title: Ligation of ameroid-stenosed coronary artery leads to reproducible myocardial infarction--a pilot study in a porcine model.
abstract: OBJECTIVE
  Myocardial gene and cellular therapies have revived the use of porcine ischemic heart models. Commonly applied ameroid-obstruction produces inconsistent coronary stenoses and myocardial lesions, whereas abrupt coronary occlusion causes arrhythmias and sudden death. To produce a constant myocardial lesion after adaptation to ischemia, we surgically modified the ameroid-model by ligation. As a pilot study for further cell therapy research, the spontaneous myocardial response is described.
  
  
  METHODS
  Simultaneously with ameroid application, a loose loop of nonabsorbable thread was placed around the left circumflex artery (LCx) on 11 domestic piglets. Three weeks later, the loop was tightened. Coronary arteriograms with Rentrop collateral grading from 0 to 3, and 99mTc-single photon emission computerized tomography studies were performed 1 to 5 wk after ligation. At autopsy, the hearts were analyzed macroscopically, histologically, and with von Willebrandt factor-staining.
  
  
  RESULTS
  LCx-banding was well-tolerated in nine animals, of which angiographic occlusion was gained in eight. Postmortem analysis revealed a 5 to 10 cm(2) transmural or subendocardial lateral myocardial infarction in all except one heart. One week after occlusion, LCx showed well-developed collateral filling (Rentrop-grade 2.7 +/- 0.4), which remained unchanged at 5 wk. On single photon emission computerized tomography-scans, lateral wall perfusion increased spontaneously between 1 and 5 wk (P = 0.02), and von Willebrandt factor revealed clusters of neovascularization at the borders of infarct areas.
  
  
  CONCLUSIONS
  This new modification of ameroid model standardizes myocardial lesion, which might reduce animal number in preclinical studies, thus having ethical aspect. The remarked potential for spontaneous recovery in ischemic porcine myocardium should be considered in preclinical therapeutic studies.
authors.affiliation: Department of Vascular Surgery, University of Helsinki, Meilahti Hospital, Helsinki, Finland.
authors.forename: Tuija S
authors.initials: TS
authors.lastname: Ikonen
authors.forename: Tommi
authors.initials: T
authors.lastname: Pätilä
authors.forename: Kari
authors.initials: K
authors.lastname: Virtanen
authors.forename: Jyri
authors.initials: J
authors.lastname: Lommi
authors.forename: Kimmo
authors.initials: K
authors.lastname: Lappalainen
authors.forename: Esko
authors.initials: E
authors.lastname: Kankuri
authors.forename: Leena
authors.initials: L
authors.lastname: Krogerus
authors.forename: Ari
authors.initials: A
authors.lastname: Harjula
mesh_terms: D000792:Angiography; D000818:Animals; D002364:Caseins; D003327:Coronary Disease / Q000150:complications / Q000473:pathology; D023921:Coronary Stenosis / Q000139:chemically induced* / Q000150:complications* / Q000473:pathology; D004195:Disease Models, Animal; D006321:Heart / Q000502:physiology; D020100:Hydrogels; D008026:Ligation; D009203:Myocardial Infarction / Q000209:etiology* / Q000473:pathology; D017202:Myocardial Ischemia / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D010865:Pilot Projects; D012038:Regeneration / Q000502:physiology; D013552:Swine; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002364:Caseins; D020100:Hydrogels; C009719:ameroid