Bradycardia After Intravenous Ondansetron with Asystole on Rechallenge: A Case Report.

PURPOSE: There have been 3 published reports (4 cases) of symptomatic sinus bradycardia occurring after intravenous (IV) administration of the selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonist ondansetron. We report a fifth case in which the patient developed asystole after rechallenge with ondansetron. SUMMARY: A 36-year-old pregnant patient with no cardiac history, status post cerclage for cervical insufficiency, experienced nausea in the post ambulatory care unit after administration of morphine and indomethacin for pain. After IV administration of ondansetron, the patient's heart rate decreased to the 40s and improved spontaneously. The patient experienced a second episode of nausea, another dose of ondansetron was administered, and the patient went into asystole. Advanced cardiac life support measures were initiated and chest compressions were conducted for 3 minutes with return of spontaneous circulation. The patient was monitored overnight with no development of new cardiac arrhythmias and was discharged from the hospital in stable condition. CONCLUSIONS: Sinus bradycardia after IV administration of ondansetron was observed in a 36-year-old pregnant patient status post cerclage. On rechallenge, the patient went into asystole. This case report adds to the available literature regarding ondansetron-induced cardiac arrhythmias and the possibility of asystole upon rechallenge.

Coil Efficiency for Inductive Peripheral Nerve Stimulation.

Magnetic stimulation of peripheral nerves is evoked by electric field gradients caused by high-intensity, pulsed magnetic fields created from a coil. Currents required for stimulation are very high, therefore devices are large, expensive, and often too complex for many applications like rehabilitation therapy. For repetitive stimulation, coil heating due to power loss poses a further limitation. The geometry of the magnetic coil determines field depth and focality, making it the most important factor that determines the current required for neuronal excitation. However, the comparison between different coil geometries is difficult and depends on the specific application. Especially the distance between nerve and coil plays a crucial role. In this investigation, the electric field distribution of 14 different coil geometries was calculated for a typical peripheral nerve stimulation with a 27 mm distance between axon and coil. Coil parameters like field strength and focality were determined with electromagnetic field simulations. In a second analysis, the activating function along the axon was calculated, which quantifies the efficiency of neuronal stimulation. Moreover, coil designs were evaluated concerning power efficacy based on ohmic losses. Our results indicate that power efficacy of magnetic neurostimulation can be improved significantly by up to 40% with optimized coil designs.

Closure of a Thoracic Aortic Graft Pseudoaneurysm With an Amplatzer Septal Occluder.

We describe the case of a young man 7 weeks postoperative from repair of a Stanford type A aortic dissection who developed an expanding pseudoaneurysm of the proximal graft anastomosis. Owing to the morbidity and mortality associated with reoperation, an interdisciplinary team of interventional cardiologists and cardiothoracic surgeons implanted an Amplatzer septal occluder device in a hybrid operating room, successfully excluding the defect from the true lumen of the aorta. This case highlights the utility of a team approach and creative thinking for the treatment of a pseudoaneurysm in a high-risk, recently postoperative patient.

Role of neurohormonal modulators in heart failure with relatively preserved systolic function.

Cardiovascular disease remains the leading cause of mortality in the developed world. It is estimated that 5 million Americans suffer from heart failure (HF), and roughly 550,000 new cases are diagnosed annually. Studies have found that 40% to 71% of patients who have HF have relatively preserved systolic functions, or diastolic heart failure (DHF). Although there are abundant data to guide the treatment of heart failure and systolic dysfunction (systolic HF), evidence-based data are lacking in the management of DHF. This article examines the role of neurohormonal modulators in the management of DHF.

Clinical applications of blood-derived and marrow-derived stem cells for nonmalignant diseases.

