Heat shock protein 72 and apoptosis indicate cardiac decompensation during early multiple organ failure in sheep.
OBJECTIVE
Inducible heat shock protein 72 (HSP 72) preserves myocardial function and prevents apoptosis. We investigated the expression and localization of HSP 72 and apoptosis in our previously described new model of multiple organ failure.


METHODS
Eighteen adult-instrumented sheep and three healthy controls were randomly assigned to one of three groups: (a) norfenefrine-masked hypovolemia plus endotoxemia (NMH+ENDO); (b) norfenefrine-masked hypovolemia without endotoxemia (NMH); (c) recurrent endotoxemia during normovolemia (ENDO); and (d) normovolemia without endotoxemia (CONTROLS).


RESULTS
Hearts were analyzed by light microscopy, Western blots, immunohistochemistry, and TUNEL staining. HSP 72 expression was approximately threefold increased in NMH+ENDO compared with the other groups ( p<0.05) and was localized mainly in left ventricular cardiomyocytes. HSP 72 was elevated in animals with norfenefrine-refractory shock compared to survivors ( p=0.015). TUNEL-positive cells in the left ventricle were significantly elevated in the NMH+ENDO group ( p=0.05) and correlated with HSP 72 expression (r=0.51, p=0.018). HSP 72 correlated positively with heart rate (r=0.76, p<0.0001), the prefinal hourly dose of norfenefrine (r=0.88, p<0.0001), and negatively with left ventricular stroke work index (r=-0.52, p=0.028). Double staining revealed TUNEL-positive cells with and without HSP 72 expression. Micronecroses were only detectable in NMH and NMH+ENDO without intergroup difference or correlations with hemodynamics.


CONCLUSIONS
HSP 72 overexpression and apoptosis, but not necrosis, indicate cardiovascular decompensation and poor outcome during early multiple organ failure.
Baba
Hideo A
HA
Institut für Pathologie, Universität Essen, Hufelandstrasse 55, 45147 Essen, Germany. hideo.baba@medizin.uni-essen.de
Wohlschlaeger
Jeremias
J
Stubbe
Henning D
HD
Grabellus
Florian
F
Aken
Hugo Van
HV
Schmitz
Klaus J
KJ
Otterbach
Friedrich
F
Schmid
Kurt W
KW
August
Christian
C
Levkau
Bodo
B
Hinder
Frank
F
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D004195:Disease Models, Animal; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000032:analysis* / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D009102:Multiple Organ Failure / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D012756:Sheep
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins