Endogenous Ouabain Changes Rapidly During Cardiac Pulmonary by Pass

Bignami, Elena

doi:10.4172/2157-7536.s3-002

Cited by 6 publications

(9 citation statements)

References 32 publications

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“…Thus, we find that the adrenal hormone EO, released under stress conditions (15, 36), is able to identify those patients who have a higher probability to develop postoperative AKI. Furthermore, the experimental studies in rats indicate that small sustained increases of plasma ouabain (i.e., two-fold the basal level and similar to those observed in humans) is itself sufficient to trigger the deterioration of renal function as measured by increased plasma creatinine, reduction of creatinine clearance, increased proteinuria, and decreased expression of podocyte nephrin; the latter being a structural protein involved in the formation of the glomerular filtration barrier (37).…”

Section: Discussionmentioning

confidence: 80%

Preoperative Endogenous Ouabain Predicts Acute Kidney Injury in Cardiac Surgery Patients*

Bignami¹,

Casamassima²,

Frati³

et al. 2013

Critical Care Medicine

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Objectives Acute kidney injury is a frequent complication of cardiac surgery and increases morbidity and mortality. As preoperative biomarkers predicting the development of acute kidney injury are not available, we have tested the hypothesis that preoperative plasma levels of endogenous ouabain may function as this type of biomarker. Rationale and Design Endogenous ouabain is an adrenal stress hormone associated with adverse cardiovascular outcomes. Its involvement in acute kidney injury is unknown. With studies in patients and animal settings, including isolated podocytes, we tested the above mentioned hypothesis. Patients Preoperative endogenous ouabain was measured in 407 patients admitted for elective cardiac surgery and in a validation population of 219 other patients. We also studied the effect of prolonged elevations of circulating exogenous ouabain on renal parameters in rats and the influence of ouabain on podocyte proteins both “in vivo” and “in vitro.” Main Results In the first group of patients, acute kidney injury (2.8%, 8.3%, 20.3%, p < 0.001) and ICU stay (1.4 ± 0.38, 1.7 ± 0.41, 2.4 ± 0.59 days, p = 0.014) increased with each incremental preoperative endogenous ouabain tertile. In a linear regression analysis, the circulating endogenous ouabain value before surgery was the strongest predictor of acute kidney injury. In the validation cohort, acute kidney injury (0%, 5.9%, 8.2%, p < 0.0001) and ICU stay (1.2 ± 0.09, 1.4 ± 0.23, 2.2 ± 0.77 days, p = 0.003) increased with the preoperative endogenous ouabain tertile. Values for preoperative endogenous ouabain significantly improved (area under curve: 0.85) risk prediction over the clinical score alone as measured by integrate discrimination improvement and net reclassification improvement. Finally, in the rat model, elevated circulating ouabain reduced creatinine clearance (–18%, p < 0.05), increased urinary protein excretion (+ 54%, p < 0.05), and reduced expression of podocyte nephrin (–29%, p < 0.01). This last finding was replicated ex vivo by incubating podocyte primary cell cultures with low-dose ouabain. Conclusions Preoperative plasma endogenous ouabain levels are powerful biomarkers of acute kidney injury and postoperative complications and may be a direct cause of podocyte damage.

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Section: Discussionmentioning

confidence: 80%

Preoperative Endogenous Ouabain Predicts Acute Kidney Injury in Cardiac Surgery Patients*

Bignami¹,

Casamassima²,

Frati³

et al. 2013

Critical Care Medicine

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“…In order to support the hypothesis that EO was secreted during hemodynamics stress [ 40 ], we investigated the change in EO plasmatic level according to different kind of cardiac pathology or surgical technique.…”

Section: Resultsmentioning

confidence: 99%

Endogenous Ouabain: An Old Cardiotonic Steroid as a New Biomarker of Heart Failure and a Predictor of Mortality after Cardiac Surgery

Simonini

Pozzoli

Bignami

et al. 2015

BioMed Research International

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Cardiovascular diseases remain the main cause of mortality and morbidity worldwide; primary prevention is a priority for physicians. Biomarkers are useful tools able to identify high-risk individuals, guide treatments, and determine prognosis. Our aim is to investigate Endogenous Ouabain (EO), an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. In a population of 845 patients undergoing elective cardiac surgery, we have investigated the relationships between EO and echocardiography parameters/plasmatic biomarker of cardiac function. EO was found to be correlated negatively with left ventricular EF (p = 0.001), positively with Cardiac End-Diastolic Diameter (p = 0.047), and positively with plasmatic NT-proBNP level (p = 0.02). Moreover, a different plasmatic EO level (both preoperative and postoperative) was found according to NYHA class (p = 0.013). All these results have been replicated on an independent cohort of patients (147 subjects from US). Finally, a higher EO level in the immediate postoperative time was indicative of a more severe cardiological condition and it was associated with increased perioperative mortality risk (p = 0.023 for 30-day morality). Our data suggest that preoperative and postoperative plasmatic EO level identifies patients with a more severe cardiovascular presentation at baseline. These patients have a higher risk of morbidity and mortality after cardiac surgery.

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“…However, with the advent of end stage failure and near zero urinary excretion, plasma EO rises substantially into the low nanomolar range 23 . This scenario, analogous to unwanted and uncontrollable digitalization, is worrisome in terms of the potential for undesirable cardiac and vasopressor effects, and because neither hemodialysis nor peritoneal dialysis are effective in removing EO 23,98 . Further, among patients with ESRD in dialysis, plasma EO was strongly associated with left ventricular mass and geometry 23 .…”

Section: Implications For Therapymentioning

confidence: 99%

“…Indeed, circulating EO rises with an interesting time course during the induction of anesthesia in patients about to undergo elective cardiac surgery 98 . In a follow up cross-sectional study, the preoperative plasma levels of EO were measured in 407 patients admitted for cardiac surgery and in a second (validation) population of 219 patients.…”

Section: Implications For Therapymentioning

confidence: 99%

Endogenous Cardiotonic Steroids in Kidney Failure: A Review and an Hypothesis

Hamlyn

Manunta

2015

Advances in Chronic Kidney Disease

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In response to progressive nephron loss, volume and humoral signals in the circulation have increasing relevance. These signals, including plasma sodium, angiotensin II and those related to volume status, activate a slow neuromodulatory pathway within the central nervous system (CNS). The slow CNS pathway includes specific receptors for angiotensin II, mineralocorticoids, and endogenous ouabain (EO). Stimulation of the pathway leads to elevated sympathetic nervous system activity (SNA) and increased circulating EO. The sustained elevation of circulating EO (or ouabain) stimulates central and peripheral mechanisms that amplify the impact of SNA on vascular tone. These include: changes in synaptic plasticity in the brain and sympathetic ganglia that increase preganglionic tone and amplify ganglionic transmission, amplification of the impact of SNA on arterial tone in the vascular wall, and the reprogramming of calcium signaling proteins in arterial myocytes. These increase SNA, raise basal and evoked arterial tone, and elevate blood pressure (BP). In the setting of chronic kidney disease, we suggest that sustained elevation of the slow CNS pathway, plasma EO and the cardiotonic steroid marinobufagenin (MBG), comprise a feed-forward system that raises BP and accelerates kidney and cardiac damage. Block of the slow CNS pathway and/or circulating EO and MBG may reduce BP and slow the progression to end stage renal disease.

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Endogenous Ouabain Changes Rapidly During Cardiac Pulmonary by Pass

Cited by 6 publications

References 32 publications

Preoperative Endogenous Ouabain Predicts Acute Kidney Injury in Cardiac Surgery Patients*

Preoperative Endogenous Ouabain Predicts Acute Kidney Injury in Cardiac Surgery Patients*

Endogenous Ouabain: An Old Cardiotonic Steroid as a New Biomarker of Heart Failure and a Predictor of Mortality after Cardiac Surgery

Endogenous Cardiotonic Steroids in Kidney Failure: A Review and an Hypothesis

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