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Biomedical subjects

W H Frishman

Publications and source records attributed to W H Frishman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Herbal medicine for the treatment of cardiovascular disease: clinical considerations.

Herbs have been used as medical treatments since the beginning of civilization and some derivatives (eg, aspirin, reserpine, and digitalis) have become mainstays of human pharmacotherapy. For cardiovascular diseases, herbal treatments have been used in patients with congestive heart failure, systolic hypertension, angina pectoris, atherosclerosis, cerebral insufficiency, venous insufficiency, and arrhythmia. However, many herbal remedies used today have not undergone careful scientific assessment, and some have the potential to cause serious toxic effects and major drug-to-drug interactions. With the high prevalence of herbal use in the United States today, clinicians must inquire about such health practices for cardiac disease and be informed about the potential for benefit and harm. Continuing research is necessary to elucidate the pharmacological activities of the many herbal remedies now being used to treat cardiovascular diseases.

Angina Pectoris↗
PubMed1998

Biologic markers as predictors of cardiovascular disease.

Epidemiologic data obtained over the past 30 years suggest that a number of new biologic markers are associated with increased risk for cardiovascular disease. These include indices related to (1) altered glucose metabolism, particularly insulin resistance; (2) hyperlipidemia; (3) elevated levels of lipoprotein(a) and homocysteine; (4) increased levels of molecules reflecting decreased fibrinolysis and increased activation of the coagulation cascade; (5) elevations in cell adhesion molecules and other markers of endothelial function; and (6) elevations in molecules associated with infection, inflammation, and vascular remodeling. Changes in molecules associated with increased risk usually occur in clusters. This clustering suggests that effective treatment of one marker may have positive effects on multiple markers. Indeed, several studies have demonstrated that therapies designed to reduce hyperlipidemia may also lower the plasma levels of factors associated with increased coagulation and reduced fibrinolysis. Thus, careful assessment of patient risk factors, and the development of therapies directed toward chains of markers associated with increased risk, may significantly alter the course of cardiovascular disease.

Biomarkers↗
PubMed1998

Differences between male and female patients with regard to baseline demographics and clinical outcomes in the Asymptomatic Cardiac Ischemia Pilot (ACIP) Trial.

BACKGROUND: Coronary artery disease (CAD) is a common problem in men and women; however, men and women with similar clinical presentations of myocardial ischemia may receive different revascularization treatments. HYPOTHESIS: Using the data base of the Asymptomatic Cardiac Ischemia Pilot (ACIP) trial, this study was undertaken to compare by gender the baseline demographic data and the clinical outcome results in patients randomized to various treatments in the ACIP study. METHODS: This randomized trial compared three treatment regimens [pharmacologic management of angina, pharmacologic management of angina and ambulatory electrocardiographic (ECG) evidence of ischemia, and revascularization--that is, angioplasty and coronary artery bypass surgery], in patients with known CAD, positive stress ECG tests, and ECG evidence of ischemia during 48 h ambulatory monitoring. In all, 558 patients were randomized, 79 of whom were women (mean age: men 61.6 years, women 60.6 years) Ambulatory ECG evidence of ischemia, clinical events, that is, death, myocardial infarction, hospital admission for coronary events, and exercise performance were monitored. RESULTS: Although of the same age as men at baseline, women had a higher prevalence of hypertension and diabetes. Women had less severe CAD by angiography and higher left ventricular ejection fractions. Men had longer exercise tolerance times on the treadmill. However, men and women had similar numbers and duration of ambulatory ECG ischemic abnormalities. Regarding revascularization, men more commonly underwent coronary artery bypass surgery (p = 0.025) while women underwent percutaneous transluminal coronary angioplasty more frequently (p = 0.10). Clinical outcomes were comparable in men and women, although the numbers of events were relatively small. CONCLUSIONS: Men and women of comparable age manifest CAD with similar ischemic ECG abnormalities seen on both exercise tolerance and ambulatory ECG examinations. In ACIP, women tended to have more risk factors for CAD and less severity in anatomical disease, which may explain why women are less likely than men to have coronary bypass surgery.

Coronary Disease↗
PubMed1998

Additional antianginal and anti-ischemic efficacy of mibefradil in patients concomitantly treated with long-acting nitrates for chronic stable angina pectoris.

