Pyrrolidine dithiocarbamate improves mortality in a rat model of severe hemorrhage.

BACKGROUND: Hemorrhagic shock is a life threatening condition characterized by diminishing organ function. The aim of this study was to determine whether an effective pyrrolidine dithiocarbamate (PDTC) treatment protocol could be established to decrease organ dysfunction and mortality in a lethal hemorrhagic shock-resuscitation (HSR) model. MATERIALS AND METHODS: Sprague-Dawley rats were randomized into three experimental groups; HSR alone (HSR), PDTC (100 mg/kg) administered 12 h pre-HSR (PDTC-12), and PDTC administered 1 h post-shock prior to resuscitation (PDTC+1). Hemorrhage was induced by arterial blood withdrawal to a mean arterial pressure (MAP) of 25 ± 5 mmHg for 1 h. Resuscitation was performed until pre-HSR MAP was attained. Blood was collected immediately prior to HSR, 1 h post-shock, and at protocol end. Measurements of base excess, lactate, arterial partial pressure of carbon dioxide (PaCO(2)) and oxygen (PaO(2)), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, blood urea nitrogen (BUN), and lipase were performed. RESULTS: In PDTC+1 animals, PDTC was ineffective in improving survival. In contrast, survival was significantly increased in the PDTC-12 animals versus PDTC+1 and HSR groups. Analysis of physiologic parameters demonstrated that elevations in base deficit and lactate levels following hemorrhage were blunted by PDTC administration in the PDTC-12 group. At time of death, creatinine, ALT, and AST levels were significantly higher in HSR versus PDTC-12 animals. CONCLUSIONS: Administration of PDTC 12 h prior to HSR significantly improves survival through preservation of organ function.

Coronary artery stents and antiplatelet therapy in patients with cirrhosis.

GOALS: To describe our experience with coronary artery stenting and antiplatelet therapy in cirrhotic patients and compare rates of bleeding with a control group. BACKGROUND: Although there are data on cardiac evaluation and perioperative cardiac risk in cirrhotic patients, there is a paucity of information on outcomes in cirrhotic patients with coronary artery stents. Cirrhotic patients may be at increased risk for complications, including gastrointestinal bleeding as a result of antiplatelet therapy prescribed after stenting. STUDY: We performed a retrospective study of complications in cirrhotics that received a coronary artery stent followed by clopidogrel and aspirin prescribed to prevent stent occlusion. Cirrhotics with stents were compared with an age and sex-matched control group with cirrhosis without stents and not on aspirin. RESULTS: Among 423 cirrhotic patients who underwent liver transplant evaluation, 16 patients (3.8%) received a stent of which 9 underwent liver transplant. Two patients with varices (12.5%) in the stent group had fatal variceal bleeding and 2 controls (6.3%) had nonfatal variceal bleeding during follow-up while on antiplatelet therapy (P=0.86). There were no significant differences in transfusion requirements between the 9 liver transplant recipients with stents compared with the control group, P=0.69 for packed red blood cells. CONCLUSIONS: In our experience, it is safe for cirrhotic patients without varices to receive a coronary artery stent and for cirrhotic patients with coronary artery stents to be considered for liver transplantation. Larger prospective studies are needed to confirm these results and evaluate the risk of bleeding in cirrhotics with varices who receive coronary artery stents and antiplatelet therapy.