Noninvasive detection of impaired pulmonary artery endothelial function in people living with HIV

Objective: People living with HIV (PLWH) have an increased risk of pulmonary vascular disease and pulmonary hypertension. 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 mediated PAEF by quantifying changes in pulmonary artery area and blood flow during isometric handgrip exercise (IHE), an endothelial nitric oxide dependent stressor. We used this to test the hypothesis that PLWH have impaired PAEF, even before development of pulmonary hypertension. Design: A prospective cohort study. Methods: We enrolled 25 HIV-positive viral-suppressed individuals on stable antiretroviral therapy without known or suspected pulmonary hypertension and 19 matched seronegative control individuals (HIV-negative). Pulmonary artery area and blood flow changes in response to IHE were measured with noncontrast MRI. Data previously collected during nitric oxide-synthase inhibition were analysed to determine the role of nitric oxide in the pulmonary artery response to IHE. Results: Seronegative individuals exhibited the anticipated PA vasodilatory response to IHE, but this was completely absent in HIV-positive individuals who exhibited an impaired area change (-1.1 ± 1.2 vs. þ7.7 ± 2.2%, HIV-positive vs. HIV-negative, mean ± SEM, respectively, P = 0.002) and blood flow response (0.2 ± 2.3 vs. 13.5 ± 4.8%, P ¼ 0.005). The pulmonary artery vasodilatory effect of IHE in healthy individuals was fully blocked by nitric oxide-synthase, demonstrating this pulmonary artery response is predominantly nitric oxide mediated. Conclusion: Using noninvasive MRI methods to quantify PAEF, we observed significantly impaired PAEF in PLWH compared with matched HIV-negative controls. Noninvasive PAEF testing may be useful in evaluating early HIV-related pulmonary vascular disease.