QT间期离散度与心肌梗塞预后的关系

目的探讨ＣＴ间期离散度对急性心肌梗塞近期预后的预测价值．方法计算方法：每导联均测ＱＴ间期３～５个．取均值．则ＱＴ间期离散度（ＱＴｄ）＝ＱＴｍａｘ－ＱＴｍｉｎ，用心率校正后的ＱＴ间期（ＱＴｃ）的离散度（ＱＴｃｄ）＝ＱＴｃｍａｘ－ＱＴｃｍｉｎ．结果急性心肌梗塞组与对照组ＱＴｃ、ＱＴｄ．ＱＴｃｄ值比较有显著差异（Ｐ＜０．００１）．梗塞组有无恶性心律失常及猝死者ＱＴｃ、ＱＴｄ、ＱＴｅｄ对比有显著差异（Ｐ＜０．０１）．当ＱＴＣ≥４４０ｍｓ，ＱＴｄ、ＱＴＣｄ≥６０ｍｓ时发生恶性心律失常及猝死的诊断正确指数ＱＴｃｄ与ＱＴＣ、ＱＴｄ比较有明显差异（Ｐ＜０．０５）．但ＱＴｄ与ＱＴＣ比较无明显差异（Ｐ＞０．０５）．结论ＱＴ离散度能更好反映心室复极过程，尤其是用心率校正后的ＱＴ离散度，对判断急性心肌梗塞近期预后具有重要指导价值．     

In vivo pharmacological interactions between a type II positive allosteric modulator of α7 nicotinic ACh receptors and nicotinic agonists in a murine tonic pain model

Background and Purpose

The α7 nicotinic ACh receptor subtype is abundantly expressed in the CNS and in the periphery. Recent evidence suggests that α7 nicotinic ACh receptor (nAChR) subtypes, which can be activated by an endogenous cholinergic tone comprising ACh and the α7 agonist choline, play an important role in chronic pain and inflammation. In this study, we evaluated whether type II α7 positive allosteric modulator PNU-120596 induces antinociception on its own and in combination with choline in the formalin pain model.

Experimental Approach

We assessed the effects of PNU-120596 and choline and the nature of their interactions in the formalin test using an isobolographic analysis. In addition, we evaluated the interaction of PNU-120596 with PHA-54613, an exogenous selective α7 nAChR agonist, in the formalin test. Finally, we assessed the interaction between PNU-120596 and nicotine using acute thermal pain, locomotor activity, body temperature and convulsing activity tests in mice.

Key Results

We found that PNU-120596 dose-dependently attenuated nociceptive behaviour in the formalin test after systemic administration in mice. In addition, mixtures of PNU-120596 and choline synergistically reduced formalin-induced pain. PNU-120596 enhanced the effects of nicotine and α7 agonist PHA-543613 in the same test. In contrast, PNU-120596 failed to enhance nicotine-induced convulsions, hypomotility and antinociception in acute pain models. Surprisingly, it enhanced nicotine-induced hypothermia via activation of α7 nAChRs.

Conclusions and Implications

Our results demonstrate that type II α7 positive allosteric modulators produce antinociceptive effects in the formalin test through a synergistic interaction with the endogenous α7 agonist choline.