bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of Amiodarone for the Termination of Chronic Atrial Fibrillation and Maintenance of Normal Sinus Rhythm: A Prospective, Multicenter, Randomized, Controlled, Double Blind Trial
Authors: Galperin Jorge , Elizari Marcelo V. , Chiale Pablo A. , Molina Remberto Torres , Ledesma Rauil , Scapin Angel O. , Blanco Manuel Vaizquez
Published: June 2007

Objective: We sought to assess the efficacy and safety of amiodarone for restoration and maintenance of sinus rhythm in patients with chronic atrial fibrillation in a prospective, randomized, double blind trial.

Background: Restoration and preservation of sinus rhythm is difficult in patients with chronic atrial fibrillation. The efficacy of oral amiodarone has not been conclusively established.

Methods: Ninety-five patients with chronic atrial fibrillation, lasting an average of 35.6 months, were randomized to either amiodarone (600 mg/d) (47 patients) or placebo (48 patients) during four weeks. Nonresponders underwent electric cardioversion, and those who reverted continued with amiodarone (200 mg/d) or placebo. End-points were successful cardioversion and sinus rhythm maintenance.

Results: Sixteen patients (34.04%) in the amiodarone group reverted within 27.28 ± 8.85 days in comparison with 0% in the placebo group (P < 0.000009). The conversion rate rose to 51.72% in patients with chronic atrial fibrillation lasting less than 12 months. Twenty-eight patients in the amiodarone group and 39 in the placebo group underwent electric cardioversion, which was successful in 19 patients (67.8%) of the amiodarone group and in 15 (38.46%) of the placebo group (P = 0.017). Altogether, conversion was obtained in 79.54% of the amiodarone group patients and in 38.46% of the placebo group patients (P < 0.0001). During follow-up, atrial fibrillation relapsed in 13 (37.14%) of 35 patients of the amiodarone group within 8.84 + 8.57 months and in 12 (80%; P = 0.009) of 15 patients of the placebo group within 2.74 ± 3.41 months.

Conclusions: Oral amiodarone restored sinus rhythm in one third of patients with chronic atrial fibrillation, increased the success rate of electric cardioversion, decreased the number of relapses and delayed their occurrence.
Variations in Plasma Free Radicals in Patients with Venous Hypertension with HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides): A Clinical, Prospective, Placebo-Controlled, Randomized Trial
Authors: Cesarone M. R. , Incandela L. , DeSanctis M. T. , Belcaro G. , Dugall M. , Acerbi G.
Published: June 2007

The aim of this study was to demonstrate whether HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides), was effective in improving levels of plasma free radicals (PFRs) in patients with chronic venous insufficiency (CVI) and venous microangiopathy. Patients were randomized into the treatment group, which received oral HR (Ig sachets, twice daily, for 4 weeks), and a placebo group, which received comparable placebo. Below-knee Sigvaris stockings were used during the study. PFRs were measured with the D-Rom test at the finger and at a vein of the leg in an area of CVI. The mean age of included subjects was 46 years (SD 11) in the treatment group (20 patients; 6 females) and 46.4 (SD 8) in the placebo group (20 patients; 7 females). There were no differences between placebo and treatment groups at inclusion in age and sex distribution and in parameters indicating venous hypertension. The decrease of PFRs levels in the treatment group was significant, both at the finger and in the distal blood taken in areas of CVI. There there were no significant changes in the control group. In areas of venous hypertension, PFRs values were on average higher than at the finger (systemic) level (P < 0.05). In parallel with the progressive decrease in PFRs associated with treatment, the analogue score was significantly decreased at 2 (P < 0.05) and 4 weeks (P < 0.02) in the HR group. No changes were observed in the placebo group. No adverse effects were observed. In conclusion, HR treatment is effective in decreasing both the systemic and local values of PFRs and therefore may have a positive effect on the evolution of CVI.
Effects of Diltiazem and Esmolol on Cycle Length and Spontaneous Conversion of Atrial Fibrillation
Authors: Sticherling Christian , Tada Hiroshi , Hsu William , Bares Anton C. , Oral Hakan , Pelosi Frank , Knight Bradley P. , Strickberger S. Adam , Morady Fred
Published: June 2007

Background: Calcium channel blocking agents have been shown to prolong the duration of atrial fibrillation. This study compared the effects of intravenous diltiazem and esmolol on the cycle length and conversion rate of pacing-induced atrial fibrillation.

Methods and Results: In 41 adults without structural heart disease, atrial fibrillation was induced by rapid atrial pacing. After 3 minutes, either diltiazem (n = 13), esmolol (n = 15), or saline (n = 13) was infused. In the diltiazem group, the atrial fibrillation cycle length shortened by a mean of 43 milliseconds and became significantly shorter than in the control group, while the atrial fibrillation cycle length in the esmolol group did not change. Spontaneous termination of atrial fibrillation occurred significantly less often in the diltiazem group (23%) than in the esmolol (67%, P < 0.05) or placebo groups (77%, P = 0.01).

Conclusions: Intravenous diltiazem shortens the atrial fibrillation cycle length and lowers the probability of spontaneous conversion of recent-onset atrial fibrillation to sinus rhythm. These results suggest that the use of diltiazem for acute rate control may unwittingly prolong the duration of recent-onset atrial fibrillation.
Cariporide for Pharmacologic Defibrillation After Prolonged Cardiac Arrest
Authors: Wann Shue-ren , Weil Max Harry , Sun Shijie , Tang Wanchun , Yu Ting
Published: June 2007

Background: We hypothesized that cariporide, a sodium-hydrogen exchange inhibitor, would be as cardioprotective during the global myocardial ischemia of prolonged cardiac arrest as it is in settings of coronary occlusion.

