Acute effect of cerivastatin on cardiac regional ischemia in a rat model mimicking off-pump coronary surgery.
BACKGROUND
Although the off-pump technique is becoming widely used in coronary bypass surgery, there has been no experimental rat heart model of regional reversible ischemia. The aims of this study were to investigate the optimal duration of coronary occlusion for making reversible ischemia and to examine whether cerivastatin increases myocardial tolerance against prolonged coronary occlusion.


METHODS
Study 1--Male Sprague-Dawley rats (350 to 450 g) underwent temporary occlusion of either left anterior descending artery (LAD; for 3, 5, 7.5, 10, 12.5, 15, or 20 min) or circumflex artery (CX; for 5, 10, or 15 min). Study 2--Rats were divided into two groups, control and cerivastatin groups, which had 0.1 mg/kg cerivastatin intravenously after anesthesia. LAD was occluded for 10, 15, or 20 minutes. In the both studies, hearts were stained to determine the area at risk (AR) and infarcted (IF) area 24 hours after reperfusion.


RESULTS
In LAD occlusion, IF/AR increased in a time dependent manner: 4.5 +/- 3.2%, 9.7 +/- 5.2%, 17.2 +/- 3.0%, 16.8 +/- 2.7%, 23.9 +/- 9.5% (p < 0.01 vs. 3 min), 62.4 +/- 2.9% (p < 0.0001), and 63.4 +/- 2.9% (p < 0.0001) at 3, 5, 7.5, 10, 12.5, 15, and 20 min, respectively. Also in CX, IF/AR increased with time: 14.3 +/- 2.3%, 25.9 +/- 2.1%, and 40.9 +/- 6.2% (p < 0.001 vs. 5 min) at 5, 10, and 15 min, respectively. Cerivastatin significantly reduced IF/AR at 15 minutes (43.7 +/- 6.2%) and at 20 minutes (44.6 +/- 5.3%) compared to control (62.4 +/- 2.9% and 60.6 +/- 2.5%, respectively, p < 0.05).


CONCLUSIONS
Cerivastatin increased myocardial tolerance after prolonged coronary occlusion over 10 minutes, which was considered to be the upper limit for creating a regional reversible ischemia in rats.
Nakamura
Koki
K
The National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Harefield Hospital, Middlesex, UK.
Al-Ruzzeh
Sharif
S
Ilsley
Charles
C
Yacoub
Magdi H
MH
Amrani
Mohamed
M
D000818:Animals; D047549:Coronary Artery Bypass, Off-Pump / Q000009:adverse effects; D003327:Coronary Disease; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000601:surgery; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011725:Pyridines; C086276:cerivastatin