Protection of human left ventricular myocardium from cutting injury with 2,3-butanedione monoxime.

Mulieri, Louis A.; Hasenfuß, Gerd; Ittleman, Frank P.; Blanchard, E. M.; Alpert, Norman R.

doi:10.1161/01.res.65.5.1441

Cited by 242 publications

(153 citation statements)

References 18 publications

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“…Adult mice, weighing between 20 and 30 g, were anesthetized/euthanized by either halothane inhalation, cervical dislocation, or an injection of urethane. After intracardiac heparinization, the heart was rapidly excised using a bilateral thoracotomy and placed in Krebs-Henseleit buffer containing (in mM) 120 NaCl, 5 KCl, 2 MgSO 4, 1.2 NaH2PO4, 20 NaHCO3, 0.25 Ca 2ϩ , and 10 glucose (pH 7.4) Additionally, 20 mM 2,3-butanedionemonoxime (BDM) was added to the dissection buffer to prevent cutting injury (28). The effects of BDM after a brief exposure have been found to be reversible (22).…”

Section: Methodsmentioning

confidence: 99%

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

Janssen

2010

American Journal of Physiology-Heart and Circulatory Physiology

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Janssen PM. Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere. Am J Physiol Heart Circ Physiol 299: H1092-H1099, 2010. First published July 23, 2010; doi:10.1152/ajpheart.00417.2010.-The regulation of myocardial contraction and relaxation kinetics is currently incompletely understood. When the amplitude of contraction is increased via the Frank-Starling mechanism, the kinetics of the contraction slow down, but when the amplitude of contraction is increased with either an increase in heart rate or via ␤-adrenergic stimulation, the kinetics speed up. It is also unknown how physiological mechanisms affect the kinetics of contraction versus those of relaxation. We investigated contraction-relaxation coupling in isolated trabeculae from the mouse and rat and stimulated them to contract at various temperatures, frequencies, preloads, and in the absence and presence of ␤-adrenergic stimulation. In each muscle at least 16 different conditions were assessed, and the correlation coefficient of the speed of contraction and relaxation was very close (generally Ͼ0.98). Moreover, in all but one of the analyzed murine strains, the ratio of the minimum rate of the derivative of force development (dF/dt) over maximum dF/dt was not significantly different. Only in trabeculae isolated from myosin-binding protein-C mutant mice was this ratio significantly lower (0.61 Ϯ 0.07 vs. 0.84 Ϯ 0.02 in 11 other strains of mice). Within each strain, this ratio was unaffected by modulation of length, frequency, or ␤-adrenergic stimulation. Rat trabeculae showed identical results; the balance between kinetics of contraction and relaxation was generally constant (0.85 Ϯ 0.04). Because of the great variety in underlying excitation-contraction coupling in the assessed strains, we concluded that contraction-relation coupling is a property residing in the cardiac sarcomere. trabeculae; mouse; rat; calcium handling; exitation-contraction coupling NOT ONLY IS THE FORCEFULNESS of contraction of the myocardium important, but the speed at which the contraction and relaxation takes place is a critical determinant of cardiac performance. When the heart cannot relax sufficiently fast, and as a result cannot adequately fill the ventricles before the next excitation stimulus, cardiac output is compromised. Whether called heart failure with preserved ejection fraction, diastolic dysfunction, or impaired myocardial relaxation, inadequate relaxation kinetics of the heart pose a clinical problem that affects a very large fraction of patients with cardiac pathology (5, 16). To treat, manage, or possibly cure impaired myocardial relaxation kinetics, a better understanding of the cardiac relaxation process at the level of the cardiac muscle is warranted. It has become increasingly clear that myocardial relaxation is not a mere passive process that follows a contraction but a complex systems biology property that is brought about by a multitude of factors (30). These factors include cytosolic Ca 2ϩ ...

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Section: Methodsmentioning

confidence: 99%

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

Janssen

2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Myocardial Strip Preparation-Mice were killed by cervical dislocation, and the hearts were rapidly excised and placed in O 2 (95%)/CO 2 (5%)-bubbled Krebs solution containing 30 mM 2,3-butanedione monoxime at 22°C (29). The right ventricle was trimmed, and the papillary muscles from the left ventricle were removed.…”

Section: Methodsmentioning

confidence: 99%

“…The right ventricle was trimmed, and the papillary muscles from the left ventricle were removed. Papillary muscles were dissected to yield at least three thin strips (ϳ100 -140 m in diameter and ϳ600 m in length) consisting of longitudinally oriented bundles of myocytes as described previously (29,30). Strips were skinned for 2 h at 22°C and stored at Ϫ20°C for no more than 1 week.…”

Section: Methodsmentioning

confidence: 99%

The Essential Light Chain N-terminal Extension Alters Force and Fiber Kinetics in Mouse Cardiac Muscle

Miller

Palmer

Ruch

et al. 2005

Journal of Biological Chemistry

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The functional significance of the actin-binding region at the N terminus of the cardiac myosin essential light chain (ELC) remains elusive. In a previous experiment, the endogenous ventricular ELC was replaced with a protein containing a 10-amino acid deletion at positions 5-14 (ELC1v⌬5-14, referred to as 1v⌬5-14), a region that interacts with actin (Sanbe, A., Gulick, J., Fewell, J., and Robbins, J. (2001) J. Biol. Chem. 276, 32682-32686). 1v⌬5-14 mice showed no discernable mutant phenotype in skinned ventricular strips. However, because the myofilament lattice swells upon skinning, the mutant phenotype may have been concealed by the inability of the ELC to reach the actin-binding site. Using the same mouse model, we repeated earlier measurements and performed additional experiments on skinned strips osmotically compressed to the intact lattice spacing as determined by x-ray diffraction. 1v⌬5-14 mice exhibited decreased maximum isometric tension without a change in calcium sensitivity. The decreased force was most evident in 5-6-month-old mice compared with 13-15-month-old mice and may account for the greater ventricular wall thickness in young 1v⌬5-14 mice compared with age-matched controls. No differences were observed in unloaded shortening velocity at maximum calcium activation. However, 1v⌬5-14 mice exhibited a significant difference in the frequency at which minimum complex modulus amplitude occurred, indicating a change in cross-bridge kinetics. We hypothesize that the ELC N-terminal extension interaction with actin inhibits the reversal of the power stroke, thereby increasing isometric force. Our results strongly suggest that an interaction between residues 5-14 of the ELC N terminus and the C-terminal residues of actin enhances cardiac performance.

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“…For many years this limited the choice of animals from which satisfactory preparations could be obtained, to rats, guinea pigs, rabbits, and kittens (right ventricle only). The heart species and papillary muscle size constraints have been abolished, however, since Mulieri et al [50] showed that the addition of compound 2,3-butanedione monoxime (BDM) to a physiological buffer solution protects the myocardium against dissection damage, thereby allowing small viable preparations to be obtained from the human left ventricle [51]. By making use of BDM, we have shown [52] that large muscles dissected from the left ventricle of rats have normal mechanical and energetic properties.…”

Section: (I) Whole Heartsmentioning

confidence: 98%

Cardiac Basal Metabolism.

Gibbs

Loiselle²

2001

JJP

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The cardiac basal metabolism is the rate of energy expenditure of the quiescent myocardium. It is also called the resting metabolism or the arrested heart metabolism. It has been measured in numerous ways, and in vivo there is good evidence that it accounts for about 1/5 to 1/3 of the total energy flux. The difficulty arises, however, when the heart is stopped because the magnitude of the basal metabolism depends, as blood viscosity, on how and under what physiological condition it is measured. It is possible for the in vivo basal value to fall to less than 1/5 of its original value without cellular damage or to increase to values 5 times greater than its probable in vivo magnitude (i.e., to rise to values in excess of the energy flux of the normally beating heart) by altering the composition of the perfusion medium. We have written on this subject several times [1][2][3], but believe that developments in knowledge now make it possible for us to speculate in a more informed manner. Since several million openheart operations are performed on arrested hearts worldwide each year, it would seem imperative that we understand the cellular mechanisms that can change the magnitude of basal metabolism.A. V. Hill [4] has pointed out that in examining physiological activities, it is necessary to assume a baseline from which some quantity or rate can be measured. If the energy flux produced by the beating heart were very large compared with the energy flux of the arrested heart, baseline ambiguity would be relatively unimportant. But this is not so in regard to the heart; its basal metabolism is high. Within a species, the basal metabolism of cardiac tissue is several-fold higher than the resting metabolism of skeletal muscle and is an order of magnitude greater than the resting metabolism of amphibian skeletal muscle.Species differences are clearly evident in the magnitude of cardiac basal metabolism, and we believe that the major reason for these differences relates to the leakiness of cell membranes, such as those of the sarcolemma and sarcoplasmic reticulum and those of Japanese Journal of Physiology, 51, 399-426, 2001 Key words: whole hearts, isolated preparations, biochemical contributors, modifiers, species difference, temperature, substrate, hypoxia. Abstract:We endeavor to show that the metabolism of the nonbeating heart can vary over an extreme range: from values approximating those measured in the beating heart to values of only a small fraction of normal-perhaps mimicking the situation of nonflow arrest during cardiac bypass surgery. We discuss some of the technical issues that make it difficult to establish the magnitude of basal metabolism in vivo. We consider some of the likely contributors to its magnitude and point out that the biochemical reasons for a sizable fraction of the heart's basal ATP usage remain unresolved. We consider many of the physiological factors that can alter the basal metabolic rate, stressing the importance of substrate supply. We point out that the protective effect of hypothermia ...

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Protection of human left ventricular myocardium from cutting injury with 2,3-butanedione monoxime.

Cited by 242 publications

References 18 publications

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

Kinetics of cardiac muscle contraction and relaxation are linked and determined by properties of the cardiac sarcomere

The Essential Light Chain N-terminal Extension Alters Force and Fiber Kinetics in Mouse Cardiac Muscle

Cardiac Basal Metabolism.

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