Elevated uric acid levels predict allograft vasculopathy in cardiac transplant recipients.

Background: Cardiac allograft vasculopathy (CAV) poses the greatest threat to the long-term survival of cardiac transplant recipients, and these individuals often exhibit elevated levels of uric acid (UA), a stimulator of T cells. We hypothesized that hyperuricemia is associated with CAV in cardiac transplant recipients.

Methods: UA levels were measured in cardiac transplant recipients between January 2003 and January 2005.

Chronic allopurinol administration ameliorates maladaptive alterations in Ca2+ cycling proteins and beta-adrenergic hyporesponsiveness in heart failure.

Xanthine oxidase (XO) activity contributes to both abnormal excitation-contraction (EC) coupling and cardiac remodeling in heart failure (HF). beta-Adrenergic hyporesponsiveness and abnormalities in Ca(2+) cycling proteins are mechanistically linked features of the HF phenotype. Accordingly, we hypothesized that XO influences beta-adrenergic responsiveness and expression of genes whose products participate in deranged EC coupling.

Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction.

Although clinical trials of autologous whole bone marrow for cardiac repair demonstrate promising results, many practical and mechanistic issues regarding this therapy remain highly controversial. Here, we report the results of a randomized study of bone-marrow-derived mesenchymal stem cells, administered to pigs, which offer several new insights regarding cellular cardiomyoplasty. First, cells were safely injected by using a percutaneous-injection catheter 3 d after myocardial infarction.

Xanthine oxidase inhibition ameliorates cardiovascular dysfunction in dogs with pacing-induced heart failure.

We hypothesized that chronic xanthine oxidase inhibition (XOI) would have favorable effects on both ventricular and vascular performance in evolving heart failure (HF), thereby preserving ventricular-vascular coupling. In HF, XOI reduces oxidative stress and improves both vascular and myocardial function. Dogs were randomized to receive either allopurinol (100 mg/day p.

Treatment of saphenous vein graft thrombosis with distal protection, thrombectomy, and adenosine prior to reperfusion: a complete approach to preserving microvascular integrity.

We report the treatment of an acute myocardial infarction presenting late with thrombotic total occlusion of a saphenous vein graft. A novel approach was used to prevent microvascular obstruction and reperfusion injury, with a distal protection system, a thrombectomy device, and administration of intracoronary adenosine prior to restoration of flow, so that initial reperfusion was done with maximal microvascular vasodilatation.

Positive inotropic and lusitropic effects of HNO/NO- in failing hearts: independence from beta-adrenergic signaling.

Nitroxyl anion (HNONO(-)), the one-electron reduced form of nitric oxide (NO), induces positive cardiac inotropy and selective venodilation in the normal in vivo circulation. Here we tested whether HNO/NO(-) augments systolic and diastolic function of failing hearts, and whether contrary to NO/nitrates such modulation enhances rather than blunts beta-adrenergic stimulation and is accompanied by increased plasma calcitonin gene-related peptide (CGRP). HNO/NO(-) generated by Angelis' salt (AS) was infused (10 microg/kg per min, i.

Imbalance between xanthine oxidase and nitric oxide synthase signaling pathways underlies mechanoenergetic uncoupling in the failing heart.

Inhibition of xanthine oxidase (XO) in failing hearts improves cardiac efficiency by an unknown mechanism. We hypothesized that this energetic effect is due to reduced oxidative stress and critically depends on nitric oxide synthase (NOS) activity, reflecting a balance between generation of nitric oxide (NO) and reactive oxygen species. In dogs with pacing-induced heart failure (HF), ascorbate (1000 mg) mimicked the beneficial energetic effects of allopurinol, increasing both contractility and efficiency, suggesting an antioxidant mechanism.