ST-segment elevation in patients with cocaine abuse and chest pain.

Use of cocaine may complicate the diagnosis of myocardial infarction (MI) and may influence treatment strategy. Patients with symptoms suggestive of acute coronary syndrome (ACS) should be questioned about the use of cocaine. Initial management of cocaine users presenting with chest pain and ST segment elevation should include administration of glyceryl trinitrate (GTN). Assessment for resolution of chest discomfort and ECG changes should be undertaken before fibrinolytic therapy or angiography is considered. We present a case of patient with chest pain (CP) and ST elevation after cocaine use, whose symptoms and ST changes promptly resolved after medical therapy. Our case highlights the importance of medical therapy in patient with CP and ST elevation after cocaine abuse, before activating cardiac catheterization laboratory for emergent angiography.

R and S wave changes produced by experimental nontransmural and transmural myocardial infarction.

Electrocardiographic R and S wave changes occur after transmural myocardial infarction. It was the purpose of this study to define the spatial characteristics of these changes and their pathologic determinants after nontransmural as well as transmural necrosis. Twenty-six dogs were studied after occlusion of the left circumflex coronary artery for 60 to 240 minutes, followed by reperfusion. Electrocardiographic potentials were recorded before and 1 week after infarction using an 84 electrode array to compute maximal and root-mean-square R and S wave voltages. Infarct size was quantitated by computer-aided evaluation of heart slices stained by triphenyltetrazolium chloride. R and S wave amplitudes after infarction varied widely from one torso site to another in a pattern generally consistent with the inferoposterior location of the infarcted zones. Although changes in peak R and S wave potentials did not significantly correlate with infarct size, differences in pre- and postocclusion root-mean-square R and S wave amplitudes did, with correlation coefficients of -0.79 and -0.63, respectively. Root-mean-square values increased for small lesions and decreased for larger ones. These data indicate that nontransmural as well as transmural infarction can produce R and S wave changes that are dependent on overall lesion size and the specific lead studied. Such changes may represent useful methods to quantitate lesion size.

Effects of experimental myocardial infarction on the ST segment response to tachycardia.

Prior studies have shown that tachycardia results in ST segment depression in dogs with chronic, gradual coronary occlusion. This response was compared with that produced by acute, total occlusion of the left anterior descending artery. Ten dogs served as controls; in another 10 dogs, an ameroid constrictor was implanted about the left anterior descending artery. This artery was acutely ligated in a third set of 10 animals, and in a final set of 10, the distal left anterior descending coronary vasculature was embolized by latex injection. Tachycardia was produced by atrial pacing from rates of 90 to 250 beats/min using implanted atrial electrodes. Electrocardiographic signals registered from 84 torso electrodes were used to construct body surface isopotential maps during the ST segment. In normal dogs, pacing increased repolarization potentials without shifts in spatial features. New and abnormal anterior negativity, correlating with significant ST depression, appeared at rates of 170 beats/min or faster in dogs with ameroid constriction. However, in both groups with acute occlusion that produced transmural myocardial infarction, tachycardia resulted in increases in anterior ST elevation and reciprocal ST depression. Specific findings demonstrated the lead dependency of the response to tachycardia and the greater than normal increase in potential magnitudes after infarction than in control cases. The similarity of the response with acute occlusion and with embolization suggested that the response to tachycardia after infarction was not dependent on coronary collateral function but may represent a direct electrophysiologic effect of rate. Thus, these acute occlusion models simulate exercise-induced ST segment elevation as it may be seen clinically.

Left ventricular hypertrophy: effect on survival.

OBJECTIVES: The aim of the study was to determine whether left ventricular hypertrophy has an independent adverse effect on survival. BACKGROUND: Left ventricular hypertrophy is considered to be a significant risk factor for coronary heart disease mortality; however, the impact of coexisting coronary artery stenosis on survival statistics is not clear. METHODS: The relations among electrocardiographic (ECG) left ventricular hypertrophy, ST-T segment abnormality, coronary artery disease and survival were examined in 18,969 patients undergoing coronary arteriography between 1972 and 1985. Patients were excluded if they underwent coronary revascularization or had unstable angina, rheumatic or congenital heart disease, cardiomyopathy, pericardial disease or ECG changes other than left ventricular hypertrophy or repolarization abnormalities, leaving 4,824 patients for analysis. RESULTS: Left ventricular hypertrophy was present in 249 patients, whereas 4,575 were free of left ventricular hypertrophy. Five-year survival was 90.2% in the group without left ventricular hypertrophy and was significantly lower (81.9%, p < 0.001) in the group with left ventricular hypertrophy. Five-year survival was significantly lower in patients with left ventricular hypertrophy, regardless of whether coronary artery disease was present: 84.4% versus 94.5% (p = 0.016) in the absence of coronary artery disease and 81.0% versus 87.7% (p < 0.001) in the presence of coronary artery disease. The presence of ST segment abnormalities was not associated with a significant reduction in survival in patients without coronary disease, although mortality was less in those without ST changes who had coronary disease (p = 0.012). CONCLUSIONS: It is concluded that ECG left ventricular hypertrophy has an adverse effect on survival, even in patients who are free of coronary artery disease.

