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 response to injury. Expression of hepatic acute-phase and heat-shock genes likely contributes to the restoration of homeostasis after stressful events. However, after prolonged ischemia, hepatic transcription of heat-shock genes can exclude the simultaneous transcription of acute-phase genes. The issue of whether hepatic 72-kd heat-shock protein (hsp72) gene expression is induced under perioperative conditions that do not result in prolonged liver ischemia and whether this might further affect the expression of the acute-phase reactant inter-alpha-trypsin inhibitor (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 hepatic blood flow were measured. Subsequent biopsies were obtained at 1, 2, 3, 4, and 6 h after the initial biopsy. Arterial norepinephrine concentrations were measured using high-pressure liquid chromatography. Nuclear runoff (run on) analysis and Northern blotting were applied to estimate 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 time. 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 transcription rates. The increases in hsp72 RNA levels correlated with accumulation of hsp72 (up to sevenfold). Increases in alpha-Ti transcription rates up to 42-fold were associated with respective increases in alpha-Ti RNA levels (up to 17-fold).


CONCLUSIONS
These data demonstrate that hepatic expression of hsp72 is not confined to conditions that lead to prolonged liver ischemia but is also part of the response of the liver to surgery under general anesthesia. Furthermore, these conditions are permissive for the simultaneous RNA expression of the acute-phase reactant alpha-Ti.
Pannen
B H
BH
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins, Medical Institutions, Baltimore, Maryland, USA.
Maeda
K
K
Ayuse
T
T
Brienza
N
N
Revelly
J P
JP
Robotham
J L
JL
Buchman
T G
TG
D000005:Abdomen / Q000601:surgery; D000209:Acute-Phase Proteins / Q000235:genetics*; D000510:Alpha-Globulins / Q000235:genetics*; D000768:Anesthesia, General; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013552:Swine; D014361:Trypsin Inhibitors / Q000235:genetics*
D000209:Acute-Phase Proteins; D000510:Alpha-Globulins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D014361:Trypsin Inhibitors; C011877:inter-alpha-inhibitor