Mechanoenergetic studies in isolated mouse hearts

Abstract

We tested the feasibility of an isolated, balloon-in-ventricle, isovolumically contracting, crystalloid-perfused mouse heart preparation ( n = 10) for studies of cardiac mechanoenergetics using the end-systolic pressure-volume relation (ESPVR) and myocardial oxygen consumption (V˙o 2)-pressure-volume area (PVA) framework employed in larger species. The intraventricular balloon method was shown to be accurate for measurement of left ventricular volume, especially at relatively higher volumes. The ESPVR demonstrated contractility-dependent curvilinearity. Average slope of the ESPVR was 1,299 ± 369 (SD) mmHg ⋅ g ⋅ ml−1, with a volume intercept of 0.018 ± 0.006 ml. TheV˙o 2-PVA relation was well fitted by a straight line, with average slope andV˙o 2 intercept of 3.57 ± 1.31 × 10−5 ml O2 ⋅ mmHg−1 ⋅ ml−1and 0.92 ± 0.21 × 10−3 ml O2 ⋅ beat−1 ⋅ g−1, respectively. Decreasing perfusate Ca2+ concentration resulted in a decrease in the slope of the ESPVR, a decrease in theV˙o 2 intercept of theV˙o 2-PVA relation, but no significant change in its slope. Hearts from hypothyroid ( n = 8) mice demonstrated similar mechanoenergetic changes. We conclude that delineation of the ESPVR and the V˙o 2-PVA relation is feasible in the mouse heart. Our method should allow an assessment of cardiac mechanoenergetics as sophisticated as that previously possible only in larger hearts.

Cardiac Basal Metabolism.

“…In general, we would believe that the basal metabolism of the heart will show the predicted species differences, i.e., the mouse basal metabolism will be 8-fold higher than man's, so that a basal contribution of 5 mW g Ϫ1 in man will rise to 40 mW g Ϫ1 in mice. It therefore follows that the basal metabolic component in mice may be of the same order of magnitude as the active energy flux (see Table 3 and the mouse data from Kameyama et al [122]), whereas in man the basal:total energy flux may be as low as 1/6. For reasons already enumerated, we believe that the mouse heart will use only about 1/3 as much energy per beat as the human heart, so there may be only a 4-fold difference in its total myocardial energy flux compared with man's (see Table 3a).…”

“…Because of dimensional arguments, we would expect the basal metabolism of the mouse heart to be twice as high as that of rat heart and 8-fold higher than that of man's. Only one paper has examined mouse heart energetics [122]. The authors did not measure the basal metabolism directly, but because they made a pressure-volume-area, PVA, analy- sis [123] of their data and found, as we predicted [65], that the energy expenditure per beat is low, it is easy to calculate from the zero PVA intercept on the VO 2 axis that basal metabolism is very high (see their Figs.…”

Effect of Cardiac Myosin Binding Protein-C on Mechanoenergetics in Mouse Myocardium

“…27 Briefly, after anesthesia and mechanical ventilation the heart was excised, and the aorta cannulated and perfused with buffer (2.5 mmol/L Ca 2ϩ , 35°C to 37°C, pH 7.35 to 7.45). A custom-made balloon mounted on a catheter was placed in the LV via the mitral orifice.…”

“…Coronary arteriovenous O 2 content difference (AVO 2 ⌬) was measured continuously with a platinum O 2 electrode system. 27 After a 30-minutes stabilization period, balloon volume was varied from 0 to 30 or 40 L in increments of 2 to 4 L using a manual micrometer syringe driver. LV pressure (P), coronary flow, and arterio-venous O 2 content difference (AVO 2 ⌬) were measured under steady-state conditions at each volume.…”

“…LV pressure (P), coronary flow, and arterio-venous O 2 content difference (AVO 2 ⌬) were measured under steady-state conditions at each volume. 27,28 Total VO 2 (mL ⅐ beat Ϫ1 ) was calculated as coronary flow (mL ⅐ min Ϫ1 ) ϫ AVO 2 ⌬ (volume fraction of O 2 ) divided by heart rate. RV VO 2 in mL ⅐ beat Ϫ1 was estimated at zero balloon volume and assumed to be constant at all LV volumes, and LV VO 2 ϭ (total VO 2 Ϫ RV VO 2 at zero balloon volume).…”