Biomedical subjects
Publications and source records attributed to D C Harrison.
Bacterial endocarditis is a rare complication of cardiac catheterization. We present the history of a patient who developed fatal, acute bacterial endocarditis following diagnostic cardiac catheterization. The implications regarding antibiotic prophylaxis and catheterization technique are discussed.
Eleven consecutive patients with recurrent ventricular arrhythmias were treated by an aggressive protocol and followed up prospectively. Arrhythmias, symptoms, and cardiac lesions were defined. Antiarrhythmic drugs were given on schedule, with blood levels determining dose; success or failure was defined by elimination or recurrence of symptomatic arrhythmias. When drug therapy failed, left ventricular aneurysmectomy was done when appropriate. Recurrent ventricular tachycardia was most frequently responsible for symptoms; coronary artery disease was the most frequent underlying disease. Symptomatic arrhythmias were eliminated in 8 of 11 patients (5 with drugs and 3 with aneurysmectomies), with a 16.5-month symptom-free average follow-up. An average of 2.9 therapeutic trials per patient was needed to control symptomatic arrhythmias. The average time from entry into the study until the start of ultimately effective therapy was 18 days. Therapy that eliminated symptoms did not eliminate all premature ventricular contractions, and occasionally even brief asymptomatic episodes of ventricular tachycardia persisted. Recurrent symptomatic ventricular arrhythmias can be controlled in many patients by rigorous application of current therapies.
Some of the laboratory difficulties in assessing infarction size produced by intermittent coronary artery occlusion were demonstrated by using an epicardial mapping technique in anesthetized open-chest dogs. Intermittent occlusion of a left anterior descending coronary artery branch resulted in a marked elevation of the ST segment above the baseline in the areas of the myocardium supplied by this vessel. Repeated occlusions after administration of normal saline as a control produced less ST-segment elevation thn that noted during control occlusions; however, repeated occlusions after infusion of quinidine produced a further lessening in ST-segment elevation. The problems encountered in interpreting these results are emphasized. Long-term coronary occlusion studies were performed in order to correlate epicardial electrograms with histological findings of ischemia or myocardial necrosis. Our investigations show that epicardial mapping tended to underestimate the area of injury, and this limits the interpretation of drug intervention studies such as those in which quinidine is administered. Therefore, caution should be exerted when using epicardial mapping techniques to assess the effect of various pharmacological interventions on infarction size in open-chest dogs.
The current status of the human cardiac transplant experience at Stanford University Medical Center is presented in order to reassess its role in the treatment of end-stage cardiac disease. Of 109 patients undergoing transplantation at Stanford between January 1968 and August 1976, 44 were still alive as of August 1, 1976. The overall 1- and 2-year survival rates for the series are 52% and 43%, respectively. Sixty-nine patients have survived more than 3 months, and their overall 1- and 2-year survival rates are 80% and 66%, respectively. Of the 3-month survivors, 62 (90%) returned to functional Class I New York Heart Association cardiac status and most of these returned to their pre-illness activities. Of 40 patients selected for transplantation for whom a donor did not become available, 38 were dead in less than 6 months. Complications related to immunosuppression with steroids are currently the major barrier to longer survival and improved rehabilitation postransplantation. On the basis of these data we conclude that cardiac transplantation not only prolongs survival, but can return carefully selected recipients to an active life.
An acetyl-homologue-metabolite, present in concentrations of up to ten times those of the unchanged drug, in the plasma of patients receiving oral doses of acebutolol, is reported. Combined gas chromatography--mass spectrometry has been utilized to determine the structure of the acetyl-metabolite. This acetyl-metabolite has been measured as acebutolol by previously published non-specific methods for the determination of acebutolol in biological fluids. A specific and sensitive gas chromatographic method is described for the separate quantitation of acebutolol and its acetyl-metabolite in plasma and urine. Using our method, preliminary data on the disposition kinetics of acebutolol are presented. The difficulties in interpreting previously published pharmacokinetic data for acebutolol, based on a non-specific method of analysis, are emphasized.
A patient first seen with cardiac cachexia was found to have a large left atrial myxoma. The diagnosis was first suggested by echocardiographic examination. Cure was achieved by surgery. Light and electron microscopic studies indicate a multipotential mesenchymal cell origin of myxomata.
