Improvement of exercise-induced left ventricular dysfunction with oral propranolol in patients with coronary heart disease.

The effect of propranolol on global cardiac function during exercise was analyzed with equilibrium fadionuclide angiography in 10 patients with ischemic heart disease. All patients had angina pectoris and S-T segment depression of more than 0.1 mv during treadmill exercise when not taking propranolol. Each patient was stressed with supine bicycle exercise to the same work load on a maintenance dose of propranolol (120 to 400 mg/day) and on a second occasion without the drug, the two tests being separated by an average of 16 days. The mean heart rate was reduced both at rest and during exercise after propranolol, but propranolol caused no significant reduction of the left ventricular ejection fraction at rest. In the study without administration of propranolol the average ejection fraction during exercise decreased from 0.56 ± 0.09 (standard deviation) to 0.50 ± 0.14. With propranolol, the ejection fraction was improved from the control value in every patient, the average value during peak exercise reaching 0.60 ± 0.15. Thus, the average ejection fraction increased by 22 percent (±12 percent) relative to the value during the same exercise without propranolol (P < 0.001). In 16 other patients with ischemic heart disease who did not take propranolol, reproducibility of the ejection fraction both at rest and at peak exercise on two occasions within 15 days was good (r = 0.95 and 0.97, respectively). It is concluded that oral propranolol therapy in patients with coronary artery disease can ameliorate left ventricular dysfunction induced by exercise and thereby may reduce myocardial ischemia.     

End-systolic dimension-wall thickness relations during myocardial ischemia in conscious dogs: A new approach for defining regional function

Overall and regional left ventricular (LV) function was studied during progressive coronary stenosis in conscious dogs by determining the relations at end-systole between LV pressure, chamber dimensions, and regional LV wall thickness. An index of regional wall stress was also analyzed. Using ultrasonic dimension gauges, measurements were made of LV wall thickness in control and ischemic regions, and the external long- and short-axis LV diameters were determined; an implanted micromanometer measured LV pressure. Internal LV diameters were obtained from the external diameters by subtraction of wall thickness, and the index of regional wall stress employed a thick-walled ellipsoidal model. During regional ischemia, the LV long axis at end-systole did not change, whereas the short-axis diameter progressively increased (from 24 ± 7 mm [standard deviation] to 30 ± 9 mm, p < 0.001, indicating a more spherical LV shape during ischemia). The end-systolic pressure did not change, and therefore the end-systolic pressure-diameter relation shifted progressively, suggesting a global decrease in LV contactility. The end-systolic points relating LV wall thickness in the ischemic region to the end-systolic LV pressure revealed the regional nature of the abnormality, showing a progressive displacement to the left, whereas there was no significant displacement of this relation in the control region. The application of this index over a range of loading conditions during partial vena caval occlusion was illustrated. Thus, the regional endsystolic wall thickness-pressure relation provides a new index for defining the regional contractile state of the LV myocardium which is potentially load-independent and offers the possibility for echocardiographic application.     

Reduction of exercise-induced ischemic regional myocardial dysfunction by verapamil in conscious dogs

The effects of verapamil on exercise-induced changes in left ventricular (LV) function were examined in nine conscious dogs in which an Ameroid constrictor and Doppler flow probe were placed around the left circumflex coronary artery. Ultrasonic crystals were implanted for measuring LV systolic wall thickness (SWTh) in control and ischemic regions, and a micromanometer measured high fidelity LV pressure. At 23 days (average) postoperatively, coronary collaterals had developed and complete cessation of coronary flow was confirmed by the flowmeter. Control treadmill exercise was then performed for 3.8 minutes at speed 12.1 km/hr and grade 5.3% (average). Two hours after oral administration of verapamil (120 to 160 mg), the same exercise bout was repeated. During the control runs, significant increases occurred in heart rate (101 to 243 bpm), LV end-diastolic pressure (13.3 to 27.5 mm Hg), peak LV pressure (129.8 to 165.7 mm Hg) and its first derivative (3140 to 6275 mm Hg/sec) with an increase of SWTh in control regions, while percent SWTh in ischemic regions decreased markedly (19.6% to 5.9%, p < 0.001); wall thickening velocity also decreased (0.90 to 0.44 SWTh/sec). During the runs after verapamil, the exercise heart rate was significantly lower than in the control run (221 ± 30 bpm), but other hemodynamic measures were similar. SWTh in control regions was unchanged, but exercise-induced dysfunction in the ischemic zone was substantially less (SWTh during exercise 11.5%, p < 0.01 compared to control runs) and wall thickening velocity did not fall. Thus verapamil can reduce regional LV dysfunction produced by exercise in collateral dependent zones, indicating a beneficial effect of this agent on stress-induced ischemia.     

