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Updated: Sep 27, 2026
Model of Ischemia and Reperfusion Injury in Rabbits
Published on: November 3, 2023
Effects of N-(2-mercaptopropionyl)-glycine on mitochondrial function in ischemic-reperfused heart
Kouichi Tanonaka1, Takeshi Iwai, Kanataka Motegi
1Department of Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
Objective:
A possible mechanism for N-(2-mercaptopropionyl)-glycine (MPG) underlying the improvement of contractile function and mitochondrial activity of ischemic-reperfused rat hearts was examined.
Methods:
Isolated, perfused hearts were subjected to 35 min ischemia-60 min reperfusion. At the end of ischemia or reperfusion, myocardial Na(+) content and mitochondrial oxygen consumption rate (OCR) were examined. The perfused heart was treated with 0.1-1 mM MPG for 30 min prior to ischemia or for the first 30 min of reperfusion.
Results:
Ischemia increased myocardial Na(+) content (sodium overload) and decreased mitochondrial OCR. The left ventricular developed pressure (LVDP) of the untreated heart recovered to 19.8+/-3.8% of the preischemic value and the infarct area amounted to 23.3+/-1.7% of the left ventricle. The thiobarbiturate-reacting substance (TRS) was also increased in the reperfused, but not ischemic, myocardium. Pretreatment of the perfused heart with 0.3-1 mM MPG attenuated the ischemia-induced sodium overload and decrease in the OCR. Pretreatment with the agent also enhanced the postischemic recovery of LVDP, attenuated reperfusion-induced increase in TRS, and reduced the infarct area. Although the postischemic treatment with MPG suppressed the increase in TRS in the reperfused myocardium, a LVDP recovery of reperfused hearts was not observed. Cardiac mitochondria were isolated and examined for the direct effect of MPG on their function. Incubation with either 12.5 mM sodium lactate or 1 microM phenylarsine oxide neither altered the mitochondrial membrane potential nor induced mitochondrial swelling, whereas incubation with a combination of these agents elicited the membrane potential depolarization and swelling. Incubation of mitochondria with 1 mM MPG attenuated these events.
Conclusion:
These results suggest that both attenuation of sodium overload and preservation of the mitochondrial function may largely contribute to cardioprotection of MPG in the ischemic-reperfused heart.
Insights
N-(2-mercaptopropionyl)-glycine (MPG) protects ischemic-reperfused hearts by reducing sodium overload and preserving mitochondrial function. This cardioprotective effect enhances recovery of contractile function and reduces infarct size in rat hearts.
Area of Science:
- Cardiovascular Science
- Mitochondrial Biology
- Pharmacology
Background:
- Ischemia-reperfusion injury significantly impairs heart function.
- Mitochondrial dysfunction and sodium overload are key contributors to this injury.
- N-(2-mercaptopropionyl)-glycine (MPG) has shown potential in improving cardiac outcomes.
Purpose of the Study:
- To investigate the cardioprotective mechanisms of MPG in an in vitro model of ischemic-reperfused rat hearts.
- To determine if MPG mitigates sodium overload and preserves mitochondrial oxygen consumption rate (OCR).
- To assess the impact of MPG on cardiac contractile function and infarct size.
Main Methods:
- Isolated rat hearts underwent 35 minutes of ischemia followed by 60 minutes of reperfusion.
- Hearts were treated with MPG (0.1-1 mM) either before ischemia or during early reperfusion.
- Myocardial sodium content, mitochondrial OCR, left ventricular developed pressure (LVDP), and infarct area were measured.
- Direct effects of MPG on isolated cardiac mitochondria were also examined.
Main Results:
- Ischemia led to increased myocardial sodium and decreased mitochondrial OCR, reduced LVDP, and increased infarct size.
- MPG pretreatment attenuated sodium overload, preserved mitochondrial OCR, improved LVDP recovery, and reduced infarct size.
- MPG also reduced markers of oxidative stress (thiobarbiturate-reacting substance) during reperfusion.
- While MPG suppressed oxidative stress during reperfusion, post-ischemic treatment did not restore LVDP.
Conclusions:
- MPG demonstrates significant cardioprotection in ischemic-reperfused hearts.
- Attenuation of sodium overload and preservation of mitochondrial function are key mechanisms of MPG's protective effects.
- MPG holds promise for therapeutic intervention in cardiac ischemia-reperfusion injury.
