Ischemic preconditioning can overcome the effect of moderate to severe cold ischemia on concordant mouse xeno-heart transplants.
OBJECTIVE
Concordant mouse xeno-heart transplants are relatively sensitive to ischemia-reperfusion injury. We investigated the effect of an ischemic preconditioning (IPC) protocol on the functional and biochemical outcome of mouse xenohearts transplanted to the Lewis rat.


METHODS
NMRI mice (30 to 40 g) were anesthetized, intubated, and mechanically ventilated. They were subjected either to a IPC protocol leading to an SaO(2) of 70% for 5 minutes followed by normoxia (defined as SaO(2) >90%) for 10 minutes (n = 9) or normoxia only (n = 11). The hearts were then heterotopically transplanted to Lewis rats (220 g). The frequencies of immediate onset and early dysfunction and late dysfunction were registered. The hearts surviving for 6 hours were explanted and the absolute concentrations of phosphocreatine and adenosine triphosphate (ATP) were determined in micromole per gram of heart tissue with high-pressure liquid chromatography. The phosphorylation ratio, PCr/ATP, a known correlate to biochemical and functional outcome, was calculated.


RESULTS
Four of 11 (36.4%) of control hearts experienced immediate onset and early dysfunction versus 0% (0/9) in M hearts subjected to IPC (P = .01). Furthermore, the IPC protocol increased the PCr concentration, 15.08 +/- 1.00 versus 9.04 +/- 2.04 micromol/g in controls (P = .01), and the PCr/ATP ratio, 1.80 +/- 0.17 versus 1.27 +/- 0.21 (NS; P = .06).


CONCLUSIONS
IPC provides a protective PCr overshoot overcoming the short-term effects of moderate to severe ischemic injury on mouse xeno-heart transplants.
Lukes
D J
DJ
Department of Surgery and Transplantation, and Wallenberg Laboratory for Cardiovascular Research, Sahlgrenska University Hospital, 413-45 Göteborg, Sweden. annette.daniel.lukes@swipnet.se
Lundgren
A
A
Skogsberg
U
U
Karlsson-Parra
A
A
Soussi
B
B
Olausson
M
M
D000818:Animals; D006085:Graft Survival; D016027:Heart Transplantation / Q000502:physiology*; D019194:Ischemic Preconditioning; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous / Q000502:physiology*