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Intraperitoneal bilirubin administration decreases infarct area in a rat coronary ischemia/reperfusion model.

Ben-Amotz R, Bonagura J, Velayutham M, Hamlin R, Burns P, Adin C - Front Physiol (2014)

Bottom Line: We hypothesized that intraperitoneal bilirubin administration 1 h before injury would decrease infarct area and preserve left ventricular (LV) systolic function when compared to non-treated rats.LV function was estimated by measurements of fractional shortening (FS) and fractional area shortening using echocardiography.This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Clinical Sciences, The Ohio State University Columbus, OH, USA.

ABSTRACT
Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome) are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 h before injury would decrease infarct area and preserve left ventricular (LV) systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min) ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-h period of reperfusion. LV function was estimated by measurements of fractional shortening (FS) and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats FS was less depressed during the period of ischemia (18.8 vs. 25.8%, p = 0.034). Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34 vs. 25.5%, p = 0.0067). Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

No MeSH data available.


Related in: MedlinePlus

Bilirubin improves fractional shortening at the end of ischemia. Mean (s.e.m.) fractional shortening measurements obtained by echocardiography of sham (non-ischemic), control (ischemia + vehicle) and control (ischemia + 20 uM bilirubin IP 1 h before induction) groups at baseline, at the end of 30 min of ischemia and 1 h after reperfusion. Left ventricular function remained relatively constant throughout the anesthetic period in the sham group while ischemia caused significant decreases in fractional shortening in both control and bilirubin treated rats. LV systolic function was higher in the bilirubin-treated group during ischemia, but this effect was not evident after reperfusion. *p < 0.05 vs. control, †p < 0.05 vs. sham.
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Figure 4: Bilirubin improves fractional shortening at the end of ischemia. Mean (s.e.m.) fractional shortening measurements obtained by echocardiography of sham (non-ischemic), control (ischemia + vehicle) and control (ischemia + 20 uM bilirubin IP 1 h before induction) groups at baseline, at the end of 30 min of ischemia and 1 h after reperfusion. Left ventricular function remained relatively constant throughout the anesthetic period in the sham group while ischemia caused significant decreases in fractional shortening in both control and bilirubin treated rats. LV systolic function was higher in the bilirubin-treated group during ischemia, but this effect was not evident after reperfusion. *p < 0.05 vs. control, †p < 0.05 vs. sham.

Mentions: Left ventricular systolic function was profoundly decreased in both experimental groups after IR, with segmental LV wall dysfunction and resulting decreases in FS% (Figure 2) and AS% (Figure 3). LV function as estimated by FS% was less depressed during the period of ischemia in BR-treated rats, when compared to control (vehicle treated) rats (p = 0.034). However, no significant difference in measurements of LV function remained at the time of reperfusion (Figure 4). Left ventricular function was relatively unchanged throughout the anesthetic period in sham rats, validating the model and echocardiographic technique. For FAS, LV function decreased significantly in both experimental groups after IR. Although FAS showed a similar trend toward improvement in the bilirubin group during the time of ischemia (Figure 5), differences from control were not statistically significant (p = 0.098). Furthermore, there was no significant difference in measurements of LV, FAS at the time of reperfusion.


Intraperitoneal bilirubin administration decreases infarct area in a rat coronary ischemia/reperfusion model.

Ben-Amotz R, Bonagura J, Velayutham M, Hamlin R, Burns P, Adin C - Front Physiol (2014)

Bilirubin improves fractional shortening at the end of ischemia. Mean (s.e.m.) fractional shortening measurements obtained by echocardiography of sham (non-ischemic), control (ischemia + vehicle) and control (ischemia + 20 uM bilirubin IP 1 h before induction) groups at baseline, at the end of 30 min of ischemia and 1 h after reperfusion. Left ventricular function remained relatively constant throughout the anesthetic period in the sham group while ischemia caused significant decreases in fractional shortening in both control and bilirubin treated rats. LV systolic function was higher in the bilirubin-treated group during ischemia, but this effect was not evident after reperfusion. *p < 0.05 vs. control, †p < 0.05 vs. sham.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927123&req=5

Figure 4: Bilirubin improves fractional shortening at the end of ischemia. Mean (s.e.m.) fractional shortening measurements obtained by echocardiography of sham (non-ischemic), control (ischemia + vehicle) and control (ischemia + 20 uM bilirubin IP 1 h before induction) groups at baseline, at the end of 30 min of ischemia and 1 h after reperfusion. Left ventricular function remained relatively constant throughout the anesthetic period in the sham group while ischemia caused significant decreases in fractional shortening in both control and bilirubin treated rats. LV systolic function was higher in the bilirubin-treated group during ischemia, but this effect was not evident after reperfusion. *p < 0.05 vs. control, †p < 0.05 vs. sham.
Mentions: Left ventricular systolic function was profoundly decreased in both experimental groups after IR, with segmental LV wall dysfunction and resulting decreases in FS% (Figure 2) and AS% (Figure 3). LV function as estimated by FS% was less depressed during the period of ischemia in BR-treated rats, when compared to control (vehicle treated) rats (p = 0.034). However, no significant difference in measurements of LV function remained at the time of reperfusion (Figure 4). Left ventricular function was relatively unchanged throughout the anesthetic period in sham rats, validating the model and echocardiographic technique. For FAS, LV function decreased significantly in both experimental groups after IR. Although FAS showed a similar trend toward improvement in the bilirubin group during the time of ischemia (Figure 5), differences from control were not statistically significant (p = 0.098). Furthermore, there was no significant difference in measurements of LV, FAS at the time of reperfusion.

Bottom Line: We hypothesized that intraperitoneal bilirubin administration 1 h before injury would decrease infarct area and preserve left ventricular (LV) systolic function when compared to non-treated rats.LV function was estimated by measurements of fractional shortening (FS) and fractional area shortening using echocardiography.This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Clinical Sciences, The Ohio State University Columbus, OH, USA.

ABSTRACT
Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome) are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 h before injury would decrease infarct area and preserve left ventricular (LV) systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min) ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-h period of reperfusion. LV function was estimated by measurements of fractional shortening (FS) and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats FS was less depressed during the period of ischemia (18.8 vs. 25.8%, p = 0.034). Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34 vs. 25.5%, p = 0.0067). Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

No MeSH data available.


Related in: MedlinePlus