Article Text
Abstract
Objective We investigated the impact of cardioprotective drugs on ST-elevation, arrhythmias and infarct size in a rat model of repetitive coronary artery occlusion.
Methods Seventy Sprague-Dawley rats were randomised to two control and five treatment groups. Placebo was either implantation of a pneumatic occluder onto the left anterior descending coronary artery (LAD) without starting repetitive occlusion (SHAM) or subsequent RO of the LAD over 10 days without medication (ROP). Treatment groups underwent RO and additionally received nitroglycerin (NTG), metoprolol, verapamil (VER), ranolazine (RAN) or candesartan (CAN). Two weeks after the intervention, rats underwent a single, sustained LAD occlusion followed by reperfusion. To evaluate differences in cardiac resistance against myocardial ischaemia and reperfusion injury, cardiac surrogate parameters including maximal ST-elevation, arrhythmias and infarct size were assessed.
Results Compared with sham, RO alone and RO plus nitroglycerin were associated with significantly lower maximal ST-elevation and percentage of infarcted myocardium (SHAM 0.12 mV, ROP 0.06 mV (p=0.004), NTG 0.05 mV (p=0.005); SHAM 16.2%, ROP 6.6% (p=0.008), NTG 5.9% (p=0.006). Compared with RO alone, RO plus RAN was accompanied by increased ST-elevation (0.13 mV, p=0.018) and RO plusVER or CAN by more infarcted myocardium (14.2%, p=0.004% and 15.5%, p=0.003, respectively). Rats treated with VER, RAN or CAN tended to severe arrhythmias more frequently than those of the control groups.
Conclusions RO led to an increased myocardial resistance against ischaemia and reperfusion injury. Concomitant administration of nitroglycerin did not affect the efficacy of RO. Cardiovascular channel or receptor blockers reduced the efficacy of RO.
- angiotensin II receptor blockers
- arteriogenesis
- beta-blockers
- calcium channel blockers
- collateral circulation
- coronary artery disease
- ischemic preconditioning
- myocardial ischemia
- myocardial infarction
- nitroglycerine
- ranolazine
- reperfusion injury
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Footnotes
Contributors Substantial contributions to the conception or design of the work: NG, NGü, PH, AD, FLN, EEB, IRB; or the acquisition, analysis or interpretation of data for the work: NG, NGü, PH, AD, FLN, EEB, MI, PB, IRB; drafting the work: MI, PB; or revising it critically for important intellectual content: NG, NGü, PH, AD, FLN, EEB, IRB; final approval of the version to be published: all authors; agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: all authors.
Funding The study was funded by a grant from the German Cardiac Society, Düsseldorf, Germany.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The animal procedures were approved by the Regional Office for Health and Social Affairs Berlin (G 0387/10 and G0040/14) and performed according to the guidelines from Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes and the German Animal Welfare Act as amended on May 2006.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.