Methods and Results: Fifteen Sprague-Dawley rats were randomized to receive bolus injections of cariporide or placebo in a dose of 3 mg.kg-1into the right atrium either 5 minutes before, or at 8 minutes after, onset of ventricular fibrillation. Ventricular fibrillation was electrically induced and untreated for 8 minutes. Precordial compression, together with mechanical ventilation, was then started and continued for an interval of 8 minutes prior to attempted resuscitation. All but one placebo-treated animal were successfully resuscitated. Spontaneous defibrillation with restoration of circulation was observed in both cariporide-pretreatment and post-treatment groups but in none of the placebo-treated animals. Postresuscitation cardiac index, end-tidal CO2, mean aortic pressure, left ventricular systolic pressure, left ventricular end-diastolic pressure, and left ventricular contractile and lusitropic functions (dP/dt40, and -dP/dt) were significantly less impaired after cariporide, especially in the pretreated group, compared to electrically defibrillated controls. Postresuscitation ventricular premature beats were significantly reduced after cariporide. The duration of postresuscitation survival was significantly increased in animals pretreated with cariporide.

Conclusions: Cariporide, when administered prior to and during cardiac arrest, improved both the success of resuscitation and postresuscitation myocardial function.
Anti-thrombotic Effects of Atorvastatin-An Effect Unrelated to Lipid Lowering
Authors: Gaddam V. , Li D. Y. , Mehta J. L.
Published: June 2007

Statins (3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have been shown to reduce clinical events in excess of what can be explained by altering lipid profile. Statins have been shown to possess modest antioxidant and antiplatelet aggregatory effect. We postulated that statins may accordingly inhibit arterial thrombus formation. To assess the antithrombotic effects of atorvastatin, a commonly used statin, in response to an oxidant stimulus, we fed Sprague-Dawley rats either regular chow, or chow mixed with atorvastatin (1.25 mg/kg) for 10 days (n = 16 in each group). Eight rats in each group were also given oxidized low-density lipoprotein intravenously prior to the induction of thrombus. An occlusive thrombus was created in the abdominal aorta by application of Whatman paper soaked in 35% FeCl3. The time to occlusive thrombus formation was not altered by administration of oxidized low-density lipoprotein in the rats fed regular chow or chow mixed with atorvastatin. However, time to thrombosis was increased in the group given chow mixed with atorvastatin (26 ± 4 minutes vs. 20 ± 5 minutes, P < 0.02). To determine the mechanism of atorvastatin's antithrombotic effect, we measured the expression of endothelial constitutive nitric oxide synthase (cNOS) in rat aortas by Western analysis. The cNOS protein expression was enhanced 75% in rats fed chow with atorvastatin (P < 0.01 vs. rats fed regular chow). Plasma levels of total cholesterol and low-density lipoprotein-cholesterol were similar in all groups. This study shows that atorvastatin delays thrombus formation in arterial channels exposed to oxidant stress. This effect of atorvastatin appears to be related to increased expression of cNOS, which is known to inhibit platelet aggregation and induce vasodilatation. The effects of atorvastatin are independent of its effects on plasma cholesterol levels.
Peroxisome Proliferator-Activated Receptor Ligands as Antiatherogenic Agents: Panacea or Another Pandora's Box?
Authors: Molavi Behzad , Rasouli Neda , Mehta Jawahar L.
Published: June 2007

Peroxisome proliferator activated receptors (PPARs) are members of the nuclear receptor super family that modulate gene expression upon ligand activation. They are 3 major subtypes of PPARs: alpha, delta (also called beta), and gamma. PPAR-γ is widely expressed in the cardiovascular system and is involved in the regulation of tissue inflammation and smooth muscle cell growth pathways as well as in lipoprotein metabolism and coagulation cascades. PPAR-γ ligands of (e.g., rosigitazone and pioglitazone) have been shown to exert antiatherogenic effects both in vitro and in vivo. PPAR-α ligands (e.g., clofibrate and benzofibrate) modulate lipoprotein metabolism, and affect inflammation and coagulation cascade. These effects may be helpful in resolving the dilemma arising from studies that showed significant mortality and morbidity benefits of fibrates in the face of minimal changes in HDL-cholesterol levels. The role of PPAR-δ in atherogenesis remains largely unknown, although it appears that PPAR-δ activation affects lipoprotein metabolism. PPAR ligands appear to be promising agents in limiting atherosclerosis; however, large-scale clinical trials are required to assess their safety and efficacy before they can be added to the clinicians' arsenal of antiatherosclerotic agents.
Acute Effects of Zatebradine on Cardiac Conduction and Repolarization
Authors: Sen Luyi , Cui Guanggen , Zhou Li-Ming , Sakaguchi Yoshiheda , Singh Bramah N.
Published: June 2007

