Pressure-calcium relationships in perfused mouse hearts

Area of Science:

• Cardiovascular Physiology
• Cardiac Excitation-Contraction Coupling
• Mammalian Heart Mechanics

Background:

• Understanding the relationship between intracellular calcium and left ventricular (LV) pressure is crucial for comprehending cardiac function.
• Previous studies in various mammalian species suggest a direct correlation between peak intracellular calcium and developed pressure.

Purpose of the Study:

• To investigate the relationship between intracellular free calcium concentration ([Ca](i)) and LV pressure in the isolated perfused mouse heart.
• To determine if mouse myocardium exhibits unique calcium-pressure dynamics compared to other mammalian species.

Main Methods:

• Simultaneous recording of intracellular free calcium ([Ca](i)) using rhod-2 and LV pressure in isolated perfused mouse hearts.
• Application of Frank-Starling (FS) and mechanical restitution (MR) protocols to alter LV volume and stimulus interval.
• Model-based analysis to assess the contribution of [Ca](i) to LV pressure changes.

Main Results:

• During the FS protocol, increased LV volume elevated developed pressure without altering [Ca](i) magnitude or morphology.
• During the MR protocol, developed pressure increased with minimal change in peak systolic [Ca](i), but prolonged [Ca](i) relaxation.
• Model analysis indicated [Ca](i) changes fully explained LV pressure variations during MR, and a gain parameter change explained FS data.

Conclusions:

• Mouse myocardium demonstrates a unique characteristic where significant changes in developed LV pressure can occur with minimal alteration in peak [Ca](i).
• Unlike other mammals, mouse hearts lack load-dependent prolongation of pressure relaxation, which is primarily governed by intracellular calcium relaxation kinetics.