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Biomedical subjects

B Pitt

Publications and source records attributed to B Pitt.

At least 127 records · Page 7Linked to original sources
PubMed1993

Ramipril prevents impaired endothelium-dependent relaxation in arteries from rabbits fed an atherogenic diet.

Endothelium-dependent relaxation in arteries is attenuated in clinical and experimental atherosclerosis. This study investigates the endothelial preservation properties of the angiotensin converting enzyme inhibitor, ramipril, by assessing its ability to restore endothelium-dependent responsiveness in blood vessels from rabbits fed an atherogenic diet (0.25% cholesterol; 3% coconut oil; 12 weeks). Seven rabbits fed the atherogenic diet received ramipril (3 mg/kg mixed into their food daily) and 6 rabbits were maintained on the atherogenic diet alone. Control rabbits (n = 6) were fed a standard diet and did not receive ramipril. At the end of the dietary intervention, the rabbits were killed and blood was collected for measurement of the lipid profile. The thoracic aorta was isolated and half was frozen for pathologic review while the other half was cut into rings and placed in a muscle bath for measurement of isometric force development. Dose response curves to phenylephrine (10(-9) to 10(-5) M) and angiotensin II (10(-10) to 3 x 10(-7) M) were completed. There was a minimal decrease in responsiveness to phenylephrine in vessels from rabbits eating the atherogenic diet compared with controls and no significant differences in the response to angiotensin II for any of the vessels. Following contraction by phenylephrine, acetylcholine (10(-9) to 10(-5) M) and nitroglycerin (10(-10) to 10(-5) M) dose response curves were completed. Relaxation to acetylcholine in aortic rings from control rabbits was observed, although in arteries from atherogenic rabbits relaxation was attenuated. This effect was prevented in the atherogenic rabbits fed ramipril. Responsiveness to the endothelium-independent vasodilator, nitroglycerin, was similar in arteries from the three rabbit groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Use of converting enzyme inhibitors in patients with asymptomatic left ventricular dysfunction.

The Studies of Left Ventricular Dysfunction (SOLVD) prevention trial evaluated 4,228 patients with a left ventricular ejection fraction < or = 35% who were not receiving drug therapy for heart failure. Patients were randomized to treatment with enalapril or placebo in a dose of 2.5 to 20 mg/day. Patients randomized to enalapril showed a 37% reduction in the development of heart failure and a 36% reduction in hospitalization for heart failure (p < or = 0.001). However, there was only an 8% reduction in total mortality and a 14% reduction in cardiovascular mortality (p = NS). On the basis of the SOLVD prevention trial, patients with asymptomatic left ventricular dysfunction due to either ischemic or nonischemic cardiomyopathy should be started on treatment with an angiotensin-converting enzyme inhibitor to prevent the development of and hospitalization for heart failure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

A prospective evaluation of the hepatotoxicity of lofepramine in the elderly.

Lofepramine has been acclaimed as an effective and safe antidepressant, particularly for the elderly. Recent case reports of hepatic toxicity following treatment with lofepramine, however, caused clinicians to question its use in a patient population who frequently have concomitant physical illness. From published data the incidence of serious side effects as well as the implications for its use remain unclear. In this study, 52 patients over the age of 65 years treated with lofepramine were monitored over a 12-week period. The results suggest that for the overwhelming majority of patients, any rise in liver enzyme activity is transient. It is recommended, however, that LFTs be monitored for the first 12 weeks of treatment.

Aged↗
PubMed1993

Early reocclusion after successful thrombolysis is related to lesion length and roughness.

BACKGROUND: Reocclusion is a significant problem after thrombolysis. Results of previous studies conflict regarding the association of various features of postlytic lesions that might predict reocclusion. METHODS: A computer-assisted algorithm was therefore used to quantitatively measure edge roughness in the 90-minute postlysis angiogram of 84 patients receiving recombinant tissue plasminogen activator within 6 hours of chest pain. RESULTS: Twenty-five patients had reocclusion, and 59 did not. The baseline angiogram showed no differences between these two groups with respect to minimal dimensions or relative percentage of stenosis. Length was greater in the reocclusion group (12.2 +/- 5.0 vs 10.0 +/- 4.2 mm, P < 0.05). Three of four roughness indices based on curvature analysis indicated greater roughness in those patients with reocclusion. These differences were largely due to the increased length of these lesions. The scaled edge-length ratio, an index of roughness that is independent of length, was, however, significantly greater in the reocclusion group (1.15 +/- 0.10 vs 1.09 +/- 0.08, P < 0.006). Multiple regression analysis showed that lesion length, the scaled edge-length ratio, and the number of features (invaginations and evaginations) per cm correlated independently with the risk for reocclusion. CONCLUSIONS: The length and roughness of postlytic residual lesions are determinants of reocclusion.

Algorithms↗
PubMed1993

Effect of cold stress on coronary sinus blood flow in patients with scleroderma.

