The lack of functional dystrophin protein in Duchenne muscular dystrophy (DMD) renders muscle fibers highly fragile and susceptible to damage during contractions. Contraction-mediated injury is a major contributor to the progressive degeneration and etiology of muscle wasting in DMD. The prevailing understanding is that large fibers are highly susceptible to contraction damage and are affected preferentially, whereas smaller fibers are relatively spared in DMD. We tested the hypothesis that a pharmacological treatment that caused myofiber hypertrophy would increase the susceptibility of muscles from dystrophindeficient mdx mice to contraction-induced injury, and thus aggravate the dystrophic pathology. The -agonist formoterol (100 g/kg per day , i.p.) was administered to mdx mice for 28 days. Formoterol increased muscle mass , fiber cross-sectional area, and maximum force producing capacity by 30%, 23% , and 21% , respectively , in fast-twitch tibialis anterior muscles of mdx mice. Myofiber hypertrophy and increased maximum force producing capacity were also observed in the predominantly slow-twitch soleus muscles of mdx mice. Our original hypothesis was rejected since tibialis anterior muscles from formoterol-treated mdx mice had lower cumulative force deficits , indicating that they were less susceptible to contraction-induced injury. Formoterol treatment did not affect injury susceptibility in soleus muscles. These findings indicate that making dystrophic muscles bigger protects them from contraction damage and does not aggravate the dystrophic pathophysiology. These novel results further support the contention that anabolic agents have therapeutic potential for muscle wasting conditions including DMD. (Am J
Redo-sternotomy and aortic valve replacement in patients with advanced liver disease is rare and associated with a prohibitive morbidity and mortality. Refractory coagulopathy is common and a consequence of intense activation of the coagulation system that can be triggered by contact of blood with the cardiopulmonary bypass circuitry, bypass-induced fibrinolysis, platelet activation and dysfunction, haemodilution, surgical trauma, hepatic decompensation and hypothermia. Management can be further complicated by right heart dysfunction, porto-pulmonary hypertension, poor myocardial protection, and hepato-renal syndrome. Complex interactions between coagulation/fibrinolysis and systemic inflammatory response syndrome reactions like "post-perfusion-syndrome" also compound haemostatic failure. Given the limited information available for the specific management and prevention of cardiopulmonary bypass-induced haemostatic failure, this report serves to guide the anaesthesia and medical management of future cases of a similar kind. We discuss our multimodal management of haemostatic failure using pharmacological strategies, thromboelastography, continuous cerebral and liver oximetry, and continuous cardiac output monitoring.
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