LINCS: L-NAME (a NO synthase inhibitor) In the treatment of refractory Cardiogenic Shock A prospective randomized study

Cotter, Gad; Kaluski, Edo; Milo, Olga; Blatt, Alex; Salah, Ahmed; Hendler, Alberto; Krakover, Ricardo; Golick, A.; Vered, Zvi

doi:10.1016/s0195-668x(03)00193-3

Cited by 141 publications

(86 citation statements)

References 22 publications

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“…4,12,13 The present analysis elucidated the role that perturbations of the NO synthetic pathway may play in CS by quantifying systemic levels of arginine-related metabolites involved in NO biosynthesis. The results demonstrate that levels of several metabolites and protein products of oxidative stress are abnormal in patients with CS and that levels of some metabolites correlate with hemodynamic abnormalities and mortality risk, suggesting their possible utility as prognostic indicators.…”

Section: Discussionmentioning

confidence: 99%

“…11 Some preliminary clinical studies suggest that these hemodynamic effects may increase survival and decrease the need for support with intra-aortic balloon pumps and mechanical ventilation. 4,12,13 Despite evidence that NOS and NO play a role in CS, little is known about the levels of the NOS substrate arginine and its metabolites. Arginine availability may limit NO synthesis, particularly in cells expressing iNOS.…”

Section: Clinical Perspective P 2324mentioning

confidence: 99%

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Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction

et al. 2007

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Background-It is unclear whether abnormalities of arginine and nitric oxide metabolism are related to hemodynamic dysfunction and mortality in patients with cardiogenic shock (CS) after acute myocardial infarction. Methods and Results-Plasma metabolites reflecting arginine bioavailability, nitric oxide metabolism, and protein oxidation were analyzed by mass spectrometry in patients with CS (nϭ79) and age-and gender-matched patients with coronary artery disease and normal left ventricular function (nϭ79). CS patients had higher levels of asymmetric dimethylarginine (ADMA; PϽ0.0001), symmetric dimethylarginine (PϽ0.0001), monomethylarginine (Pϭ0.0003), nitrotyrosine (PϽ0.0001), and bromotyrosine (PϽ0.0001) and lower levels of arginine (PϽ0.0001), ratio of arginine to ornithine (Pϭ0.03), and ratio of arginine to ornithine plus citrulline) (Pϭ0.0003). CS patients with elevated ADMA levels were 3.5-fold (95% confidence interval, 1.4 to 11.3; Pϭ0.02) more likely to die in 30 days than patients with low ADMA levels. ADMA remained the only independent predictor of mortality on multiple logistic regression analysis. In patients with normal renal function, symmetric dimethylarginine levels inversely correlated with mean arterial pressure and systemic vascular resistance, whereas levels of ADMA correlated with pulmonary capillary wedge pressure and both systolic and diastolic pulmonary artery pressures. Despite dramatic elevations, levels of protein oxidation products did not predict hemodynamic dysfunction or mortality in CS patients. Conclusions-CS is characterized by an arginine-deficient and highly specific pro-oxidant state, with elevated levels of methylated arginine derivatives, including endogenous nitric oxide synthase inhibitors. Levels of methylated arginine derivatives strongly correlate with hemodynamic dysfunction. Among all clinical and laboratory parameters monitored, ADMA levels were the strongest independent predictor of 30-day mortality.

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Section: Discussionmentioning

confidence: 99%

Section: Clinical Perspective P 2324mentioning

confidence: 99%

Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction

et al. 2007

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“…Although difficult to directly compare with our study, data regarding the potential protective effects of NOS inhibition in acute cardiogenic shock have been presented by Cotter et al (3). Unlike our present study, such studies by Cotter et al (3) involved small human populations with varied genetic/risk Fig.…”

Section: Discussionmentioning

confidence: 60%

Deficiency of iNOS does not attenuate severe congestive heart failure in mice

Jones

Greer²,

Ware³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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. Deficiency of iNOS does not attenuate severe congestive heart failure in mice. Am J Physiol Heart Circ Physiol 288: H365-H370, 2005. First published August 19, 2004; doi:10.1152/ajpheart.00245.2004.-Inducible nitric oxide synthase (iNOS) has been implicated in the pathophysiology of congestive heart failure (CHF). Given the extensive evidence supporting this concept, we hypothesized that iNOS deficiency (iNOS Ϫ/Ϫ ) would attenuate the severity of CHF in mice. Mice were subjected to permanent occlusion [myocardial infarction (MI)] of the proximal left anterior descending coronary artery to produce CHF. Cardiac function was assessed in vivo using echocardiography and ultraminiature ventricular pressure catheters. Sham wild-type (n ϭ 17), sham iNOS Ϫ/Ϫ (n ϭ 8), MI wild-type (n ϭ 56), and MI iNOS Ϫ/Ϫ (n ϭ 48) mice were subjected to MI (or sham MI) and followed for 1 mo. Deficiency of iNOS did not alter survival during CHF compared with wild type (35% vs. 32%, P ϭ not significant). Furthermore, fractional shortening and cardiac output were not significantly different between wild-type (9.6 Ϯ 2.0% and 441 Ϯ 20 l ⅐ min Ϫ1 ⅐ g Ϫ1 ) and iNOS Ϫ/Ϫ (9.8 Ϯ 1.3% and 471 Ϯ 26 l ⅐ min Ϫ1 ⅐ g Ϫ1 ) mice. The extent of cardiac hypertrophy and pulmonary edema was also similar between wild-type and iNOS Ϫ/Ϫ mice. None of the indexes demonstrated any significant differences between iNOS Ϫ/Ϫ and wild-type mice subjected to MI. These findings indicate that deficiency of iNOS does not significantly affect severe CHF in mice after MI. myocardial infarction; nitric oxide; physiology; inducible nitric oxide synthase

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“…38 Death at 1 month (Fig. 3) was 27% in the L-NAME-treated patients and 67% in the control group (p = 0.008).…”

Section: Nitric Oxide Synthase Inhibitors In Percutaneous Coronary Inmentioning

confidence: 93%

Nitric oxide synthase inhibitors in post‐myocardial infarction cardiogenic shock—an update

Kaluski

Hendler

Blatt

et al. 2006

Clinical Cardiology

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Summary: Cardiogenic shock (CS) in acute myocardial infarction, after successful coronary angioplasty, still carries a case fatality rate of 50%. These patients succumb to a systemic metabolic storm, superimposed on extensive myocardial necrosis and stunning. Nitric oxide (NO) overproduction contributes to the pathophysiology of this morbid state. Current data regarding the physiologic effects of NO and nitric oxide synthase (NOS) inhibitors on the cardiovascular system are reviewed. Clinical trials assessing the safety and efficacy of NOS inhibitors in CS are summarized.

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LINCS: L-NAME (a NO synthase inhibitor) In the treatment of refractory Cardiogenic Shock A prospective randomized study

Abstract: The results of the present study further support our previous observation that NO synthase inhibitors are beneficial in the treatment of patients with refractory cardiogenic shock.

Cited by 141 publications

References 22 publications

Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction

Metabolic Profiling of Arginine and Nitric Oxide Pathways Predicts Hemodynamic Abnormalities and Mortality in Patients With Cardiogenic Shock After Acute Myocardial Infarction

Deficiency of iNOS does not attenuate severe congestive heart failure in mice

Nitric oxide synthase inhibitors in post‐myocardial infarction cardiogenic shock—an update

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