Time-course of recovery of gastric emptying and motility in rats with experimental spinal cord injury

Abstract

We have shown recently that spinal cord injury (SCI) decreases basal gastric contractions 3 days after injury. In the present study we used the [(13)C]-octanoic acid breath test and gastric strain gauges with the aim to investigate the time-course of recovery from postinjury gastric stasis in rats that underwent experimental SCI at the level of the third thoracic (T3) vertebra. Following verification of the [(13)C]-breath test sensitivity in uninjured rats, we conducted our experiments in rats that underwent T3-spinal contusion injury (T3-CI), T3-spinal transection (T3-TX) or laminectomy (control) surgery at 3 days, 1, 3 or 6 weeks postinjury. Our data show that compared to rats that underwent laminectomy, rats that received SCI showed a significant reduction in the cumulative per cent [(13)C] recovery. Although more marked in T3-TX rats, the delayed gastric emptying in T3-CI and T3-TX rats was comparable in the 3 days to 3 weeks period postinjury. At 6 weeks postinjury, the gastric emptying in T3-CI rats recovered to baseline values. Conversely animals in the T3-TX group still show a significantly reduced gastric emptying. Interestingly, the almost complete functional recovery observed in T3-CI rats using the [(13)C]-breath test was not reflected by analysis of spontaneous gastric contractions after SCI. These data indicate that T3-SCI produces a significant reduction in gastric emptying independent of injury severity (T3-CI vs T3-TX) that persists for at least 3 weeks after injury. However, 6 weeks postinjury T3-CI, but not T3-TX, rats begin to demonstrate functional recovery of gastric emptying.

Figure 1

Summary of [¹³C]-breath test data in animals administered saline, bethanechol and atropine. Animals received each drug in randomized order. A. Graphic representation of the cumulative percent recovery of [¹³C] for animals pretreated with either saline, the pro-motility muscarinic cholinergic agonist bethanechol (5mg kg⁻¹, ip) or the motility-reducing muscarinic cholinergic antagonist atropine (7.5mg kg⁻¹, ip). The final percent cumulative recovery of [¹³C] at the termination of the 6 h test was unaffected. B. Graphic representation of the gastric half emptying time (T_½). Compared to the T_½ of saline injected animals, bethanechol induced a significant acceleration of T_½ while in the same cohort of animals, atropine significantly delayed T_½. Data expressed as mean ± SEM, * = p<0.05.

Figure 2

Summary of [¹³C]-breath test data in control and SCI animals using the 3 d post-surgery (3 DPO) test as a representative example. A. T3 SCI leads to a significant reduction in cumulative percent recovery of [¹³C]. B. Graphic summary of the cumulative percent recovery of [¹³C] for all test days through 6 wk post-surgery (6 WPO). Cumulative recovery of [¹³C] was significantly reduced in both contusion and transection SCI groups (* = p<0.05 vs. control, # = p<0.05 vs. T3- CI). C. At 3 d post-surgery, the group averages of the fractional dose demonstrate an initial acceleration in the early phase of gastric emptying in animals with complete SCI (T3-TX). This early peak was followed by a rapid reduction in [¹³C] values, suggesting retention of the test meal that led to the reduced cumulative recovery of [¹³C]-substrate. D. Graphic summary of the peak fractional dose of [¹³C] (T_max) for all test days. The early phase of gastric emptying was significantly accelerated by SCI through the first 3 wk after surgery (3 WPO; * = p<0.05 vs. control, # = p<0.05 vs. T3-CI).

Figure 3

Summary of the gastric half emptying time reveals a significant reduction of gastric emptying after SCI in both groups of animals through the first 3 wk after surgery (3 WPO). Animals with the more severe complete spinal cord transection continued to display reduced gastric emptying throughout the entire 6 wk post-injury time period (6 WPO; * = p<0.05 vs. control).

Figure 4

A. Original polygraph records of gastric motility in a separate cohort of fasted experimental animals. Animals with both contusion and transection SCI (T3-CI and T3-TX, respectively) display a marked reduction in both the amplitude and periodicity of gastric motility at all three time points that coincide with reduced gastric emptying of a solid test meal, as measured by [¹³C]-octanoic breath test. B. Graphic summary of the calculated motility index of animals tested at 3 d, 3 wk and 6 wk after surgery (3 DPO, 3 WPO * 6 WPO, respectively). Gastric motility was significantly reduced in all SCI groups compared to respective controls. Furthermore, the gastric motility of T3-TX animals was significantly lower than all other groups in the cohort of animals tested at 3 d after surgery (3 DPO; * = p<0.05 vs. control, # = p<0.05 vs. T3-CI).