Calcium equally increases the internal calcium recirculation fraction before and after β-blockade in canine left ventricles

Hosogi, Shingo; Araki, Junichi; Syuu, Yi; Suzuki, Shunsuke; Mohri, Satoshi; Mikane, Takeshi; Matsubara, Hiromi; Ohe, Tohru; Hirakawa, Masahisa; Suga, Hiroyuki

doi:10.1007/bf02766804

Cited by 12 publications

(77 citation statements)

References 23 publications

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“…Either an increased Ca 2ϩ handling, an augmented Ca 2ϩ responsiveness of contractility or both will enhance E max generally [5,6,[26][27][28][29][30]. Either an increased futile Ca 2ϩ cycling, a suppressed Ca 2ϩ responsiveness or both may increase the O 2 cost of E max [26][27][28][29][30].…”

Section: Discussionmentioning

confidence: 99%

“…Even a single composite VO 2 -PVA line reflects the O 2 cost of E max [14]. This cost quantitates the energy wasting of the E-C coupling [5,6,[26][27][28][29][30].…”

Section: Methodsmentioning

confidence: 99%

“…The slope (a) of the VO 2 -PVA relation represents the O 2 cost of PVA, and the VO 2 intercept (b) represents PVA-independent VO 2 . The VO 2 above basal metabolism is primarily for Ca 2ϩ handling in the E-C coupling [26][27][28][29][30]. The PVA-dependent VO 2 above b seems exclusively related to crossbridge cycling [5].…”

Section: Methodsmentioning

confidence: 99%

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Mechanoenergetics Characterizing Oxygen Wasting Effect of Caffeine in Canine Left Ventricle.

Takasago

Goto

Hata

et al. 2000

JJP

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has a considerable O 2 wasting effect [1,2] and various approaches have elucidated its mechanisms [2][3][4]. However, this O 2 wasting effect remains to be characterized by the E max -PVA-VO 2 relation, which at present seems one of the most powerful integrative frameworks of cardiac mechanoenergetics [5,6]. Here, E max is the end-systolic maximum pressure-volume ratio (or elastance) and serves as an index of contractility reasonably independent of cardiac loading conditions [5][6][7]. PVA is the systolic pressure-volume (P-V ) area that quantitates the total mechanical energy of ventricular contraction [5,6,8]. VO 2 is O 2 consumption by ventricular contraction. The E max -PVA-VO 2 framework is compatible with the Starling law of the heart [9]. In this framework, the O 2 cost of E max serves as a physiologically sound quantitative measure of the O 2 demand for unit increment in E max [5,[10][11][12][13][14][15][16].We have already shown that calcium, catecholamines, digitalis, and phosphodiesterase inhibitors (DPI 201-106, OPC-8212, EMD-53998, milrinone, sulmazole, etc.) have comparable O 2 cost of E max in the normal canine heart [5,10,11,15]. We have also shown that the O 2 cost of E max increases by 50-100% of the control in failing hearts produced by myocardial acidosis [12], postischemic and post-acidotic Key words: Cardiac energetics, E max , myocardial O 2 consumption, pressure-volume area, PVA.Abstract: Caffeine causes a considerable O 2 waste for positive inotropism in myocardium by complex pharmacological mechanisms. However, no quantitative study has yet characterized the mechanoenergetics of caffeine, particularly its O 2 cost of contractility in the E max -PVA-VO 2 framework. Here, E max is an index of ventricular contractility, PVA is a measure of total mechanical energy generated by ventricular contraction, and VO 2 is O 2 consumption of ventricular contraction. The E max -PVA-VO 2 framework proved to be powerful in cardiac mechanoenergetics. We therefore studied the effects of intracoronary caffeine at concentrations lower than 1 mmol/l on left ventricular (LV) E max and VO 2 for excitationcontraction (E-C) coupling in the excised crosscirculated canine heart. We enhanced LV E max by intracoronary infusion of caffeine after ␤-blockade with propranolol and compared this effect with that of calcium. We obtained the relation between LV VO 2 and PVA with E max as a parameter. We then calculated the VO 2 for the E-C coupling by subtracting VO 2 under KCl arrest from the PVA-independent (or zero-PVA) VO 2 and the O 2 cost of E max as the slope of the E-C coupling VO 2 -E max relation. We found that this cost was 40% greater on average for caffeine than for calcium. This result, for the first time, characterized integratively cardiac mechanoenergetics of the O 2 wasting effect of the complex inotropic mechanisms of intracoronary caffeine at concentrations lower than 1 mmol/l in a beating whole heart.

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Section: Discussionmentioning

confidence: 99%

“…Even a single composite VO 2 -PVA line reflects the O 2 cost of E max [14]. This cost quantitates the energy wasting of the E-C coupling [5,6,[26][27][28][29][30].…”

Section: Methodsmentioning

confidence: 99%

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Mechanoenergetics Characterizing Oxygen Wasting Effect of Caffeine in Canine Left Ventricle.

Takasago

Goto

Hata

et al. 2000

JJP

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“…To better understand myocardial Ca 2ϩ handling, we have recently developed a new integrative method to quantify total Ca 2ϩ handling in the left ventricle (LV) of the canine beating heart [2][3][4][5][6][7]. This method combines LV myocardial contractility (E max ) and O 2 consumption (VO 2 ) with the internal Ca 2ϩ recirculation fraction (RF).…”

mentioning

confidence: 99%

“…We considered the former decay term to reflect the time course of recovery of intracellular Ca 2ϩ from the transiently augmented level caused by extrasystole to the steady-state level. Therefore RF could be calculated from the beat constant of this decay [2][3][4][5][6][7]. The PESP , contractility, arrhythmia, beat constant, extrasystole.…”

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New Calculation of Internal Ca2+ Recirculation Fraction from Alternans Decay of Postextrasystolic Potentiation.

Iribe

Araki

Mohri

et al. 2001

JJP

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Myocardial Ca 2ϩ handling in excitation-contraction (E-C) coupling consumes the second largest fraction of myocardial energy (ATP and hence oxygen) next to cross-bridge cycling in a physiologically working heart [1]. To better understand myocardial Ca 2ϩ handling, we have recently developed a new integrative method to quantify total Ca 2ϩ handling in the left ventricle (LV) of the canine beating heart [2][3][4][5][6][7]. This method combines LV myocardial contractility (E max ) and O 2 consumption (VO 2 ) with the internal Ca 2ϩ recirculation fraction (RF). RF is the fraction of total released Ca 2ϩ that is removed by the sarcoplasmic reticulum (SR) without being extruded transsarcolemmally [8][9][10][11].RF has been obtained from the exponential decay beat constant (but not time constant; see METHODS) of the postextrasystolic potentiation (PESP) when it decays monotonically or exponentially [8][9][10][11]. We have demonstrated, however, that PESP most frequently decays in transient alternans, or with the alteration of large and small contraction, in the excised cross-circulated canine heart preparation [12]. We were then able to characterize this transient alternans decay as the sum of an exponential function and an exponentially decaying sinusoidal function [13]. We considered the former decay term to reflect the time course of recovery of intracellular Ca 2ϩ from the transiently augmented level caused by extrasystole to the steady-state level. Therefore RF could be calculated from the beat constant of this decay [2][3][4][5][6][7]. The PESP Key words: myocardial Ca 2ϩ , contractility, arrhythmia, beat constant, extrasystole. Abstract:In our previous studies, we calculated the internal Ca 2ϩ recirculation fraction (RF) after obtaining the beat decay constant ( e ) of the monoexponential component in the postextrasystolic potentiation (PESP) of the alternans decay by curve fitting. However, this method sometimes suffers from the sensitive variation of e with small noises in the measured contractilities of the 5th and 6th postextrasystolic (PES) beats in the tail of the exponential component. We now succeeded in preventing this problem by a new method to calculate RF without obtaining e . The equation for the calculation in the new method expresses an alternans decay of PESP as a recurrence formula of PESP. It can calculate RF directly from the contractilities of the 1st through the 4th PES beats without any fitting procedure. To evaluate the reliability of the new method, we calculated RF from the alternans decay of PESP of the left ventricle (LV) of the canine excised cross-circulated heart preparation by both the original fitting and the new method.Although there was no significant difference in the mean value of the obtained RF between these two methods, the variance of RF was smaller with the new method than with the original method. Thus the new method proved useful and more reliable than the original fitting method.

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Total Ca handling in canine mild Ca overload failing heart

et al. 1999

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We analyzed total Ca handling of the left ventricle (LV) in the mildly failing heart preparation induced by a temporary intracoronary Ca overloading intervention in eight excised and cross-circulated canine hearts. This Ca intervention consisted of interruption of coronary blood perfusion by Ca-free oxygenated Tyrode perfusion for 10 min followed by high-Ca (16mmol/l) oxygenated Tyrode perfusion for 5 min. This intervention decreased the LV contractility index, Emax (end-systolic maximum elastance), by 40% after restoration of the blood cross-circulation. We expected a Ca overload or paradox failing heart resembling the postischemic stunned heart and being characterized by an increased O2 cost of Emax. However, LV O2 consumption under mechanically unloading conditions decreased by 30% from control without increasing the O2 cost of Emax. To obtain a mechanistic view of this failing heart, we investigated cardiac total Ca handling by our integrative analysis method. In this method, we obtained the internal Ca recirculation fraction (RF) from the decay beat constant of the postextrasystolic potentiation following each sporadic spontaneous extrasystole in these failing LVs. We combined the RF with the decreased Emax and the unchanged O2 cost of Emax in our recently developed formula of total Ca handling. We found that these failing LVs had a slightly but significantly increased RF accompanied by either a slightly increased futile Ca cycling or a slightly decreased Ca reactivity of Emax, or both. Any of these three possible changes can account for the unchanged O2 cost of Emax. This result indicates that the present mildly failing heart has not yet fallen into a typical Ca overload or paradox by the temporary Ca overloading intervention.

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Calcium equally increases the internal calcium recirculation fraction before and after β-blockade in canine left ventricles

Cited by 12 publications

References 23 publications

Mechanoenergetics Characterizing Oxygen Wasting Effect of Caffeine in Canine Left Ventricle.

Mechanoenergetics Characterizing Oxygen Wasting Effect of Caffeine in Canine Left Ventricle.

New Calculation of Internal Ca2+ Recirculation Fraction from Alternans Decay of Postextrasystolic Potentiation.

Total Ca handling in canine mild Ca overload failing heart

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