Arora, Amindra S.

Calpain proteases contribute to hepatocyte necrosis during anoxia. Our aim was to ascertain the mechanism causing calpain activation during anoxia. In rat hepatocytes, a twofold increase in calpain activity occurred despite the lack of an increase in cytosolic Ca2+ concentration ([Ca2+]i). The increase in calpain activity was not associated with an increase in calpain mRNA or a decrease in calpastatin mRNA expression. Because phospholipid degradation products generated by phospholipases can activate calpains at physiological [Ca2+]i, we determined the effect of phospholipase inhibitors and activators on calpain activity. Pretreatment of hepatocytes with fluphenazine, a phospholipase inhibitor, decreased calpain activation and improved cell survival. Melittin, a phospholipase A2 activator, increased calpain activity and potentiated cell killing. Finally, phospholipid degradation preceded the increase in calpain activity. Thus the enhanced calpain activity occurring in hepatocytes during anoxia 1) is regulated at the posttranslational level and 2) appears to be dependent on phospholipase activity. These data suggest a novel cascade for degradative hydrolase activity during hepatocyte necrosis by anoxia with phospholipase-mediated activation of calpains.

AbstractBackgroundBloating, flatulence, early satiety, and dysphagia resolve in more than 90% of patients early after fundoplication. Gastric dysfunction can persist, however, and a small number of patients develop severe gastric dysfunction (gastroparesis). Management of gastroparesis after antireflux procedures is generally conservative, but gastroparesis can become refractory to medical therapy. The aim of this study was to assess the role of gastric resection in the management of the unusual patient with severe postfundoplication gastric dysfunction.MethodsFrom January 1990 to October 2010, a total of 5,129 gastric resections were performed at our institution. From this cohort, we identified nine patients with postfundoplication gastric dysfunction managed with gastric resection. Clinical records were reviewed retrospectively for preoperative evaluation, perioperative course, and long‐term outcomes.ResultsOver 20 years, nine patients were treated with gastric resection for debilitating gastric dysfunction after antireflux surgery. Seven of the nine patients were female; the median preoperative body mass index was 25 kg/m2 (18–31 kg/m2). Median follow‐up was 23 months (1–97 months). Preoperatively, five patients required enteral feeding. Postoperatively, although there were no deaths, one patient required operative drainage of a subphrenic abscess, one developed temporary respiratory failure, and one was readmitted for partial small bowel obstruction. Six of the nine patients maintain their nutrition orally, but three are maintained with enteral nutrition. Only two patients are subjectively asymptomatic.ConclusionsOutcomes after gastric resection for postfundoplication gastric dysfunction are poor, with three of the nine patients requiring supplemental nutrition and seven of the nine having persistent symptoms.