Effects of post-resuscitation administration with sodium hydrosulfide on cardiac recovery in hypoxia-reoxygenated newborn piglets.
Hydrogen sulfide may protect multiple organ systems against ischemic-reperfusion injuries. It is unknown if treatment with sodium hydrosulfide (NaHS, a hydrogen sulfide donor) will improve myocardial function and minimize oxidative stress in hypoxic-reoxygenated newborn piglets. Mixed breed piglets (1-5 day, 1.5-2.5 kg) were anesthetized and acutely instrumented for the measurement of systemic, pulmonary and regional (carotid, superior mesenteric and renal) hemodynamics and blood gas parameters. The piglets were induced with normocapnic alveolar hypoxia (10-15% oxygen, 2h) followed by reoxygenation with 100% (1h) then 21% oxygen (3h). At 10 min of reoxygenation, either NaHS (10mg/kg, 5 ml) or saline (5 ml) was administered intravenously for 30 min (5 min bolus followed by 25 min of continuous infusion) in a blinded, block-randomized fashion (n = 7/group). Plasma lactate and troponin I levels and tissue markers of myocardial oxidative stress were also determined. Two hours hypoxia caused cardiogenic shock (45 ± 3% of respective normoxic baseline), reduced regional perfusion with metabolic acidosis (pH 6.94 ± 0.02). NaHS infusion significantly improved recovery of cardiac index (84 ± 3% vs. 72 ± 5% in controls), systemic oxygen delivery (84 ± 3% vs. 72 ± 5% in controls) and systemic oxygen consumption (102 ± 5% vs. 84 ± 6% in controls) at 4h of reoxygenation. NaHS had no significant effect on systemic and pulmonary blood pressures, regional blood flows, plasma lactate and troponin I levels. The myocardial glutathionine ratio was reduced in piglets treated with NaHS (vs. controls, P<0.05). Post-resuscitation administration of NaHS improves cardiac function and systemic perfusion and attenuates myocardial oxidative stress in newborn piglets following hypoxia-reoxygenation.
Departments of Surgery, University of Alberta, Edmonton, Alberta, Canada; Departments of Pediatrics, University of Alberta, Edmonton, Alberta, Canada. Electronic address: poyin@ualberta.ca.
Po-Yin
PY
Cheung
Margaret
M
Miedzyblocki
Tze-Fun
TF
Lee
David L
DL
Bigam
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000378:metabolism / Q000503:physiopathology; D001692:Biological Transport / Q000187:drug effects; D001784:Blood Gas Analysis; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D019344:Lactic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects*; D012151:Resuscitation; D013440:Sulfides / Q000494:pharmacology*; D013552:Swine
D013440:Sulfides; D019344:Lactic Acid; C025451:sodium bisulfide; D005978:Glutathione; D010100:Oxygen
Hemodynamics; Hydrogen sulfide; Neonatal asphyxia; Oxidative stress; Reoxygenation; Swine