Zinc-bis-Histidinate Preserves Cardiac Function in a Porcine Model of Cardioplegic Arrest

Powell, Saul R.; Nelson, Ronald J.; Finnerty, JeanMarie; Alexánder, Daniel; Pottanat, George; Kooker, Karlene; Schiff, Robert; Moyse, Jeffrey; Teichberg, Saul; Tortólani, Anthony J.

doi:10.1016/s0003-4975(97)00300-7

Cited by 13 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cardiac adaptation to oxidative stress temporally redistributes systemic Zn into the heart, leading to low serum Zn and increased cardiac Zn levels at the early stage of cardiac pathogenesis (Yarom et al 1977;Ripa et al 1998;Norishima et al 1999). In support of an antioxidant action of Zn in the heart, Zn supplementation indeed significantly protects the heart against the oxidative damage by a variety of oxidative stresses, including isoproterenol (Chvapil & Owen 1977), catecholamine (Singal et al 1981), vitamin D3 (Wrzolek 1985), ischemia or/and perfusion (Powell et al 1994(Powell et al , 1997 and adriamycin (Satoh et al 2000;Ali et al 2002).…”

Section: Zinc Supplementation Prevents Cardiac Toxicity From Non-diabmentioning

confidence: 98%

Zinc and the Diabetic Heart

Song

Wang

et al. 2005

Biometals

View full text Add to dashboard Cite

Zinc (Zn) is an essential mineral that is required for various cellular functions. Its abnormal metabolism is related to certain disorders such as diabetic complications. Oxidative stress has been considered as the major causative factor for diabetic cardiomyopathy. Zn has a critical antioxidant action in protecting the heart from various oxidative stresses. Zn deficiency was found to be a risk factor for cardiac oxidative damage and supplementation with Zn provides a significant prevention of oxidative damage to the heart. Diabetes causes a significant systemic oxidative stress and also often is accompanied by Zn deficiency that increases the susceptibility of the heart to oxidative damage. Therefore, there is a strong rationale to consider the strategy of Zn supplementation to prevent or delay diabetic cardiomyopathy. This short article collects the preliminary evidence, based on our own studies and those by others, for a preventive effect of Zn supplementation on diabetes-induced injury to the heart in animals and under in vitro conditions. Possible mechanisms by which Zn supplementation prevents diabetic heart disease are discussed. They include an antioxidant action of Zn, insulin function and metallothionein induction. In the final section, the future of Zn supplementation for diabetic patients is also briefly discussed. Although Zn supplementation has not been clinically used to prevent diabetic complications, because several issues need to be addressed, the fact that Zn supplementation is being used clinically for other disorders encourages us to explore its direct clinical application for the prevention of diabetic cardiomyopathy.

show abstract

Section: Zinc Supplementation Prevents Cardiac Toxicity From Non-diabmentioning

confidence: 98%

Zinc and the Diabetic Heart

Song

Wang

et al. 2005

Biometals

View full text Add to dashboard Cite

show abstract

“…In the present study, we examine possible mechanisms by which extracellular Zn 2ϩ exposure enhances cardiac relaxation as observed previously at the whole heart (23)(24)(25) and cellular levels (20,39). We found that Zn 2ϩ did not affect myofilament force production, thin-filament sensitivity to calcium activation or Na ϩ /Ca 2ϩ exchanger (NCX), but did reduce L-type channel inward current, sarcoplasmic reticulum (SR) Ca 2ϩ load, and ryanodine receptor (RyR) and phospholamban (PLB) phosphorylation status, which are all consistent with a reduced cellular Ca 2ϩ load that improves relaxation function by a concomitant reduction in diastolic intracellular Ca 2ϩ .…”

mentioning

confidence: 90%

“…Cardiac zinc content correlates positively with ejection fraction (EF) in humans (18), and zinc supplementation to cardioplegic solution protects against the loss of systolic function and enhances diastolic function during and after ischemia-reperfusion injury (23)(24)(25). It has been suggested that zinc combats oxidative stress associated with ischemia-reperfusion and diabetes in part by enhancing the capacity of the zinc-binding protein metallothionein (15), which shields against reactive oxygen species (13, 23-25, 27, 36).…”

mentioning

confidence: 99%

Identifying cellular mechanisms of zinc-induced relaxation in isolated cardiomyocytes

