缺血预处理合并低温及晶体停搏液对兔未成熟心肌的保护作用(英文)

Myocardioprotective effects of the combination of ischemic preconditioning with hypothermia and crystalloid cardioplegia in immature rabbits

本文拟探讨缺血预处理(ischemic preconditioning,IP)合并低温及晶体停搏液对幼兔的离体心脏是否具有心肌保护作用。采用Langendorff离体心脏灌注模型,灌注液为Krebs-Henseleit液(K-H液)。取3～4周龄幼兔心脏,在第一部分实验中分为Con、IP1、IP2、IP3组(n=6),分别给予0、1、2、3次IP,其后各组心脏均在20℃低温下停灌2h,37℃常温下再灌注30min。在第二部 分实验中分为SCon1、SCon2、SCon3、SIP1、SIP2、SIP3组(n=8),其中SIP1、SIP2、SIP3组给予2次IP后灌注St.Tho-mas Ⅱ晶体停搏液(CCS)使心脏停搏,然后分别使心脏在32℃、25℃、20℃下停灌30、90和120min,其后各组均在37℃冉灌注30min。SCon1,SCon2,SCon3三组则不给予IP,继续灌注20min后灌注CCS使心脏停搏,然后分别在32℃、25℃、20℃下停灌30、90和120min,其后各组均在37℃再灌注30min。以Maclab/4s生理实验系统记录平衡末、缺血前、再灌注后1、3、5、10、20、30min时心率(HR)、左心室发展压(LVDP)以及左心室内压上升及下降最大速率(±dp/dt_(max)),测定再灌注末心肌组织中ATP和丙二醛(MDA)的含量,以及超氧化物歧化酶(SOD)的活性。在20℃低温停灌且停灌期间不给予CCS时,再灌注末IP2组LVDP×HR、+dp/dt_(max)和-dp/dt_(max)的恢复率分别为96%±21%、101%?

This study was undertaken to explore the myocardioprotective effects of the combination of ischemic preconditioning (IP) with hypothermia and St Ⅱ Thomas crystalloid cardioplegic solution (CCS) on immature hearts in the rabbit.Isolated immature rabbit hearts were perfused with Krebs-Henseleit bicarbonate buffer on Langendorff apparaus. In experiment 1,24 heart were divided into 4 groups (n=6 in each group): Con, IP1, IP2 and IP3 group. Hearts of the four groups underwent 0, 1, 2 or 3 cycles of IP respectively. Then all the hearts were subjected to a sustained ischemia period of 2 h at 20℃ and a postischemic reperfusion period of 30 min at 37℃. In experiment 2, 48 hearts were divided into 6 groups (n=8 in each group): SConl, SIP1, SCon2, SIP2, SCon3 and SIP3 group, according to hypothermia and the duration of sustained ischemia (30 min at 32℃; 90 min at 25℃, 2 h at 20℃). The SIP1, SIP2 and SIP3 groups were preconditioned twice before the sustained hypothermic ischemia, while the SConl, SCon2 and SCon3 groups were not preconditioned. CCS was applied during sustained ischemia, all the hearts were reperfused for 30 min at 37℃. Heart rate (HR), left ventricular developed pressure (LVDP) and peak rate of increase or decrease of left ventricular pressure (±dP/dt_(max)) were recorded. Tissue concentration of adenosine triphosphate (ATP), malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured. At the end of reperfusion, values of product of LVDP and HR, ±dp/dt_(max) in IP2 group were 96%±21%, 101%±19% and 84%±15% of the baseline values respectively, which were significantly higher than those of Con group and IP3 group (P<0.01, P<0.05); also, the ATP content of IP2 group was higher than that of the Con group (P<0.01). When CCS was applied during sustained period of hypothermic ischemia at 32℃ or 25℃, recovery rates of RPP (rate product,=LVDP×HR) and +dp/dt_(max). in SIP1 group were 87%±14% or 99%±26% of the baseline values respectively (P<0.05, vs SConl group), the values in SIP2 group changed to 87%±16% or 102%±20% respectively (P<0.05, vs SCon2 group). Contents of ATP in SIP1 and SIP2 groups were significantly higher than those of SCon1 or SCon2 groups respectively (P<0.05), but MDA content of the two groups were significantly lower than those of SCon1 or SCon2 groups (P<0.05) respectively. The study indicates that IP attenuates hypothermic ischemia/reperfusion injury to immature rabbit hearts under 20℃ ischemia, two cycles of IP showing better myocardioprotective effects than 1 or 3 cycles of IP. When IP was combined with CCS which were applied during hypothermic ischemia period, the beneficial effects of IP were weakened as the temperature during the hypothermic period was elevated.