To treat patients with ventricular arrhythmias properly, one must characterize the arrhythmia, define the underlying heart disease and look for and treat reversible causes. When arrhythmias are suitable for pharmacologic suppression, it is necessary to predefine therapeutic goals, then carefully document that the drug accomplishes these goals. Knowledge of a drug's metabolism, excretion, active metabolites and plasma protein binding is often required for full understanding of its clinical effect. Pharmacokinetic principles require that antiarrhythmic drugs be given on a rigid schedule and that plasma drug levels be frequently determined. Use of compartment models and the principle of superposition can enable one to achieve and maintain therapeutic drug concentrations while avoiding toxic side effects. The drugs commonly used to treat arrhythmias, lidocaine, propranolol, procainamide, diphenylhydantoin and quinidine, as well as some newer agents, have specific pharmacokinetics and toxic effects that must be understood.
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The kinetics of distribution and elimination of lidocaine and two of its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX), were studied in 4 uremic patients on chronic hemodialysis. Each patient received a loading dose of 75 mg of lidocaine, followed by a 30 mug/kh/min lidocaine infusion. No toxic side effects from lidocaine were seen during the study. Average values for lidocaine steady-state plasma levels (2.3 mug/ml) clearance (12.3 ml/min/kg), terminal half-life (148 min), and total volume of distribution (1.9 L/kg) were found, and are similar to those values reported for normal subjects MFGX and after lidocaine infusion averaged 1/5-2/3 of the corresponding lidocaine level, as in nonuremic subjects, and plateaued by 6-8 hr. GX levels did not reach plateau by 12 hr and remained relatively unchanged after infusion. It is concluded that lidocaine infusion in uremic patients is safe, with no abnormal cumulation of lidocaine or MEGX. GX levels, however, may increase progressively, even after 12 hr.
Eighty patients with various forms of heart disease were studied with the use of a newly developed ultrasonic system having 20 transducers arranged in a linear array. This system allows visualization of the heart in two dimensions in real time. All 15 patients with the mitral valve prolapse syndrome, 13 patients with mitral stenosis, five patients with pericardial effusion, four patients with atrial septal defect, and one patient with left ventricular dyssynergy were properly recognized with this system. One of five patients with hypertrophic myopathy and one of four patients with congestive myopathy were not recognized with this system. Criteria for the recognition of these system. Criteria for the recognition of these conditions are presented as well as the probable cause for false-positive and false-negative diagnoses in this series. Since only qualitative criteria were used, it was not possible to differentiate patients with coronary artery disease or patients with left ventricular volume overload from patients without cardiac pathology. The accuracy of this new system was judged against the clinical examination, conventional echocardiography, cardiac catheterization, and left ventricular angiography. It is assumed that the criteria for diagnosis developed during this study will be supplemented and the equipment improved in the future; however, the ease of operation of this system and the relative accuracy of diagnosis at this stage of its development are extremely interesting. It presents an excellent opportunity to obtain additional information about the cardiac patient without using invasive procedures and without risk.
The hemodynamic effects of tazolol, a new long-acting beta-stimulating drug, were studied in dogs with acute pump failure caused by experimental myocardial infarction and the results were compared with the actions of isoproterenol given in small and large doses. Tazolol produced a significant and sustained increase in cardiac output and stroke volume, while causing a decrease in peripheral resistance and mean aortic pressure. Heart rate was only modestly increased. Compared with isoproterenol at equivalent doses. tazolol appeared to cause less S-T segment elevation at the margin of infarction. The increase in double product (systolic pressure X heart rate) produced by tazolol was also considerably less than that of isoproterenol. Tazolol may prove to be a useful addition to the drugs available for the treatment of myocardial failure of various causes. It is now being studied in patients with heart failure due to coronary artery disease.
Dopamine and isoproterenol were each administered in two different doses to 12 patients with coronary artery disease in the period immediately after open heart surgery. The two doses of dopamine resulted in respective increases in cardiac output of 23 and 43 percent and reductions in systemic vascular resistance of 23 and 32 percent; neither dose significantly altered heart rate. The two doses of isoproterenol caused respective increases of 23 and 37 percent in cardiac output and 18 and 28 percent in heart rate and reductions in systemic vascular resistance of 22 and 29 percent. We conclude that lack of chronotropic effect of dopamine as compared with isoproterenol may make the former the agent of choice in patients requiring inotropic agents for their care in the early period after cardiac surgery.
