without early recurrence compared with 16 percent among those with recurrence. Logistic regression analysis indicated that obese women with initial subendocardial infarction and repeated episodes of prolonged chest pain had a high probability rate (60 percent) of recurrence in contrast to the low probability (2 percent) in patients without these features. Thus, early recurrent infarction is frequent after subendocardial infarction and is associated with a marked increase in mortality. These results suggest that patients with subendocardial infarction are at particularly high risk for recurrent infarction and that patients with this type of infarction require vigorous monitoring and prolonged surveillance.     

Natural history of S-T segment elevation after acute myocardial infarction

Clinical, electrocardiographic and cineventriculographic data in two patient groups were analyzed to define the natural history of S-T segment elevation after myocardial infarction. In sixteen of 22 patients (73 percent) with acute inferior myocardial infarction, S-T segment elevation was present on hospital admission, persisting in 1 (5 percent) by the 2nd week. S-T segment elevation was present on admission in 18 of 23 patients (78 percent) with acute anterior myocardial infarction and persisted in 13 after 1 week and in 9 of 14 (64 percent) during a follow-up period of 1 to 6 months. S-T segment elevation lasting more than 2 weeks after myocardial infarction did not resolve. Compared with patients with inferior myocardial infarction or anterior infarction without persistent S-T segment elevation, patients with anterior infarction and persistent S-T segment elevation had a higher level of mean maximal serum creatine phosphokinase (CPK), more severe left ventricular decompensation and a greater frequency of death in the early follow-up period. In a separate series of 95 patients with cineangiographically documented coronary artery disease, 40 of 65 patients (62 percent) with advanced anterior and apical asynergy had persistent S-T segment elevation. By contrast, only 1 of 30 (3 percent) with coronary disease and normal ventriculograms had persistent S-T segment elevation.We concluded that (1) the natural history of S-T segment elevation after myocardial infarction is resolution within 2 weeks in 95 percent of inferior but in only 40 percent of anterior infarctions; (2) S-T segment elevation persisting more than 2 weeks after myocardial infarction does not resolve; (3) persistent S-T segment elevation is associated with clinically more severe myocardial infarction; and (4) in patients with coronary artery disease, persistent S-T segment elevation after myocardial infarction is a specific but insensitive index of advanced asynergy.     

Preponderance of acute proximal left anterior descending coronary arterial lesions in fatal myocardial infarction: A clinicopathologic study

To determine whether an acute lesion in a specific segment of the cororiary tree is more likely than other obstructions to cause fatal myocardial infarction, 77 autopsy patients Who died of acute myocardial infarction were studied. Multiple coronary stenoses were present in 92 percent of these patients, arid the proximal left anterior descending coronary artery before the first septal perforator accounted for only 23 percent of the critical narrowings (greater than 70 percent of luminal diameter). In contrast, acute thrombotic coronary events associated with fatal myocardial infarction occurred most often in the proximal left anterior descending artery, accounting for 61 percent of acute lesions; this rate compared with 8 percent of acute lesions occurring in the mid or distal left anterior descending artery, 18 percent of those in the right, 6 percent of those in the left circumflex and 7 percent of those in the left main coronary artery. Of the autopsy patients, 32 (40 percent) had 77 prior nonfatal myocardial infarcts of which only 17 (22 percent) were anteroseptal infarcts related to occlusion of the proximal left anterior descending coronary artery. The amount of infarcted myocardium in the hearts with acute proximal left anterior descending coronary arterial lesions was somewhat more extensive but not significantly different from that of hearts with other acute coronary lesions.

Fifty survivors of myocardial infarction who underwent cardiac catheterization were studied for comparison. In those patients, proximal left anterior descending coronary disease accounted for 17 percent of critical narrowings and only 22 percent of nonfatal infarcts. These findings suggest that an acute proximal left anterior descending coronary arterial lesion is more likely to result in fatal myocardial infarction than are critical obstructions elsewhere in the coronary arterial tree. Because the quantity of the infarct does not appear to be sufficient to explain these differences, qualitative differences in anteroseptal myocardium are suggested.     

