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

Abstract

Abstract 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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mover> <mml:mtext>V</mml:mtext> <mml:mo>˙</mml:mo> </mml:mover> <mml:mtext>CO</mml:mtext> </mml:mrow> <mml:mtext>2</mml:mtext> </mml:msub> </mml:mrow> </mml:math> ) and O 2 consumption ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mover> <mml:mtext>V</mml:mtext> <mml:mo>˙</mml:mo> </mml:mover> <mml:mtext>O</mml:mtext> </mml:mrow> <mml:mtext>2</mml:mtext> </mml:msub> </mml:mrow> </mml:math> ). Continuous hemodynamic monitoring was performed via indwelling femoral and pulmonary artery catheters. Results <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mover> <mml:mtext>V</mml:mtext> <mml:mo>˙</mml:mo> </mml:mover> <mml:mtext>CO</mml:mtext> </mml:mrow> <mml:mtext>2</mml:mtext> </mml:msub> </mml:mrow> </mml:math> , <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mover> <mml:mtext>V</mml:mtext> <mml:mo>˙</mml:mo> </mml:mover> <mml:mtext>O</mml:mtext> </mml:mrow> <mml:mtext>2</mml:mtext> </mml:msub> </mml:mrow> </mml:math> , 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 <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mover> <mml:mtext>V</mml:mtext> <mml:mo>˙</mml:mo> </mml:mover> <mml:mtext>CO</mml:mtext> </mml:mrow> <mml:mtext>2</mml:mtext> </mml:msub> </mml:mrow> </mml:math> and <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msub> <mml:mrow> <mml:mover> <mml:mtext>V</mml:mtext> <mml:mo>˙</mml:mo> </mml:mover> <mml:mtext>O</mml:mtext> </mml:mrow> <mml:mtext>2</mml:mtext> </mml:msub> </mml:mrow> </mml:math> , 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.