Is the cyclic GMP system underestimated by intensive care and emergency teams?

Évora, Paulo Roberto Barbosa; Rodrigues, Alfredo José; Vicente, Walter Villela de Andrade; Vicente, Yvone Avalloni de Andrade; Basseto, Solange; Basile-Filho, Aníbal; Capellini, Verena Kise

doi:10.1016/j.mehy.2007.01.041

Cited by 14 publications

(13 citation statements)

References 13 publications

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“…The disclosure and possible consecration of this therapy will be passed on as verbal information and, depending on the increase of publications, in studies based on evidence. In the literature data and medical practice set remains the certainty that the soluble guanylate cyclase blockage in distributive shock control remains underestimated [59,60].…”

Section: Discussionmentioning

confidence: 99%

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties

Évora¹,

Ribeiro

Vicente³

et al. 2009

Rev Bras Cir Cardiovasc

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Azul de metileno no tratamento da síndrome vasoplégica em cirurgia cardíaca. Quinze anos de perguntas, respostas, dúvidas e certezasMethylene blue for vasoplegic syndrome treatment in heart surgery. Fifteen years of questions, answers, doubts and certainties AbstractObjective: There is strong evidence that methylene blue (MB), an inhibitor of guanylate cyclase, is an excellent therapeutic option for vasoplegic syndrome (VS) treatment in heart surgery. The aim of this article is to review the MB's therapeutic function in the vasoplegic syndrome treatment.Methods: Fifteen years of literature review.Results: 1) Heparin and ACE inhibitors are risk factors; 2) In the recommended doses it is safe (the lethal dose is 40 mg/ kg); 3) The use of MB does not cause endothelial dysfunction; 4) The MB effect appears in cases of nitric oxide (NO) upregulation; 5) MB is not a vasoconstrictor, by blocking of the GMPc system it releases the AMPc system, facilitating the norepinephrine vasoconstrictor effect; 6) The most used dosage is 2 mg/kg as IV bolus followed by the same continuous infusion because plasmatic concentrations strongly decays in the first 40 minutes; 7) There is a possible "window of opportunity" for the MB's effectiveness.Conclusions: Although there are no definitive multicentric studies, the MB used to treat heart surgery VS, at the present time, is the best, safest and cheapest option, being a Brazilian contribution for the heart surgery.

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Section: Discussionmentioning

confidence: 99%

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties

Évora¹,

Ribeiro

Vicente³

et al. 2009

Rev Bras Cir Cardiovasc

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“…Methylene blue does not interfere with NOS and has played a longstanding beneficial role in many other clinical conditions. As a potent guanylate cyclase inhibitor, MP blocks the increase in cGMP levels and, consequently, prevents vascular smooth muscle NO endothelium-dependent relaxation [70]. We feel that a controlled randomized trial to assess MB as a viable coadjuvant therapeutic tool of fluid resuscitation in burn injury is a necessary next step.…”

Section: Oxidative Stress and Inflammationmentioning

confidence: 99%

Curbing Inflammation in Burn Patients

Farina

Rosique

2013

International Journal of Inflammation

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Patients who suffer from severe burns develop metabolic imbalances and systemic inflammatory response syndrome (SIRS) which can result in multiple organ failure and death. Research aimed at reducing the inflammatory process has yielded new insight into burn injury therapies. In this review, we discuss strategies used to curb inflammation in burn injuries and note that further studies with high quality evidence are necessary.

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“…We believe that these specialists should pay much more attention to the MB therapeutic approach. Perhaps the very low MB commercial value may be confounding commercial interests of the pharmaceutical industry as well [44,45].…”

Section: Sgc Blockersmentioning

confidence: 99%

Cardiovascular Therapeutics Targets on the NO–sGC–cGMP Signaling Pathway: A Critical Overview

Évora

Évora²,

Celotto³

et al. 2012

CDT

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In a brief overview, in NO-sGC-cGMP signaling in a blood vessel, l-arginine is converted in the endothelium monolayer by the endothelial nitric oxide synthase (eNOS) to NO which diffuses into both the vessel lumen and the vessel wall, thereby activating soluble guanylate cyclase (sGC). Heme-dependent sGC stimulators and hem-independent sGC activators increase the cellular cGMP concentration via the direct activation of sGC, which results in both vasorelaxation and inhibition of platelet aggregation. Studies of the 90's definitively established the role of endothelium in all cardiovascular diseases, which were associated with endothelial dysfunction by impaired release of endothelium-derived relaxing factors with consequent risk of spasm and thrombosis. The rationale of this review is based on the fact that the discovery of NO changed the concepts of cardiovascular disease mechanisms. However, considering the jargon "from the bench to clinical practice" we concluded that a potential therapeutic revolution did not follow the pathophysiological revolution. The review is focused on general aspects without regard for advanced research aspects, and designed in two main groups: the NO/cGMP positive stimulators and blockers as "future and encouraging" new therapeutic drugs. The potential vasodilators include 1) NOS uncoupling; 2) NOS enhancers (AVE compounds); 3) NO donors (nitrovasodilators); 4) NO-independent activators (BAY compounds), and; 5) PDE5 inhibitors. The potential vasoconstrictors include 1) NOS-blockers (L-NAME, L-NMMA); 2) sGC-blockers (methylene blue), and; 3) PDEs. Few texts, selected by excellence and relevance, were crucial and considerably facilitated the elaboration of this text, in addition to our own experimental and clinical experience working on vasoplegic endothelium dysfunction.

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Is the cyclic GMP system underestimated by intensive care and emergency teams?

Cited by 14 publications

References 13 publications

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties

Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties

Curbing Inflammation in Burn Patients

Cardiovascular Therapeutics Targets on the NO–sGC–cGMP Signaling Pathway: A Critical Overview

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