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Biomedical subjects

P C Deedwania

Publications and source records attributed to P C Deedwania.

At least 19 recordsLinked to original sources
PubMed1997

Role of beta blockade in the treatment of myocardial ischemia.

A number of antianginal drugs and therapeutic strategies are now available for the treatment of patients with coronary artery disease (CAD) and myocardial ischemia. Of the available antianginal drugs, beta blockers appear to be most effective in suppressing myocardial ischemia. The superior anti-ischemic efficacy of beta blockers can be explained by their beneficial actions on hemodynamic parameters, vasomotion, and platelet function. Compared with other anti-ischemic drugs, beta blockers appear to be more efficacious in reducing the magnitude of myocardial ischemia during routine daily activities. In addition, the results of recent studies indicate that treatment with beta blockers not only suppresses myocardial ischemia, but also improves the clinical outcome in patients with CAD. These beneficial effects, along with the well-demonstrated cardioprotective effects of beta blockade in the postinfarction period, clearly suggest that this class of anti-ischemic drugs is an ideal therapeutic choice in most patients with CAD.

Adrenergic beta-Antagonists↗
PubMed1997

Effect of morning versus evening dosing of diltiazem on myocardial ischemia detected by ambulatory electrocardiographic monitoring in chronic stable angina pectoris. Dilacor XR Ambulatory Ischemia Study Group.

Myocardial ischemia occurs frequently during daily life and has a circadian pattern similar to that reported for myocardial infarction and sudden death. Because of the increased risk of myocardial ischemia in the morning hours, it has been suggested that the administration of anti-ischemic medication before bedtime may be more effective than the traditional morning dosing. This randomized, double-blind, placebo-controlled, crossover study evaluated the effects of 480-mg/day diltiazem (given either in the A.M. or the P.M.) on myocardial ischemia using ambulatory electrocardiographic monitoring in 68 patients with chronic stable angina and > or = 2 minutes of ischemia per 48 hours. During treatment with diltiazem, the duration and number of myocardial ischemic episodes were reduced by 45% (94 to 52 minutes, p <0.004) and by 40% (4.5 to 2.7 episodes, p <0.003), respectively. The duration and number of myocardial ischemic episodes during daytime (6 A.M. to 6 P.M.) hours were also reduced by 52% (74 to 36 minutes, p <0.002) and by 48% (3.1 to 1.6 episodes, p <0.001), respectively. There was no significant difference between A.M. and P.M. dosing. Morning ischemia (6 A.M. to noon), considered separately from daytime ischemia, was also significantly reduced by both A.M. and P.M. dosing regimens, with no difference between the regimens. The results of this study showed that both A.M. and P.M. dosing of long-acting diltiazem were equally effective in suppressing episodes of ambulatory myocardial ischemia at all times.

Analysis of Variance↗
PubMed1997

Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE)

BACKGROUND: To determine whether specific angiotensin II receptor blockade with losartan offers safety and efficacy advantages in the treatment of heart failure over angiotensin-converting-enzyme (ACE) inhibition with captopril, the ELITE study compared losartan with captopril in older heart-failure patients. METHODS: We randomly assigned 722 ACE inhibitor naive patients (aged 65 years or more) with New York Heart Association (NYHA) class II-IV heart failure and ejection fractions of 40% or less to double-blind losartan (n = 352) titrated to 50 mg once daily or captopril (n = 370) titrated to 50 mg three times daily, for 48 weeks. The primary endpoint was the tolerability measure of a persisting increase in serum creatinine of 26.5 mumol/L or more (> or = 0.3 mg/dL) on therapy; the secondary endpoint was the composite of death and/or hospital admission for heart failure; and other efficacy measures were total mortality, admission for heart failure, NYHA class, and admission for myocardial infarction or unstable angina. FINDINGS: The frequency of persisting increases in serum creatinine was the same in both groups (10.5%). Fewer losartan patients discontinued therapy for adverse experiences (12.2% vs 20.8% for captopril, p = 0.002). No losartan-treated patients discontinued due to cough compared with 14 in the captopril group. Death and/or hospital admission for heart failure was recorded in 9.4% of the losartan and 13.2% of the captopril patients (risk reduction 32% [95% CI -4% to + 55%], p = 0.075). This risk reduction was primarily due to a decrease in all-cause mortality (4.8% vs 8.7%; risk reduction 46% [95% CI 5-69%], p = 0.035). Admissions with heart failure were the same in both groups (5.7%), as was improvement in NYHA functional class from baseline. Admission to hospital for any reason was less frequent with losartan than with captopril treatment (22.2% vs 29.7%). INTERPRETATION: In this study of elderly heart-failure patients, treatment with losartan was associated with an unexpected lower mortality than that found with captopril. Although there was no difference in renal dysfunction, losartan was generally better tolerated than captopril and fewer patients discontinued losartan therapy. A further trial, evaluating the effects of losartan and captopril on mortality and morbidity in a larger number of patients with heart failure, is in progress.

