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Updated: Jun 7, 2026
Postconditioning with Lactate-enriched Blood for Cardioprotection in ST-segment Elevation Myocardial Infarction
Published on: May 28, 2019
Ischemic preconditioning decreases mitochondrial proton leak and reactive oxygen species production in the
Ricardo Quarrie1, Brandon M Cramer, Daniel S Lee
1Division of Cardiothoracic Surgery, The Ohio State University Medical Center, Columbus, Ohio 43210, USA. juan.crestanello@osumc.edu
Background:
Proton leak (H(+) leak) dissipates mitochondrial membrane potential (mΔΨ) through the re-entry of protons into the mitochondrial matrix independent of ATP synthase. Changes in H(+) leak may affect reactive oxygen species (ROS) production. We measured H(+) leak and ROS production during ischemia-reperfusion and ischemic preconditioning (IPC) and examined how changing mitochondrial respiration affected mΔΨ and ROS production.
Materials And Methods:
Isolated rat hearts (n = 6/group) were subjected to either control-IR or IPC. Rate pressure product (RPP) was measured. Mitochondria were isolated at end reperfusion. Respiration was measured by polarography and titrated with increasing concentrations of malonate (0.5-2 mM). mΔΨ was measured using a tetraphenylphosphonium electrode. H(+) leak is the respiratory rate required to maintain membrane potential at -150 mV in the presence of oligomycin-A. Mitochondrial complex III ROS production was measured by fluorometry using Amplex-red.
Results:
IPC improved recovery of RPP at end reperfusion (63% ± 4% versus 21% ± 2% in control-IR, P < 0.05). Ischemia-reperfusion caused increased H(+) leak (94 ± 12 versus 31 ± 1 nmol O/mg protein/min in non-ischemic control, P < 0.05). IPC attenuates these increases (55 ± 9 nmol O/mg protein/min, P < 0.05 versus control-IR). IPC reduced mitochondrial ROS production compared with control-IR (31 ± 2 versus 40 ± 3 nmol/mg protein/min, P < 0.05). As mitochondrial respiration decreased, mΔΨ and mitochondrial ROS production also decreased. ROS production remained lower in IPC than in control-IR for all mΔΨ and respiration rates.
Conclusions:
Increasing H(+) leak is not associated with decreased ROS production. IPC decreases both the magnitude of H(+) leak and ROS production after ischemia-reperfusion.
Insights
Ischemic preconditioning (IPC) reduces mitochondrial proton leak and reactive oxygen species (ROS) production following ischemia-reperfusion injury. This protective effect improves heart function and lowers oxidative stress.
Area of Science:
- Cardiovascular Physiology
- Mitochondrial Biology
- Oxidative Stress
Background:
- Proton leak dissipates mitochondrial membrane potential (mΔΨ) independent of ATP synthase.
- Changes in proton (H+) leak can influence reactive oxygen species (ROS) production.
- Investigating H+ leak and ROS during ischemia-reperfusion and preconditioning is crucial for understanding mitochondrial function.
Purpose of the Study:
- To measure H+ leak and ROS production during ischemia-reperfusion and ischemic preconditioning (IPC).
- To examine how altered mitochondrial respiration affects mΔΨ and ROS production.
- To determine the relationship between H+ leak and ROS production under these conditions.
Main Methods:
- Isolated rat hearts underwent control ischemia-reperfusion (IR) or IPC.
- Mitochondrial respiration, mΔΨ, and ROS production were measured.
- H+ leak was quantified as the respiratory rate needed to maintain mΔΨ at -150 mV with oligomycin-A.
Main Results:
- IPC improved the recovery of heart function (rate pressure product).
- Ischemia-reperfusion increased H+ leak, which IPC attenuated.
- IPC reduced mitochondrial ROS production compared to control-IR, irrespective of mΔΨ or respiration rates.
Conclusions:
- Increased H+ leak is not linked to decreased ROS production.
- IPC effectively reduces both H+ leak magnitude and ROS production post-ischemia-reperfusion.
- IPC offers cardioprotection by modulating mitochondrial energetics and oxidative stress.
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