Magnesium reduces myocardial infarct size via enhancement of adenosine mechanism in rabbits

Matsusaka, Tomoyuki; Hasebe, Naoyuki; Jin, Yin Tie; Kawabe, Jun‐ichi; Kikuchi, Kenjiro

doi:10.1016/s0008-6363(02)00253-5

Cited by 27 publications

(24 citation statements)

References 39 publications

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“…Apart from their antiarrhythmic actions, the three components of the prophylactic antiarrhythmic regimen used in this study, i.e., magnesium sulfate, lidocaine, and amiodarone, have all been shown to protect against myocardial I/R injury (15,17,22). This may have influenced infarct size.…”

Section: Discussionmentioning

confidence: 95%

Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression

Bouma

Noma

Kanemoto

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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The female sex has been associated with improved myocardial salvage after ischemia and reperfusion (I/R). Estrogen, specifically 17beta-estradiol, has been demonstrated to mediate this phenomenon by limiting cardiomyocyte apoptosis. We sought to quantitatively assess the effect of sex, ovarian hormone loss, and I/R on myocardial Bax, Bcl-2, and apoptosis repressor with caspase recruitment domain (ARC) expression. Male (n = 48), female (n = 26), and oophorectomized female (n = 20) rabbits underwent 30 min of regional ischemia and 3 h of reperfusion. The myocardial area at risk and infarct size were determined using a double-staining technique and planimetry. In situ oligo ligation was used to assess apoptotic cell death. Western blot analysis was used to determine proapoptotic (Bax) and antiapoptotic (Bcl-2 and ARC) protein levels in all three ischemic groups and, additionally, in three nonischemic groups. Infarct size (43.7 +/- 3.2%) and apoptotic cell death (0.51 +/- 0.10%) were significantly attenuated in females compared with males (56.4 +/- 1.6%, P < 0.01, and 4.29 +/- 0.95%, P < 0.01) and oophorectomized females (55.7 +/- 3.4%, P < 0.05, and 4.36 +/- 0.51%, P < 0.01). Females expressed significantly higher baseline ARC levels (3.62 +/- 0.29) compared with males (1.78 +/- 0.18, P < 0.01) and oophorectomized females (1.08 +/- 0.26, P < 0.01). Males expressed a significantly higher baseline Bax-to-Bcl-2 ratio (4.32 +/- 0.99) compared with females (0.65 +/- 0.13, P < 0.01) and oophorectomized females (0.42 +/- 0.10, P < 0.01). I/R significantly reduced Bax-to-Bcl-2 ratios in males. In all other groups, ARC levels and Bax-to-Bcl-2 ratios did not significantly change. These results support the conclusion that in females, endogenous estrogen limits I/R-induced cardiomyocyte apoptosis by producing a baseline antiapoptotic profile, which is associated with estrogen-dependent high constitutive myocardial ARC expression.

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Section: Discussionmentioning

confidence: 95%

Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression

Bouma

Noma

Kanemoto

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…Inhibition of NO synthesis reduced infarct size via release of adenosine [624]. Magnesium reduced infarct size also via enhancement of the action of adenosine in rabbits [625]. Over-expression of A1R protected mice against MI [626].…”

Section: Myocardial Infarctionmentioning

confidence: 97%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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“…In experiments on cardiac ischemia-reperfusion, magnesium has been reported to reduce myocardial calcium overload (44), free radical generation (11), and myocardial infarct size (26). High magnesium levels have been reported to suppress ␤-adrenergic desensitization (9).…”

mentioning

confidence: 99%

Magnesium attenuates isoproterenol-induced acute cardiac dysfunction and β-adrenergic desensitization

Jin

Hasebe²,

Matsusaka³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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nervous activation is a crucial compensatory mechanism in heart failure. However, excess catecholamine may induce cardiac dysfunction and ␤-adrenergic desensitization. Although magnesium is known to be a cardioprotective agent, its beneficial effects on acute cardiac dysfunction remain to be elucidated. We examined the effects of magnesium on left ventricular (LV) dysfunction induced by a large dose of isoproterenol in dogs. Sixteen anesthetized dogs underwent a continuous infusion of isoproterenol (1 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) with or without a magnesium infusion (1 mg ⅐ kg Ϫ1 ⅐ min Ϫ1 ). The dose response to small doses of isoproterenol (0.025-0.2 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was tested hourly. A large dose of isoproterenol decreased LV systolic function, increased the time constant of LV isovolumic relaxation, and suppressed the dose response to small doses of isoproterenol in a time-dependent manner. Magnesium significantly attenuated isoproterenol-induced LV systolic and diastolic dysfunction and preserved the dose response to isoproterenol. Serum-ionized calcium significantly decreased with a large dose of isoproterenol but was fully maintained at baseline level with magnesium. A large dose of isoproterenol increased serum lipid peroxide levels and serological markers of myocardial damage, which were significantly suppressed by magnesium. In conclusion, magnesium significantly attenuated excess isoproterenol-induced acute cardiac dysfunction and ␤-adrenergic desensitization. calcium overload; free radical; dog, left ventricular; tau SYMPATHETIC ACTIVATION IS a crucial compensatory mechanism in heart failure, and serum catecholamine levels are an indicator of the clinical severity (8). However, excess catecholamine may actually induce cardiac cell injury, leading to cardiac dysfunction (34). This is one of the rationales for the clinical beneficial effects of ␤-adrenergic receptor blockade on the prognosis and cardiac function in chronic heart failure (7, 13, 27, 32). Excess isoproterenol (ISO), a selective ␤-adrenergic receptor agonist, induces myocardial necrosis and apoptosis, interstitial fibrosis, and left ventricular (LV) hypertrophy and dysfunction (14, 36). The mechanism of cardiac dysfunction induced by excess ISO may be attributed to calcium overload (19) and free radical generation (37). Moreover, excess ISO induces ␤-adrenergic desensitization (18), one of the hallmarks of heart failure, which potentially exacerbates cardiac dysfunction.Magnesium is known as a cardioprotective factor in the treatment of hypertension, ischemic heart disease, and chronic heart failure (2, 21, 38, 43). In experiments on cardiac ischemia-reperfusion, magnesium has been reported to reduce myocardial calcium overload (44), free radical generation (11), and myocardial infarct size (26). High magnesium levels have been reported to suppress ␤-adrenergic desensitization (9). However, the beneficial effects of magnesium in acute heart failure remain to be elucidated.The goal of the present study was to investigate whether magnesium prev...

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Magnesium reduces myocardial infarct size via enhancement of adenosine mechanism in rabbits

Abstract: Magnesium administration has an infarct size limiting effect independent of its effects on myocardial oxygen consumption and incidence of arrhythmia in rabbits. The infarct size limiting effect of magnesium is attributable, at least in part, to augmentation of adenosine mechanism.

Cited by 27 publications

References 39 publications

Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression

Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression

Cardiac purinergic signalling in health and disease

Magnesium attenuates isoproterenol-induced acute cardiac dysfunction and β-adrenergic desensitization

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