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A Rat Lung Transplantation Model of Warm Ischemia/Reperfusion Injury: Optimizations to Improve Outcomes
Published on: October 28, 2021
Magnesium sulfate mitigates lung injury induced by bilateral lower limb ischemia-reperfusion in rats
Ming-Chang Kao1, Woan-Ching Jan, Pei-Shan Tsai
1Department of Anesthesiology, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, Taiwan.
Background:
Lower limb ischemia-reperfusion (I/R) elicits oxidative stress and causes inflammation in lung tissues that may lead to lung injury. Magnesium sulfate (MgSO(4)) possesses potent anti-oxidation and anti-inflammation capacity. We sought to elucidate whether MgSO(4) could mitigate I/R-induced lung injury. As MgSO(4) is an L-type calcium channel inhibitor, the role of the L-type calcium channels was elucidated.
Materials And Methods:
Adult male rats were allocated to receive I/R, I/R plus MgSO(4) (10, 50, or 100 mg/kg), or I/R plus MgSO(4) (100 mg/kg) plus the L-type calcium channels activator BAY-K8644 (20 μg/kg) (n = 12 in each group). Control groups were run simultaneously. I/R was induced by applying rubber band tourniquets high around each thigh for 3 h followed by reperfusion for 3 h. After euthanization, degrees of lung injury, oxidative stress, and inflammation were determined.
Results:
Arterial blood gas and histologic assays, including histopathology, leukocyte infiltration (polymorphonuclear leukocytes/alveoli ratio and myeloperoxidase activity), and lung water content, confirmed that I/R caused significant lung injury. Significant increases in inflammatory molecules (chemokine, cytokine, and prostaglandin E(2) concentrations) and lipid peroxidation (malondialdehyde concentration) confirmed that I/R caused significant inflammation and oxidative stress in rat lungs. MgSO(4), at the dosages of 50 and 100 mg/kg but not 10 mg/kg, attenuated the oxidative stress, inflammation, and lung injury induced by I/R. Moreover, BAY-K8644 reversed the protective effects of MgSO(4).
Conclusions:
MgSO(4) mitigates lung injury induced by bilateral lower limb I/R in rats. The mechanisms may involve inhibiting the L-type calcium channels.
Insights
Magnesium sulfate (MgSO(4)) protects against lung injury caused by lower limb ischemia-reperfusion (I/R) in rats. This protective effect may be linked to MgSO(4) inhibiting L-type calcium channels.
Area of Science:
- Physiology
- Pharmacology
- Toxicology
Background:
- Lower limb ischemia-reperfusion (I/R) induces oxidative stress, inflammation, and lung injury.
- Magnesium sulfate (MgSO(4)) exhibits anti-oxidative and anti-inflammatory properties.
- The potential of MgSO(4) to mitigate I/R-induced lung injury requires investigation, considering its role as an L-type calcium channel inhibitor.
Purpose of the Study:
- To determine if MgSO(4) can prevent lung injury resulting from lower limb I/R.
- To explore the involvement of L-type calcium channels in the protective mechanisms of MgSO(4).
Main Methods:
- Adult male rats underwent I/R injury (3h ischemia, 3h reperfusion) and received varying doses of MgSO(4) or MgSO(4) with an L-type calcium channel activator (BAY-K8644).
- Lung injury, oxidative stress, and inflammation markers were assessed post-reperfusion.
- Control groups were included for comparison.
Main Results:
- I/R significantly increased lung injury markers, inflammation, and oxidative stress.
- MgSO(4) at 50 and 100 mg/kg, but not 10 mg/kg, significantly reduced I/R-induced lung injury, inflammation, and oxidative stress.
- The L-type calcium channel activator BAY-K8644 reversed the protective effects of MgSO(4).
Conclusions:
- Magnesium sulfate (MgSO(4)) effectively mitigates lung injury caused by bilateral lower limb ischemia-reperfusion in rats.
- The protective mechanism of MgSO(4) likely involves the inhibition of L-type calcium channels.

