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Biomedical subjects

M Rubenfire

Publications and source records attributed to M Rubenfire.

At least 19 recordsLinked to original sources
PubMed1991

The effect of pravastatin on plasma lipoprotein and apolipoprotein levels in primary hypercholesterolemia. The Southeastern Michigan Collaborative Group.

Pravastatin is a metabolic product of mevastatin and a potent inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. It was investigated for its cholesterol-lowering properties in a double-blind, placebo-controlled, multicenter study of 82 patients with primary hypercholesterolemia. Following a 6- to 8-week dietary lead-in period, patients were randomized to twice-daily placebo or active drug for 16 weeks. Patients receiving 10 mg of pravastatin twice a day for 8 weeks experienced mean total cholesterol and low-density lipoprotein cholesterol (LDL-C) level reductions of 20% (6.85 vs 5.48 mmol/L [265 vs 212 mg/dL]) and 28% (5.17 vs 3.75 mmol/L [200 vs 145 mg/dL]), respectively. At 20 mg twice a day for an additional 8 weeks, pravastatin reduced plasma total cholesterol, LDL-C, and apolipoprotein B-100 levels by 23% (6.85 vs 5.30 mmol/L [265 vs 205 mg/dL]), 31% (5.17 vs 3.59 mmol/L [200 vs 139 mg/dL]), and 23% (118 vs 91 mg/dL), respectively. High-density lipoprotein cholesterol (HDL-C), HDLb-C, HDLb-C, and apolipoprotein A-I plasma concentrations increased by 11%, 60%, 7%, and 10%. Plasma triglyceride concentrations decreased in both the pravastatin- and placebo-treated patients. Pravastatin was generally well tolerated and an effective agent for the treatment of primary hypercholesterolemia.

Apolipoproteins↗
PubMed1990

Mexiletine. Long-term efficacy and side effects in patients with chronic drug-resistant potentially lethal ventricular arrhythmias.

The antiarrhythmic efficacy of mexiletine hydrochloride (Mexitil) was evaluated in 100 patients with potentially lethal and drug-resistant ventricular arrhythmia. The efficacy of arrhythmia suppression was assessed by Holter monitoring. The overall arrhythmia suppression of ventricular premature contractions of 70% and greater was low and seen in only 22% of patients, with an additional 16% responding to a combination of mexiletine and an additional antiarrhythmic drug. The suppression of high-grade forms, couplets of 90% and greater, and complete abolition of nonsustained runs of ventricular tachycardia was achieved in 22% of patients, with 9% responding to the addition of another antiarrhythmic agent. Ventricular premature contractions, couplets, and nonsustained ventricular tachycardia were suppressed in only 16% of the cohort. The drug was poorly tolerated, with intolerable side effects developing in 49% of patients receiving mexiletine alone and in 57% of patients receiving a combination of antiarrhythmic agents. Tolerable adverse effects were relatively common but transient and dose related.

Administration, Oral↗
PubMed1989

Classification of antiarrhythmic drugs.

Although many classification schemes for antiarrhythmic drugs have been proposed, the system introduced by Vaughan Williams and later modified by Harrison has been widely accepted. This classification system is comprised of four categories. Class I agents block sodium channels. Class II agents are Beta blockers. Class III agents prolong the cardiac action potential. Class IV agents are calcium channel blockers. This classification scheme, based largely on clinical observation continues to be useful almost two decades after its introduction. The electrophysiologic bases, strengths and weaknesses of this system are discussed.

Amiodarone↗
PubMed1989

Long-term efficacy and toxicity of high- and low-dose amiodarone regimens.

Amiodarone is an effective antiarrhythmic drug for the control of potentially lethal and lethal ventricular arrhythmias (VA). In the United States, a high-dose regimen has been used at the expense of a high toxicity profile for the control of lethal VAs. Significant antiarrhythmic efficacy has also been established with low-dose regimens, which carry a low rate of intolerable side effects (5.4%) when compared with the high-dose regimen (16.7%). The high incidence of tolerable and intolerable adverse side effects is probably related to high amiodarone loading (31.92 g) and maintenance doses (520 mg/d). In contrast, the low-dose regimen uses much lower loading (7.2 g) and maintenance (280 mg/d) doses.