Interactive effects of age and other risk factors on long-term survival after coronary artery surgery.

The effect of age at the time of coronary artery bypass graft surgery on postoperative survival was studied in 2,507 patients with significant coronary artery disease. Patients were subdivided into five groups based on age at the time of surgery: 20 to 39, 40 to 49, 50 to 59, 60 to 69 and greater than or equal to 70 years. The observed death rate was compared with that expected for subjects from the general U.S. population matched for age, gender, race and calendar year. For patients less than or equal to 59 years of age, the ratio of observed to expected death rates was significantly greater than unity (observed/expected = 4.9 for ages 20 to 39, 1.9 for ages 40 to 49 and 1.3 for ages 50 to 59 years, p less than 0.01). The prevalence of risk factors, including diabetes mellitus, hypertension, hypercholesterolemia and cigarette smoking, was evaluated in the different age subgroups. When patients were subdivided on the basis of history of cigarette smoking, the decreased relative survival rate of younger (less than 60 years old) patients existed only in those who smoked (observed/expected = 6.0 for ages 20 to 39, 2.2 for ages 40 to 49 and 1.4 for ages 50 to 59 years). In nonsmokers, observed/expected ratios for every age group were not significantly different from unity. Thus, the reduced relative survival rate of younger patients after coronary artery bypass graft surgery may be attributed to the interactive harmful effects of cigarette smoking.

Interactive effects of ST-T wave abnormalities on survival of patients with coronary artery disease.

Previous studies have documented a reduced survival time in patients with an electrocardiographic (ECG) ST-T wave abnormality. This study was designed to determine the clinical, hemodynamic and angiographic correlates of this observation. Data from 9,731 patients undergoing cardiac catheterization from 1976 through 1986 were analyzed; 5,531 had severe (greater than 70%) obstruction of at least one major coronary artery, 1,706 had mild (10 to 69%) obstruction and 2,494 had no obstruction. Of the patients with severe obstruction, 2,536 were treated medically and 2,995 were treated by surgical revascularization. Patients with an ST-T abnormality had more clinical risk factors (including older age and greater prevalence of diabetes mellitus, hypertension and prior myocardial infarction) and greater left ventricular dysfunction (including higher end-diastolic pressure and ventricular volume, reduced ejection fraction and greater prevalence of contraction abnormality) than did those without this ECG pattern. Survival time was significantly (p less than 0.01) reduced in subsets of patients with an ST-T abnormality and with severe or mild coronary artery disease; in those without coronary disease, ST-T changes did not correlate with reduced survival. Stepwise regression analysis was applied to each group to determine the independent predictors of 5-year survival. In patients with severe disease or no disease, an ST-T abnormality was not chosen as an independent predictor of 5-year survival; in the group with mild disease, ST-T changes were an independent predictor of reduced survival. Thus, the independent impact of an ST-T abnormality on survival is dependent on the severity of underlying coronary artery disease.

Hemodynamic effects of intravenous sematilide in patients with congestive heart failure: a class III antiarrhythmic agent without cardiodepressant effects.