Aged↗
PubMed1997

Testosterone worsens endothelial dysfunction associated with hypercholesterolemia and environmental tobacco smoke exposure in male rabbit aorta.

OBJECTIVES: To assess the effects of interaction of sex hormones, hypercholesterolemia (HC) and environmental tobacco smoke (ETS) exposure on endothelium-dependent relaxation, we examined vascular reactivity in vitro in an animal model of atherogenesis. BACKGROUND: Animal and human studies indicate the presence of interactions between classic coronary artery disease risk factors and endothelium-dependent relaxation. Sex hormones have also been shown to influence release of endothelium-derived relaxing factor. METHODS: New Zealand White rabbits were randomized to receive either an HC diet (n = 8) or ETS exposure plus HC diet (n = 8). Eight rabbits receiving a normal diet, without exposure to ETS, served as the control group. The HC diet consisted of 3% soybean oil and 0.3% cholesterol by weight over 13 weeks. The source of ETS was sidestream smoke of 4 cigarettes/15 min, 6 h/day, 5 days/week over 10 weeks in a smoking chamber. Rabbits were killed, and fresh aortic rings were harvested and maintained in oxygenated Krebs solution in an organ bath at 37 degrees C. Rings were precontracted with norepinephrine and exposed to acetylcholine in increasing doses, and isometric tension was recorded. Rings were also exposed to physiologic concentrations (1 nmol/liter) of either 17-beta-estradiol, testosterone or progesterone before pre-contraction with norepinephrine and relaxation with acetylcholine. Endothelium-independent relaxation was studied using nitroglycerin. The surface area of the ring covered by lipids was measured by Sudan IV staining. RESULTS: HC and ETS significantly reduced endothelium-dependent relaxation (p = 0.01 and p < 0.0005, respectively) and caused atherogenesis (p < 0.0005 and p = 0.047, respectively) but did not affect endothelium-independent relaxation. Incubation with estradiol and estradiol plus progesterone did not influence endothelium-dependent relaxation. Testosterone reduced endothelium-dependent relaxation (p = 0.049) and augmented the endothelial dysfunction associated with ETS exposure and HC (p = 0.03). CONCLUSIONS: Both HC and ETS are atherogenic and impair endothelial function but do not affect endothelium-independent relaxation. Physiologic levels of estradiol and estradiol plus progesterone do not affect endothelium-dependent relaxation. Physiologic levels of testosterone impair relaxation and augment the endothelial dysfunction associated with ETS exposure and HC.

Animals↗
PubMed1997

Evidence-based, cost-effective risk stratification and management after myocardial infarction. California Cardiology Working Group on Post-MI Management.

Current management of patients after an acute myocardial infarction (AMI) reflects a variety of approaches ranging from conservative to aggressive. Although each method is appropriate in certain subgroups, their application frequently lacks a scientific basis. Current, clinically relevant, evidence-based practice guidelines are needed for secondary prevention for survivors after an AMI. To meet this need, the California Cardiology Working Group was assembled to evaluate the available data from clinical trials and other published studies and develop evidence-based, cost-effective guidelines for clinicians to use as a basis for patient management after an AMI. The group consisted of 18 members, including cardiologists from academic institutions and physicians working in cardiac intensive care, private practices, and managed care settings, representing a broad spectrum of expertise pertaining to patients who have had an AMI. The members had expertise in cardiac intensive care, interventional cardiology, nuclear cardiology, lipid disorders, echocardiography, and cardiac rehabilitation. The intended audience for these practice guidelines includes all physicians who treat survivors of MI. A literature review of all relevant clinical trials and other published data about the natural history after AMI and the effects of current therapeutic modalities are discussed herein. Case histories served as models for application of the literature-based data. The recommendations for management were reached by consensus vote based on the scientific evidence. When more than 1 management option applied, this was recognized in the recommendations. The recommendations accompany the text.

