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Manganese reduces myocardial reperfusion injury on isolated rat heart
C E Barandier1, F R Boucher, J P de Leiris
1Groupe de Physiopathologie Cellulaire Cardiaque, ESA CNRS 5077, Université Joseph Fourier, Grenoble, France.
Abstract:
It has been shown that reactive oxygen species produced during the early phase of myocardial post-ischemic reperfusion are one of the main causes of reperfusion injury. This observation has led to various antioxidant strategies using many reactive oxygen species scavengers, including manganese complexes. The aim of the present work was to provide a reference study of the effects of manganese itself (MnCl2) on isolated rat hearts submitted to global total normothermic ischemia (30 min) and reperfusion (60 min). McCl2 was administered either during the first 10 min reperfusion (10(-5)M and 10(-4)M) or throughout reperfusion (10(-4)M). After 10 min reperfusion, no functional difference was evidenced between control and manganese-treated groups, whereas high energy phosphate contents were significantly higher in treated groups. MnCl2 10(-4)M enhanced the recovery of developed pressure between 40 and 55 min reperfusion. At the end of reperfusion, hearts treated during the first 10 min reperfusion showed a better metabolic recovery. The group treated throughout reperfusion showed a better metabolic recovery, but a reduced coronary flow and a weak recovery of developed pressure. These results suggest that MnCl2, administered during the early phase of reperfusion, protects against myocardial reperfusion injury. This effect might be mediated by manganese antioxidant properties.
Insights
Manganese chloride (MnCl2) given early during reperfusion protects isolated rat hearts from injury. This study suggests manganese
Area of Science:
- Cardiovascular Science
- Biochemistry
- Pharmacology
Background:
- Reactive oxygen species (ROS) contribute to myocardial reperfusion injury.
- Antioxidant strategies, including manganese complexes, are explored to mitigate this damage.
Purpose of the Study:
- To investigate the protective effects of manganese chloride (MnCl2) on isolated rat hearts subjected to ischemia-reperfusion.
- To evaluate the impact of MnCl2 administration timing and concentration on cardiac function and metabolism.
Main Methods:
- Isolated rat hearts underwent global normothermic ischemia (30 min) followed by reperfusion (60 min).
- MnCl2 was administered at varying concentrations (10⁻⁵M, 10⁻⁴M) during the initial 10 minutes of reperfusion or throughout reperfusion.
- Cardiac function (developed pressure) and high-energy phosphate content were assessed.
Main Results:
- Early MnCl2 administration (10⁻⁴M) improved the recovery of developed pressure between 40-55 minutes of reperfusion.
- Hearts treated with MnCl2 during the first 10 minutes of reperfusion exhibited better metabolic recovery.
- Treatment throughout reperfusion showed metabolic recovery but impaired coronary flow and pressure development.
Conclusions:
- Manganese chloride, when administered early in the reperfusion phase, demonstrates protective effects against myocardial reperfusion injury.
- The antioxidant properties of manganese may mediate this protective effect.
- Optimal therapeutic benefit is observed with early, short-term administration of MnCl2.