OBJECTIVES: This study sought to evaluate the hemodynamic effects of intravenous sematilide hydrochloride, a selective class III antiarrhythmic agent, in patients with heart failure and left ventricular systolic dysfunction. BACKGROUND: Class I antiarrhythmic agents, which primarily slow conduction, can depress ventricular function, particularly in patients with heart failure. In contrast, pure class III agents, which selectively prolong repolarization, do not adversely affect hemodynamic variables in animal models, but there are no data evaluating their hemodynamic effects in humans. METHODS: In 39 patients with congestive heart failure and a left ventricular ejection fraction < 40%, hemodynamic and electrocardiographic measurements were obtained at baseline, after a loading dose and during a maintenance infusion of intravenous sematilide using either a low (0.75 then 0.3 mg/min) or high dose (1.5 then 0.6 mg/min) regimen. The study had an 80% power to detect clinically meaningful differences in hemodynamic variables. RESULTS: Both low (n = 20) and high (n = 19) dose sematilide infusions produced dose-dependent increases in QT interval (5 +/- 8% [mean +/- SD] and 18 +/- 10%, respectively) and corrected QT interval (4 +/- 8% and 14 +/- 10%), and high dose sematilide decreased heart rate by 7 +/- 10% (all p < 0.025 vs. baseline). Neither dose regimen had a statistically significant effect on any other hemodynamic variable, including mean arterial, right atrial, pulmonary artery and pulmonary capillary wedge pressures; cardiac index, stroke volume, systemic and pulmonary vascular resistances; and left ventricular stroke work index. Sematilide showed no adverse hemodynamic effects in patients with left ventricular ejection fraction < or = 25% or > 25% and in patients with cardiac index < 2 or > or = 2 liters/min per m2. Sustained polymorphic ventricular tachycardia (n = 1) and excessive QT prolongation (n = 4) were seen during the high dose. CONCLUSIONS: Sematilide, in the doses administered, prolonged repolarization but did not alter hemodynamic variables in patients with heart failure. These data suggest that class III antiarrhythmic agents, which selectively prolong repolarization, are not cardiodepressant but may be proarrhythmic in humans, especially at high doses.

Natural history of chronic mitral insufficiency: relation of peak systolic pressure/end-systolic volume ratio to morbidity and mortality.

The ratio of peak systolic pressure to end-systolic volume (PSP/ESV) is a measure of contractility that is relatively independent of loading conditions. To define the relation of this index to the natural history of chronic mitral insufficiency, follow-up studies were performed in 76 patients. All had isolated mitral insufficiency and were followed up for an average of 48 months. None underwent surgery. Cardiac volumes, ejection fraction and PSP/ESV ratio were calculated and Cox multiple regression analyses were performed to determine the relation of functional status, ejection fraction and PSP/ESV ratio to morbidity and mortality. Twenty-three patients died during follow-up; in 70% of those who died, the PSP/ESV ratio was reduced below the 20th percentile. However, as an independent predictor of mortality, this ratio was less sensitive (p greater than 0.05) than ejection fraction (p less than 0.01). Similarly, functional status change was predicted more accurately by ejection fraction (p less than 0.01) than by the PSP/ESV ratio (p greater than 0.05). Thus, although a decreased PSP/ESV ratio was associated with a higher mortality rate, other clinical and laboratory variables were superior to this index for determining morbidity and mortality in patients with isolated mitral insufficiency.

Percutaneous coronary intervention versus coronary bypass graft surgery for diabetic patients with unstable angina and risk factors for adverse outcomes with bypass: outcome of diabetic patients in the AWESOME randomized trial and registry.

OBJECTIVES: This study compared survival after percutaneous coronary intervention (PCI) with survival after coronary artery bypass graft surgery (CABG) among diabetics in the Veterans Affairs AWESOME (Angina With Extremely Serious Operative Mortality Evaluation) study randomized trial and registry of high-risk patients. BACKGROUND: Previous studies indicate that CABG may be superior to PCI for diabetics, but no comparisons have been made for diabetics at high risk for surgery. METHODS: Over five years (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior CABG, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, or an intra-aortic balloon being required to stabilize) were identified. A total of 781 were acceptable for CABG and PCI, and 454 consented to be randomized. The 1,650 patients not acceptable for both CABG and PCI constitute the physician-directed registry, and the 327 who were acceptable but refused to be randomized constitute the patient-choice registry. Diabetes prevalence was 32% (144) among randomized patients, 27% (89) in the patient-choice registry, and 32% (525) in the physician-directed registry. The CABG and PCI survival rates were compared using Kaplan-Meier curves and log-rank tests. RESULTS: The respective CABG and PCI 36-month survival rates for diabetic patients were 72% and 81% for randomized patients, 85% and 89% for patient-choice registry patients, and 73% and 71% for the physician-directed registry patients. None of the differences was statistically significant. CONCLUSIONS: We conclude that PCI is a relatively safe alternative to CABG for diabetic patients with medically refractory unstable angina who are at high risk for CABG.

