Catheter-directed gastric artery chemical embolization suppresses systemic ghrelin levels in porcine model

Abstract

Purpose: To prospectively test, in a porcine model, the hypothesis that catheter-directed gastric artery chemical embolization (GACE) can result in suppression of systemic ghrelin levels and affect weight gain.

Materials and methods: This study, which had Animal Care and Use Committee approval, was performed in healthy, growing swine (weight range, 40-45 kg; n = 10). GACE was performed in five swine with the infusion of sodium morrhuate (125 mug) selectively into the gastric arteries that supply the fundus. Five control animals underwent a sham procedure with 5 mL of saline. Weight and fasting plasma ghrelin levels were obtained in animals at baseline and in weeks 1-4. Statistical testing for substantial differences in ghrelin blood levels over time and between treated and untreated animals was performed by using a cross-sectional time-series linear model with feasibility generalized least squares.

Results: The pattern of the change in ghrelin levels over time was significantly different between control and treated animals (P < .004). In treated animals, ghrelin levels were significantly reduced at week 1 (mean, 664.1 pg/mL +/- 103.1 [standard error of the mean], P < .02), week 2 (mean, 618.1 pg/mL +/- 180.4, P < .001), week 3 (mean, 578.4 pg/mL +/- 214.9, P < .001), and week 4 (mean, 876.6 pg/mL +/- 228.6, P < .03) relative to baseline (mean, 1006.3 pg/mL +/- 190.1). The percentage change in serum ghrelin values in swine treated with GACE decreased from baseline to -34%, -38.6%, -42.5%, and -12.9% during weeks 1-4, respectively. In control swine, percentage change in serum ghrelin was -1.7%, -9.7%, +2.6%, and +18.2% during weeks 1-4, respectively. At the end of 4 weeks, control swine continued to gain weight, with a 15.1% increase from their original weight, while the weight in swine treated with GACE plateaued at an increase of 7.8% from the original weight.

Conclusion: Catheter-directed GACE can suppress the appetite hormone ghrelin and affect weight gain.

Figure 1:

Catheter-directed GACE technique. Celiac artery angiography is performed in anteroposterior projection to identify the celiac artery, two left gastric arteries (black arrow), and a left accessory gastric artery (white arrow). Superselective catheterization of the arteries that supply the gastric fundus was performed. For the GACE procedure, sodium morrhuate (50 mg/mL, 5%) was infused into the arteries that supply the fundus.

Figure 2:

Bar graph shows mean serum ghrelin levels (mean of all postprocedure ghrelin samples over the 4-week period) before and after the procedure in five control swine (teal bars) and five GACE-treated swine (red bars). Error bars = standard errors of the mean.

Figure 3:

Graph shows mean ghrelin values in control and GACE-treated swine at baseline and at weeks 1–4. The pattern of the change in ghrelin levels over time was significantly different between control and treated animals (P < .004). * = P < .02, + = P < .001, ** = P < .001, # = P < .03 (ghrelin levels were significantly reduced at all time end points relative to baseline). Error bars = standard errors of the mean.

Figure 4:

Bar graph shows mean percentage change from baseline in serum ghrelin levels in control and GACE-treated swine over a 4-week period. In control swine, there was no noteworthy change in systemic ghrelin levels from baseline until week 4. In GACE-treated swine, there was a significant decrease in ghrelin levels at all weeks. Maximum suppression of ghrelin was noted at week 3. * = P < .05. Error bars = standard errors of the mean.

Figure 5:

Graph shows percentage change in weight over the 4-week period for control and GACE-treated swine. Control swine continued to grow over the time period, while GACE-treated swine plateaued in growth. The pattern of weight gain over 4 weeks was significantly different between GACE-treated and control swine. * = P < .04. Error bars = standard errors of the mean.