The Journal of thoracic and cardiovascular surgery
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J. Thorac. Cardiovasc. Surg. · Nov 2017
CommentPreclinical efficacy and safety of KCNH2-G628S gene therapy for postoperative atrial fibrillation.
Postoperative atrial fibrillation (POAF) is the most common complication occurring after cardiac surgery. Multiple studies have shown significantly increased risks of stroke, myocardial infarction, and death associated with POAF. Current prophylaxis strategies are inadequate to eliminate this problem. We examined the preclinical efficacy and safety of KCNH2-G628S gene transfer to prevent POAF. ⋯ These data indicate that KCNH2-G628S gene therapy can successfully and safely reduce the risk of AF.
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J. Thorac. Cardiovasc. Surg. · Nov 2017
Lungs donated after circulatory death and prolonged warm ischemia are transplanted successfully after enhanced ex vivo lung perfusion using adenosine A2B receptor antagonism.
The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. ⋯ Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donor cardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality.
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J. Thorac. Cardiovasc. Surg. · Nov 2017
Cardiac reprogramming factor Gata4 reduces postinfarct cardiac fibrosis through direct repression of the profibrotic mediator snail.
The administration of a variety of reprogramming factor cocktails has now been shown to reprogram cardiac fibroblasts into induced cardiomyocyte-like cells. However, reductions in ventricular fibrosis observed after reprogramming factor administration seem to far exceed the extent of induced cardiomyocyte-like cell generation in vivo. We investigated whether reprogramming factor administration might primarily play a role in activating antifibrotic molecular pathways. ⋯ Gata4 administration reduces postinfarct ventricular fibrosis and improves ventricular function in a rat coronary ligation model, potentially as a result of Gata4-mediated downregulation of the profibrotic mediator Snail.
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J. Thorac. Cardiovasc. Surg. · Nov 2017
Pulmonary hypertension due to left heart disease causes intrapulmonary venous arterialization in rats.
A rat model of left atrial stenosis-associated pulmonary hypertension due to left heart diseases was prepared to elucidate its mechanism. ⋯ We successfully established a novel, feasible rat model of pulmonary hypertension due to left heart diseases by generating left atrial stenosis. Although pulmonary hypertension was moderate, the pulmonary hypertension due to left heart diseases model rats demonstrated characteristic intrapulmonary venous arterialization and should be used to further investigate the mechanism of pulmonary hypertension due to left heart diseases.