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Updated: Jun 23, 2026
Rodent Working Heart Model for the Study of Myocardial Performance and Oxygen Consumption
Published on: August 16, 2016
Ryanodine wastes oxygen consumption for Ca2+ handling in the dog heart. A new pathological heart model
T Takasago1, Y Goto, O Kawaguchi
1Department of Cardiovascular Dynamics, National Cardiovascular Center, Osaka, Japan.
Abstract:
Ryanodine (RYA) at a low concentration (several tens of nM) is known to selectively bind to Ca2+ release channels in sarcoplasmic reticulum (SR) and to fix them open. The present study was designed to investigate the effects of the selective change in Ca2+ release channel activity on cardiac mechanoenergetics as a model of Ca(2+)-leaky SR observed in pathological hearts. We analyzed the negative inotropic effect of RYA at a low concentration (up to 30 +/- 13 nM) on left ventricular (LV) mechanoenergetics using frameworks of LV Emax (a contractility index) and the myocardial oxygen consumption (LV VO2)-systolic pressure-volume area (PVA) (a measure of total mechanical energy) relation in 11 isolated, blood-perfused dog hearts. RYA significantly decreased Emax by 42%, whereas PVA-independent VO2 remained disproportionately high (93% of control). This oxygen-wasting effect of RYA was quite different from ordinary inotropic drugs, which alter Emax and PVA-independent VO2 proportionally. The present result suggests that RYA suppresses force generation of cardiac muscle for a given amount of total sequestered Ca2+ by SR in a similar way to myocardial ischemia and stunning. We speculate about the underlying mechanism that RYA makes SR leaky for Ca2+ and thereby wastes energy for Ca2+ handling by SR.
Insights
Low-concentration ryanodine (RYA) causes cardiac energy waste by making calcium channels leaky. This negatively impacts heart contractility, mimicking conditions like myocardial ischemia.
Area of Science:
- Cardiovascular Physiology
- Cardiac Energetics
- Calcium Channel Pharmacology
Background:
- Ryanodine (RYA) at low concentrations selectively opens cardiac sarcoplasmic reticulum (SR) Ca2+ release channels.
- This action serves as a model for Ca2+-leaky SR in pathological heart conditions.
Purpose of the Study:
- To investigate the effects of altered Ca2+ release channel activity on cardiac mechanoenergetics.
- To analyze the negative inotropic effect of RYA on left ventricular (LV) function and energy consumption.
Main Methods:
- Used isolated, blood-perfused dog hearts (n=11).
- Analyzed LV Emax (contractility) and myocardial oxygen consumption (LV VO2) in relation to systolic pressure-volume area (PVA).
- Administered low concentrations of RYA (up to 30 +/- 13 nM).
Main Results:
- RYA significantly decreased LV Emax by 42%.
- PVA-independent LV VO2 remained high (93% of control), indicating disproportionate oxygen consumption.
- This "oxygen-wasting" effect differs from typical inotropic drugs.
Conclusions:
- RYA suppresses cardiac muscle force generation for a given SR Ca2+ load, similar to myocardial ischemia.
- The mechanism likely involves RYA inducing SR Ca2+ leakiness, leading to wasted energy in Ca2+ handling.
