TY - JOUR
T1 - Inhaled hydrogen sulfide improves graft function in an experimental model of lung transplantation
AU - George, Timothy J.
AU - Arnaoutakis, George J.
AU - Beaty, Claude A.
AU - Jandu, Simran K.
AU - Santhanam, Lakshmi
AU - Berkowitz, Dan E.
AU - Shah, Ashish S.
N1 - Funding Information:
Funding: This research was supported by grant 90038390 from the Thoracic Surgery Foundation for Research and Education and by grant T32 2T32DK007713-12 from the National Institutes of Health . Dr. George is the Hugh R. Sharp Cardiac Surgery Research Fellow. Drs. Arnaoutakis and Beaty are the Irene Piccinini Investigators in Cardiac Surgery.
PY - 2012/12
Y1 - 2012/12
N2 - Objectives: Ischemia/reperfusion injury (IRI) is a common complication of lung transplantation (LTx). Hydrogen sulfide (H2S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pretreatment with inhaled H2S would improve graft function in an ex vivo model of LTx. Methods: Rabbits (n = 10) were ventilated for 2 h prior to heart-lung bloc procurement. The treatment group (n = 5) inhaled room air (21% O2) supplemented with 150 ppm H2S while the control group (n = 5) inhaled room air alone. Both groups were gradually cooled to 34°C. All heart-lung blocs were then recovered and cold-stored in low-potassium dextran solution for 18 h. Following storage, the blocs were reperfused with donor rabbit blood in an ex vivo apparatus. Serial clinical parameters were assessed and serial tissue biochemistry was examined. Results: Prior to heart-lung bloc procurement, rabbits pretreated with H2S exhibited similar oxygenation (P = 0.1), ventilation (P = 0.7), and heart rate (P = 0.5); however, treated rabbits exhibited consistently higher mean arterial blood pressures (P = 0.01). During reperfusion, lungs pretreated with H2S had better oxygenation (P < 0.01) and ventilation (P = 0.02), as well as lower pulmonary artery pressures (P < 0.01). Reactive oxygen species levels were lower in treated lungs during reperfusion (P = 0.01). Additionally, prior to reperfusion, treated lungs demonstrated more preserved mitochondrial cytochrome c oxidase activity (P = 0.01). Conclusions: To our knowledge, this study represents the first reported therapeutic use of inhaled H2S in an experimental model of LTx. After prolonged ischemia, lungs pretreated with inhaled H2S exhibited improved graft function during reperfusion. Donor pretreatment with inhaled H2S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration.
AB - Objectives: Ischemia/reperfusion injury (IRI) is a common complication of lung transplantation (LTx). Hydrogen sulfide (H2S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pretreatment with inhaled H2S would improve graft function in an ex vivo model of LTx. Methods: Rabbits (n = 10) were ventilated for 2 h prior to heart-lung bloc procurement. The treatment group (n = 5) inhaled room air (21% O2) supplemented with 150 ppm H2S while the control group (n = 5) inhaled room air alone. Both groups were gradually cooled to 34°C. All heart-lung blocs were then recovered and cold-stored in low-potassium dextran solution for 18 h. Following storage, the blocs were reperfused with donor rabbit blood in an ex vivo apparatus. Serial clinical parameters were assessed and serial tissue biochemistry was examined. Results: Prior to heart-lung bloc procurement, rabbits pretreated with H2S exhibited similar oxygenation (P = 0.1), ventilation (P = 0.7), and heart rate (P = 0.5); however, treated rabbits exhibited consistently higher mean arterial blood pressures (P = 0.01). During reperfusion, lungs pretreated with H2S had better oxygenation (P < 0.01) and ventilation (P = 0.02), as well as lower pulmonary artery pressures (P < 0.01). Reactive oxygen species levels were lower in treated lungs during reperfusion (P = 0.01). Additionally, prior to reperfusion, treated lungs demonstrated more preserved mitochondrial cytochrome c oxidase activity (P = 0.01). Conclusions: To our knowledge, this study represents the first reported therapeutic use of inhaled H2S in an experimental model of LTx. After prolonged ischemia, lungs pretreated with inhaled H2S exhibited improved graft function during reperfusion. Donor pretreatment with inhaled H2S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration.
KW - Animal model
KW - Hydrogen sulfide
KW - Ischemia/reperfusion injury, lung
KW - Transplantation, lung
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U2 - 10.1016/j.jss.2012.06.037
DO - 10.1016/j.jss.2012.06.037
M3 - Article
C2 - 22771242
AN - SCOPUS:84869080587
VL - 178
SP - 593
EP - 600
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 2
ER -