Zatebradine, a potent bradycardic agent, is believed to act selectively at the sinoatrial node. The selectivity of such a property relative to various electrophysiologic classes of action is not well defined. To characterize the electrophysiologic properties of zatebradine, the corrected sinus node recovery time, sinoatrial conduction time, conduction intervals, atrial effective refractory period and monophasic action potential duration in the ventricle were measured before and after incremental doses of zatebradine (0.1-1.5 mg/kg) in 15 anesthetized dogs. The electrophysiologic effects of zatebradine developed immediately after a single IV bolus dose, reaching steady-steady-state at 15 minutes with the maximum effect evident at 0.75 mg/kg. The IC50was 0.23 mg/kg. There was no significant effect on the sinus node recovery time. The PR interval on the electrocardiogram was significantly increased when the dose was higher than 0.25 mg/kg. The duration of the P wave and the PA interval were not changed. Zatebridine greatly increased the AH (from 135 to 178 milliseconds) without changing the HH and HV intervals in His bundle recordings. The EC50of this effect was 0.58 mg/kg. The QRS interval was not changed. The QTc was significantly increased from 0.43 to 0.56 s½ (P < 0.05). The action potential duration was significantly increased by high dose zatebradine (> 0.5 mg/kg), the EC50for this effect was 0.76 mg/kg. The atrium effective refractory period was significantly increased (31%) with an EC500.69 mg/kg. These results indicate that zatebradine selectively inhibits sinus node automaticity at low doses. The inhibition of the AV nodal conduction and the lengthening of the refractory period and repolarization in the atria and the ventricles occur at higher dose.
Rhythm or Rate Control in Atrial Fibrillation: Insights from the Randomized Controlled Trials
Authors: Gronefeld Gerian , Hohnloser Stefan H.
Published: June 2007

Pharmacologic treatment remains the mainstay of therapy in patients with atrial fibrillation for the maintenance of normal sinus rhythm. Initial therapy of atrial fibrillation is often directed toward the maintenance of sinus rhythm by means of cardioversion and the use of antiarrhythmic drugs. Heart rate control is often only pursued when rhythm control fails. Four randomized controlled trials have carefully evaluated the yield of these two treatment strategies as the initial approach to patients with paroxysmal or persistent atrial fibrillation. In essence, all four trials demonstrated that an initial strategy of rate control is equally effective compared to the rhythm control approach in terms of clinically important outcome measures including mortality, stroke prevention, or quality of life. Accordingly, rate control can be considered as an initial approach to therapy in patients with paroxysmal or persistent atrial fibrillation. The four randomized trials clearly demonstrate that continuous anticoagulation is mandatory in all patients with atrial fibrillation and risk factors for stroke, irrespective of the initial therapeutic approach of rhythm or rate control.
Sinus Tachyarrhythmias and the Specific Bradycardic Agents: A Marriage Made in Heaven?
Authors: Yusuf Shamil , Camm A. John
Published: June 2007

A relatively novel group of drugs that inhibit the funny current in the sinus node pacemaker cells, the so-called specific bradycardic agents, are likely to play a significant role in the management of a wide range of cardiovascular disorders, including the sinus tachyarrhythmias. This comprehensive review initially provides an insight into these agents, their historical background, and their mechanism of action. It then discusses the differential diagnosis of the sinus tachyarrhythmias (normal sinus tachycardia, inappropriate sinus tachycardia, postural orthostatic tachycardia syndrome, and sinus node reentry tachycardia), elaborates on their pathophysiologic basis, and provides up-to-date evidence-based information on their optimum management. The specific bradycardic agents, by the very nature of their mode of action, may prove ideal therapies for the management of the sinus tachyarrhythmias, and this is explored at every stage.
Resident Cardiac Mast Cells and Ischemia-Reperfusion Injury
Authors: Singh Manjeet , Saini Harjot K.
Published: June 2007

Background: The intense inflammatory reaction following reperfusion of ischemic myocardium has been implicated as a factor in the extension of myocardial injury. One of the therapeutic goals of modem cardiology is to design strategies to limit the infarct size following myocardial infarction. A sound understanding of the inflammatory cascade that involves the release of various proinflammatory mediators from cardiac cells is necessary before a specific intervention is pursued.Observation: Summarized is the role of resident cardiac mast cells, which are noted to release inflammatory mediators, in ischemia-reperfusion-induced myocardial injury. Various pharmacologic interventions, such as disodium cromoglycate and ketotifen, that stabilize cardiac mast cells, or agents such as chlorpheniramine and cetirizine that prevent their degranulation during ischemia and reperfusion, may prove to be potential therapeutic agents to limit or salvage ischemia-reperfusion-induced injury.Conclusion: On the basis of the effects of histamine H1antagonists, adrenoceptor blockers, cellular calcium and nitric oxide modulators, as well as inhibitors of phosphodiesterase and mitogen-activated protein kinase on mast cells, cardiac resident mast cells may represent a novel target for the development of cardioprotective agents.
Acid-Base and Electrolyte Abnormalities Observed in Patients Receiving Cardiovascular Drugs
Authors: Miltiadous G. , Mikhailidis D. P. , Elisaf M.
Published: June 2007

Cardiovascular drugs can cause a variety of acid-base and electrolyte abnormalities that need to be considered when clinicians manage the large number of patients who receive these agents. Diuretic-induced metabolic alkalosis is the most common acid-base disorder observed and is associated with hypokalemia. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Multifactorial-origin diuretic-induced hyponatremia is mostly due to thiazides and should be carefully managed. This review focuses on the pathogenetic mechanisms as well as on the treatment of these metabolic derangements that are commonly encountered in patients who receive cardiovascular drugs.
Effects of Acetaminophen on Myocardial Infarct Size in Rats
Authors: Dai Wangde , Kloner Robert A.
Published: June 2007

Objective: Acetaminophen is widely prescribed as an analgesic agent in hospitals and clinics. However, acetaminophen theoretically could influence myocardial infarct size by reducing prostaglandin synthesis in vivo. To date, the effect of acetaminophen on myocardial infarct size is unknown. The present study investigated (1) whether acetaminophen has any effect on myocardial infarct size when given in an analgesic dose and (2) whether acetaminophen can affect the cardioprotective effect of the early phase of ischemic preconditioning in rats.