CONTEXT: Stem cell therapy is rapidly developing and has generated excitement and promise as well as confusion and at times contradictory results in the lay and scientific literature. Many types of stem cells show great promise, but clinical application has lagged due to ethical concerns or difficulties in harvesting or safely and efficiently expanding sufficient quantities. In contrast, clinical indications for blood-derived (from peripheral or umbilical cord blood) and bone marrow-derived stem cells, which can be easily and safely harvested, are rapidly increasing. OBJECTIVE: To summarize new, nonmalignant, nonhematologic clinical indications for use of blood- and bone marrow-derived stem cells. EVIDENCE ACQUISITION: Search of multiple electronic databases (MEDLINE, EMBASE, Science Citation Index), US Food and Drug Administration [FDA] Drug Site, and National Institutes of Health Web site to identify studies published from January 1997 to December 2007 on use of hematopoietic stem cells (HSCs) in autoimmune, cardiac, or vascular diseases. The search was augmented by hand searching of reference lists in clinical trials, review articles, proceedings booklets, FDA reports, and contact with study authors and device and pharmaceutical companies. EVIDENCE SYNTHESIS: Of 926 reports identified, 323 were examined for feasibility and toxicity, including those with small numbers of patients, interim or substudy reports, and reports on multiple diseases, treatment of relapse, toxicity, mechanism of action, or stem cell mobilization. Another 69 were evaluated for outcomes. For autoimmune diseases, 26 reports representing 854 patients reported treatment-related mortality of less than 1% (2/220 patients) for nonmyeloablative, less than 2% (3/197) for dose-reduced myeloablative, and 13% (13/100) for intense myeloablative regimens, ie, those including total body irradiation or high-dose busulfan. While all trials performed during the inflammatory stage of autoimmune disease suggested that transplantation of HSCs may have a potent disease-remitting effect, remission duration remains unclear, and no randomized trials have been published. For reports involving cardiovascular diseases, including 17 reports involving 1002 patients with acute myocardial infarction, 16 involving 493 patients with chronic coronary artery disease, and 3 meta-analyses, the evidence suggests that stem cell transplantation performed in patients with coronary artery disease may contribute to modest improvement in cardiac function. CONCLUSIONS: Stem cells harvested from blood or marrow, whether administered as purified HSCs or mesenchymal stem cells or as an unmanipulated or unpurified product can, under appropriate conditions in select patients, provide disease-ameliorating effects in some autoimmune diseases and cardiovascular disorders. Clinical trials are needed to determine the most appropriate cell type, dose, method, timing of delivery, and adverse effects of adult HSCs for these and other nonmalignant disorders.

A comprehensive comparative review of adenosine diphosphate receptor antagonists.

INTRODUCTION: Thrombosis risk necessitates dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist, in patients who have acute coronary syndrome. Current guidelines emphasize the critical role of dual antiplatelet therapy in both medical management and invasive strategy, especially in patients undergoing percutaneous coronary intervention. With the availability of multiple ADP-receptor antagonists, it is crucial to select the most appropriate agent for each patient. AREAS COVERED: The pertinent trials were identified through a MEDLINE search, in addition to a manual search from the articles retrieved. This review examines the differences between clopidogrel, prasugrel and ticagrelor in terms of their pharmacological/pharmacokinetic properties, clinical efficacy, drug interactions and safety parameters. EXPERT OPINION: Prasugrel and ticagrelor exhibit greater platelet inhibition and superior efficacy compared with clopidogrel, at the expense of higher bleeding risk. Prasugrel and ticagrelor should be preferred over clopidogrel in patients who are at a high risk of thrombotic events with low risk of bleeding. Additionally, these two agents may offer advantage over clopidogrel in those patients who might have risk for drug resistance due to CYP2C19 polymorphism. In selecting the ideal agent for patients, clinicians should tailor the antiplatelet regimen by considering individual risk factors and medication characteristics.

Daptomycin: evaluation of a high-dose treatment strategy.

With a decreasing pipeline of novel antibiotics and increasing antibacterial resistance, the need to optimise the current antibiotics in our armamentarium has become vitally important. Daptomycin is a novel lipopeptide antibiotic that exhibits concentration-dependent activity. Currently, the daptomycin dosage is 4 mg/kg/day for treatment of complicated skin and soft-tissue infections and 6 mg/kg/day for Staphylococcus aureus bloodstream infections, including those with right-sided endocarditis, however higher doses (>6 mg/kg/day) have been explored as a possible alternative. A comprehensive review of published data identified through a MEDLINE search of the literature from 1967-2011 and a manual search of references was performed with the primary objective of critically evaluating the safety and efficacy of high-dose daptomycin. Search results yielded two prospective trials, three retrospective reviews, case reports and in vitro simulation studies on high-dose daptomycin. To date, clinical trials, retrospective reviews, case reports and in vitro simulation models have documented the safety and tolerability of high-dose daptomycin, even when administered for a prolonged duration. Additionally, in vitro benefits observed include suppression of the emergence of daptomycin resistance and increased rapidity of bactericidal activity.

