BN-063, a newly synthesized adenosine A1 receptor agonist, attenuates myocardial reperfusion injury in rats

Yen Mei Lee, Joen Rong Sheu, Mao Hsiung Yen

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

To assess the efficacy of the newly synthesized selective adenosine A1 receptor agonist, BN-063 (1-cyclopropylisoguanosine), against myocardial reperfusion injury, 31 rats underwent 45 min of left coronary artery occlusion and 1 h of reperfusion. Animals were randomly assigned to four groups: control, I0.5-R0.5, in which BN-063 (0.5 mg/kg i.v. bolus) was administered during both ischemia and reperfusion, R-0.5 and R-1.0, in which BN-063 was administered only during reperfusion at 0.5 and 1.0 mg/kg, respectively. The area at risk was determined by intravascular injection of blue dye during coronary artery occlusion, which was performed by retightening the ligature at the end of reperfusion, and infarct size was determined by incubation of heart slices in nitro blue tetrazolium chloride. A significant reduction in infarct size, as a percentage of the area at risk, was noted with all three BN-063 treatment groups (control: 63.5 ± 4.0%, I0.5-R0.5: 39.6 ± 3.7%, R-0.5: 37.5 ± 3.5%, R-1.0: 38.1 ± 5.2%). However, the I0.5-R0.5 group did not shown a more beneficial effect than the other two BN-063-treated groups. In addition, BN-063 exerted a protective effect on the number of ventricular premature contractions associated with reperfusion (control: 906 ± 52, I0.5-R0.5: 325 ± 61, R-0.5: 321 ± 95, R-1.0: 340 ± 46). The results of this study demonstrate that BN-063, through activation of adenosine A1 receptors, exerts antiarrhythmic and anti-infarct effects during myocardial ischemia-reperfusion. Therefore, BN-063 would be useful clinically in the treatment and prevention of acute myocardial infarction.

Original languageEnglish
Pages (from-to)251-256
Number of pages6
JournalEuropean Journal of Pharmacology
Volume279
Issue number2-3
DOIs
Publication statusPublished - Jun 12 1995
Externally publishedYes

Fingerprint

Adenosine A1 Receptor Agonists
Myocardial Reperfusion Injury
Reperfusion
Coronary Occlusion
Coronary Vessels
Adenosine A1 Receptors
1-cyclopropylisoguanosine
Myocardial Reperfusion
Control Groups
Ventricular Premature Complexes
Myocardial Ischemia
Ligation
Chlorides
Coloring Agents
Ischemia
Myocardial Infarction

Keywords

  • Adenosine A receptor agonist
  • Infarct
  • Myocardial ischemia
  • Reperfusion injury

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

BN-063, a newly synthesized adenosine A1 receptor agonist, attenuates myocardial reperfusion injury in rats. / Lee, Yen Mei; Sheu, Joen Rong; Yen, Mao Hsiung.

In: European Journal of Pharmacology, Vol. 279, No. 2-3, 12.06.1995, p. 251-256.

Research output: Contribution to journalArticle

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abstract = "To assess the efficacy of the newly synthesized selective adenosine A1 receptor agonist, BN-063 (1-cyclopropylisoguanosine), against myocardial reperfusion injury, 31 rats underwent 45 min of left coronary artery occlusion and 1 h of reperfusion. Animals were randomly assigned to four groups: control, I0.5-R0.5, in which BN-063 (0.5 mg/kg i.v. bolus) was administered during both ischemia and reperfusion, R-0.5 and R-1.0, in which BN-063 was administered only during reperfusion at 0.5 and 1.0 mg/kg, respectively. The area at risk was determined by intravascular injection of blue dye during coronary artery occlusion, which was performed by retightening the ligature at the end of reperfusion, and infarct size was determined by incubation of heart slices in nitro blue tetrazolium chloride. A significant reduction in infarct size, as a percentage of the area at risk, was noted with all three BN-063 treatment groups (control: 63.5 ± 4.0{\%}, I0.5-R0.5: 39.6 ± 3.7{\%}, R-0.5: 37.5 ± 3.5{\%}, R-1.0: 38.1 ± 5.2{\%}). However, the I0.5-R0.5 group did not shown a more beneficial effect than the other two BN-063-treated groups. In addition, BN-063 exerted a protective effect on the number of ventricular premature contractions associated with reperfusion (control: 906 ± 52, I0.5-R0.5: 325 ± 61, R-0.5: 321 ± 95, R-1.0: 340 ± 46). The results of this study demonstrate that BN-063, through activation of adenosine A1 receptors, exerts antiarrhythmic and anti-infarct effects during myocardial ischemia-reperfusion. Therefore, BN-063 would be useful clinically in the treatment and prevention of acute myocardial infarction.",
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AB - To assess the efficacy of the newly synthesized selective adenosine A1 receptor agonist, BN-063 (1-cyclopropylisoguanosine), against myocardial reperfusion injury, 31 rats underwent 45 min of left coronary artery occlusion and 1 h of reperfusion. Animals were randomly assigned to four groups: control, I0.5-R0.5, in which BN-063 (0.5 mg/kg i.v. bolus) was administered during both ischemia and reperfusion, R-0.5 and R-1.0, in which BN-063 was administered only during reperfusion at 0.5 and 1.0 mg/kg, respectively. The area at risk was determined by intravascular injection of blue dye during coronary artery occlusion, which was performed by retightening the ligature at the end of reperfusion, and infarct size was determined by incubation of heart slices in nitro blue tetrazolium chloride. A significant reduction in infarct size, as a percentage of the area at risk, was noted with all three BN-063 treatment groups (control: 63.5 ± 4.0%, I0.5-R0.5: 39.6 ± 3.7%, R-0.5: 37.5 ± 3.5%, R-1.0: 38.1 ± 5.2%). However, the I0.5-R0.5 group did not shown a more beneficial effect than the other two BN-063-treated groups. In addition, BN-063 exerted a protective effect on the number of ventricular premature contractions associated with reperfusion (control: 906 ± 52, I0.5-R0.5: 325 ± 61, R-0.5: 321 ± 95, R-1.0: 340 ± 46). The results of this study demonstrate that BN-063, through activation of adenosine A1 receptors, exerts antiarrhythmic and anti-infarct effects during myocardial ischemia-reperfusion. Therefore, BN-063 would be useful clinically in the treatment and prevention of acute myocardial infarction.

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