Myocardial dysfunction in sepsis is associated with an increased risk of 
mortality. The mitochondrial aldehyde dehydrogenase (ALDH2) enzyme is crucial 
for protecting the heart from ischemic injury. The aim of the present study was 
to determine the role of ALDH2 in cardiac dysfunction induced by 
lipopolysaccharide (LPS). Male rats were treated intraperitoneally with LPS, and 
their stroke volume and cardiac output were evaluated using an M‑mode 
echocardiograph. The expression levels and activity of ALDH2, nitric oxide 
content and inducible nitric oxide synthase (iNOS) activity, and the opening of 
the mitochondrial permeability transition pore (MPTP) were also evaluated. 
Treatment with LPS (5, 10, or 20 mg/kg) resulted in a steady decrease in cardiac 
output and stroke volume. The ALDH2 activity was decreased in a dose‑dependent 
manner; however, the ALDH2 protein expression levels remained unchanged. Alda‑1, 
a specific activator of ALDH2, increased the activity of ALDH2 and lessened 
LPS‑induced cardiac dysfunction. A marked opening of the MPTP was observed 12 h 
following treatment with LPS, which was prevented by Alda‑1. The improvement in 
cardiac function in response to treatment with Alda‑1, was partially prevented 
by treatment with the MPTP inhibitor atractyloside. LPS treatment induced an 
increase in iNOS activation and inhibition of ALDH2 activity. The iNOS selective 
inhibitor, aminoguanidine, partially reversed the LPS‑induced ALDH2 activity 
decrease and MPTP opening. These results indicate that ALDH2 activity may have a 
role in protecting against LPS‑induced cardiac dysfunction. The potential 
mechanism may involve inhibition of MPTP opening and iNOS expression.