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Biomedical subjects

J R Benotti

Publications and source records attributed to J R Benotti.

34 records · Page 2Linked to original sources
PubMed1985

Hemodynamic effects of intravenous bepridil in patients with normal left ventricular function.

Calcium-channel blockers are known to have depressant effects on atrioventricular (AV) nodal conduction and myocardial contractility. Because of these known depressant effects, bepridil hydrochloride, a new, long-acting, antianginal and antiarrhythmic calcium-channel blocker, was administered intravenously to patients without heart failure to determine acute hemodynamic effects. The patients studied had normal ventricular function, were without electrocardiographic conduction disturbances and were taking no drug except sublingual nitroglycerin for at least 24 hours before bepridil infusion. The study protocol included right- and left-sided cardiac catheterization with infusion of bepridil at 2 mg/kg for 15 minutes followed by 1 mg/kg for 15 minutes in 10 patients, and infusion of bepridil at 3 mg/kg for 15 minutes followed by 1 mg/kg for 15 minutes in 8 patients. Pressures, Fick cardiac output, resistances, left ventricular (LV) dP/dt, LV stroke work index and rate-pressure product of the left ventricle were monitored. There were no significant changes during bepridil infusion at either dose for cardiac output, systemic vascular and pulmonary vascular resistances, LV stroke work index, heart rate, arterial blood pressure and rate-pressure product. There was mild depression of LV dP/dt during bepridil infusion. Further, LV end-diastolic pressure, pulmonary capillary wedge pressure and pulmonary arterial pressures were significantly increased during bepridil infusion. There were no apparent changes in AV nodal or intraventricular conduction during bepridil infusion. We conclude that bepridil appears to be a safe drug for intravenous administration despite mild depression of myocardial function in patients with normal baseline hemodynamic function who are not receiving concomitant beta-blocker therapy.

Adult↗
PubMed1984

Balloon-occlusion pulmonary cineangiography for diagnosing pulmonary embolism.

For the angiographic diagnosis of pulmonary embolism (PE) we performed balloon-occlusion pulmonary cineangiography in ten consecutive patients. The technical aspects of the balloon-occlusion cineangiographic technique are reviewed, and its complementary role in the diagnosis of PE are outlined and illustrated with several examples.

Adult↗
PubMed1984

Oral amrinone for the treatment of chronic congestive heart failure: results of a multicenter randomized double-blind and placebo-controlled withdrawal study.

A placebo-controlled study was employed to evaluate the effects of oral amrinone in patients with congestive heart failure. After a baseline period of at least 4 weeks of standard treatment for refractory congestive heart failure, oral amrinone was added to the treatment regimen of 173 patients. Patients were predominantly male (89%), aged 24 to 76 years (mean 54), with ischemic (52%) or idiopathic (37%) dilated cardiomyopathy, in New York Heart Association functional class II (40%), III (59%) and IV (1%) and having a mean (+/- standard deviation) left ventricular ejection fraction of 25 +/- 15%. Phase 1: After the addition of amrinone (113 +/- 33 mg three times daily), 52 patients (30%) showed a maximal increase in treadmill exercise time exceeding 2 minutes (Naughton protocol), 72 (42%) had a lesser increase, 24 (14%) developed limiting adverse reactions, 20 (12%) died and 5 dropped out of the study. Fifty-two "responders" (30%) who were free of limiting side effects and had a greater than 2 minute increase in exercise time were randomized in double-blind fashion to continued amrinone or switched to placebo (each plus standard treatment) for an additional 12 weeks. Phase 2: Comparison of 31 of these 52 responders who continued to receive amrinone with the remaining 21 randomized to placebo revealed no significant differences in vital signs, indexes of left ventricular size and function, systolic time intervals or maximal exercise time. Continued follow-up study of patients receiving either amrinone or placebo revealed decreases in exercise times of 7 and 10%, respectively (both p less than 0.05 compared with before randomization). Episodes of worsened congestive heart failure severe enough to mandate termination of double-blind treatment were as frequent in patients taking placebo (4[18%] of 21) as in those taking amrinone (4[13%] of 31; p = NS). The average symptom score and functional class of each treatment group remained comparable. Adverse effects such as gastrointestinal and central nervous system complaints were more common with amrinone treatment as were elevations of serum liver enzymes and reduced platelet counts. This large multicenter, randomized double-blind withdrawal study revealed no change in estimates of cardiac performance after the discontinuation of amrinone. These findings suggest that amrinone, in the dosages tested, does not importantly improve cardiac function beyond that provided by standard treatment with digoxin, diuretic drugs and vasodilators.

