Left ventricular function measurements in a mouse myocardial infarction model

Summary

Aim: To assess the accuracy of ECG-gated micro (µ)-SPECT in a mouse myocardial infarction (MI) model in comparison to 3D-echocardiography. Animals, methods: In a mouse (Swiss mice) MI model we compared the accuracy of technetium-99m sestamibi (^99mTc-sestamibi) myocardial perfusion, electrocardiogram (ECG) gated µSPECT to 3D-echocardiography in determining left ventricular function. 3D-echocardiography and myocardial perfusion ECG-gated µSPECT data were acquired in the same animal at baseline (n = 11) and 7 (n = 8) and 35 (n = 9) days post ligation of the left anterior descending coronary artery (LAD). Sham operated mice were used as a control (8, 6 and 7 mice respectively). Additionally, after day 35 µSPECT scans, hearts were harvested and 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) staining and autoradiography was performed to determine infarct size. Results: In both infarcted and sham-operated mice we consistently found comparable values for the end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) obtained by 3D-echocardiography and ECG-gated µSPECT. Excellent correlations between measurements from 3D-echocardiography and ECG-gated µSPECT were found for EDV, ESV and EF (r = 0.9532, r = 0.9693 respectively and r = 0.9581) in infarcted mice. Furthermore, comparable infarct size values were found at day 35 post MI by TTC staining and autoradiography (27.71 ± 1.80% and 29.20 ± 1.18% with p = 0.43). Conclusion: We have demonstrated that ECG-gated µSPECT imaging provides reliable left ventricular function measurements in a mouse MI model. Obtained results were comparable to the highly accurate 3D-echocardiography. This, in addition to the opportunity to simultaneously image multiple biological processes during a single acquisition makes µSPECT imaging a serious option for studying cardiovascular disease in small animals.

Zusammenfassung

Ziel: Um die Genauigkeit der EKG-getriggerte [uni03BC]SPECT in einem Maus-Myokardinfarkt(MI)-Modell im Vergleich zu 3D-Echokardiography zu bewerten. Methoden: Wir vergleichen die Genauigkeit von Technetium-99m-Sestamibi(^99mTc-Sestamibi)-Myokardperfusion und EKG-getriggerte µSPECT mit der 3D-Echokardiographie zur Bestimmung der linksventrikulären Funktion. Beide Techniken wurden vor sowie 7 und 35 Tage nach Ligatur der linken anterioren Koronararterie (LAK) am selben Tier durchgeführt. Als Kontrolle wurden Mäuse mit Sham-Operation verwendet. Nach dem letzten µSPECT, wurden die Herzen entnommen. Zur Bestimmung der Infarktgröße wurden sie mit 2,3,5-Triphenyl-2H-tetrazolium chlorid (TTC) markiert und zum Vergleich wurde auch eine Autoradiographie durchgeführt. Ergebnisse: In beiden Gruppen (Infarktund Kontrolltiere) wurden vergleichbare Werte für das post-diastolische Volumen (PDV), das post-systolische Volumen (PSV) und die Ejektionsfraktion (EF) mit 3D-Echokardiographie und µSPECT ermittelt. Es zeigte sich eine exzellente Korrelation zwischen den beiden Methoden für PDV, PSV und SV (r = 0,95, r = 0,97 und r = 0,96) in Tieren mit Infarkt. Des Weiteren wurde kein signifikanter Unterschied der gemessenen Infarktgrößen post mortem durch TTC und Autoradiographie festgestellt (27,71 ± 1,80% vs 29,20 ± 1,18%; p = 0,43). Schlussfolgerung: In dieser Studie zeigen wir, dass EKG-getriggerte µSPECT verlässliche Informationen zur linksventrikulären Funktion im Tiermodell bieten kann. Die Ergebnisse sind vergleichbar mit der 3D-Echokardiographie. Es besteht die Möglichkeit mit Multiple-Tracer-µSPECT verschiedene pathophysiologische Aspekte mit einem Scan zu evaluieren. µSPECT kann als ein wichtiges Tool zur Untersuchung kardiovaskulärer Erkrankungen bei Tiermodellen angesehen werden.

Keywords

ECG-gated SPECT - 3D-echocardiography - left ventricular function - myocardial infarction

Schlüsselwörter

EKG getriggerte SPECT - 3D-Echokardiographie - linksventrikuläre Funktion - Myokardinfarkt

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