Myocardial dysfunction associated with low-dose endotoxin administration in adult horses.

Overview

• This study investigated how low doses of endotoxin affect heart muscle function in healthy adult horses.
• It specifically examined whether experimental endotoxemia causes measurable impairments in heart function, and if these impairments correlate with heart muscle damage biomarkers.

Background and Purpose

• Endotoxemia refers to the presence of endotoxins such as lipopolysaccharide (LPS) in the bloodstream, often from bacterial infections, which can trigger systemic inflammation.
• In horses, endotoxemia can affect heart function, but the exact severity and duration of myocardial dysfunction (MD) associated with endotoxin exposure are not well understood.
• The study aimed to evaluate both systolic (pumping) and diastolic (relaxation) heart function in adult horses after administration of low doses of Escherichia coli LPS.
• It also aimed to determine whether changes in myocardial performance are accompanied by increases in cardiac troponin I (cTnI), a biomarker of heart muscle injury.

Methods

• Twelve healthy adult horses were included in the study.
• Each horse was given a controlled dose of E. coli LPS at 30 ng/kg intravenously over a 60-minute period to induce endotoxemia experimentally.
• Echocardiographic assessments and cardiac troponin I measurements were taken at baseline (pre-endotoxin administration) and at 1, 3, and 5 hours after administration.
• After 5 hours, horses received standard supportive treatments: 10 liters of intravenous fluid therapy, polymyxin B (6000 IU/kg) to neutralize endotoxin, and flunixin meglumine (1.1 mg/kg) as an anti-inflammatory agent.
• Echocardiography and cTnI measurements were repeated after treatment to assess potential functional recovery.
• Data analysis utilized linear mixed models, controlling for multiple comparisons, with statistical significance set at P < 0.05.

Key Findings

• All horses developed measurable myocardial dysfunction following LPS administration.
• Heart rate increased significantly at all post-endotoxin time points compared to baseline (P < 0.001), indicating systemic physiological stress.
• Cardiac troponin I levels did not rise significantly at any timepoint, suggesting no overt myocardial cell injury despite functional changes.
• Ejection fraction, an indicator of systolic function, decreased significantly at 3 and 5 hours post-LPS (from ~72% at baseline to 62% and 65% respectively, P < 0.001), reflecting impaired pumping ability.
• Tissue Doppler imaging (TDI) revealed an increased myocardial performance index at 1, 3, and 5 hours (values rising from 0.40 at baseline to as high as 0.66, P < 0.01), signifying combined systolic and diastolic dysfunction.
• Two-dimensional speckle tracking (2DST) showed a significant reduction in global longitudinal strain—a measure of myocardial deformation, important for contractile function—at 3, 5 hours, and post-treatment (-21% baseline reduced to -16% and -17%, and -19% post-treatment; P values from <0.0001 to 0.04), indicating persistent regional myocardial impairment.

Interpretation and Conclusions

• Low-dose endotoxin exposure induces both systolic and diastolic myocardial dysfunction in adult horses without causing detectable myocardial cell injury as per cTnI levels.
• The absence of cTnI elevation suggests that functional impairment occurs without significant necrosis or irreversible myocardial damage.
• Advanced echocardiographic techniques such as tissue Doppler imaging and two-dimensional speckle tracking provide enhanced sensitivity to detect subtle regional myocardial abnormalities that conventional measures may miss.
• These findings highlight that horses undergoing endotoxemia can experience temporary myocardial impairment, which may contribute to clinical signs and influence treatment considerations.
• Post-treatment measurements suggest partial persistence of myocardial dysfunction despite standard supportive care, underlining the need for careful cardiac monitoring in endotoxemic horses.