LAUSR

OBJECTIVE People living with HIV (PLWH) have an increased risk of pulmonary vascular disease and pulmonary hypertension (PH). Endothelial cell dysfunction is thought to contribute, but human studies have been limited by the invasive nature of conventional measures of pulmonary artery endothelial function (PAEF). We report here a noninvasive MRI approach to measure nitric-oxide (NO) mediated PAEF by quantifying changes in PA area and blood flow during isometric handgrip exercise (IHE), an endothelial NO-dependent stressor. We used this to test the hypothesis that PLWH have impaired PAEF, even before development of PH. DESIGN Prospective cohort study. METHODS We enrolled 25 HIV+ viral-suppressed subjects on stable anti-retroviral therapy without known or suspected PH and 19 matched seronegative control subjects (HIV-). PA area and blood flow changes in response to IHE were measured with non-contrast MRI. Data previously collected during NO-synthase inhibition were analyzed to determine the role of NO in the PA response to IHE. RESULTS Seronegative subjects exhibited the anticipated PA vasodilatory response to IHE, but this was completely absent in HIV+ subjects who exhibited an impaired area change (-1.1 ± 1.2% vs +7.7 ± 2.2%, HIV+ vs HIV-, mean±SEM, respectively, P = 0.002) and blood flow response (0.2 ± 2.3% vs 13.5 ± 4.8%, P = 0.005). The PA vasodilatory effect of IHE in healthy subjects was fully blocked by NO-synthase, demonstrating this PA response is predominantly NO-mediated. CONCLUSION Using noninvasive MRI methods to quantify PAEF, we observed significantly impaired PAEF in PLWH compared to matched HIV- controls. Noninvasive PAEF testing may be useful in evaluating early HIV-related pulmonary vascular disease.