Unreliability of conventional electrocardiographic monitoring for arrhythmia detection in coronary care units

To evaluate the reliability of conventional coronary care unit electrocardiographic monitoring, a study was made of 31 consecutive patients with uncomplicated verified acute myocardial infarction. All patients were monitored routinely with conventional equipment, and at the same time the electrocardiogram for each patient was recorded continuously on electromagnetic tape and stored for later analysis by an automated arrhythmia detection system. All patients studied were within 24 hours of the onset of chest pain and on entry into study all were free of shock, heart block, bundle branch block, severe heart failure or an existing arrhythmia. By conventional monitoring, premature ventricular contractions were recognized in 64.5 percent of patients compared with 100 percent using the automated detection system (P <0.01). The corresponding percentages for recognition of premature atrial contractions were 45.2 vs. 96.8 percent (P < 0.001); serious ventricular arrhythmias, 16.1 vs. 93.5 percent (P <0.001); multifocal premature ventricular contractions, 6.5 vs. 87.1 percent (P < 0.001); and consecutive premature ventricular contractions, 13.0 vs. 77.5 percent (P < 0.001), respectively. The delay from the time of first occurrence as detected by the automated system to recognition by the conventional monitoring system averaged 18 hours for premature ventricular contractions, 10 hours for serious ventricular arrhythmias and 23 hours for premature atrial contractions. The on-line use of an automated arrhythmia detection system in the coronary care unit is suggested if further improvement in the elimination of arrhythmias as a primary cause of death after myocardial infarction is to be achieved. The presence of serious ventricular arrhythmias in virtually all patients after myocardial infarction suggests that prophylactic antiarrhythmic agents be used in this setting; however, none of the presently available antiarrhythmic agents have been shown to reduce mortality when given prophylactically following myocardial infarction.     

Nonobstructive hypertrophic cardiomyopathy mimicking mitral stenosis. Documentation by echocardiography, phonocardiography and intracardiac pressure and sound recordings.

The physical findings in hypertrophic cardiomyopathy with left ventricular outflow tract obstruction are well described. In the absence of outflow tract obstruction the findings are less distinctive. There have been several reported cases in which the cardiac findings have suggested the diagnosis of mitral stenosis, In this report we describe a patient whose auscultatory and roentgenographic findings more closely mimicked mitral stenosis. The patient had a loud first heart sound, mitral opening snap and an apical presystolic murmur; left atrial enlargement was present. Noninvasive studies, including phonocardiography, echocardiography and apex cardiography, strongly suggested the correct diagnosis of nonobstructive hypertrophic cardiomyopathy. The diagnosis and unusual auscultatory findings were confirmed by results of cardiac catheterization and intracardiac phonocardiography. The importance of recognizing this syndrome and the use of noninvasive methods to establish the diagnosis are stressed.     

Influence of gemfibrozil on high-density lipoproteins

In animal studies, gemfibrozil markedly elevates high-density lipoprotein (HDL) cholesterol levels, In humans with primary hyperlipoproteinemia and lipoprotein phenotypes IIA, IIB and IV, gemfibrozil, 1,200 mg/day, was associated with a 25%, 20% and 17% increase in HDL cholesterol, respectively. Gemfibrozil also substantially increased the ratio of HDL to total cholesterol, reflecting both an increase in HDL cholesterol and a decrease in very low density lipoprotein cholesterol and low-density lipoprotein cholesterol. Compared with a placebo in subjects with types IIA, IIB and IV lipoprotein phenotypes, therapy with gemfibrozil led to an increase of 33%, 34% and 23%, respectively, in the ratio of HDL cholesterol to total cholesterol. With gemfibrozil therapy, about 80% of subjects with hypertriglyceridemia had a reduction in triglycerides of 35 % or a return to normal levels; 50 % of subjects with hypercholesterolemia had a cholesterol reduction of 20% or a return to normal levels.     

