ObjectiveThe worldwide prevalence of obesity has increased to 10% in men and 15% in women and is associated with severe comorbidities such as diabetes, cancer, and cardiovascular disease. Animal models of obesity are central to experimental studies of disease mechanisms and therapeutic strategies. Diet-induced obesity (DIO) models in rodents have provided important insights into the pathophysiology of obesity and, in most instances, are the first in line for exploratory pharmacology studies. To deepen the relevance towards translation to human patients, we established a corresponding DIO model in Göttingen minipigs (GM).MethodsYoung adult female ovariectomized GM were fed a high-fat/high-energy diet for a period of 70 weeks. The ration was calculated to meet the requirements and maintain body weight (BW) of lean adult minipigs (L-GM group) or increased stepwise to achieve an obese state (DIO-GM group). Body composition, blood parameters and intravenous glucose tolerance were determined at regular intervals. A pilot chronic treatment trial with a GLP1 receptor agonist was conducted in DIO-GM. At the end of the study, the animals were necropsied and a biobank of selected tissues was established.ResultsDIO-GM developed severe subcutaneous and visceral adiposity (body fat >50% of body mass vs. 22% in L-GM), increased plasma cholesterol, triglyceride, and free fatty acid levels, insulin resistance (HOMA-IR >5 vs. 2 in L-GM), impaired glucose tolerance and increased heart rate when resting and active. However, fasting glucose concentrations stayed within normal range throughout the study. Treatment with a long-acting GLP1 receptor agonist revealed substantial reduction of food intake and body weight within four weeks, with increased drug sensitivity relative to observations in other DIO animal models. Extensive adipose tissue inflammation and adipocyte necrosis was observed in visceral, but not subcutaneous, adipose tissue of DIO-GM.ConclusionsThe Munich DIO-GM model resembles hallmarks of the human metabolic syndrome with extensive adipose tissue inflammation and adipocyte necrosis reported for the first time. DIO-GM may be used for evaluating novel treatments of obesity and associated comorbidities. They may help to identify triggers and mechanisms of fat tissue inflammation and mechanisms preventing complete metabolic decompensation despite morbid obesity.

Surgical castration of male piglets without analgesia is a painful procedure. This prospective, randomized and double-blinded study aimed to evaluate the analgesic effects of four different local anesthetics for piglet castration during the first week of life. In total, 54 piglets aged 3 to 7 days were distributed into 6 treatment groups: handling (H); castration without pain relief (sodium chloride, NaCl); and castration with a local anesthetic: 4% procaine (P), 2% lidocaine (L), 0.5% bupivacaine (B) or 20 mg/ml mepivacaine (M). By excluding stress and fear as disruptive factors via a minimum anesthesia model, all piglets received individual minimum alveolar concentration (MAC) isoflurane anesthesia. Twenty minutes before castration, all treatment groups except group H received one injection per testis. Then, 0.5 ml of a local anesthetic or NaCl was injected intratesticularly (i.t.), and 0.5 ml was administered subscrotally. Acute physiological responses to noxious stimuli at injection and castration were evaluated by measuring blood pressure (BP), heart rate (HR), cortisol, epinephrine, norepinephrine and chromogranin A (CgA); limb movements were quantified. The results confirm that castration without analgesia is highly painful. Surgical castration without pain relief revealed significant changes in mean arterial blood pressure (MAP) and HR. Local anesthetic administration significantly reduced changes in BP and HR associated with castration. Piglets receiving a preoperative local anesthetic exhibited the fewest limb movements during castration, while the NaCl group exhibited the most. Injection itself was not associated with significant changes in MAP or HR. However, many piglets exhibited limb movements during injection, indicating that the injection itself causes nociceptive pain. No significant differences were found between groups regarding parameters of plasma cortisol, catecholamines and CgA. In conclusion, all four local anesthetics administered are highly effective at reducing signs of nociception during castration under light isoflurane anesthesia. However, injection of a local anesthetic seems to be painful.

Zusammenfassung Ziel Untersuchung von Abwehrreaktionen, Ferkelverlusten und Aufwachphase unter automatisierter Isoflurannarkose kastrierter Saugferkel, Erhebung von Isoflurankonzentrationen in der Umgebung sowie des Erfolgs von Reinigung und Desinfektion der Narkosemasken. Material und Methoden Insgesamt 955 männliche Saugferkel (Alter 4,0 ± 1,2 Tage; Gewicht 2,0 ± 0,5 kg) aus 5 Abferkeldurchgängen (DG) wurden nach Applikation eines nicht steroidalen Antiphlogistikums unter Isoflurannarkose (PorcAnest 3000®) kastriert. Zur Beurteilung von Reaktionen der Tiere dienten der Zwischenklauenreflex vor sowie Abwehrbewegungen und Lautäußerungen während der Kastration. Die Aufwachphase wurde im Stallgang (DG 1) bzw. in der Abferkelbucht (DG 4–5) evaluiert. Bei 73 Tieren wurde der Samenstrang mit dem Skalpell abgesetzt und Nachblutungen visuell überprüft. Isofluranmessungen fanden an verschiedenen Lokalisationen statt. Die Narkosemasken wurden vor und nach der Anwendung sowie nach Desinfektion auf Gesamtkeimbelastung und Indikatorkeime untersucht. Ergebnisse Bei der Kastration wiesen 94,3 % der Saugferkel nach der Einleitungszeit von 90 Sekunden und 95,3 % der Ferkel mit vorheriger Testung des Zwischenklauenreflexes und gegebenenfalls Verlängerung der Isofluranzufuhr keine oder nur eine kurze Abwehrbewegung auf. Bei 0,9 % der Ferkel trat ein Narkosezwischenfall auf, kein Tier verendete. Die Aufwachphase dauerte 7,3 ± 4,7 Minuten (DG 1) bzw. 6,2 ± 3,3 Minuten (DG 4–5). Das Absetzen des Samenstrangs mittels Skalpells führte zu einem höheren Nachblutungsscore (p < 0,001) als die Anwendung des Emaskulators. Die Isoflurankonzentrationen in der Umgebungsluft lagen zwischen 4,5 und 28,1 mg/m3. Die Maskendesinfektion reduzierte die Gesamtkeimzahl um 99,8 %. Kontaminationen mit Escherichia coli und MRSA waren in 4 von 6 Fällen nach Desinfektion nicht mehr nachweisbar. Schlussfolgerung Die Isoflurannarkose führte bei über 94 % der Ferkel zu keiner bzw. einer geringgradigen Abwehrreaktion während der Kastration. Narkosezwischenfälle waren selten und hatten keine vermehrten Ferkelverluste zur Folge. Somit ist die automatisierte Isoflurannarkose bei sorgfältiger Anwendung mit einem geringen Risiko für die Saugferkel verbunden. Die Isoflurankonzentration in der Atemluft der beteiligten Personen lag unter dem international niedrigsten Grenzwert. Die Desinfektion der Narkosemasken könnte eine Keimübertragung zwischen Tiergruppen über diesen potenziellen Vektor verhindern.

The aim of the present study was to investigate the effect of four local anesthetics on pain relief during surgical castration under standardized conditions in conscious piglets. Therefore, 71 male piglets (three to seven days) were distributed into control groups (handling, castration without anesthesia or analgesia) and local anesthetic trial groups (procaine, lidocaine, bupivacaine, mepivacaine). Then, 20 min prior to castration, animals of the treatment groups, except piglets in the handling group, received an injection of a local anesthetic or sodium chloride of 0.5 mL intratesticularly and 0.5 mL subscrotally. During injection and castration, defensive behavior was evaluated. Locomotor activity, as well as postoperative bleeding, wound healing and average daily weight gain were assessed to detect side effects. The injection caused increased defensive movements, significantly in the bupivacaine group. Lidocaine and mepivacaine significantly reduced defensive movements during castration, and procaine and bupivacaine only during severing of the spermatic cord. Impairments of locomotor activity were found in piglets injected with lidocaine, bupivacaine or sodium chloride. Considering healing, bleeding and weight gain, no negative impacts were observed. In conclusion, lidocaine and mepivacaine were able to achieve significant pain relief during the castration procedure, whereas procaine and bupivacaine only during the severing of the spermatic cord. Moreover, the injection of bupivacaine seemed to be painful itself.