Journal of Cardiovascular Pharmacology and Therapeutics current issue

Intracoronary Abciximab Use in Patients Undergoing PCI at a Community Hospital: A Single Operator Experience

Patel, S. S., Rana, H., Mascarenhas, D. A. N. — 2008-05-21

Objective: To evaluate the safety of intracoronary (IC) abciximab during percutaneous coronary intervention (PCI). Background: Adjunctive treatment with glycoprotein IIb/IIIa inhibitors, especially abciximab, during PCI has been shown to improve clinical and procedural outcomes in numerous studies. However, significant bleeding complications exist with its use and this has limited its standard use. Interest has grown in local (IC) use with studies showing safety and long-term effectiveness, especially in patients with high thrombus loads. Methods: A retrospective review of records in a database of patients who had PCI by a single operator at the Easton Hospital. Results: 611 patients received IC abciximab, and there were no complications in 610 (98.3%) patients; only 1 had an allergic reaction. Conclusions: IC abciximab is safe and has a unique role in the catheterization lab and in patients at high risk of bleeding complications who would benefit from its limited use.

Oral Midodrine Is Effective for the Treatment of Hypotension Associated With Carotid Artery Stenting

Sharma, S., Lardizabal, J. A., Bhambi, B. — 2008-05-21

Hypotension is commonly encountered during carotid artery stenting (CAS), mediated by vagal stimulation and suppression of sympathetic outflow. Some patients require treatment with intravenous vasopressors (dopamine, nor-epinephrine, or phenylephrine). The authors describe the successful use of the oral agent midodrine as an alternative to intravenous vasopressors in the treatment of hypotension related to CAS. Of 55 patients who underwent elective CAS, 19 (35%) experienced significant hypotension, and 15 (27%) required vasopressor therapy. Eleven patients received intravenous dopamine infusion in an intensive care setting, whereas 4 received oral midodrine in a regular telemetry unit. All patients eventually recovered and were discharged without any residual cardiovascular or neurological complications. No major side effects were noted with the use of both dopamine and midodrine. Cost of hospitalization was significantly higher in the dopamine group because of the need for ICU admission.

Effects of Nitric Oxide and Noradrenergic Activation in the Posterior Hypothalamus on Arterial Pressure Tolerance to Nitroglycerin in Rats

Guettler, D. L., Ma, S.-X. — 2008-05-21

The effects of nitric oxide (NO) and noradrenergic activation in the posterior hypothalamus on arterial pressure tolerance induced by subcutaneous injection of nitroglycerin (NTG) was investigated in anesthetized Sprague-Dawley rats. Intravenous injections of NTG (3, 10, and 30 µg/kg) and sodium nitroprusside (1, 3, and 10 µg/kg) produced dose-dependant decreases in arterial blood pressure. Tolerance to NTG was produced by subcutaneous administration of 4.0 mg of NTG as 4 separate hourly injections of 1.0 mg each, affecting the dose-dependent response of NTG IV injection. The 4 high-dose NTG pulse injections produced a marked shift in the dose—response curves for arterial pressure depression induced by intravenous injection of the challenge doses of NTG, but did not alter hypotensive responses to sodium nitroprusside. The tolerance responses to arterial pressure depression were enhanced by a bilateral microinjection of NTG (1 nmol) and by diethylamine NONOate (1 nmol), an NO donor, into the posterior hypothalamus. Bilateral microinjection of guanethidine (1.5 nmol), a noradrenergic blocker, into the posterior hypothalamus inhibits NTG tolerance in a period of time within 2 hours. We conclude that exogenous NO and noradrenergic activation in the posterior hypothalamus play an important role in arterial pressure tolerance to systemically administered NTG.

Pharmacoeconomic Concepts in Antiplatelet Therapy: Understanding Cost-Effectiveness Analyses Using Clopidogrel as an Example

Weintraub, W. S. — 2008-05-21

The rising cost of drug therapy has been accompanied by demands from payers for pharmacoeconomic studies to assess the value for money of new treatments.There are 5 types of such analyses: cost analysis (evaluates only costs); cost minimization (compares costs of treatments with identical outcomes); cost-effectiveness (evaluates the cost of treatment in relation to clinical benefit to derive a cost per outcome); cost utility (evaluates cost of treatment in relation to survival adjusted for quality of life,) and cost benefit (evaluates all clinical outcomes, such as prolonged life, in monetary terms). The most commonly used are cost-effectiveness and cost utility. The aim of this article is to provide the nonexpert reader with a basic understanding of these analyses, using pharmacoeconomic evaluations of clopidogrel for acute coronary syndromes as examples. Greater clinician understanding of pharmacoeconomic principles (and pitfalls) will enhance input of the physicians into the decision-making process to maximize the benefit of limited health care resources.

The Protective Effect of Bergamot Oil Extract on Lecitine-like OxyLDL Receptor-1 Expression in Balloon Injury-related Neointima Formation

2008-05-21

Lectin-like oxyLDL receptor-1 (LOX-1) has recently been suggested to be involved in smooth muscle cell (SMC) proliferation and neointima formation in injured blood vessels. This study evaluates the effect of the nonvolatile fraction (NVF), the antioxidant component of bergamot essential oil (BEO), on LOX-1 expression and free radical generation in a model of rat angioplasty. Common carotid arteries injured by balloon angioplasty were removed after 14 days for histopathological, biochemical, and immunohistochemical studies. Balloon injury led to a significant restenosis with SMC proliferation and neointima formation, accompanied by increased expression of LOX-1 receptor, malondialdehyde and superoxide formation, and nitrotyrosine staining. Pretreatment of rats with BEO-NVF reduced the neointima proliferation together with free radical formation and LOX-1 expression in a dose-dependent manner. These results suggest that natural antioxidants may be relevant in the treatment of vascular disorders in which proliferation of SMCs and oxyLDL-related endothelial cell dysfunction are involved.

Physiologic Properties and Regulation of the Actin Cytoskeleton in Vascular Smooth Muscle

Tang, D. D., Anfinogenova, Y. — 2008-05-21

Vascular smooth muscle tone plays a fundamental role in regulating blood pressure, blood flow, microcirculation, and other cardiovascular functions. The cellular and molecular mechanisms by which vascular smooth muscle contractility is regulated are not completely elucidated. Recent studies show that the actin cytoskeleton in smooth muscle is dynamic, which regulates force development. In this review, evidence for actin polymerization in smooth muscle upon external stimulation is summarized. Protein kinases such as Abelson tyrosine kinase, focal adhesion kinase, Src, and mitogen-activated protein kinase have been documented to coordinate actin polymerization in smooth muscle. Transmembrane integrins have also been reported to link to signaling pathways modulating actin dynamics. The roles of Rho family of the small proteins that bind to guanosine triphosphate (GTP), also known as GTPases, and the actin-regulatory proteins, including Crk-associated substrate, neuronal Wiskott-Aldrich Syndrome protein, the Arp2/3 complex, and profilin, and heat shock proteins in regulating actin assembly are discussed. These new findings promote our understanding on how smooth muscle contraction is regulated at cellular and molecular levels.

Ischemic Postconditioning's Benefit on Reperfusion Ventricular Arrhythmias Is Maintained in the Senescent Heart

Dow, J., Bhandari, A., Kloner, R. A. — 2008-05-21

The purpose of this study is to determine if postconditioning's beneficial effect on ventricular arrhythmias is maintained in elderly hearts. In elderly populations, the cardioprotective effects of ischemic preconditioning are lost. Previously, the authors observed that ischemic postconditioning markedly reduced reperfusion-induced ventricular arrhythmias in adult rats. Whether this benefit is maintained in senescent hearts is unknown. Here, the authors study young adult rats compared with senescent animals. They chose 24-month-old Fischer female rats as these rats are approaching the end of their normal life span. Unlike some studies that suggest that the benefits of preconditioning and postconditioning are lost in the elderly, their data show that antiarrhythmic protection conferred by postconditioning is present in both the young and old rats.