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Biomedical subjects

B Pitt

Publications and source records attributed to B Pitt.

At least 109 records · Page 6Linked to original sources
PubMed1994

Ramipril prevents hypersensitivity to phenylephrine in aorta from streptozotocin-induced diabetic rats.

This study investigated the protective effect of the angiotensin converting enzyme inhibitor, ramipril, on endothelium-dependent responses in arteries from control (CON) and streptozotocin-induced (STZ) diabetic rats. Three hypotheses were tested: 1) there is an endothelium-dependent component to the increased alpha-adrenergic responsiveness characteristic of diabetes; 2) endothelium-dependent, acetylcholine-induced relaxation is attenuated in aorta from diabetic rats; and 3) ramipril (3 mg/kg daily in the food, 12-15 weeks) will prevent functional vascular changes in diabetic rats. Vascular function was assessed in aortic rings using standard muscle bath procedures for measurement of isometric force. Sensitivity to phenylephrine was increased in aortic rings from diabetic compared to control values [pD2 values (-log ED50): CON = 6.22 +/- 0.12, STZ = 7.54 +/- 0.11), and removal of the endothelium (-Endo) increased phenylephrine sensitivity (CON-Endo = 7.40 +/- 0.11, STZ-Endo = 8.32 +/- 0.18). The magnitude of the shift in responsiveness following endothelium removal was greatest in control rats. Ramipril treatment (Ram) partially normalized phenylephrine responsiveness in intact (STZ + Ram = 6.55 +/- 0.11) and denuded (STZ-Endo + Ram = 7.75 +/- 0.10) vessels. Vasodilatation to acetylcholine and nitroglycerin was not altered in diabetic rats nor was it affected by ramipril treatment. Diabetes increases contractile sensitivity to phenylephrine but not to vasodilators and chronic ramipril treatment prevents this increase in contractile sensitivity. Ramipril treatment did not alter the hyperglycaemic condition induced by streptozotocin. The changes in phenylephrine sensitivity appear to involve an endothelial and a smooth muscle component.

Acetylcholine↗
PubMed1994

Angiotensin-converting enzyme inhibitors in patients with coronary atherosclerosis.

Activation of the renin-angiotensin-aldosterone system has been shown to be an independent risk factor for myocardial infarction (MI). The importance of this risk factor has been confirmed by the finding that patients with a DD genotype for the angiotensin-converting enzyme (ACE) gene, which is associated with increased serum ACE levels, have a higher incidence of MI than do patients without this genotype. ACE inhibitors have been shown to significantly reduce the incidence of recurrent MI in patients with left ventricular dysfunction. The mechanism by which activation of the renin-angiotensin-aldosterone system leads to MI has not been ascertained, but it may be related to the effect of angiotensin II or aldosterone on the development of atherosclerosis, endothelial dysfunction, plaque rupture, or thrombosis after plaque rupture. Experimental data suggest that each of these mechanisms may be of importance. Several prospective randomized studies are under way to determine the effect of ACE inhibitors on recurrent ischemic events and the progression of atherosclerosis in patients without left ventricular dysfunction. If these studies yield positive results, ACE inhibitors might assume an important role in the secondary and possibly primary prevention of ischemic heart disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Making judgements about treatment effectiveness based on health outcomes: theoretical and practical issues.

ISSUES: This article considers the problem of deciding which health care outcomes are important and relevant for (1) developing management recommendations for clinical practice guidelines and (2) evaluating patients' responses to treatment. DECISIONS: The Heart Failure Guideline Panel sponsored by the Agency for Health Care Policy and Research (AHCPR) decided that for both purposes the relevant outcomes are those experienced directly by patients: mortality and health-related quality of life (HRQOL). Changes in intermediate outcomes, such as test results of various kinds, were deemed insufficient evidence of effectiveness. CONCLUSIONS: In the context of heart failure, mortality risk (prognosis) can be measured using a variety of biochemical and physiological variables, but changes in these variables do not appear to correspond to changes in prognosis. For this reason, the Heart Failure Guideline Panel recommended that patients' responses to treatment be guided by signs and symptoms, rather than test results (for example, echocardiographic measurement of left-ventricular function or exercise-tolerance testing). HRQOL is best assessed by direct patient self-reports. Although patients may be influenced by a host of other variables (for example, mood, adaptation to chronic disease, placebo effect), self-reports will probably always represent the "gold standard" in assessing HRQOL. The reliability and validity of these reports can be enhanced by using standardized instruments or by incorporating questions from such instruments into the history-taking aspect of patient evaluation and monitoring. Finally, physical examination and submaximal exercise testing can provide additional information that can supplement patient reports. Information from these sources must be evaluated carefully in light of patients' self-reported HRQOL.

Health Status↗
PubMed1994

Pharmacologic treatment of heart failure with standard drugs.

During 1993 the indications for the use of angiotensin-converting enzyme (ACE) inhibitors were expanded to include patients with left ventricular dysfunction and acute myocardial infarction. The role and use of ACE inhibitors in patients with chronic systolic ventricular dysfunction, established in earlier trials, has been further clarified. Increasing attention is being focused on ACE inhibitors, specifically the mechanisms by which they improve mortality, their side effects, and the possibility of further increasing their use by avoiding renal dysfunction and first-dose hypotension. Although most of the interest has centered on ACE inhibitors, the importance of diuretics and their use in combination with ACE inhibitors is being clarified. Most important has been the demonstration over the past year of the effectiveness of digoxin in preventing cardiac deterioration in patients with systolic left ventricular dysfunction and sinus rhythm. The increased understanding of the renin-angiotensin-aldosterone system, its modification by ACE inhibitors, and the interaction of ACE inhibition with other drugs provides the basis for a further improvement in morbidity and mortality in patients with heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction.

BACKGROUND: Animal studies have demonstrated a burst of oxygen free radical generation after reperfusion of ischemic myocardium that could be blocked by administration of the free radical scavenger recombinant human superoxide dismutase (h-SOD). A multicenter, randomized, placebo-controlled clinical trial was designed to test the hypothesis that free radical-mediated reperfusion injury could be reduced by intravenous administration of h-SOD begun before percutaneous transluminal coronary angioplasty (PTCA) in patients with acute transmural myocardial infarction. METHODS AND RESULTS: One hundred twenty patients were randomized to receive placebo (n = 59) or h-SOD (n = 61) given as a 10-mg/kg intravenous bolus followed by a 60-minute infusion of 0.2 mg.kg-1.min-1. Left ventricular function was analyzed via paired contrast left ventriculograms performed before PTCA and after 6 to 10 days and paired radionuclide ventriculograms performed within 24 hours of PTCA and after 4 to 6 weeks. Both h-SOD- and placebo-treated patients showed improvement in global and regional left ventricular function after successful reperfusion. Compared with the placebo group, no additional improvement was observed in the patients treated with h-SOD. CONCLUSIONS: The results of this clinical trial failed to demonstrate a beneficial effect of h-SOD on global or regional left ventricular function in patients who underwent successful PTCA for treatment of acute myocardial infarction.

Angioplasty, Balloon, Coronary↗
PubMed1994

Heart failure: clinical implications of recent trials.

The frustration has been in identifying drugs that have a positive impact on cardiac performance and a negative effect on mortality. ACE inhibitors, often with diuretics and possibly with digoxin, continue to show impressive outcomes in major studies.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Theoretical basis for the use of angiotensin II antagonists in the treatment of heart failure.

Angiotensin converting enzyme (ACE) inhibitors have been shown to improve morbidity and mortality in patients with heart failure. However, despite the demonstrated clinical benefits many physicians are reluctant to prescribe ACE-inhibitors to the mostly elderly heart failure patients due to concern for side effects which may be related to ACE-inhibitor-induced bradykinin accumulation. Angiotensin II receptor antagonists may provide more effective blockade of the renin-angiotensin-aldosterone system without causing bradykinin accumulation and thus associated side effects. The potential benefits of treating heart failure patients with an angiotensin II receptor antagonist instead of or in addition to an ACE-inhibitor are discussed.

Angiotensin II↗
PubMed1994

Blockade of the renin-angiotensin system. Effect on mortality in patients with left ventricular systolic dysfunction.

Blockade of the renin-angiotensin-aldosterone system (RAAS) has been shown to be effective in reducing morbidity and mortality in patients with symptomatic left ventricular dysfunction. Angiotensin converting enzyme inhibitors (ACE-I) should be administered to all patients with symptomatic left ventricular dysfunction unless contraindicated or not tolerated. Although ACE-Is are effective, there is reason to believe that further blockade of the RAAS by aldosterone antagonists and/or alternative means of blocking the RAAS by use of renin inhibitors or angiotensin II receptor blocking agents may have an important role in the future. The finding in the SOLVD and SAVE trials that ACE-Is are effective in reducing recurrent ischemic events in patients with left ventricular dysfunction also holds great promise for the future, not only for patients with left ventricular dysfunction but also as a possible secondary prevention of ischemic heart disease in patients without left ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Clinical consequences of angiotensin-converting enzyme inhibitor withdrawal in chronic heart failure: a double-blind, placebo-controlled study of quinapril. The Quinapril Heart Failure Trial Investigators.