BACKGROUND: Mibefradil, a newly approved antihypertensive and antianginal drug, is the first member of a new class of calcium antagonists (CAs), the tetralol derivatives, that selectively blocks T-type Ca2+ channels in contrast to classical CAs which, at therapeutic concentrations, block only L-type Ca2+ channels. Since patients with chronic stable angina pectoris typically may be treated with the combination of a long-acting nitrate and a CA, the additive efficacy and safety of mibefradil in combination with nitrate therapy needs to be determined. HYPOTHESIS: This study was designed to assess the efficacy, tolerability, and safety of mibefradil when added to long-acting nitrate therapy in patients with chronic stable angina pectoris. METHODS: Following a 1-week placebo run-in period, patients were randomized to receive either mibefradil 50 mg (n = 96) or placebo (n = 93) once daily in addition to their nitrate therapy. After 2 weeks of active treatment, patients receiving the mibefradil were force titrated to 150 mg once daily for an additional 2 weeks. Exercise tolerance tests (ETTs) were performed at the end of Weeks 2 and 4; patients also maintained an anginal diary during the 4-week treatment period. RESULTS: After 2 weeks of treatment with 50 mg mibefradil (within the current recommended dose range), a statistically significant but modest increase in total exercise duration was observed (treatment effect 16.4 s, p = 0.04). Similarly, there was a significant increase in time to onset of ischemia (treatment effect 26 s, p = 0.008). The adverse event profile of the 50 mg dose was indistinguishable from placebo, indicating that this dose was extremely well tolerated. At Week 4, the mibefradil-treated patients were taking 150 mg, which is above the current recommended dose range. The increase in total exercise duration was larger for the mibefradil 150 mg group than for the placebo group. For the intent-to-treat population, this difference did not reach statistical significance, whereas in the standard population it did (treatment effect 21 s, p = 0.05). The other two ETT variables, time to onset of angina and time to onset of 1 mm ST-segment depression, demonstrated significantly greater effect with mibefradil 150 mg (treatment effects 40 s, p = 0.002, and 55 s, p < 0.001, respectively, for the intent-to-treat population). Mibefradil 150 mg was associated with more adverse events than placebo, specifically, dizziness, leg edema, and postural hypotension. CONCLUSIONS: This study demonstrates that mibefradil 50 mg once daily in the setting of the background long-acting nitrate therapy produces additive antianginal and anti-ischemic effects and is extremely well tolerated.

Adolescent↗
PubMed1998

Fenoldopam: a new dopamine agonist for the treatment of hypertensive urgencies and emergencies.

Fenoldopam is a selective dopamine agonist that is being considered for the parenteral treatment of systemic hypertension. In both an oral and parenteral form, the drug causes peripheral vasodilation by stimulating dopamine-1 adrenergic receptors. Its pharmaco-dynamics are reviewed in this article, along with the clinical experiences in patients with hypertensive urgencies and emergencies. Intravenous fenoldopam may provide advantages over sodium nitroprusside because it can induce both a diuresis and natriuresis, is not light sensitive, and is not associated with cyanide toxicity. There is no evidence for rebound hypertension after discontinuation of fenoldopam influsion.

Animals↗
PubMed1998

Sodium ion/hydrogen ion exchange inhibition: a new pharmacologic approach to myocardial ischemia and reperfusion injury.

Over the past few years, it has been shown that the cardiac myocyte plasma membrane sodium ion/hydrogen ion exchanger (NHE) plays an important role in the maintenance of intracellular pH, sodium, and calcium ion homeostasis. From the results of various experimental studies, it is clear that this ion exchanger is an important mediator of ischemic-reperfusion injury of the heart. During myocardial ischemia, intracellular acidosis develops quickly, activating the exchanger to extrude H+ into the extracellular environment and bring Na+ into the cell. With further progression of ischemia, the cell is unable to handle the overload of Na+, causing it to use its Na+/Ca2 exchanger to unload intracellular Na+ into the extracellular space. At the same time, however, calcium is being transported into the cell. This can lead to detrimental cardiac injury, such as contracture and necrosis. During myocardial reperfusion, these events are magnified because the return of blood flow lowers the extracellular H+ concentration, stimulating the NHE to extrude more intracellular H+ ion. This leads to intracellular Na+ excess and eventually, intracellular Ca2+ overload and cardiac injury. In an effort to alter these pathophysiologic events, a number of investigators have studied the ability of various NHE inhibitors, such as amiloride, analogues of amiloride, and other drugs (HOE 694, HOE 642), to prevent cardiac ischemic-reperfusion damage. Preliminary results from studies in animal models have revealed that most of these agents are able to attenuate the development of myocardial contracture, infarction, and arrhythmias during both ischemia and reperfusion. Their efficacy and cardioprotective effects in human beings have yet to be determined. These agents appear to be promising not only in the prevention and treatment of ischemic heart disease, but also in avoiding cardiac damage in situations where low-flow states are followed by immediate recovery of flow, as in coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, thrombolytic therapy, and coronary arterial vasospasm. This article reviews the physiology of the NHE and analyzes the potential role of NHE inhibitors in the prevention of ischemic-reperfusion injury and other cardiac disease states.