Vick

Vecchio

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Yi T, Vick JS, Vecchio MJ, Begin KJ, Bell SP, Delay RJ, Palmer BM. Identifying cellular mechanisms of zinc-induced relaxation in isolated cardiomyocytes. Am J Physiol Heart Circ Physiol 305: H706-H715, 2013. First published June 28, 2013 doi:10.1152/ajpheart.00025.2013.-We tested several molecular and cellular mechanisms of cardiomyocyte contraction-relaxation function that could account for the reduced systolic and enhanced diastolic function observed with exposure to extracellular Zn 2ϩ . Contraction-relaxation function was monitored in isolated rat and mouse cardiomyocytes maintained at 37°C, stimulated at 2 or 6 Hz, and exposed to 32 M Zn 2ϩ or vehicle. Intracellular Zn 2ϩ detected using FluoZin-3 rose to a concentration of ϳ13 nM in 3-5 min. Peak sarcomere shortening was significantly reduced and diastolic sarcomere length was elongated after Zn 2ϩ exposure. Peak intracellular Ca 2ϩ detected by Fura-2FF was reduced after Zn 2ϩ exposure. However, the rate of cytosolic Ca 2ϩ decline reflecting sarcoplasmic reticulum (SR) Ca 2ϩ -ATPase (SERCA2a) activity and the rate of Na ϩ /Ca 2ϩ exchanger activity evaluated by rapid Na ϩ -induced Ca 2ϩ efflux were unchanged by Zn 2ϩ exposure. SR Ca 2ϩ load evaluated by rapid caffeine exposure was reduced by ϳ50%, and L-type calcium channel inward current measured by whole cell patch clamp was reduced by ϳ70% in cardiomyocytes exposed to Zn 2ϩ . Furthermore, ryanodine receptor (RyR) S2808 and phospholamban (PLB) S16/T17 were markedly dephosphorylated after perfusing hearts with 50 M Zn 2ϩ . Maximum tension development and thinfilament Ca 2ϩ sensitivity in chemically skinned cardiac muscle strips were not affected by Zn 2ϩ exposure. These findings suggest that Zn 2ϩ suppresses cardiomyocyte systolic function and enhances relaxation function by lowering systolic and diastolic intracellular Ca 2ϩ concentrations due to a combination of competitive inhibition of Ca 2ϩ influx through the L-type calcium channel, reduction of SR Ca 2ϩ load resulting from phospholamban dephosphorylation, and lowered SR Ca 2ϩ leak via RyR dephosphorylation. The use of the low-Ca 2ϩ -affinity Fura-2FF likely prevented the detection of changes in diastolic Ca 2ϩ and SERCA2a function. Other strategies to detect diastolic Ca 2ϩ in the presence of Zn 2ϩ are essential for future work.cardiac; myocyte; sarcomere; L-type channel; ryanodine receptor THE IMPORTANCE of zinc and zinc ion (Zn 2ϩ ) in cardiac muscle function is only partially understood at this time. Cardiac zinc content correlates positively with ejection fraction (EF) in humans (18), and zinc supplementation to cardioplegic solution protects against the loss of systolic function and enhances diastolic function during and after ischemia-reperfusion injury (23-25). It has been suggested that zinc combats oxidative stress associated with ischemia-reperfusion and diabetes in part by enhancing the capacity of the zinc-binding protein metallothionein (15), which shields against reactive oxygen species (13, 23-25, 27, 36).Zinc deficiency (Ͻ10.7 M plasm...

show abstract

“…Zinc was shown, for example, to reduce catecholamine-induced cardiac oxidative injury (158,183) and preserve postischemic function in models of cardiac ischemic injury (162,163). Hearts from rats receiving dietary supplementation of the zinc ionophore pyrithione recovered fully from ischemia=reperfusion, via a mechanism that was reported to involve the zinc-mediated protection from degradation of PKC isoforms (101).…”

Section: A Putative Role For Nutritional Zinc Supplementation In Cvdmentioning

confidence: 99%

Zinc and Redox Signaling: Perturbations Associated with Cardiovascular Disease and Diabetes Mellitus

Foster

Samman

2010

Antioxidants & Redox Signaling

130

View full text Add to dashboard Cite

Cellular signal transduction pathways are influenced by the zinc and redox status of the cell. Numerous chronic diseases, including cardiovascular disease (CVD) and diabetes mellitus (DM), have been associated with impaired zinc utilization and increased oxidative stress. In humans, mutations in the MT-1A and ZnT8 genes, both of which are involved in the maintenance of zinc homeostasis, have been linked with DM development. Changes in levels of intracellular free zinc may exacerbate oxidative stress in CVD and DM by impacting glutathione homeostasis, nitric oxide signaling, and nuclear factor-kappa B-dependent cellular processes. Zinc ions have been shown to influence insulin and leptin signaling via the phosphoinositide 3′-kinase/Akt pathway, potentially linking an imbalance of zinc at the cellular level to insulin resistance and dyslipidemia. The oxidative modification of cysteine residues in zinc coordination sites in proteins has been implicated in cellular signaling and regulatory pathways. Despite the many interactions between zinc and cellular stress responses, studies investigating the potential therapeutic benefit of zinc supplementation in the prevention and treatment of oxidative stress-related chronic disease in humans are few and inconsistent. Further well-designed randomized controlled trials are needed to determine the effects of zinc supplementation in populations at various stages of CVD and DM progression.

show abstract

Zinc-bis-Histidinate Preserves Cardiac Function in a Porcine Model of Cardioplegic Arrest

Cited by 13 publications

References 18 publications

Zinc and the Diabetic Heart

Zinc and the Diabetic Heart

Identifying cellular mechanisms of zinc-induced relaxation in isolated cardiomyocytes

Zinc and Redox Signaling: Perturbations Associated with Cardiovascular Disease and Diabetes Mellitus

Contact Info

Product

Resources

About