Peptides 24 (2003) 1381–1386 Octreotide: a new approach to the management of acute abdominal hypertension Ayhan Kaçmaz a , Ali Polat a , Yılmaz User a , Metin Tilki a , Sırrı Özkan a , Göksel ¸ Sener b,∗ a Department of 3rd Surgery, Haydarpa¸ sa Numune Hospital, Istanbul, Turkey b Department of Pharmacology, School of Pharmacy, Marmara University, Istanbul, Turkey Received 9 June 2003; accepted 8 September 2003 Abstract Acutely increased intra-abdominal pressure (IAP) may lead to abdominal compartment syndrome (ACS), which ischaemia/reperfusion (I/R) injury plays an important role. The main goal of the management of ACS is to lower the intra-abdominal pressure despite reperfusion injury. Octreotide (OCT), a synthetic somatostatin analogue, lowers the splanchnic perfusion. The aim of this study was to investigate whether OCT improves the reperfusion injury after decompression of acute abdominal hypertension. Under anesthesia, a catheter was inserted intraperitoneally and using an aneroid manometer connected to the catheter, IAP was kept at 20 mmHg (ischemia group; I) for 1 h. In the I/R group, pressure applied for an hour was decompressed and 1 h reperfusion period was allowed. In another group of I/R, OCT was administered (50 g/kg i.p.) immediately before the decompression of IAP. The results demonstrate that kidney and lung tissues of malondialdehyde (MDA; an end product of lipid peroxidation) levels and myeloperoxidase (MPO; index of tissue neutrophil infiltration) activity were elevated, while glutathione (GSH; a key to antioxidant) levels were reduced in I/R group (P< 0.001). Moreover, OCT treatment applied in the I/R group reduced the elevations in blood urea nitrogen (BUN) and serum creatinine levels. Our results implicate that IAP causes oxidative organ damage and OCT, by reducing splanchnic perfusion and controlling the reperfusion of abdominal organs, could improve the reperfusion-induced oxidative damage. Therefore, its therapeutic role as a “reperfusion injury-limiting” agent must be further elucidated in IAP-induced abdominal organ injury. © 2003 Published by Elsevier Inc. Keywords: Abdominal hypertension; Octreotide; Myeloperoxidase; Lipid peroxidation; Glutathione 1. Introduction There are many clinical situations that can lead to in- creased intra-abdominal pressure (IAP) [6], which, in turn, can cause fatal multiple organ failure called intra-abdominal compartment syndrome (ACS) [42]. The detrimental effects on the cardiac, pulmonary, hepatic, and renal systems with raised IAP and ACS are well known and the easiest to de- tect clinically [18,42]. The ensuing organ dysfunction will often resolve following surgical decompression of the ab- domen; however, this may then lead to complications which can cause serious additional morbidity [10,38]. Since increased intra-abdominal pressure reduces blood flow to intra-abdominal organs, ischaemia/reperfusion (I/R) injury plays an important role in the pathogenesis of ACS [11]. It is well known that reperfusion of the ischemic tis- ∗ Corresponding author. Tel.: +90-216-414-29-62; fax: +90-216-345-29-52. E-mail address: gokselsener@hotmail.com (G. ¸ Sener). sue may promote the generation of various reactive oxygen metabolites, which are known to have deleterious effects on various cellular functions [41]. Lipid peroxidation mediated by oxygen-free radicals is believed to be an important cause of destruction and damage to cell membranes and attention has been focused on the role of reactive oxygen species in mediating the microvascular disturbances that precede organ damage induced by various chemicals and by ischemia and reperfusion [8,32]. Besides their direct damaging effects on tissues, free radicals seem to trigger the accumulation of leukocytes in the tissue involved, and thus cause tissue injury also indirectly through activated neutrophils. It has been shown that activated neutrophils secrete enzymes (e.g. myeloperoxidase, elastase, proteases) and liberate oxygen radicals [9,37]. As the source of reactive oxygen metabolites (ROM) could be neutrophils sequestered in systemic organs as a result of the systemic inflammatory reaction to a reperfusion insult, it is possible that agents which inhibit the activation and adherence of neutrophils might exert protective effects against reperfusion injury [32]. 0196-9781/$ – see front matter © 2003 Published by Elsevier Inc. doi:10.1016/j.peptides.2003.09.004