Amiloride↗
PubMed1998

Chelation therapy in cardiovascular disease: ethylenediaminetetraacetic acid, deferoxamine, and dexrazoxane.

This review was conducted to assess whether there is sufficient evidence for the clinical use of chelation therapy in cardiovascular disease based on original articles and abstracts published in the last 30 years, with emphasis placed on the most recent placebo-controlled studies. Articles postulating the mechanisms of chelation also were included. The majority of the literature focused on three chelators in particular, ethylenediaminetetraacetic acid (EDTA), deferoxamine, and dexrazoxane (ICRF-187). Historically, much has been written on the beneficial effects of EDTA. However, there are few controlled studies, and the mechanism of action of EDTA is poorly understood. Although studies of deferoxamine are more recent, most of the research is limited to animals and ex vivo models. Recently, dexrazoxane was approved, but only for parenteral use for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer. Given these limitations, it is concluded that more controlled studies are required to determine the efficacy of chelation therapy in cardiovascular disease before it can be used broadly in the clinical setting.

Antibiotics, Antineoplastic↗
PubMed1998

Innovative drug treatments for viral and autoimmune myocarditis.

Myocarditis has been shown to be a common cause of cardiomyopathy and is believed to account for 25% of all cases in human beings. Unfortunately, the disease is difficult to detect before a myopathic process ensues. Treatment of myocarditis-induced heart failure includes the standard regimen of diuretics, digoxin, angiotensin-converting enzyme inhibitors, and currently, beta-adrenergic blockers. Treatment of myocarditis itself is dependent on the etiology of the illness. Treatments under investigation include immunosuppressants, nonsteroidal antiinflammatory agents, immunoglobulins, immunomodulation, antiadrenergics, calcium-channel blockers, angiotensin-converting enzyme inhibitors, nitric oxide inhibition (e.g., aminoguanidine), and antiviral agents. Despite advances in treatment, more work needs to be done in the early detection of myocarditis. Additionally, better means need to be established for distinguishing between viral and autoimmune forms of the disease, so that appropriate treatment can be instituted.

Adjuvants, Immunologic↗
PubMed1998

The sodium-calcium ion membrane exchanger: physiologic significance and pharmacologic implications.

The Na(+)-Ca2+ exchanger is a non-ATP-dependent protein that, under steady-state conditions, extrudes Ca2+ from the interior of the cell into the extracellular space via facilitated transport. The activity of the exchanger seems to be reduced in myocardial ischemia, leading to increased intracellular Ca2+ in the ischemic heart, which can result in arrhythmia, myocardial stunning, and necrosis. In contrast, congestive heart failure and myocardial hypertrophy are associated with increased exchanger activity and a decreased inotropic state. Pharmacologic agents are being developed to modulate sodium ion levels in the cell, which could enhance or reduce sodium-calcium exchange as needed in various pathophysiologic states. At this time there are no available drugs that act specifically on the Na(+)-Ca2+ exchanger itself. The exchanger has been cloned, and inhibitory peptides of the exchanger may soon be available for possible use in treatment of congestive heart failure.

Azetidines↗
PubMed1998

Use of angiotensin-converting enzyme inhibitors as monotherapy and in combination with diuretics and calcium channel blockers.

Angiotensin-converting enzyme (ACE) inhibitors have earned an important place in medical therapy since their discovery about two decades ago. This family of drug has grown tremendously since the introduction of captopril in 1981. There are currently more than 14 ACE inhibitors in the world and 9 are available in the United States. Although these agents share many similarities, they differ in their pharmacokinetic properties, approved indications, and cost. This paper provides guidance for selection of ACE inhibitors by examining the pharmacokinetics, pharmacodynamics, drug interactions, adverse effects, and cost of these agents. Combination products of ACE inhibitors with either diuretics or calcium channel blockers also are reviewed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Thyroid hormone and cardiovascular disease.

Thyroid hormone directly affects the heart and peripheral vascular system. The hormone can increase myocardial inotropy and heart rate and dilate peripheral arteries to increase cardiac output. An excessive deficiency of thyroid hormone can cause cardiovascular disease and aggravate many preexisting conditions. In severe systemic illness and after major surgical procedures changes in thyroid function can occur, leading to the "euthyroid sick syndrome." Patients will have normal or decreased levels of T4, decreased free and total T3, and usually normal levels of thyroid stimulating hormone. This syndrome may be an adaptive response to systemic illness that usually will revert to normal without hormone supplementation as the illness subsides. Recently, however, many investigators have explored the benefits of thyroid hormone supplementation in those diseases associated with euthyroid sick syndrome. Thyroid hormone's effects on the cardiovascular system make it an attractive therapy for those patients with impaired hemodynamics and low T3. Thyroid hormone has also been considered a treatment for patients with congestive heart failure, for patients undergoing cardiopulmonary bypass and heart transplantation, and for patients with hyperlipidemia. At present there is no evidence suggesting a favorable treatment outcome using thyroid hormone supplementation for any systemic condition except in those patients with documented hypothyroidism.

