Discussion of the best time to use dobutamine after myocardium ischemia/reperfusion

Abstract

Objective Using isolated rat heart ischemia/reperfusion injury(I/RI) model to compare the effects of dobutamine giving at different time points after reperfusion on cardiac function and myocardial injury and to explore the best time to use dobutamine after myocardium ischemia/reperfusion(I/R). Methods Thirty-six male SD rats, establishing isolated heart I/RI model in Langendorff perfusion apparatus with 15 min equilibrium, 30 min global ischemia and followed by 60 min reperfusion, were randomly divided into four groups(n=9). Different treatment was taken in reperfusion period. Group I/R: reperfused with Kreb's-Henseleit(K-H) solution, dobutamine group one(group D1): received dobutamine for 30 min after 5 min of reperfusion, other time perfused with K-H solution. Dobutamine group two (group D2): given dobutamine for 30 min after 15 min of reperfusion, other time perfused with K-H solution. Dobutamine group three(group D3): administrated dobutamine for 30 min after 25 min of reperfusion, other time perfused with K-H solution. Dobutamine infusion dose was 10 μg·kg-1·min-1. Heart function indexes of each group at the end of balance reperfusion(T0) and 10 min (T1), 20 min(T2), 30 min(T3), 60 min(T4) of reperfusion: HR, left ventricular end diastolic pressure(LVEDP), left ventricular developed pressure(LVDP), the maximum rate of left ventricular pressure change(±dp/dtmax) and coronary flow(CF) were recorded. The coronary flow at T0-T4 time points was used to measure the activity of lactate dehydrogenase (LDH) and creatine kinase(CK) according to the test methods attached to LDH and CK test kit. Myocardial infarct size(MIS) were measured with 2,3,5-triphenyl tetrazolium chloride (TTC) staining method. Sarcoendoplasmic reticulum Ca2+-ATPase (SERCA2a) and ryanodine receptors(RyR2) expression were determined by Western bloting. Results After giving dobutamine, HR, LVEDP, LDH and CK activity and MIS of group D1 were higher than those in group I/R(P 0.05). SERCA2a expression between the above groups was no significant difference. While RyR2 expression was higher in groups with dobutamin compared to group I/R. There was no significant difference in above data between group D2 and D3 after using dobutamine. Conclusions Giving dobutamine after 15 min of myocardial I/R in rats is superior to the other time points. Using dobutamine at this time point can timely and effectively improve HR, increase CF, improve myocardial contractile function, and does not aggravate myocardial injury. Key words: Myocardial; Ischemia/reperfusion injury; Dobutamine