Left ventricular remodeling after infarction: sequential MR imaging with oral nicorandil therapy in rat model.
OBJECTIVE
To use magnetic resonance (MR) imaging in quantification of the short- and long-term effects of therapy with orally administered nicorandil on left ventricular (LV) geometry and function independent of infarction size.


METHODS
Forty-six rats were subjected to reperfused infarction and randomly divided into two groups. Group 1 rats (n = 21) were treated with nicorandil (3 mg/kg/day in drinking water) for 4 days before infarction and 8 weeks after infarction (hereafter, the nicorandil group). Group 2 rats (n = 25) received tap water for the same period and served as the control group. Mesoporphyrin- (as a necrosis-specific agent) enhanced MR imaging was used to define necrotic myocardium on day 2 after infarction in all 46 animals. Contrast material-enhanced MR images showed large but identical infarction size in 11 control and 11 nicorandil rats. Only these 22 rats underwent repeat MR imaging at 8 weeks after infarction. The following variables were measured: LV volumes, ejection fraction, mass, wall thickness, and infarction size. Student t test and analysis of variance for repeated measurements were used for statistical analysis.


RESULTS
The size of the necrotic region on mesoporphyrin-enhanced MR images was 39% +/- 3 of the size of the left ventricle in the control group and 41% +/- 2 in the nicorandil group (difference not significant, unpaired Student t test). Pretreatment with nicorandil for 6 days before imaging did not reduce LV dilation or improve function compared with those in control animals with identical infarction size. Eight weeks after infarction, control animals showed deterioration in LV function, wall thinning, and gradient in regional dysfunction (analysis of variance test). Nicorandil produced significant salutary effects on LV ejection fraction (37% +/- 3 in the nicorandil group vs 24% +/- 3 in the control group), end-diastolic volume (0.53 mL +/- 0.03 vs 0.65 mL +/- 0.04), end-systolic volume (0.36 mL +/- 0.03 vs 0.49 mL +/- 0.05), LV wall thickening in remote noninfarcted myocardium (28% +/- 2 vs 19% +/- 1), and a rim of infarction (16% +/- 2 vs 8% +/- 1) (P <.05 for all parameters). The increase in LV mass was reduced in the nicorandil group (0.73 g +/- 0.03) compared with that in the control group (0.89 g +/- 0.04) (P <.05).


CONCLUSIONS
In animals studied longitudinally, MR imaging demonstrated the deleterious changes in LV geometry and function in the period after infarction and the salutary effects of medical therapy.
Saeed
Maythem
M
Department of Radiology, University of California, San Francisco, 505 Parnassus Ave, Rm L-308, 94143-0628, USA. maythem.saeed@radiology.ucsf.edu
Watzinger
Norbert
N
Krombach
Gabriele A
GA
Lund
Gunnar K
GK
Wendland
Michael F
MF
Chujo
Mitsuaki
M
Higgins
Charles B
CB
D000284:Administration, Oral; D000818:Animals; D002306:Cardiac Volume; D004195:Disease Models, Animal; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008652:Mesoporphyrins / Q000494:pharmacology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D020108:Nicorandil / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*
D008652:Mesoporphyrins; D014665:Vasodilator Agents; D020108:Nicorandil; C031468:mesoporphyrin IX