The mechanism of cardiac involvement in scleroderma is not known. Histologic studies of the myocardium in patients who died of scleroderma revealed that half had myocardial damage. Characteristic involvement ranges from focal contraction-band necrosis to diffuse fibrosis despite the absence of obstructive coronary artery disease of the major epicardial vessels. These findings suggest that scleroderma heart disease might result from episodic reduction of coronary blood flow due to abnormalities of coronary vasomotor tone. Studies using cold pressor thallium 201 myocardial perfusion scans support this hypothesis. Our study measured coronary blood flow during hand immersion in ice water at cardiac catheterization to determine whether patients with scleroderma had an abnormal coronary blood flow response. Coronary sinus blood flow was measured using a thermodilution method. Five patients with scleroderma were compared with 5 control subjects. All patients and controls had normal coronary angiograms. The coronary blood flow at baseline in the scleroderma and the control group (130 +/- 33 mL/min and 86 +/- 27 mL/min, respectively) was not significantly different. During the cold pressor test, both groups had a small, insignificant increase in coronary blood flow from baseline to 60 seconds (130 to 144 mL/min, scleroderma patients; 86 to 89 mL/min, control subjects). Our findings suggest that the cold pressor test does not cause an abnormal increase in coronary vasomotor tone or an absolute reduction in coronary blood flow in patients with scleroderma, as previously suggested by thallium 201 cold pressor studies.

Adult↗
PubMed1992

Effect of enalapril on myocardial infarction and unstable angina in patients with low ejection fractions.

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Angina, Unstable↗
PubMed1992

Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions.

BACKGROUND: It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity. We studied the effect of an angiotensin-converting--enzyme inhibitor, enalapril, on total mortality and mortality from cardiovascular causes, the development of heart failure, and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure. METHODS: Patients were randomly assigned to receive either placebo (n = 2117) or enalapril (n = 2111) at doses of 2.5 to 20 mg per day in a double-blind trial. Follow-up averaged 37.4 months. RESULTS: There were 334 deaths in the placebo group, as compared with 313 in the enalapril group (reduction in risk, 8 percent by the log-rank test; 95 percent confidence interval, -8 percent [an increase of 8 percent] to 21 percent; P = 0.30). The reduction in mortality from cardiovascular causes was larger but was not statistically significant (298 deaths in the placebo group vs. 265 in the enalapril group; risk reduction, 12 percent; 95 percent confidence interval, -3 to 26 percent; P = 0.12). When we combined patients in whom heart failure developed and those who died, the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group (630 vs. 818; risk reduction, 29 percent; 95 percent confidence interval, 21 to 36 percent; P less than 0.001). In addition, fewer patients given enalapril died or were hospitalized for heart failure (434 in the enalapril group; vs. 518 in the placebo group; risk reduction, 20 percent; 95 percent confidence interval, 9 to 30 percent; P less than 0.001). CONCLUSIONS: The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril.

Blood Pressure↗
PubMed1992

Prognostic importance of quantitative analysis of coronary cineangiograms.

Many studies have shown the prognostic value of angiographic data, but few have examined quantitative parameters of wall motion and shape or coronary stenosis severity. To determine whether these parameters have prognostic importance, baseline angiograms of 283 patients with up to 11.2 years (mean 8.3) of follow-up were quantitated. Event-free survival curves were constructed using log-rank testing. These indexes were also considered in 2 predictive models (Cox regression models): 1 with ("clinical") and 1 without ("quantitative") subjective angiographic analysis and clinical information. Regional shape (anterior and inferior walls) and motion (anterior wall only) indexes were predictive of event-free survival when considered singly. But these parameters were not of independent prognostic importance in the regression models. The most important independent parameters in the quantitative model for predicting overall cardiac mortality or an initial lethal cardiac event were the ejection fraction and the percent diameter narrowing of each major coronary artery. Myocardial infarction was predicted by the percent diameter stenosis of the left main and left anterior descending arteries but not the ejection fraction. In the clinical model, the factors of overriding prognostic importance were the ejection fraction and the subjective determination of the number of vessels involved with "significant" stenoses. Quantitative coronary arteriography still contributed independent prognostic value. Thus, quantification of the ejection fraction and severity of coronary lesions were of independent, prognostic importance, whereas indexes of regional function and shape were not.

Adult↗
PubMed1992

The effect of treatment on survival in congestive heart failure.

Congestive heart failure (CHF) is a disorder characterized by a variety of clinical, biochemical, electrophysiological, and hemodynamic abnormalities. During the past two decades, numerous drugs have been employed in the treatment of this complex syndrome, and many agents have been shown to improve symptoms and ventricular function in patients with CHF. Because CHF is associated with a high risk of death, treatment should be directed not only toward the relief of symptoms, but also toward a reduction in mortality. Many variables have been shown to be related to survival; taken individually, however, each is limited in its utility in predicting prognosis. In recent years, large-scale studies with large sample sizes have directly assessed the effects of treatment on mortality in CHF. Results from these trials indicate that vasodilators and angiotensin-converting enzyme (ACE) inhibitors may improve mortality in patients with symptoms of heart failure. Additional trials are now in progress to evaluate the effect of treatment on patients with asymptomatic left ventricular dysfunction.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Is the tyramine test for depressive illness useful in elderly patients?

