Altered calcium handling in left ventricular pressure-overload hypertrophy as detected with aequorin in the isolated, perfused ferret heart.

Bentivegna, L; Ablin, L.; Kihara, Yasuki; Morgan, James P.

doi:10.1161/01.res.69.6.1538

Cited by 42 publications

(19 citation statements)

References 22 publications

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“…At the end of the experiment, the heart was perfused with a 50 mM 95% Ca 2ϩ -5% Triton X-100 solution, which lysed the cells and exposed the remaining aequorin to high amounts of Ca 2ϩ (3). Luminescence signals to be converted to Ca 2ϩ signals, L, were normalized by the total light emission, Lmax, which was estimated as the integral of the aequorin signal collected during the lysis procedure multiplied by the rate constant for aequorin consumption (2.11/s) (3).…”

Section: Methodsmentioning

confidence: 99%

Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart

Mohri

Shimizu

Mika

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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hoff. Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart. Am J Physiol Heart Circ Physiol 284: H1119-H1123, 2003. First published November 21, 2002 10.1152/ajpheart.00378. 2002We investigated the mechanism of positive inotropism of electric currents applied during the absolute refractory period. Ten Langendorff-perfused ferret hearts were instrumented to measure isovolumic left ventricular pressure (LVP) and the aequorin luminescence. Biphasic squarewave electric currents (Ϯ20 mA, total duration 30 ms) were delivered between pairs of electrodes. Six hearts were per- ]i were increased significantly from 48.7 Ϯ 8.18 to 56.3 Ϯ 6.11 mmHg and from 0.61 Ϯ 0.11 to 1.17 Ϯ 0.20 M, respectively (P Ͻ 0.05). In conclusion, positive inotropism of such electrical currents was due to increased peak [Ca 2ϩ ]i and Ca 2ϩ responsiveness of the myofilaments did not change significantly. calcium responsiveness; aequorin; ␤-blocker STUDIES USING CURRENT CLAMP techniques have shown that increases in either the duration or amplitude of the action potential enhance cardiac contractility by increasing transarcolemmal Ca 2ϩ entry (1, 15). This results in sarcoplasmic reticular Ca 2ϩ loading and an increase in the peak of the intracellular Ca 2ϩ transient (15). It has recently been reported (5) that extracellularly applied electric fields can prolong action potential duration, influence action potential amplitude and similarly enhance myocardial contractility in isolated papillary muscles. When applied locally to intact canine hearts, such electric impulses enhance myocardial contractility in the region of signal application, an effect that results in enhanced global contractility (10). These signals also appear effective in enhancing contractility in animals and humans with heart failure (11-13). However, the mechanism of regional myocardial contractility enhancement with extracellular electrical impulses has not been clarified.The purpose of the present study was to test the hypothesis that the primary inotropic mechanism of cardiac contractility modulating (CCM) electrical impulses, analogous to voltage-clamp techniques, is by enhancing peak intracellular Ca 2ϩ . The effects of CCM signals on myofilament Ca 2ϩ sensitivity were tested by measuring CCM effects at different extracellular Ca 2ϩ concentration ([Ca 2ϩ ] o ). The contribution of ␤-adrenergic stimulation to inotropic effects of CCM signals were investigated through studies performed in the presence of high-dose ␤-blockers. METHODS

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Section: Methodsmentioning

confidence: 99%

Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart

Mohri

Shimizu

Mika

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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“…Saturation transfer 31P-NMR studies in the setting of myocardial hypertrophy have suggested that CK forward flux is reduced (as compared with normal) during inotropic stimulation (38). Alterations in calcium (Ca2") dynamics, and the Ca2" ATPase activities ofmyosin and the sarcoplasmic reticulum have also been described in hypertrophied myocardium, as have abnormalities ofthe mitochondrial/myofibrillar ratio and capillary to mitochondrial diffusion distances (30,(39)(40)(41). Lastly, there is evidence of a switch in substrate preference away from fatty acid utilization and toward glucose in hypertrophied myocardium (33,(42)(43)(44).…”

Section: Myocardial Bloodflow Myocardial Blood Flows Measuredmentioning

confidence: 99%

Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

et al. 1993

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Transmurally localized 31P-nuclear magnetic resonance spectroscopy (NMR) was used to study the effect of severe pressure overload left ventricular hypertrophy (LVH) on myocardial high energy phosphate content. Studies were performed on 8 normal dogs and 12 dogs with severe left ventricular hypertrophy produced by banding the ascending aorta at 8 wk of age. Spatially localized 31P-NMR spectroscopy provided measurements of the transmural distribution of myocardial ATP, phosphocreatine (CP), and inorganic phosphate (Pi); spectra were calibrated from measurements of ATP content in myocardial biopsies using HPLC. Blood flow was measured with microspheres. In hypertrophied hearts during basal conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio by 32% in comparison with normal. Increasing myocardial blood flow with adenosine did not correct these abnormalities, indicating that they were not the result of persistent hypoperfusion. Atrial pacing at 200 and 240 beats per min caused no change in high energy phosphate content in normal hearts but resulted in further CP depletion with Pi accumulation in the inner left ventricular layers of the hypertrophied hearts. These changes were correlated with redistribution of blood flow away from the subendocardium in LVH hearts. These findings demonstrate that high energy phosphate levels and the CP/ATP ratio are significantly decreased in severe LVH. These abnormalities are proportional to the degree of hypertrophy but are not the result of persistent abnormalities of myocardial perfusion. In contrast, depletion of CP and accumulation of Pi during tachycardia in LVH are closely related to the pacing-induced perfusion abnormalities and likely reflect subendocardial ischemia. (J. Clin. Invest. 1993. 92:993-1003

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“…The spontaneously hypertensive rat (SHR) is a model that in many respects parallels the course of human hypertensive heart disease. Studies of both failing human 13 and hypertrophied and failing SHR 4 -5 myocardia reveal altered calcium transients and impaired force development; however, the possible role of altered intracellular calcium handling in the development of depressed contractile function during the transition from compensated hypertrophy to failure remains unclear. Recent isolated muscle studies have demonstrated differences systolic pressure, and ±dP/dt fell in SHR-F hearts.…”

Section: Effects Of Treppe and Calcium On Intracellular Calcium And Fmentioning

confidence: 99%

“…The spontaneously hypertensive rat (SHR) is a model that in many respects parallels the course of human hypertensive heart disease. Studies of both failing human 13 ], and pressure decrease in parallel in the SHR-F heart with increasing stimulation rate, suggesting that impaired calcium cycling may contribute to compromised pump function in the SHR-F heart. (Hypertension.…”

mentioning

confidence: 99%

Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

Brooks¹,

Bing²,

Litwin³

et al. 1994

Hypertension

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We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca 2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30°C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O 2 /5% CO 2 ) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca 2+ ]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca 2+ ] o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca 2+ ]| and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca 2+ ]i, peak R elatively few models of cardiac pressure overload have stable hypertrophy persisting over most of the animal's life followed by a state in which chamber and muscle function are impaired. The spontaneously hypertensive rat (SHR) is a model that in many respects parallels the course of human hypertensive heart disease. Studies of both failing human 13 ], and pressure decrease in parallel in the SHR-F heart with increasing stimulation rate, suggesting that impaired calcium cycling may contribute to compromised pump function in the SHR-F heart. (Hypertension. 1994^4J47-356.) Keywords • calcium • heart hypertrophy muscle, cardiac heart failure, congestive in the force-frequency response between failing and nonfailing human myocardia and a reduced ability of the failing heart to increase force at increasing stimulation rates.6 Studies of isolated ventricular strips from failing human ventricles demonstrate that increased stimulation rates enhance disturbances in calcium handling 1 ' 2 and force development.6 It is well recognized that treppe and increasing [Ca 2+ ] o lead to an increase in [Ca 2+ ], and the number of occupied crossbridges per unit time, which in turn results in an increase in myocardial energy demands. In addition, both of these interventions lead to increases in [Ca 2+ ], and a greater load on intracellular calcium control systems. However, one problem with isolated muscle studies is the uncertainty regarding diffusion, inherent in isolated muscle studies, and the applicability to in vivo physiology. To bridge the gap between isolated muscle studies and in vivo physiology, we have carried out studies in the isolated perfused heart prepa...

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Altered calcium handling in left ventricular pressure-overload hypertrophy as detected with aequorin in the isolated, perfused ferret heart.

Cited by 42 publications

References 22 publications

Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart

Electric currents applied during refractory period enhance contractility and systolic calcium in the ferret heart

Bioenergetic abnormalities associated with severe left ventricular hypertrophy.

Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

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