Agents For Cardiovascular Diseases Research Articles

Elevated toxicant yields with narghile waterpipes smoked using a plastic hose

The effect of hose permeability on toxicant yields for the narghile waterpipe is investigated, with special reference to the recent adoption of plastic as a hose construction material. Measurements of air infiltration rates for 23 leather and plastic hoses representing 11 types commonly available in Beirut, Lebanon were made, revealing that while leather hoses allowed significant outside air infiltration during a puff constituting up to 31% of the puff volume, plastic hoses were found to be air-tight, indicating that the smoke reaching the waterpipe user can be considerably more concentrated when delivered via a plastic hose. Total particulate matter (TPM), nicotine and carbon monoxide (CO) yields were compared when a waterpipe was machine smoked using a highly permeable leather and an air-tight plastic hose. It was found that the plastic hose resulted in similar yields of nicotine, but more than double the CO yielded with the highly permeable leather hose. Thus, even if narghile smokers titrate for nicotine intake, the use of a plastic hose will likely greatly increase the exposure to CO, a major causative agent in cardiovascular disease.

Cannabinoids as therapeutic agents in cardiovascular disease: a tale of passions and illusions

In addition to their classical known effects, such as analgesia, impairment of cognition and learning and appetite enhancement, cannabinoids have also been related to the regulation of cardiovascular responses and implicated in cardiovascular pathology. Elevated levels of endocannabinoids have been related to the extreme hypotension associated with various forms of shock as well as to the cardiovascular abnormalities that accompany cirrhosis. In contrast, cannabinoids have also been associated with beneficial effects on the cardiovascular system, such as a protective role in atherosclerosis progression and in cerebral and myocardial ischaemia. In addition, it has also been suggested that the pharmacological manipulation of the endocannabinoid system may offer a novel approach to antihypertensive therapy. During the last decades, the tremendous increase in the understanding of the molecular basis of cannabinoid activity has encouraged many pharmaceutical companies to develop more potent synthetic cannabinoid analogues and antagonists, leading to an explosion of basic research and clinical trials. Consequently. not only the synthetic THC dronabinol (Marinol) and the synthetic THC analogue nabilone (Cesamet) have been approved in the United States, but also the standardized cannabis extract (Sativex) in Canada. At least three strategies can be foreseen in the future clinical use of cannabinoid-based drugs: (a) the use of CB(1) receptor antagonists, such as the recently approved rimonabant (b) the use of CB(2)-selective agonists, and (c) the use of inhibitors of endocannabinoid degradation. In this context, the present review examines the effects of cannabinoids and of the pharmacological manipulation of the endocannabinoid system, in cardiovascular pathophysiology.

Anticoagulants in heart disease: current status and perspectives

Drugs interfering with blood coagulation are a mainstay of cardiovascular therapy. Despite their widespread use, there are a number of unmet needs for current parenteral and oral anticoagulants in cardiovascular diseases. This therapeutic area is undergoing unprecedented changes with the clinical introduction of new drugs. This document, initiated by a committee appointed by the European Society of Cardiology (ESC) Working Group on Thrombosis, intends therefore: This document is intended to follow-up on the Task Force Document on the use of antiplatelet agents in cardiovascular disease, proposed by the committee of experts appointed similarly by the ESC Working Group on Thrombosis1 and is intended to be regularly updated. The Writing Committee of this document has decided against issuing graded recommendations on the use and dosing of drugs, because this might conflict with the task of guidelines, some of which are being finalized at the same time by the ESC. ### Haemostasis When a blood vessel is damaged, the site of disruption must be rapidly sealed to prevent blood loss. Haemostasis requires the formation of an impermeable platelet and fibrin plug at the site of injury. Preventing clot propagation through the …

Brain type natriuretic peptide (BNP)-A marker of new millennium in diagnosis of congestive heart failure.

The burden of disease in patients with congestive heart failure is high. The future of BNP looks promising as it may be a better diagnostic tool for the diagnosis of CHF in developing countries in new millennium. Natriuretic peptide hormones, a family of vasoactive peptides with many favourable physiological properties, have emerged as important contenders for development of diagnostic tools and therapeutic agents in cardiovascular disease. Measurement of B-type natriuretic peptide has become as an easy-to-perform bedside test. The clinical and diagnostic significance of the measurement of plasma Nt-proBNP in the diseases of the cardiovascular system with particular emphasis on the assessment of patients with heart failure and their effects on predicting survival rate. The plasma levels of Nt-proBrain Natriuretic peptide responds more vigorously after myocardial infarction than those of other natriuretic peptides. This article is an attempt to give a short overview on the utility of BNP-blood levels for the diagnosis and treatment of heart failure.