Methods: Female Sprague-Dawley rats were randomly assigned to four groups (n = 12 each). Group 1 (no preconditioning): Vehicle (intravenous ethanol, 0.9 mL/kg) was given 39 minutes prior to ischemia. Group 2 (acetaminophen plus no preconditioning): intravenous acetaminophen (125 mg/kg) was given 39 minutes prior to ischemia. Group 3 (preconditioning): The heart was preconditioned before ischemia, and the vehicle (intravenous ethanol, 0.9 mL/kg) was given 39 minutes prior to the ischemia. Group 4 (acetaminophen plus preconditioning): The heart was preconditioned before ischemia, and intravenous acetaminophen (125 mg/kg) was given 39 minutes prior to the ischemia. The preconditioning protocol consisted of three cycles of 3 minutes of coronary occlusion and 5 minutes of reperfusion. The left coronary artery was then occluded for 60 minutes, followed by 3 hours of reperfusion. The end points were hemodynamics, body temperature, and risk area and area of necrosis of the left ventricle.

Results: The area of risk was similar among the four groups. The area of necrosis, expressed as a percentage of the area at risk, was 55.7% ± 6.1% in the no-preconditioning group, 62.8% ± 2.4% in the acetaminophen plus no-preconditioning group, 24.7% ± 7.3% in the preconditioning group, and 17.2% ± 6.4% in the acetaminophen plus preconditioning group. The area of necrosis/area at risk was decreased significantly in the preconditioning group and in the acetaminophen plus preconditioning group compared with the no-preconditioning group ( P < .05); but there were no significant differences between the no-preconditioning group and the acetaminophen plus no-preconditioning group (P = .29), or between the preconditioning group and acetaminophen plus preconditioning group (P = .45). Among the four groups, heart rate and body temperature were similar. The infusion of the vehicle or acetaminophen increased blood pressure in the four groups, but to a lesser extent in the acetaminophen group. However, during coronary artery occlusion and reperfusion, the four groups had comparable blood pressures.

Conclusion: Acetaminophen had no beneficial or adverse effects on infarct size in nonpreconditioned rats, and the beneficial effects of preconditioning were not blocked or prevented by acetaminophen at this analgesic dose.
Differential Effects of Peroxisome Proliferator Activator Receptor-α and γ Ligands on Intimal Hyperplasia After Balloon Catheter-Induced Vascular Injury in Zucker Rats
Authors: Desouza Cyrus V. , Murthy S. N. , Diez Jose , Dunne Bruce , Matta Anil S. , Fonseca Vivian A. , McNamara Dennis B.
Published: June 2007

Background: Patients with type 2 diabetes mellitus have a higher rate of restenosis following angioplasty. Peroxisome proliferator activator receptor-x (PPAR) and y ligands such as fenofibrate and rosiglitazone, respectively, have been shown to have protective effects on the vessel wall. We studied the effect of fenofibrate and rosiglitazone on intimal hyperplasia in the Zucker rat, a model for insulin resistance and type 2 diabetes mellitus, following balloon catheter-induced injury.

Methods and Results: Three groups of 13-week-old female fatty Zucker rats were administered an aqueous suspension of either 3 mg/kg/d rosiglitazone (n = 7) or 150 mg/kg/d fenofibrate (n = 6) by gavage, or served as controls (n = 9). In addition, two groups of 13-week-old female lean Zucker rats were either administered 3 mg/kg/d rosiglitazone (n = 6) or served as controls (n = 6). Carotid balloon injury was induced 1 week after the drugs were started. The drug administration was continued for 3 weeks. A 2-mm balloon catheter was introduced through the femoral artery to the left carotid. The balloon was inflated to 4 atmospheres for 20 seconds and then was deflated to 2 atmospheres and dragged down to the aorta. The rats were killed 3 weeks after the injury. The carotid intima/media ratio was calculated. Intimal hyperplasia after carotid balloon-induced injury in the fatty Zucker rats was significantly reduced in the group treated with rosiglitazone (0.18 ± 0.29) compared with the untreated group (0.97 ± 0.13; P < .01). Plasma glucose, triglyceride, and insulin levels were elevated, indicative of the presence of insulin resistance; rosiglitazone treatment significantly reduced insulin and triglyceride levels without decreasing glucose. Rosiglitazone treatment also reduced, but to a lesser extent, the intimal hyperplasia in the lean Zucker rats (0.57 ± 0.10 vs 1.06 ± 0.12 treated and untreated, respectively; P < .01); however, it had no effect on insulin, triglyceride, or glucose levels in this group. The intimal hyperplasia in the fatty Zucker rats treated with fenofibrate was not reduced compared with controls (0.84 ± 0.26 vs 0.97 ± 0.13, respectively); fenofibrate reduced insulin and triglyceride, but not glucose levels, in these animals.