Estrogen replacement and coronary artery disease. Effect on survival in postmenopausal women.

The relationship among postmenopausal estrogen use, coronary stenosis, and survival was examined retrospectively in 2268 women undergoing coronary angiography. The patients were selected for study if their age was 55 years or older at the time of angiography or if they had previously undergone bilateral oophorectomy. Postmenopausal estrogen use in 1178 patients with coronary artery disease (greater than 70% stenosis) and 644 patients with mild to moderate coronary artery disease (5% to 69% stenosis) was compared with 446 control subjects (0% stenosis) using life-table analysis. Over 10 years of follow-up, there was no significant difference in survival among patients initially free of coronary lesions on arteriography who had either never used (377) or ever used (69) estrogens. Among patients with mild to moderate coronary stenosis, 10-year survival of those who had never used estrogens was 85.0% and it was 95.6% among 99 "ever users." Survival was 60.0% among those with more than 70% coronary stenosis who had never used estrogen and it was 97.0% among 70 ever users. The "never users" group were older (65 vs 59 years), had a lower proportion of cigarette smokers (40% vs 57.1%), a higher proportion of subjects with diabetes (21.7% vs 12.9%) and hyperlipidemia (58% vs 44%), and approximately equal numbers of hypertensives (56.0% vs 54.3%). Cox's proportional hazards model was used to estimate survival as a function of multiple covariables. Estrogen use was found to have a significant, independent effect on survival in women. We conclude that estrogen replacement after menopause prolongs survival when coronary artery disease is present, but it has less effect in the absence of coronary artery disease.

Dilevalol in severe hypertension. A multicenter trial of bolus intravenous dosing.

Dilevalol, the R-R optical isomer of labetalol, a nonselective beta-antagonist with vasodilation from selective beta 2 agonism, was administered in sequential multiple bolus intravenous injections of 10 to 100 mg in total doses ranging from 35 to 585 mg (mean dose, 414 mg) to 101 patients with supine diastolic blood pressures above 120 mm Hg. Mean blood pressure was reduced from 200 (+/- 3)/129 (+/- 1) mm Hg to 149 (+/- 2)/101 (+/- 1) mm Hg, a mean reduction of 51/28 mm Hg. The therapeutic goal was established as a reduction in supine diastolic blood pressure to less than 100 mm Hg or a reduction of at least 30 mm Hg. This was achieved in 62 (61%) of 101 patients, with an additional 7 patients having a final supine diastolic blood pressure of 100 mm Hg. Treatment with dilevalol was less successful in black male patients than in the group at large. There was a tendency for older patients to respond better than younger patients. Prior recent treatment of patients with beta-adrenergic antagonists decreased the effectiveness of the drug. Significant orthostatic hypotension was not noted. Sixty-four patients were transferred to oral dilevalol treatment in combination with a diuretic, and blood pressure in this group averaged 160/100 mm Hg after 1 month of therapy. Dilevalol appears to be a safe and effective drug that can be used intravenously successfully in the majority of patients with severe hypertension and provides an alternative to therapy with other agents. It also is a useful agent for oral treatment of these patients after successful intravenous therapy.

Guanabenz and methyldopa on hypertension and cardiac performance.

In previous placebo-controlled studies, guanabenz was shown to be a safe and effective antihypertensive drug without acute effects on cardiac function. In view of its therapeutic advantages, a double-blind comparison of guanabenz with methyldopa was performed in a group of 36 patients over 6 mo. Both drugs produced statistically and clinically significant decreases in blood pressure with similar side effects. No laboratory or electrocardiographic abnormalities were found other than positive Coombs' tests which developed in 3 patients during methyldopa therapy. Cardiac performance in 26 of the patients, as measured by noninvasive techniques, showed no significant changes from either drug except for a progressive and statistically significant increase in systolic time interval (QS2) and the ratio of the pre-ejection period to left ventricular ejection time (PEP/LVET) during methyldopa therapy. For an additional 6 mo, continued efficacy and safety were shown under open conditions in those patients who had received guanabenz. The study suggests that guanabenz may be an important new antihypertensive drug because of effectiveness, absence of adverse cardiac effects, and paucity of side effects.

Comparative effects of fenoldopam mesylate and nitroprusside on left ventricular performance in severe systemic hypertension.

