High Pressure Liquid Chromatography Systems

Ramwell, Peter

Abstract

Certain metabolites of arachidonic acid such as thromboxane A2 have important pathophysiological properties in cardiovascular renal related disease processes. A comprehensive high performance liquid chromatographic system is requested to permit the more effective prosecution of six closely related projects dealing with arachidonic acid metabolism. These projects are directed to: (1) the use of thromboxane B2 (TXB2) as an indicator of clinical renal allograft rejection; (2) the causal role of thromboxane A2 (TXA2) and leukotrienes in experiment cardiac allograft rejection; (3) arachidonate metabolism in experimental radiation exposure; (4) the role of arachidonate metabolites in experimental sudden death; (5) sex differences in the cyclooxygenase and lipoxygenase products of the vascular endothelium, and (6) renal urinary prostaglandins. An automated and comprehensive HPLC system will permit the processing of both human clinical and experimental animal samples for determination of TXB2 and 2,3 dinor TXB2 which may differentiate between renal and extrarenal sources of thromboxane. The HPLC system will also permit determination of the relation of the thromboxanes to other arachidonate products, especially where radio-isotopic arachidonate incorporation is used to follow cyclooxygenase and lipoxygenase product formation. This latter procedure will be particularly important in fine needle transplant aspiration cytology studies of rejection of clinical renal allografts and in the studies of gender differences in endothelial arachidonate metabolism. The significance of these studies lies in the possible causal role of TXA2 and lipoxygenase products as mediators of vascular injury of multiple etiologies. In this context considerable protection has been achieved in experimental models using TXA2 receptor antagonists and TXA2 synthase inhibitors. Such studies will facilitate the clinical decision to use these two new classes of drugs in the transplant clinic and situations involving risks of thrombosis, vasospasm and endothelial or other types of vascular damage. The importance of these investigations has been recognized by several federal and private agencies that have provided financial support.