Sterol and bile acid metabolism during development. 3. Occurrence of neonatal hypercholesterolemia in guinea pig and its possible relation to bile acid pool

The relationship of the changes in plasma cholesterol to bile acid pool was studied in the newborn guinea pig. Plasma cholesterol reached the maximum on the fifth day and gradually declined to adult levels. The cholesterol concentration in the high density lipoproteins (HDL) was higher in the newborn guinea pig than in the adult. Plasma triglycerides peaked on the third day and decreased markedly. The bile acid pool increased progressively after birth with a 13-fold increase at 5 days of age. While the hepatic triglycerides decreased sharply in the newborn guinea pig, hepatic cholesterol increased in the first 5 days and then decreased to adult levels. This study has described the occurrence of “neonatal hypercholesterolemia” in the guinea pig and its possible relationship to the low level of bile acid synthesis.     

Influence of clofibrate, bile-sequestering agents and probucol on high-density lipoprotein levels

The management of lipid disorders has been greatly improved by advances in our understanding of lipoprotein metabolism. New developments in the isolation and quantitation of the lipoprotein apoproteins have shed light on their essential role in normal and abnormal lipid transport and have helped clarify the mode of action of lipid-lowering drugs. Excess lipid levels can occur because of overproduction, faulty degradation or defective removal of 1 or more lipoproteins. Clofibrate appears to decrease levels of very low density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL) by enhancing their intravascular degradation. Although it often slightly decreases low-density lipoprotein (LDL) levels, it may markedly increase LDL levels in patients with initially high VLDL levels. Its effects on high-density lipoproteins (HDL) are small, often increasing HDL slightly. Bile acid sequestrants act by enhancing the rate of removal of LDL. Their effects on VLDL and IDL are slight. In some subjects there is a moderate increase in both VLDL and IDL levels. HDL concentrations are increased minimally. Probucol's mechanism of action is still unclear, but it appears to enhance LDL removal. Its effects on VLDL and IDL are minimal. Of concern is the repeated observation that probucol reduces HDL concentrations by decreasing HDL synthesis. The resultant reduction in HDL concentrations often rivals its effect in decreasing LDL levels. Knowledge of the selective effect of lipid-lowering drugs on specific lipoprotein fractions is essential for their proper therapeutic selection.     

Effects of ischemia and coronary reperfusion on myocardial digoxin uptake

The effects of coronary reperfusion on the uptake of digoxin by ischemic myocardium were studied in 17 open chest dogs undergoing anterior wall infarction produced by snaring confluent branches of the left coronary arterial system. Epicardial electrograms delineated ischemic, border and nonischemic zones. The hearts were reperfused by snare release after 1, 2 and 6 hours of occlusion. After 15 minutes of reperfusion, 1.0 mg of tritiated digoxin (³H-digoxin) was given intravenously, and 2 hours later the hearts were excised and endocardial and epfcardial samples from each zone were analyzed for ³H-digoxin concentration. In another group of eight dogs regional myocardial blood flow was assessed utilizing 15 μ of radio-labeled microspheres administered during occlusion and reperfusion. In five dogs with 1 hour of coronary occlusion and subsequent reperfusion, ³H-digoxin uptake was comparable in endocardial and epicardial layers of all three zones. In six dogs undergoing reperfusion after 2 hours of occlusion, mean ³H-digoxin concentration was significantly (P < 0.001) reduced from the mean nonischemic concentration, by 54 percent in endocardial and 35 percent in epicardial layers of the ischemic zone. Border zone endocardial and epicardial ³H-digoxin uptake was reduced by 21 percent and 16 percent, respectively (P < 0.05). In six dogs undergoing reperfusion after 6 hours of occlusion, ³H-digoxin uptake in the ischemic zone was significantly (P < 0.001) reduced by 85 percent in endocardial and 60 percent in epicardial layers from the concentration in the nonischemic zone. Border zone uptake was decreased by 54 percent in endocardial and 36 percent in epicardial regions (P < 0.01). These alterations of in vivo digoxin binding could not be explained by impaired reflow of blood to ischemic myocardium. We conclude that coronary reperfusion after 2 to 6 hours of occlusion is associated with a marked reduction in myocardial digoxin uptake, which is more pronounced in subendocardial than in subepicardial regions of ischemic tissue.     

Exercise electrocardiogram, blood pressure, and working capacity in young patients with valvular or discrete subvalvular aortic stenosis

Electrocardiographic changes, blood pressure, and working capacity (total work) were recorded during an upright cycle exercise test in 65 children and young adults (mean age 12 years) with valvular or discrete subvalvular aortic stenosis. All patients had cardiac catheterization, but none had surgical treatment. Controls consisted of 164 normal subjects (mean age 15 years). In the patients, the intervals between the exercise test and cardiac catheterization were 1 month or less in 66%, 2 to 12 months in 28%, and 12 to 24 months in 6%. The patients were classified by resting left ventricular to aortic peak systolic pressure gradient into Groups I (gradient less than 30 mm Hg), II (30 to 49 mm Hg), III (50 to 69 mm Hg), and IV (70 mm Hg or greater). The mean frequency and magnitude of exercise-induced S-T depression were greater in the patients than in the control subjects (p less than 0.005) and increased with increasing obstruction in the patients. Mean total work and peak exercise systolic pressure were significantly decreased in the patients with a left ventricular to aortic systolic gradient of 30 mm Hg or greater as compared with the control subjects (p less than 0.03). An exercise profile consisting of S-T depression of 2 mm or more, and markedly decreased total work and systolic blood pressure were characteristic of the 19 patients (Group IV) with a resting left ventricular to aortic systolic gradient of 70 mm Hg or greater. At least 2 or more components of this exercise profile occurred in 11 (24%) of the 46 patients with a resting left ventricular to aortic systolic gradient less than 70 mm Hg. This study demonstrates that exercise testing reveals serious abnormalities in patients otherwise classified as having trivial or moderate obstruction, and that a properly performed exercise study can be done at minimal risk to the patient.     

Pregnancy, parturition, and lactation in familial homozygous hypercholesterolemia

Lipids and lipoproteins were studied during pregnancy, parturition, and lactation in a subject homozygous for familial hypercholesterolemia and her obligate heterozygote neonate. At the end of the 1st trimester, plasma cholesterol had risen from a preconception level of 530 to 621 mg/dl, C-LDL rose from 489 to 550 mg/dl, C-HDL from 36 to 46 mg/dl, and triglyceride from 23 to 125 mg/dl. During the 2nd trimester, mean cholesterol (615 mg/dl) was significantly higher compared to preconception levels, C-LDL remained elevated at 531, C-HDL was increased to 50 mg/dl, and triglyceride had risen appreciably to 174 mg/dl. In the 3rd trimester, total cholesterol increased to 632 mg/dl, C-LDL rose to 548, triglycerides rose sharply to 275, and C-HDL fell to 30 mg/dl. The neonate's cord blood C-LDL was elevated at 52 mg/dl. Breast milk cholesterol 7 wk postpartum was 6.5 mg/g total milk fat, considerably greater than levels in 14 normals (2.4 ± 0.4). Placental lipid distribution revealed sharply reduced levels of phospholipids, triglyceride, and cholesterol, and increased free fatty acids. The linoleic acid content of the free fatty acid and triglyceride in the placenta (13.8% and 15.1%) was higher than in normal placentas, 10.0% and 10.2%, respectively. The arachidonic acid content of the triglyceride and cholesterol ester in the placenta, 3.5% and 17.8%, were considerably lower than in normal placentas (29.6% and 32.7%). Gross and microscopic examination of placental vasculature did not reveal any evidence for placental insufficiency or accelerated fetal or maternal atherosclerosis.     

Neonatal familial hyperalphalipoproteinemia.

A kindred with four-generation vertical transmission of familial hyperalphalipoproteinemia was ascertained by measurement of elevated levels of cord blood high-density lipoprotein cholesterol (C-HDL) in a neonatal propositus. Quantitation of cord blood C-HDL coupled with family studies and longitudinal follow-up allows the diagnosis of familial hyperalphalipoproteinemia in infancy.     

