Autonomic Dysfunction of Rat Jejunum Submitted to Cold Ischemic Preservation Is Prevented by Heparin

Abstract

Previous studies suggest that cold ischemic preservation (CIP) employed in small bowel transplantation promotes loss of intestinal motility due to severe lesions in autonomic enteric nerves. This autonomic dysfunction may be prevented by antioxidant agents. In this work, we investigated whether preservation with heparin prevented autonomic dysfunction of rat jejunum submitted to CIP for a long time. Jejunal segments (2 cm) of Wistar rats (12 to 16 weeks old) were preserved at 4°C in Ringer’s lactate solution without (−) or with (+) 100 UI/mL heparin (H). After preservation for 12 hours, H+ and H− preparations were mounted in parallel in isolated organ baths containing 10 mL Tyrode’s solution at 37°C for the study of neurogenic contractions evoked by electrical field stimulation (EFS; 10–30 Hz, 1-ms duration, 60 V) or by stimulation of nicotinic (NIC) or muscarinic (carbachol, CCh) cholinoceptors. The effects of NIC (hexamethonium, HEX) and muscarinic (atropine, ATR) antagonists were studied on these contractions. Contractions induced by EFS (30 Hz) were four times greater in H+ (1.02 ± 0.12 g) versus H− (0.26 ± 0.07 g), while contractions induced by NIC (1 mmol/L) were also four times higher in H+ (1.07 ± 0.10 g) than H− (0.25 ± 0.09 g) preparations. In addition, contractions induced by CCh (1 mmol/L) were two times higher in H+ (1.21 ± 0.13 g) than in H− (0.65 ± 0.10 g). EFS, NIC, and CCh contractions were inhibited by pretreatment of jejunum with HEX or ATR (1 μmol/L/30 min), in H+ and H−. These results indicated that addition of heparin to a preservation solution attenuated the autonomic dysfunction of rat jejunum submitted to CIP for a long time.