Effects of prostaglandin E1 on nitric oxide and oxygen dynamics during rat myocardial ischemia–reperfusion utilizing sol–gel derived microsensors

Abstract

Prostaglandin E1 (Alprostadil®, PGE1) is often used for patients with critical limb ischemia due to its vasodilator and anti-platelet effects. Although PGE1 is considered to have a cardioprotective effect against myocardial ischemia–reperfusion (IR) injury, its mechanism and correlation with nitric oxide (NO) for cardioprotection are not clear. In this study, we used sol–gel-modified electrochemical NO and O2 microsensors to simultaneously measure the changes in NO level and oxygen tension (pO2) in the myocardium during myocardial IR that were induced by PGE1 pretreatment. Rat hearts were randomly divided into two groups: a control group (n=5) and a PGE1 group (n=5, with PGE1 pretreatment). Myocardium that underwent PGE1 pretreatment (26.0±13.1%, p<0.001) demonstrated more highly reduced endogenous NO production during the ischemic period than that of the control group (86.7±18.5%). After the onset of reperfusion, %NO level in the PGE1 group increased to a maximum of 82.0±6.4 but did not exceed the pre-ischemic basal NO level. However, in the control group, the maximum %NO response (164.9±41.0) on reperfusion was approximately double that of the PGE1 group (p<0.01, n=5). The restoration value of pO2 in the PGE1 group significantly increased and was restored to pre-ischemic level (82.2±21.3%); however, the pO2 of the control group did not increase throughout the reperfusion period (12.3±7.9%, p<0.001). As a result, we suggest that the cardioprotective effect of PGE1 might be attributed to a reduction in excessive NO production during reperfusion. Therefore, simultaneous and real-time monitoring of NO and pO2 dynamics in the myocardium would be effective in evaluating the effects of therapeutic treatments such as drug administration. Also, the reduction in excessive NO release during the early reperfusion period might be helpful as a therapeutic strategy to protect the myocardium from IR injury.