Prevention of calcium paradox-related myocardial cell injury with diltiazem,a calcium channel blocking agent

The effect of diltiazem on creatine kinase release and tissue adenosine triphosphate content was investigated during calcium paradox in the isolated perfused rat heart. Creatine kinase loss was minimal during the calcium-free phase, but there was a 100-fold increase in creatine kinase release after reperfusion with normal calcium-containing medium. Diltiazem reduced creatine kinase loss by 35 percent when added to calcium-free medium and by approximately 80 percent when added to both calcium-free and reperfusion media. Adenosine triphosphate content was significantly increased from 2.98 μmol in untreated calcium paradox hearts to 5 μmol/g dry weight in diltiazem-treated hearts. With hyopthermia the calcium paradox injury was completely inhibited if the temperature of calcium-free perfusion was maintained at 15 ° C. Diltiazem appears to exert its protective effect through its ability to prevent the cellular separation and alterations in the gap junctions during calcium deprivation of cells and to limit calcium entry into the cells after reperfusion with calcium-containing medium.     

Effects of excess glucose and insulin on glycolytic metabolism during experimental myocardial ischemia

The selective metabolic effects of glucose and insulin were tested in an intact working swine heart preparation. Supplements of glucose (26.6 millimolar [mM] and insulin (0.025 units/ml) were provided to 18 hearts, 9 control hearts (coronary flow 151 ml/min) and 9 hearts rendered globally ischemic (coronary flow reduced from 167 to 85 ml/min). These hearts were compared with 14 additional hearts (6 control and 8 ischemic) given no supplements (glucose 8.6 mM, no excess insulin). In hearts without supplements, ischemia significantly decreased mechanical performance, myocardial oxygen consumption, fatty acid oxidation and tissue high energy phosphate stores. Glucose consumption was reduced from 133 micromoles (μmol)/hr per g (before ischemia) to 58 μmol/hr per g (P < 0.05), presumably from inhibition at glyceraldehyde-3-phosphate dehydrogenase. Data for control hearts with excess glucose and insulin were similar to data in control hearts without supplements except that glucose consumption and glycolytic flux were increased. Ischemia in treated hearts, as compared with untreated ischemic hearts, effected similar significant decreases in myocardial oxygen consumption, fatty acid oxidation and high energy phosphate stores and resulted in greater reductions in mechanical performance and in 10 minutes' less average survival time. Glucose consumption was reduced from 483 (before ischemia) to 242 μmol/hr per g (P < 0.005) and inhibition at glyceraldehyde-3-phosphate dehydrogenase was again noted. Thus, excess carbohydrate and insulin hormone, when infused directly into the ischemic myocardium, did not provide an efficacious increase in either glycolytic flux or energy production. These findings suggest that an alternative explanation for the reported efficacy of glucose-insulin-potassium infusions must be sought.     

A 12-lead patient cable for electrocardiographic exercise testing

A simple electrocardiographic cable for use with exercise testing has been developed which has proved to have many advantages over commercially available cables used with standard single-channel recorders. It can be adapted easily for multiple channel equipment.     

An appraisal of the nitroblue tetrazolium reduction test

The available literature on the nitroblue tetrazolium reduction test is reviewed. The mechanism of this test is poorly understood. There are two basic methods of performing the test, namely, the stimulated and the spontaneous methods. However, the test procedure has not been standardized, and numerous modifications have ensued resulting in a number of technics. The stimulated test has proved to be valuable for screening patients or carriers with chronic granulomatous disease of childhood. It is one of the useful tests in studying neutrophil dysfunction. On the other hand, extensive accumulated data indicate that this test, be it stimulated or spontaneous, cannot be relied upon as an absolute test to differentiate bacterial from nonbacterial infections and noninfectious diseases as there have been numerous false-positive and false-negative results. When this test is used, the result should be interpreted in the context of other laboratory test results and the clinical picture of the patient. Preliminary data indicate that in certain diseases, If the initial test is positive in a particular patient, it may be useful as one of the follow-up tests to ascertain the activity of the disease process.     

