Mechanoenergetic studies in isolated mouse hearts

Area of Science:

• Cardiovascular Physiology
• Cardiac Mechanoenergetics
• Mouse Model Research

Background:

• Assessing cardiac mechanoenergetics is crucial for understanding heart function.
• Previous methods were limited to larger animal models.
• A need exists for sophisticated analysis in smaller organisms like mice.

Purpose of the Study:

• To test the feasibility of an isolated, perfused mouse heart preparation for cardiac mechanoenergetics studies.
• To adapt established frameworks like the end-systolic pressure-volume relation (ESPVR) and myocardial oxygen consumption (VO2)-pressure-volume area (PVA) for mouse hearts.
• To enable advanced cardiac function assessments in mice.

Main Methods:

• Utilized an isolated, isovolumically contracting, crystalloid-perfused mouse heart preparation (n=10).
• Employed an intraventricular balloon for accurate left ventricular volume measurement.
• Applied the end-systolic pressure-volume relation (ESPVR) and myocardial oxygen consumption (VO2)-pressure-volume area (PVA) framework.
• Manipulated perfusate Ca2+ concentration and studied hypothyroid mouse hearts (n=8).

Main Results:

• The intraventricular balloon method accurately measured left ventricular volume.
• The ESPVR showed contractility-dependent curvilinearity with an average slope of 1,299 ± 369 mmHg·g·ml⁻¹.
• The VO2-PVA relation was linear, with an average slope of 3.57 ± 1.31 x 10⁻⁵ ml O2·mmHg⁻¹·ml⁻¹.
• Decreased Ca2+ reduced ESPVR slope and VO2 intercept, but not VO2-PVA slope.
• Hypothyroid hearts showed similar mechanoenergetic changes.

Conclusions:

• Delineation of the ESPVR and VO2-PVA relation is feasible in the mouse heart.
• The developed method allows for sophisticated cardiac mechanoenergetics assessment in mice.
• This technique bridges the gap in advanced cardiac function analysis between small and large animal models.