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

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.

Myocardial protection: an approach with alterations in cations and trace elements in rats

This study was undertaken to investigate the cation and trace element changes in experimentally induced myocardial isehaemia like lesion evoked by isoprenaline. Rats were treated with 30 mg/kg S.C isoprenaline alone or in combination with the calcium entry blocker felodipine 1 mg/kg i.p or the free radical scavenger superoxide 15000 U/kg i.p. Our results showed that the isoprenaline-produced hypocupraernia and hypozincaemia, and the cardiac damage is accompanied by calcium overload, magnesium and zinc depletion, Felodipine and superoxide disinutase altered these changes in different manners. We conclude that manipulations of cardiac cations and trace elements can provide myocardial protections in experimental model of cardiac ischaemia induced by isoprenaline