There were no significant differences in tyramine sulphate excretion following tyramine ingestion between elderly depressed, demented or control patient groups, in contrast with younger subjects where this test is a trait marker for unipolar endogenous depression. There are inherent problems in urine collection studies in the elderly and the results may have been influenced by the medication that elderly patients have to take for other disorders. This study suggests that the tyramine test is unlikely to be of clinical usefulness in the over 65 age group.

Aged↗
PubMed1992

Eicosapentaenoic acid inhibits endothelium-dependent relaxation to acetylcholine in guinea pig coronary resistance vessels.

Dietary supplementation with eicosapentaenoic acid (EPA) alters arachidonate metabolism. This study characterizes the effect of dietary EPA on endothelium-dependent vasodilation to acetylcholine (ACH) and ATP in guinea pig coronary resistance vessels. Guinea pigs were fed standard chow (n = 6), standard chow+sesame seed oil (n = 6), or standard chow+menhaden fish oil (17% EPA; n = 6). Coronary vasodilations were examined in the isolated, potassium-arrested heart utilizing a modified Langendorff preparation. Coronary vessels were constricted with prostaglandin F2 alpha and relaxed with ACH (5.5 x 10(-9)-10(-6) moles) or ATP (10(-10)-10(-7) moles). Endothelium-dependent dilations to ACH, but not ATP, were attenuated by dietary supplementation with EPA. To assess the role of the endothelium in modulating vascular responses to agonists following dietary manipulation, the perfusate was stimulated by electrolysis (9 V, 4 Hz, 2 msec) in order to generate free radicals, which we have shown to preferentially damage the endothelium. After endothelial damage, responses to ACH, ATP, and nitroprusside were similar between the dietary groups. In an additional group of standard diet animals (n = 6) experiments were performed to assess the role of prostanoid metabolism in affecting coronary vascular reactivity. Perfusion of hearts with indomethacin (14 microM) reduced endothelium-dependent vasodilations to ACH (5.5 x 10(-9)-10(-6) moles), but not to ATP (10(-10)-10(-7) moles). After endothelial damage, infusion of ACH resulted in vasoconstriction, whereas vasodilation responses to ATP were absent. We conclude that dietary supplementation with EPA inhibits endothelium-dependent dilations to ACH in guinea pig coronary microvessels. These diet-related differences in vascular reactivity may be related to the fish-oil-induced alteration of vasodilator prostaglandin metabolism. In the coronary bed, different endothelial factors appear to mediate relaxation to ACH and ATP.

Acetylcholine↗
PubMed1992

The role of beta-adrenergic blocking agents in preventing sudden cardiac death.

The failure of encainide and flecainide to reduce mortality after infarction in the Cardiac Arrhythmia Suppression Trial and the failure of low-dose amiodarone to prevent sudden cardiac death in patients with a low left ventricular ejection fraction has shifted attention to other strategies, such as beta-adrenergic blocking agents, to prevent sudden cardiac death. Evidence suggesting that beta-adrenergic blocking agents might be useful, especially in patients with low left ventricular ejection fraction, is accumulating. Previous data from studies using beta-adrenergic blocking agents and the mechanisms by which beta-adrenergic blocking agents might be of value in preventing sudden cardiac death are reviewed. These considerations and the availability of new investigational beta-adrenergic blocking agents with vasodilator properties provide a new opportunity to test the hypothesis that beta-adrenergic blocking agents are useful in preventing sudden cardiac death, especially in patients with a low left ventricular ejection fraction.

Adrenergic beta-Antagonists↗
PubMed1992

Congestive heart failure: new therapeutic strategies.

Angiotensin converting enzyme inhibitors (ACE-I) are widely used in patients with severe heart failure on the basis of the significant improvement in mortality in the CONSENSUS-I trial in patients with Class IV heart failure. Recent data from the 5-year clinical trial Studies of Left Ventricular Dysfunction (SOLVD) suggest a role for ACE-I in patients with mild to moderate heart failure as well as in those with asymptomatic left ventricular dysfunction. The SOLVD treatment trial in patients with a left ventricular ejection fraction (LVEF) less than or equal to 35% and treated for heart failure with conventional therapy including digitalis, diuretics, or vasodilators demonstrated that the addition of enalapril resulted in a significant reduction in mortality from heart failure as well as in the combined end point of death plus hospitalization from heart failure. These data suggest that ACE-I should be the base of therapy for patients with mild to moderate heart failure, as well as for those with severe heart failure.

Angiotensin-Converting Enzyme Inhibitors↗