Approach to the estimation of myocardial infarct size by analysis of precordial S-T segment and R wave maps

To assess the correlation of S-T segment elevations and the height of R waves of the precordial electrocardiogram with myocardial infarct size, we performed 35 lead precordial electrocardiograms (maps) in 24 patients with uncomplicated acute anterior transmural myocardial infarction. The initial analysis was carried out in 14 patients. Infarct size was estimated from the integration, from normal baseline to baseline, of serial serum creatine kinase (CK) values obtained at 2 to 4 hour intervals and expressed as IU/liter·hours. The first electrocardiographic maps were recorded 12 hours or less after the onset of symptoms. All S-T segment elevations and R waves were summed for each map (∑S-T and ∑R). There were positive correlations between the ultimate CK infarct size and the initially recorded ∑S-T (r = 0.69), the initially recorded log ∑R (r = ? 0.70) and the initial early decline in log ∑R per hour [(Δlog ∑R/Δhour)·10³, r = 0.88]. Therefore, these variables were combined in a multiple regression analysis; CK infarct size = 0.23 ∑S-T + 0.20 [(Δlog ∑R/Δhour)·10³]? 14.9 log ∑R + 36.8 (r = 0.97). In addition, on the basis of previous studies the initially recorded ∑S-T and log ∑R values were normalized with respect to time by calculating the expected ∑S-T value at 12 hours after the onset of symptoms (∑S-T₁₂) and the 12 hour interpolated values for ∑R (∑R₁₂). These values also showed a good correlation with infarct size: CK infarct size = 0.37 ∑S-T₁₂ + 0.16 [(Δlog ∑R/Δhour)·10³]^t- 18.2 log ∑R₁₂ + 40.4 (r = 0.97).To validate this approach, 10 additional patients were studied prospectively. Correlations between CK infarct size and the various measurements from the serial precordial maps were similar to those in the first study group, and CK infarct size correlated well with the electrocardiographic infarct estimates (r = 0.90 and r = 0.95, respectively). It is concluded that in selected patients CK infarct size can be directly related to the initial height of S-T segment elevations and the early rate of R wave decline and inversely related to later ∑R values, thereby providing a general approach for use in studies on the estimation of myocardial infarct size from precordial electrocardiographic maps.     

Prognostic importance of digitalis after acute myocardial infarction

Because previous reports have suggested that digitalis administration may lead to increased mortality after hospital discharge for acute myocardial infarction, the independent importance of digitalis therapy in long-term prognosis after acute myocardial infarction was investigated by analyzing 1,599 patients after definite myocardial infarction. After hospital discharge, mortality rate for the entire group at 4 months was 7.7% and after 1 year 14.2%. At discharge, 36.6% of the patients were taking digitalis. Compared with those not taking digitalis, those taking digitalis had more historical risk factors and a higher incidence of important clinical prognostic variables during the hospitalization. Their cardiac mortality rate after 4 months and 1 year (12.5 and 22.4%, respectively) was significantly higher than that of patients not taking digitalis (5.0 and 9.6%, respectively). Mortality was higher for patients taking digitalis whether or not they had congestive heart failure during hospitalization. However, in a multivariate Cox analysis for 1 year outcome, neither digitalis nor any other medication variable displaced the important clinical variables of age, congestive heart failure during the hospitalization, previous myocardial infarction, maximal heart rate during the hospitalization and previous angina. Quinidine and digitalis at discharge were selected sixth and seventh (not significant) by the analysis. It is concluded that digitalis therapy at discharge after myocardial infarction was not an independent predictor of late mortality in these patients.     

Survival after hospital discharge in matched populations with inferior or anterior myocardial infarction

Prognostic differences between patients with anterior or inferior myocardial infarction are often related to such variables as previous infarction or the size of the myocardial infarct. We examined the determinants of mortality in 997 hospital survivors of acute Q wave infarction (anterior in 449, inferior in 548) who, although not preselected, were well matched with respect to age, sex and prior infarction or congestive heart failure. Additionally, there was no significant difference in peak serum creatine kinase (CK) between the groups with anterior and inferior infarction (1,459 +/- 1,004 versus 1,357 +/- 1,036). Among the patients with anterior infarction who died during the 1 year follow-up period, 56% died in the first 60 days after hospital discharge compared with 18% of those without inferior infarction (p less than 0.01). Survival curves then became nearly identical at 3 months, and remained so until 1 year when the total mortality rate was 10% for the anterior and 7% for the inferior infarction group (p = NS). Variables associated with heart failure during the hospital phase were more prevalent in anterior infarction, but rales above the scapulae during the hospital stay (p less than 0.0001) and ventricular gallop at the time of discharge (p less than 0.0001) were the top two predictors of 1 year mortality by both univariate and multivariate analysis in inferior infarction. Age (p less than 0.0001) and peripheral edema (p less than 0.0001) were the strongest predictors of mortality in anterior infarction. Previous infarction, although just as common in the group with anterior infarction, was present at 1 year in 48% of nonsurvivors of the group with inferior infarction compared with only 19% of survivors (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Usefulness of preoperative and postoperative Tc-99m (Sn)-pyrophosphate scans in patients with ischemic and valvular heart disease.

To assess the usefulness of myocardial imaging with technetium-99m-stannous pyrophosphate for detecting acute myocardial necrosis in patients undergoind cardiac surgery, 66 such patients were stldied. Tc-99m (Sn)-pyrophosphate scans were obtained in all patients 3 to 6 days postoperatively and in 45 preoperatively. Electrocardiograms and serum samples for measuring myocardial isoenzyme of creatine kinase (MB CK) levels were obtained before and serially after cardiac surgery. Seven of the 46 patients undergoing myocardial revascularization had a definite new myocardial infarction as indicated by electrocardiogram and MB CK isoenzyme concentrations, and postoperative pyrophosphate scans were abnormal in all but one. In addition, six of the eight patients with possible myocardial infarction (elevated MB CK levels and persistent ST-T wave depressions) had an abnormal scan postoperatively. Seven of the 20 patients undergoing aortic or mitral valve replacement, or both, had a possible postoperative myocardial infarction by electrocardiogram and MB CK criteria and the myocardial scan was positive in two. All the patients with a normal electrocardiogram and normal MB CK levels had a normal pyrophosphate scan. Preoperative scans were obtained in 22 patients wit; valvular heart disease and were positive in two with a heavy calcified mitral valve on fluoroscopy and in one with a calcified aortic valve. After valve replacement, the pyrophosphate scan became normal in two patients and remained abnormal in the third patient with electrocardiograms and MB CK levels suggesting acute myocardial infarction. We conclude that the Tc-99m (Sn)-pyrophosphate scan is useful for analyzing the occurrence of acute myocardial infarction in patients undergoing cardiac surgery and that, in conjunction with the electrocardiogram, it permits confirmation or exclusion of that diagnosis. Furthermore, false positive pyrophosphate scans may occur in patients with heavy valve calcifications.     

Cardiac function and myocardial contractility: a perspective

An experimental study was designed to validate postextrasystolic potentiation assessment of myocardial viability or functional reserve of cardiac segments after acute coronary occlusion. Segmental systolic fractional area changes and wall thickening in pacing-induced postextrasystolic beats were mapped in 12 closed chest dogs by two-dimensional echocardiography during a control period and from 20 minutes to 3 hours after occlusion of the left anterior descending coronary artery. The extent of myocardial ischemic and necrotic zones was evaluated in left ventricular slices and subsegements corresponding to echographic cross sections. During two-dimensional echocardiography, left ventricular segments that were found to be neither ischemic nor necrotic always exhibited a significant augmentation of both fractional area change and wall thickening during the postextrasystolic beat that followed an induced premature contraction with a 42.4% coupling interval. In segments without necrosis but with varying degrees of ischemia, significant postextrasystolic potentiation was also demonstrated, even after 3 hours of occlusion. In contrast, segments that developed more than 80% necrosis failed to potentiate systolic fractional area change after 2 hours, and systolic wall thickening, even after 20 minutes of coronary occlusion. Statistical evaluation revealed a characteristic threshold at 41 to 60% necrosis, beyond which no potentiation of function could be elicited 3 hours after occlusion. Extrapolation from the experimental data suggests that when two-dimensional echographic studies in myocardial ischemia indicate postextrasystolic augmentation of segmental left ventricular function, the latter segments may be assumed to contain only small infarcts or to consist of reversibly ischemic and normal myocardium. Conversely, segments that fail to exhibit postextrasystolic potentiation can be assumed to be more than 60% necrotic.     

