Practical considerations in the use of a porcine model (Sus scrofa domesticus) to assess prevention of postoperative peritubal adhesions

Abstract

38Infertility has been a common postoperative problem caused by peritoneal adhesions. Since several 39 prophylactic agents have recently shown promising preliminary results, more complete studies comparing 40 their real efficacy and safety are needed urgently. The aim of this study was to investigate and describe 41 practical considerations of a porcine model that can be used to assess such prophylactic agents. First, 10 42 healthy 5½ months old female pigs (24.3 -31.3 Kg) underwent a standardized laparoscopy to provoke 43 peritubal adhesion formation without prophylactic agents. After 30 days, a second-look laparoscopy was 44 performed to evaluate adhesions and perform adnexectomy for histopathological evaluation. Adhesions 45 at different sites were classified by grade, for which the scores range from 0 (no adhesion) to 3 (very 46 strong vascularized adhesions), and also by area, with scores ranging from 0 (no adhesion) to 4 (>75% of 47 the injured area). The histopathological evaluation of the distal uterine horns, oviducts and ovaries were 48 compared withthose from a control group of six healthy pigs with no previous surgery. Biological samples 49 were collected to assess vitality, inflammation and renal, hepatic and hematopoietic systems. There were 50 small (but significant) changes in serum albumin (P=0.07), globulin (P=0.07), C-reactive protein 51 (P=0.011), fibrinogen (P=0.023) and bilirubin (P<0.01) after 30 days, but all values were within the normal 52 range. No inflammation or abscess formation was observed, but different degrees of adhesion were 53 identified. The estimated occurrence of adhesion (scores >0) and of strong / very strong adhesion (scores 54 >1) was 75% (95% CI: 55 -94.9) and 65% (95% CI: 45 -85), respectively. The porcine model represents 55 a useful animal platform that can be used to test the efficacy and safety of candidate prophylactic agents 56 intended to prevent postoperative peritubal adhesions formation. We present several practical 57 considerations and measures that can help to minimize animal suffering and avoid problems during such 58 experiments. 59 60 61 62 63 3 64 128 Suprema; Protocol Number 004/2017). Besides the health certificate issued by a veterinarian provided by 129 the supplier (Fazenda Penalva, Juiz de Fora, MG), the veterinarian responsible for the study (F.L.F.M.) 130 clinically evaluated all the animals before and during this study. 132In order to optimize the sample size, we considered as realistic an experimental model in which 133 adhesion formation would occur in 90% rather than all of the animals [10,18,19,20]. Assuming a 20%