Carvedilol-Enriched Cold Oxygenated Blood Cardioplegia Improves Left Ventricular Diastolic Function After Weaning From Cardiopulmonary Bypass

Objectives: To investigate whether adding carvedilol, a nonselective beta- and selective alpha(1)-receptor blocking agent with antioxidant properties, to oxygenated blood cardioplegia improves myocardial function after weaning from bypass.Design: A randomized controlled study.Setting: A university laboratory.Participants: Twenty anesthetized pigs, Norwegian Landrace.Interventions: On cardiopulmonary bypass, cardiac arrest was induced with cold (12 degrees C), oxygenated blood cardioplegia, enriched with carvedilol or vehicle, and repeated every 20 minutes. After 100 minutes, the heart was reperfused and weaned.Measurements and Main Results: Left ventricular function was evaluated with pressure-volume loops, local myocardial systolic strain, and strain rate from Speckle tracking analysis and multilayer short-axis tissue Doppler Imaging. In the carvedilol group, the load-independent logarithmic end diastolic pressure volume relationship, beta, decreased from 1 to 3 hours of reperfusion and was low, 0.028 +/- 0.004 v 0.042 +/- 0.007 (p < 0.05) in controls at 3 hours, demonstrating improved left ventricular compliance. The diastolic relaxation constant tau was decreased, 28.9 +/- 0.6 ms v 34.6 +/- 1.3 ms (p(g) < 0.035), and dP/dt(min) was more negative, -1,462 +/- 145 mmHg/s v -1,105 +/- 105 mmHg/s (p(g) = 0.024), for carvedilol v control group. The systolic variables, preload recruitable stroke work and end-systolic pressure volume relationship, did not differ between groups, neither did left ventricular systolic strain and strain rate. Myocardial oxidative stress, measured as tissue levels of malondialdehyde, was reduced by carvedilol, 0.19 +/- 0.01 compared to 0.24 +/- 0.01 nmol/mg (p = 0.004) in controls.Conclusions: Carvedilol added to blood cardioplegia improved diastolic cardiac function and reduced oxidative stress during the first 3 hours after reperfusion in a porcine model, with 100 minutes of cardioplegic arrest. (C) 2016 The Authors. Published by Elsevier Inc. All rights reserved

Stem Cell-Based and Tissue Engineering Approaches for Skeletal Muscle Repair

Skeletal muscle tissue exhibits significant regeneration capacity upon injury or disease. This intrinsic regeneration potential is orchestrated by stem cells termed satellite cells, which undergo activation and differentiation in response to muscle insult, giving rise to fusion-competent myogenic progenitors responsible for tissue rejuvenation. Skeletal muscle diseases such as Duchenne muscular dystro-phy are characterized by progressive loss of muscle mass which precipitates reduced motility, paralysis, and in some occurrences untimely death. A manifold of muscle pathologies involve a failure to efficiently regenerate the muscle tissue, rendering stem cell-based approaches an attractive therapeutic strategy. Here we will present past and contemporary methods to treat skeletal muscle degeneration by stem cell therapy, covering prominent challenges facing this technology and potential means to overcome current hurdles. A primary focus of this chapter is directed toward illustrating innovative ways to utilize stem cells alone or in conjunction with biomaterials and tissue engineering techniques to remedy Duchenne muscular dystrophy or volumetric muscle loss