Cardiac and coronary function in the Langendorff-perfused mouse heart model

Area of Science:

• Cardiovascular Research
• Physiology
• Pharmacology

Background:

• The Langendorff mouse heart model is essential for studying myocardial function and injury responses.
• Significant variability in preparation and functional properties necessitates optimization.

Purpose of the Study:

• To investigate the impact of age, sex, perfusate calcium, and pacing rate on mouse heart function and ischemia-reperfusion responses.
• To assess the influence of mouse strain on these parameters.
• To evaluate the model's utility for studying coronary function.

Main Methods:

• Utilized the Langendorff mouse heart model with varying mouse ages (8-24 weeks), sex, perfusate calcium concentrations, and pacing rates.
• Subjected hearts to 20 minutes of ischemia followed by 45 minutes of reperfusion.
• Assessed contractile function (left ventricular developed pressure) and coronary flow.
• Compared responses across different mouse strains (C57BL/6, 129/sv, Quackenbush Swiss, FVBN, BALB/c).

Main Results:

• Lower perfusate calcium significantly improved contractile recovery after ischemia (>30%).
• Elevated pacing rate did not alter ischemic outcome, while reduced calcium improved recovery.
• Age-related decline in ischemic tolerance was observed, differing between sexes.
• Mouse strain significantly impacted ischemia tolerance, with BALB/c hearts showing greater resilience.
• The model demonstrated robust coronary vascular reactivity.

Conclusions:

• Optimizing mouse age, sex, and perfusate calcium levels in the Langendorff model reduces variability in contractile function and ischemia responses.
• Perfusate calcium concentration is a critical factor influencing ischemia tolerance.
• Mouse strain is a significant determinant of ischemic response.
• The Langendorff model is well-suited for studying vascular reactivity with reproducible results.