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ON THE BIOCHEMICAL MECHANISM OF STUNNING IN THE CHRONICALLY INSTRUMENTED DOG

Meissner, A. MD; Gombosova, I. PhD; Rolf, N. MD; Van Aken, H. MD; Boknik, P. PhD; Knapp, J. MD; Luss, H. MD; Muller, FU. MD; Vahlensieck, U. MD; Schmitz, W. MD; Neumann, J. MD

doi: 10.1097/00000539-199802001-00089
Abstracts of Posters Presented at the International Anesthesia Research Society; 72nd Clinical and Scientific Congress; Orlando, FL; March 7-11, 1998: Cardiovascular Anesthesia
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(Meissner, Rolf, Van Aken) Klinik und Poliklinik fur Anasthesiologie und operative Intensivmedizin, (Gombosova, Boknik, Knapp, Luss, Muller, Vahlensieck, Schmitz, Neumann) Institut fur Pharmakologie und Toxikologie, WWU Munster, Germany.

Abstract S89

Reversible contractile dysfunction after transient ischemia is termed myocardial stunning. Stunning is accompanied by reduced regional wall thickening fraction (WTF) and impaired cardiac relaxation. Previous work centered on open chest preparations. However, data are lacking for expression of regulatory proteins in stunned myocardium from conscious animals which may mimic clinical situations more closely. Here we focussed on SERCA2a, the Ca2+ pump of the sarcoplasmic reticulum which initiates relaxation and the inducible form of the heat shock protein 72 (HSP 72) which is increased in some open chest models of stunning and may convey protection against reperfusion injury.

METHODS: Dogs were chronically instrumented to measure continuously WTF in tissue perfused by the left anterior descending coronary artery (LAD) and as a control, by the ramus circumflexus (RCX). A ballon occluder was positioned around the LAD. After complete recovery from surgery, conscious animals were subjected to 10 min of complete LAD occlusion to induce stunning. This treatment reduced WTF in the LAD area but not in control tissue. After reperfusion WTF was allowed to recover to about 50% of pre-ischemic values. Then anesthesia was initiated, hearts were rapidly excised and tissue from area perfused by the LAD and RCX was frozen in liquid nitrogen. Frozen tissue samples were homogenized, extracts were prepared, separated via gel electrophoresis, transferred to nitrocellulose and incubated with antigen specific primary antibodies and radioactive secondary antibodies for quantification.

RESULTS: Ischemia reduced WTF to negative values in LAD area whereas RCX area was unchanged. Time to 50% WTF amounted to 40 +/- 12 min. The expression of SERCA2a was unaltered on protein level in LAD versus RCX from the same animals (n=4). Expression of HSP 72 was increased by 34% in LAD compared to RCX (n=4, p<0.05).

CONCLUSIONS: We could extend previous findings on HSP 72 expression from open chest to intact animals. This indicates that acutely altered gene expression could contribute to stunning in the conscious animal.

© 1998 International Anesthesia Research Society