Effects of preconditioning and postconditioning with fructose-1, 6-bisphosphate on ischemia-reperfusion injury in isolated rat hearts

Abstract

Objective To evaluate the effects of preconditioning and postconditioning with fructose-1, 6-bisphosphate (FBP) on ischemia-reperfusion (I/R) injury in isolated rat hearts. Methods Healthy male Sprague-Dawley rats, aged 5-6 months, weighing 210-240 kg, were heparinized and anesthetized with isoflurane. Their hearts were excised and retrogradely perfused in a Langendorff apparatus with K-H solution saturated with 95% O2 and 5% CO2 at 37-38 ℃ in a Langendorff apparatus.Sixty isolated rat hearts were randomly divided into 4 groups (n= 15 each) using a random number table: control group (group C) , FBP preconditioning group (group Fpr) , I/R group, and FBP postconditioning group (group Fpo) . After 30 min of stabilization, the hearts were continuously perfused with K-H solution for 100 min in group C, with K-H solution for 10 min in the other three groups, or with K-H solution containing FBP 5 mmol/L for 10 min in group Fpr.In I/R, Fpr and Fpo groups, the hearts were perfused with cardioplegic solution 20 ml to induce cardiac arrest, and perfusion was stopped at the same time.After 30 min of suspension of perfusion, I/R and Fpr groups were perfused with K-H solution for 60 min, and group Fpo was first perfused with K-H solution containing FBP 5 mmol/L for 10 min, and then perfused with K-H solution for 50 min.At the end of stabilization (T0) , at 1 min before suspension of perfusion (T1) , and at 5, 15, 30 and 60 min of reperfusion (T2-5) , heart rate (HR) , left ventricular developed pressure (LVDP) , and left ventricular end-diastolic pressure (LVEDP) were recorded.At T0 and T5, the coronary flow (CF) was measured, and the coronary effluent was collected for determination of creatine kinase (CK) and lactic dehydrogenase (LDH) activities.The histopathologic changes of myocardium were examined with light microscope at T5. Results Compared to group C, HR and LVDP were significantly decreased, and LVEDP was increased at T2-5 in I/R, Fpr and Fpo groups, the CF was decreased at T5 in I/R and Fpr groups, and CK and LDH activities in coronary effluent were increased in I/R, Fpr and Fpo groups.Compared to group I/R, HR and LVDP were significantly decreased, and LVEDP was increased at T2-4, and the CF was increased, and CK and LDH activities in coronary effluent were decreased at T5 in Fpr and Fpo groups.Compared to group Fpr, HR and LVDP were significantly increased, and LVEDP was decreased at T2-5, and the CF was increased, and CK and LDH activities in coronary effluent were decreased at T5 in Fpo group.The histopathologic changes of myocardium were significantly mitigated in group Fpo compared with group Fpr. Conclusion Both FBP postconditioning and preconditioning can reduce I/R injury and improve cardiac function in isolated rat hearts, and FBP postconditioning offers better effect than FBP preconditioning. Key words: Fructosediphosphates; Ischemic preconditioning; Myocardial reperfusion injury; Ischemic postconditioning