The Effects of Intravenous Clonidine on Regional Myocardial Function in a Canine Model of Regional Myocardial Ischemia

1994 ◽  
Vol 78 (6) ◽  
pp. 1047???1052 ◽  
Author(s):  
Masashi Kono ◽  
Shigeho Morita ◽  
Takayuki Hayashi ◽  
Mieko Saitoh ◽  
Nobuo Fuke ◽  
...  
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.


1994 ◽  
Vol 24 (6) ◽  
pp. 921-928 ◽  
Author(s):  
Shawn C. Black ◽  
Michael R. Gralinski ◽  
James G. McCormack ◽  
Edward M. Driscoll ◽  
Benedict R. Lucchesi

1993 ◽  
Vol 126 (3) ◽  
pp. 514-520
Author(s):  
Eric K. Louie ◽  
Robert J. Hariman ◽  
Rick L. Krahmer ◽  
Abe F. Goldbaum ◽  
Darrel P. Prechel ◽  
...  

2006 ◽  
Vol 291 (3) ◽  
pp. H1126-H1137 ◽  
Author(s):  
Isaac George ◽  
Geng-Hua Yi ◽  
Allison R. Schulman ◽  
Brad T. Morrow ◽  
Yanping Cheng ◽  
...  

The purpose of this study was to test if HBOC-201, a hemoglobin-based oxygen-carrying solution, can decrease infarct size (or Inf) during acute, severe myocardial ischemia and reperfusion. To test the impact of HBOC-201 on infarct size, ischemia was produced in 18 dogs by coronary stenosis to achieve 80–95% flow reduction for 195 min along with pacing 10% above the spontaneous heart rate, followed by 180 min of reperfusion. Animals were randomized to intravenous infusion of HBOC-201 (1 g/kg) ( n = 6), normal saline (NS) ( n = 6), or phenylephrine (Phe) ( n = 6, as a control for the increased blood pressure seen with HBOC-201), given 15 min after the start of ischemia. Amount of infarct was quantified as the ratio between area at risk (AAR) and Inf after Evans blue and 2,3,5-triphenyltetrazolium chloride staining. Hearts were divided into five layers from base ( layer A) to apex ( layer E) and photographed for digital image analysis of AAR and Inf. Regional myocardial function (RMF) was also measured after 60 min of ischemia and 15 min of reperfusion. Inf/AAR was significantly reduced after HBOC-201 therapy (4.4 ± 2.2%) vs. NS (26.0 ± 3.6%) and Phe (25.7 ± 4.1%) (both, P < 0.05). RMF after reperfusion was restored to 92% of baseline with HBOC-201 compared with 11% of baseline after NS ( P < 0.05) and 49% after Phe ( P = not significant). HBOC-201 administration after induction of severe myocardial ischemia by acute coronary stenosis reduces infarct size and improves myocardial viability.


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