Deletion of soluble epoxide hydrolase modulates coronary reactive hyperemia in isolated mouse hearts (837.10)

Abstract

Coronary reactive hyperemia (RH) is impaired in hypertrophic hearts and in hearts with metabolic syndrome. Epoxyeicosatrienoic acids (EETs) exert cardioprotective effects against ischemia / reperfusion injury. Soluble epoxide hydrolase (sEH) is the main enzyme responsible for EETs breakdown. We hypothesized that in the absence of sEH, isolated mouse hearts exhibit increased RH through increased generation of EETs in response to no‐flow ischemia compared to wild type (sEH+/+). Coronary flow (CF) in isolated sEH+/+ and sEH‐/‐ mouse hearts was measured using Langendorff system. Perfused isolated hearts were exposed to 15 second ischemia and RH parameters were assessed. Following ischemia, flow repayment (calculated as the area under the curve and normalized to heart weight (ml/g)) was significantly higher in sEH‐/‐ compared to sEH+/+ hearts (7.62 ± 0.47 in sEH‐/‐ vs. 5.86 ± 0.68 in sEH+/+, p<0.05). Moreover, sEH‐/‐ hearts exhibited significantly higher repayment to debt ratio when compared to sEH+/+ hearts (2.06 ± 0.17 in sEH‐/‐ vs. 1.48 ± 0.14 in sEH+/+, p<0.05). No significant differences were observed in baseline coronary flow, debt area, peak hyperemic flow and repayment duration between the two groups. Our results demonstrate that RH, as measured by flow repayment and repayment to debt ratio, is significantly higher in sEH‐/‐ compared to sEH+/+mice. These data suggest that targeting or silencing sEH could have a beneficial effect on myocardial recovery from ischemia. Supported by HL‐114559 to MAN and z01‐ES025034 to DCZ.Grant Funding Source: Supported by HL‐114559 to MAN and z01‐ES025034 to DCZ