Adult↗
PubMed1984

Restrictive cardiomyopathy.

Restrictive cardiomyopathy is a descriptive clinical and hemodynamic syndrome emphasizing the pathophysiologic mechanisms by which myocardial hypertrophy and/or infiltrative processes cause cardiocirculatory morbidity. This diagnosis can be made with precision only after pericardial construction is excluded and myocardial biopsy has identified the restrictive process. Though a variety of rather rare infiltrative pathological entities may be responsible for the restrictive cardiomyopathic picture, most commonly no definitive pathologic diagnosis is established despite extensive hemodynamic and histologic investigation. Nonetheless, a therapeutic trial with a calcium entry blocking agent is warranted.

Amyloidosis↗
PubMed1984

Aortic and mitral insufficiency complicating fulminant systemic lupus erythematosus.

The cardiac complications of systemic lupus erythematosus (SLE) include a multitude of valvular, myocardial, and pericardial abnormalities resulting from acute and chronic inflammation involving the endocardium, myocardium, and/or pericardium. A case of acute, severe, aortic, and mitral insufficiency occurring as discrete complications of consecutive flares of SLE in the same patient is described with particular emphasis on the clinical and gross pathologic findings. The cardiac complications of SLE, both from a pathologic and clinical standpoint, are reviewed in the context of the uniqueness of this case.

Adolescent↗
PubMed1984

The natural history of pulmonary embolism.

It has been found that the proper management of pulmonary embolism improves survival. This article reviews the natural history of pulmonary embolism as it relates to the appropriateness of several alternative therapeutic strategies.

Fibrinolytic Agents↗
PubMed1984

Amrinone-induced thrombocytopenia.

The frequency and characteristics of thrombocytopenia resulting from administration of amrinone, a new inotropic and vasodilator agent, was evaluated in 43 patients. Thrombocytopenia attributable to amrinone developed in eight patients (18.6%). The thrombocytopenia was due to accelerated peripheral loss of platelets. There appeared to be a dose relationship with regard to the rapidity of onset and degree of thrombocytopenia. Although platelet-associated IgG levels were elevated when measured in patients with thrombocytopenia, the clinical features were suggestive of a direct, perhaps nonimmunologic effect of amrinone on platelets. Thrombocytopenia was mild in most cases and bleeding attributable to thrombocytopenia did not occur. Several patients continued amrinone therapy over long periods despite low platelet counts, showing that mild to moderate thrombocytopenia is not necessarily an indication that therapy should be discontinued, but that platelet counts should be observed closely.

Adult↗
PubMed1983

The clinical profile of unresolved pulmonary embolism.

Nearly all patients with pulmonary embolism (PE) have complete clinical and hemodynamic and at least near complete roentgenographic and angiographic resolution within four to six weeks of the acute event. To classify the syndrome of unresolved pulmonary embolism we reviewed our experience and that of the English literature to extract 30 well-described cases. The mean age at presentation was 45 years, and most patients were less than 60 years old. Almost all complained of dyspnea, and the majority had at least one clinical event suggestive of PE. Most had clinical evidence of pulmonary hypertension. Roentgenographic, arterial blood gas and electrocardiographic findings were nonspecific, though the perfusion lung scan was always abnormal. Most patients exhibited mild-to-moderate pulmonary hypertension. The severity of pulmonary artery obstruction was quite variable and did not correlate with the magnitude of arterial hypoxemia or pulmonary hypertension. Most patients did not improve with long-term anticoagulation therapy and underwent pulmonary embolectomy with acceptable mortality. Postoperative improvement correlated with improved arterial blood gas levels, abatement of pulmonary hypertension, and more satisfactory pulmonary perfusion.