Five patients who had received a transplanted human heart 1 to 3 years previously were studied to determine the effects of norepinephrine, isoproterenol and propranolol on the atrioventricular (A-V) conduction system. Using the His bundle technique, atrial, His bundle and ventricular electrograms were recorded, and central aortic pressure was monitored during the administration of these drugs. Norepinephrine was given by continuous infusion to four patients in doses ranging from 4 to 8 mug/min, with the systolic arterial pressure increasing by an average of 72 mm Hg. Concomitantly, there was an average increase in the rate of the donor atrium of 32 beats/min, and a reflex slowing of the recipient atrium of 23 beats/min. The A-H interval shortened by an average of 27 msec. Isoproterenol dose-response curves were performed in three patients, with the maximal dose being 5.2 mug by intravenous bolus infusion. The rate of the donor atrium increased by an average of 40 beats/min, and that of the recipient atrium by 18 beats/min. The A-H time shortened by an average of 25 msec, with a drop in systolic blood pressure averaging 23 mm Hg. Propranolol (7 mg intravenously) was given to three patients and the peak doses of norepinephrine and isoproterenol were again infused. Beta adrenergic blockade was achieved at this dose of propranolol since there was only a minimal increase in the donor atrial rate after infusion of the drug. The A-H interval was not altered by catecholamine infusion after achievement of beta blockade. However, the levels of systolic hypertension noted after infusion of norepinephrine was not altered by propranolol. The denervated transplanted human heart appears to respond normally to norepinephrine and isoproterenol, and the electrophysiologic effects of these agents are blocked by propranolol. Extensive investigative work in the denervated canine model has demonstrated the presence of the alpha and beta cardiovascular receptors. Although the automonic nervous system is important in cardiac performance, this work is the first validation in man that (1) the functional integrity of the beta receptor is maintained even when the autonomic nerves are absent, and (2) the intrinsic properties of the sinus and atrioventricular nodes are the keystone in stabilizing cardiac electrophysiology after denervation.
An improved technique for identification, diagnosis and quantification of arrhythmias during rest or ambulatory electrocardiographic recording is described. With simultaneous plotting of the R-R interval and the QRS duration and QRS vector measurement of each beat versus time, all periods of arrhythmias or abnormal complexes can be identified and characterized. Analog electrocardiographic samplings are used to confirm the diagnosis of the arrhythmia and to exclude artifact. The availability of a permanent record for the characterization of each QRS complex enables the physician to check the technician's analysis of the recording and to relate all events to the patient's heart rate and clinical symptoms. This technique also provides data for quantification of ventricular arrhythmias.
An echocardiogram from the left ventricle may be used to estimate left ventricular volume and rate of circumferential fiber shortening, to measure posterior wall and interventricular septal thickness and to evaluate the normality of septal motion. Extended application of this technique in this laboratory has emphasized the need for a more standardized means of transducer location and direction. The effect of placing the ultrasonic transducer in several intercostal spaces along the left sternal border was tested in 14 patients. Variability in the left ventricular dimension and the difference in this dimension from end-diastole to end-systole were greater than for duplicate measurements from the same interspace. A system has been developed for more consistent placement of the transducer in each patient, using intracardiac landmarks and observation of transducer orientation to record specific cardiac structures.
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The first 81 patients who underwent coronary artery bypass surgery at Stanford University Hospital for unstable angina pectoris have been followed up for an average of 18 months. The over-all surgical mortality was 8.6 per cent (seven patients). There have been no operative deaths in last 32 patients, which may be due to over 75 per cent of these patients being stabilized on intensive medical therapy from 24 to 72 hours before study or surgery. There was a 16 per cent (13 patients) perioperative and 15 per cent (12 patients) late incidence of myocardial infarction. Of 74 patients who survived the initial operation 2 died 2 and 3 months postoperatively. Good or complete relief from pain was obtained in 94 per cent (70 patients) of the survivors. Of 57 longterm survivors tested, 49 per cent (28 patients) had a definite ischemic response to treadmill exercise testing. This may reflect the severe nature of the occlusive coronary disease or mechanisms other than increased coronary flow being responsible for the relief of pain. Although coronary bypass surgery appears to be effective in relieving the pain of patients with unstable angina pectoris, the 18 month average follow-up indicates that the incidence of myocardial infarction in surgically treated patients is comparable to that in medically treated patients.
High grade atrioventricular (A-V) block is a rarely described complication of Reiter's syndrome. This 65 year old man had recurrent episodes of arthritis, conjunctivitis and urethritis beginning at age 16. A prolonged P-R interval was first noted at age 32. The conduction distrubance progressed to intermittent episodes of high grade and complete heart block by age 65. His bundle electrograms located the site of block above the level of the bundle of His. Atrial pacing to rates of 150/min produced 5:1 A-V block, whereas exercise and atropine administration resulted in 1:1 A-V conduction. In view of these results, artificial pacemaker therapy is not indicated. The association of conduction disorders and Reiter's syndrome is reviewed.