Rebuilding the damaged heart: the potential of cytokines and growth factors in the treatment of ischemic heart disease.

Cytokine therapy promises to provide a noninvasive treatment option for ischemic heart disease. Cytokines are thought to influence angiogenesis directly via effects on endothelial cells or indirectly through progenitor cell-based mechanisms or by activating the expression of other angiogenic agents. Several cytokines mobilize progenitor cells from the bone marrow or are involved in the homing of mobilized cells to ischemic tissue. The recruited cells contribute to myocardial regeneration both as a structural component of the regenerating tissue and by secreting angiogenic or antiapoptotic factors, including cytokines. To date, randomized, controlled clinical trials have not reproduced the efficacy observed in pre-clinical and small-scale clinical investigations. Nevertheless, the list of promising cytokines continues to grow, and combinations of cytokines, with or without concurrent progenitor cell therapy, warrant further investigation.

Role of combination therapy in the treatment of pulmonary arterial hypertension.

As a result of the multimechanistic pathology of pulmonary arterial hypertension (PAH), combination therapy is emerging as a potential treatment option. Recent guidelines from the American College of Chest Physicians and expert consensus from the American College of Cardiology Foundation and American Heart Association do not definitively support or disapprove of combination pharmacotherapy for the treatment of PAH. Published trials have investigated different combinations including endothelin receptor antagonists with prostanoids, prostanoids with phosphodiesterase inhibitors, and phosphodiesterase inhibitors with endothelin receptor antagonists. Pertinent trials on combination pharmacotherapy for PAH were identified through a MEDLINE search of literature from 1967-2009 in addition to a manual search of references from the articles retrieved. Search results identified 12 trials that evaluated combination therapy for PAH; some included an add-on agent for patients who failed treatment with monotherapy and others were placebo controlled. Even with the published data, the overall consensus is unclear. Well-designed, larger trials with validated end points are needed to further identify when to initiate combination therapy for the treatment of PAH. Meanwhile, perhaps the most appropriate situation for using combination pharmacotherapy may be in the setting of a lack of clinical improvement or deterioration.

Granulocyte-colony stimulating factor administration after myocardial infarction in a porcine ischemia-reperfusion model: functional and pathological effects of dose timing.

BACKGROUND: Acute MI results in cardiomyocyte death, left ventricular (LV) dysfunction and adverse remodeling. The use of growth factors may prevent this. The aim of this study was to assess early and delayed administration of granulocyte colony-stimulating factor (G-CSF) in a porcine model of myocardial infarction (MI) and reperfusion. METHODS: MI was induced by balloon occlusion followed by reperfusion. There were 3 groups: Control (n = 11), Early (n = 17), and Delayed treatment (n = 8). The Early group received G-CSF 10 microg/kg/d every other day for 20 days beginning immediately. The Delayed group received G-CSF 10 microg/kg/d daily for 10 days beginning on day 5. Magnetic resonance imaging was performed on days 5 and 56. LV end-diastolic volumes (EDV), end-systolic volumes, ejection fraction, expansion index, sphericity index, thinning ratio, and infarct mass were calculated. Histology was analyzed at 56 days. RESULTS: At 56 days the change in EDV was 53% less in the Early (p = 0.005) and 24% greater in the Delayed (p = NS) group versus Control. The Delayed group also showed a 60% increase in normalized infarct mass (p = 0.055) and an 88% increase in expansion index (p = 0.003). Both groups had significantly less capillary density in the infarct border zone. The Delayed also had decreased arteriolar density in the mid scar. CONCLUSIONS: Early treatment with G-CSF after MI decreases ventricular dilatation, while delayed treatment has a deleterious effect on LV remodeling. This may be related to changes in myocardial vascularity. The effects of G-CSF therapy and its dose timing help to elucidate the results of recent human trials.