Effect of sleeve gastrectomy, Roux-en-Y gastric bypass, and ileal transposition on myocardial ischaemia-reperfusion injury in non-obese non-diabetic rats

Abstract

Bariatric surgery (BS) improves outcomes in patients with myocardial infarction (MI). Here we tested the hypothesis that BS-mediated reduction in fatal MI could be attributed to its infarct-limiting effect. Wistar rats were randomized into five groups: control (CON), sham (SHAM), Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and ileotransposition (IT). Ten weeks later, animals were subjected to 30-min myocardial ischemia plus 120-min reperfusion. Infarct size (IS) and no-reflow area were determined histochemically. Fasting plasma levels of glucagon-like peptide-1 (GLP-1), leptin, ghrelin, and insulin were measured using ELISA. Compared with SHAM, RYGB and SG reduced IS by 22% (p = 0.011) and 10% (p = 0.027), and no-reflow by 38% (p = 0.01) and 32% (p = 0.004), respectively. IT failed to reduce IS and no-reflow. GLP-1 level was increased in the SG and RYGB groups compared with CON. In both the SG and RYGB, leptin level was decreased compared with CON and SHAM. In the SG group, ghrelin level was lower than that in the CON and SHAM. Insulin levels were not different between groups. In conclusion, RYGB and SG increased myocardial tolerance to ischemia-reperfusion injury of non-obese, non-diabetic rats, and their infarct-limiting effect is associated with decreased leptin and ghrelin levels and increased GLP-1 level.

Figure 1

(A) Food consumption. (B) Effects of bariatric surgery on rat body weight. CON control, SHAM sham surgery, IT ileal transposition, RYGB Roux-en-Y gastric bypass, SG sleeve gastrectomy.

Figure 2

Levels of glucose and hormones in the oral glucose tolerance test. (A) Fasting plasma glucose levels. (B) Plasma glucose levels during oral glucose tolerance test. (C) Area under the curve of glucose levels. (D) Blood levels of insulin within 2 h after glucose loading. (E) Blood levels of leptin within 2 h after glucose loading. (F) Blood levels of ghrelin within 2 h after glucose loading. (G) Blood levels of GLP-1 within 2 h after glucose loading. (H) AUC of GLP-1 levels. (a) The difference between the control group and the other groups is significant at p < 0.05. (b) The difference between the sham surgery and bariatric surgery groups is significant at p < 0.05. Mean ± standard error of mean. AUC area under the curve, CON control, SHAM sham surgery, IT ileal transposition, RYGB Roux-en-Y gastric bypass, SG sleeve gastrectomy, GLP-1 glucagon-like peptide-1.

Figure 3

Flowchart showing the exact numbers of animals in each experimental group at different stages of the protocol, as well as the numbers of excluded/dead animals. CON control, SHAM sham surgery, IT ileal transposition, RYGB Roux-en-Y gastric bypass, SG sleeve gastrectomy.

Figure 4

Myocardial area at risk and infarct size in the experimental groups. (A) Area at risk expressed as a percentage of the whole slice area. (B) Infarct size expressed as a percentage of the area at risk. (C) Representative images of heart slices stained with Evans blue and triphenyltetrazolium chloride. n = 7, 9, 7, 6, and 7 for the CON, SHAM, IT, RYGB, and SG groups, respectively. *p < 0.05 versus the CON group. CON control, SHAM sham surgery, IT ileal transposition, RYGB Roux-en-Y gastric bypass, SG sleeve gastrectomy, TTC triphenyltetrazolium chloride.

Figure 5

(A) Size of the no-reflow area expressed as a percentage of the area at risk. (B) Representative images of heart slices stained with Evans blue and indocyanine green. n = 7, 9, 7, 6, and 7 for the CON, SHAM, IT, RYGB and SG groups, respectively. *p < 0.05 versus the CON group. CON control, SHAM sham surgery, IT ileal transposition, RYGB Roux-en-Y gastric bypass, SG sleeve gastrectomy, ICG indocyanine green.

Figure 6

(A) Size of blood stasis areas expressed as a percentage of the total slice area after quantifying 10 visual fields in the area at risk. (B) Representative histological images demonstrating blood stasis. n = 7, 9, 7, 6, and 7 for the CON, SHAM, IT, RYGB and SG groups, respectively. *p < 0.05 versus the CON group. CON control, SHAM sham surgery, IT ileal transposition, RYGB Roux-en-Y gastric bypass, SG sleeve gastrectomy.

Figure 7

Experimental design. BS bariatric surgery, MI myocardial infarction, OGTT oral glucose tolerance test, CON control, SHAM sham surgery, IT ileal transposition, RYGB Roux-en-Y gastric bypass, SG sleeve gastrectomy.