Periods of differing mortality distribution during the first year after acute myocardial infarction

The mortality rate after acute myocardial infarction (AMI) has generally been modeled by a single exponential function. The present study was undertaken to determine, in 3 different populations, whether or not periods exist during the first year after AMI which have mortality distributions that differ from this pattern. The 3 patient populations included San Diego (346 patients, 71 deaths), Vancouver (704 patients, 146 deaths), and Copenhagen (1,140 patients, 262 deaths). Hospital admission was within 24 hours of the onset of symptoms, and patients dying within the first 24 hours after hospital admission or of noncardiac or unknown causes were not analyzed. The mortality between 2 and 21 days in the combined data base was 11.4% (range 10.9 to 11.7) and from 3 weeks to 1 year 10.5% (range 9.0 to 11.3). A high degree of similarity was noted among the shapes of the 3 survival curves. The hypothesis of an exponential mortality rate during the entire first year was rejected. Using a special statistic, changepoints at days 17,23, and 24 in the 3 populations (21 days for the combined data base) were identified and used thereafter to divide the year into 2 separate periods of mortality within which exponentiality for the mortality rate was not rejected. The point by which exactly 50% of deaths had occurred was day 19, with 75% of deaths occurring by day 100. These data further define the natural history after AMI and indicate optimal follow-up periods for short- and longer-term management strategies based on risk assessment or trials of risk reduction after AMI.     

Interventricular septal motion and left ventricular function after coronary bypass surgery: evaluation with echocardiography and radionuclide angiography.

To evaluate interventricular septal motion and left ventricular function after coronary bypass graft surgery, 40 patients were studied early postoperatively and serially for up to 16 months with echocardiography and radionuclide angiography. Early after operation mean left septal excursion decreased significantly from 4.6 +/- 0.4 (standard error) to 0.8 +/- 0.6 mm (P less than 0.001), and left septal motion was abnormal in 23 of the 40 patients. Mean right septal excursion reversed from 2.1 +/- 0.5 to -2.1 +/- 0.5 mm early after operation in the 22 patients in whom these measurements could be made, and 15 patients showed paradoxical right septal excursion. At a mean of 4 months after operation, only 7 of 35 patients followed up had abnormal left septal motion, and mean left septal excursion had returned toward normal (3.6 +/- 0.7 mm); mean right septal excursion remained reversed (--1.1 +/- 0.7 mm), and 6 of the 14 patients followed up had paradoxical motion. In the 22 patients whose wall thickness could be measured, mean septal thickening during systole decreased significantly from 35 +/- 4 to 21 +/- 3 percent early after operation (P less than 0.01). During late follow-up septal thickening returned toward normal (32 +/- 4 percent). Mean normalized posterior wall velocity increased significantly after operation from 0.76 +/- 0.03 to 1.01 +/- 0.05 sec-1 (P less than 0.001), but posterior wall thickening remained unchanged. Left ventricular end-diastolic dimension and the radionuclide-determined left ventricular ejection fraction were unchanged postoperatively. It is concluded that (1) echocardiographically detected abnormal septal movement is frequent early after coronary bypass graft operation; (2) both decreased myocardial contraction in the septum and increased anterior movement of the whole heart contribute to this abnormality; (3) the abnormalities in septal movement decrease during late follow-up in many patients but persist in some patients; and (4) posterior wall function tends to increase early after operation and therefore overall left ventricular function remains normal.     

Dynamic changes in left ventricular wall thickness and their use in analyzing cardiac function in the conscious dog: A study based on a modified ultrasonic technique

The thickness of the left ventricular free wall and internal chamber diameter were continuously measured by pairs of ultrasonic crystals together with left ventricular pressure in normal conscious dogs. During the resting state, wall thickness decreased abruptly with the onset of atrial contraction from 10.5 mm to an average end-diastolic value of 9.8 mm. In contrast to most previous studies, there was no change in wall thickness during isovolumic systole, and with ejection the wall thickened by 31.3 percent of end-diastolic wall thickness. Atrial pacing, phenylephrine, isoproterenol and propranolol produced significant changes in chamber size with reciprocal changes in wall thickness. In addition, changes in the extent and velocity of left ventricular chamber shortening in the minor equator were associated with comparable reciprocal changes in the extent and velocity of free wall thickening (correlation coefficients 0.97 to 0.99). During acute coronary occlusion, progressive reductions in the extent and velocity of regional wall shortening with partial ischemia were associated with comparable changes in systolic wall thickening characteristics (r = 0.96 and 0.95), and holosystolic elongation in fully ischemic areas was associated with holosystolic wall thinning. During chronic pressure overload, despite wall thickening, the relation between chamber shortening and wall thickening were retained and direct computation of dynamic wall stress variations was possible. These measurements allowed precise definition of the dynamics of the left ventricular wall during normal and abnormal cardiac states. The demonstration that in the absence of regional dysfunction analysis of wall thickness in a single region of ventricular free wall can be used to describe myocardial and overall left ventricular function, as well as regional function in the presence of ischemia, constitutes a new approach to the assessment of cardiac function that has potential for echocardiographic applications.     

