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Background: The objective of this study was to evaluate the feasibility of dynamic monitoring of myocardial cell death using 99m Tc-Duramycin single photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging in a mouse model of acute myocardial infarction, and the anti-apoptosis effect of atorvastatin for cardio protection.
Methods: Forty-five male Kunming mice were randomized into three groups: acute myocardial infarction (AMI) group, acute myocardial infarction with atorvastatin treatment (T-AMI) group, and the sham group. The mice of the AMI group and T-AMI group were subjected left coronary artery ligation. The T-AMI group was orally administered with atorvastatin 20 mg/ (kg day) 24 h before the surgery, the other two groups received only saline. Three groups of model mice were randomly selected at day 1 (D1), day 3 (D3), and day 7 (D7) day after surgery with 99m Tc-Duramycin micro-SPECT/CT imaging. Transthoracic echocardiography test was performed at D3 and D7 after surgery. The pathological evaluation, TUNEL assay and Western blot analysis were performed on heart specimens on D1, D3 and D7.
Results: For up-taking of 99m Tc-duramycin in infarcted region, the mean value of semi-quantitative of AMI group were 2.62 on D1, 3.89 on D3 and 1.20 on D7. And for the T-AMI group, the mean value of semi-quantitative were 2.20 on D1, 2.97 on D3 and 1.30 on D7. The sham group had no positive imaging in myocardium, the mean value of semi-quantitative were 1.09, 1.14 and 1.10 on D1, D3 and D7, respectively. Meanwhile, 99m Tc-linear-duramycin imaging as control showed that there’s no radioactive uptake in the area of infarction region. But the T-AMI group imaging showed the tracer uptake decreased obviously compared to the uptake of AMI mice in infarcted region (L/N: 2.2 versus 2.62; 2.97 versus 3.89) on D3 and D7. LVEF was significantly reduced on D3 (42.67±2.51%) and D7 (27.71±2.52%) compared with the sham group (71.00±2.65%). The number of TUNEL positive cells decreased significantly on D3 (37.00±3.01 vs 51.00±3.61) and D7 (21.67±2.08 vs 27.65±2.51) post-MI after atorvastatin treatment. Additionally, the atorvastatin increased the expression level of anti-apoptotic protein BCL-2 and decreased the expression level of pro-apoptotic protein BAX.
Conclusions: 99m Tc-Duramycin SPECT/CT imaging allowed to the non-invasively monitoring of myocardial cell death in a mouse model of acute myocardial infarction. Furthermore, this investigation and analysis could be used to assess and verify the anti-apoptosis effect of atorvastatin for cardio protection by in-vivo molecular imaging.
Keywords
duramycin, acute myocardial infarction (AMI), apoptosis, atorvastatin, SPECT/CT
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Original research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
View the published article at Chemical Biology & Drug Design.
Version 1
Posted 17 Feb, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Nuclear Medicine & Medical Imaging
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Chemical Biology & Drug Design.
Background: The objective of this study was to evaluate the feasibility of dynamic monitoring of myocardial cell death using 99m Tc-Duramycin single photon emission computed tomography/computed tomography (micro-SPECT/CT) imaging in a mouse model of acute myocardial infarction, and the anti-apoptosis effect of atorvastatin for cardio protection.
Methods: Forty-five male Kunming mice were randomized into three groups: acute myocardial infarction (AMI) group, acute myocardial infarction with atorvastatin treatment (T-AMI) group, and the sham group. The mice of the AMI group and T-AMI group were subjected left coronary artery ligation. The T-AMI group was orally administered with atorvastatin 20 mg/ (kg day) 24 h before the surgery, the other two groups received only saline. Three groups of model mice were randomly selected at day 1 (D1), day 3 (D3), and day 7 (D7) day after surgery with 99m Tc-Duramycin micro-SPECT/CT imaging. Transthoracic echocardiography test was performed at D3 and D7 after surgery. The pathological evaluation, TUNEL assay and Western blot analysis were performed on heart specimens on D1, D3 and D7.
Results: For up-taking of 99m Tc-duramycin in infarcted region, the mean value of semi-quantitative of AMI group were 2.62 on D1, 3.89 on D3 and 1.20 on D7. And for the T-AMI group, the mean value of semi-quantitative were 2.20 on D1, 2.97 on D3 and 1.30 on D7. The sham group had no positive imaging in myocardium, the mean value of semi-quantitative were 1.09, 1.14 and 1.10 on D1, D3 and D7, respectively. Meanwhile, 99m Tc-linear-duramycin imaging as control showed that there’s no radioactive uptake in the area of infarction region. But the T-AMI group imaging showed the tracer uptake decreased obviously compared to the uptake of AMI mice in infarcted region (L/N: 2.2 versus 2.62; 2.97 versus 3.89) on D3 and D7. LVEF was significantly reduced on D3 (42.67±2.51%) and D7 (27.71±2.52%) compared with the sham group (71.00±2.65%). The number of TUNEL positive cells decreased significantly on D3 (37.00±3.01 vs 51.00±3.61) and D7 (21.67±2.08 vs 27.65±2.51) post-MI after atorvastatin treatment. Additionally, the atorvastatin increased the expression level of anti-apoptotic protein BCL-2 and decreased the expression level of pro-apoptotic protein BAX.
Conclusions: 99m Tc-Duramycin SPECT/CT imaging allowed to the non-invasively monitoring of myocardial cell death in a mouse model of acute myocardial infarction. Furthermore, this investigation and analysis could be used to assess and verify the anti-apoptosis effect of atorvastatin for cardio protection by in-vivo molecular imaging.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
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