Hepatic apoptotic activity following transient normothermic inflow occlusion and reperfusion in the swine model.

Accelerated hepatic apoptosis was first described in portal vein-ligated livers but has since been reported in a variety of liver injuries. Because porto-prival states can induce apoptosis we sought to determine whether transient ischemic periods followed by reperfusion would trigger such cell death. The cytokines TNF-alpha and TGF-beta are known to facilitate apoptosis and are released in response to a number of stimuli including ischemia. We also investigated alterations in plasma and tissue levels of these cytokines which might lend support to their role in increased apoptotic activity following ischemia/reperfusion. Female pigs were used as the experimental model. Inflow occlusion of portal and hepatic arterial blood was performed to a portion of the swine liver directing the entire splanchnic flow to the remaining hepatic lobes for a period of 2 h. The livers were then reperfused and plasma and tissue samples taken for determination of apoptotic activity utilizing cell death immunoperoxidase staining of 3'-OH DNA ends generated by fragmentation and ELISA assay of histone-associated DNA fragments. Plasma and tissue levels of TNF-alpha and plasma levels of TGF-beta were determined by ELISA assay. An increase in apoptotic activity following reperfusion was seen at Day 2 and Day 4 compared to preischemic values by the cell death stain. The ELISA cell death assay showed an increase in apoptotic activity at 60 min, Day 2, and Day 4. Moreover, the ELISA cell death assay showed enhanced apoptotic activity in "hyperperfused" hepatic lobes compared to preischemic, or resting, liver. This was also observed when compared to sham-operated animals. Surprisingly, there was no detectable increase in plasma TNF-alpha or TGF-beta levels following ischemia/reperfusion, although homogenized liver TNF-alpha levels were increased at 60 min and Day 2 following reperfusion. We conclude that transient hepatic inflow occlusion followed by reperfusion can induce increased apoptotic activity in the swine model. Furthermore, increased apoptotic activity also occurs in the hyperperfused liver raising the possibility of a locally active factor or global hepatic expression of receptor activity in response to ischemia/reperfusion. This period of ischemia/reperfusion did not produce a detectable increase in circulating cytokine levels, and accelerated apoptosis could not be linked to heightened TNF-alpha or TGF-beta plasma activity. Higher tissue levels of TNF-alpha could reflect enhanced binding to TNF cell surface receptors or amplified receptor expression.

The effect of prostaglandin E1 on liver adenine nucleotides and cytoplasmic enzymes in a porcine model of normothermic hepatic ischemia.

The liver has been judged relatively resistant to ischemia, but prolonged inflow occlusion at normothermic conditions can produce evidence of reversible or irreversible hepatocellular damage. Cytoprotective agents have been used both experimentally and clinically to afford extended viability of hepatocytes under reduced perfusion. One agent, prostaglandin E1, has been described clinically as effective in sustaining liver function under ischemic conditions. We have sought to verify this observation in an experimental model using prolonged normothermic inflow occlusion. Twenty miniature pigs were anesthetized and subjected to subtotal normothermic hepatic inflow occlusion (portal vein, hepatic artery, choledochal vessels) to allow for sufficient splanchnic decompression. Half of the animals received pretreatment with prostaglandin E1 (alprostadil) 500 micrograms intravenously. Inflow occlusion was maintained for 2 hours followed by reperfusion and killing 24 hours later. As a measure of functional preservation, the tissue adenine nucleotides adenosine monophosphate, diphosphate, and triphosphate (AMP, ADP, ATP) were measured in ischemic liver by freeze-clamping and high-performance liquid chromatography during occlusion and after reperfusion. Cytosolic enzyme determinations (aspartate transaminase, alanine transaminase, lactate dehydrogenase) were also made before occlusion and after reperfusion. As a possible indicator of cellular injury, blood ionized Ca++ was measured before inflow occlusion and after reperfusion. Although no difference was found in levels of AMP and ADP between prostaglandin E1 and control animals, ATP levels rose significantly higher during recovery in prostaglandin E1 animals at 60 minutes and 24 hours after reperfusion (13.97 +/- 1.29 and 13.60 +/- 0.91 mumoles/gm dry weight prostaglandin E1 vs. 9.25 +/- 0.97 and 9.80 +/- 0.85 mumoles/gm dry weight co control, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency of cardiac contusion in nonpenetrating chest injury.

Seventy-five patients with nonpenetrating chest injuries were evaluated with electrocardiography, cardiac enzyme determination, 2-dimensional echocardiography and radionuclide ventriculography to document the incidence of cardiac abnormalities. Although the electrocardiograms showed ST-T wave changes in 25 patients (33%), sensitivity (47%) and specificity (79%) for echocardiographic and radionuclide abnormalities were poor. Cardiac enzymes were abnormal in 10 patients (13%), sensitivity for echocardiographic or radionuclide abnormalities, or both, was 29% and specificity 90%. Wall motion abnormalities were detected in 11 patients (18%) by radionuclide studies and in 3 patients (6%) by echocardiography. A pericardial effusion was present in 5 patients (10%). Two patients (4%) died of noncardiac causes; neither had wall motion abnormalities. This study documents the favorable outcome of patients with blunt chest injuries and does not suggest that echocardiography or radionuclide studies should be performed routinely on such patients.

Operative versus endoscopic gastrostomy. Preliminary results of a prospective randomized trial.

Percutaneous endoscopic gastrostomy in 23 patients was compared with operative gastrostomy in 25 patients in a prospective randomized fashion. Procedure-related morbidity occurred in five patients in each group. Tube feeding was initiated within 48 hours in 96 percent of the percutaneous endoscopic gastrostomy group and in 82 percent of the operative gastrostomy group (p less than 0.1). There were no deaths in the percutaneous endoscopic gastrostomy group, but two patients in the operative gastrostomy group died within 30 days of operation (p less than 0.1). Neither death appeared directly attributable to gastrostomy placement. The cost for a percutaneous endoscopic gastrostomy was less than that of an operative gastrostomy ($757 versus $1,446); however, if endoscopically placed tubes required replacement, as was seen in six patients, total percutaneous endoscopic gastrostomy cost increased to $1,198. Definitive conclusions regarding the superiority of one technique over the other cannot be drawn from this data. Trends favoring the use of percutaneous endoscopic gastrostomy merit continued study.

Massive pneumatosis intestinalis and subcutaneous emphysema: complication of needle catheter jejunostomy.

The safety and efficacy of enteral feeding by needle catheter jejunostomy has prompted its use after many major gastrointestinal operations. Indeed, the technical complications of this procedure are infrequent. This report details the development of massive pneumatosis intestinalis associated with elemental feeding via jejunostomy. The proposed etiology includes excessive gas accumulation within the small intestine secondary to 1) inadequate nasogastric suction, 2) post-traumatic intestinal ileus, and 3) disaccharide fermentation; combined with a mucosal defect created by the catheter jejunostomy. Successful management consists of nasogastric suction and immediate termination of the enteral feeding.