Instituţia Medico-Sanitară Publică Institutul Mamei și Copilului
Abstract
Department of Pediatrics, State University of Medicine and Pharmacy "Nicolae Testemitanu", Chisinau, Republic of MoldovaEndothelial dysfunction in chronic heart failure (CHF) secondary to congenital systemic-to-pulmonary shunts
(CSPS) associated with Pulmonary Arterial Hypertension (PAH) conducts to chronically impaired production of vasodilator and antiproliferative agents,e.g. NO, further leading to the overexpression of vasoconstrictor and proliferative
substances - endothelin-1 (ET-1).
The aim: To accentuate the pathophysiological particularities of NO and ET-1 in CHF secondary to CSPS associated with PAH.
Methods and materials:Seventy children with CHF secondary to CSPS associated with PAH (mean age 37,4±3,4
months) were involved in the study. The patients were separated into 3 groups: 1st – 16 pts with CHF and PAH moderate,
and 2nd – 54 pts with CHF (the majority with RV’s dysfunction) and PAH severe, 3rd - 16 pts with CHF and without PAH.
15 health children with innocent cardiac murmur constituted the witness group. The groups were comparable w.r.t. the
age and sex. Using ELISA method (DRG International Inc., SUA)NO and ET-1 were determined.
Results: Patients with CHF and PAH moderate had a higher level of NO - 116,45±6,1 fl mol/l comparing to children
with PAH severe - 93,06±3,34 (p<0,05) and to those with CHF but without PAH - 90,91±4,07 (p<0,05), and versus the
healthy children - 77,32±5,1 (p<0,001). In PAH severe the pulmonary vasodilators’ mechanisms with the diminishing of
NO got worse. ET-1 had higher values in children with PAH severe - 7,78±0,28 pg/ml with high statistical significance
w.r.t. patients with PAH moderate - 3,88±0,21, vs those without PAH - 3,69±0,24 (p<0,001) and healthy - 2,9±0,27
(p<0,001). The hemodynamic stress within the CSPS associated with PAH is responsible for the endothelium’s lesion
which leads to the stimulation of ET-1 production by the endothelium cells.
Conclusions:The overall results reveal the major role ET-1 and NO in pathophysiology of PAH secondary to CSPS
with CHF. At patients with CHF and PAH severe the endothelium’s lesion leads to a disequilibrium between the production of the mediators with vasodilators effects and those with vasoconstrictor properties; at patients with PAH moderate
the NO level being significantly higher vs those with PAH severe, while the ET-1 values were higher at pts with PAH
severe vs those with a moderate level and without PAH
