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 ($ H_{2} $S) reduces metabolism in mice, doses higher than 200 ppm of $ H_{2} $S were required to depress metabolism in rats. We therefore hypothesized that higher concentrations of $ H_{2} $S are required to reduce m...
Ausführliche Beschreibung

Introduction Although inhalation of 80 parts per million (ppm) of hydrogen sulfide ($ H_{2} $S) reduces metabolism in mice, doses higher than 200 ppm of $ H_{2} $S were required to depress metabolism in rats. We therefore hypothesized that higher concentrations of $ H_{2} $S are required to reduce metabolism in larger mammals and humans. To avoid the potential pulmonary toxicity of $ H_{2} $S inhalation at high concentrations, we investigated whether administering $ H_{2} $S 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 $ H_{2} $S for intervals of 1 hour. Metabolic rate was estimated on the basis of total $ CO_{2} $ production () and $ O_{2} $ consumption (). Continuous hemodynamic monitoring was performed via indwelling femoral and pulmonary artery catheters. Results , , 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 $ H_{2} $S. Administration of 100, 200 and 300 ppm $ H_{2} $S increased pulmonary vascular resistance by 46, 52 and 141 dyn·s/$ cm^{5} $, respectively (all P ≤ 0.05 for air vs. 100, 200 and 300 ppm $ H_{2} $S, 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 $ H_{2} $S decreased systemic vascular resistance from 1,561 ± 553 to 870 ± 138 dyn·s/$ cm^{5} $ (P ≤ 0.05) and mean arterial pressure from 121 ± 15 mmHg to 66 ± 11 mmHg (P ≤ 0.05). In addition, exposure to 300 ppm $ H_{2} $S impaired arterial oxygenation ($ P_{a} %$ O_{2} $ 114 ± 36 mmHg with air vs. 83 ± 23 mmHg with $ H_{2} $S; P ≤ 0.05). Conclusions Administration of up to 300 ppm $ H_{2} $S via ventilation of an extracorporeal membrane lung does not reduce and , but causes dose-dependent pulmonary vasoconstriction and systemic vasodilation. These results suggest that administration of high concentrations of $ H_{2} $S in venoarterial cardiopulmonary bypass circulation does not reduce metabolism in anesthetized sheep but confers systemic and pulmonary vasomotor effects. Ausführliche Beschreibung