Amiodarone↗
PubMed1989

Potentially lethal ventricular arrhythmias: from mundane to esoteric.

Patients with potentially lethal ventricular arrhythmias (VAs) represent a heterogenous group with frequent and high grade ventricular arrhythmias (including couplets and runs of nonsustained ventricular tachycardia), structural heart disease and decreased left ventricular function. This is a group at intermediate risk of sudden death, with risks varying from 10% to 38%. The electrical and mechanical risks of patients with potentially lethal VA is discussed in relation to their ability of promoting sudden death. The studies reviewing the impact of antiarrhythmic treatment on survival of patients with potentially lethal VA is discussed.

Arrhythmias, Cardiac↗
PubMed1989

Dopamine and dobutamine induce hypokalemia in anesthetized dogs.

Epinephrine-induced hypokalemia appears to be mediated by beta 2-agonist activation of Na+/K+ ATPase. To determine whether dopamine and dobutamine induce hypokalemia, eight adult mongrel dogs were anesthetized and studied in random crossover fashion. Potassium [K+] was measured with an ion-selective microelectrode, and central hemodynamics were measured continuously. After stabilization, dopamine and dobutamine were infused at doses of 2, 4, 8, and 20 micrograms/kg/min (15-min increments/dose), and 0.9% NaCl was infused at equivalent volumes, with a 1-h washout between treatments. The mean change in [K+] at each infusion rate was compared between treatments among dogs with an adequate hemodynamic response. Among dopamine responders (n = 5), [K+] decreased from 3.74 +/- 0.42 mEq/L at baseline to 3.63 +/- 0.51 at 2 micrograms/kg/min (p less than 0.02) and was not significantly different at higher doses. Among dobutamine responders (n = 7), [K+] decreased from 3.52 +/- 0.74 at baseline to 3.31 +/- 0.87 at 8 micrograms/kg/min (p less than 0.02) and 3.25 +/- 0.86 at 20 micrograms/kg/min (p less than 0.02), and was not significantly different at lower doses. We conclude that dopamine and dobutamine induce significant hypokalemia, consistent with their adrenergic agonist activity, and this may be related to the known arrhythmogenicity of these agents.

Anesthesia, Intravenous↗
PubMed1988

Risks associated with intraaortic balloon pumping in patients with and without diabetes mellitus.

Between 1967 and 1982, intraaortic balloon pumping (IABP) was attempted in 733 patients. Of these, 132 were diabetic: 51 patients were managed with diet alone, 46 patients took oral hypoglycemic agents and 35 patients required insulin. Vascular complications associated with IABP occurred in 34% of the insulin-dependent diabetics, in 18% of other diabetics and in 14% of nondiabetic patients. Infectious complications were 37, 22 and 25%, respectively. Seventy-five diabetic patients (57%) were discharged alive from the hospital after balloon pumping, essentially the same proportion as among nondiabetic patients (58%). It is concluded that although diabetics incur a higher complication rate, IABP is not contraindicated.

Adult↗
PubMed1988

Long-term efficacy, safety and survival of patients with potentially lethal ventricular arrhythmias treated with low-dose amiodarone.