Conclusions: The PPAR-y ligand rosiglitazone, but not the PPAR-x ligand fenofibrate, decreases intimal hyperplasia following balloon injury in both fatty and lean Zucker rats. This effect of the PPAR-y ligand was independent of glycemia, insulin, and lipid levels, and was more pronounced in insulin-resistant rats.
Effect of Acute Intravenous Cocaine Administration on Endothelium-Dependent Vasodepressor Responses to Acetylcholine
Authors: Pradhan Leena , Dabisch Paul A. , Liles John T. , Agrawal Krishna C. , Kadowitz Philip J.
Published: June 2007

Background: Cardiovascular events commonly associated with acute and chronic cocaine abuse include coronary vasospasm, arrhythmias, myocardial infarction, and sudden death. It has been suggested that cocaine causes endothelial dysfunction and vasoconstriction by inhibiting local production of nitric oxide and that endothelial dysfunction may be involved in the cardiovascular events associated with cocaine use. The present study investigated the effect of acute intravenous cocaine administration on endothelium-dependent vasodepressor responses to acetylcholine in the anesthetized rat.

Methods and Results: Rats were anesthetized with intraperitoneally Inactin (140 mg/kg) and catheters were inserted into the jugular vein and iliac artery for the injection of drugs and measurement of systemic arterial pressure. A thermistor catheter was advanced to the aortic arch for the measurement of cardiac output via the thermal dilution technique. A 5 mg/kg intravenous dose of cocaine, which enhances the vasopressor response to norepinephrine and blocks the vasopressor response to tyramine, had no effect on the vasodepressor response to the endothelium-dependent vasodilator acetylcholine. In addition, responses to the nitric oxide-donor sodium nitroprusside and the vasoconstrictor peptide angiotensin II were not altered by administration of cocaine.

Conclusions: Acute administration of cocaine in a dose that blocks norepinephrine uptake into adrenergic terminals had no effect on endothelial function as measured by the absence of an effect on the vasodepressor response to intravenous injections of acetylcholine. Although chronic cocaine exposure has been shown to cause vascular dysfunction, eventually leading to impairment of the nitric oxide pathway, it appears that acute cocaine administration does not inhibit this pathway in the anesthetized rat.
Relationship Between Cyclooxygenase-2 Inhibition and Thrombogenesis
Authors: Dai Wangde , Kloner Robert A.
Published: June 2007

Recently there has been considerable interest in the role of cyclooxygenase-2 (COX-2) in thrombosis and myocardial infarction. A large number of clinical and basic studies have focused on whether COX-2 inhibitors can induce a prothrombotic disorder and increase the risk of cardiovascular thrombosis. This article reviews (1) the roles of COX-2 in the metabolism of prostaglandins; (2) the influence of COX-2 inhibition in the platelet aggregation and the antithrombotic function of vascular endothelium; (3) the roles of COX-2 inhibition in atherothrombosis; and (4) clinical trials that examine COX-2 inhibition in relationship to the risk of myocardial infarction. Based on the published data, this review suggests that COX-2 plays varying and sometimes conflicting roles in thrombogenesis, in prostaglandins' metabolism of endothelium in healthy or dysfunctional conditions, and in atherothrombosis. Future investigations under different pathologic conditions are needed to fully understand the net effect of COX-2 inhibition on thrombogenesis. The roles of COX-2 in the pathophysiologic process of cardiovascular thrombosis are diverse and controversial, and need to be further studied to guide clinical practice.
Intracoronary Administration of Abciximab During Percutaneous Coronary Interventions: Should This Be the Routine and Preferred Approach?
Authors: Sharma Sanjiv , Makkar Raj , Lardizabal Joel
Published: June 2007

The authors have had experience with administering abciximab as an intracoronary bolus in 96 high-risk patients undergoing percutaneous coronary interventions, specifically in situations in which there was anticipation of a high embolic load from thrombus/plaque burden at the site of the culprit lesion, saphenous vein graft culprit lesion, threatened abrupt closure, developing slow-flow, or no-reflow phenomena with distal embolization. Our uncontrolled data basically substantiate the safety of intracoronary administration of abciximab. The data summarizing the potential superiority of this method of administration of the drug and the likely mechanisms of this effect are summarized. These incite a need for reevaluation of the method of administration of the drug, especially in high-risk percutaneous coronary interventions cases
Effects of Bezafibrate on HDL2/HDL3 Ratio in Postmenopausal Hypertriglyceridemic Women
Authors: Ushiroyama Takahisa , Sakuma Kou , Nosaka Sakura
Published: June 2007

The short-term effects of bezafibrate on high-density lipoprotein cholesterol quality and triglyceride-rich lipoprotein metabolism in 186 postmenopausal hypertriglyceridemic women were investigated. Patients were randomized to an untreated group and to bezafibrate (400 mg/d) for 6 months. Fasting lipid concentrations, high-density lipoprotein 2, and high-density lipoprotein 3 levels were measured at baseline and after 3 and 6 months. At 3 months, bezafibrate had significantly decreased mean serum triglycerides and remnant-like particle cholesterol levels (105.7 ± 43.4 mg/dL and 5.33 ± 2.1 mg/dL, P < .001, respectively) from baseline values (232.5 ± 63.9 mg/dL and 9.69 ± 3.8 mg/dL, respectively). It also maintained lower total cholesterol, low-density lipoprotein cholesterol, triglycerides, and remnant-like particle cholesterol concentrations to 6 months. After 3 months, it significantly increased mean serum high-density lipoprotein cholesterol (55.1 ± 14.7 vs 64.8 ± 12.1 mg/dL; P < .0001) and maintained higher high-density lipoprotein cholesterol at 6 months. The high-density lipoprotein 2-high-density lipoprotein 3 ratio was decreased after 3 months of therapy with bezafibrate (2.13 ± 0.68) from the baseline (2.42 ± 0.71) ( P < .01)
Lack of Deleterious Interaction Between Angiotensin Receptor Blockers and β-Blockers in the Treatment of Patients With Heart Failure
Authors: Hennekens Charles H. , Kowalczykowski Magda , Hollar Danielle
Published: June 2007

