Improved myocardial preservation with short hyperthermia prior to cold cardioplegic ischemia in immature rabbit hearts.
OBJECTIVE
Recent observations have been shown that the induction and accumulation of heat shock proteins (HSPs) by short exposure to nonlethal whole-body hyperthermia with normothermic recovery are closely associated with transient resistance to subsequent ischemia-reperfusion challanges. Here, this study was performed to investigate whether a shortly heat shock pretreatment affects the left ventricular (LV) function after cold cardioplegic ischemia in reperfused neonatal rabbit hearts.


METHODS
Hearts from neonatal New Zealand White rabbits were isolated perfused (working heart preparation) and exposed to 2 h of cold cardioplegic ischemia followed by reperfusion for 60 min. To induce the heat shock response neonatal rabbits (n=5, HT-group) were subjected to whole-body hyperthermia at 42.0-42.5 degrees C for 15 min, followed by a normothermic recovery period of 60 min, before harvesting and the onset of global hypothermic cardioplegic arrest. Another set of hearts (n=5, control group) without a heat treatment underwent a similar perfusion and ischemia protocol served as control. The postischemic recovery was assessed by measuring several parameters of LV function. LV biopsies from all control and heat treated animals were taken before ischemia and at the end of reperfusion to examine myocardial HSP levels by Western blot analysis.


RESULTS
At 60 min of reperfusion the HT-group showed significant better recovery of ventricular function such as LV developed pressure (DP) (74.6+/-10 vs. 52.1+/-8.5%, P<0.05), LV positive dP/dt (910+/-170 vs. 530+/-58 mmHg/s, P<0.01) and LV end-diastolic pressure (LVEDP) (8+/-2 vs. 18.4+/-5 mmHg, P<0.05) than control. Myocardial oxygen consumption (MVO(2)) was significantly higher in the HT-group compared with control (0.054+/-0.006 vs. 0.041+/-0.002 ml/g per min, P<0.05). Significant postreperfusion lower level in lactate production was observed in the HT-group (0.83+/-0.11 vs. 1.67+/-0.8 mmol/l, P<0.05). Also, the recovery of hemodynamic parameters such as aortic flow, coronary flow and cardiac output was significantly superior (P<0.05) in the HT-group. Furthermore, high expression of HSP72(+)/73(+) were detected in the myocardial tissue samples of heat-treated rabbits by immunoblotting, appearing even at 60 min of normothermic recovery after heat stress.


CONCLUSIONS
These data in the immature rabbit heart indicate that previous shortly heat treatment with high level expression of heat shock proteins (HSP72(+)/73(+)) before hypothermic cardioplegic ischemia provides transient tolerance against myocardial injury and could be an improvement for the postischemic functional recovery of neonatal hearts.
Clinic for Heart Surgery, Philipps-University Marburg/Lahn, Baldingerstrasse, D-35033, Marburg/Lahn, Germany. vogts@mailer.uni-marburg.de
S
S
Vogt
D
D
Troitzsch
H
H
Abdul-Khaliq
W
W
Böttcher
P E
PE
Lange
R
R
Moosdorf
D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers; D015153:Blotting, Western; D002314:Cardioplegic Solutions / Q000009:adverse effects*; D002352:Carrier Proteins / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins; D006339:Heart Rate; D006360:Heat-Shock Proteins / Q000378:metabolism; D006979:Hyperthermia, Induced; D007036:Hypothermia, Induced / Q000009:adverse effects*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015425:Myocardial Reperfusion / Q000379:methods*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption; D011817:Rabbits
D015415:Biomarkers; D002314:Cardioplegic Solutions; D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D019344:Lactic Acid