scholarly journals Intravenous injection of extracellular vesicles to treat chronic myocardial ischemia

PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0238879
Author(s):  
Laura A. Scrimgeour ◽  
Brittany A. Potz ◽  
Ahmad Aboul Gheit ◽  
Yuhong Liu ◽  
Guangbin Shi ◽  
...  
2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
C Heilmann ◽  
S Tascher ◽  
L Bredow ◽  
T Renner ◽  
H G�bel ◽  
...  

1959 ◽  
Vol 197 (2) ◽  
pp. 437-440 ◽  
Author(s):  
Paul R. Saunders ◽  
Peter B. Taylor

Extracts prepared from the venomous dorsal spines of lionfish ( Pterois volitans) were investigated in mice and rabbits. Intravenous injection into mice produced death in from less than a minute up to about one-half hour. The primary action in rabbits was a fall in blood pressure, accompanied by increase in respiratory rate; with larger doses there was evidence of myocardial ischemia or injury. After injection of fatal doses a variety of electrocardiographic changes occurred and the blood pressure fell to zero; respiratory arrest occurred terminally, but artificial respiration did not prolong the life of the animal. The active material was nondialyzable and the extracts contained considerable amounts of protein. Extracts retained substantial activity after lyophilization or addition of glycerol when stored for over a year at –20°C. The mean ld50 following intravenous injection into mice was about 1 mg of protein/kg.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rabea Hinkel ◽  
Andrea Howe ◽  
Sarah Straub ◽  
Wira Husada ◽  
Seugmin Lee ◽  
...  

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.


2014 ◽  
pp. 143-167
Author(s):  
Jens Kastrup ◽  
Annette Ekblond ◽  
Mandana Haack-Sørensen ◽  
Anders B. Mathiasen ◽  
Abbas A. Qayyum

Circulation ◽  
2010 ◽  
Vol 122 (11_suppl_1) ◽  
pp. S142-S149 ◽  
Author(s):  
M. P. Robich ◽  
R. M. Osipov ◽  
R. Nezafat ◽  
J. Feng ◽  
R. T. Clements ◽  
...  

1995 ◽  
Vol 268 (2) ◽  
pp. H720-H728 ◽  
Author(s):  
J. R. Kersten ◽  
P. S. Pagel ◽  
D. C. Warltier

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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