The rapid expression of myocardial hsp 70 mRNA and the heat shock 70 kDa protein can be achieved after only a brief period of retrograde hyperthermic perfusion.
The induction of heat shock proteins in the myocardium has been suggested as a possible intervention to allow for enhanced cardioprotection. We have postulated that a brief period of retrograde hyperthermic perfusion would be sufficient to induce Hsp 70 mRNA and protein accumulation. To investigate this hypothesis, rat hearts (n = 45) were perfused at 37 degrees C for 30 min, then perfused for 15 min at 42 degrees C, and allowed to recover at 37 degrees C for 120 min. Control hearts (n = 23) were perfused at 37 degrees C continuously. Northern analysis indicated that in hearts treated with a brief period of retrograde hyperthermic perfusion Hsp 70 mRNA levels were increased 2.85 +/- 0.02-fold (P < 0.01) by 10 min, 4.88 +/- 0.94-fold (P < 0.01) by 15 min, 9.19 +/- 0.62-fold (P < 0.001) by 30 min, 9.4 +/- 0.52-fold (P < 0.001) by 60 min, 9.45 +/- 0.57-fold (P < 0.001) by 90 min and 9.66 +/- 0.99-fold (P < 0.001) by 120 min of normothermic recovery as compared to control hearts. Western analysis revealed that the heat inducible Hsp 72 kDa protein was increased 2.37 +/- 0.45-fold (P < 0.01) at 60 min, 2.53 +/- 0.25-fold (P < 0.01) at 90 min, and 2.7 +/- 0.6&-fold (P < 0.01) at 120 min when compared to control hearts. Our results indicate that the induction of the heat shock protein Hsp 70 can be rapidly achieved through retrograde hyperthermic perfusion of the myocardium.
McCully
J D
JD
Division of Cardiothoracic Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215, USA.
Myrmel
T
T
Lotz
M M
MM
Krukenkamp
I B
IB
Levitsky
S
S
D000818:Animals; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006321:Heart / Q000503:physiopathology*; D006339:Heart Rate; D006439:Hemodynamics; D006979:Hyperthermia, Induced; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger