DYNAMIC CHANGES OF PERIOPERATIVE PLASMA ET AND CGRP IN CONGENITAL HEART DISEASE AND THE RELATION WITH PULMONARY HYPERTENSION

Zhang ZW，Li JH, Hu J

Children's Hospital, Medical College, Zhejiang University. Hangzhou, P. R. China

Objective: To evaluate the pathophysiologic significance of dynamic changes of peri operative plasma endothelin (ET) and calcitonin gene-related peptide (CGRP) in pulmonary hypertension (PH) associated with congenital heart defects (CHD).

Methods: We measured the plasma levels of ET and CGRP pre- and post-cardiopulmonary bypass (CPB) by using radio-immunoassay (RIA) and we analyzed the correlation between ET, CGRP and the preoperative hemodynamic factors. We characterized the time course of ET and CGRP in plasma, and elucidated the relation of ET CGRP in concentration with PH. Thirty-three children were divided into two groups. Those with a mild pulmonary hypertension (group A, 20 cases) , and those with a middle or severe pulmonary hypertension (group B, 13 cases, the PP/PS ratio is ³0.5 by using the right cardiac catheterization). Thirty healthy children were taken as control group. Blood samples from control group were drawn from peripheral vein, while blood samples from patients' group were drawn from right atrium during operation and from femoral vein at 3, 24, 72 hours after operation. Additionally, the pulmonary artery pressure, the pressure in cardiac cavities, and the oxygen saturation were measured repeatedly by cardiac catheterization in 13 cases of severe PH.

Results: (1) There is a significant difference in ET concentration between groups, the plasma level of ET in group B is much higher than that in group A and controls. Whereas no significant difference in the plasma CGRP levels was observed between groups (p>0.05). (2) Dynamic changes of plasma levels of ET, CGRP after bypass operation: in group A, the plasma levels of ET significantly increased after operation immediately, decreased slightly at 3 hours postoperation (q test, p<0.001), and returned to the preoperative levels at 24 hours postoperation. In group B, there is no significant changes of ET levels after operation immediately, slightly but not significantly decreased at 3 and 24 hours postoperation , but significantly decreased at 72 hours postoperation comparing to the preoperative levels ( q test, p<0.001) and showed high level than the normal levels ( t test, p<0.001). Plasma levels of CGRP in both group A and B significantly increased after the operation. They immediately reached the peak levels at 24 hours operation (q test. p<0.001), slightly decreased but higher than the preoperative levels at 72 hours operation, however, no significant difference was observed at 72 hours (q test, p>0.05). (3) In patients with severe PH (group B), increasing plasma levels of ET was positively correlated with the ratio of PP/PS, and the pulmonary resistance（r= 0.683，0.698 respectively, p<0.05 and <0.01 respectively）. The plasma CGRP levels showed significant negative correlation with plasma ET levels（r=0.701, p<0.01）.

Conclusions: (1) Patients with PH exist an imbalance between plasma levels of ET and CGRP. (2) The pulmonary vessels may be of a trend to spasm at 72 hours postoperation. (3) The overproduction of endogenous CGRP after bypass is able to supply the pulmonary vessel to resist the constriction, and be beneficial to the recovery of cardiac function. The measurement of the plasma levels of ET, CGRP and the ratio of ET/ CGRP after CPB operation will be of clinical significance for the predicting the outcome, however, a further study is needed.

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