Predicting Chronic Myocardial Ischemia Using CCTA-Based Radiomics Machine Learning Nomogram

Diabetes and hypercholesterolemia are two of the major risk factors for developing cardiovascular disease, especially in combination with chronic myocardial ischemia it represents one of the most common causes of disability or death. New pro-angiogenic factors like Thymosin ß4 (Tß4), a small 4.9 kDa peptide influences cell motility and migration might be suitable for inducing therapeutic neovascularization in chronic myocardial ischemia a cardiovascular risk factors. Methods: Chronic ischemia was induced via reduction stent graft in the circumflex artery, leading to a total occlusion on day 28 (d28). Beside wildtyp animals (wt) ± high fat diet (hypercholesteric (hyp), choselsterol 78±1 wt vs 90±2 hyp), d iabetic transgenic pigs were used (increased blood glucose 305 ±12 mg/dL) . Regional application of rAAV Tß4 (5x10E12 viral particles, d28) was performed in wt, hyp and diabetic pigs respectively. Global myocardial function was obtained at day 28 and 56. Regional myocardial function and post mortem angiography were examined on day 56. Histological analysis of capillary density (capillaries/field (C/F)) was performed in the ischemic tissue. Results: rAAV.Tß4 transduction significantly enhanced capillaries (278±6 vs. 148±6 c/hpf) and collaterals (9±1 vs. 3±1) compared to control wt animals. Furthermore, global (EF: 47±4 vs. 29±3 %); and regional myocardial function (SES at 150 b/min: 73±5 vs. 10±6 % of non-ischemic area) were increased after Tß4 overexpression. In the models of cardiovascular risk factors and chronic myocardial ischemia increased neovascularization and improved myocardial function could be achieved after rAAV Tß4 application, albeit at a lower level (capillaries: diabetic: 190±4 (Tß4) vs. 120±5 (control) c/hpf hyp: 188±6 (Tß4) vs 130±12 (control) c/hpf; collaterals: diabetic: 4±1 (Tß4) vs. 2±1 (control) hyp: 6±1 (Tß4) vs 3±1 (control); EF: diabetic: 32±2 % (Tß4) vs. 27±1 % (control) hyp: 42±4 % (Tß4) vs 28±3 % (control)). Conclusion: Long term Thymosin ß4 expression induced neovascularization and improved myocardial perfusion and function even in pigs with additional risk factors. Therefore, rAAV.Tß4 appears suitable for treatment of ischemic cardiomyopathy associated with these cardiovascular risk factors.

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Clinical Gene and Stem Cell Therapy in Patients with Acute and Chronic Myocardial Ischemia

Adult and Pluripotent Stem Cells ◽

10.1007/978-94-017-8657-7_8 ◽

2014 ◽

pp. 143-167

Author(s):

Jens Kastrup ◽

Annette Ekblond ◽

Mandana Haack-Sørensen ◽

Anders B. Mathiasen ◽

Abbas A. Qayyum

Keyword(s):

Stem Cell ◽

Myocardial Ischemia ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Chronic Myocardial Ischemia

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Machine Learning in the Evaluation of Myocardial Ischemia Through Nuclear Cardiology

Current Cardiovascular Imaging Reports ◽

10.1007/s12410-019-9480-x ◽

2019 ◽

Vol 12 (2) ◽

Cited By ~ 1

Author(s):

Luis Eduardo Juarez-Orozco ◽

Octavio Martinez-Manzanera ◽

Andrea Ennio Storti ◽

Juhani Knuuti

Keyword(s):

Machine Learning ◽

Myocardial Ischemia ◽

Nuclear Cardiology

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Coronary Collateral Circulation in Acute and Chronic Myocardial Ischemia

Microcirculation in Circulatory Disorders ◽

10.1007/978-4-431-68078-9_42 ◽

1988 ◽

pp. 323-325

Author(s):

Bernd Winkler ◽

Thomas Schmidt ◽

Wolfgang Schaper

Keyword(s):

Myocardial Ischemia ◽

Collateral Circulation ◽

Coronary Collateral Circulation ◽

Coronary Collateral ◽

Chronic Myocardial Ischemia

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Resveratrol Improves Myocardial Perfusion in a Swine Model of Hypercholesterolemia and Chronic Myocardial Ischemia

Circulation ◽

10.1161/circulationaha.109.920132 ◽

2010 ◽

Vol 122 (11_suppl_1) ◽

pp. S142-S149 ◽

Cited By ~ 74

Author(s):

M. P. Robich ◽

R. M. Osipov ◽

R. Nezafat ◽

J. Feng ◽

R. T. Clements ◽

...

Keyword(s):

Myocardial Perfusion ◽

Myocardial Ischemia ◽

Swine Model ◽

Chronic Myocardial Ischemia

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Protamine inhibits coronary collateral development in a canine model of repetitive coronary occlusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.268.2.h720 ◽

1995 ◽

Vol 268 (2) ◽

pp. H720-H728 ◽

Cited By ~ 8

Author(s):

J. R. Kersten ◽

P. S. Pagel ◽

D. C. Warltier

Keyword(s):

Blood Flow ◽

Myocardial Ischemia ◽

Contractile Function ◽

Regional Myocardial Blood Flow ◽

Collateral Development ◽

Coronary Collateral ◽

Debt Repayment ◽

Chronic Myocardial Ischemia

Protamine has been demonstrated to inhibit angiogenesis in vitro and in vivo; however, its effect on coronary collateral development has not been examined. The present investigation tested the hypothesis that subcutaneously administered protamine inhibits canine coronary collateral development in response to chronic myocardial ischemia. Dogs underwent daily, repetitive, 2-min, left anterior descending coronary artery (LAD) occlusions for 22 consecutive days. Regional myocardial blood flow (radioactive microspheres), LAD segment shortening, and coronary flow debt repayment were measured in saline-treated (n = 7) and protamine-treated (n = 6) dogs on days 1, 8, 15, and 22. Coronary collateral development in saline-treated dogs was demonstrated by time-dependent significant (P < 0.05) increases in collateral blood flow to ischemic myocardium [day 1 0.10 +/- 0.01 vs. day 22 0.88 +/- 0.05 (SE) ml.min-1.g-1], progressive normalization of myocardial contractile function during LAD occlusion, and successive reduction in flow debt repayment. In contrast, protamine treatment significantly attenuated, increases in collateral perfusion (day 1 0.13 +/- 0.02 vs. day 22 0.36 +/- 0.03 ml.min-1.g-1). Regional contractile dysfunction and postocclusive reactive hyperemic responses were sustained over time in protamine-treated compared with saline-treated dogs. The results demonstrate that protamine inhibits coronary collateral development in response to chronic myocardial ischemia.

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