Sustained-Release Erythropoietin Ameliorates Cardiac Function in Infarcted Rat - Heart Without Inducing Polycythemia

Abstract

Background The usefulness of sustained-release erythropoietin for improving left ventricular (LV) function without polycythemia was evaluated in a rat chronic myocardial infarction model. Methods and Results Four weeks after left coronary artery ligation, 50 Sprague-Dawley rats were assigned to 5 groups (n=10, each). Control group had a gelatin sheet (20×20 mm) containing saline applied to the infarct area, whereas the 4 treatment groups had gelatin sheets incorporating erythropoietin 0.1 U, 1 U, 10 U and 100 U, respectively. Endpoint measurements performed at 8 weeks after the coronary ligation revealed that the fractional area change was larger for erythropoietin 1 U and 10 U than in the other 3 groups. The LV end-systolic elastance and the time constant of isovolumic relaxation were better for erythropoietin 1 U and 10 U than in the other 3 groups. The density of vessels larger than 50 m in diameter was the highest in the erythropoietin 1 U group. The number of red blood cells was significantly increased in groups receiving erythropoietin 10 U and 100 U. Conclusions Gelatin hydrogel sheets incorporating 1 U erythropoietin improved LV function without inducing polycythemia in a rat chronic myocardial infarction model. (Circ J 2007; 71: 132 -137)

Controlled Release of Matrix Metalloproteinase-1 Plasmid DNA Prevents Left Ventricular Remodeling in Chronic Myocardial Infarction of Rats

“…MI was created by proximal ligation of the left anterior descending coronary artery (LAD) through left thoracotomy, as described previously. 14,15 The rate of mortality by coronary artery ligation and the size of the MI created were similar to our previous reports. 14,15 At 4 weeks following ligation, cardiac function was evaluated by echocardiography.…”

“…The carboxyl groups of gelatin were chemically converted by introducing amino groups for cationization of gelatin. 13,14 Briefly, ethylenediamine (Wako Pure Chemical, Ltd, Osaka, Japan) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride salt were added into 250 ml of 100 mmol/L phosphate buffered saline (PBS) containing 5 g of gelatin.…”

“…14,15 In brief, LV dimensions and function were assessed at baseline, and 2 and 4 weeks after the treatment. Images were recorded using a 10-12-MHz phased array transducer (HP SONOS 5500, Andover, MA, USA).…”

“…The LV end-diastolic dimension (EDD) and end-systolic dimension (ESD) were measured by M-mode tracings from the short-axis view of the LV at the papillary muscle level. 14,15,17 Fractional area change (FAC) and akinetic endocardial length to the whole LV endocardial circumference (AL) were also calculated from the same short-axis view of the 2-dimensional image. All measurements were performed in a blind fashion according to the American Society for Echocardiology and averaged over 3 consecutive cardiac cycles.…”

Amelioration of Anemia in the ICGN Mouse, a Renal Anemia Model, with a Subcutaneous Bolus Injection of Erythropoietin Adsorbed to Hydroxyapatite Matrix

“…Based on their network structure of polymer crosslinkings, hyaluronic acid hydrogels have shown the sustained release of rhEPO for 7 days in vivo [9,23]. Gelatin-based sheets, which are applicable to the new treatments for ischemic cardiomyopathy, released rhEPO for 4 weeks [16]. Percutaneous administration of self-dissolving micropile made from dextrin provided a release of rhEPO for 10 days [10].…”