HEPATIC HEAT-SHOCK AND ACUTE-PHASE GENE-EXPRESSION ARE INDUCED SIMULTANEOUSLY AFTER CELIOTOMY IN THE ANESTHETIZED PIG

Background: The liver plays a central role in the whole organism's res ponse to injury. Expression of hepatic acute-phase and heat-shock gene s likely contributes to the restoration of homeostasis after stressful events. However, after prolonged ischemia, hepatic transcription of h eat-shock genes can exclude the simultaneous transcription of acute-ph ase genes. The issue of whether hepatic 72-kd heat-shock protein (hsp7 2) gene expression is induced under perioperative conditions that do n ot result In prolonged liver ischemia and whether this might further a ffect the expression of the acute-phase reactant inter-alpha-trypsin i nhibitor (alpha-Ti) was examined. Methods: Pigs were anesthetized with sodium pentobarbital and ketamine hydrochloride, tracheally intubated , and their lungs ventilated. After celiotomy, a hepatic biopsy sample was obtained. Arterial blood pressure, cardiac output, and total hepa tic blood now were measured. Subsequent biopsies were obtained at 1, 2 , 3, 4, and 6 h after the initial biopsy. Arterial norepinephrine conc entrations were measured using high-pressure liquid chromatography. Nu clear runoff (run on) analysis and Northern blotting were applied to e stimate changes in hsp72 and alpha-Ti gene transcription rates and RNA levels. Western blotting was used to estimate changes in hsp72 levels . Results: Hemodynamic parameters did not change significantly over ti me. Arterial norepinephrine concentrations were increased at all time points. Hepatic hsp72 RNA levels increased up to sixfold while nuclear runoff assays did not detect significant changes in hsp72 gene transc ription rates. The increases in hsp72 RNA levels correlated with accum ulation of hsp72 (up to sevenfold). Increases in alpha-Ti transcriptio n rates up to 42-fold were associated with respective increases in alp ha-Ti RNA levels (up to 17-fold). Conclusions: These data demonstrate that hepatic expression of hsp72 is not confined to conditions that le ad to prolonged liver ischemia but is also part of the response of the liver to surgery under general anesthesia. Furthermore, these conditi ons are permissive for the simultaneous RNA expression of the acute-ph ase reactant alpha-Ti.