Comparative study of myocardial ischemia during angina at rest and on exertion using thallium-201 scintigraphy

To compare the results of thallium-201 myocardial scintigraphy during angina at rest with those observed during effort angina, 81 patients were selected in whom the existence of acute myocardial ischemia was indicated both by typical transient S-T segment or T wave changes and by typical anginal pain. In these patients, scintigrams were obtained during 58 attacks of angina on effort (group 1) and during 40 attacks of angina at rest (group 2); 16 patients were studied during both types of angina. The attack at rest was spontaneous in 20 patients and induced by ergonovine maleate in 20 patients.In the presence of S-T segment elevation or transient normalization of inverted T waves, scintigrams were positive in all 24 studies at rest and in 19 of 20 studies during exercise. By contrast, in the presence of S-T segment depression scintigrams were positive in 14 (95 percent) of 15 studies during angina at rest, but in only 20 (53 percent) of 38 during angina on effort. Neither the degree of S-T segment changes nor their duration after injection of thallium was significantly different in resting studies relative to exercise studies, but the heart rate and double product were consistently higher during exercise.The marked difference in sensitivity in detecting ischemia in angina at rest with S-T segment depression compared with detection during exertional angina, even in the same patients, suggests that different pathogenetic mechanisms are responsible for the attack. Conversely, a similar mechanism operating in angina at rest and on exertion during S-T segment elevation and normalization of T waves is suggested by the similarity of thallium-201 scintigraphic findings in this situation. The findings are compatible with the hypothesis of a regional reduction in myocardial blood flow in angina at rest, independently of the direction of S-T segment change, and in exertional angina with S-T segment elevation or normalization of inverted T waves; they suggest an inadequate increase in myocardial blood flow in angina on effort with S-T segment depression.     

Pathobiology of acute myocardial ischemia: Metabolic,functional and ultrastructural studies

Acute myocardial ischemia induced by coronary occlusion in dogs is most severe in the subendocardial region, whereas more collateral blood flow is often present in the subepicardial region. Initially, all ischemic myocytes are reversibly injured, but beginning at 15 to 20 minutes after the onset, and continuing for 3 to 6 hours, there is a wave front of cell death from the subendocardial region to the less ischemic subepicardial region, such that by 6 hours, the final transmural extent of the infarct is established. Thus, ischemic myocardium cannot be salvaged by reperfusion after ≥6 hours of coronary occlusion in open-chest anesthetized dogs.In the severely ischemic subendocardial region, most of the creatine phosphate is lost within the first 3 minutes of ischemia in vivo, and adenosine triphosphate (ATP) is depleted to 35% of control by 15 minutes (when cellular injury is still reversible), and to < 10% of control at 40 minutes (when injury is irreversible). Tissue ATP content and other indexes of subcellular damage have also been compared after different periods of ischemia using a model of total myocardial ischemia in vitro. As long as the ATP of the tissue was not depleted below 5 μmol/g dry weight, incubated slices of injured myocardium resynthesized high-energy phosphates and excluded inulin. However, lower tissue ATP was associated with depressed high-energy phosphate resynthesis and failure of cell volume regulation. Overt membrane damage, as measured by an increased inulin-diffusible space, was detected only after the tissue ATP decreased to < 2.0 μmol/g of dry weight. Thus, marked ATP depletion is associated with the onset of structural and functional indexes of irreversible injury. However, whether irreversibility is caused by the marked ATP depletion or by other concomitant metabolic consequences of ischemia is not known. Myocardial ischemic cellular injury is reversible despite depletion of 70% of the control ATP. Nevertheless, when myocyte injury is reversible, there is slow repletion of adenine nucleotides. This slow metabolic recovery may explain the delayed recovery of contractile function observed after reperfusion of ischemic myocardium.