The effect of low-dose amiodarone was prospectively evaluated in 110 patients with potentially lethal ventricular arrhythmias and structural heart disease. The patient population had frequent and high-grade ventricular premature complexes (VPCs) (greater than or equal to 39/h) (multifocal, couplets, nonsustained ventricular tachycardia) refractory to conventional antiarrhythmic drugs. All patients had structural heart disease (coronary artery disease in 61%) and also a decreased left ventricular ejection fraction (LVEF) (43 +/- 16%). Patients were treated with low-dose amiodarone (maintenance dose of 275 +/- 102 mg/day.) During follow-up over a period of 15 +/- 11.5 months, 24 patients died of cardiac cause and, of these, 13 died of sudden death. Ventricular arrhythmia suppression at 1, 2, 3, and 4 years was 69%, 80%, 78%, 92% for VPCs, respectively; 96%, 90%, 92%, and 98% for couplets, respectively, and 57%, 57%, 97%, and 91% for nonsustained VTs (NVTs), respectively. Intolerable, reversible side effects requiring withdrawal were encountered in 24 patients (22%) (neurologic 10%, gastrointestinal 6.5%, skin 3.7%, proarrhythmic 0.9%, and cardiac 0.9%). Except for keratopathy (less than or equal to grade II) seen in all patients, the tolerable side effects were transient with dose adjustment. The study population was divided into two groups according to LVEF: Group A (LVEF greater than or equal to 40%, mean 54.4 +/- 9.7) and Group B (LVEF less than 40% mean, 27.7 +/- 7.2). The patients were further classified into responders (suppression of at least 70% of VPCs, 90% of couplets, and 100% of NVTs) and nonresponders. The difference in survival between responders and nonresponders in groups A and B was not statistically significant. Cumulative survival at 1, 2, 3, and 4 years was 90%, 85%, 85%, and 85%, respectively. In conclusion, low-dose amiodarone treatment: 1) Is effective in controlling VPCs and its complex forms and maintains long-term arrhythmia suppression. 2) The side effect profile compares favorably with conventional antiarrhythmics; severe side effects associated with high dosages (pulmonary, hepatic, neurologic, etc.) were rare or absent. 3) Amiodarone improves survival of patients with potentially lethal ventricular arrhythmias.

Aged↗
PubMed1988

The incidence, magnitude, and time course of the amiodarone-warfarin interaction.

Eight patients concurrently treated with amiodarone and warfarin sodium were studied to characterize the interaction between these drugs. All fulfilled the following criteria: (1) stable and therapeutic prothrombin time (PT) at baseline, defined as at least two consecutive PTs obtained within two weeks before beginning amiodarone therapy that varied by less than or equal to 15%; (2) no warfarin dosage adjustment in the two weeks prior to amiodarone therapy; (3) no other drugs given that alter coagulation study results; and (4) follow-up PTs obtained 1, 2, 4, and 8 weeks after initiation of amiodarone treatment. A clinically significant change in PT was defined as greater than 15%. Mean baseline PT was 19.8 s for patients receiving 5.99 mg/d of warfarin sodium. Patients had a mean maximum increase in PT of 44% (range, 22% to 108%), which occurred during the first two weeks. In six patients, the PT returned to within 15% of baseline by week 4 or 8, and the daily warfarin requirement had decreased by 35% (range, 25% to 50%). Two patients had PTs varying by greater than 15% from baseline at week 8 despite a 33% reduction in warfarin dosage in each case. No patient in this series encountered complications of anticoagulant therapy, perhaps due to early recognition and dosage reduction. Although the mechanism remains unclear, our study indicates that amiodarone potentiation of warfarin effects occurs in all patients, occurs in the first two weeks of amiodarone therapy, variably increases PT by 22% to 108%, and lowers the warfarin requirement by 25% to 50%. We recommend a 25% prophylactic reduction of warfarin dosage and weekly measurements of PT for one month when amiodarone therapy is initiated.

Amiodarone↗
PubMed1987

The prognostic value of functional capacity in patients with mild to moderate heart failure.

Thirty patients with ischemic (n = 14) or idiopathic dilated (n = 16) cardiomyopathy were followed long-term to determine the prognostic value of measuring entry exercise capacity. At the time of referral for management of symptomatic heart failure, studies included radionuclide angiography, M-mode echocardiography, 24-hour Holter and graded exercise testing with measured oxygen peak consumption (peak VO2). Inclusion criteria were NYHA class II (n = 16) or III (n = 14) despite at least 3 months of treatment with digitalis and diuretics, left ventricular ejection fraction less than 50%, left ventricular end-diastolic diameter (LVEDD) greater than 50 mm, and exercise capacity limited by dyspnea or fatigue. Patients were treated with diuretics (100%), digitalis (83%), and vasodilators (60%) and were followed for at least 6 months (mean 15). The 1-, 2- and 3-year cumulative survival rates were 75.4%, 70.2%, and 70.2%, respectively. Univariate predictors of survival included measured peak VO2 (p = 0.0026), as well as age, estimated peak VO2 (based on exercise time), presence of left bundle branch block, LVEDD, and frequency of ventricular arrhythmias. Multivariate analysis revealed that measured peak VO2 was the single best independent predictor of survival (p less than 0.001). We conclude that assessment of functional capacity provides useful independent prognostic information in patients with mild to moderate heart failure.