Infarct expansion: The “second event” after acute myocardial infarction

This 57-year-old man suffered a large transmural anteroseptal myocardial infarct. After an initial stable period of several days, he developed episodes of chest pain, hypotension, and congestive failure. The left-sided congestive failure persisted until death. Study of the heart at autopsy showed that the worsened clinical state could be explained by expansion of the area of infarcted myocardium. Infarct expansion may be regarded as a subtle form of myocardial rupture. Intramural tearing of necrotic muscle may occur abruptly or insidiously and may lead to worsened cardiac function and symptoms and signs suggestive of new infarction. The phenomenon of expansion should be distinguished from extension, defined as additional myocardial necrosis, since it may have important long-term effects on the heart's topography and function.     

Myocardial infarct expansion: recognition, significance and pathology.

Infarct expansion can be defined pathologically as a distortion of ventricular topography produced by thinning and disproportionate dilation of the infarct segment. Large transmural infarcts tend to be associated with greater propensity for infarct expansion. Two-dimensional echocardiography has made it feasible to detect these acute alterations in cardiac topography by serial examination of patients with acute myocardial infarction. A practical approach to the echocardiographic quantification of expansion involves analysis of end-diastolic cross-sectional echo views at the papillary muscle level, which can be used as fixed internal landmarks to divide the left ventricle into 2 segments, anterior and posterior. An off-line computer system can be used to track relative lengths of these segments as well as their thicknesses over time. In the initial clinical study, one third of patients with acute anterior transmural infarcts showed an average 50% increase in the infarct segment length beginning within the first 3 days of infarction, characterized by disproportionate progressive dilation and transmural thinning of this zone. These patients demonstrated a significantly higher mortality than those without expansion. Later studies demonstrated not only continuing dilation of the infarcted anterior wall, but also progressive dilation of the noninfarcted posterior wall, underscoring the importance of continuing long-term noninvasive follow-up. Not only is expansion associated with a poor clinical outcome; it has also been shown experimentally and clinically to be modifiable or even preventable by various therapeutic maneuvers, which may well improve survival. Because of the limitations of the echocardiographic window, it is often possible to obtain only a single cross-sectional view of high quality, and even then technical quality may not be sufficiently high to enable detailed quantitative analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinicopathologic correlates of acute ischemic heart disease syndromes

To better define the relations among acute and chronic coronary arterial lesions and different syndromes of acute ischemic heart disease, the clinicopathologic findings in 100 recent myocardial infarcts in 83 patients were reviewed and the results correlated with those of previous studies. Severe atherosclerosis (greater than 75 percent narrowing of luminal cross-sectional area) involved three or more major coronary arteries in 65 percent; two arteries in 16 percent, one artery in 15 percent, and no arteries in 4 percent of cases. The incidence rate of recent occlusive coronary arterial lesions was 61 percent, including 50 (90.2 percent) of 55 grossly apparent transmural infarcts, 9 (34.6 percent) of 26 grossly evident subendocardial infarcts and 2 (10.5 percent) of 19 multifocal microinfarcts associated with clinical episodes of acute coronary insufficiency (p <0.001). The 61 recent occlusive lesions consisted of two thromboemboli, two isolated plaque hemorrhages and 57 in situ thrombi that were associated with a high incidence rate of plaque erosion, rupture and hemorrhage. Clinical conditions predisposing to reduced coronary perfusion were identified before the onset of 26.2 percent of infarcts with recent occlusions and 61.5 percent of infarcts without recent occlusions (p <0.001). Clinical onset of infarction was followed by severe cardiac pump failure or congestive heart failure in 63.9 percent of infarcts with and 41.0 percent of infarcts without recent occlusions (p = 0.04).From this and previous studies, it is concluded that (1) acute ischemic heart disease does not have a constant relation with the severity of chronic atherosclerosis; (2) myocardial necrosis commonly occurs in the absence of acute permanent coronary occlusion, but in this setting is usually limited to subendocardial involvement of variable extent; (3) acute coronary thrombosis frequently acts as a major factor in determining the extent and distribution of an evolving infarct, as indicated by the large incidence of occlusive coronary thrombi with regional transmural infarcts; and (4) coronary thrombus formation is not dependent on a generalized impairment of coronary perfusion, either before or after the onset of infarction.     

