Calcitonin gene-related peptide in myocardial ischaemia and reperfusion in the pig.
OBJECTIVE
In myocardial ischaemia, slow conducting capsaicin-sensitive C-fibres are activated. Apart from the mediation of pain, activation of these fibres causes release of various peptides, such as calcitonin gene-related peptide (CGRP), which is a potent vasodilator. The aim of this study was to investigate the role of CGRP in the context of myocardial ischaemia in vivo.


METHODS
The left anterior descending coronary artery (LAD) was occluded during 45 min in 27 anaesthetised open-chest pigs. LAD flow, mean arterial pressure (MAP), heart rate, peak dP/dt, arterial and coronary venous concentration of CGRP was measured prior to ischaemia, and during 4 h of reperfusion. The extent of myocardial infarction was measured using staining with triphenyl tetrazolium chloride.


RESULTS
Retroinfusion of CGRP (100 micrograms) into the ischaemic myocardium was associated with a more pronounced hyperaemia, and systemic hypotension, during early reperfusion. The infarct size in relation to the area at risk was not affected by CGRP or the CGRP antagonist CGRP(8-37), and averaged 67 +/- 3%. There were no changes in plasma CGRP levels during ischaemia or reperfusion.


CONCLUSIONS
Exogenously administered CGRP can cause systemic hypotension and augments postischaemic coronary flow. In this model, no cardioprotective effect of CGRP could be proven.
Department of Thoracic Surgery, Karolinska Hospital, Stockholm, Sweden.
G
G
Källner
A
A
Gonon
A
A
Franco-Cereceda
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008916:Miotics / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D013552:Swine
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D008916:Miotics; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide