Nitrosative Stress and Myocardial Sarcoplasmic Endoreticular Calcium Adenosine Triphosphatase Subtype 2a Activity after Lung Resection in Swine

Heerdt, Paul M.; Lane, Paul; Pan, Brian Y.; Schäefer, Ulrich; Crabtree, Mark J.; Hong, R; Singer, A; Levi, Roberto; Park, Bernard J.

doi:10.1097/01.anes.0000291446.70921.61

Cited by 14 publications

(10 citation statements)

References 32 publications

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“…4,30,31 This dysfunction can result from diabetes mellitus-induced post-translational modifications to SERCA2a, including oxidative (eg, at 674 Cys), advanced glycation, or other modifications of SERCA2a-thiol oxidation. 4,[32][33][34] In the present study, 1-NCA prevented all impairments in both diastolic function and LV SERCA2a expression in diabetic mice compared with vehicle control. Although elucidating the impact of 1-NCA on SERCA2a function was beyond the scope of the current study, HNO is known to undergo thiol-mediated interaction with SERCA2a to acutely enhance its function.…”

Section: -Nca Prevents Diabetes Mellitus-induced LV Diastolic Dysfunsupporting

confidence: 59%

Chronic Administration of the Nitroxyl Donor 1-Nitrosocyclo Hexyl Acetate Limits Left Ventricular Diastolic Dysfunction in a Mouse Model of Diabetes Mellitus In Vivo

Cao

Wong

Rosli

et al. 2015

Circ: Heart Failure

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Background-Nitroxyl (HNO), a redox congener of nitric oxide (NO•), is a novel regulator of cardiovascular function, combining concomitant positive inotropic, lusitropic, and vasodilator properties. Moreover, HNO exhibits myocardial antihypertrophic and superoxide-suppressing actions. Despite these favorable actions, the impact of chronic HNO administration has yet to be reported in the context of cardiomyopathy. Diabetic cardiomyopathy is characterized by early diastolic dysfunction and adverse left ventricular (LV) structural remodeling, with LV superoxide generation playing a major causal role. We tested the hypothesis that the HNO donor 1-nitrosocyclohexylacetate (1-NCA) limits cardiomyocyte hypertrophy and LV diastolic dysfunction in a mouse model of diabetes mellitus in vivo. Methods and Results-Diabetes mellitus was induced in male FVB/N mice using streptozotocin. After 4 weeks, diabetic and nondiabetic mice were allocated to 1-NCA therapy (83 mg/kg per day IP) or vehicle and followed up for a further 4 weeks. Diabetes mellitus-induced LV diastolic dysfunction was evident on echocardiography-derived E and A wave velocities, E:A ratio, deceleration, and isovolumic relaxation times; LV systolic function was preserved. Increased LV cardiomyocyte size, hypertrophic and profibrotic gene expression, and upregulation of LV superoxide were also evident. These characteristics of diabetic cardiomyopathy were largely prevented by 1-NCA treatment. Selectivity of 1-NCA as an HNO donor was demonstrated by sensitivity of acute 1-NCA to L-cysteine but not to hydroxocobalamin in the normal rat heart ex vivo. Conclusions-Our studies provide the first evidence that HNO donors may represent a promising strategy for treatment of diabetic cardiomyopathy and implies therapeutic efficacy in settings of chronic heart failure. (Circ Heart Fail. 2015;8:572-581.

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Section: -Nca Prevents Diabetes Mellitus-induced LV Diastolic Dysfunsupporting

confidence: 59%

Chronic Administration of the Nitroxyl Donor 1-Nitrosocyclo Hexyl Acetate Limits Left Ventricular Diastolic Dysfunction in a Mouse Model of Diabetes Mellitus In Vivo

Cao

Wong

Rosli

et al. 2015

Circ: Heart Failure

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“…28,30 However, serine-16 is the predominant site of PLB phosphorylation, both at baseline and after cardiac challenge. 18,22 285Ab is specific for phosphorylation of PLB at serine-16. Future studies with antibodies specific for threonine-17 phosphorylation will be illuminating.…”

Section: Discussionmentioning

confidence: 99%

“…In previous studies, negligible changes in levels of PLB phosphorylation were detected in isolated pig SR membranes subject to various cardiac challenges. 17,18 However, it is possible that the time required to isolate SR membranes in these studies allowed endogenous phosphatase activity to mask changes in PLB phosphorylation. Therefore, in this study, we analyzed flash-frozen tissue that was rapidly processed in the presence of phosphatase inhibitors and we used positive controls to validate these procedures.…”

Section: Introductionmentioning

confidence: 99%

Insulin-dependent rescue from cardiogenic shock is not mediated by phospholamban phosphorylation

Ablorh

Nitu

Engebretsen

et al. 2009

Clinical Toxicology

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Introduction We used immunoblots to determine whether inotropic and lusitropic effects of high-dose insulin (HDI) in cardiogenic shock, induced by a β-blocker (BB) or a calcium channel blocker (CCB), are mediated by phosphorylation of phospholamban (PLB). PLB is a membrane protein that regulates calcium uptake into the sarcoplasmic reticulum (SR) by inhibition of the cardiac calcium pump (SERCA2a). Phosphorylation of PLB relieves SERCA inhibition, thus enhancing diastolic relaxation and preload. Methods Our Institutional Animal Care and Use Committee approved this research. Swine myocardia from six groups were flash frozen immediately upon death or sacrifice. Groups 1–6 received: (1) no medications, (2) HDI and glucose only, (3) toxic propranolol infusions and saline resuscitation, (4) toxic propranolol infusions and HDI resuscitation, (5) toxic verapamil infusions and saline resuscitation, and (6) toxic verapamil infusions and HDI resuscitation. Groups 3–6 were resuscitated for 4 h. Tissue samples from all six groups were analyzed by quantitative immunoblots, using antibodies to both unphosphorylated PLB (uPLB) and phosphorylated PLB (pPLB), to determine the total PLB content and the fraction of PLB phosphorylated. Results There were no differences in either pPLB or total PLB in cardiac tissue among any of the six groups. However, infusion of a pig with the β-adrenergic agonist, isoproterenol, produced enhanced PLB phosphorylation. Conclusion The mechanism by which HDI produces its inotropic and lusitropic effects in CCB- and BB-induced cardiovascular toxicity, resulting in resuscitation, is not due to changes in phosphorylation of PLB or a change in the total PLB in the SR.

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“…The surgery-induced injury depends on the duration and invasiveness of the procedure [13][14][15], the lung resection type [16] and location of the thoracic surgical procedure [17]. Hypoperfusion induced by hypoxic pulmonary vasoconstriction [18], dysfunction of the surfactant system [19] and oxidative stress resulting from reexpansion [20], ischemia and reperfusion [21] may increase alveolar injury during and after thoracic surgery as observed in rabbit lungs after complete collapse and reventilation [22]. Impaired lymphatic drainage and fluid overload were also identified as corroborating the deleterious effect of mechanical ventilation.…”

Section: Pathogenesis Of Lung Injury: Surgical Traumamentioning

confidence: 99%

Protective Ventilatory Approaches to One-Lung Ventilation: More than Reduction of Tidal Volume

Kozian

Schilling

2014

Curr Anesthesiol Rep

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The thoracic surgical patient is at special risk for increased postoperative pulmonary complications, such as atelectasis, impaired lung function and pneumonia, as well as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) with high mortality after lung resections. One-lung ventilation (OLV) induces proinflammatory responses especially in the ventilated lung, based on mechanical stress, persistent hyperperfusion, increased gas content and ventilation to perfusion mismatching. ALI may occur, even in previously healthy lungs. Ventilation management can cause and exacerbate but also attenuate ALI after OLV. Protective ventilatory approaches can improve the outcome by minimizing lung damage. However, ventilation with lower tidal volumes during OLV does not completely abolish alveolar inflammation. The present review addresses the effects of OLV and their role in ventilator-induced lung injury. Lung protective strategies to one-lung ventilation that additionally include reduction of cyclic alveolar recruitment, PEEP ventilation, limitation of inspired oxygen and pharmacological preconditioning by volatile anesthetics are discussed.

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Nitrosative Stress and Myocardial Sarcoplasmic Endoreticular Calcium Adenosine Triphosphatase Subtype 2a Activity after Lung Resection in Swine

Cited by 14 publications

References 32 publications

Chronic Administration of the Nitroxyl Donor 1-Nitrosocyclo Hexyl Acetate Limits Left Ventricular Diastolic Dysfunction in a Mouse Model of Diabetes Mellitus In Vivo

Chronic Administration of the Nitroxyl Donor 1-Nitrosocyclo Hexyl Acetate Limits Left Ventricular Diastolic Dysfunction in a Mouse Model of Diabetes Mellitus In Vivo

Insulin-dependent rescue from cardiogenic shock is not mediated by phospholamban phosphorylation

Protective Ventilatory Approaches to One-Lung Ventilation: More than Reduction of Tidal Volume

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