Using multidimensional scaling in model choice for congenital oesophageal atresia: similarity analysis of human autopsy organ weights with those from a comparative assessment of Aachen Minipig and Pietrain piglets

Abstract

Swine models had been popular in paediatric oesophageal surgery in the past. Although being largely replaced by rodent models, swine experienced a revival with the establishment of minipig models. However, none of them has ever been investigated for similarity to humans. We conducted a pilot study to determine whether three-week old Pietrain piglets and three-month old Aachen Minipigs are suitable for experimental paediatric oesophageal atresia surgery. We tested the operation's feasibility, performed a necropsy, weighed organs, measured organ length and calculated relative weights and lengths, and measured laboratory parameters. We used multidimensional scaling to assess the similarity of the swine breeds with previously published human data. Pietrain piglets had a higher a priori bodyweight than Aachen Minipigs (Δ = 1.31 kg, 95% confidence interval (CI): 0.37–2.23, p = 0.015), while snout-to-tail length was similar. Pietrain piglets had higher absolute and relative oesophageal lengths (Δ = 5.43 cm, 95% CI: 2.2–8.6; p = 0.0062, [Formula: see text] = 0.0083 and Δ = 11.4%, 95% CI: 5.1–17.6; p = 0.0025, [Formula: see text] = 0.0053). Likewise, absolute and relative small intestinal lengths were higher in Pietrains, but all other parameters did not differ, with the exception of minor differences in laboratory parameters. Multidimensional scaling revealed three-week old Pietrain piglets to be similar to two-month old humans based on their thoracoabdominal organ weights. This result indicates three-week old Pietrain piglets are a suitable model of paediatric oesophageal atresia surgery, because clinically many procedures are performed at around eight weeks age. Three-month old Aachen Minipigs were more dissimilar to eight-week old humans than three-week old Pietrain piglets.

Comparing Aachen Minipigs and Pietrain Piglets as Models of Experimental Pediatric Urology to Human Reference Data

“…As anatomical parameters have been compared between the pig breeds before without finding a difference [5], we compared estimated renal function based on Gasthuys ’ formula, which was also similar (Δ = 1.3 mL/kg, 95% CI –0.9–4.7, p = 0.293) between Pietrain piglets (x̄ = 13.7 mL/kg, 95% CI 11.5–16.6) and Aachen Minipigs (x̄ = 12.4 mL/kg, 95% CI 11.6–13.4). Comparison to humans was not suitable, as Gasthuys ’ formula has only been validated for swine [14].…”

“…In a previous study [5], we obtained 5 freshly weaned, 2-week old Pietrain piglets of both sexes from a local organic farmer and purchased five 3-month old Aachen Minipigs [11] from their official breeder (Gerd Heinrichs, Heinsberg, Germany) for comparison. These ages were chosen based on previous experiences and recommendations from their breeders because the weight of the swine would be in the range of newborn humans as it was required for the study involving the esophageal operation.…”

“…These ages were chosen based on previous experiences and recommendations from their breeders because the weight of the swine would be in the range of newborn humans as it was required for the study involving the esophageal operation. Pigs were kept at our closed facility for a week of acclimatization as described elsewhere [5]. We used 5 animals per group as this has been suggested by Monte-Carlo simulation studies to achieve a sufficient power for a pilot study [11].…”

“…The age of 2 months was chosen because we have been able to demonstrate a high degree of similarity between Pietrain piglets and humans based on organ weights by the use of multidimensional scaling [5]. Based on the presentation of published results as mean and SD, we assumed a normal distribution of their data as the respective authors would have otherwise reported median and range.…”

“…Consequently, the endoscopic subureteral Teflon injection has been developed in piglets [3] and has been translated successfully into everyday clinical practice [4]. Following these pioneering works, landrace piglets were the porcine model of choice in experimental pediatric urology -similar to pediatric esophageal surgery [5] -for endourologic investigations [6], robotic [7], and fetal surgery [8]. Although the Göttingen Minipig as the archetype of a minipig has been bred at the beginning of the 1960s [9], it was not until 1993 that minipigs first appeared as a model in experimental pediatric urology with a laparoscopic Lich-Gregoir procedure in Hanford Minipigs [10].…”