Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Copenhagen, Denmark.
Department of Clinical Experimental Research, Glostrup Research Institute, Glostrup University Hospital, Nordstjernevej 42, 2600, Glostrup, Denmark.
J Nucl Cardiol. 2022 Oct;29(5):2090-2099. doi: 10.1007/s12350-021-02678-8. Epub 2021 Jun 4.
Endogenous calcitonin gene-related peptide (CGRP) induces cardioprotective effects through coronary vasodilation. However, the systemic administration of CGRP induces peripheral vasodilation and positive chronotropic and inotropic effects. This study aims to examine the net effect on coronary perfusion of the systemically administered α-calcitonin gene-related peptide analogue, SAX, in rats during myocardial infarction.
Forty Sprague-Dawley rats underwent myocardial infarction. Following left anterior descending artery occlusion, [Tc]Tc-sestamibi was administered to determine the myocardial perfusion before treatment. Twenty minutes, 24 and 48 h after [Tc]Tc-sestamibi injection, the rats were treated with either SAX or placebo. Final infarct size was determined three weeks later by [Tc]Tc-sestamibi SPECT/CT scan.
Thirty-one rats survived the surgery and 20 completed the follow-up SPECT/CT scan (SAX n = 12; Placebo n = 8). At baseline, there was no difference in size of perfusion defect between the groups (P = .88), but at follow-up the SAX group had improved myocardial recovery compared to the placebo group (P = .04), corresponding to a relative perfusion recovery of 55% in SAX-treated rats.
The CGRP analogue, SAX, has a cardioprotective effect in this rat model of myocardial infarction, improving myocardial perfusion recovery after chronic occlusion of the coronary artery.
内源性降钙素基因相关肽(CGRP)通过冠脉扩张产生心脏保护作用。然而,CGRP 的全身给药会引起外周血管扩张以及正性变时和变力作用。本研究旨在探讨在心肌梗死大鼠中,全身给予α-降钙素基因相关肽类似物 SAX 对冠脉灌注的净效应。
40 只 Sprague-Dawley 大鼠行心肌梗死造模。左前降支闭塞后,给予[Tc]Tc- sestamibi 以确定治疗前的心肌灌注情况。在[Tc]Tc-sestamibi 注射后 20 分钟、24 小时和 48 小时,大鼠分别接受 SAX 或安慰剂治疗。3 周后通过[Tc]Tc-sestamibi SPECT/CT 扫描确定最终梗死面积。
31 只大鼠存活至手术结束,其中 20 只完成了后续的 SPECT/CT 扫描(SAX 组 n=12;安慰剂组 n=8)。在基线时,两组间的灌注缺损大小无差异(P=0.88),但在随访时,SAX 组与安慰剂组相比,心肌恢复得到改善(P=0.04),对应于 SAX 治疗组心肌灌注恢复相对增加 55%。
在本大鼠心肌梗死模型中,CGRP 类似物 SAX 具有心脏保护作用,可改善慢性冠状动脉闭塞后的心肌灌注恢复。