Novel modulators of poly(ADP-ribose) polymerase

The nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 has an important role in regulating cell death and cellular responses to DNA repair. Pharmacological inhibitors of PARP have entered clinical testing as cytoprotective agents in cardiovascular diseases and as adjunct antitumor therapeutics. Initially, it was assumed that the regulation of PARP occurs primarily at the level of DNA breakage: recognition of DNA breaks was considered to be the primary regulator (activator) or the catalytic activity of PARP. Recent studies have provided evidence that PARP-1 activity can also be modulated by several endogenous factors, including various kinases, purines and caffeine metabolites. There is a gender difference in the contribution of PARP-1 to stroke and inflammatory responses, which is due, at least in part, to endogenous estrogen levels. Several tetracycline antibiotics are also potent PARP-1 inhibitors. In this article, we present an overview of novel PARP-1 modulators.

Uric Acid Is a Risk Factor for Myocardial Infarction and Stroke

The role of uric acid as a risk factor for myocardial infarction is controversial, and little is known about its role as a risk factor for stroke. Recent evidence suggests that uric acid may be an important causal agent in cardiovascular disease, for example, by inducing renal disease and hence hypertension. We investigated the association between serum uric acid and coronary heart disease and stroke in a large prospective population-based study. The study was based on 4385 participants of the Rotterdam Study who, at baseline (1990 to 1993), were > or =55 years of age, free from stroke and coronary heart disease, and had blood taken. Follow-up for incident stroke and myocardial infarction was complete until January 1, 2002. Data were analyzed with Cox proportional hazards models with adjustment for relevant confounders. Average follow-up was 8.4 years. High serum uric acid levels were associated with risk of myocardial infarction and stroke; age- and sex-adjusted hazard ratios (95% CIs) for highest versus lowest quintile of uric acid were 1.68 (1.24 to 2.27) for cardiovascular disease (515 cases), 1.87 (1.12 to 3.13) for myocardial infarction (194 cases), 1.57 (1.11 to 2.22) for stroke (381 cases), 1.77 (1.10 to 2.83) for ischemic stroke (205 cases), and 1.68 (0.68 to 4.15) for hemorrhagic stroke (46 cases). Adjustment for other vascular risk factors only slightly attenuated these associations. Associations were stronger in persons without hypertension than in those with hypertension. Uric acid is a strong risk factor for myocardial infarction and stroke.

Pharmacokinetic, Tissue Distribution, and Excretion of Puerarin and Puerarin-Phospholipid Complex in Rats

ABSTRACTPuerarin is a potential therapeutic agent for cardiovascular diseases. But its poor oral bioavailability restricts its clinical application. In present study, as an evaluation of a formulation to improve the bioavailability of the drug, puerarin and its phospholipid complex were given to rats by intragastrically (i.g.) administration to compare pharmacokinetic, tissue distribution, and excretion. Serum samples were obtained at designated times after a single oral dose of 400 mg/kg puerarin or its complex. Tissue samples (heart, liver, spleen, kidney, lung, and brain), urine, and feces were collected and analyzed by a sensitive and specific high performance liquid chromatography (HPLC) method after i.g. administration of puerarin or its phospholipid complex. Compartmental and non-compartmental analyses were applied to the serum concentration versus time data. Pharmacokinetic parameters were calculated using the 3P97 pharmacokinetic software package. An open two-compartment, first-order model was selected for pharmacokinetic modeling. The results showed that after i.g. administration of 400 mg/kg puerarin and its phospholipid complex (equivalent to 400 mg/kg of puerarin), the pharmacokinetic parameters of the two formulations were different. The serum concentrations reached peaks at 0.894 ± 0.521 h and 0.435 ± 0.261 h, respectively, indicating the complex was more readily absorbed in serum than puerarin. The maximum concentrations for puerarin and its complex were 1.367 ± 0.586 mg·L−1 and 2.202 ± 1.28 mg·L−1 and AUC were 5.779 ± 1.662 mg·h. L−1 and 8.456 ± 0.44 mg·h L−1, respectively, indicating a higher bioavailability for the complex. The widely distribution characteristics of puerarin and its complex in tissues post-i.g. administration was identical and in a descending order as follows: lung, kidney, liver, heart, spleen, and brain. However, the amount was different. Puerarin distribution was higher in heart, lung, and brain after administering the complex. The cumulative 72 h urinary excretion of puerarin after i.g. administration of puerarin and its complex accounted for 1.05%, 1.11% of the administered dose, respectively. The cumulative feces excretion of puerarin was 32.3% and 25.5%. To sum up, oral administration of puerarin phospholipid complex modified the pharmacokinetics and tissue distribution of puerarin and it could be an effective oral formulation for puerarin.

