Metabolic and functional response of neonatal pig hearts to the development of ischemic contracture: is recovery possible?
The potential for functional and metabolic recovery in neonatal hearts after the development of ischemic contracture remains controversial and undefined. This study documents post-ischemic recovery of metabolism and function in the in vivo neonatal heart after the development of onset and peak ischemic contracture. In piglets on cardiopulmonary bypass, hearts were reperfused after the development of either onset (TICo) or peak (TICp) ischemic contracture. Systolic (developed and systolic function, contractility) and diastolic (diastolic function, relaxation) performance was assessed throughout reperfusion. Biopsies were obtained at end-ischemia or end-reperfusion to assess metabolism. By end-ischemia, the metabolic profiles of both TICo and TICp hearts confirmed energy-store depletion and purine degradation that was quantitatively greater in TICp hearts. Hearts reperfused at TICo had consistent moderate impairment of developed function, contractility, diastolic function, and relaxation, whereas hearts reperfused at TICp had much more profound functional impairment. Diastolic function showed the worst functional recovery. In contrast, systolic function was not significantly altered in either study group and, thus, did not reflect the actual extent of injury. In addition, TICo hearts either did not further deplete or partially regenerated energy stores during reperfusion, whereas TICp hearts had further energy-store depletion and lactate accumulation. In summary, neonatal hearts reperfused after TICo maintained or partially restored energy stores and had significant but incomplete functional recovery. In contrast, further metabolic deterioration and profound functional impairment occurred with reperfusion after TICp, potentially indicating ongoing mitochondrial injury and compromised oxidative phosphorylation.
Institute of Medical Science, University of Toronto, Ontario, Canada .
S M
SM
Torrance
M P
MP
Belanger
W J
WJ
Wallen
C
C
Wittnich
D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D004734:Energy Metabolism; D006019:Glycolysis; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D017202:Myocardial Ischemia / Q000378:metabolism / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D012263:Ribonucleosides / Q000378:metabolism; D013552:Swine
D000227:Adenine Nucleotides; D012263:Ribonucleosides