Key result
Repeated sodium lactate worsens post-MI survival, whereas LDH inhibition trends toward improved survival.
Why the study?
Emerging evidence suggests that lactate may mitigate damaging inflammation, prompting investigation into the effects of lactate on post-MI cardiac remodeling.
Does exogenous sodium lactate administration affect post-MI survival, cardiac remodeling, and macrophage activation in mice with myocardial infarction?
Does exogenous sodium lactate administration affect post-MI survival, cardiac remodeling, and macrophage activation in mice with myocardial infarction?
Exogenous lactate administration in mice following myocardial infarction worsens survival and exacerbates adverse cardiac remodeling via extracellular matrix disruption, inflammatory activation, and macrophage metabolic dysregulation.
Exogenous lactate may worsen post-MI survival in male mice; leaves open whether LDH inhibition confers protection in larger studies.
Myocardial infarction (MI) induces cardiac remodeling characterized by inflammation, scar formation, and metabolic remodeling of surviving tissue. Emerging evidence suggests that lactate, an alternative metabolic fuel, may also have therapeutic effects by mitigating damaging inflammation. To investigate the effects of lactate on post-MI remodeling, male and female mice underwent permanent coronary artery ligation for up to 7-days post-MI. In untreated animals, MI induced progressive myocardial lactate accumulation, accompanied by increased Lactate Dehydrogenase-A (LDHA) and reduced LDHB expression in both male and female. In untreated male, cardiac macrophages exhibited dynamic changes in Ldha, Ldhb, and Mct1 gene expression between Day-1, 3, and 7. Repeated sodium lactate administration significantly reduced Day-7 survival in male and promoted ventricular wall thinning, reduced collagen deposition, increased myocardial inflammatory markers ( Ccl2, Il18, Il6) and reduced CD206+ reparative macrophages in both infarct and remote regions at Day-3. To distinguish acute from sustained lactate effects, we administered a single sodium lactate injection 30 minutes before tissue collection at Day-3 post-MI (D3-30min), which rapidly increased myocardial lactate levels and induced inflammatory and endoplasmic reticulum stress–associated gene expression. Moreover, acute lactate treatment (D3-30min) increased circulating and bone marrow neutrophils, increased bone marrow and cardiac monocytes, and reduced ATP-linked mitochondrial respiration in isolated cardiac macrophages. In parallel experiments, sodium oxamate (a lactate dehydrogenase inhibitor), displayed a trend towards improving post-MI survival (p=0.09) but otherwise did not significantly impact cardiac functional or remodeling parameters. These findings demonstrate that exogenous lactate exacerbates adverse post-MI remodeling, promoting extracellular matrix disruption, inflammatory activation, and macrophage metabolic dysregulation. Collectively, our results suggest that lactate metabolic signaling, production, accumulation or downstream may represents a potential therapeutic strategy for limiting adverse cardiac remodeling after MI.
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Khan et al. (2026) studied Myocardial infarction (preclinical mouse model). Sodium lactate (and sodium oxamate in parallel experiments) vs. Untreated post-MI mice was evaluated on Post-MI survival and adverse cardiac remodeling parameters (p=0.09 (for sodium oxamate trend on survival)). Repeated sodium lactate administration significantly reduced Day-7 post-MI survival in male mice, while sodium oxamate showed a trend toward improved survival (p=0.09).
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