To compare the effects of fenoldopam (n = 15), a selective dopamine-1 agonist, and nitroprusside (n = 14) on left ventricular (LV) function in severely hypertensive subjects (diastolic blood pressure (BP) greater than 120 mm Hg), both agents were infused to reduce diastolic BP by 40 mm Hg (or less than 110 mm Hg). Indexes of LV systolic and diastolic functions were obtained using gated radionuclide angiography before the initiation of treatment and after targeted BP was achieved. Both fenoldopam and nitroprusside effectively reduced systolic and diastolic BP to target levels. Changes in heart rate, peak filling rate and relative end-diastolic volume were similar with both agents. Baseline ejection fraction increased after infusion of both drugs. The magnitude of the increase in ejection fraction was far greater with fenoldopam than with nitroprusside (+22% vs +8%; p = 0.04), despite a lesser reduction in systolic BP (-12 vs -22%, p = 0.002). Furthermore, the reduction in relative end-systolic volume (-35 vs -20%; p = 0.04), and increase in the ratio of peak systolic pressure to relative end-systolic volume (+43 vs +6%; p = 0.007) were greater after fenoldopam than after nitroprusside. The greater increment in parameters of LV systolic function produced by fenoldopam than by nitroprusside suggests an effect on LV performance that is independent of afterload reduction.

Impact of patency of the left anterior descending coronary artery on long-term survival.

This study examines the relative importance of patency of the left anterior descending (LAD) coronary artery on long-term survival when the LAD is the only significantly narrowed coronary artery. From a cardiac disease registry of 21,786 patients, 826 medically treated patients with isolated LAD disease were identified. These patients were followed for > 5 years. Patients were divided into those with open versus those with closed arteries. With the use of univariate and multivariate analysis, the relative importance of the patency of the LAD was determined. All patients with previous anterior wall infarction were analyzed as a separate group, and those with and without a patent LAD were compared. Overall, survival was significantly better in patients with an open LAD. However, multivariate analysis of either the entire study group or the group with myocardial infarction showed that coronary artery patency was not an independent predictor of long-term survival. Analysis of patients with prior anterior myocardial infarction showed significantly improved 5-year survival in younger patients (< 70 years) who had an open (but stenosed) versus a closed LAD without angiographic collateral formation (94% vs 81%, p = 0.025). Furthermore, this survival difference was most striking in patients with left ventricular dysfunction. Survival in younger patients with an open LAD was similar to that of patients with a closed LAD with collateral formation (94% vs 92%, p = 0.55). No differences in survival were observed in the groups without infarction. This study implies that an open LAD improves long-term survival for younger patients with a previous anterior myocardial infarction and no collateral support to the ischemic or infarcted myocardium.

Effect on survival of estrogen replacement therapy after coronary artery bypass grafting.

We examined the relation between postmenopausal estrogen placement therapy (ERT) and survival in 1,098 women who underwent coronary artery bypass grafting (CABG). Patients were selected for the study if their age was > or = 55 years at the time of preoperative coronary angiography or if they had previously undergone bilateral oophorectomy. Life-table analysis was used to compare survival after surgery in 92 women who received ERT and 1,006 women who did not. Five-year survival was 98.8% in the estrogen users and 82.3% in the non-users. Ten-year survival was 81.4% in the users and 65.1% in the nonusers (p = 0.0001 by Lee Desu test). The women who did not take estrogen were significantly older (p < 0.001), had more vessels with significant stenosis (p = 0.033), lower ejection fractions (p = 0.051), and more prior myocardial infarctions (p = 0.054). However, a Cox proportional-hazards model selected the number of coronary arteries narrowed (RR 1.43, p < 0.0001), estrogen use (RR 0.38, p = 0.001), left main coronary stenosis (RR 1.83, p = 0.001), and diabetes mellitus (RR 1.57, p = 0.003) as the significant independent predictors of survival. These data suggest that ERT improves survival significantly after CABG in postmenopausal women with coronary artery disease.

Contrasting effects of dopamine and isoproterenol in experimental myocardial infarction.