Arrhythmias, Cardiac↗
PubMed1997

Pulmonary effect of amiodarone in patients with heart failure. The Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) Investigators (Veterans Affairs Cooperative Study No. 320).

OBJECTIVES: The purpose of this study was to evaluate the pulmonary effects of amiodarone in patients with heart failure, in those with chronic obstructive pulmonary disease (COPD) and in those undergoing a surgical procedure. BACKGROUND: Amiodarone has been known to cause pulmonary complications; especially in those with COPD and in those undergoing a surgical procedure. METHODS: Patients receiving vasodilator therapy for congestive heart failure were prospectively randomized to placebo or amiodarone at 800 mg/day for 14 days, 400 mg/day for 50 weeks and then 300 mg/day thereafter. Chest X-ray film and pulmonary function tests with diffuse capacity of carbon monoxide (DLCO) were obtained at baseline and annually. The power to detect a 20% difference in DLCO at 1 year exceeded 90% in all patients and in those with COPD (two-sided alpha = 0.05). The sample allowed a 75% power to detect pulmonary complications (1% vs. 5%) between the two treatment groups. RESULTS: There was no difference in baseline characteristics between patients randomized to amiodarone (n = 269) or placebo (n = 250). The DLCO measurements at randomization were 18.3 +/- 6.9 and 17.7 +/- 7.6 ml/min per mm Hg for the amiodarone and placebo groups, respectively (p = 0.3). At 1 and 2 years, DLCO measurements were 17.7 +/- 7.0 and 18.3 +/- 7.7 ml/min per mm Hg for the amiodarone group and 17.9 +/- 7.2 and 18.2 +/- 7.2 for the placebo group, respectively. There were no significant differences between the groups, with corresponding p values of 0.73 ad 0.96 at years 1 and 2, respectively. Among patients with COPD, DLCO measurements at randomization were 17.9 +/- 6.7 and 15.8 +/- 6.8 ml/min per mm Hg for the amiodarone and placebo groups, respectively. At years 1 and 2, DLCO measurements were 16.6 +/- 7.8 and 17.8 +/- 9.5 ml/min per mm Hg for the amiodarone group and 16.5 +/- 6.6 and 16.3 +/- 7.0 ml/min per mm Hg for the placebo group, with corresponding p values of 0.95 and 0.48, respectively. There was no difference in survival free of noncardiac or perioperative deaths between patients assigned to amiodarone or placebo. Pulmonary fibrosis was diagnosed in four patients (1.1%) treated with amiodarone and in three patients (0.8%) receiving placebo. CONCLUSIONS: Our study shows that amiodarone can be safely used, with an acceptable pulmonary toxicity, in patients with heart failure.

Aged↗
PubMed1997

Effects of second-hand smoke and gender on infarct size of young rats exposed in utero and in the neonatal to adolescent period.

OBJECTIVES: We sought to assess the effects of second-hand smoke (SHS) and gender on infarct size in young rats exposed in utero or in the neonatal to adolescent period, or both. BACKGROUND: We previously demonstrated that exposure to SHS increases infarct size in a rat model of ischemia and reperfusion, with a dose-response relation. These results are consistent with epidemiologic studies demonstrating that SHS increases risk of death from heart disease. METHODS: Thirty-one pregnant female rats were randomly divided into two groups: those exposed to SHS and a control group (non-SHS). After 3 weeks, each rat had given birth to 10 to 12 rats. One hundred one neonatal rats were divided into four groups according to exposure to SHS in utero (SHSu) and randomized to SHS exposure in the neonatal to adolescent period (SHSna). After 12 weeks, all rats were subjected to 17 min of left coronary artery occlusion and 2 h of reperfusion. RESULTS: Birth mortality was higher in the SHSu group than in the non-SHSu group (11.9% vs. 2.8%, p < 0.001). Body weight of neonatal rats at 3 and 4 weeks in the two SHSu groups was lower than that of rats in the two non-SHSu groups (p < 0.001). Exposure to SHSna increased endothelin-1 levels in plasma (p = 0.001). In all 70 young rats who survived the neonatal period, infarct size (Infarct mass/Risk area x 100%) was greater in the SHSna groups than in the non-SHSna groups (p = 0.005) and in the male groups than in the female groups (p < 0.001). CONCLUSIONS: Exposure to SHS in the neonatal to adolescent period and male gender increased myocardial infarct size in a young rat model of ischemia and reperfusion. These results are consistent with epidemiologic studies demonstrating that SHS increases the health risk to neonates and adolescents.

