Confined ischemia may improve remote myocardial outcome after rat cardiac arrest

Abstract

Background. Confined ongoing ischemia after ischemia-reperfusion injury (IRI) may alter myocardial recovery. We evaluated in a rat cardiac transplantation model whether distal persistent myocardial ischemia (dMI) and remote preconditioning (RPreC) have a remote myocardial impact after IRI. Material and methods. Syngeneic heterotopic cardiac transplantation was performed on 29 Fischer344 rats to induce IRI, including nine rats which underwent distal ligation of the left anterior coronary artery (LAD) to yield distal MI (IRI+ dMI). RPreC was applied by occluding the left renal artery 5 min prior to reperfusion in six rats with IRI (IRI+ RPreC) as well as in seven with distal MI (IRI+ dMI+ RPreC). Microdialysis, histology and qRT-PCR for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) were performed after graft harvesting. Results. In contrast to IRI + dMI + RPreC (39 ± 7 μmol), glutamate decreased in IRI + RPreC and IRI + dMI as compared with IRI (26 ± 3 and 31 ± 8 vs 91 ± 20, μmol respectively, p < 0.007). The relative number of vacuolated intramyocardial artery nuclei decreased in IRI + dMI as compared with IRI (0.02 ± 0.01, range 0–12 vs. 0.42 ± 0.31, range 0–3.25 PSU respectively, p < 0.04). iNOS expression decreased in IRI + RPreC as compared with IRI (p < 0.04), and eNOS expression decreased in IRI + dMI + RPreC as compared with IRI + dMI (p < 0.006) along with increased glycerol release. Conclusions. dMI after IRI has a potentially beneficial myocardial impact after cardiac arrest, which is hampered by RPreC.

Key Words::

• Cardiac arrest
• ischemia-reperfusion
• rat
• remote preconditioning
• distal myocardial infarction

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This study was supported by research funding from The Competitive Research Funding of Pirkanmaa Hospital District, Finland, Tuberculosis Foundation, The Finnish Heart Association and The Finnish Cultural Foundation. Dr A. Mennander is the recipient of the Ingegeerd and Viking O. Bjork award for Scandinavian Cardiovascular Research.