Influence of transmurality, infarct size, and severe microvascular obstruction on left ventricular remodeling and function after primary coronary angioplasty

Infarct size has been considered an established marker of left ventricular (LV) remodeling. We assessed the predictive value of myocardial/microvascular injury assessed by delayed enhanced magnetic resonance imaging (MRI) on LV remodeling and LV ejection fraction after primary coronary intervention (PCI) compared with peak troponin levels, an established index of myocardial infarct size. We performed MRI in 76 patients with first acute myocardial infarction 6 +/- 2 days after successful PCI. Necrosis was judged as transmural when delayed enhancement was extended to >or=75% of LV segment thickness. Severe microvascular obstruction was identified as areas of late hypoenhancement surrounded by delayed enhancement. Infarct size was expressed as an index by dividing the total percentage of delayed enhancement involvement by the number of LV segments. LV end-diastolic volume index and function were quantified by 2-dimensional echocardiography at 6 +/- 1 months after acute myocardial infarction. Remodeling was evaluated as a change in LV end-diastolic volume index at follow-up compared with baseline. At univariate analyses, transmural necrosis, severe microvascular obstruction, infarct size, and troponin level were correlated directly with remodeling and inversely with LV function at follow-up (p <0.001). At multiple regression, only transmural necrosis and troponin level remained independent predictors of LV remodeling and function. With respect to troponin, transmural necrosis improved the predictive power of LV remodeling (R2 for change = 0.19) and function (R2 for change = 0.16). In conclusion, in patients with acute myocardial infarction undergoing PCI, the amount of transmural necrosis as assessed by MRI is a major determinant of LV remodeling and function, with significant additional predictive value to infarct size and severe microvascular obstruction.     

Clinical value of delayed thallium-201 myocardial imaging in suspected acute myocardial infarction.

Fifty patients with acute chest pain had thallium-201 myocardial imaging performed three to six days after emergency admission to hospital. The image was abnormal in 20 out of 22 patients with acute transmural myocardial infarcts but in only 1 of 5 with acute subendocardial infarcts. Indistinguishable scan abnormalities caused by old infarcts were seen in 7 patients, and caused by myocardial ischaemia in 1 patient. A single thallium-201 myocardial scan some days after the onset of symptoms appears to be of little value in the clinical assessment of patients with suspected acute myocardial infarction.     

Role of delayed intraaortic balloon pumping in treatment of experimental myocardial infarction

Intraaortic balloon pumping improves coronary blood flow characteristics while simultaneously reducing myocardial oxygen demands by reducing aortic systolic pressure. Clinical application of intraaortic balloon pumping has largely been in the “high risk” patient (cardiogenic shock, postinfarction angina, left main coronary artery disease and unstable angina) for support during diagnostic studies or cardiac surgery, or both. In addition, there is some evidence that balloon pumping immediately after coronary occlusion reduces the size of experimentally induced myocardial infarcts.

In this study, myocardial infarcts were produced by ligatlon of the left anterior descending coronary artery in 12 dogs, 6 of which were treated with balloon counterpulsation beginning 3 hours after coronary occlusion. All dogs were killed 8 hours after coronary ligation. Intraaortic balloon pumping resulted in the expected hemodynamlc changes (decreased aortic systolic pressure, left ventricular end-diastolic pressure and heart rate and increased aortic peak diastolic pressure). In addition, there was a significant reduction in infarct size in the group with balloon pumping as determined with epicardial S-T segment mapping, myocardial imaging with technetium-99m-glucoheptonate and histochemical staining with nitroblue tetrazollum.

