Abstracts
1998 Digestive Disease Week
#1034
PRECONDITIONING PROTECTS AGAINST ISCHEMIA-REPERFUSION INJURY OF THE LIVER. B. Nilsson, B. Gustafsson, S. Friman, D. Delbro. Department of Surgery, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.
In some tissues, a brief period of ischemia may induce protection against the injury caused by longer duration of ischemia, and reperfusion. The mechanism for this ischemic preconditioning as demonstrated in the heart, brain, skeletal muscle, small intestine, and liver, may be the release of vasoactive substances from the tissue. Adenosine could be one such mediator. In the present study, performed on a standardized model of ischemia-reperfusion injury of rat liver, we investigated the possibility of pharmacological preconditioning by preventing the enzymatic degradation of adenosine by dipyridamole pretreatment.
Methods: Anesthetized Wistar rats were treated as follows: I. No ischemia (control, n=8); II. Sixty min. ischemia (by clamping of the common hepatic artery) followed by 60 min. reperfusion (n=8); III. Ten min. ischemia followed by 15 min. reperfusion, prior to the identical ischemia-reperfusion period (60 + 60 min.) as in group II (n=11); IV. Administration of dipyridamole (Persantin®, 0.4 mg/kg i.v.) prior to the identical ischemia-reperfusion period (60 + 60 min.) as in group II (n=11). In all groups, the peripheral liver blood flow was monitored by laser-Doppler flowmetry during the 60 min. before clamping, during the ischemia, and after unclamping, respectively. Blood alanine aminotransferase (ALT) was analysed once every 60 min. throughout the experiment.
Results: Peripheral liver blood flow was reduced during clamping (group II-IV), as compared to the control group I. After unclamping, blood flow was still reduced in the ischemia group (II), but returned to pre clamp values in the animals having been subjected to ischemic (III) or pharmacological (IV) preconditioning. Liver injury as measured by ALT was significantly increased in the ischemia group (II) only.
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Peripheral blood flow
(% change)
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ALT
(% change)
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Clamp
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Post clamp
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Clamp
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Post clamp
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I Sham
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+0.5 ± 0.3
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+2.4 ± 0.6
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+11.7 ± 1.6
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+13.7 ± 1.7
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II 60 min. clamp
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-33.3 ± 0.9**
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-13.4 ± 0.8**
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+125.5 ± 14.1*
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187.2 ± 15.8**
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III Isc. P.
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-32.6 -3.6**
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+1.1 ± 2.8
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+20.7 ± 4.3
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+25.1 ± 5.4
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IV Pha P.
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-31.5 ± 3.5**
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+0.7 ± 2.4
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+9.7 ± 1.9
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+12.4 ± 2.5
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Isc. P. = ischemic preconditioning. Pha. P. = pharmacological preconditioning.
* = p < 0.05, ** = p < 0.01 vs control group. ANOVA
Conclusion: In our experimental model of ischemia-reperfusion injury of rat liver, we found an equally beneficial effect of ischemic and pharmacological precon-ditioning. Adenosine appears to be a crucial factor in preventing such an injury
Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.
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