A brief period of retrograde hyperthermic perfusion enhances myocardial protection from global ischemia: association with accumulation of Hsp 70 mRNA and protein.
The induction of heat shock proteins in the myocardium has been suggested as a possible intervention to allow for enhanced cardioprotection. We examined the cardioprotective effects of Hsp 70 induction in a clinically relevant model, in which a brief period of retrograde hyperthermic perfusion (42 degrees C) was applied for 15 min, only 5 min prior to global ischemia and reperfusion in the isolated perfused rat heart. Our results indicate that in retrograde hyperthermic perfused hearts (n = 17) there was enhanced dP/dT, end diastolic pressure, and peak developed pressure during normothermic reperfusion following 15 min of global ischemia when compared to control hearts perfused at 37 degrees C (n = 18). Northern analysis indicated Hsp 70 mRNA, in retrograde hyperthermic perfused hearts, was increased 9.0 +/- 0./70-fold (P < 0.001) by 30 min and 9.1 +/- 0.45-fold (P < 0.001) by 60 min of normothermic reperfusion. Western analysis revealed that the Hsp, heat inducible 72 kD protein was increased 1.74 +/- 0.35-fold (P < 0.001) by 30 min and 1.79 +/- 0.31-fold at 60 min of normothermic reperfusion when compared to no ischemia hearts. Our results demonstrate that the use of 15 min of retrograde hyperthermic perfusion, only 5 min prior to global ischemia and reperfusion, provide for enhanced myocardial functional recovery. Enhanced myocardial functional recovery was associated with the accumulation of Hsp 70 mRNA and the Hsp 72 kD protein.
McCully
J D
JD
Division of Cardiothoracic Surgery, New England Deaconess Hospital and Harvard Medical School, Boston, MA 02215, USA.
Lotz
M M
MM
Krukenkamp
I B
IB
Levitsky
S
S
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002021:Buffers; D003326:Coronary Circulation / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D006979:Hyperthermia, Induced; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015425:Myocardial Reperfusion; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013997:Time Factors
D002021:Buffers; D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger