Evaluation cardioprotective effects of atorvastatin in rats by real time myocardial contrast echocardiography.
BACKGROUND
The ability to assess myocardial perfusion in small animals is important, especially to investigate models of myocardial ischemia. Myocardial perfusion is usually assessed by postmortem techniques, eliminating the possibility of follow-up in intervention studies. The purpose of the study was to examine the feasibility of real time myocardial contrast echocardiography (MCE) to evaluate cardioprotective effects of atorvastatin in a rat model of acute ischemia-reperfusion injury.


METHODS
The rats (n=15) underwent 20 minutes of mechanical left descending coronary artery (LAD) occlusion followed by 180 minutes of reperfusion. The animals received either atorvastatin (10 mg/kg), atorvastatin and the nitric oxide synthase (NOS)-inhibitor N-Nitro-L-Argininemethylester (L-NAME) (15 mg/kg), or vehicle. MCE was performed to assess the size of the perfusion defect and the myocardial signal intensities (A(max)) at the baseline, during occlusion, and during reperfusion. For comparison, the infarct size, risk area, and regional myocardial blood flow (MBF) were determined by the standard techniques as well.


RESULTS
The dynamics of ischemia-reperfusion injury could be visualized serially by MCE. The infarct size-to-risk area ratio progressively increased during reperfusion and was markedly reduced in the atorvastatin group. Triphenyltetrazolium chloride (TTC) staining confirmed a 23% reduction in the infarct size by atorvastatin. The infarct size by MCE correlated well with the histological methods (r=0.86, P < 0.001). A(max) was reduced in the anterior segments during LAD occlusion (0.08 +/- 0.01 dB) compared to the baseline (2.9 +/- 0.4 dB), approached higher levels post revascularization of LAD (3.22 +/- 0.50 dB), but decreased during 180 minutes of reperfusion (2.32 +/- 0.40 dB). After 180 minutes of reperfusion, A(max) in the risk area was significantly higher in the atorvastain-treated group compared to the vehicle-treated group (2.32 +/- 0.40 dB vs 1.3 +/- 0.4 dB, P <or= 0.05), indicating preserved MBF. The L-NAME-treated group showed no significant difference compared to the vehicle-treated group (A(max) 1.12 +/- 0.60 dB vs 1.3 +/- 0.4 dB). The regional blood flow ratio (ischemic-to-nonischemic wall) measured by the microspheres was significantly higher in the atorvastatin group compared to the control and the L-NAME groups, respectively (0.92 +/- 0.13 vs 0.45 +/- 0.23 vs 0.51 +/- 0.16, P <or= 0.05).


CONCLUSIONS
Atorvastatin has cardioprotective effects in acute reperfusion injury. Contrast echocardiography allows visual and quantitative evaluation of the dynamics of myocardial ischemia-reperfusion injury and can be used to monitor cardioprotective effects during pharmacological interventions even in small animals.
Filusch
Arthur
A
Department of Cardiology, University of Heidelberg, Heidelberg, Germany. arthur.filusch@med.uni-heidelberg.de
Buss
Sebastian
S
Hardt
Stefan
S
Katus
Hugo A
HA
Kuecherer
Helmut F
HF
Hansen
Alexander
A
D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage; D000069059:Atorvastatin; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D003199:Computer Systems; D003287:Contrast Media; D004452:Echocardiography / Q000379:methods*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D007089:Image Enhancement / Q000379:methods*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D011758:Pyrroles / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000209:etiology / Q000517:prevention & control*
D000924:Anticholesteremic Agents; D002316:Cardiotonic Agents; D003287:Contrast Media; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin