Biomedical subjects
Publications and source records attributed to A G Wallace.
Since its approval by the FDA six years ago, oral disopyramide has earned a recognized role in the treatment of ventricular arrhythmias. During this time, clinical experience has refined our knowledge of this agent, allowing revision of dosing guidelines and better selection of patients. This review explores the recent therapeutic experience with disopyramide.
The ability of patients with severely impaired left ventricle function to perform short-term exercise and to participate in a cardiac rehabilitation program and attain physical training effects was evaluated. Treadmill exercise tests were performed before and after physical conditioning in 10 patients with a prior myocardial infarction and a left ventricular ejection fraction at rest of less than 27 percent (range 13 to 26) determined by radionuclide angiography. All patients participated in a supervised exercise program with a follow-up period of 4 to 37 (mean 12.7) months. Baseline exercise capacity showed marked variability, ranging from 4.5 to 9.4 (mean 7.0 +/- 1.9) METS, and improved to 5.5 to 14 (mean 8.5 +/- 2.9) METS after conditioning (p = 0.05). The oxygen pulse (maximal oxygen uptake/maximal heart rate) before and after conditioning was used to assess a training effect and increased significantly from 12.8 +/- 2.0 to 15.7 +/- 3.2 ml/beta (p less than 0.01). There was no exercise-related morbidity or mortality, although two patients died during the study period. It is concluded that selected patients with severely imparied left ventricular function can safely participate in a conditioning program and achieve cardiovascular training effects.
Previous research has documented high rates of noncompliance to prescribed medical therapy in patients recovering from myocardial infarction (MI). This study was undertaken to determine if patients who subsequently drop out of a structured cardiac rehabilitation program could be prospectively distinguished from those who remain in the program based upon their initial baseline characteristics. Thirty-five consecutive patients with recent MIs underwent comprehensive physical and psychological assessments at entry into the program, and were followed for a period of 1 year. The 14 patients who dropped out of the program could be distinguished from the compliers on the basis of their reduced left ejection fraction assessed by first pass radionuclide angiography at rest and during peak exercise. In addition, their psychological profiles assessed by the MMPI indicated the dropouts were more depressed, hypochondriacal, anxious, and introverted and had lower ego strength than those who remained in the program. Statistical analysis further indicated that psychological variables were associated with noncompliance independently of physical status. These findings suggest that MI patients who are unlikely to adhere to this form of medical therapy may be prospectively identified based upon their initial physical and psychological characteristics.
An attempt was made to assess the effects of aerobic exercise on the psychological functioning of a nonclinical sample of healthy middle-aged adults. Sixteen subjects participated in a 10-week program of regular walking-jogging, while a matched control group maintained their sedentary life-styles. All subjects completed a battery of psychological tests, including the Profile of Mood States, the State-Trait Anxiety Inventory and a retrospective questionnaire regarding self-perceptions of change. Examination of test scores revealed that scores for the exercise group almost always improved, whereas the scores for the control group remained the same or deteriorated. The exercisers exhibited less state and trait anxiety, less tension, depression, and fatigue, and more vigor than the controls. These results document the potential utility of regular aerobic exercise in promoting psychological health in normal adults.
We evaluated the effects of 6 months of exercise training (bicycle ergometry, walking and jogging) on exercise performance and ventricular function in patients with recent myocardial infarction. Fifteen patients were selected on the basis of myocardial infarction at least 6 weeks but not more than 6 months before the study and age younger than 65 years. The patients were evaluated by maximal treadmill exercise testing and radionuclide angiography at rest and exercise before and after training. Before exercise training, maximal treadmill exercise time ranged from 1.5 to 11 minutes, ejection fraction at rest from 18% and 67% and end-diastolic volume from 108 to 208 ml. The mean EF was 48 +/- 5% (+/- SD) at rest and did not change at maximal exercise (48.5 +/- 5%). All 11 patients who completed the exercise training program achieved a significant training effect, as defined by a reduction in heart rate at 50% maximal pretraining effort or an increase in maximal treadmill time. The mean ejection fraction and end-diastolic volume and wall motion abnormalities at rest and at comparable pretraining exercise work loads and heart rates were not significantly different after training. Despite a wide range of rest and exercise ventricular function, patients with recent uncomplicated myocardial infarcts significantly increased their exercise performance. Because rest and exercise ventricular function were comparable before and after training, improvement in exercise performance probably resulted from training effects on the peripheral vasculature.
To address the autonomic mechanisms underlying the bradycardia of physical training in human subjects, we performed a cross-sectional study comparing the heart-rate responses to graded doses of isoproterenol in 7 elite marathon runners and 7 age-matched controls, and a longitudinal study in 12 normal volunteers of the effects of 6 wk of intense physical training on lymphocyte beta-adrenergic receptors identified by l-[3H]dihydroalprenolol. We observed no significant differences between marathoners and controls in the dose of isoproterenol that produced a 25-beat/min increment in heart rate, either in the absence (1.9 +/- 0.6 vs. 2.5 +/- 0.6 microgram; P, 0.509) or in the presence of cholinergic blockade (4.4 +/- 1.3 vs. 3.1 +/- 0.4 microgram: P, 0.320). Likewise, we observed no effects of physical training on lymphocyte beta-adrenergic receptors in terms of receptors number (53 +/- 11 vs. 56 +/- 10 fmol/mg protein) or receptor affinity (Kd 4.0 +/- 0.7 vs. 3.6 +/- 0.7 nM) (P, 0.9178). Although our data cannot exclude reduced chronotropic sensitivity to catecholamines as contributing to lowered heart rate in some highly conditioned individuals, these results are consistent with the hypothesis that altered neuronal input to the sinus node is usually a more important mechanism of training bradycardia.
Ventricular fibrillation was induced in eight of 10 open-chest dogs by reperfusion after a 15-minute occlusion of the proximal circumflex coronary artery. Simultaneous recordings were made from 27 epicardial electrodes spaced over both ventricles. Analysis of the initial 1.5--2.5 seconds of the transition from sinus rhythm or ventricular tachycardia to fibrillation revealed that ventricular activation occurred in an orderly, rapidly repeating sequence in all hearts. Each activation from arose near the border of the ischemic-reperfused region and passed across the nonischemic portion of the ventricles to the opposite side of the heart as a single, organized wavefront. As the arrhythmia progressed, the time between the appearance of successive activation fronts on the epicardium decreased. Concurrently, the time for each activation front to traverse the ventricles increased. The stimulation increase in rate of appearance and decrease in conduction velocity for each successive cycle resulted in overlapping cycles in which a new activation front arose from the ischemic-reperfused region before the previous front terminated over the right ventricle. The overlap between successive activation fronts increased as the arrhythmia continued. Thus, ventricular activation during the transition to ventricular fibrillation arose near the border of the ischemic-reperfused region and was organized as it passed across the nonischemic tissue, but the body surface ECG appeared disorganized because of variable spacing between successive, coexistent activation fronts.
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Patients with exercise-induced S-T elevation or S-T depression were evaluated with demographic, treadmill and angiographic data. When 541 patients with S-T depression were compared with 109 patients with S-T elevation, a greater proportion of the former had chest pain (71 versus 58 percent) and a normal-sized ventricle (86 versus 61 percent) with normal wall motion (54 versus 30 percent). A greater proportion of patients with S-T elevation had had a previous myocardial infarction (61 versus 33 percent). Among patients without prior infarction (360 with S-T depression and 42 with S-T elevation), these differences disappeared. In this group of 42 patients with S-T elevation, 83 percent had a normal-sized ventricle, 64 percent had normal contractility and none had a ventricular aneurysm; the severity of coronary disease and ventricular dysfunction did not differ from the severity in patients with S-T depression. Thus, in patients without prior myocardial infarction, the cause of the development of S-T elevation or S-T depression during exercise does not appear to be related to the severity of the coronary lesions, ventricular function or wall abnormalities at rest. In patients with prior myocardial infarction, exercise-induced S-T elevation appears to be a marker of depressed left ventricular function.
The effects of a 10-week physical-conditioning program on fibrinolytic activity at rest and after stimulation by venous occlusion were studied in 69 healthy adults 25 to 69 years old. Physical conditioning was documented by treadmill performance, and fibrinolysis was measured with a newly developed radioenzymatic assay. Whereas fibrinolysis declined at rest from 16.2 +/- 1.3 to 11.4 +/- 0.8 units (mean +/- S.E.M.) (P = 0.0017), the increment in fibrinolysis produced by venous occlusion was increased from 21.7 +/- 2.9 to 33.8 +/- 4.7 units (P = 0.0037). This augmentation was most marked in women, persons with low initial levels of stimulated fibrinolysis, and persons with low initial physical fitness. We conclude that physical conditioning can enhance the augmentation of fibrinolytic activity that occurs in response to venous occlusion. Enhanced fibrinolysis in response to thrombotic stimuli could be an important mechanism in the beneficial effect of habitual physical activity on the risk of cardiovascular disease.
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This study presents the initial findings of an attempt to reduce the risk of coronary heart disease (CHD) in a group of health, middle-aged adults by participation in a ten-week, supervised exercise program. Forty-six subjects were classified as Type A or Type B based on their scores on the Jenkins Activity Survey (JAS). Measures of physiologic (blood pressure, serum lipids, body weight, plasminogen activator release, and treadmill performance) and psychologic (scores on the JAS) variables were obtained before and after the exercise program. Subjects were able to successfully reduce the physiologic cardiovascular risk factors. Moreover, Type A subjects lowered their scores on the JAS Type A scale after training, while the scores of the Type B subjected remained unchanged. It is concluded that a supervised program of regular exercise can successfully modify the physiological and psychological variables associated with increased risk for CHD in a nonclinical sample of healthy adults.
The conventional technique for mapping the sequence of epicardial activation uses a hand-held electrode moved over the heart to record from a number of epicardial sites one at a time, and requires 5-15 minutes to record from 50 or more sites distributed over the entire ventricular epicardium. This method is inadequate for arrhythmias that are transient or vary from beat to beat. To overcome these limitations the "sock electrode array," a contour-fitting sock containing 26 or 52 electrodes, has been developed. The nylon mesh sock is pulled over the heart and permits simultaneous recording of potentials from electrodes distributed over the entire ventricular epicardium. The electrograms are recorded and converted to digital form for computer generation of isochronous maps. Most of the epicardial activation sequence derived from the sock electrode were compared to those obtained by the hand-held electrode in six normal dogs during sinus rhythm and ventricular pacing. The sequence of local activation times acquired by both methods showed similar areas of early and late activation and comparable isochronous maps. The hand-held electrode technique required 10-15 minutes for data acquisition and another 15-30 minutes for analysis. The sock electrode array allowed electrograms from 26 epicardial electrodes to be recorded simultaneously during one cardiac cycle and computer generated isochronous maps could be displayed within 10 minutes. This method allows rapid recording and analysis of epicardial electrical phenomena and should meet the time constraints imposed during the intraoperative study of ventricular tachyarrhythmias in patients.
We used a cryosurgical technique to ablate the atrioventricular (AV) node-His bundle in twenty-two selected patients with disabling supraventricular tachyarrhythmias unresponsive to medical management. Successful AV block was achieved in seventeen. There was no intraoperative mortality and significant surgical complications were not encountered. Electrophysiologic studies performed 7-10 days after surgery revealed that the subsidiary pacemaker had a narrow QRS complex morphology and a mean cycle length of 1244 msec. Isoproterenol (1-4 microgram/min i.v.) significantly increased (p less than 0.01) the rate of the subsidiary pacemaker (mean maximum response 1008.3 msec); atropine (2 mg i.v.) had no effect on its rate. The cycle length of the subsidiary pacemaker during long-term follow-up (mean 14.8 months) showed a small but significant (p = 0.024) increase (mean cycle length 1430 msec). Treadmill exercise in seven patients did not result in the subsidiary pacemaker exceeding the rate of the implanted demand pacemaker set at 70 beats/min. The properties of the subsidiary pacemaker suggest an intra-Hisian site of impulse formation.
To determine the hemodynamic effects of afterload reduction at rest and during upright exercise in patients with coronary artery disease and left ventricular dysfunction, 12 patients were studied before and after taking 50-75 mg of oral hydralazine every 6 hours for 48 hours. Oxygen consumption and heart rate were unchanged from control both at rest and during two work loads on a bicycle ergometer. Cardiac output was significantly increased at rest and during both workloads. The arteriovenous oxygen difference was significantly reduced at rest and during exercise. Pulmonary capillary wedge pressure was also significantly lower at rest and during exercise. Systemic vascular resistance was reduced at rest, and exercise-induced vasodilation was augmented by the administration of hydralazine. Left ventricular end-diastolic volume and ejection fraction assessed by radionuclide angiocardiography were not significantly changed at rest or during exercise after hydralazine. Seven of the 12 patients have maintained clinical improvement during a follow-up of 6-12 months. Hemodynamic improvement provided by oral hydralazine at rest is maintained during moderate exertion in patients with coronary artery disease and left ventricular dysfunction. In selected patients, chronic afterload reduction with oral hydralazine may result in increased cardiac reserve, decreased pulmonary congestion or decreased myocardial oxygen demands, thereby improving or abolishing resting or exertional dyspnea or angina.
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The effects of a 6-week program of vigorous exercise were studied in 14 non-obese females aged 22--26. Preceding and following a regimen consisting of 30--45 min of jogging 5 days per week, treadmill performance, body weight, total plasma cholesterol, and plasma high density lipoprotein (HDL) cholesterol were assessed. Aerobic performance improved markedly after training as demonstrated by a reduced heart rate at each submaximal treadmill workload, and by an increase in maximal attainable workload. In the absence of a significant change in body weight, total cholesterol fell significantly after training (171 +/- 6 vs 161 +/- 5 mg/dl, P less than 0.05) whereas HDL cholesterol was not significantly altered (63 +/- 5 vs 58 +/- 3 mg/dl). The ratio of total cholesterol to HDL cholesterol fell insignificantly (2.92 +/- 0.19 vs 2.86 +/- 0.14). Our findings differ from prior reports of elevations of high density lipoprotein levels following physical conditioning in men. We suggest that hormonal or other factors leading to higher baseline levels of HDL in women counteract the expected alterations in lipoprotein metabolism induced by physical training.
Bidirectional tachycardia was observed on Holter tracings recorded from a dog three days after the production of a small freeze lesion on the wall of the left ventricle. A bigeminal rhythm with fixed coupling of ventricular premature contractions was interrupted by a burst of ventricular tachycardia of different morphology. The ventricular premature contractions, originally coupled to the sinus beats, became coupled to the new ventricular tachycardia with an identical coupling interval. This resulted in a dibirectional tachycardia, created by the "transfer" of coupling of premature ventricular contractions to a separate ectopic ventricular tachycardia.