These results suggest that even when instituted as long as 3 hours after coronary occlusion, intraaortic balloon pumping results in significant reduction in infarct size and, it might be speculated, the mortality and morbidity associated with acute myocardial infarction may also be decreased.     

Electrocardiographic diagnosis of right ventricular infarction

The electrocardiographic findings in 11 cases of acute right ventricular infarction associated with acute left ventricular inferior wall myocardial infarction are described. The diagnosis of right ventricular infarction was proved by autopsy findings in five cases and supported by hemodynamic data in the other six. Ten of the 11 patients had typical electrocardiographic changes of acute inferior myocardial infarction and one had that of inferior wall injury. Transient S-T segment elevation was present in one (lead V₁) or more of the right precordial leads in eight cases. In the absence of other explanations for the S-T segment elevation, acute right ventricular infarction was most likely the cause. Therefore, when acute inferior myocardial infarction is accompanied by S-T segment elevation in the right precordial leads, the coexistence of right ventricular infarction should be suspected. The sensitivity and specificity of this electrocardiographic sign are yet to be determined.     

Pathologic findings in pre-hospital deaths due to coronary atherosclerosis

On the basis of medicolegal autopsy series from large metropolitan cities, it has been thought that only 10 percent of patients dying suddenly from coronary atherosclerosis show histologic evidence of acute myocardial infarction. It has been inferred that these patients die before the tissue changes of a myocardial infarct can take place. This study characterizes the anatomic changes in the hearts of a group of patients dying suddenly of coronary atherosclerosis in Albany County, N.Y.

Autopsy records and slides were reviewed from 150 men and 33 women who were pronounced dead on arrival, from coronary atherosclerosis, in Albany County hospitals. Histologic evidence of acute myocardial infarcts from 6 hours to 1 week old were found in 47 percent of the cases. When the witnessed final episode was 1 hour or less, 49 percent of the hearts had gross and histologic evidence of acute infarcts. The presence of large areas of myocardial necrosis, often of days' duration, apparently does not ensure hospitalization or necessarily interfere with normal activity. Approximately two thirds of the hearts with recent acute infarcts also had evidence of a previous myocardial infarct. Thus, the final myocardial insult in these patients was not the first.     

Effects of hypoxemia on the extent of myocardial necrosis after experimental coronary occlusion

Arterial oxygen tension is variable in patients with acute myocardial infarction, and the effect of hypoxemia on the extent of myocardial necrosis after coronary occlusion has not been defined. In 11 anesthetized open chest dogs the left anterior descending coronary artery or one of its major branches was occluded for 20 minutes, and 10 to 15 epicardial electrocardiographic leads were recorded in the distribution and vicinity of the site of occlusion. Average S-T segment elevation and the number of sites showing S-T segment elevation greater than 2 mv, 15 minutes after occlusion were used as indexes of the severity and extent of ischemic injury. After occlusion with an inspired oxygen concentration of 20 percent these indexes were, respectively, 2.0 ± 0.5 mv (mean ± standard error) and 3.6 ± 0.8 sites; the respective values increased to 3.3 ± 0.5 mv (P < 0.01) and 6.7 ± 0.7 sites (P < 0.01) after occlusion with an inspired oxygen concentration of 10 percent, and arterial partial pressure of oxygen decreased from 92 ± 5 to 45 ± 3 mm Hg. In 23 dogs the occlusion was maintained for 24 hours and the S-T segment elevation 15 minutes after occlusion was compared with myocardial creatlne phosphokinase (CPK) activity and histologic appearance 24 hours later. In control dogs (inspired oxygen concentration of 20 percent) sites with no S-T segment elevation 15 minutes after occlusion showed normal myocardial CPK activity 24 hours later, whereas in sites with S-T segment elevation exceeding 2 mv there was an inverse relation between S-T segment elevation in each site and its myocardial CPK activity 24 hours later. Histologic examination revealed early myocardial necrosis in 98 percent (82 of 84) of sites with S-T segment elevation greater than 2 mv. In experimental dogs (inhaling a 10 percent Oxygen concentration for the first 8 of the 24 hours of occlusion) many sites that showed no S-T segment elevation before hypoxemia was induced exhibited S-T segment elevations 30 minutes later and showed abnormally low CPK activity and histologic evidence of early necrosis. We conclude that after experimental coronary occlusion, hypoxemia is deleterious because it substantially increases myocardial damage.     