OBJECTIVES: This study was performed to assess the efficacy, safety and clinical consequences of abrupt cessation of quinapril therapy in a placebo-controlled, randomized, double-blind withdrawal trial. BACKGROUND: Angiotensin-converting enzyme inhibitor therapy has assumed a pivotal role in the treatment of chronic heart failure. Quinapril hydrochloride, a nonsulfydryl angiotensin-converting enzyme inhibitor, has shown beneficial clinical effects in previous studies. METHODS: After > or = 10 weeks of single-blind quinapril therapy, 224 patients with New York Heart Association class II or III heart failure were randomized in double-blind fashion to continue quinapril (n = 114) or to receive placebo (n = 110) for 16 weeks. Changes in treadmill exercise time, New York Heart Association functional class, quality of life and symptoms of heart failure were assessed. RESULTS: Patients withdrawn to placebo had a significant deterioration in exercise tolerance (median change -16 s with placebo vs. +3 s with quinapril, p = 0.015). New York Heart Association functional class (p = 0.004) and quality of life were improved and signs and symptoms of congestive heart failure were lessened in those remaining on quinapril therapy compared with those receiving placebo. During double-blind treatment, 18 patients were withdrawn from the placebo group because of worsening heart failure compared with 5 patients withdrawn from quinapril treatment (p < 0.001). Rather than a precipitous deterioration of clinical status or early incidence of adverse events, withdrawal from quinapril was associated with steady worsening of heart failure, beginning 4 to 6 weeks after randomization to placebo. CONCLUSIONS: Quinapril is effective and safe for maintaining clinical stability in patients with moderate congestive heart failure. Withdrawal of quinapril from patients with heart failure results in a slow progressive decline in clinical status.

Aged↗
PubMed1993

Design and recruitment in the United States of a multicenter quantitative angiographic trial of pravastatin to limit atherosclerosis in the coronary arteries (PLAC I).

The present study was designed to test the effect of pravastatin, a new, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on the progression of coronary artery disease in patients with moderate hypercholesterolemia. Angiographic entry criteria included the presence of > or = 1 stenosis > or = 50% in a major epicardial coronary artery, and certification of film quality through the core angiography laboratory. Patients qualified for randomization if after diet stabilization their low density lipoprotein cholesterol concentrations were > or = 130 and < 190 mg/dl, and triglycerides were < or = 350 mg/dl. Pravastatin (40 mg) or placebo is administered once daily at bedtime. Arteriography will be repeated at the end of 3 years of treatment. The primary end point of the study is the change in absolute mean coronary artery diameter. During a 30-month recruitment period, 44,145 patients were screened, and 408 were randomized. The most frequent reason for excluding patients during the screening and dietary lead-in periods was a low serum cholesterol level. A large proportion of patients with documented coronary artery disease have cholesterol concentrations that are considered to be normal or only modestly increased. Adherence to strict standards of quality control for digital analysis of angiograms ensures that baseline angiograms can be interpreted at the end of 3-year follow-up.

Adult↗
PubMed1993

Therapy of left ventricular dysfunction: implications of recent therapeutic trials and future directions for therapy.

The natural history of patients with heart failure has changed relatively little until recently. Several large randomized trials have however recently changed our approach to the patient with symptomatic as well as asymptomatic left ventricular dysfunction. Although the effect of digoxin on survival is still uncertain there is still good evidence from the Radiance study in which patients were randomly withdrawn from digoxin that patients who remain on digoxin have a significant improvement in exercise tolerance and well being. The Consensus trial in patients with class IV heart failure suggested that ACE inhibitors were effective in improving survival. This therapy has not however been widely adapted in patients with mild to moderate heart failure. The recent randomized SOLVD treatment trial in conjunction with the VHEFT II study clearly shows that ACE inhibitors should be the basis for therapy along with a diuretic and digoxin if necessary in all patients with symptomatic left ventricular dysfunction unless contraindicated or not tolerated. There is also evidence from the SOLVD prevention trial that ACE inhibitors can prevent the development of manifest heart failure and hospitalization for heart failure in patients with asymptomatic left ventricular dysfunction. The importance of ACE inhibitors in patients with asymptomatic left ventricular dysfunction is confirmed by data from the SAVE trial which examine both symptomatic and asymptomatic patients with left ventricular dysfunction 3-16 days post infarction. Of interest in both the SOLVD treatment and prevention trials as well as the SAVE trial was the finding that ACE inhibitors reduced the incidence of recurrent ischemic events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1993

The QUinapril Ischemic Event Trial (QUIET) design and methods: evaluation of chronic ACE inhibitor therapy after coronary artery intervention.

The rationale, trial design, and statistical aspects of QUIET, the QUinapril Ischemic Event Trial, are described. QUIET is a prospective, double-blind placebo-controlled study that will assess the ability of the angiotensin-converting enzyme (ACE) inhibitor quinapril to reduce the rate of cardiac ischemic events and to slow or prevent the development of coronary artery atherosclerosis as assessed by serial angiography in a normolipidemic population without left ventricular dysfunction. The study began in September 1991 and has completed recruitment with 1740 patients across 38 centers (28 U.S., 4 Canada, 6 Europe) by the end of 1992. Patients are randomized to 20 mg of quinapril or placebo once daily and continue in the study for 3 years. Study completion is projected for 1995.

Adult↗