Adolescent↗
PubMed1982

Acute pharmacodynamics and pharmacokinetics of oral amrinone.

Amrinone was administered orally as a single 100-mg dose to six male patients with moderate-severe congestive heart failure to determine the acute pharmacodynamic effects and pharmacokinetics of the drug. Following right heart catherization and amrinone administration, measurements of hemodynamic parameters including cardiac index (Cl), right atrial pressure (RA), pulmonary capillary wedge pressure (PCW), and serum amrinone concentrations (SAC) were made at hourly intervals for up to 8 hours. Cl increased (29.0 per cent) significantly (P less than 0.05) at 3 hours after dose. PCW declined quickly after dose and was significantly (P less than 0.05) lower (-31.3 per cent) than control at 3 hours. RA declined gradually, and a significant (P less than 0.05) reduction (-25.2 per cent) was achieved 5 hours after the dose. Amrinone was absorbed quickly (tmax = 1.4 hour), and the disappearance of amrinone from serum was log-linear (t1/2 = 5.1 hours). The time courses of per cent change in Cl and SAC were similar, and the correlation between the average per cent change in Cl and average SAC was linear and significant (r = 0.80; P less than 0.05).

Administration, Oral↗
PubMed1981

Problems in assessment of new pharmacologic agents for the heart failure patient.

Modern management of congestive heart failure (CHF) employs inotropic drugs, vasodilators, and diuretics. Although pharmacologic classification of drugs is possible in animals, identification of predominant hemodynamic mechanisms in humans is more complex, because many effects of vasodilators and inotropic drugs are similar. We compared the effects of a vasodilator, prazosin, and two agents with both inotropic and vasodilatory properties, amrinone and pirbuterol, on cardiac index (CI), mean aortic pressure, left ventricular stroke work index (LVSWI), LV filling pressure (LVFP), systemic vascular resistance, LV ejection fraction (LVEF), and myocardial O2 consumption (MVO2) in 34 patients with advanced CHF. We concluded that (1) a rise in CI and LVEF, together with a fall in LVFP, does not necessarily indicate an inotropic effect; (2)both CI and LVEF may be increased by an inotropic mechanism in advanced CHF without a rise in MVO2; and (3) a drug-induced rise in LVSWI with stable or lower LVFP suggests an inotropic mechanism of action.

Aminopyridines↗
PubMed1980

Oral amrinone in refractory congestive heart failure.

The acute effects of an oral preparation of amrinone, a recently synthesized cardiotonic agent, were assessed noninvasively in nine patients who had advanced heart failure that persisted despite treatment with digitalis, diuretic drugs and afterload-reducing agents. All patients demonstrated an improvement in left ventricular ejection fraction determined by radionuclide ventriculography (20.3 +/- 2.8 to 30.8 +/- 4.8 percent [mean +/- standard error of the mean], p less than 0.005) after a single dose of amrinone. Initial effects were seen within 1 hour, with the peak effect occurring at 1 to 3 hours; persistent effects were demonstrable at 4 to 6 hours. No change in blood pressure, heart rate or rhythm was observed, and there was no clinical evidence of myocardial ischemia. Continued benefit was demonstrated by radionuclide ventriculography in two patients treated for 1 and 6 weeks, respectively, although two other patients experienced major side effects with the chronic administration of amrinone. Although orally administered amrinone shows promise as a potentially useful agent in the treatment of advanced heart failure, the safety of this drug remains to be established.

Aged↗
PubMed1980

Clinical profile of restrictive cardiomyopathy.