Large dose sublingual nitroglycerin in acute myocardial infarction: Relief of chest pain and reduction of Q wave evolution

Thirty patients with acute myocardial infarction admitted 2.1 ± 1.1 (mean ± standard deviation) hours after the onset of pain and with S-T segment elevation in multiple leads in the standard electrocardiogram were given either intravenous morphine (15 patients) or sublingual nitroglycerin (15 patients), and the effect on pain and QRS changes was observed. Nitroglycerin was administered repetitively in large doses while systolic blood pressure was maintained above 100 mm Hg. Chest pain failed to respond within 30 minutes In two patients who received nitroglycerin. In the remaining 13 patients nitroglycerin produced partial relief of pain in 17 ± 5 minutes and complete relief in 127 ± 65 minutes, requiring a cumulative dosage of 23.7 ± 38.7 mg in 16 ± 7 divided doses. An average of 14.9 ± 7.1 mg of morphine in 3.3 ±1.5 divided doses produced complete relief of pain in a similar period (134 ± 77 minutes [difference not significant]). In patients receiving morphine, Q waves developed at 24 and 48 hours, respectively, in 62 (72 percent) and 66 (77 percent) of a total of 86 sites with initial S-T segment elevation in the standard 12 lead electrocardiogram. In nitroglycerin responders, Q waves developed at 24 and 48 hours, respectively, in only 21 (28 percent, p < 0.001) and 22 (29 percent, p < 0.001) of the 76 sites with initial S-T segment elevation. Other electrocardiographic estimates of the extent of myocardial necrosis, including the percent reduction in R wave amplitude and the relative changes in R and Q wave amplitude, also were significantly less in those receiving nitroglycerin. There was no in-hospital mortality. Thus, large and frequent doses of nitroglycerin when used in the hyperacute phase of acute myocardial infarction can effectively abolish chest pain and limit later electrocardiographic signs of myocardial necrosis.     

Platelet trapping in myocardial infarct in baboons: Therapeutic effect of aspirin

Blood platelet trapping has been demonstrated in the area of evolving myocardial infarction in baboons. Sixteen baboons were subjected to ligation of the diagonal branch of the left anterior descending coronary artery, and the extent of myocardial ischemia was monitored with a 64 to 72 electrode epicardial electrocardiographic grid. Eight animals received no treatment and eight were pretreated twice (at 12 hours and at 2 hours before ligation) with aspirin, 600 mg orally. Measurement of infarct extent included all electrode points with S-T segment elevation of 2 mV or greater. Chromium-51-tagged autologous platelets were injected 15 minutes before ligation. In all animals an area of ischemia developed in which typical changes evolved in S-T segments. In three of the eight aspirin-treated animals, double ligation was carried out. Aspirin was administered after release of the first ligature but before religation, and the area of S-T segment elevation was reduced by as much as 23 percent after aspirin treatment.Platelet trapping outside the area of S-T elevation was seen in 25± 3 percent of the total wall samples in aspirin-treated animals compared with 44 ± 7 percent of those in control animals (p <0.05). There was increased platelet trapping in the epicardium compared with the endocardium in all areas (normal and ischemic) at a ratio of 1:0.7. It is concluded that platelet trapping occurs at the margins of myocardial infarcts in primates and can be significantly reduced by pretreatment with aspirin.