A minimally-invasive closed chest myocardial occlusion-reperfusion model in rhesus monkeys (Macaca mulatta): monitoring by contrast-enhanced ultrasound imaging
- 205 Downloads
Myocardial infarction is frequently developed in canine and porcine models but exceptionally in non-human primates. The aim of this study was to develop a minimally invasive myocardial ischemic/reperfusion model in the monkey intended to be combined with imaging techniques, in particular myocardial contrast echocardiography (MCE). A balloon-tipped catheter was advanced via the femoral artery into the left anterior descending artery (LAD) under fluoroscopic guidance in ten anaesthetized male rhesus monkeys (Macaca mulatta). The balloon was inflated to completely occlude the vessel. Coronary angiography (CA) was performed to control the reality of the LAD occlusion/reperfusion. The ischemia period was followed by 3–6 h of reperfusion. Myocardial perfusion was evaluated during ischemia and at reperfusion by MCE using a novel ultrasound contrast agent (BR38). Occlusion was successfully induced during 18–50 min in nine out of the ten evaluated monkeys. ST segment elevation indicated myocardial ischemia. MCE showed complete transmural arrest of myocardial blood flow during the ischemia period and no persistent microvascular perfusion defects during reperfusion. A minimally invasive closed-chest model was successfully developed for creating myocardial ischemia in the rhesus monkey (Macaca mulatta). This technique could have an important role in mimicking acute coronary syndrome under physiologically and ethically-acceptable conditions. MCE provides non-invasively information on myocardial perfusion status, information not available from CA.
KeywordsBR38 Myocardial contrast echocardiography Macaca mulatta Myocardial ischemic/reperfusion Primate
The authors would like to acknowledge Marianne Depecker, Anais Michon (VetAgro Sup, Veterinary Campus of Lyon, Equine department, Anesthesiology, 69280- Marcy l’Etoile, France) and Fabrice Taborik (Cynbiose, 69280- Marcy l’Etoile, France) for their valuable technical assistance.
Conflict of interest statement
Hugues Contamin, Gilles Rioufol, Karine G Portier, Olivier M Lepage declare that they have no conflict of interest. Thierry Bettinger, Alexandre Helbert, Anne Broillet, Michel Schneider, François Tranquart, Regi Thomas* are employees of Bracco Suisse SA and Bracco Research USA (*).
- 1.Y-T Shen et al. (1996) Innate protection of baboon myocardium: effect of coronary artery occlusion and reperfusion. Am J Physiol 270 (Heart Circ Physiol) 39:H812–H818Google Scholar
- 6.Lavallee M, Vatner SF (1984) Regional myocardial blood flow and necrosis in primates following coronary occlusion. Am J Physiol 246 (Heart Circ Physiol) 15:H635–H639Google Scholar
- 8.Chahal NS, Senior R (2010) Clinical applications of left ventricular opacification. J Am Coll Cardiol Img 3:188–196Google Scholar
- 22.Schneider M, Anantharam B, Arditi M, Bokor D, Broillet A, Bussat P, Fouillet X, Frinking P, Tardy I, Terrettaz J, Senior R, Tranquart F (2011) BR38, a new ultrasound blood pool agent. Invest Radiol (Accepted for publication)Google Scholar
- 24.Kessler D et al (1995) Contrast echocardiography in monkeys: dose response and reproducibility of blood pool and myocardial enhancement following intravenous administration of Echogen® 2% emulsion. J Am Soc Echocardiogr 8(3):363Google Scholar
- 25.Yoshioka T, Ageyama N, Shibata H, Yasu T, Misawa Y, Takeuchi K, Matsui K, Tera K, Shimada K, Ikeda U, Ozawa K, Hanazono Y (2005) Repairs of infracted myocardium mediated by transplanted bone marrow-derived CD34 + stem cells in a nonhuman primate model. Stem Cells 23:355–364PubMedCrossRefGoogle Scholar
- 26.Wasmeier GH, Asmussen S, Voigt JU, Flachskampf FA, Daniel WG, Nixdorff U (2008) Real-time myocardial contrast stress echocardiography using bolus application Ultrasound. Med Biol 34(11):1724–1731Google Scholar