Angiotensin II↗
PubMed1997

The progression from hypertension to heart failure.

Heart failure (HF) still presents a major health problem despite significant understanding of its underlying pathophysiology and recent therapeutic advances. Hypertension is a major risk factor for HF and plays a key role in the evolution of the disease. In an attempt to compensate for the increased peripheral resistance frequently noted in hypertension, the heart may hypertrophy, with the left ventricular enlargement accompanied by fibrosis and resulting in reduced contractility. Ultimately the hypertrophied or fibrosed myocardium is no longer able to maintain normal cardiac output and left ventricular failure occurs. Evidence shows that treating hypertension effectively can have a major beneficial impact on some, but not all, forms of adult cardiovascular disease. For example, the incidence of HF and stroke are clearly reduced; however, until recently, treating hypertension has had relatively little effect on coronary heart disease (CHD) events. The benefits of antihypertensive treatment are, however, clearly underestimated, possibly because many studies are too short and because more subtle benefits of treatment have been overlooked. Also, it must be realized that hypertension is a complex disorder and antihypertensive drugs do indeed differ regarding their effects on associated metabolic derangements often seen in hypertensive patients. Angiotensin converting enzyme (ACE) inhibitors have been shown to be highly efficacious and safe antihypertensive agents, and have additional favorable effects on metabolic parameters, renal functions, and cardiac hypertrophy. ACE inhibitors are now the mainstay of therapy in the patients with heart failure and it is now well recognized that earlier and more aggressive treatment of hypertension may reduce the incidence of HF. ACE inhibitors are an excellent choice as an antihypertensive agent; however, many physicians limit their use of ACE inhibitors due to concern about possible renal side-effects, which accompanied the early use of these agents at very high doses.

Aged↗
PubMed1997

Chronic dietary L-arginine prevents endothelial dysfunction secondary to environmental tobacco smoke in normocholesterolemic rabbits.

Our goal was to determine whether environmental tobacco smoke causes endothelial dysfunction in the absence of hypercholesterolemia and whether such an effect can be prevented by supplementation with L-arginine. Environmental tobacco smoke exposure is associated with an increase in coronary artery disease events and mortality. We have previously demonstrated that environmental tobacco smoke causes endothelial dysfunction and atherosclerosis in rabbits with diet-induced hypercholesterolemia and atherosclerosis and that chronic dietary L-arginine supplementation prevents this. The effects of L-arginine supplementation (2.25% solution ad libitum) and environmental tobacco smoke (smoking chambers for 10 weeks) were examined with a 2 x 2 design in 32 rabbits fed a normal diet. Acetylcholine, calcium ionophore A23187, and nitroglycerin-induced vasorelaxation were assessed in aortic rings precontracted with phenylephrine. Endothelial L-arginine levels were measured by chromatography. Chronic L-arginine supplementation increased serum (P < .001) and endothelial (P = .003) L-arginine levels. Environmental tobacco smoke reduced endothelium-dependent acetylcholine-induced relaxation, and L-arginine blocked this adverse effect (P = .04). Environmental tobacco smoke tended to increase phenylephrine-induced contraction (P = .06). Neither environmental tobacco smoke nor L-arginine influenced A23187-induced relaxation nor endothelium-independent nitroglycerin-induced relaxation. Endothelial dysfunction secondary to environmental tobacco smoke may occur in the absence of diet-induced hypercholesterolemia and atherosclerosis. Chronic dietary supplementation with a nitric oxide donor such as L-arginine offsets the endothelial dysfunction associated with environmental tobacco smoke in normocholesterolemic rabbits, possibly through substrate loading of the nitric oxide pathway.

Animals↗
PubMed1996

Effect of amiodarone on clinical status and left ventricular function in patients with congestive heart failure. CHF-STAT Investigators.

