How to interpret relationship between ischemic time and ischemia/reperfusion injury in langendorff perfused rat hearts

Abstract

Objective: Diversities in ischemia time and injury assessment criteria used in Langendorff perfused isolated heart models complicate evaluation of the results. In this study, relationship between myocardial functional recovery, tissue viability and ultrastructural changes following ischemia were investigated in order to determine criteria which should be used to make precise interpretations. Material and Methods: Hearts were perfused in the constant flow Langendorff mode and were subjected to either continuous perfusion (Control), or to 15 (Ischemia15), 30 (Ischemia30) or 45 (Ischemia45) minutes ischemia followed by 30 minutes reperfusion. Left ventricular developed pressure, maximum contraction and relaxation rates, heart rate, arrhythmia incidence and duration were evaluated. Coronary effluent and heart cross-sections were used for creatine kinase-MB (CK-MB) measurements and morphological studies, respectively. Results: All functional parameters remained unchanged in Control and Ischemia15 groups. In Ischemia30 group, LVDP, +dP/dtmax and -dP/dtmax declined in early reperfusion, +dP/dtmax returned to basal values and heart rate declined at the end of reperfusion. In Ischemia45 group, all functional parameters except for heart rate declined in early reperfusion and returned to basal values at the end of reperfusion. Arrhythmia scores increased in all hearts subjected to ischemia. CK-MB was not elevated and triphenyltetrasolium staining showed that tissues were viable in Control, Ischemia15 and Ischemia30 groups. Necrotic fields were found and CK-MB increased in Ischemia45 group. Despite low myofibril scores, most marked ultrastructural pathological changes were found in Ischemia15 group. As ischemia time increased, the ultrastructural changes expressed as edema, glycogen, mitochondria and nuclei scores decreased. Conclusion: Our findings show that functional parameters should be evaluated in conjunction with morphological and biochemical data to make precise interpretation in ischemia reperfusion studies in isolated Langendorff perfused rat hearts. © 2013 by Türkiye Klinikleri.