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在离体大鼠模型中,应变、年龄、来源和麻醉对局部和远程缺血预处理的心脏保护效果的影响。

Influence of strain, age, origin, and anesthesia on the cardioprotective efficacy by local and remote ischemic conditioning in an ex vivo rat model.

机构信息

Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark.

Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.

出版信息

Physiol Rep. 2021 Apr;9(7):e14810. doi: 10.14814/phy2.14810.

Abstract

BACKGROUND

Local ischemic preconditioning (IPC) and remote ischemic conditioning (RIC) induced by brief periods of ischemia and reperfusion protect against ischemia-reperfusion injury.

METHODS

We studied the sensitivity to IR-injury and the influence of strain, age, supplier, and anesthesia upon the efficacy of IPC and RIC in 7- and 16-weeks-old Sprague-Dawley and Wistar rats from three different suppliers. The influence of sedation with a hypnorm and midazolam mixture (rodent mixture) and pentobarbiturate was compared.

RESULTS

IPC attenuated infarct size in both 7-weeks-old Sprague-Dawley (48.4 ± 17.7% vs. 20.3 ± 6.9, p < 0.001) and 7-weeks-old Wistar (55.6 ± 10.9% vs. 26.8 ± 5.0%, p < 0.001) rats. Infarct size was larger in 16-weeks-old Sprague-Dawley rats, however, IPC still lowered infarct size (78.8 ± 9.2% vs. 58.3 ± 12.3%, p < 0.01). RIC reduced infarct sizes in 7-weeks-old Sprague-Dawley (75.3 ± 11.8% vs. 58.6 ± 8.9%, p < 0.05), but not in 7-weeks-old Wistar rats (31.7 ± 17.6% and 24.0 ± 12.6%, p = 0.2). In 16-weeks-old Sprague-Dawley rats, RIC did not induce protection (76.4 ± 5.5% and 73.2 ± 14.7%, p = 0.6). However, RIC induced protection in 16-weeks-old Wistar rats (45.2 ± 8.5% vs. 14.7 ± 10.8%, p < 0.001). RIC did not reduce infarct size in 7-weeks-old Sprague-Dawley rats from Charles River (62.0 ± 13.5% and 69.4 ± 10.4% p = 0.3) or 16-weeks-old Wistar rats from Janvier (50.7 ± 11.3 and 49.2 ± 16.2, p = 0.8). There was no difference between sedation with rodent mixture or pentobarbiturate.

CONCLUSION

The cardioprotective effect of IPC is consistent across rat strains independent of age, strain, and supplier. RIC seems to be less reproducible, but still yields protection across different rat strains. However, age, animal supplier, and anesthetics may modulate the sensitivity of IR-injury and the response to RIC.

摘要

背景

通过短暂的缺血再灌注诱导的局部缺血预处理(IPC)和远程缺血预处理(RIC)可预防缺血再灌注损伤。

方法

我们研究了在来自三个不同供应商的 7 周龄和 16 周龄 Sprague-Dawley 和 Wistar 大鼠中,IR 损伤的敏感性以及应变、年龄、供应商和麻醉对 IPC 和 RIC 功效的影响。比较了用 hypnorm 和咪达唑仑混合物(啮齿动物混合物)和戊巴比妥进行镇静的影响。

结果

IPC 减轻了 7 周龄 Sprague-Dawley(48.4±17.7%比 20.3±6.9%,p<0.001)和 7 周龄 Wistar(55.6±10.9%比 26.8±5.0%,p<0.001)大鼠的梗死面积。然而,16 周龄 Sprague-Dawley 大鼠的梗死面积更大,但 IPC 仍降低了梗死面积(78.8±9.2%比 58.3±12.3%,p<0.01)。RIC 降低了 7 周龄 Sprague-Dawley 大鼠的梗死面积(75.3±11.8%比 58.6±8.9%,p<0.05),但未降低 7 周龄 Wistar 大鼠的梗死面积(31.7±17.6%和 24.0±12.6%,p=0.2)。在 16 周龄 Sprague-Dawley 大鼠中,RIC 未诱导保护(76.4±5.5%和 73.2±14.7%,p=0.6)。然而,RIC 在 16 周龄 Wistar 大鼠中诱导了保护(45.2±8.5%比 14.7±10.8%,p<0.001)。RIC 未降低 7 周龄 Sprague-Dawley 大鼠(62.0±13.5%和 69.4±10.4%,p=0.3)或 16 周龄 Wistar 大鼠(50.7±11.3 和 49.2±16.2,p=0.8)来自 Charles River 的梗死面积。麻醉用啮齿动物混合物或戊巴比妥之间没有差异。

结论

IPC 的心脏保护作用在不同大鼠品系中是一致的,与年龄、品系和供应商无关。RIC 似乎不太可重复,但仍在不同大鼠品系中产生保护作用。然而,年龄、动物供应商和麻醉可能会调节 IR 损伤的敏感性和对 RIC 的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edc4/8020046/dd5783cb7a08/PHY2-9-e14810-g008.jpg

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