Phenylephrine postconditioning increases myocardial injury: Are alpha-1 sympathomimetic agonist cardioprotective.
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Date
2014-07
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Abstract
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-fl ow 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 fl uorescent 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 fi nding may be of clinical and therapeutic relevance.
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Keywords
Apoptosis, Ischemia-reperfusion, Myocardial function, Phenylephrine
Citation
Mourouzis Iordanis, Saranteas Theodosios, Ligeret Heidi, Portal Christophe, Perimenis Philippos, Pantos Constantinos. Phenylephrine postconditioning increases myocardial injury: Are alpha-1 sympathomimetic agonist cardioprotective. Annals of Cardiac Anaesthesia. 2014 Jul; 17(3): 200-209.