Aerosolized Perfluorochemical Rescue Against Acute Altitude‐Induced Pulmonary Compromise

Rationale Current methods of mitigating pulmonary complications of altitude are not deployable far forward or have long‐lasting side effects. When the whole lung is exposed to hypobaric hypoxia, pulmonary vasoconstriction (HPV) occurs and results in a significant increase in pulmonary vascular resistance and pulmonary arterial pressure. Inhomogeneity of HPV may account for regional overperfusion leading to ventilation:perfusion mismatch and increased pulmonary capillary pressure that causes structural changes leading to alveolar‐capillary leak, pulmonary edema, decreased pulmonary compliance, all contributors to hypoxemia. Perfluorochemical (PFC) liquids are effective pulmonary agents due to their high gas solubility and low surface tension that supports homogenous distribution through the lung to recruit lung volume and improve ventilation:perfusion matching. This study tests the hypothesis that aerosolized PFC alone or as a vehicle to deliver inhaled nitric oxide may blunt altitude‐induced pulmonary complications following rapid ascent. Methods Anesthetized, spontaneously breathing sheep (n = 32; ~ 25 kg) were supported with CPAP and instrumented to serially assess hemodynamics, pulmonary compliance, gas exchange, and blood chemistry at sea level and while in a hypobaric chamber controlled to simulate rapid ascent to hypobaric hypoxia of 15k feet altitude (P barometric = 429 mm Hg). Sheep (4 gr; n = 8/gr) were maintained for 3 hrs without (control) or with aerosolized PFC, iNO at ~25 ppm alone or iNO delivered in aerosolized PFC, initiated by 15 min after ascent. Results Data shown as mean(SD). Comparing values at sea level vs 15min after ascent, there were no significant group differences on the effect of acute response to altitude for systemic [SAP: 95(4) vs 114(2) mm Hg; p < 0.05] and pulmonary arterial pressure [PAP: 22(1) vs 36(1) mm Hg; p<0.01], or systemic [SVR: 29(0.9) vs 28(1) Woods Units] and pulmonary vascular resistance [PVR: 6.7(0.4) vs 9(0.4) Woods Units; p < 0.05] or PaO 2 [110(6) vs 33(2) mm Hg; p < 0.001]. By 3 hr (table), there were significant group differences. Treatment with PFC, alone or to deliver iNO resulted in significantly lower PAP and PVR, and higher PaO2 than control or iNO alone. While there were no significant group differences in compliance [C: 1.30(0.1) mL/cmH20kg] at sea level prior to altitude, upon return from altitude (table) aerosolized PFC and iNO delivered by PFC attenuated the altitude‐induced decrease in C as compared to control or iNO alone. Conclusions Aerosolized PFC alone and as a delivery vehicle for iNO temporized altitude‐induced pulmonary complications following rapid ascent. While iNO alone was effective, the response to lower pulmonary pressures and vascular resistance and improve oxygenation was amplified when delivered in aerosolized PFC. These results support the notion that delivery of this vasoactive gas was improved through the mechanism of being dissolved in the PFC that is effectively distributed more distally into the PFC stabilized lung providing NO access to the pulmonary vasculature. These findings support a fieldable option to mitigate progression of acute altitude‐induced pulmonary compromise. Support or Funding Information Department of Defense/Office of Naval Research: Semper Fi‐Air: N000141210597Mean(SD) Control PFC alone iNO alone iNO by PFCSAP 97(8) 96(9) 88(7) 89(11)PAP 39(1) 23(2) ** 27(2) * 22(1) **SVR 24(2) 35(3) 27(3) 29(1)PVR 10(1) 8(0.7) * 8.5(0.9) 7(0.7) * PaO 2 34(3) 76(13) ** 54(10) * † 74(8) **C 0.63(0.12) 1.15(0.17) ** 0.53(0.24) 1.10(0.17) *** p < 0.05 and ** p < 0.001 vs control; † p < 0.05 vs control, PFC alone, iNO by PFC