Prediction of late mortality after myocardial infarction from variables measured at different times during hospitalization

The long-term prognostic importance of sets of variables from different times in the hospital course after acute myocardial infarction was examined in 818 patients discharged from the hospital. Cardiac mortality during the first year after discharge was 11.1 %. For the end point death within 1 year after admission, discriminant function analysis identified 5 important factors from the history and the first 24 hours of hospitalization: maximal level of blood urea nitrogen, previous myocardial infarction, age, displaced left ventricular apex (abnormal apex) on physical examination, and sinus bradycardia (negative correlation). When data from the entire hospitalization were included, extension of infarction and maximal heart rate were also selected. When variables obtained at discharge were included, only the presence of S₃ gallop and abnormal apex were selected. In subgroups of patients, neither the left ventricular ejection fraction nor the presence of complex ventricular arrhythmias during a 24-hour ambulatory monitoring were independent predictors. Correct prediction was similar for each analysis, with 55 to 60% of the deaths and 79 to 81 % of survivors correctly identified. The high-risk group consisted of 25 % of the patients with 28 to 30 % predictive value for death in the first year. In conclusion, outcome up to 1 year after acute myocardial infarction can be predicted early after admission. Addition of more information later during the hospitalization and at discharge did not improve correct prediction and may be redundant for prognostic evaluation.     

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.     

Left ventricular function in exercise-induced hypertrophy in dogs.

Indexes of left ventricular function and diastolic compliance were studied in 10 awake exercise-trained greyhounds with left ventricular hypertrophy. Mean left ventricular to body weight ratio and mean myocardial cell diameter were significantly greater than in normal dogs (8.73 +/- 2.7 [standard error of the mean] versus 4.63 +/- 0.24 g/kg, P less than 0.01; and 18.3 +/- 0.67 versus 12.5 +/- 0.71 mu, P less than 0.01, respectively). In awake resting animals, 7 to 50 days after implantation of a high fidelity micromanometer and sonomicrometer crystals, left ventricular contractility indexes were similar to those measured previously in normal dogs (maximal derivative of left ventricular pressure [dP/dt] 3,800 +/- 250 versus 3,810 +/- 330 mm Hg/sec, difference not significant; and mean rate of circumferential fiber shortening 1.54 +/- 0.12 versus 1.43 +/- 0.12 sec-1, difference not significant). During volume loading sufficient to produce a left ventricular end-diastolic pressure of 20 mm Hg, changes in contractility indexes were similar to those in normal dogs; however, heart rate increased significantly (74 percent, P less than 0.005) in the trained greyhounds but not in normal dogs. Left ventricular diastolic stiffness did not differ from normal (51.6 +/- 3.0 versus 45.9 +/- 5.9 mm Hg/cm, P less than 0.01). These findings suggest that left ventricular function in exercise-induced left ventricular hypertrophy is substantially normal.     

Usefulness of the chest x-ray for predicting abnormal left ventricular function after acute myocardial infarction

We evaluated 229 patients discharged after a definite acute myocardial infarction. Pulmonary venous congestion determined from chest x-ray films during the hospitalization and at discharge and the cardiothoracic ratio at discharge were compared to the left ventricular ejection fraction measured at discharge by a gated radionuclide technique. During hospitalization, pulmonary venous congestion was found on at least one x-ray frame in 94 patients (41%). At discharge 134 patients (59%) had abnormal ejection fraction (less than 0.51) and 35 had pulmonary venous congestion (15%). The sensitivity of the x-ray for detecting an abnormal ejection fraction was 20% when pulmonary venous congestion was observed on the discharge x-ray film (specificity 92% and predictive value 77%), 52% if pulmonary venous congestion was present on any x-ray film during the hospitalization (specificity 74% and predictive value 73%), and 47% if the cardiothoracic ratio was abnormal (greater than or equal to 0.50) on the discharge x-ray film (specificity and predictive value 66%). We conclude that an abnormal x-ray film at discharge or during the hospitalization will identify approximately one-half of the abnormal ejection fractions at the time of hospital discharge. Therefore, to reliably assess left ventricular function, either for prognostic or therapeutic purposes in the individual patient, a more direct measure of left ventricular function such as radionuclide angiography must be obtained.     

