Left ventricular outflow tract obstruction provoked during dobutamine stress echocardiography predicts future chest pain, syncope, and near syncope.

Background: Although dobutamine stress echocardiography (DSE) is associated with dynamic left ventricular (LV) obstruction, it is unknown whether such obstructive event, in general, and the specific site of obstruction, in particular, have unique clinical prognostic significance. We sought to determine whether dynamic LV outflow tract (LVOT) versus LV midcavitary obstruction provoked during DSE would predict future chest pain, syncope, and/or near syncope.

Methods: Two hundred thirty-seven patients (145 men and 92 women, mean age 58 +/- 13 [+/-SD] years) without DSE-provoked ischemia underwent continuous wave Doppler interrogation to detect any inducible dynamic flow obstruction.

Tumor necrosis factor-alpha does not modulate ischemia/reperfusion injury in naïve myocardium but is essential for the development of late preconditioning.

The role of tumor necrosis factor (TNF)-alpha in myocardial ischemia/reperfusion injury remains controversial. We used homozygous TNF-alpha null mice (TNF-alpha(-/-)) to determine whether TNF-alpha modulates myocardial ischemia/reperfusion injury. Mice were subjected to a 30-min coronary occlusion followed by 24 h of reperfusion.

Cardioprotection during the final stage of the late phase of ischemic preconditioning is mediated by neuronal NO synthase in concert with cyclooxygenase-2.

The infarct-sparing effect of the late phase of ischemic preconditioning (late PC) lasts for 72 hours. Upregulation of both cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) has been shown to be essential to the protection in the initial stage of late PC (24 hours after PC); however, the mechanisms underlying the protection in the final stage of late PC (48 to 72 hours after PC) are unknown. Conscious rabbits were preconditioned with six cycles of 4-minute coronary occlusion/4-minute reperfusion.

Mechanism of cyclooxygenase-2 upregulation in late preconditioning.

Although the cardioprotection of late preconditioning (PC) is known to be mediated by both inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), the signaling mechanism responsible for COX-2 upregulation and the interaction between iNOS and COX-2 remain unknown. A total of 122 mice were used to address this issue. In wild-type mice preconditioned with six cycles of 4-min coronary occlusion-4-min reperfusion, ischemic PC resulted in rapid activation of nuclear STAT1/3 through tyrosine phosphorylation (STAT1: 339 +/- 48% of control; STAT3: 389 +/- 46% of control) and increased STAT1/3-DNA binding activity (687 +/- 58% of control) at 30 min after PC, with subsequent upregulation of COX-2 protein (373 +/- 60% of control) and activity(increased myocardial levels of PGE2, PGF(2alpha), and 6-keto-PGF(1alpha)) at 24 h.

Effect of aspirin on late preconditioning against myocardial stunning in conscious rabbits.

Objectives: The goal of this study was to investigate the effect of three different doses of acetylsalicylic acid (aspirin) (ASA) on the late phase of ischemic preconditioning (PC) against myocardial stunning.

Background: Although recent evidence indicates that the late phase of ischemic PC is mediated by cyclooxygenase-2 (COX-2), the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-2 activity on late PC has not been evaluated; ASA is the most widely used NSAID. Therefore, we determined whether ASA impedes the development of late PC.

Mitochondrial PKCepsilon and MAPK form signaling modules in the murine heart: enhanced mitochondrial PKCepsilon-MAPK interactions and differential MAPK activation in PKCepsilon-induced cardioprotection.

Although activation of protein kinase C (PKC) epsilon and mitogen-activated protein kinases (MAPKs) are known to play crucial roles in the manifestation of cardioprotection, the spatial organization of PKCepsilon signaling modules in naïve and protected myocardium remains unknown. Based on evidence that mitochondria are key mediators of the cardioprotective signal, we hypothesized that PKCepsilon and MAPKs interact, and that they form functional signaling modules in mitochondria during cardioprotection. Both immunoblotting and immunofluorescent staining demonstrated that PKCepsilon, ERKs, JNKs, and p38 MAPK co-localized with cardiac mitochondria.

Intermediate-term results after partial left ventriculectomy for end-stage dilated cardiomyopathy: is there a survival benefit?

Background: The mortality of congestive heart failure remains high despite advances in medical therapy. Partial left ventriculectomy (PLV) has been advocated as a surgical alternative for select patients with dilated cardiomyopathy.

Methods: A prospective clinical trial of PLV for patients with end-stage idiopathic dilated cardiomyopathy was performed.

Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: an overview of a decade of research.

Over the past decade, an enormous number of studies (>100) have focused on the role of nitric oxide (NO) in myocardial ischemia. It is important to distinguish the function of NO in unstressed (non-preconditioned) myocardium from its function in preconditioned myocardium (i.e.

An essential role of the JAK-STAT pathway in ischemic preconditioning.

The goal of this study was to determine the role of the Janus tyrosine kinase (JAK)-signal transducers and activators of transcription (STAT) pathway in the late phase of ischemic preconditioning (PC). A total of 230 mice were used. At 5 min after ischemic PC (induced with six cycles of 4-min coronary occlusion/4-min reperfusion), immunoprecipitation with anti-phosphotyrosine (anti-pTyr) antibodies followed by immunoblotting with anti-JAK antibodies revealed increased tyrosine phosphorylation of JAK1 (+257 +/- 53%) and JAK2 (+238 +/- 35%), indicating rapid activation of these two kinases.

Cardiac-specific abrogation of NF- kappa B activation in mice by transdominant expression of a mutant I kappa B alpha.

Nuclear factor-kappaB (NF-kappa B) is a pleiotropic oxidant-sensitive transcription factor that is present in the cytosol in an inactive form complexed to an inhibitory kappaB (I kappa B) monomer. Various stimuli, including ischemia, hypoxia, free radicals, cytokines, and lipopolysaccharide (LPS), activate NF-kappa B by inducing phosphorylation of I kappa B. Phosphorylation of serine residues at positions 32 and 36 is critical for ubiquitination and degradation of I kappa B alpha with consequent migration of NF-kappa B to the nucleus.

Initial experience with the AbioCor implantable replacement heart at the University of Louisville.

Potential benefits of heart transplantation are limited by the severe donor organ shortage. The AbioCor implantable replacement heart has been developed as a potential alternative to heart transplantation. We report our initial experience with the AbioCor in a bovine model.

Bradykinin-induced preconditioning in patients undergoing coronary angioplasty.

Objectives: The purpose of this study was to determine whether administration of bradykinin reproduces the cardioprotective effects of ischemic preconditioning (PC) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA).

Background: Experimental studies suggest that activation of the bradykinin B2 receptor is an important trigger of ischemic PC. However, it is unknown whether bradykinin can precondition human myocardium against ischemia in vivo.