Peripheral Vasodilatory Dysfunction in Adult Patients with Congenital Heart Disease and Severely Elevated Pulmonary Vascular Resistance

Abstract

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.

Impaired endothelium-dependent and endothelium-independent systemic vasodilatory reserve in pulmonary hypertension regardless the clinical group: A generalized dysfunction beyond the pulmonary arteries?

“…The growing evidence from studies performed in patients with IPAH and scleroderma-PAH suggest the presence of a wide spectrum of systemic metabolic and inflammatory alterations and vascular dysfunction (5,6, manifested by Impaired brachial artery vasodilatory reserve (5,6,(15)(16)(17)(18)(19)(20)(21)(22). Blood flow abnormalities in the middle cerebral artery, reduced cerebrovascular reactivity to blood PCO 2 , decreased NO production by cerebral endothelial cells, impairment in perception of dyspnea and sleep-disordered breathing (5,6,(23)(24)(25).…”

“…Flow-mediated dilatation (FMD) was first described in femoral and brachial arteries and is mediated by potassium channel dependent release of NO produced from the nitroglycerine that leaks into the smooth muscle cells (5,6,(14)(15)(16)(17)(18)(19)(20). ED-FMD (ischemia response) assesses the hyperemia occurring in medium muscular arteries as a response to shear stress following ischemia induced by inflating the blood pressure cuff (5,6,(14)(15)(16)(17)(18)(19)(20). In patients with PAH, studies with duplex ultrasound in BA revealed impaired FMD as a marker for systemic endothelial disfunction (5,6,(14)(15)(16)(17)(18)(19)(20).…”

“…ED-FMD (ischemia response) assesses the hyperemia occurring in medium muscular arteries as a response to shear stress following ischemia induced by inflating the blood pressure cuff (5,6,(14)(15)(16)(17)(18)(19)(20). In patients with PAH, studies with duplex ultrasound in BA revealed impaired FMD as a marker for systemic endothelial disfunction (5,6,(14)(15)(16)(17)(18)(19)(20). Hughes et al (17) reported significant reductions in BA FMD in 2.7% of patients with IPAH and 6.3% of patients with SSc-PAH, and a trend toward a reduced response in family members of the patients with IPAH.…”

“…Lower ED-FMD in patients with Eisenmenger is considered to be a compensatory response to chronic hypoxia rather than caused by increased vasoconstrictor mediator levels. Nakamura et al (20) reported that cardiovascular shunt lesions with increased pulmonary blood flow may be associated with a trend toward decreased cardiac output owing to decreased vascular wall shear stress and endothelial dysfunction. Besides, Ciftel et al (41) found that compared with the control group, the mean FMD was significantly reduced in the cyanotic PH group.…”

“…Most of the blood vessels respond to shear stress by vasodilatation known as flow-mediated dilatation (FMD), and the most effective mediator of FMD is endothelium-derived nitric oxide (NO) (5,(14)(15)(16)(17)(18)(19)(20). Although endothelium-dependent (ED) and endothelium-independent (EI) FMD have been used for noninvasive assessment of systemic arterial vasodilatory reserve in various cardiovascular diseases, their clinical relevance in patients with different PH etiologies remains to be determined (5,(14)(15)(16)(17)(18)(19)(20).…”