Clen g 135 plusHowever, whether the combination therapy of G-CSF clen g 135 plus clenbuterol Clen contributes to improved left ventricular LV function remains uncertain. We evaluated LV function and remodeling with the use of echocardiography clen g 135 plus addition to hemodynamics 3 weeks after MI. The epidemic of chronic heart failure CHF is growing, and advances in the clen g 135 plus of coronary artery disease have led to an increased population of survivors with acute ischemic syndromes and LV dysfunction. Almost two-thirds of systolic heart failure is caused by coronary artery disease and at least one-half of patients with heart failure have a depressed ejection fraction EF. Earlier work suggests that granulocyte colony-stimulating factor G-CSF may play an important role in cardiac repair by inducing the generation of new cardiac tissue through either mobilizing bone marrow—derived stem cells, direct effects on cardiomyocytes, 4 — 8 or the release of proangiogenic mediators.
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However, whether the combination therapy of G-CSF and clenbuterol Clen contributes to improved left ventricular LV function remains uncertain. We evaluated LV function and remodeling with the use of echocardiography in addition to hemodynamics 3 weeks after MI.
The epidemic of chronic heart failure CHF is growing, and advances in the treatment of coronary artery disease have led to an increased population of survivors with acute ischemic syndromes and LV dysfunction. Almost two-thirds of systolic heart failure is caused by coronary artery disease and at least one-half of patients with heart failure have a depressed ejection fraction EF. Earlier work suggests that granulocyte colony-stimulating factor G-CSF may play an important role in cardiac repair by inducing the generation of new cardiac tissue through either mobilizing bone marrow—derived stem cells, direct effects on cardiomyocytes, 4 — 8 or the release of proangiogenic mediators.
Heart failure is created in rats with the use of standard techniques developed in our laboratory. The treatment groups for this study were: In addition, both sham and CHF control animals were generated for comparison.
Sham-operated animals underwent thorocotomy and suture placement without ligation and CHF rats received saline injections at time points mirroring the treatment groups. We performed closed chest transthoracic echocardiography with the use of a Vingmed Vivid 7 system echo machine GE Ultra-sound with Echopac GE Ultrasound programming software and a MHz multiplane transducer as previously described. The LV pressure-volume relationship was measured as outlined in our previous work.
One end of the double-lumen LV catheter was connected to a volume infusion pump Harvard Apparatus and the other end to a pressure transducer zeroed at the level of the heart. The LV was filled 1.
Ischemia time was limited to 10 minutes. Volume infused is a function of filling rate. Blood was drawn from the tail vein catheter, anticoagulated with sodium citrate Sigma , and diluted with Pharmingen Staining Buffer BD Biosciences. Diluted whole blood was aliquotted into 2 samples.
Both samples were incubated for 25 minutes with phycoerythrin-Cy5—conjugated anti-CD45 BD Pharmingen , a panleukocyte marker.
One sample was treated with an IgG isotype control and the second sample with fluorescein isothiocyanate—conjugated anti-CD34 Santa Cruz Biotechnology.
A total of , events were acquired and the monocyte population gated to identify the CDpositive cells. Reverse-transcription polymerase chain reaction PCR was performed as described previously. Ten microliters of template cDNA diluted 1: The number of cross-section vessels per field was counted by 2 people blinded to treatment, and the average measurements from 6 different fields was recorded for each value. Positive factor VIII microvessel staining was quantified within the epicardium, myocardium, and endocardium.
For the physiologic and echocardiographic measurements, the Student t test was used for single comparison of sham versus other study groups. Pressure-volume relationships were evaluated with the use of multiple linear and polynominal regression analysis. The correlation of statistical difference was based on the Durbin-Watson statistic, F-statistic, P value, and variance coefficients. Three weeks after MI, rats had developed heart failure resulting in a decrease in LV systolic pressure, mean arterial pressure, prolonged tau, and peak developed pressure with increases in LV end-diastolic pressure Table 1.
Low-dose Clen increased peak developed pressure whereas high-dose Clen increased LV systolic pressure and mean arterial pressure. There was no observable change in heart rate with any treatment, except for a decrease with Clen alone compared with sham.
Abbreviations as in Table 1. Factor VIII stain of border region of the endocardial infarct zone. Brown coloring represents positive factor VIII stain.
Red arrowheads denote microvasculature. Abbreviations as in Fig. Infarct microvessel density counts as reflected by positive factor VIII. Although the main driver of microvessel formation appeared to correlate with Clen administration, functional improvements were not observed except as a dual therapy with G-CSF.
Furthermore, the observed circulating endothelial precursor cell mobilization after MI correlates with data generated from clinical studies, thus suggesting that the combined pharmacologic approach outlined here is potentially clinically applicable. Although earlier investigators have reported up-regulated mRNA expression of SDF-1 within 4 days after MI, 31 other groups showed expression during MI, peaking at 1 week, and remaining through 6 weeks.
Taking together the work highlighted in peripheral studies and the results reported in the present study, it can be assumed that evaluation of both SDF-1 and IGF-1 mRNA levels 1 to 3 days after MI precede physiologic mRNA expression and should be evaluated at later time points. National Center for Biotechnology Information , U. Author manuscript; available in PMC Mar The publisher's final edited version of this article is available at J Card Fail.
See other articles in PMC that cite the published article. Neovascularization, beta 2 -adrenergic receptor agonist. Echocardiography We performed closed chest transthoracic echocardiography with the use of a Vingmed Vivid 7 system echo machine GE Ultra-sound with Echopac GE Ultrasound programming software and a MHz multiplane transducer as previously described.
Results Hemodynamic Data Three weeks after MI, rats had developed heart failure resulting in a decrease in LV systolic pressure, mean arterial pressure, prolonged tau, and peak developed pressure with increases in LV end-diastolic pressure Table 1. Open in a separate window. Day 3 Day 7 Day 21 Sham N Engl J Med. Economic impact of heart failure in the United States: J Heart Lung Transplant. Cost effective management of heart failure. Mobilized bone marrow cells repair the infarcted heart, improving function and survival.
Bone marrow cells differentiate in cardiac cells lineages after infarction independently of cell fusion. Cardiac stem cells and mechanisms of myocardial regeneration. Synergistic effect of bone marrow mobilization and vascular endothelial growth factor-2 gene therapy in myocardial ischemia.
Neovascularization of ischemic myocardium by human bone marrow—derived angioblasts prevents cardiomyocyte apoptosis, reducing remodeling and improves cardiac function. Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment.
Granulocyte colony-stimulating factor promotes neovascularization by releasing vascular endothelial growth factor from neutrophils. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes.
Granulocyte colony-stimulating factor attenuates early ventricular expansion after experimental myocardial infarction. Stem cell mobilization by granulocyte colony-stimulating factor in patients with acute myocardial infarction: Stem cell mobilization induced by subcutaneous granulocyte-colony stimulating factor to improve cardiac regeneration after acute ST-elevation myocardial infarction: Use of granulocyte-colony stimulating factor during acute myocar-dial infarction to enhance bone marrow stem cell mobilization in humans: Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing later revascularization: J Am Coll Cardiol.
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