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Updated: Apr 28, 2026
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
Mitochondria selective S-nitrosation by mitochondria-targeted S-nitrosothiol protects against post-infarct heart
Carmen Methner1, Edward T Chouchani, Guido Buonincontri
1Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Aims:
Recently it has been shown that the mitochondria-targeted S-nitrosothiol MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting the reactivation of mitochondrial complex I in the first minutes of reperfusion of ischaemic tissue, thereby preventing free radical formation that underlies IR injury. However, it remains unclear how this transient inhibition of mitochondrial complex I-mediated free radicals at reperfusion affects the long-term recovery of the heart following IR injury. Here we determined whether the acute protection by MitoSNO at reperfusion prevented the subsequent development of post-myocardial infarction heart failure.
Methods And Results:
Mice were subjected to 30 min left coronary artery occlusion followed by reperfusion and recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac function were measured by magnetic resonance imaging (MRI) 24 h after infarction. MitoSNO-treated mice exhibited reduced infarct size and preserved function. In addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR, including preserved systolic function (63.7 ±1.8% LVEF vs. 53.7 ± 2.1% in controls, P = 0.01) and tissue fibrosis.
Conclusions:
MitoSNO action acutely at reperfusion reduces infarct size and protects from post-myocardial infarction heart failure. Therefore, targeted inhibition of mitochondrial complex I in the first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for preventing subsequent heart failure in patients undergoing IR injury.
Insights
MitoSNO protects the heart from ischemia/reperfusion injury by inhibiting mitochondrial complex I. This treatment reduces infarct size and prevents long-term heart failure after myocardial infarction.
Area of Science:
- Cardiovascular Research
- Mitochondrial Biology
- Ischemia/Reperfusion Injury
Background:
- Ischemia/reperfusion (IR) injury is a major cause of heart damage.
- Mitochondria-targeted S-nitrosothiol MitoSNO acutely inhibits mitochondrial complex I, preventing free radical formation during reperfusion.
- The long-term effects of MitoSNO on post-myocardial infarction heart failure remain unclear.
Purpose of the Study:
- To determine if acute protection by MitoSNO at reperfusion prevents the development of post-myocardial infarction heart failure.
- To investigate the long-term recovery of heart function following IR injury with MitoSNO treatment.
Main Methods:
- Mice underwent 30 minutes of coronary artery occlusion followed by 28 days of recovery.
- MitoSNO was administered before reperfusion and during reperfusion.
- Infarct size and cardiac function were assessed using magnetic resonance imaging (MRI).
Main Results:
- MitoSNO treatment significantly reduced infarct size and preserved cardiac function 24 hours post-infarction.
- MitoSNO improved long-term outcomes, including preserved systolic function (left ventricular ejection fraction) and reduced tissue fibrosis at 28 days post-IR.
- MitoSNO-treated mice showed significantly better systolic function compared to controls (63.7 ±1.8% vs. 53.7 ± 2.1%, P = 0.01).
Conclusions:
- Acute administration of MitoSNO at reperfusion reduces infarct size and protects against subsequent heart failure.
- Targeted inhibition of mitochondrial complex I by MitoSNO is a promising therapeutic strategy for preventing heart failure after IR injury.
- MitoSNO offers a rational approach to mitigate long-term cardiac dysfunction following myocardial infarction.
