Intramyocardial thrombin promotes angiogenesis and improves cardiac function in an experimental rabbit model of acute myocardial infarction Sofoklis.

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Presentation transcript:

Intramyocardial thrombin promotes angiogenesis and improves cardiac function in an experimental rabbit model of acute myocardial infarction Sofoklis Mitsos, PhD, Efstratios N. Koletsis, PhD, Konstantinos Katsanos, PhD, Vassiliki Bravou, PhD, Fevronia Kolonitsiou, PhD, Evangelos Marinos, PhD, Christodoulos S. Flordellis, PhD, Dimitrios Dougenis, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 147, Issue 4, Pages 1376-1383 (April 2014) DOI: 10.1016/j.jtcvs.2013.05.036 Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 ECG and troponin. Myocardial ischemia was confirmed by ST-segment elevation on ECG in all subjects. There was no statistically significant difference between the 2 groups with regard to ST-segment elevation (left) or troponin T levels at 24 hours (right). THR, Thrombin-treated group. The Journal of Thoracic and Cardiovascular Surgery 2014 147, 1376-1383DOI: (10.1016/j.jtcvs.2013.05.036) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 Histologic examination. Masson trichrome staining (A and D) of myocardial infarct in the 2 groups. Representative cases of thrombin-treated (A; top) and control group (D; bottom) are presented (magnification ×40). CD31-immunostaining of vessels at the infarct border zone for MVD measurements. Representative cases of thrombin-treated (B; top) and control group (E; bottom) (magnification ×400). VEGF-A expression in vessels at the infarct border zone. Representative cases of thrombin-treated (C; top) and control group subjects (F; bottom) (magnification ×400). The Journal of Thoracic and Cardiovascular Surgery 2014 147, 1376-1383DOI: (10.1016/j.jtcvs.2013.05.036) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 MVD and infarct size. MVD measured at the infarct border zone was significantly higher in the hearts treated with 2500 IU thrombin compared with the saline-treated control group (left; *P < .05). Histomorphometry of the myocardial infarct area shows a similar extent of necrosis in the 2 groups (right). THR, Thrombin-treated group. The Journal of Thoracic and Cardiovascular Surgery 2014 147, 1376-1383DOI: (10.1016/j.jtcvs.2013.05.036) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 Transmission electron microscopy. Examples images of (A) remote zone and (B) infarct area after experimental myocardial infarction in the New Zealand White rabbit. Representative transmission electron microscopy images of (C) capillary sprouting on the border zone of the thrombin group, compared with images of (D) capillaries on the border zone of the control group. Note the improved neovascularization in the infarct border-zone of thrombin-treated rabbit hearts compared with saline-treated control cases (C and D). The Journal of Thoracic and Cardiovascular Surgery 2014 147, 1376-1383DOI: (10.1016/j.jtcvs.2013.05.036) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 5 LVEDP measurements (mm Hg). Induction of AMI produced a significant increase in LVEDP in both groups because of a disrupted cardiac systolic function. Four weeks post-infarction, restoration of cardiac systolic function was noted in the thrombin-treated hearts as evidenced by normalization of the recorded LVEDP compared with no significant change in the control group (*P < .05). LVEDP, Left ventricular end-diastolic pressure; THR, thrombin-treated group. The Journal of Thoracic and Cardiovascular Surgery 2014 147, 1376-1383DOI: (10.1016/j.jtcvs.2013.05.036) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions

Figure 6 LVEF measurements (%). Induction of AMI produced a significant decrease of LVEF in both groups because of cardiac dysfunction. Four weeks post-infarction, restoration of cardiac systolic function was noted in the thrombin-treated hearts as evidenced by partial restoration of the recorded LVEF compared with no significant change in the control group (*P < .05). LVEF, Left ventricular ejection fraction; THR, thrombin-treated group. The Journal of Thoracic and Cardiovascular Surgery 2014 147, 1376-1383DOI: (10.1016/j.jtcvs.2013.05.036) Copyright © 2014 The American Association for Thoracic Surgery Terms and Conditions