The Valsartan-Heart Failure trial formulated the hypothesis that combination therapy with angiotensin-converting enzyme inhibitors and β-blockers with an angiotensin-receptor blocker had a deleterious interaction. Furthermore, the Food and Drug Administration (FDA)-approved heart failure indication for valsartan included the statement that concomitant use of an angiotensin-converting enzyme inhibitor, a β-blocker was not recommended. The Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)-Added and the VALsartan In Acute Myocardial Infarction Trial (VALIANT) provide reassuring evidence to support concomitant use of angiotensin-receptor blockers, angiotensin-converting enzyme inhibitors, and β-blockers. The FDA-approved heart failure indication for candesartan included the statement of additive benefits with angiotensin-converting enzyme inhibitors and β-blockers and led to a change in the valsartan label. These considerations have great clinical and public health importance given the increasing numbers of patients with heart failure, their high morbidity and mortality, and the relatively limited number of effective drug therapies
Variable Response of Conductance and Resistance Coronary Arteries to Endothelial Stimulation in Patients With Heart Failure Due to Nonischemic Dilated Cardiomyopathy
Authors: Bitar Fahed , Lerman Amir , Akhter Mohammed W. , Hatamizadeh Parta , Janmohamed Munir , Khan Salman , Elkayam Uri
Published: June 2007

Attenuation of endothelial-dependent coronary vasodilation has been reported in idiopathic dilated cardiomyopathy and anatomically normal coronaries; however, data are insufficient for understanding the incidence and extent of this finding. The response of conductance and resistance coronary arteries to endothelial stimulation with acetylcholine was examined in 25 patients. Coronary blood flow had a variable response to acetylcholine and suggested coronary endothelial dysfunction in approximately half of the patients. Abnormal endothelial dysfunction involved the large conductance epicardial coronary arteries and the small resistance vessels. Abnormal endothelial response of coronary blood flow to acetylcholine could not be predicted by demographic and hemodynamic data. Conclusions: Coronary artery endothelial function is heterogeneous in patients with idiopathic dilated cardiomyopathy. Endothelial dysfunction is present in approximately half of the cases and involves both resistance as well as conductance coronary blood vessels. Furthermore, coronary endothelial function cannot be predicted by demographic and hemo-dynamic parameters or left ventricular ejection fraction.
Ventricular Fibrillation Induced by Ischemia-Reperfusion Is Not Prevented by the NPY Y2 Receptor Antagonist BIIE0246
Authors: Ilebekk Arnfinn , Eriksen Morten , Sevre Knut , Aspelin Trude , Björkman Jan-Arne , Lyberg Torstein , Nordlander Margareta
Published: June 2007

Neuropeptide Y is released together with norepinephrine from sympathetic nerve terminals during conditions of increased sympathetic activity. Neuropeptide Y is known to inhibit vagal activity, and accordingly, it might increase the risk for ventricular fibrillation during myocardial ischemia-reperfusion, with concomitant sympathetic stimulation. Counteracting the inhibiting effect of neuropeptide Y by the specific neuropeptide Y2 antagonist, BIIE0246, we expected occurrence of ventricular fibrillation in association with repeated periods of myocardial ischemia-reperfusion to decrease. The midleft anterior descending coronary artery was repeatedly occluded in 16 open-chest pigs. Eight pigs received BIIE0246, and the controls received the vehicle only. Ventricular fibrillation developed in 2 animals of the control group, but in 4 pigs receiving BIIE0246. Occurrence of ventricular fibrillation and ventricular tachycardia did not differ significantly between the 2 groups, and in association with repeated periods of regional myocardial ischemia, did not decline in pigs treated by the specific neuropeptide Y2-receptor antagonist BIIE0246.
An Isotope-Diagnostic Approach to Erdheim-Chester's Disease of the Heart
Authors: Palotás András , Bogáts Gábor , Lázár Mátá , Papós Miklós , Matin Keyvan , Pávics László
Published: June 2007

Erdheim-Chester's disease is a form of histiocytic granulomatosis afflicting the skeletal system and various inner organs. Apart from incidental findings of involvement of various structures and tissues, a complete diagnostic workup to evaluate afflicted bodily parts is not known. The authors we present several specific isotope-diagnostic techniques of a case to support the identification of this rare multisystem infiltrative disease.
A Case and Review of Acromegaly-Induced Cardiomyopathy and the Relationship Between Growth Hormone and Heart Failure: Cause or Cure or Neither or Both?
Authors: Schwarz Ernst R. , Jammula Praveen , Gupta Rajiv , Rosanio Salvatore
Published: June 2007

Growth hormone plays an integral role in the development and maintenance of structure and function of the heart. Specific involvement of the heart in acromegaly is termed acromegalic cardiomyopathy, manifested as concentric left ventricular hypertrophy and diastolic dys-function. Left untreated, it ultimately progresses to systolic heart failure. Heart failure from acromegalic cardiomyopathy is one of the most common causes of death in acromegaly. Current treatment options include different approaches to lower elevated growth hormone levels with improvement in symptoms, exercise tolerance, and echocardiographic improvement in regression of left ventricular hypertrophy and indices of diastolic dysfunction. On the other hand, growth hormone is essential for cardiac growth and function and exerts beneficial and protective effects on the cardiovascular system. Its potential role as adjunctive therapy in the treatment of heart failure as derived from experimental studies and clinical trials is discussed.
Hypokalemia, Cardiac Failure, and Reporting NXY-059 Safety for Acute Stroke
Authors: Serebruany Victor L.
Published: June 2007

NXY-059, an alpha-phenyl-N-tert-butyl nitrone derivative, is a free radical–trapping agent presently in late clinical trials as a potential neuroprotectant limiting reperfusion injury following acute stroke. Two recent trials suggest that NXY-059 causes hypokalemia and associated cardiac disturbances. With regard to the mechanism of such association, most investigators agree that potent trapping of free radicals leads to the 11 beta-hydroxysteroid dehydrogenase blockade in kidneys, diminishing renal hydrocortisone oxidation and increasing K+ ion urine excretion. Importantly, potassium deficiency represents the major avoidable cause of the array of serious cardiac adverse reactions: QT-prolongation, Torsades de pointes and other life-threatening arrhythmias, and higher risks for perioperative cardiopulmonary resuscitation and cardiac death. Because a prime target for NXY-059 use will likely be acute strokes in the emergency room environment, the potential combination of the drug with intensive therapy including fluid infusions, particularly with diuretics, might be especially harmful because of the synergic depletion of potassium, which might also jeopardize the fate of the novel nitrone neuroprotectant.
Pathophysiological Basis of Right Ventricular Remodeling
Authors: Kret Marcus , Arora Rohit
Published: June 2007

The pathophysiology of right ventricular (RV) remodeling is a complex process and may include unique elements not observed in left ventricular (LV) remodeling. The RV also has a relatively irregular geometry not accounted for in LV analyses. RV remodeling includes basic changes in geometry, wall thickness, and ventricular pressure-volume relationships. Also, myocyte dimensions and number increase, and myocardial extracellular matrix and biochemical milieu are modified. Remodeling has been associated with such diseases as pulmonary hypertension, lung transplant, LV pathology, Chagas' disease, and arrhythmogenic right ventricular cardiomyopathy. Disease progression may lead to further RV changes, including hypertrophy, dilatation, and subsequently to variable alterations in RV hemodynamic status. The multiple methods to assess RV hypertrophy include cine magnetic resonance imaging and 3-D echocardiography. Each technique offers different precision in evaluating RV dimensions and functional performance characteristics. Strategies to prevent RV remodeling include pharmacological agents, such as vasodilators and angiotensin-converting enzyme inhibitors, as well as more invasive interventions, such as ventricular assist devices.
Reference Ranges of the Dilute Tissue Thromboplastin Inhibition and Dilute Russell's Viper Venom Tests Revisited
Authors: Gerbutavicius Rolandas , Fareed Jawed , Messmore Harry L. , Jqbal Omer , Wehrmacher William H. , Hoppensteadt Debra A. , Demir Muzaffer , Piccolo Peter , Ahmad Sarfraz , Ma Qing , Griniute Rasa
Published: June 2007

Reference ranges for two well-recognized tests for the lupus anticoagulant were determined utilizing 98 healthy subjects. The purpose of the study was to compare the reference ranges for the dilute tissue thromboplastin inhibition test on this group of healthy subjects calculated by parametric and nonparametric statistical methods, and to compare these results with results obtained on subsets of 20 and 40 randomly selected individuals from the group of 98. The same procedures were followed for the dilute Russell's viper venom test. Results were recorded in seconds of clotting times and in ratios (subject/mean of that set or subset). Statistical analysis revealed Gaussian distribution of the results in the large group as well as in each subset for both tests. The results showed more variation between sets of the dilute tissue thromboplastin inhibition test than of the dilute Russell's viper venom test. Nonparametrically calculated reference ranges were wider than those determined by a parametric method, especially if confidence intervals are provided for both reference ranges in the group of 94 controls or in a subset of 40 subjects. The nonparametric technique utilizes all data for the calculation of reference ranges of such sample sizes no matter how wide the results are spread. There was no significant difference between the reference ranges of subsets and the whole group (p > 0.05) calculated by both statistical techniques.
Effects of a Low Molecular Weight Heparin, Bemiparin, and Unfractionated Heparin on Hemostatic Properties of Endothelium
Authors: Perez-Ruiz Ana , Montes Ramon , Carrasco Pilar , Rocha Eduardo
Published: June 2007

Human endothelial cells synthesize and secrete a variety of molecules involved in fibrinolysis and coagulation. The effects of a low molecular weight heparin, Bemiparin, and unfractionated heparin (UFH) were compared on plasminogen activator inhibitor-i (PAI-1), tissue-plasminogen activator (t-PA), tissue factor (TF), tissue factor pathway inhibitor (TFPI) release, and PAl-i gene expression by human umbilical vein endothelial cells (HUVEC). Cell cultures were supplemented with Bemiparin or UFH at 1 or 10 U/mL. Culture media samples were obtained before the addition of the drugs and 2, 6, and 24 hours afterward to measure the antigen levels of TF, TFPI, t-PA, and PAI-1. RNA was obtained to study the endothelial expression of PAM by reverse transcriptase-polymerase chain reaction (RT-PCR). Bemiparin at 1 U/mL resulted in a decreased messenger RNA (mRNA) PAI-I expression, which remained unaltered when UFH had been added. PAM-levels increased after the cultures had been supplemented with either Bemiparin or UFH at both doses. UFH induced an increase in t-PA either at 1 or 10 U/mL. Both doses of UFH, but not Bemiparin, induced an important increase in TF secretion. An increase in the TFPI levels was seen with UFH at 1 U/mL. The decrease in PAM-i gene expression observed with a therapeutic dose of Bemiparin might confer this drug interesting profibrinolytic properties. The fact that Bemiparin, in contrast with UFH, does not induce an increase in TF could give this drug another positive feature.
The Role of the Bone Marrow Examination in the Diagnosis of Immune Thrombocytopenic Purpura: Case Series and Literature Review
Authors: Jubelirer Steven J. , Harpold Robert
Published: June 2007

