Jacob I. Haft

Inheritance of combined hyperlipoproteinemia: Evidence for a new lipoprotein phenotype☆

Abstract There are patients whose serum contains elevated levels of low density and very low density lipoproteins (LDL and VLDL). These lipoproteins exhibit normal beta and prebeta electrophoretic mobility. To ascertain whether these patterns are genetic traits, lipoproteins have been quantified by preparative ultracentrifugation in the members of three kindreds with familial hyperlipoproteinemia and in one set of monozygotic twins. Elevations in both LDL and VLDL levels followed a heritable pattern. Among alternative genetic interpretations, the most plausible is that the combined pattern results from the chance combination of two separate genetic determinants, one for elevated LDL levels and another for elevated VLDL levels, with modification by other genetic factors. The genotype for elevated LDL levels is not likely to be identical with that of familial hyperbeta lipoproteinemia (type II), since a low frequency of isolated elevations in LDL levels in these kindreds and absence of the abnormality in childhood members who were at risk are incompatible features. Subjects with combined hyperlipoproteinemia manifested characteristics that are usually prevalent in type IV kindreds; that is, impaired glucose tolerance, obesity and hyperuricemia, whereas clinical characteristics of the familial type II disorder, notably xanthomas, were absent. Ischemic heart disease seemed to be associated with the combined pattern primarily when concurrent abnormalities of glucose tolerance were present, suggesting synergy between disturbed carbohydrate and lipoprotein metabolism in the genesis of coronary artery insufficiency in these subjects.

Termination of atrial flutter by rapid electrical pacing of the atrium

Abstract A technic has been developed for converting atrial flutter to normal sinus rhythm utilizing an intra-atrial electrode catheter and rapid impulses 10 milliamperes in magnitude delivered directly to the atrial wall. Atrial flutter has been converted to normal sinus rhythm in 3 patients after premedication with small doses of quinidine or procainamide. No anesthesia is required, the ventricle is at no time depolarized by the shock, and there is no ventricular irritability produced.

Atrial Fibrillation Produced by Atrial Stimulation

Twenty-six episodes of atrial fibrillation and flutter-fibrillation, each lasting less than 23 sec, were recorded in three normal subjects during atrial pacing studies. The cause of these atrial arrhythmias was determined to be the result of stimulation within the atrial vulnerable period.

Role of blood platelets in coronary artery disease

Over the past decade, research in blood platelet physiology has led to the suggestion that platelets play an important part in the pathogenesis and complications of coronary artery disease. Occlusive intravascular platelet aggregates have been shown to cause ischemic myocardial damage in the experimental animal and to be present in some patients who die suddenly. The interplay between endothelial damage and platelet aggregation has been implicated in the etiology of atherosclerosis. Products released from platelets during aggregation may cause arterial spasm. Patients with overt ischemic heart disease and with the risk factors associated with coronary artery disease have been found to have abnormally reactive platelets. Clinical studies of drugs that inhibit platelet aggregation have been reported to show a beneficial effect in preventing cardiac deaths or myocardial infarction; other studies have been negative or shown only a trend toward benefit. This report reviews the theoretical and experimental basis for the platelet hypothesis and the current data on the use of antiplatelet drugs in patients with coronary disease.

Experimental Production of Aberrant Ventricular Conduction in Man

Aberrant ventricular conduction (AbC) was produced in 17 of 18 subjects, including six normal persons, by the introduction of electric stimuli via a transvenous catheter situated in the right atrium.Analysis of electrophysiological determinants indicated that AbC was favored by a long cycle preceding the short cycle which terminated in the aberrant complex, a short R to stimulus coupling interval, and fast atrioventricular conduction time.Electrocardiographic analysis of AbC revealed that all patients had right bundle-branch block (RBBB). In addition, incomplete right bundle-branch block was present in eight patients and was transformed to RBBB in all cases by shortening the coupling interval. Ten patients had slight but distinct variations of their RBBB pattern. There were two instances each of left bundle-branch block and intraventricular conduction disturbance. Hence, any patient may have the potential to produce a variety of AbC patterns. AbC was produced in six normal subjects and must be considered a physiological event which does not require covert pathology of the specialized conduction system.

Controlled Heart Rate by Atrial Pacing in Angina Pectoris A Determinant of Electrocardiographic S-T Depression

This study was undertaken with a consideration of the physiological relationship between myocardial oxygen consumption and heart rate. Atrial pacing was performed in 63 resting subjects, 36 of whom had been referred for evaluation of angina pectoris. Pacing at critical controlled heart rates evoked angina pectoris in six patients of this group with chest pain and, consistently and more frequently, produced significant S-T segmental depression in 28 patients as a manifestation of myocardial ischemia. The functional test employing controlled heart rates has several advantages over other stress tests. The use of the sole stress of controlled atrial tachycardia is a new technique which has provided relatively safe, reproducible results in the objective evaluation and investigation of myocardial ischemia.