Arrhythmias, Cardiac↗
PubMed1987

Intraaortic balloon pump insertion: a randomized study comparing percutaneous and surgical techniques.

To compare the percutaneous and surgical techniques of intraaortic balloon pump insertion, 101 patients referred for this procedure were randomly assigned to either percutaneous or surgical insertion. Insertion using the designated technique was successful in 45 (88%) of 51 patients with percutaneous insertion and 48 (96%) of 50 patients with surgical insertion (difference not statistically significant). The time from the beginning of the insertion procedure to the initiation of counterpulsation was 13 +/- 8 minutes for the percutaneous technique versus 31 +/- 16 minutes for the surgical technique (p less than 0.001). In the percutaneous group, 10 patients required Fogarty thrombectomy after balloon pump removal, and 1 patient developed severe leg ischemia requiring immediate termination of balloon pump support. In the surgical group, one patient developed leg ischemia requiring surgical intervention, three patients developed sepsis with bacteremia (including one patient who required vein patch repair of the femoral artery), one patient developed a wound infection requiring debridement and one patient had a cerebral embolus. Aortic dissection, aortoiliac perforation or amputation did not occur in either group. Major vascular complications occurred in 11 patients (22%) with percutaneous insertion versus 2 patients (4%) with surgical insertion (p less than 0.05). It is concluded that although the percutaneous technique for intraaortic balloon pump insertion is faster than the surgical technique and is technically easy, it is associated with a higher incidence of vascular complications.

Blood Pressure↗
PubMed1987

The effect of coadministration of verapamil on the pharmacokinetics and metabolism of quinidine.

We have previously found that verapamil pretreatment significantly inhibits the metabolism of antipyrine. To assess more fully the implications of this observation, we examined the effect of verapamil on the pharmacokinetics and metabolism of quinidine. Pretreatment with verapamil, 80 mg and 120 mg (every 8 hours for 3 days), reduced the oral clearance of quinidine from 17.0 L/hr to 11.6 and 11.3 L/hr, respectively (P less than 0.01). The half-life of quinidine was also significantly prolonged by verapamil. The formation clearance of 3-hydroxyquinidine was reduced by 61.2% and 70.6% after verapamil pretreatment (80 and 120 mg, respectively) (P less than 0.01), whereas the renal clearance of unchanged quinidine was not affected. These results indicate that verapamil impairs the metabolism of quinidine to 3-hydroxyquinidine and reduces the oral clearance of quinidine to a degree that could be of clinical significance given the narrow therapeutic index of this drug.

Adult↗
PubMed1987

Amiodarone in the management of refractory atrial fibrillation.

Thirty-eight patients were studied to evaluate amiodarone hydrochloride in the treatment of refractory atrial fibrillation. Among them were 25 with sustained atrial fibrillation and 13 with paroxysmal atrial fibrillation. All patients were symptomatic and refractory to therapeutic doses of at least two conventional drug trials, and patients with atrial fibrillation had relapsed from electroversion. Amiodarone hydrochloride was administered in doses of 5 mg/kg intravenously, then 600 to 800 mg/d for seven to ten days, followed by 200 to 400 mg/d. Holter recordings were obtained every one to three months. The effect of amiodarone on the ventricular rate during sustained atrial fibrillation was evaluated in 18 patients and decreased from 99/min (range, 72/min to 143/min) at baseline to 75/min (range, 60/min to 102/min) at follow-up before conversion. Conversion to normal sinus rhythm occurred in 19 patients (76%), including 11 with and eight without direct-current cardioversion. During long-term treatment, sinus rhythm was sustained on an average of 16 months (range, three to 27 months) in 20 patients (53%). This included 11 of 25 patients with sustained atrial fibrillation and nine of 13 patients with paroxysmal atrial fibrillation, with only four of these patients relapsing. Four patients (11%) developed intolerable side effects, but no serious toxic effects were encountered, perhaps because of the relatively low doses of amiodarone hydrochloride that were used (average, 232 +/- 80 mg/d). Amiodarone is a safe and effective alternative to standard therapy in patients with refractory sustained or paroxysmal atrial fibrillation.

Adult↗