Alterations in body weight, breaking strength, and wound healing in Wistarrats treated pre- and postoperatively with erythropoietin or granulocyte macrophage-colony stimulating factor: Evidence of a previously unknown anabolic effect of erythropoietin?

Several growth factors, such as growth hormone and insulin-like growth fact or-1, have been used to reverse the high rate of catabolism observed either after an operation or during serious illness. We conducted a pilot study i n Wistar rats in an attempt to assess whether regulatory peptides widely us ed in clinical practice, such as erythropoietin (EPO) and granulocyte macro phage colony-stimulating factor (GM-CSF), alone or in combination, might in fluence the metabolism after surgery. Forty animals were randomly allocated into four groups tone control group and three experimental groups; 10 anim als per group). The rats in the control group received isotonic NaCl; the r ats in one experimental group received recombinant human EPO (rHuEPO) at a dose of 500 IU/kg (EPO group) and those in another received recombinant GM- CSF at a dose of 20 mu g/kg (GM-CSF group); in the fourth group, each anima l received the two drugs in combination (EPO/GM-CSF group). In all groups, rats were given the drug(s) or NaCl daily for 15 days before the operation and for 7 days after the operation until they were killed. We estimated the body weight (g) and the hematocrit (%) on the first day of the experiment (baseline values) and on the seventh day after the operation, and we estima ted the rate of healing and the breaking strength of the intestinal anastom osis on the day the rats were killed. At the end of the study we found that the body weight (median 250 g, minimum 230 g, maximum 270 g) and the level s of hematocrit (median 64%, minimum 60%, maximum 65%) were significantly i ncreased in the EPO group (P < .001 and P < .005, respectively) as compared with the baseline values (median 217.5 g, minimum 200 g, maximum 250 g; me dian 51.5%, minimum 45%, maximum 55%, respectively). A similar significant increase in body weight (median 230 g; minimum 200 g; maximum 250 g) and he matocrit (median 64%; minimum 59%; maximum 67%) was found at the end of the study in the EPO/GM-CSF group (P = .01 and P < .005, respectively) as comp ared with the baseline values (median 210 g; minimum 200 g; maximum 250 g; median 50%, minimum 48%, maximum 54%, respectively). The breaking strength (in newtons (N)) statistically differed in the four groups (Kruskal-Wallis, P = .0008). A comparison between groups showed that the breaking strength had been significantly increased in the animals in the EPO group (median 2. 18 N, minimum 1.98 N, maximum 2.44 N) as compared with those in the control group (median 1.66 N, minimum 1.33 N, maximum 1.87 N; P = .004), GMCSF gro up (median 1.73 N, minimum 1.25 N, maximum 2.07 N; P < .005), and EPO/GM-CS F group (median 1.71 N, minimum 1.37 N, maximum 1.91 N; P = .0005). In conc lusion, this study demonstrated that the administration of rHuEPO appears t o have a beneficial positive effect on the body weight, hematocrit, and hea ling rate and the breaking strength of large bowel anastomoses in rats. The se observations provide evidence of an as-yet-unknown anabolic effect of EP O, and they may expand its usual applications. However, more studies are ne eded to confirm our findings and furthermore to define the optimal dose and timing of EPO administration.