Resolution of sickle cell crisis following administration of amiodarone

Sickle cell disease is a prevalent hematologic condition, but some of the factors that lead to erythrocyte sickling are not fully known. A 58-year-old male patient with a history of sickle cell disease (SCD) and paroxysmal atrial fibrillation was transferred from an outside hospital for further management of refractory sickle cell crisis with acute chest syndrome. Before transfer, the patient received antibiotics and multiple packed red blood cell (pRBC) transfusions, with minimal effect on symptoms or anemia. After transfer, the patient developed rapid supraventricular tachycardia and atrial fibrillation (rates >160) with a drop in blood pressure. He was started on IV amiodarone. His heart rate was subsequently better controlled and converted to sinus rhythm the following day. Three days following initiation of amiodarone, the patient, with a hemoglobin count of 6.4 g/dl, required one additional unit of pRBC. On the fourth day, the patient’s hemoglobin count rose to 9.4 g/dl, and he reported a marked improvement in symptoms. The improvements in symptoms and hemoglobin count were sustained, and the patient was discharged two days later. This remarkable improvement in anemia and symptoms triggered a search for potential causes. Amiodarone is a complex drug shown to have effects on multiple cell types, including erythrocytes. A recent preclinical study demonstrated reduced sickling and improved anemia in a murine model of SCD. This case report raises the possibility that amiodarone may have contributed to the rapid improvement in anemia and should be further explored in clinical trials

Tracheal obstruction secondary to extravasation of intravenous fluids from a central catheter port

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30358/1/0000760.pd

Valsartan Improves Insulin Sensitivity without Altering Vascular Function in Healthy Overweight Adults without the Metabolic Syndrome

Background. We investigated hyperactivity of the renin-angiotensin system (RAS) as a cause of endothelial dysfunction in obese humans. Methods. Thirty five healthy overweight (BMI = 33.6 ± 6.6 kg m −2) adults (33 ± 10 years old) without cardiovascular risk factors received valsartan (160 mg) orally daily or a matching placebo for 6 weeks each. Results. Baseline flow-mediated dilatation (FMD) and nitroglycerin-mediated dilatation (NMD) were not altered by placebo or valsartan. However, fasting plasma insulin was significantly decreased by valsartan compared to placebo (−4.6 ± 16.0 μUmL−1 versus −0.4 ± 11.6 μUmL−1, P = 0.032) with no changes in glucose. A secondary analysis in patients with elevated waist to hip ratios (ÿ0.85, n = 18) showed an increase in FMD with valsartan. Conclusions. Our findings suggest that angiotensin 2 receptor blockade may aid in the prevention of diabetes even at the earliest stages of risk due solely to uncomplicated obesity. The lack of an improvement in FMD does not support a central role of RAS-hyperactivity in the etiology of the vascular dysfunction due solely to obesity. However, it is possible that obese patients with central adiposity may improve FMD with RAS blockade, and future investigation is warranted in this subgroup.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63259/1/met.2007.0002.pd

Blood Pressure and Vascular Effects of Leptin in Humans

Background: Leptin may play a role in mediating obesity-related hypertension. However, its effects on the vasculature and blood pressure (BP) remain poorly defined in humans. Methods: In the first study, we performed a short-term, placebo-controlled, randomized, double-blind, cross-over experiment investigating the actions of recombinant human leptin (r-metHuLeptin) in 15 nonobese adults. To compliment the acute study, we retrospectively analyzed available BP results from a previously performed 85–day, placebo-controlled, randomized, double-blind, parallel weight-loss study using r-metHuLeptin in 284 obese adults. Results: In the acute study, conduit artery endothelial function determined by brachial flow-mediated dilatation (FMD) increased 2 hours following 0.2 mg · Kg−1 subcutaneously (SC) of r-metHuLeptin versus placebo (+3.3% versus −2.8%, P = .02). BP remained unchanged 4 hours after injections. In the retrospective analysis of the weight loss study data, 10 mg every day before noon (QAM), 10 mg every day after noon (QPM), or 10 mg twice a day (BID) SC of r-metHuLeptin was found to not alter the degree of weight loss (−3.2 ± 3.7 versus −2.9 ± 3.2 Kg, P = .54), change in systolic (−1.6 + 12.9 versus −2.0 ± 13.9 mmHg, P = .85) and diastolic BP (−0.2 ± 8.7 versus −1.5 ± 8.6, P = .30), as well as heart rate (−1.4 ± 10.7 versus −1.4 ± 10.4 beats/min, P = .98) compared to placebo. Conclusions: In our acute study, marked hyperleptinemia rapidly enhanced endothelial function and did not alter BP. The available data from a longer-term study in healthy obese adults did not demonstrate a significant effect of hyperleptinemia upon BP. These combined findings do not support a direct role for leptin in linking obesity to hypertension, however more studies are required to corroborate these observations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63121/1/met.2006.0023.pd

Membraneâ Tethered Metalloproteinase Expressed by Vascular Smooth Muscle Cells Limits the Progression of Proliferative Atherosclerotic Lesions

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142430/1/jah32412-sup-0001-TableS1-FigS1-S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142430/2/jah32412.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142430/3/jah32412_am.pd

Paradoxical protection from atherosclerosis and thrombosis in a mouse model of sickle cell disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98139/1/bjh12342.pd

Type I interferons modulate vascular function, repair, thrombosis, and plaque progression in murine models of lupus and atherosclerosis

Objective Patients with systemic lupus erythematosus (SLE) have a notable increase in atherothrombotic cardiovascular disease (CVD) which is not explained by the Framingham risk equation. In vitro studies indicate that type I interferons (IFNs) may play prominent roles in increased CV risk in SLE. However, the in vivo relevance of these findings, with regard to the development of CVD, has not been characterized. This study was undertaken to examine the role of type I IFNs in endothelial dysfunction, aberrant vascular repair, and atherothrombosis in murine models of lupus and atherosclerosis. Methods Lupus‐prone New Zealand mixed 2328 (NZM) mice and atherosclerosis‐prone apolipoprotein E– knockout (apoE −/− ) mice were compared to mice lacking type I IFN receptor (INZM and apoE −/− IFNAR −/− mice, respectively) with regard to endothelial vasodilatory function, endothelial progenitor cell (EPC) function, in vivo neoangiogenesis, plaque development, and occlusive thrombosis. Similar experiments were performed using NZM and apoE −/− mice exposed to an IFNα‐containing or empty adenovirus. Results Loss of type I IFN receptor signaling improved endothelium‐dependent vasorelaxation, lipoprotein parameters, EPC numbers and function, and neoangiogenesis in lupus‐prone mice, independent of disease activity or sex. Further, acute exposure to IFNα impaired endothelial vasorelaxation and EPC function in lupus‐prone and non–lupus‐prone mice. Decreased atherosclerosis severity and arterial inflammatory infiltrates and increased neoangiogenesis were observed in apoE −/− IFNAR −/− mice, compared to apoE −/− mice, while NZM and apoE −/− mice exposed to IFNα developed accelerated thrombosis and platelet activation. Conclusion These results support the hypothesis that type I IFNs play key roles in the development of premature CVD in SLE and, potentially, in the general population, through pleiotropic deleterious effects on the vasculature.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93543/1/34504_ftp.pd

Management of myocardial stunning associated with electroconvulsive therapy guided by hyperventilation echocardiography

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31693/1/0000629.pd