Administration of hydrogen sulfide via extracorporeal membrane lung ventilation in sheep with partial cardiopulmonary bypass perfusion: A proof of concept study on metabolic and vasomotor effects

Introduction: Although inhalation of 80 parts per million (ppm) of hydrogen sulfide (H₂S) reduces metabolism in mice, doses higher than 200 ppm of H₂S were required to depress metabolism in rats. We therefore hypothesized that higher concentrations of H₂S are required to reduce metabolism in larger mammals and humans. To avoid the potential pulmonary toxicity of H₂S inhalation at high concentrations, we investigated whether administering H₂S via ventilation of an extracorporeal membrane lung (ECML) would provide means to manipulate the metabolic rate in sheep.Methods: A partial venoarterial cardiopulmonary bypass was established in anesthetized, ventilated (fraction of inspired oxygen = 0.5) sheep. The ECML was alternately ventilated with air or air containing 100, 200, or 300 ppm H₂S for intervals of 1 hour. Metabolic rate was estimated on the basis of total CO₂ production (V̇ CO2) and O₂ consumption (V̇ O2). Continuous hemodynamic monitoring was performed via indwelling femoral and pulmonary artery catheters.Results: V̇ CO2, V̇ O2, and cardiac output ranged within normal physiological limits when the ECML was ventilated with air and did not change after administration of up to 300 ppm H₂S. Administration of 100, 200 and 300 ppm H₂S increased pulmonary vascular resistance by 46, 52 and 141 dyn·s/cm⁵, respectively (all P ≤ 0.05 for air vs. 100, 200 and 300 ppm H₂S, respectively), and mean pulmonary artery pressure by 4 mmHg (P ≤ 0.05), 3 mmHg (n.s.) and 11 mmHg (P ≤ 0.05), respectively, without changing pulmonary capillary wedge pressure or cardiac output. Exposure to 300 ppm H₂S decreased systemic vascular resistance from 1,561 ± 553 to 870 ± 138 dyn·s/cm⁵ (P ≤ 0.05) and mean arterial pressure from 121 ± 15 mmHg to 66 ± 11 mmHg (P ≤ 0.05). In addition, exposure to 300 ppm H₂S impaired arterial oxygenation (P_aO₂ 114 ± 36 mmHg with air vs. 83 ± 23 mmHg with H₂S; P ≤ 0.05).Conclusions: Administration of up to 300 ppm H₂S via ventilation of an extracorporeal membrane lung does not reduce V̇ CO2 and V̇ O2, but causes dose-dependent pulmonary vasoconstriction and systemic vasodilation. These results suggest that administration of high concentrations of H₂S in venoarterial cardiopulmonary bypass circulation does not reduce metabolism in anesthetized sheep but confers systemic and pulmonary vasomotor effects.