The comparative effects of dopamine and isoproterenol on local myocardial contraction and ischemic injury after coronary occlusion were evaluated in 10 dogs. Dopamine (2.5 to 5 mug/kg per min) and isoproterenol (0.125 to 0.25 mug/kg per min) were randomly infused for 20 minutes, and segmental tension (Walton-Brodie gauge) of central ischemic, border and nonischemic myocardial zones and epicardial electrograms (10 to 12 sites) were simultaneously recorded. After coronary occlusion, tension in border zones decreased to 73.5 +/- 6.4 percent (mean +/- standard error of the mean) and tension in central zones to 60.6 +/- 9.9 percent (P less than 0.001) of control level, whereas total S-T elevation (sigmaST) rose from 10.8 +/- 1.6 to 98.4 +/- 14.0 mv and average S-T elevation (ST) from 1.6 +/- 0.2 to 10.8 +/- 1.6 mv (P less than 0.001). Isoproterenol increased heart rate from 148.7 +/- 6.9 to 170.6 +/- 7.7 beats/min (P less than 0.010) and improved tension in the border zone to 110.5 +/- 8.5 percent (P less than 0.010) and improved tension in the border zone to 110.5 +/- 8.5 percent (P less than 0.005) and nonischemic zone to 128.4 +/- 6.7 percent (P less than 0.02). Tension in the central zone was unchanged. However, sigmaST increased from 98.4 +/- 14.0 to 126.9 +/- 14.7 mv (P less than 0.005) and ST from 10.8 +/- 1.6 to 14.2 +/- 1.6 mv (P less than 0.001). Dopamine did not change heart rate but increased tension in the border zone from 72.4 +/- 7.9 to 124.4 +/- 16.8 percent (P less than 0.001) and tension in the nonischemic zone from 86.0 +/- 10.0 to 133.3 +/- 10.0 percent (P less than 0.01). Tension in the central zone was unimproved. However, sigmaST and ST did not increase (sigmaST from 99.8 +/- 10.8 to 97.7 +/- 13.9 mv and ST from 11.1 +/- 1.3 to 10.8 +/- 1.5 mv). Atrial pacing was used to increase heart rate during infusion of dopamine to 180.0 +/- 7.6 beats/min but neither sigmaST nor ST increased. In summary, both dopamine and isoproterenol decrease contraction abnormalities in the border and nonischemic zones after after acute coronary occlusion. Although isoproterenol increases both heart rate and S-T segment elevation, dopamine does not adversely affect either variable.

Progressive transmural electrographic, myocardial potassium ion/sodium ion ratio and ultrastructural changes as a function of time after acute coronary occlusion.

The progressive transmural electrographic, biochemical and ultrastructural changes as a function of time after acute coronary occlusion were systematically assessed in eight dogs. Transmural plunge electrodes with poles 1 mm apart were placed in the ischemic and nonischemic zones, and coronary occlusion was maintained for 4 hours. Transmural full thickness biopsy specimens were obtained from each zone for electron microscopy before, and 1 and 4 hours after occlusion. Endocardial and epicardial layers were also obtained for assessment of myocardial potassium ion (K+) and sodium ion (Na+) concentrations. Before coronary occlusion, local Q waves were recorded an average depth of 1.0 +/- 0.34 mm from the endocardial surface. After 1 hour of occlusion, Q waves appeared at an average depth of 3.8 +/- 0.67 mm and progressed to a depth of 5.2 +/- 0.7 mm at 2 hours, 6.2 +/- 0.5 mm at 3 hours and 7.0 +/- 0.5 mm at 4 hours. After 1 hour, ultrastructural changes of early ischemia, including a decrease in glycogen and mild mitochondrial swelling, were seen in the endocardial layer; the epicardial layer showed normal morphologic features. After 4 hours, the endocardial layer showed well developed ischemic changes marked by the loss of mitochondrial cristae, vacuolization, the appearance of amorhopous mitochondrial cristae, vacuolization, the appearance of amorphous mitochondrial densities, an increase in interfibrillary space and the appearance of I bands. In contrast, the epicardial layer at this time showed only early ischemic changes. At the end of 4 hours, the endocardial layer showed a marked decrease in myocardial K+ concentration and an increase in Na+ concentration leading to complete reversal of K+/Na+ ratio (0.7 +/- 1.0; P less than 0.001). In the epicardial layer, a smaller decrease in K+ concentration and an increase in Na+ concentration occurred, resulting in a diminution but not a reversal of K+/Na+ ratio (1.4 +/- 0.2; P less than 0.005). Thus, the dynamic evolution of an acute myocardal infarction involves a sequential progression from endocardium to epicardium as a function of time, resulting in an epicardial "border zone" in the early stages after acute coronary occlusion.

