Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Vahlhaus, C; Schulz, R; Post, H; Rose, J; Heusch, G.
Prevention of ischemic preconditioning only by combined inhibition of protein kinase C and protein tyrosine kinase in pigs.
J Mol Cell Cardiol. 1998; 30(2):197-209
Doi: 10.1006/jmcc.1997.0609
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Post Heiner
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- Abstract:
- In rabbits, inhibition of either protein kinase C or protein tyrosine kinase abolishes the infarct size reduction achieved by ischemic preconditioning. In pigs, however, inhibition of protein kinase C does not attenuate ischemic preconditioning. The present study tested whether inhibition of protein tyrosine kinase alone or in combination with inhibition of protein kinase C interferes with ischemic preconditioning in pigs. In 29 enflurane-anesthetized pigs, the LAD was cannulated and perfused from an extracorporeal circuit. Protein tyrosine kinase and protein kinase C were inhibited by continuous intracoronary infusion of genistein (5x10(-6) mol/l) and staurosporine (10(-7) mol/l), respectively. Subendocardial blood flow (ENDO) was measured with microspheres. Infarct size was analysed by TTC staining (% of LV area at risk) following 90 min low-flow ischemia and 120 min reperfusion. In the presence of genistein, 90 min ischemia at an ENDO of 0.06+/-0.01 (+/-s.e.m.) ml/min/g resulted in an infarct size of 16.7+/-4.2% (n=8). With genistein, ischemic preconditioning by 10 min ischemia and 15 min reperfusion still reduced infarct size to 6.5+/-2.7% (ENDO: 0.05+/-0. 01 ml/min/g, n=7, P<0.05). In the presence of both genistein and staurosporine, infarct size following 90 min ischemia was 14.1+/-3. 6% (ENDO: 0.06+/-0.01 ml/min/g, n=7). With genistein and staurosporine, ischemic preconditioning no longer reduced infarct size significantly (11.5+/-3.1%, ENDO: 0.06+/-0.01 ml/min/g, n=7). The effective attenuation of ischemic preconditioning only by simultaneous inhibition of both, protein kinase C and protein tyrosine kinase, suggests a complex signal cascade involving both protein kinases.Copyright 1998 Academic Press Limited.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Coronary Circulation - drug effects
- Enzyme Activation - drug effects
- Enzyme Inhibitors - pharmacology
- Female - pharmacology
- Genistein - pharmacology
- Hemodynamics - drug effects
- Ischemic Preconditioning, Myocardial - drug effects
- Male - drug effects
- Myocardial Infarction - pathology
- Protein Kinase C - antagonists and inhibitors
- Protein-Tyrosine Kinases - antagonists and inhibitors
- Rabbits - antagonists and inhibitors
- Signal Transduction - antagonists and inhibitors
- Staurosporine - pharmacology
- Swine - pharmacology
- Swine, Miniature - pharmacology
- Find related publications in this database (Keywords)
- infarction
- ischemia
- ischemic preconditioning
- protein kinase C
- protein tyrosine kinase
- pig