Measurement of coronary flow reserve in isolated hearts from mice

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Abstract
Langendorff-perfused murine hearts are increasingly used in cardiovascular research, but coronary cardiovascular haemodynamics vary considerably from one research group to another. The aim of this study was to establish an isolated, retrogradely perfused mouse heart preparation for the simultaneous measurement of left ventricular haemodynamics and of coronary flow (CF).Heart rate was controlled by right atrial pacing (480 beats min(-1)) and heart temperature was kept constant. Accurate flow values of <0.5 mL min(-1) could be determined, and this methodology was then used to study the stability of this preparation, as well as coronary response to vasoactive drugs and to short-term ischaemia.The CF and maximum systolic pressure were well maintained over a 2-h perfusion period, both showing a 10% decline per hour. Sodium-nitroprusside (endothelium-independent) and adenosine (endothelium-dependent) increased CF relatively modest (30-50% above baseline values). Short-term no-flow ischaemia caused a transient 40-50% increase in CF on reperfusion. Peak reflow occurred approximately 15 s after start of reperfusion and flow returned to baseline during the following 1-2 min. Increased coronary blood flow following infusion of vasoactive drugs (nitroprusside or adenosine) or short-term ischaemia were associated with minor changes in ventricular pressure development.Blood flow and haemodynamics can readily be determined in this isolated perfused mouse heart model, but CF reserve is relatively small, compared with blood-perfused organs.