Background: Cardiac PostC reduces ischemia/reperfusion (I/R) injury via a redox-sensitive mechanism. However in the presence of comorbidities the effectiveness of PostC is reduced. We studied whether PostC can reduce I/R injury in the presence of ventricular hypertrophy induced by hypertension or ND, an anabolic-androgenic steroid. Methods: A) Hypertension model: hearts isolated from SHR and Wistar-Kyoto (WKY) rats were subjected to: 30-min ischemia and 120-min reperfusion (I/R); I/R+PostC (5 cycles 10s I/R); 4-weeks pretreatment with an angiotensin-converting enzyme inhibitor (ACE- I) before to subject the hearts to I/R with or without PostC maneuvers; ACE-I infusion during early reperfusion (20 or 40 min) with or without PostC maneuvers. B) Drug-abuse: hearts isolated from ND pretreated (14-days or 10-weeks) rats and untreated rats underwent to I/R and PostC protocols. Infarct size and left ventricular pressure were evaluated. WB studies were also performed. Results and Conclusions: Data confirm PostC effectiveness in normotensive WKY and PostC ineffectiveness in SHR in limiting infarct size. Chronic ACE inhibition favors infarct size reduction in SHR; yet in WKY ACE-I reduces infarct size, but attenuates infarct-size limiting effects of PostC. ACE-I given in reperfusion does not reduce infarct size and does not recover PostC protection in SHR. In ND groups data show that 14-days ND does not induce hypertrophy and improves the post-ischemic cardiac function via β2-adrenoreceptor involvement with and without PostC. However, 10-weeks ND treatment induces cardiac hypertrophy, increases myocardial susceptibility to I/R injury and abolishes cardioprotection by PostC. ND alters the responses of survival kinases to PostC.
Postconditioning (PostC) cardioprotection in experimental modelsof cardiac hypertrophy: spontaneously hypertensive (SHR) and nandrolone (ND)-abuse rats
TULLIO, FRANCESCA;ANGOTTI, CARMELINA;PERRELLI, MARIA-GIULIA;CARRIERO, VITINA MARIA ANNA;PAGLIARO, Pasquale;PENNA, Claudia
2012-01-01
Abstract
Background: Cardiac PostC reduces ischemia/reperfusion (I/R) injury via a redox-sensitive mechanism. However in the presence of comorbidities the effectiveness of PostC is reduced. We studied whether PostC can reduce I/R injury in the presence of ventricular hypertrophy induced by hypertension or ND, an anabolic-androgenic steroid. Methods: A) Hypertension model: hearts isolated from SHR and Wistar-Kyoto (WKY) rats were subjected to: 30-min ischemia and 120-min reperfusion (I/R); I/R+PostC (5 cycles 10s I/R); 4-weeks pretreatment with an angiotensin-converting enzyme inhibitor (ACE- I) before to subject the hearts to I/R with or without PostC maneuvers; ACE-I infusion during early reperfusion (20 or 40 min) with or without PostC maneuvers. B) Drug-abuse: hearts isolated from ND pretreated (14-days or 10-weeks) rats and untreated rats underwent to I/R and PostC protocols. Infarct size and left ventricular pressure were evaluated. WB studies were also performed. Results and Conclusions: Data confirm PostC effectiveness in normotensive WKY and PostC ineffectiveness in SHR in limiting infarct size. Chronic ACE inhibition favors infarct size reduction in SHR; yet in WKY ACE-I reduces infarct size, but attenuates infarct-size limiting effects of PostC. ACE-I given in reperfusion does not reduce infarct size and does not recover PostC protection in SHR. In ND groups data show that 14-days ND does not induce hypertrophy and improves the post-ischemic cardiac function via β2-adrenoreceptor involvement with and without PostC. However, 10-weeks ND treatment induces cardiac hypertrophy, increases myocardial susceptibility to I/R injury and abolishes cardioprotection by PostC. ND alters the responses of survival kinases to PostC.
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