The need for a bone marrow examination was assessed in patients with clinical and laboratory features consistent with ITP; the literature was reviewed. The records of all patients undergoing a bone marrow examination between January 1988 to January 1998 were retrospectively reviewed to determine which were motivated by the suspicion of ITP. Data were collected from hospital and outpatient medical and pathology records. Eighty-six patients with isolated thrombocytopenia (i.e., normal white blood cell count, hemoglobin, peripheral smear and clotting studies) were studied. The bone marrow was consistent with ITP in 82 patients, (i.e., normal or increased megakaryocytes and other hemopoietic lineages normal.) Four patients had decreased megakaryocytes, but all patients responded to corticosteroids. All 86 patients were followed up for a median of 22 months after bone marrow aspiration (range, 2-76 months.) During that time, none of the patients developed features to suggest an alternative diagnosis to ITP. The initial clinical and laboratory findings of 99 patients with acute leukemia were also reviewed; all had features atypical of ITP. These data suggest that routine performance of a bone marrow examination for the diagnosis of ITP is not necessary, provided that a thorough history and physical examination are performed and that the complete blood cell count, peripheral blood smear, and routine clotting studies show no abnormalities apart from thrombocytopenia. The findings of seven prior retrospective studies, two in adults and five in children are consistent with the previous findings. However, the value of marrow investigation in ITP remains unresolved and data from a large prospective study would be helpful.
Low-Molecular-Weight Heparin for Vertebral Artery Dissection
Authors: Marietta Marco , Bertesi Marcello , Rozzi Nino , Cano Maria Carmen , Vallone Stefano , Cappi Cinzia , Pozzi Samantha , Torelli Giuseppe
Published: June 2007

A case of vertebral artery dissection and consequent basilar artery thrombosis in a 6-year-old patient is reported. The patient was treated with subcutaneous low-molecular-weight heparin at therapeutic doses (enoxaparin, 100 IU/kg twice daily) for 3 weeks, then reduced to 2,000 IU/day for 3 more weeks. After this time a magnetic resonance angiogram was obtained that showed complete recanalization of the left basilar artery. Enoxaparin proved to be a safe and useful therapy for thrombosis accompanying vertebral artery dissection.
Monitoring of Argatroban in ARG310 Study: Potential Recommendations for its Use in Interventional Cardiology
Authors: Iqbal Omer , Ahmad Sarfraz , Lewis Bruce E. , Walenga Jeanine M. , Rangel Yadira , Fareed Jawed
Published: June 2007

Argatroban is a peptidomimetic synthetic direct thrombin inhibitor with reversible and specific properties resulting in predictable anticoagulant effects. Usually, argatroban therapy is monitored by the activated clotting time (ACT) or activated partial thromboplastin time (aPTT). While other global clotting tests for the monitoring of anticoagulants are useful, their applicability to antithrombin agents (particularly of argatroban at higher dosages) is rather questionable. In this study, we sought to compare the argatroban anticoagulant levels in patients undergoing percutaneous transluminal angioplasty (PTCA) and stenting procedures, utilizing both functional and absolute quantitation methods. Argatroban produced a comparable increase of ACT and HMT, 5 to 10 minutes after administration. The level of anticoagulation achieved (400-450 seconds with ACT and HMT) following a slow bolus of argatroban (350 aglkg) was maintained throughout the procedure using 25 jtg/kg/min infusion. Following discontinuation of argatroban at the end of the procedure, the ACTs and HMTs showed a comparable progressive reduction in the anticoagulant response, which reflected the elimination of argatroban 2 to 3 hours after the procedure. No significant differences between the three methods (Hemotec, Hemochron, and HMT) were noted at any given sampling time. Argatroban dosage at 350 Ag/kg intravenous slow bolus followed by 25 Ag/kg/min infusion was adequate to perform PTCA and stenting procedures. There was no incidence of bleeding complications. Absolute quantitation of argatroban levels in patient plasmas by a newly developed HPLC method was found to be quite comparable with the ecarin clotting time (ECT) results. The ECT system was found to be less sensitive when compared to other tests, and therefore, could be used as a point-of-care test during the PTCA/stenting procedures to monitor argatroban.
Direct Antithrombin Agents Ameliorate Disseminated Intravascular Coagulation in Suspected Heparin-Induced Thrombocytopenia Thrombosis Syndrome
Authors: Mukundan S. , Zeigler Z. R.
Published: June 2007

This is a case series of 5 patients who were treated with the direct antithrombin agents (lepirudin or argatroban) for known or suspected heparin-induced thrombocytopenia thrombosis syndrome (HITTs). Coincidentally all had evidence of disseminated intravascular coagulation (DIC). The DIC parameters improved with treatment and each patient was successfully discharged from the hospital. These observations provide evidence that the direct antithrombin inhibitors, lepirudin and argatroban, can improve DIC. Moreover the presence of DIC in a patient with suspected HITTs should not mitigate against the use of these agents.