Ryanodine Decreases Internal Ca2+ Recirculation Fraction of the Canine Heart as Studied by Postextrasystolic Transient Alternans.

Hata, Yoshiki; Shimizu, Juichiro; Hosogi, Shingo; Matsubara, Hiromi; Araki, Junichi; Ohe, Tohru; Takaki, Miyako; Takasago, Toshiyuki; Taylor, T. H.; Suga, Hiroyuki

doi:10.2170/jjphysiol.47.521

Cited by 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%

“…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%

“…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%

“…However, postischemic stunning [14,31], acidosis [12], postacidotic stunning [13] and ryanodine treatment [16,26,29] increase this cost by 50-100%. Thus, our E max -PVA-VO 2 framework proved to quantitate the O 2 cost of E max explicitly at the beating whole heart level [12][13][14]16].…”

Section: Methodsmentioning

confidence: 99%

“…It also increases the open probability of the ryanodine-sensitive calcium (Ca 2ϩ ) release channels in the sarcoplasmic reticulum (SR) [21,23,25]. This causes futile Ca 2ϩ cycling analogous to ryanodine treatment at nanomolar concentrations, increasing the O 2 cost of E max [16,26]. On the other hand, caffeine increases the Ca 2ϩ responsiveness of contractility [3,4,19,22] so that a smaller amount of released Ca 2ϩ achieves a comparable contractility.…”

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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%

Section: Methodsmentioning

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%

Section: Methodsmentioning

confidence: 99%

mentioning

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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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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Myocardial mechanical restitution and potentiation partly underlie alternans decay of postextrasystolic potentiation: Simulation

et al. 1999

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We have reported that the postextrasystolic potentiation (PESP) decays in alternans or monotonically, respectively, depending on whether the first postextrasystolic beat interval has a compensatory pause or not, in the canine left ventricle. To get better mechanistic insight into the alternans PESP decay, we hypothesized that the myocardial mechanical restitution and potentiation could partly account for both types of PESP decay. To test this hypothesis, we simulated PESP decay on a computer using a documented equation combining myocardial mechanical restitution and potentiation. We changed the first postextrasystolic beat interval after a fixed extrasystolic beat interval without changing regular and other postextrasystolic beat intervals. The simulated PESP decayed in alternans or monotonically as a function only of the first postextrasystolic beat interval. Thus, the myocardial mechanical restitution and potentiation could partly account for both alternans and monotonic decay of PESP. We conclude that myocardial mechanical restitution and potentiation may partly underlie the initial two alternating beats, the first beat being the most potentiated and the second beat being the most depressed, of alternans PESP decay in the canine heart.

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Ryanodine Decreases Internal Ca2+ Recirculation Fraction of the Canine Heart as Studied by Postextrasystolic Transient Alternans.

Cited by 23 publications

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

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

Total Ca handling in canine mild Ca overload failing heart

Myocardial mechanical restitution and potentiation partly underlie alternans decay of postextrasystolic potentiation: Simulation

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