Inhibition of p38 reduces myocardial infarction injury in the mouse but not pig after ischemia-reperfusion
| Autor: | Jeffrey M. Pearl, Timothy P. O'Neill, Jodie Y. Duffy, Jefferson M. Lyons, Robert A. Kaiser, Connie J. Wagner, Jeffery D. Molkentin, Kelly M. McLean |
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| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Pathology medicine.medical_specialty Heart disease Swine Physiology p38 mitogen-activated protein kinases Myocardial Infarction Ischemia Infarction Pharmacology Severity of Illness Index p38 Mitogen-Activated Protein Kinases Lesion Mice Species Specificity Physiology (medical) medicine Animals Myocardial infarction business.industry Imidazoles Reproducibility of Results medicine.disease Pyrimidines Reperfusion Injury Circulatory system medicine.symptom Cardiology and Cardiovascular Medicine business |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 289:H2747-H2751 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.01280.2004 |
| Popis: | The MAPK family member p38 is activated in the heart after ischemia-reperfusion (I/R) injury. However, the cardioprotective vs. proapoptotic effects associated with p38 activation in the heart after I/R injury remain unresolved. Another issue to consider is that the majority of past studies have employed the rodent as a model for assessing p38's role in cardiac injury vs. protection, while the potential regulatory role in a large animal model is even more uncertain. Here we performed a parallel study in the mouse and pig to directly compare the extent of cardiac injury after I/R at baseline or with the selective p38 inhibitor SB-239063. Infusion of SB-239063 5 min before ischemia in the mouse prevented ischemia-induced p38 activation, resulting in a 25% reduction of infarct size compared with vehicle-treated animals (27.9 ± 2.9% vs. 37.5 ± 2.7%). In the pig, SB-239063 similarly inhibited myocardial p38 activation, but there was no corresponding effect on the degree of infarction injury (43.6 ± 4.0% vs. 41.4 ± 4.3%). These data suggest a difference in myocardial responsiveness to I/R between the small animal mouse model and the large animal pig model, such that p38 activation in the mouse contributes to acute cellular injury and death, while the same activation in pig has no causative effect on these parameters. |
| Databáze: | OpenAIRE |
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