Myocardial perfusion recovery induced by an α-calcitonin gene-related peptide analogue

Abstract

Background: 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.

Methods: Forty Sprague-Dawley rats underwent myocardial infarction. Following left anterior descending artery occlusion, [^99mTc]Tc-sestamibi was administered to determine the myocardial perfusion before treatment. Twenty minutes, 24 and 48 h after [^99mTc]Tc-sestamibi injection, the rats were treated with either SAX or placebo. Final infarct size was determined three weeks later by [^99mTc]Tc-sestamibi SPECT/CT scan.

Results: 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.

Conclusion: 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.

Keywords: MPI; Myocardial ischemia and infarction; Physiology of myocardial/coronary perfusion; SPECT.

Figure 1

Workflow of this study: First, the rats underwent LAD occlusion. After one minute, [^99mTc]Tc-sestamibi was injected for SPECT/CT scan. Twenty minutes later, the rats were treated with either SAX or placebo. The rats were again treated with SAX or placebo at 24 and 48 h after LAD occlusion. Three weeks after a [^99mTc]Tc-sestamibi follow-up, SPECT/CT was performed

Figure 2

Two representative examples of rats with chronic LAD occlusion. 4DM software was used to analyze [^99mTc]Tc-sestamibi SPECT/CT. Top panels (A and B) show a SAX-treated rat. Bottom panels (C and D) show a placebo-treated rat. A Large perfusion defect in the anterior and apical wall in the acute scan, with a smaller perfusion defect at follow-up scan after SAX treatment (white arrow). B The perfusion defects from panel A in a 17-segment polar map. C Medium perfusion defect in the anterior wall at the acute scan, and a more severe perfusion defect at follow-up after placebo treatment (red arrow). D The perfusion defects from panel C in a 17-segment polar map. HLA horizontal long axis, VLA vertical long axis, SRS summed rest score

Figure 3

Development of SRS from acute to follow-up scan. Each line represents one rat. Rats not surviving are only shown with a dot at baseline

Figure 4

Rats divided into three groups by ΔSRS: negative recovery, no recovery, and positive recovery

Figure 5

Overall survival is shown at the top. The early mortality at the bottom shows a tendency for SAX-treated rats to survive longer than the placebo-treated rats. The first dotted line is 21 min after LAD occlusion, which shows SAX or placebo injection. The second dotted line is 60 min after LAD occlusion, which shows time of SPECT/CT scan