Development of circulatory and metabolic shock following transient portal triad occlusion.

Liver ischemia is purposefully induced by portal triad occlusion (PTO) in several clinical situations including liver surgery for trauma, tumor, and transplantation. Despite significant morbidity from PTO, the hemodynamic and metabolic effects of PTO have not been evaluated relative to duration of ischemia. We investigated this using a total hepatic ischemia model. Rats received isoflurane anesthesia, carotid artery and jugular vein cannulation, and serial measurements of cardiac output (CO), mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), stroke volume (SV), systemic vascular resistance (SVR), superior mesenteric artery blood flow (SMAF), intestinal vascular resistance (IVR), pH, pCO2, pO2, lactate, glucose, hematocrit (HCT), white blood cell count (WBC), and total neutrophils. Each group received 0, 15, 30, 45, or 60 min of PTO followed by 2 hr of reperfusion. All sham ischemia animals remained hemodynamically stable throughout the study. However, in the ischemic groups, there were significant time-dependent decreases in MAP, HR, CO, CVP, SV, SMAF, and pH, and increases in SVR, IVR, HCT, and lactate, while pCO2, pO2, glucose, and WBC remained stable. All of the ischemic animals survived except those that received 60 min of PTO. In this group, all of the animals survived the ischemic period; however, only one animal survived beyond 60 min of reperfusion. These data demonstrate a time-dependent circulatory and metabolic shock following PTO heralded by intestinal venous pooling and loss of intravascular fluid, and culminating in death. Careful hemodynamic monitoring and restoration of blood volume in the trauma patient may reduce morbidity and mortality.

Human studies on alcohol and susceptibility to HIV infection.

Here we review existing evidence that alcohol intake may influence the susceptibility to human immunodeficiency virus type 1 (HIV-1) infection and the effect that alcohol may have on accelerating the onset of AIDS after the initial infection. Possible immunological and psychosocial mechanisms to explain the increased incidence of HIV-1 infection in alcoholism are discussed.

Evidence that the large loss of glutathione observed in ischemia/reperfusion of the small intestine is not due to oxidation to glutathione disulfide.

Reperfusion injury following ischemia is thought to be the consequence of reactive oxygen species possibly generated either by xanthine oxidase activity or by processes associated with neutrophil activation in the affected organ or tissue. The conversion of xanthine dehydrogenase to the oxidase as well as the interactions between endothelium and neutrophils in the margination and activation of the latter are all considered to be results of conditions resulting from the ischemic episode. Determination of the redox status of glutathione in an ischemic/reperfused organ is frequently employed as an indicator of oxidative stress created by the production of oxygen free radicals during the reperfusion period. In this procedure, the ratio of oxidized glutathione (GSSG) to total glutathione (GSH + GSSG) is utilized to demonstrate the proportion of glutathione oxidized during reperfusion. We determined this ratio in the rat small intestine during ischemia and reperfusion and found that while the ratio of GSSG/(GSH + GSSG) does increase, this increase was the result of GSH disappearance rather than an increase in GSSG, and that essentially all of this loss occurred during the ischemic episode. We demonstrated that no oxidation of GSH occurred that was attributable to reperfusion per se; nor was there an increase of GSSG during this reoxygenation period.