Short-term, Moderate Dosage Vitamin E Supplementation May Have No Effect on Platelet Aggregation, Coagulation Profile, and Bleeding Time in Healthy Individuals

To investigate the in vivo effect of short-term, moderate dosage synthetic dl-alpha-tocopherol acetate supplementation on platelet aggregation, coagulation profile, and simulated bleeding time in healthy individuals. alpha-tocopherol is the most biologically active isomer of Vitamin E, traditionally promoted as an antioxidant and therapeutic agent in cardiovascular disease. In vitro studies have suggested that alpha-tocopherol plays a role in the inhibition of platelet aggregation. However, further investigations into the effect of alpha-tocopherol on bleeding in vivo have not duplicated these findings. A total of 42 healthy volunteers complied with a 2-week abstinence period from the use of anti-platelet agents followed by determination of baseline platelet aggregation properties and coagulation studies using citrated whole blood. Moderate dosage Vitamin E (800 IU of dl-alpha-tocopherol acetate) was then self-administered for 14 days with reevaluation of platelet aggregation and coagulation profile, and simulated bleeding time after 14 days of Vitamin E supplementation. Forty subjects completed the 4-week study period. All 40 subjects demonstrated normal baseline coagulation studies and all had collagen-stimulated platelet aggregation assessment performed in triplicate. After Vitamin E supplementation, no significant difference was demonstrated in any study parameter. Dietary supplementation with moderate dosage synthetic dl-alpha-tocopherol acetate did not significantly prolong bleeding or platelet aggregation in vivo. The affect of Vitamin E on platelet aggregation in vitro does not appear to be reproducible in vivo. Therefore, peri-operative discontinuation of Vitamin E may not be necessary.

Brain and other natriuretic peptides: molecular aspects.

Natriuretic peptides have emerged as important candidates for development of diagnostic tools and therapeutic agents in cardiovascular disease. The family contains of three major peptides-ANP, BNP, CNP-that participate in cardiovascular and cardiorenal homeostasis. Each of these natriuretic peptides binds differentially to specific receptors that signal through different mechanisms. They are cleared enzymatically by neutral endopeptidase as well as by receptor-mediated endocytosis. Because of its fast induction and specific expression in overt heart failure, BNP seems the most promising natriuretic peptide. It is predominantly synthesized in the cardiac ventricles, released as pre-proBNP and then enzymatically cleaved to BNP and the N-terminal portion of BNP(NT-proBNP). Blood measurements of BNP and NT-proBNP have been shown to identify patients with LV dysfunction. This review focuses on the physiology of natriuretic peptides as a group and brain natriuretic peptide in more detail, its structure and regulation as well as its effects at the cellular level.

Le peptide natriurétique de type b

Introduction. – B-type natriuretic peptide is a neurohormone synthesized in the cardiac ventricles upon ventricular pressure overload and ventricular dilatation. This peptide with many favourable physiological properties has emerged as important candidate for development of diagnosis and prognostic tools and therapeutic agents in cardiovascular disease. Exegesis. – Literature published until now shows the interest to measure B-type natriuretic peptide in the diagnosis of ventricular dysfunction or congestive heart failure. B-type natriuretic peptide is also a prognostic marker in patients with congestive heart failure and acute coronary syndrome. It could even help to guide patient treatment management. It is easily and rapidly measured at a reasonable cost. In general, a level less than 50 ng/l has a strong negative predictive value for congestive heart failure. Conclusion. – B-type natriuretic peptide is available in daily clinical practice. Future interest has focused on development of drugs that modulate its effects in treatment of decompensated congestive heart failure. Studies are in progress and first results seem to be promising.

The Endocrine Heart: B-type Natriuretic Peptide as a Diagnostic and Therapeutic Agent in Cardiovascular Disease

Since their discovery 20 years ago, natriuretic peptides have rapidly moved to the forefront in cardiovascular medicine, and have contributed to an appreciation that the heart is an important endocrine organ. Of the natriuretic peptides, brain (B-type) natriuretic peptide (BNP) has proven to be the most clinically useful. Physicians now measure circulating levels of BNP and the Nterminal fragment of its prohormone (N-proBNP) for diagnostic and prognostic assessment in patients with suspected congestive heart failure (CHF), and administer recombinant human BNP as a therapeutic agent for patients with decompensated CHF. This review will highlight the mechanisms of natriuretic peptide regulation, the physiologic actions of BNP, and its utilization in patients with cardiovascular diseases.

Antiplatelet and Anticoagulant Agents in Cardiovascular Disease: Basic Research and Clinical Applications

Antiplatelet and Anticoagulant Agents in Cardiovascular Disease: Basic Research and Clinical Applications

FOREWORD

This issue of Seminars in Vascular Medicine is dedicated to antiplatelet and anticoagulant agents in cardiovascular disease and produced in a joint effort by Guest Editors Dr. Schrör, pharmacologist, and Dr. Gawaz, cardiologist.

Natriuretic Peptides as a Diagnostic and Therapeutic Tool in Cardiovascular Disease

The natriuretic peptides are a family of vasoactive peptides with many favourable physiological properties. In recent years the peptides have emerged as important candidates for the development of diagnostic tools and therapeutic agents in cardiovascular disease. Natriuretic peptides play a key role in the regulation of salt and water balance, cell growth, as well as blood pressure homeostasis. They are one of the body’s major defence mechanisms against excessive salt and water retention, and high blood pressure. In particular, atrial natriuretic peptides are involved in the pathophysiology of hypertension and heart failure. Several therapeutic approaches are under development to augment the biological actions of the system. Vasopeptidase inhibitors, which inhibit the breakdown of natriuretic peptides by neutral endopeptidase, are a promising therapeutic tool in the treatment of patients with cardiovascular conditions such as hypertension and congestive heart failure. This paper summarises the pathophysiological aspects of the natriuretic family of peptides in major cardiovascular conditions and looks at the latest therapeutic use of drugs that increase natriuretic peptides levels.

Expression of immunoregulatory cytokines by recombinant coxsackievirus B3 variants confers protection against virus-caused myocarditis.

Clinical and laboratory investigations have demonstrated the involvement of viruses and bacteria as potential causative agents in cardiovascular disease and have specifically found coxsackievirus B3 (CVB3) to be a leading cause. Experimental data indicate that cytokines are involved in controlling CVB3 replication. Therefore, recombinant CVB3 (CVB3rec) variants expressing the T-helper-1 (T(H)1)-specific gamma interferon (IFN-gamma) or the T(H)2-specific interleukin-10 (IL-10) as well as the control virus CVB3(muIL-10), which produce only biologically inactive IL-10, were established. Coding regions of murine cytokines were cloned into the 5' end of the CVB3 wild type (CVB3wt) open reading frame and were supplied with an artificial viral 3Cpro-specific Q-G cleavage site. Correct processing releases active cytokines, and the concentration of IFN-gamma and IL-10 was analyzed by enzyme-linked immunosorbent assay and bioassays. In mice, CVB3wt was detectable in pancreas and heart tissue, causing massive destruction of the exocrine pancreas as well as myocardial inflammation and heart cell lysis. Most of the CVB3wt-infected mice revealed virus-associated symptoms, and some died within 28 days postinfection. In contrast, CVB3rec variants were present only in the pancreas of infected mice, causing local inflammation with subsequent healing. Four weeks after the first infection, surviving mice were challenged with the lethal CVB3H3 variant, causing casualties in the CVB3wt- and CVB3(muIL-10)-infected groups, whereas almost none of the CVB3(IFN-gamma)- and CVB3(IL-10)-infected mice died and no pathological disorders were detectable. This study demonstrates that expression of immunoregulatory cytokines during CVB3 replication simultaneously protects mice against a lethal disease and prevents virus-caused tissue destruction.

Trials of the use of antimicrobial agents in cardiovascular diseases

This era of rapidly expanding emergence of resistant bacteria and societal trends that limit the duration of hospitalization has spurred the reevaluation of patterns of use of antimicrobial agents in many therapeutic and preventive settings. In the sphere of cardiac infectious disease this has given impetus to work in the following four areas: 1. Reassessment of the risks of infective endocarditis (IE) after invasive procedures with a goal of maximizing the benefits of antimicrobial prophylaxis in select populations. 2. Refinement of the criteria that is used to establish the diagnosis of endocarditis, particularly in children and in patients with culture-negative disease, and identification of patients with staphylococcal bacteremia who are most likely to have established an endocardial focus of infection and therefore require antimicrobial regimens of longer duration. 3. Determination of the efficacy of new therapeutic regimens in IE that adapt to socioeconomic trends for shorter hospitalization, compensate for the unreliability of intravenous therapy in intravenous drug abusers, and deal with the emergence of highly resistant organisms. 4. Exploration of the role of infectious agents (ie, Chlamydia pneumoniae) in the etiology of atherosclerosis and the usefulness of intervention with antimicrobial therapy in modifying the disease outcomes.

Workshop on the Potential Role of Infectious Agents in Cardiovascular Disease and Atherosclerosis

Workshop on the Potential Role of Infectious Agents in Cardiovascular Disease and Atherosclerosis

Effects of aspirin on endothelial dysfunction in atherosclerosis

The beneficial effects of aspirin in decreasing ischemic events have been largely attributed to its activity in inhibiting platelet aggregation, an effect achieved by irreversible inhibition of cyclo-oxygenase and prevention of the formation of the platelet aggregation agonist thromboxane. 1 Fuster V. Dyken M.L. Vokonas P.S. Hennekens C. Aspirin as a therapeutic agent in cardiovascular disease. Circulation. 1993; 87: 659-675 Crossref PubMed Scopus (219) Google Scholar Whether aspirin exerts beneficial effects on endothelial function in addition to its antiplatelet effect remains a matter of investigation; aspirin has been shown to inhibit production of the vasodilator prostanoid prostacyclin in endothelial cells. In healthy vessels, acetylcholine induces endothelium-dependent vasodilation that is believed to be largely mediated by release of nitric oxide (NO) and endothelium-derived hyperpolarizing factor. In the presence of atherosclerosis or its risk factors, response to acetylcholine is either a decreased vasodilator effect or paradoxical vasoconstriction; this effect has been attributed to decreased activity of endothelium-derived vasodilators. 2 Vanhoutte P.M. The endothelium modulator of vascular smooth muscle tone. N Engl J Med. 1988; 319: 512-513 Crossref PubMed Scopus (245) Google Scholar However, there is evidence that acetylcholine may also induce production of cyclo-oxygenase-dependent vasodilator and vasoconstrictor substances. Acetylcholine-induced production of vasoconstrictor prostaglandins has been observed in numerous animal studies, including animal models of endothelial dysfunction, hypertension, diabetes, and congestive heart failure. 3 Lscher T.F. Diedrich D. Weber E. Vanhoutte P.M. Bhler F.R. Endothelium-dependent responses in carotid and renal arteries of normotensive and hypertensive rats. Hypertension. 1988; 11: 573-578 Crossref PubMed Scopus (138) Google Scholar , 4 Kaiser L. Spickard R.C. Olivier N.B. Heart failure depresses endothelium-dependent responses in canine femoral artery. Am J Physiol. 1989; 256: H962-H967 PubMed Google Scholar In humans, cyclo-oxygenase inhibition with indomethacin was found to improve acetylcholine-induced vasodilation in congestive heart failure patients. 5 Katz S.D. Schwarz M. Yuen J. LeJemtel T.H. Impaired acetylcholine-mediated vasodilation in patients with congestive heart failure role of endothelium-derived vasodilating and vasoconstricting factors. Circulation. 1993; 88: 55-61 Crossref PubMed Scopus (211) Google Scholar Although most studies have shown no effect of cyclo-oxygenase inhibition on the acetylcholine response in diabetic or hypertensive patients, 6 Linder L. Kiowski W. Bhler F.R. Lscher T.F. Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo blunted response in essential hypertension. Circulation. 1990; 81: 1762-1767 Crossref PubMed Scopus (766) Google Scholar , 7 Calver A. Collier J. Vallance P. Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin-dependent diabetes. J Clin Invest. 1992; 90: 2548-2554 Crossref PubMed Scopus (492) Google Scholar one report has indicated that acetylcholine induces the release of vasoconstrictor prostaglandins in the forearm circulation of patients with hypertension. 8 Taddei S. Virdis A. Mattei P. Salvetti A. Vasodilation to acetylcholine in primary and secondary forms of human hypertension. Hypertension. 1993; 21: 929-933 Crossref PubMed Scopus (519) Google Scholar We performed studies in patients with atherosclerosis to assess whether an endothelium-derived, cyclo-oxygenase-dependent constrictor substance contributes to the abnormal acetylcholine response and whether aspirin might reverse this activity. 9 Husain S. Andrews N.P. Mulcahy D. Panza J.A. Quyyumi A.A. Aspirin improves endothelial dysfunction in atherosclerosis. Circulation. 1998; 97: 716-720 Crossref PubMed Scopus (245) Google Scholar

Aspirin as a therapeutic agent in cardiovascular disease. Special Writing Group.

Aspirin as a therapeutic agent in cardiovascular disease. Special Writing Group.

Inhibitors of ANF metabolism. Potential therapeutic agents in cardiovascular disease.

Inhibitors of ANF metabolism. Potential therapeutic agents in cardiovascular disease.