Cardiopulmonary Bypass↗
PubMed1998

Effects of verapamil and trandolapril in the treatment of hypertension. Trandolapril Study Group.

The combination of an angiotensin converting enzyme inhibitor with a calcium antagonist has become a common way of treating patients with essential hypertension who respond insufficiently to monotherapy. This double-blind, randomized, parallel, placebo-controlled, multicenter, outpatient study evaluated the antihypertensive efficacy and safety of a calcium antagonist (verapamil SR) and an angiotensin converting enzyme inhibitor (trandolapril) in patients with mild-to-moderate (stages I and II) essential hypertension. Six hundred thirty-one patients were enrolled in this 10-week study. After a 4-week single-blind placebo phase, patients received one of the following daily dosage regimens in a double-blind fashion for 6 weeks: placebo, 4 mg of trandolapril, 240 mg of verapamil SR, or a combination of 4 mg of trandolapril and 240 mg of verapamil SR. Trough sitting diastolic blood pressure was lowered by 4.5 mm Hg, 4.3 mm Hg, and 8.1 mm Hg more than placebo in the trandolapril, verapamil SR, and combination groups, respectively. In the combination group, sitting diastolic blood pressure was significantly lowered (P < .01) by 3.6 mm Hg more than in the trandolapril group and by 3.8 mm Hg more than in the verapamil SR group. An analysis of the trough-to-peak ratio for sitting diastolic blood pressure revealed values of 0.75 and 0.67, for the 4-mg trandolapril and the combination groups, respectively, at end point. The overall incidence of adverse reactions was similar for all treatment groups. In this study the combination of an angiotensin converting enzyme inhibitor and calcium antagonist was well tolerated and more effective than either agent administered alone for the treatment of mild-to-moderate essential hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Serum creatinine and blood urea nitrogen over a six-year period in the very old. Creatinine and BUN in the very old.

In a population of 141 very elderly subjects, there was a small but significant decline in BUN and creatinine at 3 years, which persisted at 6 years although partially attenuated. A similar pattern of falling BUN and creatinine was seen in the 31 subjects who began the study with mild azotemia. There was no significant change in the subjects' mean Body Mass Index during the 6-year period of observation. The azotemic subjects had a rate of death or dropout from the study similar to that of the entire cohort. Mean systolic blood pressure fell by 5.4 mm Hg (p < 0.05) and diastolic blood pressure by 2.1 mm Hg (p = NS) by 6 years. Users of diuretics or NSAID had a mean BUN and creatinine comparable to those not taking these medications. We conclude that BUN and serum creatinine do not necessarily increase with time in the old old, even in those with mild azotemia, hence, several determinations of these parameters may be needed to ensure accuracy. While renal function in the elderly probably does not improve with time, it may stabilize due to improvement in blood pressure. Use of diuretics and NSAID by functioning elderly individuals is not necessarily associated with worsening azotemia.

Aged↗
PubMed1998

Matrix metalloproteinases and abdominal aortic aneurysms: a potential therapeutic target.

Abdominal aortic aneurysm (AAA) is a leading cause of death in the United States, and there is no effective treatment in the early course of disease. Therapy to retard or reverse aneurysmal growth requires an understanding of the underlying vascular pathology. Recent research has indicated that enzymatic degradation of structural matrix proteins plays a large role in the formation of AAAs. Specifically, many studies have implicated a family of matrix degrading enzymes, known as matrix metalloproteinases (MMPs), as vital factors in the disease. Although AAA was once thought to be purely secondary to atherosclerosis, investigators have demonstrated various differences between the diseases in both levels and distribution of MMPs, suggesting independent mechanisms. Experimental models have shown that inhibition of these proteinases may slow aortic wall matrix breakdown. The purpose of this article is to review the current literature regarding the role of individual MMPs in AAA, including their complex regulatory mechanisms and possible cellular sources, the importance of MMPs as a potential therapeutic target in the prevention and treatment of AAA, and their inhibition using novel pharmacologic interventions in animal models.

Aortic Aneurysm, Abdominal↗
PubMed1998

Innovative pharmacologic approaches to cardiopulmonary resuscitation.

The survival rate of patients undergoing cardiopulmonary resuscitation (CPR) is 5% to 15%. New treatment approaches under investigation for CPR include the use of vasopressin as a vasopressor, amiodarone for the treatment of ventricular tachyarrhythmia, and adenosine antagonists (i.e., theophylline) for bradyasystolic rhythms. More innovative approaches include the use of thyroid hormone and endothelin.

Amiodarone↗