A simple and easy technique to overcome anatomic challenges of transradial access in STEMI patients.

BACKGROUND: Transradial access (TRA) is associated with fewer access-related complications, earlier discharge and lower mortality than transfemoral access (TFA), being the preferred route to perform primary percutaneous coronary interventions (PPCIs) in STEMI patients. However, the radial artery is smaller, more superficial and thinner than the femoral artery, which may make PPCIs difficult. PURPOSE: This study describes a practical solution to overcome several of the anatomical difficulties during the TRA, demonstrating its outcomes during clinical practice. METHODS: The authors reviewed the clinical records of 1510 STEMI patients who underwent PPCIs over seven years. Of these, 95 (6.3%) patients experienced problems in advancing a 6F guiding catheter and underwent to STR technique. This technique consists in the use of a longer 5Fr STR flush catheter, which can be used as a "child" type rapid exchange catheter inside the 6Fr guiding catheter, adopting a 5-in-6 Fr technique and creating a smooth distal tip transition of the 6Fr guiding catheter. RESULTS: In 89/95 patients (93.7%), this new technique was successful. The majority of these patients were female (51; 53.7%) and the mean age was 67 ± 14.3 years. The mean reperfusion time since arrival at the catheterization laboratory with STR technique was 24.5 ± 9.9 min, being statistically shorter than when a crossover to TFA was used (29.3 ± 9.5 min; p < 0.017). PPCIs were successfully completed in all different coronary arteries, without complications related to the procedure. CONCLUSIONS: The STR technique is a simple and useful approach that allowed more successful passage of guiding catheters through difficult TRA, allowing a reduction of crossover to TFA in this study to 2.4 %, which translates into a shorter reperfusion time.

An Unusual Cause of Aborted Sudden Cardiac Death in a Middle-Aged Female Marathoner.

Although most congenital coronary artery anomalies have no prognostic implications, associations with sudden cardiac death have been described, particularly in the young. We report an exercise-associated collapse in an otherwise asymptomatic middle-aged female marathoner. The aborted sudden cardiac death approach revealed an unexpected initial presentation of a malignant anomalous left main coronary artery origin, with ostial stenosis and interarterial course. The present case illustrates an unusually longstanding coexistence of a malignant anatomical variant with a persistent trigger.

MicroRNA-155 Amplifies Nitric Oxide/cGMP Signaling and Impairs Vascular Angiotensin II Reactivity in Septic Shock.

OBJECTIVES: Septic shock is a life-threatening clinical situation associated with acute myocardial and vascular dysfunction, whose pathophysiology is still poorly understood. Herein, we investigated microRNA-155-dependent mechanisms of myocardial and vascular dysfunction in septic shock. DESIGN: Prospective, randomized controlled experimental murine study and clinical cohort analysis. SETTING: University research laboratory and ICU at a tertiary-care center. PATIENTS: Septic patients, ICU controls, and healthy controls. Postmortem myocardial samples from septic and nonseptic patients. Ex vivo evaluation of arterial rings from patients undergoing coronary artery bypass grafting. SUBJECTS: C57Bl/6J and genetic background-matched microRNA-155 knockout mice. INTERVENTIONS: Two mouse models of septic shock were used. Genetic deletion and pharmacologic inhibition of microRNA-155 were performed. Ex vivo myographic studies were performed using mouse and human arterial rings. MEASUREMENTS AND MAIN RESULTS: We identified microRNA-155 as a highly up-regulated multifunctional mediator of sepsis-associated cardiovascular dysfunction. In humans, plasma and myocardial microRNA-155 levels correlate with sepsis-related mortality and cardiac injury, respectively, whereas in murine models, microRNA-155 deletion and pharmacologic inhibition attenuate sepsis-associated cardiovascular dysfunction and mortality. MicroRNA-155 up-regulation in septic myocardium was found to be mostly supported by microvascular endothelial cells. This promoted myocardial microvascular permeability and edema, bioenergetic deterioration, contractile dysfunction, proinflammatory, and nitric oxide-cGMP-protein kinase G signaling overactivation. In isolate cardiac microvascular endothelial cells, microRNA-155 up-regulation significantly contributes to LPS-induced proinflammatory cytokine up-regulation, leukocyte adhesion, and nitric oxide overproduction. Furthermore, we identified direct targeting of CD47 by microRNA-155 as a novel mechanism of myocardial and vascular contractile depression in sepsis, promoting microvascular endothelial cell and vascular insensitivity to thrombospondin-1-mediated inhibition of nitric oxide production and nitric oxide-mediated vasorelaxation, respectively. Additionally, microRNA-155 directly targets angiotensin type 1 receptor, decreasing vascular angiotensin II reactivity. Deletion of microRNA-155 restored angiotensin II and thrombospondin-1 vascular reactivity in LPS-exposed arterial rings. CONCLUSIONS: Our study demonstrates multiple new microRNA-155-mediated mechanisms of sepsis-associated cardiovascular dysfunction, supporting the translational potential of microRNA-155 inhibition in human septic shock.

A high-calorie diet attenuates cachexia and adipose tissue inflammation in monocrotaline-induced pulmonary hypertensive rats.

INTRODUCTION: Cardiac cachexia is a catabolic state in which adipose tissue atrophy is accompanied by a proinflammatory state. The molecular mechanisms underlying proinflammatory activation remain, however, largely unknown. In this experimental study, the effect of a high-calorie diet was analyzed in the advanced stages of monocrotaline-induced pulmonary hypertension (PH). METHODS: Male Wistar rats (180-200 g; n=28) were randomly injected with either monocrotaline (MCT; 60 mg/kg; sc) or vehicle. Each group was then assigned to either a regular diet (2.9 kcal/g) or a high-calorie diet with a high fat and simple carbohydrate content (5.4 kcal/g). Twenty-four to 32 days after injection, adipose tissue was collected for morphometric, histological and molecular analysis. The proportional weight of the gonadal fat pad was used as an adiposity index. Detection of macrophages in adipose tissue was performed with an anti-CD6 monoclonal antibody. Interleukin-6 (IL-6) mRNA quantification was performed using real-time RT-PCR. RESULTS: MCT injection was accompanied by a reduction in adiposity (-51 +/- 3.4%) and by adipocyte atrophy (-18 +/- 1.4%). This was accompanied by IL-6 overexpression (+879 +/- 444%), but there were no changes in adipose tissue macrophage content. Exposure to a high-calorie diet in the MCT group attenuated adipose tissue atrophy as well as IL-6 gene overexpression. CONCLUSION: A high-calorie diet attenuates cachexia and proinflammatory activation in the advanced stages of monocrotaline-induced PH. These results suggest nutritional state potential therapeutic target in advanced PH