ELEVATIONS IN CIRCULATING CALCITONIN-GENE-RELATED PEPTIDE CORRELATE WITH HEMODYNAMIC DETERIORATION DURING ENDOTOXIC-SHOCK IN RIGS

Calcitonin gene-related peptide (CGRP) is a potent vasodilatory neurop eptide, which may play a role in vascular dysfunction during septic sh ock. Sixteen pigs (25-50 kg) were anesthetized with ketamine and isofl urane in O-2, and administered 100 mu g/kg Escherichia coli lipopolysa ccharide i.v. (LPS; n = 8) or saline vehicle (n = 8). Pigs were instru mented for hemodynamic determinations and blood sampling for CGRP assa y (pg/ml) from the portal vein (PV) and the pulmonary (PA) and carotid (CA) arteries. Blood samples were collected into EDTA and aprotinin b efore (baseline) and at 60, 120, and 180 min after LPS administration. LPS caused significant deterioration in indices of hemodynamic functi on and a significant increase in plasma CGRP concentration at all samp ling sites by 120 min (P < 0.01). No significant difference between sa mpling sites was recorded at any time. Plasma CGRP concentrations disp layed significant negative correlations with mean arterial pressure, c ardiac index, and left ventricular stroke work. These data confirm our previous findings of CGRP elevations in endotoxemic rats, and indicat e that 1) LPS is a potent stimulus for the systemic release of CGRP, 2 ) increasing plasma CGRP concentrations temporally correlates with car diovascular deterioration during LPS shock, and 3) there is little evi dence that the portal circulation is a major source of circulating CGR P levels during LPS shock. Vasoactive neuropeptides, such as CGRP, may interact with other documented mediators of vascular dysfunction in t he pathogenesis of septic shock. (C) 1994 Wiley-Liss, Inc.