BACKGROUND: Although trials of amiodarone therapy in patients with congestive heart failure have produced discordant results with regard to effects on survival, most studies have reported a significant rise in left ventricular ejection fraction during long-term therapy. In the present study, we determined whether this increase in ejection fraction is associated with an improvement in the symptoms and/or physical findings of heart failure or a reduction in the number of hospitalizations for heart failure. METHODS AND RESULTS: In the Department of Veterans Affairs cooperative study of amiodarone in congestive heart failure, 674 patients with New York Heart Association class II through IV symptoms and ejection fractions of < or = 40% were treated with amiodarone or placebo for a median of 45 months in a randomized, double-blind, placebo-controlled protocol. Clinical assessments and radionuclide ejection fraction were performed at baseline and after 6, 12, and 24 months. Compared with the placebo group, ejection fraction increased more in the amiodarone group at each time point (8.1 +/- 10.2% [mean +/- SD] versus 2.6 +/- 7.9% at 6 months, 8.0 +/- 10.9% versus 2.7 +/- 8.0% at 12 months, and 8.8 +/- 10.1% versus 1.9 +/- 9.4% after 24 months, all P < .001). However, this difference was not associated with greater clinical improvement, lesser diuretic requirements, or fewer hospitalizations for heart failure (11.1% for amiodarone and 13.6% for placebo group; overall relative risk in the amiodarone group, 0.81 [95% CI, 0.56 to 1.10], P = .18). Of note is the trend toward a reduction in the combined end point of hospitalizations and cardiac deaths (relative risk, 0.82 [CI, 0.65 to 1.03], P = .08), which was significant in patients with nonischemic etiology (relative risk, 0.56 [CI, 0.36 to 0.87], P = .01) and absent in the ischemic group (relative risk, 0.95). CONCLUSIONS: Although amiodarone therapy resulted in a substantial increase in left ventricular ejection fraction in patients with congestive heart failure, this was not associated with clinical benefit in the population as a whole. The substantial reduction in the combined end point of cardiac death plus hospitalizations for heart failure in the nonischemic group suggests possible benefit in these patients.

Aged↗
PubMed1996

Hemodynamic changes as triggers of cardiovascular events.

Although a large number of clinical studies during the past decade have documented that myocardial ischemia, acute myocardial infarction, and sudden cardiac death have definite circadian patterns, recently published work suggests that it is not necessarily a specific time of the day but the sleep/wake cycle and postural changes as well as the balance between triggers and protective factors that determine the onset of cardiovascular events. A clear understanding of the pathophysiologic processes responsible for ischemic events and the specific roles played by various triggers would be helpful in better defining the therapeutic strategies designed for the prevention and treatment of acute cardiac events. Because changes in hemodynamic parameters are of paramount importance in initiating an ischemic event, it is critical to review their role and relationship in the pathogenesis of acute coronary events.

Blood Pressure↗
PubMed1995

Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure.

BACKGROUND: Asymptomatic ventricular arrhythmias in patients with congestive heart failure are associated with increased rates of overall mortality and sudden death. Amiodarone is now used widely to prevent ventricular tachycardia and fibrillation. We conducted a trial to determine whether amiodarone can reduce overall mortality in patients with congestive heart failure and asymptomatic ventricular arrhythmias. METHODS: We used a double-blind, placebo-controlled protocol in which 674 patients with symptoms of congestive heart failure, cardiac enlargement, 10 or more premature ventricular contractions per hour, and a left ventricular ejection fraction of 40 percent or less were randomly assigned to receive amiodarone (336 patients) or placebo (338 patients). The primary end point was overall mortality, and the median follow-up was 45 months (range, 0 to 54). RESULTS: There was no significant difference in overall mortality between the two treatment groups (P = 0.6). The two-year actuarial survival rate was 69.4 percent (95 percent confidence interval, 64.2 to 74.6) for the patients in the amiodarone group and 70.8 percent (95 percent confidence interval, 65.7 to 75.9) for those in the placebo group. At two years, the rate of sudden death was 15 percent in the amiodarone group and 19 percent in the placebo group (P = 0.43). There was a trend toward a reduction in overall mortality among the patients with nonischemic cardiomyopathy who received amiodarone (P = 0.07). Amiodarone was significantly more effective in suppressing ventricular arrhythmias and increased the left ventricular ejection fraction by 42 percent at two years. CONCLUSIONS: Although amiodarone was effective in suppressing ventricular arrhythmias and improving ventricular function, it did not reduce the incidence of sudden death or prolong survival among patients with heart failure, except for a trend toward reduced mortality among those with nonischemic cardiomyopathy.

Actuarial Analysis↗