Effects of changes in preload,afterload and inotropic state on ejection and isovolumic phase measures of contractility in the conscious dog

Despite much investigation, the usefulness of various indexes employed clinically for detecting alterations in ventricular contractility in the intact circulation remains controversial. The effects of acute preload, afterload and contractility changes on both ejection and isovolumic phase measures of left ventricular function were analyzed in normal, trained conscious dogs instrumented with micromanometers and endocardial ultrasonic diameter gauges. Rapid volume overload increased the excursion of the left ventricular diameter (Δ LVD) by 7 percent above the control level, but mean velocity of circumferential shortening (V_CF) did not change significantly; peak rate of left ventricular pressure rise (dP/dt) increased by 11 percent and (dP/dt)/DP40 (DP = developed pressure) was augmented by 10 percent, but maximal [(dP/dt)/LVP], or “V_pm” decreased by 20 percent. Pressure overload by phenylephrine infusion decreased Δ LVD by 15 percent and mean V_CF fell by 26 percent; peak dP/dt and (dP/dt)/DP40 remained unaltered, but V_pm was reduced by 37 percent. Isoproterenol augmented peak dP/dt by 55 percent, and (dP/dt)/DP40, V_pm and mean V_CF were increased comparably. Propranolol decreased these measures equally by about 16 percent. Therefore, in the conscious animal in the steady state, isovolumic phase indexes were mildly influenced by acute volume loading, whereas ejection phase indexes were not. Acute increases in aortic pressure markedly reduced ejection phase measures, whereas the isovolumic indexes were unaffected. All of the indexes studied were comparably sensitive to acute alterations in contractility, but we conclude that no single measure can always be used for defining an acute contractility change in the intact circulation.     

Effects of heparin in large doses on the extent of myocardial ischemia after acute coronary occlusion in the dog.

Heparin in large doses significantly improved epicardial electrocardiographic findings and preserved myocardial tissue and creatine phosphokinase (CPK) after coronary ligation in the dog. Epicardial S-T segment elevation 15 minutes after occlusion was lowered 84% (from 64.5 + 8.5 [standard error of the mean] to 10.4 +/- 3.0 mv) by heparin infusions of 60,000 units. Myocardial creatine phosphokinase depletion was reduced from 39 to 24% at comparable levels of S-T segment elevation. Histologic evidence of necrosis decreased 32%. It is concluded that heparin can reduce the extent of ischemic injury after acute coronary occlusion in the dog. These results may lend insight into the factors responsible for ischemic injury.     

Effect of heparin in anticoagulant doses on the electrocardiogram and cardiac enzymes in patients with acute myocardial infarction. A clinical pilot study.

The effect of heparin in clinical anticoagulant doses on S-T segment and cardiac enzymes was studied in 18 patients with acute myocardial infarction by electrocardiogram and enzyme evaluation 1 hour and 24 hours after initial heparin infusion. Intestinal mucosa heparin was given by infusion, 10,000 units after the admission electrocardiogram, and 5,000 units every 6 hours. Data in the nine control and nine treated patients were statistically similar on admission. The electrocardiograph findings were improved, but not significantly, 1 hour after administration of heparin. At 24 hours of heparin therapy, the S-T deviations were reduced 64% (from 139 +/- 2.1 [standard error of the mean] to 50.5 +/- 1.2 mm); in control patients S-T deviations were reduced 21% (from 109 +/- 1.8 to 86 +/- 0.9 mm (t=2.9, P less than 0.019). At 24% hours electrocardiographic leads with 2 mm or more deviation were reduced 86% in heparin-treated patients and 28% in control subjects. Cardiac enzymes were comparably elevated at 24 and 48 hours in both groups, with no clear trend. It is concluded that heparin in anticoagulant doses reduces the 12 lead electrocardiographic pattern of injury without discernibly modifying cardiac enzymes. The question of heparin efficacy in acute myocardial ischemic injury, reopened by findings with large dose heparin in therapy in dogs and anticoagulant dose in this study, awaits further expanded investigation.