Comparison of the natural history of irregular and smooth coronary lesions: Insights into the pathogenesis, progression, and prognosis of coronary atherosclerosis

The coronary arteriograms of 255 patients who had two to four arteriograms within 2.6 +/- 1.7 years were reviewed. Two hundred three patients had lesions on at least one arteriogram; among the 167 patients without coronary surgery, there were 48 complex irregular lesions (suggesting a ruptured plaque and/or thrombosis) and 141 smooth lesions with follow-up, and 73 irregular and 164 smooth lesions with preceding arteriograms available. Severe irregular lesions (> or = 90% diameter occlusion) progressed to total occlusion (46%) more often than did severe smooth lesions (11.5%) (p < 0.01). Less severe lesions usually did not progress, with no difference in incidence of progression between irregular and smooth lesions (27.8% vs 23.9%). Irregular lesions > or = 80% usually occurred as a result of progression in less severe smooth lesion or occurred in areas that were minimally diseased or appeared normal, whereas smooth lesions > or = 80% had usually not changed since the previous arteriogram. Irregular lesions very rarely became smooth. A study of lesions in 36 patients with surgery was confirmatory. We conclude that plaque rupture is a common mechanism for progression of coronary disease but is not a common pathway for the growth of smooth lesions; irregular lesions remain irregular for years. There is no relationship between the severity of smooth plaques and their likelihood to rupture. Progression of coronary disease can occur by either of two modes: (1) gradual growth of a smooth-walled plaque or (2) plaque rupture with marked progression to a severe irregular lesion. Because most smooth and most irregular lesions remain stable for years, except possibly for > or = 90% irregular lesions, there is no anatomic finding that justifies urgent revascularization. Instability is a clinical diagnosis.

Electrophysiologic documentation of trifascicular block as the common cause of complete heart block

Abstract His bundle electrograms were recorded in 18 patients with chronic complete heart block to determine the site of atrioventricular (A-V) conduction defect. In 14 patients (78 percent) the site of block was distal to the common bundle, and these instances are thought to be examples of trifascicular block. All 14 patients had wide aberrant QRS complexes. In 4 patients (22 percent) the site of block was proximal to the common bundle. In these patients the QRS complex was of normal width or was unchanged after the onset of heart block. In 4 patients with block distal to the common bundle, A-V nodal conduction was shown to respond normally to the stress of rapid atrial pacing. It is concluded that the majority of cases of chronic complete heart block are probably examples of trifascicular block.

Effects of reserpine therapy on cardiac output and atrioventricular conduction during rest and controlled heart rates in patients with essential hypertension.

The effects of long-term reserpine therapy (1) on cardiac output during rest and induced atrial tachycardia and (2) on atrioventricular (A-V) conduction were examined in a group of eight men with previously untreated essential hypertension. The patients were studied before and after 20 to 205 days of reserpine therapy. All studies were performed in the cardiopulmonary laboratory with the patients supine. Heart rate was controlled with a transvenous pacing catheter and a battery-powered pacemaker. After therapy six of six patients had a fall in cardiac output with a statistically significant difference (P<0.001) between the means of paired pre-reserpine and reserpine cardiac outputs during both rest and paced tachycardia. At comparable heart rates, atrioventricular conduction increased in six of eight patients following reserpine, and a significant difference (P<0.05) was evident when the means of pooled paired pre-and post-reserpine A-V conductions were compared.This study indicates that therapeutically administered reserpine in a hypertensive population (1) may significantly lower cardiac output at rest with no further decrease during induced atrial tachycardia, and (2) may increase A-V conduction and enhance second degree heart block during induced atrial tachycardia.

Cardiovascular response to acute thermal stress (hot dry environment) in unacclimatized normal subjects

Abstract The effects of acute heat stress (a hot dry environment) on cardiac hemodynamics were studied in 16 normal unacclimatized male subjects. The results indicate that the cardiac output obtained at a comfortable environment (78° F.) remains essentially unchanged until an ambient temperature of 115° F. is exceeded. At 125° F. the cardiac output both at rest and during exercise is significantly increased over that obtained at 78° F. These increases in cardiac output are associated with inverse changes in A-V oxygen differences. A decrease in the mean pulmonary and brachial artery pressures occurred over the full range of temperatures studied.