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[Decreasing sarcoplasmic reticular calcium gives rise to myocardial protection--the effect of thapsigargin for myocardial protection under conditions of normothermia].

Abstract
Deceasing sarcoplasmic reticular (SR) calcium may contribute to the myocardiac protection against ischemia and reperfusion-induced injury. Therefore, using the isolated working rat heart model, we investigated the effect of Thapsigargin (TH)-induced SR calcium diminution on the myocardial protection when added either before onset of ischemia or at time of reperfusion under conditions of normothermic ischemia. Hearts (n = 6/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. In the experimental protocol A, this was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution No. 2 (STS) containing various concentrations of TH. Hearts were then subjected to 34 min of normothermic (37 degrees C) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). Reperfusion cardiac functions at 20 min of working perfusion was measured and compared with the preischemia values. STS added to 0.1 and 0.25 mumol/L TH improved recovery of aortic flow after 20 min reperfusion from 47 +/- 3% in the TH free controls to 62 +/- 3, 63 +/- 2% (n = 6) (p < 0.05). There was no difference in creatine kinase (CK) leakage during Langendorff reperfusion between the TH treated groups and the control group. In the experimental protocol B, 3 min of cardioplegia without TH and 34 min of ischemia (37 degrees C) were followed by a 10 min Langendorff reperfusion with various concentrations of TH, then 10 min Langendroff reperfusion for washing out, and 20 min working reperfusion. When TH was added to reperfusate the recovery of aortic flow did not change, 0.5 mumol/L TH group had the detelious effect. Thus, TH, when added to the cardioplegia, enhanced myocardial protection. We conclude that lessened uptake of Ca2+ into sarcoplasmic reticulum by inhibitors of the Ca(2+)-ATPase pump can decrease ischemia and reperfusion-induced injury.
AuthorsY Kumada, F Yamamoto, H Yamamoto, T Ishikawa, K Kagisaki, H Hirose
JournalThe Japanese journal of thoracic and cardiovascular surgery : official publication of the Japanese Association for Thoracic Surgery = Nihon Kyobu Geka Gakkai zasshi (Jpn J Thorac Cardiovasc Surg) Vol. 46 Issue 4 Pg. 368-74 (Apr 1998) ISSN: 1344-4964 [Print] Japan
PMID9619037 (Publication Type: Journal Article)
Chemical References
  • Cardioplegic Solutions
  • Enzyme Inhibitors
  • Thapsigargin
  • Calcium-Transporting ATPases
  • Calcium
Topics
  • Animals
  • Body Temperature
  • Calcium (metabolism)
  • Calcium-Transporting ATPases (antagonists & inhibitors)
  • Cardioplegic Solutions (pharmacology)
  • Enzyme Inhibitors (pharmacology)
  • Heart Arrest, Induced
  • In Vitro Techniques
  • Male
  • Myocardial Reperfusion
  • Rats
  • Rats, Wistar
  • Sarcoplasmic Reticulum (metabolism)
  • Thapsigargin (pharmacology)

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