Novel rat model of ischemic cardiomyopathy induced by repetitive myocardial ischemia/reperfusion injury while conscious.
BACKGROUND
A rodent model of ischemic cardiomyopathy (ICM) induced by repetitive brief ischemia/reperfusion (I/R) injury while conscious has not been previously established.


RESULTS
A newly developed coronary occluder was implanted in male Wistar rats. A repetitive I/R protocol (20 s, 2 min, followed by main 30 min--ischemia, every 48 h, for 4 weeks) was introduced while the animals were conscious. The I/R protocol did not induce transmural scar formation but induced (1) residual myocytes with scattered infiltration of fibrosis (Masson trichrome stain), (2) coronary hypoperfusion ((201)Tl-Cl autoradiogram), (3) reduced coronary microvascular volume fraction (microCT), and (4) gradually progressive left ventricular (LV) dilation (echocardiography). These parameters of ICM showed interindividual variation; however, the percent increase in LV diastolic area on day 3 was significantly correlated with LV dilation (r=0.91, p<0.0001), fibrosis (r=0.77, p=0.0034), and reduction in microvessels (r=0.67, p=0.040) at week 4. The LV dilatory response on day 3 also correlated with inducible nitric oxide synthase expression (immunohistochemistry, day 3) in the LV (r=0.92, p=0.028).


CONCLUSIONS
A novel rat model of ICM induced by repetitive I/R while conscious showed interindividual variation in the severity of ICM in the advanced stage, but this was predictable non-invasively (by LV dilatory response) during the initial stage of repetitive I/R.
Toyota
Eiji
E
Department of Cardiology, Kawasaki Medical School, Kurashiki, Japan. etoyota@med.kawasaki-m.ac.jp
Kawaguchi
Yukie
Y
Ogasawara
Yasuo
Y
Watanabe
Nozomi
N
Neishi
Yoji
Y
Kawamoto
Takahiro
T
Okura
Hiroyuki
H
Yoshida
Kiyoshi
K
D000818:Animals; D003243:Consciousness; D003326:Coronary Circulation; D004195:Disease Models, Animal; D005355:Fibrosis; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012008:Recurrence; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016277:Ventricular Function, Left
D052247:Nitric Oxide Synthase Type II