Page 30 - Postoperative Intra-Abdominal Adhesions- New insights in prevention and consequences

Chapter 2
adhesion formation in animal models. On the contrary, in animal studies fat necrosis and fibrotic changes were found less often in anestrogenic objects. Additionally it was shown in humans that gonadotrophin- releasing hormone antagonist (GnRH) diminishes the formation of adhesions after mymetrial surgery by inhibiting the proteolytic milieu [68, 69]. Nevertheless, these results were not confirmed by a more recent study in which preoperative treatment with GnRHa did not decrease postoperative uterine adhesion formation [70].
Statins
Statins (3-hydroxy-methylglutaryl-Coenzyme A reductase inhibitors) antagonize the enzyme HMG-CoA reductase, which catalyzes the rate- limiting step in hepatic cholesterol synthesis. This leads to a reduction in the synthesis and secretion of lipoproteins by the liver, as well as upregulation of LDL receptors on hepatocytes, increasing clearance of circulating apolipoprotein E- and B-containing lipoproteins [71]. Statins are widely used for their cholesterol-lowering capacity, however there is accumulating evidence that they are effective in lowering plasma levels of CRP, have potent inflammatory properties and are effective stimulators of fibrinolytic activity by increasing tPA and lowering PAI-1 [16, 72-75]. These anti-inflammatory and pro-fibrinolytic properties may play a role in the formation of adhesions and in different experimental studies statins have shown an adhesion-reduction when administered intraperitoneally [76, 77]. When applied at high dose no toxic effects were observed in rats, however high statin doses have been correlated with various adverse effects in humans [76, 78]. In this context it is of special interest that some data suggest that a barrier, containing low doses of atorvastin, results in less adhesion formation than Seprafilm [79].
Anticoagulents-fibrinolytics
Anticoagulants such as heparin can reduce adhesion formation by inhibition of the coagulation cascade and promotion of fibrinolysis. However the effective dose was associated with hemorrhages and delayed wound healing. Low-dose heparin irrigation (2500/5000 U/l) showed no benefit in adhesion reduction [37, 43, 44, 61, 80].
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