Effects of ischaemia and reperfusion on vasoactive neuropeptide levels in the canine infrarenal aortic revascularization model

Infrarenal aortic cross-clamping is associated with remote vascular events, including myocardial infarction and renal insufficiency. The purpose of this study was to determine whether hindlimb ischaemia and reperfusion associated with infrarenal aortic cross-clamping results in the production of vasoactive regulatory neuropeptides. A canine model of infrarenal aortic cross-clamping was used for the study. Serial blood samples were drawn, prior to, at the time of, and serially following placement of the clamp and subsequent release of the clamp and reperfusion. Ischaemia resulted in increased mean(s.e.m.) plasma levels of neuropeptide Y (NPY) (initial 10.0(1.8)pmol/l versus ischaemia 24.7(2.3)pmol/l, P<0.001) and vasoactive intestinal polypeptide (VIP) (initial 2.53(0.5)pmol/l versus ischaemia, 7.3(1.3) pmol/l, P<0.05). Reperfusion produced three-fold elevation of VIP (initial 2.5(0.5) pmol/l versus reperfusion 9.6(1.5) pmol/l. P<0.001). two-fold elevation in the plasma levels of endothelin-1 (initial 1.3(0.1) pmol/l versus reperfusion maximum 2.5(0.3) pmol/1, P<0.01) and NPY (initial 10.0(0.8) pmol/l versus reperfusion maximum 23.9(2.3) pmol/l, P<0.001). Ischaemia and reperfusion did not alter calcitonin gene-related peptide (CGRP) (a potent vasodilator) levels. Endothelin-1 (ET-1) plasma levels were also increased following haemorrhagic shock (initial 1.3(0.1) pmol/1 versus exsanguination 3.4(0.4) pmol/1. P<0.001), but not during ischaemia (initial 1.3(0.1)pmol/1 versus ischaemia maximum 1.7(0.2)pmol/1, P=0.7). It was concluded that vasoactive regulatory peptides are released following ischaemia, reperfusion and shock in the canine infrarenal aortic revascularization model and, therefore could contribute to remote vascular events observed with infrarenal aortic cross-clamping.