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Phenylephrine postconditioning increases myocardial injury: Are alpha-1 sympathomimetic agonist cardioprotective?


1 Department of Pharmacology, University of Athens, 11527 Goudi, Athens, Greece
2 Department of Anaesthesia, General Hospital of Montreal, McGill University, Montreal, Canada
3 Department of Chemistry, Quidd, 50 Ettore Bugatti street, 76800 Saint Etienne du Rouvray, France
4 Department of Chemistry, University of Rouen, Place Emile Blondel, 76821 Mont Saint-Aiginan, France

Correspondence Address:
Iordanis Mourouzis
Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, 11527 Goudi, Athens
Greece
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.135850

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Year : 2014  |  Volume : 17  |  Issue : 3  |  Page : 200-209

 

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Objective: We studied effects of phenylephrine (PHE) on postischemic functional recovery and myocardial injury in an ischemia-reperfusion (I-R) experimental model. Materials and Methods: Rat hearts were Langendorff-perfused and subjected to 30 min zero-flow ischemia (I) and 60 min reperfusion (R). During R PHE was added at doses of 1 μM (n = 10) and 50 μM (n = 12). Hearts (n = 14) subjected to 30 and 60 min of I-R served as controls. Contractile function was assessed by left ventricular developed pressure (LVDP) and the rate of increase and decrease of LVDP; apoptosis by fluorescent imaging targeting activated caspase-3, while myocardial injury by lactate dehydrogenase (LDH) released during R. Activation of kinases was measured at 5, 15, and 60 min of R using western blotting. Results: PHE did not improve postischemic contractile function. PHE increased LDH release (IU/g); 102 ± 10.4 (Mean ± standard error of mean) control versus 148 ± 14.8 PHE (1), and 145.3 ± 11 PHE (50) hearts, (P < 0.05). PHE markedly increased apoptosis. Molecular analysis showed no effect of PHE on the activation of proapoptotic c-Jun N-terminal kinase signaling; a differential pattern of p38 mitogen activated protein kinase (MAPK) activation was found depending on the PHE dose used. With 1 μM PHE, p-p38/total-p38 MAPK levels at R were markedly increased, indicating its detrimental effect. With PHE 50 μM, no further changes in p38 MAPK were seen. Activation of Akt kinase was decreased implying involvement of different mechanisms in this response. Conclusions: PHE administration during reperfusion does not improve postischemic recovery due to exacerbation of myocardial necrosis and apoptosis. This finding may be of clinical and therapeutic relevance.






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1 Department of Pharmacology, University of Athens, 11527 Goudi, Athens, Greece
2 Department of Anaesthesia, General Hospital of Montreal, McGill University, Montreal, Canada
3 Department of Chemistry, Quidd, 50 Ettore Bugatti street, 76800 Saint Etienne du Rouvray, France
4 Department of Chemistry, University of Rouen, Place Emile Blondel, 76821 Mont Saint-Aiginan, France

Correspondence Address:
Iordanis Mourouzis
Department of Pharmacology, University of Athens, 75 Mikras Asias Avenue, 11527 Goudi, Athens
Greece
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.135850

Rights and Permissions

Objective: We studied effects of phenylephrine (PHE) on postischemic functional recovery and myocardial injury in an ischemia-reperfusion (I-R) experimental model. Materials and Methods: Rat hearts were Langendorff-perfused and subjected to 30 min zero-flow ischemia (I) and 60 min reperfusion (R). During R PHE was added at doses of 1 μM (n = 10) and 50 μM (n = 12). Hearts (n = 14) subjected to 30 and 60 min of I-R served as controls. Contractile function was assessed by left ventricular developed pressure (LVDP) and the rate of increase and decrease of LVDP; apoptosis by fluorescent imaging targeting activated caspase-3, while myocardial injury by lactate dehydrogenase (LDH) released during R. Activation of kinases was measured at 5, 15, and 60 min of R using western blotting. Results: PHE did not improve postischemic contractile function. PHE increased LDH release (IU/g); 102 ± 10.4 (Mean ± standard error of mean) control versus 148 ± 14.8 PHE (1), and 145.3 ± 11 PHE (50) hearts, (P < 0.05). PHE markedly increased apoptosis. Molecular analysis showed no effect of PHE on the activation of proapoptotic c-Jun N-terminal kinase signaling; a differential pattern of p38 mitogen activated protein kinase (MAPK) activation was found depending on the PHE dose used. With 1 μM PHE, p-p38/total-p38 MAPK levels at R were markedly increased, indicating its detrimental effect. With PHE 50 μM, no further changes in p38 MAPK were seen. Activation of Akt kinase was decreased implying involvement of different mechanisms in this response. Conclusions: PHE administration during reperfusion does not improve postischemic recovery due to exacerbation of myocardial necrosis and apoptosis. This finding may be of clinical and therapeutic relevance.






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