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EXPERIMENTAL STUDY

Moderate hypothermia during cardiopulmonary bypass reduces myocardial cell damage and myocardial cell death related to cardiac surgery

Jaime F. Vazquez-Jimenez, MD^*, Ma Qing, MD, Benita Hermanns, MD, Bernd Klosterhalfen, MD, Michael Wöltje, PhD, Raj Chakupurakal, MD, Kathrin Schumacher, MD, Bruno J. Messmer, MD^*, G.ötz von Bernuth, MD and Marie-Christine Seghaye, MD

^* Departments of Thoracic and Cardiovascular Surgery, Aachen, Germany
Pediatric Cardiology, Aachen, Germany
Institute of Pathology, Aachen, Germany
Interdisciplinary Center for Clinical Research "BIOMAT," Aachen University of Technology, Aachen, Germany

Manuscript received February 1, 2001; revised manuscript received May 21, 2001, accepted June 11, 2001.

Reprint requests and correspondence: Dr. Jaime F. Vazquez-Jimenez, Department of Thoracic and Cardiovascular Surgery, University Hospital, Aachen University of Technology, Pauwelsstrasse 30. D-52057 Aachen, Germany
jvazquez-jimenez{at}post.klinikum.rwth-aachen.de

OBJECTIVES

The goal of this study was to test the hypothesis that moderate hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance.

BACKGROUND

Moderate hypothermia during experimental CPB stimulates production of interleukin-10 (IL10) and blunts release of tumor necrosis factor- (TNF).

METHODS

Twelve young pigs were assigned to a temperature (T°) regimen during CPB: moderate hypothermia (T°: 28°C; n = 6) and normothermia (T°: 37°C; n = 6). Intra-myocardial TNF- and IL10-messenger RNA were detected by competitive reverse transcriptase polymerase chain reaction and quantification of cytokine synthesis by Western blot. Levels of cardiac troponin I (cTnI) in cardiac lymph and in arterial and coronary venous blood were examined during and after CPB. Myocardial cell damage was assessed by histologic and ultrastructural anomalies of tissue probes taken 6 h after CPB.

RESULTS

Synthesis of IL10 was significantly higher, while that of TNF was significantly lower, in pigs that were in moderate hypothermia during surgery than in the others. In contrast with normothermia, moderate hypothermia was also associated with significantly lower cumulative cardiac lymphatic flow during and after CPB, significantly lower lymphatic cTnI concentrations after CPB, significantly lower percentages of myocardial cell necrosis and a significantly lower score of ultrastructural anomalies of myocardial cells. While the percentage of apoptotic cells was not different between groups, the apoptosis/necrosis ratio tended to be higher in animals that were in moderate hypothermia during surgery. In all animals, TNF synthesis correlated positively while IL10 production correlated negatively with necrosis and total cell death, respectively.

CONCLUSIONS

Our results suggest that moderate hypothermia during CPB provides myocardial protection by enhancing intra-myocardial anti-inflammatory cytokine balance.

Abbreviations and Acronyms   BW = body weight   CPB = cardiopulmonary bypass   cTnI = cardiac troponin I   H&E = hematoxylin and eosin   IL10 = interleukin-10   mRNA = messenger RNA   NFB = nuclear factor kappa B   NO = nitric oxide   PCR = polymerase chain reaction   PVDF = polyvinylidene difluoride   T° = temperature   TNF = tumor necrosis factor-   TNFR1 = tumor necrosis factor- type 1 receptor   TNFR2 = tumor necrosis factor- type 2 receptor   TUNEL = terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling   US = ultrastructural score

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