Biomedical subjects
Publications and source records attributed to R R Miller.
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The effects of intravenously administered disopyramide phosphate were evaluated in seven patients with refractory ventricular tachycardia. All patients had organic heart disease, including acute infarction (three patients), chronic coronary artery disease (two patients) and cardiomyopathy (two patients). The severity of the heart disease was reflected in the advanced patient age (average 64 years) and the occurrence before disopyramide therapy of cardiac arrest in five patients and congestive heart failure in all seven patients. In five patients, disopyramide was given as a bolus injection, 2 mg/kg body weight, followed by an infusion of 20 to 40 mg/hour. The final two patients received 4 mg/kg divided as a bolus injection and an infusion over 1 hour followed by a 0.4 mg/kg infusion during the next hour. Intravenous administration of disopyramide resulted in more effective electrical stability in all patients and completely eliminated ventricular tachycardia in six. Recurrence of ventricular tachycardia was prevented in six patients with subsequent long-term oral administration of disopyramide. Possible dose-related cardiac pump depression occurred in two patients, but disopyramide was otherwise well tolerated. Therefore, these data document the therapeutic efficacy of disopyramide in the treatment of refractory life-threatening ventricular tachyarrhythmias.
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Autonomic response indexes of experimental amnesia have recently been found to have higher electroconvulsive shock (ECS) intensity thresholds and steeper retrograde gradients than have traditional somatic indexes. The present studies examined the hypothesis that recovery from somatically indexed experimental amnesia depends upon the existence of autonomically available residual memory. In a between-subjects design, a 200-mA ECS was used to produce amnesia for a tone-footshock pairing as indicated by lick suppression, defection, and bradycardia. The next day, these amnesic animals received a reminder footshock outside of the training apparatus, which was found to restore memory on a test trial 24 hr later. The behavior of control groups indicated that this reminder effect was due to the restoration of specific memory rather than systemic consequences of treatment. With a within-subjects design, a second experiment obtained a reminder effect in animals individually shown to be "fully" amnesic by all three response indexes monitored. A third experiment varied the intensity of the reminder footshock and revealed that the different memory indexes examined do not have reminder-footshock thresholds inversely related to their initial resistance to amnesia. The results support a retrieval-failure view of experimental amnesia and suggest that the same fundamental physiological processes underlie both autonomically indexed memory and somatically indexed memory.
Fifty-six patients with symptomatic chronic sinus bradycardia because of sick sinus syndrome (SSS) were followed for periods from one month to 11 years (average 3-2 years). Eleven developed stable atrial fibrillation persisting for 8 to 61 months; 52 had permanent demand pacemakers implanted before atrial fibrillation commenced. In the 11 patients with atrial fibrillation, 10 had adequate ventricular rate, 8 with rates greater than 100 beats/min requiring digoxin for rate control. The 8 patients with atrial fibrillation with pacemakers remained asymptomatic for 13 to 18 months without requiring reimplantation; battery failure occurred in 2 whose rapid ventricular rates were controlled by digoxin. In the other 6 patients with pacemakers who developed atrial fibrillation, adequate ventricular rates persisted resulting in overdrive suppression. No patient had systemic embolisation. The previous duration of symptomatic sinus bradycardia was longer in patients developing atrial fibrillation (average 5-5 years) compared (P less than 0-01) with patients without atrial fibrillation (1-9 years). Further, premature atrial contractions occurred in all 11 patients before atrial fibrillation in contrast to only 21 of the 45 patients without atrial fibrillation. It is concluded that occurrence of atrial fibrillation in SSS with symptomatic sinus bradycardia provides a natural cure of symptoms caused by bradycardia. These data indicate that permanent ventricular pacing may not be necessary if persistent atrial fibrillation develops in SSS.
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To determine whether multiple lead precordial electrocardiographic recordings offer an improved index for noninvasive estimation of left ventricular hemodynamic function and segmental dyssynergy, precordial mapping was performed in patients with anterior myocardial infarction, and the number of pathologic Q waves (greater than or equal to 0.04 sec) was counted (Q-Index). Left ventricular function was determined by cardiac catheterization and angiography and correlated with the Q-Index. The Q-Index correlated well with dyssynergy extent (r = 0.84) and inversely with ejection fraction (r= -0.87), stroke work index (r = -0.79) and cardiac index (r = =0.66). Three patient groups were defined by Q-Index; group I, 0.04 sec Q complexes less than 15; group II, 15-25; group III, 26-35. Q-Index related closely to functional classification and survival (mean follow-up 12.2 months): group I, 91%; group II, 81%; group III, 40%. Thus 35-lead precordial Q wave mapping with determination of total number of pathologic Q waves permits practical, atraumatic assessment of hemodynamic and functional status and allows prediction of survival in acute and chronic anterior myocardial infarction.
