Peripheral vasodilatory dysfunction in adult patients with congenital heart disease and severely elevated pulmonary vascular resistance

Several studies have demonstrated that pulmonary vascular abnormalities precede alterations in aortic circulation downstream in animal models of heart failure. The relationship between increased pulmonary vascular resistance (PVR) and agonist-induced limb vasodilatory response remains unknown in patients with congenital cardiovascular shunt lesions (CSL). The authors hypothesized that patients with CSL and severely elevated PVR will show a defective vasomotor response in the peripheral vascular bed. To examine this hypothesis we measured forearm blood flow (FBF) responses to the endothelium-dependent vasodilator acetylcholine and the endothelium-independent vasodilator sodium nitroprusside. The values for these FBF responses were compared with PVR in adult patients with CSL (n=20) and healthy age- and sex-matched controls (n = 15). When patients with CSL were divided into 2 subgroups by median value of PVR, in the lower PVR subgroup, acetylcholine-induced FBF changes were selectively and significantly lower than in the healthy control group (p <0.05). In the higher PVR subgroup, FBF responses to both acetylcholine and sodium nitroprusside were significantly blunted compared to healthy controls (both p < 0.01). In addition, when FBF changes above baseline for each dose of acetylcholine and sodium nitroprusside were cumulated and used as acetylcholine response and sodium nitroprusside response, the sensitivity and specificity for identifying patients with Eisenmenger's type of CSL was 100% and 80% by acetylcholine response, and 67% and 80% by sodium nitroprusside response, respectively. In conclusion, adult CSL patients with elevated PVR and severe pulmonary arterial hypertension showed generalized vasodilator dysfunction in the forearm vasculature. This result suggests that upper limb resistance vessel dysfunction may be an indicator for advanced stage of adult patients with CSL.