Dopexamine and microcirculatory flow in transplanted small bowel: The Leeds experience

Abstract

Intestinal mucosa is extremely vulnerable to ischemic injury. In transplanted small bowel, this may represent preservation, ischemia-reperfusion injury, technical errors, postimplantation ischemia, or rejection. Such injury may compromise the mucosal barrier. Barrier dysfunction can lead to bacterial translocation and endotoxemia, a trigger for multisystem organ failure (MSOF). Prevention of further ischemic injury in the postoperative period by maintaining optimal graft perfusion may have a major role to play in ensuring graft viability. Previous methods of monitoring graft function have included clinical assessment, serum procoagulant levels, serial endoscopy and mucosal biopsy, and intestinal permeability studies. These methods are not ideal for monitoring early graft function. A number of noninvasive measures of graft perfusion are now available. These include laser Doppler flowmetry (LDF) and gut tonometry. Neither of these techniques has been applied to the transplanted small bowel. LDF is easy to use, is noninvasive, allows continuous monitoring, and its use has been validated in orthotopic liver transplantation (OLT) and in postoperative monitoring of new grafts. Gut tonometry was designed to allow measurement of bowel intramucosal pH (pHi). Low intestinal pH indicates splanchnic hypoperfusion or anaerobic metabolism, is common in critical illness, and is associated with increased morbidity and mortality after major surgery and trauma. Gastric tonometry has been used to monitor early graft function in OLT. Both techniques enable evaluation both of graft function and of therapies aimed at improving perfusion. The pharmacologic profile of dopexamine suggests it would prove a valuable agent in improving splanchnic blood flow. It is a dopamine (DA) analog with action at β 2 adrenoceptors and DA 1 receptors and only moderate activity at β 1 and DA 2 receptors. Dopexamine possesses no direct α-adrenoceptor activity, but norepinephrine reuptake is inhibited. Dopexamine improves cardiac performance by vasodilatation and mild isotropic activity. These hemodynamic effects are achieved without increased myocardial oxygen consumption. Dopexamine has been shown to improve splanchnic oxygenation, an effect which appears to be independent of its systemic effects. Boyd et al have shown that deliberately increasing oxygen delivery perioperatively significantly reduces mortality and morbidity in high-risk surgical patients. We have therefore studied the effects of dopexamine on gut mucosal blood flow following small bowel transplantation, using LDF and gastric tonometry.