Heat shock protein upregulation lowers cytokine levels after ischemia and reperfusion.
OBJECTIVE
Studies showed that the expression of heat shock protein 70 (HSP70) by whole-body hyperthermia or warming of the heart is associated with protection against ischemia/reperfusion injury. The aim of this study is to determine a time-related response of HSP70 expression through topical cardiac warming with correlation to cytokine production.


METHODS
30 rats were divided into three groups: no heat shock, heat shocked, and controls. Heat shock was performed with 42 degrees C saline solution applied to the heart for 5, 30, and 60 min. HSP70 and cytokines were measured.


RESULTS
Heat shock treated animals showed a 1.2-fold increase after 5 min (NS) in HSP70 expression, a 2.0-fold increase (p < 0.02) after 30 min, and a 2.3-fold increase (p < 0.012) after 60 min compared to controls. The IL-1beta levels decreased from 14.3 pg/ml (normal controls) to 7.1 pg/ml after 5 min, to 1.6 pg/ml after 30 min (p < 0.002), and to 1.4 pg/ ml after 60 min of heat shock treatment (p < 0.002). The TNF-alpha levels also decreased, but not significantly.


CONCLUSIONS
Upregulation of HSP70 through this novel method is instant and detectable within hours. The amount of HSP70 expression induced is time dependent, showing an indirect correlation with cytokine levels. These results suggest that the protective effect of HSP70 is immediate and might be explained by reduced cytokine levels. No prior recovery period is needed.
Grünenfelder
J
J
Clinic for Cardiovascular Surgery, University Hospital, Zürich, Switzerland. jurg.grunenfelder@chi.usz.ch
Zünd
G
G
Stucki
V
V
Hoerstrup
S P
SP
Kadner
A
A
Schoeberlein
A
A
Turina
M
M
D000818:Animals; D016207:Cytokines / Q000097:blood*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D007375:Interleukin-1 / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D012769:Shock / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D007375:Interleukin-1