Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 9, Issue 4, 2011

Deep venous thrombosis (DVT) with its associated complications of pulmonary embolism and postthrombotic syndrome are an important cause of morbidity and mortality. This review article provides an overview of the pathophysiology, risk factors and the guidelines for thromboprophylaxis. It also reviews the available modalities in the diagnosis and treatment of DVT. The newer methods of treatment are also discussed.

Objective: Long-term co-administration of morphine and calcium channel antagonists (CCAs) is likely in some clinical conditions. Reciprocal interactions during chronic concomitant use of these agents are confirmed in central nervous system studies. However, there is little information regarding their chronic combination effects on the cardiovascular system. Present study was designed to assess the effects of chronic co-administration of morphine plus verapamil on some cardiovascular indices of rats with / without myocardial damage. Methods: Animals were divided to control, morphine, verapamil and morphine plus verapamil groups each consisted of two subgroups, with and without heart injury. Rats were treated with increasing doses of morphine (10-20mg/kg, i.p.) or morphine plus verapamil (10mg/kg, i.p.) daily for 7 days. Heart injury was induced by isoproterenol (50 mg/kg, i.p.), then cardiac Troponin I was measured and on day 8, blood pressure and heart rate was recorded and then the hearts were histopathologically examined. Results: The results indicated that co-administration of morphine with verapamil has stronger cardioprotective effect than morphine or verapamil alone as confirmed by the lower Troponin I level and myocardial lesion grades. However, no additional effects on mean arterial pressure and Rate-Pressure product were observed in combined use of these drugs. Conclusion: These findings suggest chronic co-administration of morphine and verapamil induced additive protective effects on rat heart exposed to myocardial injury comparing with each of them alone.

Diabetes has emerged as a major threat to worldwide health. The increasing incidence of diabetes in young individuals is particularly worrisome given that the disease is likely to evolve over a period of years. In 1972, the existence of a diabetic cardiomyopathy was proposed based on the experience with four adult diabetic patients who suffered from congestive heart failure in the absence of discernible coronary artery disease, valvular or congenital heart disease, hypertension, or alcoholism. The exact mechanisms underlying the disease are unknown; however, there is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Hyperglycemiainduced oxidative stress is a major risk factor for the development of micro-vascular pathogenesis in the diabetic myocardium, which results in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium homeostasis and endothelial dysfunction. In this review, we provide the emergence of experimental evidence supporting antioxidant supplementation as a cardioprotective intervention in the setting of diabetic cardiomyopathy.

Antiplatelet therapy is of paramount importance in the treatment and prevention of adverse cardiovascular events and stroke. Drug-drug interactions (DDIs) among antiplatelet therapies have been growing in both prevalence and clinical importance. Most DDIs with antiplatelet therapies are pharmacodynamic in nature. DDIs with thienopyridines and proton pump inhibitors have resulted in advisories from regulatory agencies although the full significance of this interaction is unknown. Other DDIs with thienopyridines may potentially exist with statins, calcium channel blockers, and warfarin but lack demonstratable evidence of harm. Aspirin may interact with a variety of medications, including non-steroidal anti-inflammatory agents and angiotensin inhibitors. DDIs requiring some level of intervention may also be present with dipyridamole and cilostazol. Overall, DDIs with antiplatelet drugs are biologically plausible and potentially clinically relevant. However, the full significance of these DDIs is largely unknown due to reliance on research of voluntary reports, registries, and claims databases to determine significance.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in hemodialysis (HD) patients. Hypertension (HT) is a major risk factor for CVD. The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of HT in HD patients. Previous studies suggested that the blockade of RAAS may be effective to control blood pressure (BP) and to prevent CVD in HD patients. A certain level of preventive effects against CVD by RAAS blockade in HD patients has been reported independently from a BP lowering effect. This review focuses on the effect of blocking RAAS in HD patients for the control of HT and the prevention of CVD

Contrast-induced acute kidney injury is one of the leading causes of hospital-acquired acute kidney injury. Thus far, no strategies have been clearly shown to be effective in preventing contrast-induced acute kidney injury beyond thorough patient selection, meticulous hydration of the patient, and minimizing the amount of contrast used. Additional studies are needed to define the optimal means of hydration, role of commonly advocated prophylaxis strategies such as N-acetylcysteine and develop newer more novel effective therapies to prevent or minimize the risk of kidney injury.

A genetic component of diabetes and its complications (including diabetic nephropathy (DN)) is obvious, but the causative genes and mechanisms have not yet been satisfactorily identified. Oxidative stress is a single mechanism relating all major pathways responsible for diabetic damage. Numerous oxidative stress-related genes are positional candidates (determined by GWAS) and candidate genes studies confirm the association of their polymorphisms with DN. We present here their overview and connection to the “new antioxidant” therapy principle.

Study Objective: To evaluate the effectiveness of our institution's heparin-induced thrombocytopenia (HIT) protocol in achieving a therapeutic activated partial thromboplastin time (aPTT) and to evaluate patient outcomes related to bleeding and thrombotic events before and after protocol implementation. Design: Retrospective, single-center, pre- and post- assessment of a protocol previously approved at our institution. Setting: 400-bed community hospital serving surrounding rural populations with emphasis in cardiothoracic surgery. Patients: Retrospective chart review based on drug charge data identified 29 patients that received either argatroban or lepirudin for greater than 24 hours. Nineteen patients received either argatroban or lepirudin prior to HIT-protocol implementation, while the remaining ten received either drug after the HIT protocol was implemented. Intervention: Implementation of HIT protocol occurred in March 2009. Patients were divided into pre-protocol and post-protocol groups. Results: Primary outcome was to evaluate the number of therapeutic, subtherapeutic, and supratherapeutic aPTTs between two groups. In the pre-protocol group, aPTTs were therapeutic, subtherapeutic, and supratherapeutic 48.5% (164/338), 14.2% (48/338), and 37.2% (126/338) of the time, respectively. Meanwhile aPTTs in the post-protocol group were therapeutic, subtherapeutic, and supratherapeutic 46.6% (89/191), 22% (42/191), and 31.4% (60/191) of the time, respectively. The number of subtherapeutic aPTTs was statistically higher in the post-protocol group compared to the pre-protocol group. Secondary endpoints included the number of bleeding events and number of thrombotic events. None of the secondary endpoints reached statistical significance. Time to therapeutic aPTT was also evaluated: in the pre-protocol group median time (range) was 15 hours (2-108.6) compared to 8.1 hours (2.3-94.2) in the post-protocol group. Conclusions: Adoption and implementation of HIT protocol at our institution resulted in significantly more subtherapeutic aPTTs as compared to time prior to protocol. Although not statistically significant, the time required to obtain therapeutic aPTT was reduced by almost 50% after protocol implementation, which could be of clinical importance. Larger studies are needed to continue to assess if standardized protocols are effective in treatment of HIT.

Medical, percutaneous interventional, and surgical treatments for the management of coronary heart disease have progressed markedly during the past decade. There is evidence to suggest that for patients with stable coronary heart disease optimal medical therapy is equal in effectiveness for lowering the risk of major cardiovascular events, such as cardiovascular death, myocardial infarction, and stroke, as are revascularization procedures, such as coronary artery bypass grafting or percutaneous coronary intervention. The landmark Surgical Treatment for Ischemic Heart Failure (STICH) trial found no significant difference between medical therapy alone and medical therapy plus coronary artery bypass grafting with respect to the primary end point of death from any cause (all-cause mortality). However, secondary outcomes showed fewer deaths from cardiovascular causes in the surgical group versus the medical group. Medical therapy has improved over time, as have surgical techniques including myocardial preservation, and both approaches have their place, especially since chest pain relief and quality of life may benefit more in some cases by revascularization. Certainly, coronary artery bypass grafting has general acceptance for three-vessel coronary heart disease, and percutaneous coronary artery intervention is the standard of care for the involved artery in acute ST-segment elevation myocardial infarction when the intervention can be accomplished rapidly. Medical management includes lifestyle changes that benefit coronary heart disease, drug therapy to improve prognosis, and drug therapy to improve symptoms. The key to clinical management is the selection of the procedure and/or medical management strategy that is in the best interest of the individual cardiovascular patient. In addition, discussing with patients their options and considering what best fits their wishes is especially critical when there is no clear-cut best strategy. Continued collaboration between cardiologists concentrating on medical approaches with interventionists and cardiac surgeons (heart team approach) is essential for optimal management for each individual patient.