The hemodynamic benefits of combining administration of dopamine with nitroprusside (NP) were evaluated in nine patients with chronic congestive heart failure due to ischemic, idiopathic myocardial or valvular cardiac disease. NP alone (68 microng/min) produced decline in left ventricular end-diastolic pressure (LVEDP) from 25.4 to 14.1 mm Hg (p less than 0.01) but modest increase in cardiac index (CI) from 2.41 to 3.02 L/min/m2 (P less than 0.05). Dopamine alone (6 microng/kg/min) caused an elevation of CI to 3.36 (P less than 0.01) but without decrease of LVEDP. Simultaneous infusion of the two agents resulted in favorable alterations in both hemodynamic variables: LVEDP decreased to 15.7 (P less than 0.01) and CI increased to 3.52 (P less than 0.01). It is concluded that dopamine substantially enhances the effectiveness of nitroprusside therapy in congestive heart failure by providing concomitantly the principal beneficial actions of the vasodilator and dopamine used separately. Thus combined dopamine with NP treatment considerably raises low CI while markedly reducing elevated LVEDP and provides a potentially efficacious pharmacologic modality for the treatment of severe congestive heart failure due to left ventricular dysfunction.
The long-term efficacy of the new oral vasodilator, prazosin (PZ), was evaluated in nine patients with refractory heart failure due to chronic coronary heart disease. Ventricular function was assessed by cardiac catheterization, echocardiography, and treadmill testing; symptomatic evaluation was carried out for two to four months. One hour following 2-7 mg PZ, control left ventricular filling pressure was reduced (32 to 18 mm Hg, P less than 0.001) and cardiac index was elevated (1.95 to 2.89 L/min/m2, P less than 0.001) for a 6-hour period. After two weeks of PZ 2 to 7 mg four times daily, echographic end-diastolic dimension fell (5.7 to 5.4 cm, P less than 0.001) while shortening fraction increased (27.6 to 30.2%, P less than 0.005). Treadmill exercise duration increased from 209 to 317 seconds (P less than 0.001). Symptoms diminished throughout the duration of follow-up (mean 94 days) with improvement in NYHA functional class (3.7 to 2.2, P less than 0.001). Thus, prazosin possesses sustained nitroprusside-like balanced dilator actions on the systemic arterial and venous systems and is effective in the ambulatory management of chronic severe heart failure.
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Based on 39 cineangiographies in 23 patients performed during respiration with tracing of the cardiac chambers and the diaphragm, it has been found that the heart moves significantly with respiration, approximately half as much as the diaphragm during shallow or normal respiration. The cardiac respiratory motion indicates that gating of the respiratory cycle as well as the cardiac cycle is necessary in three-dimensional reconstruction of the heart using a large number of heart beats for recording.
Controversy continues regarding the effects of administration of digitalis upon the exercise electrocardiogram. Thus, maximal treadmill exercise tests were performed before and two weeks after administration of 0.25 mg of digoxin daily in 15 normal subjects (documented by cardiac catheterization and coronary arteriographic studies). Administration of digitalis induced abnormal findings on exercise tests in all 14 subjects with serum levels of digoxin greater than or equal to 0.5 ng/ml; however, at workloads greater than 75 to 90 percent of maximal predicted heart rate, the changes in the ST segment reverted to a normal configuration in all subjects, thereby providing differentiation of digitalis-induced ST-segment alterations from those due to myocardial ischemia at maximal treadmill stress.
A critical analysis of information on propoxyphene that has been published since the drug's introduction is presented. Propoxyphene is discussed with regard to its chemistry, metabolism and pharmacokinetics, analgesic efficacy, analgesic efficacy of combination products, nonanalgesic uses, adverse effects, overdosage, and dependence and abuse. Both the hydrochloride and napsylate salts are covered. It is doubtful that propoxyphene hydrochloride 65 mg provides an analgesic effect equal to that of aspirin 650 mg. There is no conclusive evidence that combinations of propoxyphene with other analgesics are more effective than propoxyphene or other analgesics alone.
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Although glutaraldehyde-preserved porcine heterograft (PH) valves may have a lowered incidence of thromboembolism compared to mechanical valves, data concerning postoperative function in PH valves are incomplete. Accordingly, 26 patients receiving PH in the aortic (AO) or mitral position (MIT) were studied at cardiac postoperative catheterization (mean 19 weeks). The 12 AO patients had an average peak systolic gradient of 19 mm Hg (range 3-52 mm Hg); mean valve area (VA) 1.33 cm2 (0.75-2.5; two patients had postoperative aortic insufficiency. The 14 MIT patients had a mean gradient of 7.9 mm Hg (0-13.1); VA 1.84 cm2 (0.70-3.2; postoperative mitral regurgitation occurred in two patients. AO stent diameter (SD) related to VA, r = 0.85; and peak gradient, r = -0.75. However, MIT SD did not relate to VA or peak gradient. At the 14-month follow-up examination 9 of 11 AO and 7 of 11 MIT patients improved by at least one functional class. Thus, with the advantage of reduced thromboembolism and generally satisfactory valve hemodynamics, further clinical trial of glutaraldehyde-preserved porcine heterografts is justified.
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The findings of the Boston Collaborative Drug Surveillance Program on the toxicity of drugs are summarized, and the methodologies of this and other epidemiological drug monitoring programs are defended. It is concluded that the currently available data on adverse drug reactions provide a reasonably complete and clear picture of the "ADR problem".