The characteristic hemodynamic features of restrictive cardiomyopathy (normal or reduced cardiac index, normal ventricular systolic function, and "dip and plateau" early in diastole) are traditionally associated with pathologic evidence of inflammation, infiltration and fibrosis. Prognosis is usually poor. Nine patients with restrictive hemodynamic features were recently identified in our laboratory; six were males, three were females, and ages ranged from 23-57 years (mean 47 years). Only one was asymptomatic. Chest pain, dyspnea on exertion and fatigue were the most common symptoms. Echocardiography revealed various degrees of left ventricular wall thickening, but no significant pericardial effusion, pericardial thickening or calcification. Mean left ventricular end-diastolic pressure was 25 mm Hg, cardiac index 2.8 l/min/m2 and ejection fraction 0.63. Endomyocardial and pericardial biopsies, obtained in two patients, were normal. Follow-up (mean 22 months, range 16-42 months) revealed no cardiac deaths. These findings support the hypothesis that the restrictive hemodynamic profile does not necessarily indicate the presence of a specific pathologic process in the subendocardium or myocardium and that the prognosis is not necessarily ominous. The common pathophysiologic feature for this syndrome appears to be reduced ventricular diastolic compliance, but the etiology in many cases is unclear.

Adult↗
PubMed1980

Effects of amrinone on myocardial energy metabolism and hemodynamics in patients with severe congestive heart failure due to coronary artery disease.

Amrinone has been shown to exhibit a potent inotropic effect in patients with heart failure secondary to congestive cardiomyopathy, but its effects on myocardial oxygen consumption (MVO2) and coronary blood flow (CBF) are unknown. Accordingly, the hemodynamic, myocardial metabolic and ECG responses to amrinone (2.5 mg/kg i.v. over 1 hour) were measured in nine patients with congestive heart failure secondary to coronary artery disease. Increases were observed in cardiac index (1.3 +/- 0.4 to 2.2 +/- 0.7 l/min/m2) and left ventricular stroke work (10.6 +/- 3.0 to 19.2 +/- 6.3 g-m/m2), and decreases in mean pulmonary wedge (31 +/- 5 to 26 +/- 4 mm Hg), mean pulmonary artery (44 +/- 8 to 36 +/- 7 mm Hg) and mean right atrial pressures (18 +/- 4 to 10 +/- 4 mm Hg), myocardial arteriovenous oxygen difference (129 +/- 19 to 109 +/- 17 ml/l), CBF (215 +/- 117 to 178 +/- 84 ml/min) and MVO2 (27 +/- 14 to 19 +/- 9 ml/min). All changes were significant (p less than 0.01). No significant changes occurred in aortic mean pressure, heart rate, myocardial lactate extraction or ECG, and no patient developed angina. In explaining the decline in MVO2, it is possible that the increase in contractility was more than offset by the reductions in preload and afterload. The amrinone-induced hemodynamic improvement in patients with congestive heart failure secondary to coronary artery disease was associated with reductions in MVO2 and CBF and no evidence of myocardial ischemia.

Aged↗
PubMed1978

Hemodynamic assessment of amrinone. A new inotropic agent.

Amrinone, a new bipyridine derivative, exerts a positive inotropic action in experimental preparations and is effective when administered orally to dogs. To assess its immediate effects in man, we studied by cardiac catheterization the hemodynamic responses to amrinone (1.85 to 3.5 mg per kilogram given intravenously) in eight patients with congestive heart failure already receiving full doses of digitalis. the following statistically significant (P less than 0.01) effects were noted: cardiac index increased from a mean +/- 1 S.D. of 1.8 +/- 0.3 to 2.6 +/- 0.3 liters per minute per square meter; peak rate of left ventricular pressure rise rose from 849 +/- 233 to 1206 +/- 456 mm Hg per second; left ventricular end-diastolic pressure fell from 25 +/- 9 to 14 +/- 7 mm Hg; pulmonary-capillary pressure fell from 28 +/- 8 to 15 +/- 4 mm Hg; and right atrial pressure fell from 12 +/- 6 to 7 +/- 5 mm Hg. Mean heart rate was unchanged, and aortic mean pressure declined slightly (86 +/- 10 to 80 +/- 7 mm Hg, P less than 0.025). No toxicity was observed. Amrinone, whose mechanism of action has not yet ben defined, warrants further study as a possible treatment for heart failure.

Drug Evaluation↗