EComment. Application of prostaglandin E1 and pentoxyphylline in clinical mesenteric ischaemia

Abstract

We read with great interest the original article by San Norberto Garcia and colleagues describing the effects of intra-arterial and intravenous prostaglandin E1 (PGE1) in intestinal ischaemia-reperfusion injury [1]. Using a rat model, the study was designed to assess histopathological score following ileal segment resection, polymorphonuclear leukocytes visualized and myeloperoxidase activity following a well-designed protocol of ischaemia time and reperfusion time with variable route administration of PGE1. The ischaemic insult presents a vicious cycle at the molecular and biochemical level. Vasodilatation occurs with increased microvascular permeability and release of lysosomal hydrolases and ultimately increased proteolysis. This cascade is aggravated by reperfusion, where an already oxygen deprived organ territory is now exposed to oxygen free radicals through oxidation of the hypoxanthine-xanthine oxidase system resulting in the superoxide anion [2]. The main determinants of haemodynamic instability, and subsequent mortality, are the generation of oxygen free radicals and the increased capillary permeability [3]. The spectrum of mesenteric ischaemia encompasses either an acute insult or a chronic phase, and can be caused by thrombosis, embolism, non-occlusive mesenteric ischaemia, and significant venous obstruction. Clearly with acute mesenteric ischaemia, mortality is quite high. As pointed out by the authors, thromboembolic acute occlusion of the superior mesenteric artery is usually unpredictable, so pretreatment is not possible or practical. However, in such a case like the critically ill with non-occlusive mesenteric ischaemia, with early diagnosis and detection, the initiation of continuous intravenous PGE1 may increase survival as noted in a study by Mitsuyoshi and colleagues [4]. The 60-minute ischaemia time and 7 days reperfusion portended the best outcome with regard to Chiu classification of intestinal tissue injury as well as myeloperoxidase activity and polymorphonuclear leukocyte infiltration. Another promising vascular drug that has been evaluated experimentally is pentoxyphylline. It has specific antioxidant properties that directly inhibit the superoxide anion and indirectly blocks xanthine-oxidase enzyme activity. It has been shown to reduce histopathological changes secondary to ischaemia-reperfusion in intestinal experimental models [5]. Again, although in acute mesenteric ischaemia it is impossible to pretreat these patients with PGE1 (or even pentoxyphylline), it may be clinically appropriate to consider such pretreatment in elective revascularization of patients with chronic mesenteric ischaemia or the critically ill in whom high-dose vasoactive agents are necessary for haemodynamic control. Further translational studies are necessary to try delineate whether a functional benefit is clinically realized from a histopathological and anatomic amelioration of the ischaemia-reperfusion injury. Conflict of interest: none declared