Association between the severity of diabetes mellitus and coronary arterial atherosclerosis.

The relation between the severity of diabetes mellitus (DM) and the risk of significant coronary artery lesions were studied in 7,655 patients undergoing coronary arteriography for suspected coronary artery disease (CAD) between 1972 and 1982. The principal treatment regimen for DM was used to estimate the severity of DM. DM treated with insulin was defined as the most severe (n = 244), followed by DM treated with oral agents (n = 344) and with diet only (n = 380); 6,687 patients did not have DM. Severity of DM in patients with CAD (70% or greater diameter stenosis) was compared with that in control subjects without CAD (0% stenosis) for each of 9 anatomic locations (proximal, middle and distal portions of right, anterior descending and circumflex coronary arteries) using a retrospective case-control approach. The risk of CAD was highest in patients with DM treated with insulin (odds ratio estimate of the relative risk [OR = 3.0]), followed by patients with DM treated with oral agents (OR = 1.8) and lastly in those treated with diet alone (OR = 1.4). Severity of DM was a significant (p less than 0.05) independent predictor of CAD in a multivariate logistic regression model, whereas age at onset and duration of DM were not. The relative risk of CAD was the same (p greater than 0.05) for each of the 9 coronary segments. The data suggest that the risk of CAD increases with the severity of DM, which was a stronger predictor of CAD than duration of DM.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and pathophysiologic correlates of ST-T-wave abnormalities in coronary artery disease.

Clinical, hemodynamic and coronary angiographic data from 9,801 patients were evaluated to determine the correlates of ST-segment depression, with or without T-wave inversion, on the resting routine electrocardiogram. The relative risk (RR) of having a measured clinical or angiographic variable was computed whether or not ST-T-wave abnormalities were observed. ST-segment depression was seen significantly more often in subjects greater than 55 years of age (RR = 1.4) who were women (RR = 1.3) or nonwhite (RR = 1.5), were hypertensive (RR = 1.8), had diabetes mellitus (RR = 1.6) or who smoked cigarettes (RR = 1.5). Angiographic findings related to presence of ST-T-wave abnormalities included severe coronary obstruction (less than 70%), higher number of diseased vessels, and the presence of obstruction in the left anterior descending coronary artery. In a multivariate model, the most significant correlates of ST-T-wave abnormalities were presence of left ventricular contraction abnormality, followed by age, gender, presence of left anterior descending coronary artery disease, elevated end-systolic volume index, and a diagnosis of hypertension. Thus, electrocardiographic ST-T abnormalities has specific and significant clinical and pathophysiologic correlates.

Influence of beta 2 agonism and beta 1 and beta 2 antagonism on adverse effects and plasma lipoproteins: results of a multicenter comparison of dilevalol and metoprolol.

Dilevalol combines vasodilation due to selective beta 2 agonism and nonselective beta antagonism. We studied 311 patients randomized to dilevalol and 138 to metoprolol in a multicenter trial. After a 4-week placebo washout, dilevalol was titrated from 200 to 1,600 mg once daily and metoprolol from 100 to 400 mg to a goal supine diastolic blood pressure less than 90 and greater than or equal to 10 mm Hg decrease from baseline. Responders were followed for 1 year. The average age of patients was 51 years; 72% were men and 54% were white. Both drugs reduced blood pressure effectively to a similar level. Fewer patients discontinued dilevalol than did those taking metoprolol (9 vs 16%; p less than 0.03). More metoprolol-treated patients withdrew because of depression (6 vs less than 1%; p = 0.03) and impotence (5 vs less than 1%; p = 0.03). Lipoprotein levels before and after treatment were measured in 99 patients treated for 53.5 weeks with dilevalol (mean dose 438 mg). Dilevalol increased high-density lipoprotein (HDL) cholesterol by 2.5 mg/dl to 47.2 (p = 0.05), reduced low-density lipoprotein (LDL) cholesterol by 2.5 mg/dl, increased HDL/LDL by 0.03, and decreased total cholesterol/HDL cholesterol by 0.18. Triglycerides increased by 21 mg/dl (p = 0.06). In patients with an initial HDL cholesterol less than 35 mg/dl, dilevalol increased it by 9 mg/dl. In patients treated with metoprolol, the only significant change (p = 0.02) was a 41.9-mg/dl increase in triglyceride levels.(ABSTRACT TRUNCATED AT 250 WORDS)