Tetrahydrobiopterin improves microcirculation in experimental sepsis

Dumbarton, Tristan C.; Maxan, Alexander; Farah, Nizam; Sharawy, Nivin; Nantais, Jordan; Lehmann, Christian

doi:10.3233/ch-160207

Cited by 12 publications

(8 citation statements)

References 31 publications

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“…Considering the deleterious effects of overproduction of endogenous NO in sepsis, several NOS inhibitors, including selective and nonselective, have been developed, and the therapeutic efficacy and safety of these compounds have been widely investigated. Unfortunately, these studies have produced mixed results; thus, whether to treat sepsis by NOS inhibitors is still a matter of debate [ 111 , 163 ]. While a phase II trial showed that L-NMMA, a nonselective NOS inhibitor, improved systemic vascular response in patients with septic shock, a phase III trial conducted subsequently was terminated.…”

Section: Gaseous-mediator-based Therapeutic Strategy For Sepsis/septi...mentioning

confidence: 99%

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Zhu

Chambers

Zeng

et al. 2022

IJMS

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Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis/septic shock, taking advantage of the multiple actions played by NO, CO and H2S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H2S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.

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Section: Gaseous-mediator-based Therapeutic Strategy For Sepsis/septi...mentioning

confidence: 99%

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Zhu

Chambers

Zeng

et al. 2022

IJMS

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“…Until now, there has been no reliable and practical intervention that can improve or prevent microcirculatory dysfunction. Most previous studies on interventions to improve microcirculation were small, single-center studies showing inconsistent results [99][100][101][102][103][104][105]. Traditional hemodynamic interventions to improve macrocirculation may not improve and may even impair microcirculation.…”

Section: The Present and Future Of Microcirculationmentioning

confidence: 99%

Microcirculation during surgery

Nam

Jeon

2022

Anesth Pain Med

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Throughout the long history of surgery, there has been great advancement in the hemodynamic management of surgical patients. Traditionally, hemodynamic management has focused on macrocirculatory monitoring and intervention to maintain appropriate oxygen delivery. However, even after optimization of macro-hemodynamic parameters, microcirculatory dysfunction, which is related to higher postoperative complications, occurs in some patients. Although the clinical significance of microcirculatory dysfunction has been well reported, little is known about interventions to recover microcirculation and prevent microcirculatory dysfunction. This may be at least partly caused by the fact that the feasibility of monitoring tools to evaluate microcirculation is still insufficient for use in routine clinical practice. However, considering recent advancements in these research fields, with more popular use of microcirculation monitoring and more clinical trials, clinicians may better understand and manage microcirculation in surgical patients in the future. In this review, we describe currently available methods for microcirculatory evaluation. The current knowledge on the clinical relevance of microcirculatory alterations has been summarized based on previous studies in various clinical settings. In the latter part, pharmacological and clinical interventions to improve or restore microcirculation are also presented.

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“…[21] Intestinal microcirculation disorders can be reversed by Tolllike receptor 4 (TLR4) antagonists. [22]…”

Section: Other Pathogenesesmentioning

confidence: 99%

“…[41] Selective inhibition of adenosine triphosphate (ATP)-sensitive potassium (K ATP ) channels in vasodilatory shock by continuous infusion of glipizide could partially restore vasomotor tone in endotoxemic rats and improve systemic hemodynamics in septic rats. [42] Tetrahydrobiopterinl, [22] toll-like receptor World J Emerg Med, Vol 13, No 3, 2022 4 (TLR4) antagonist, [43] and desmopressin [44] have an effect on improving the intestinal microcirculation. There are individual reports of vasopressin V1A receptors, [45,46] physostigmine, [47] and dehydroepiandrosterone combined with orthovanadate, [48] showing that they could improve microcirculation.…”

Section: Other Treatmentsmentioning

confidence: 99%

Intestinal microcirculation dysfunction in sepsis: pathophysiology, clinical monitoring, and therapeutic interventions

Tang¹

2022

World J Emerg Med

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BACKGROUND: Intestinal microcirculation dysfunction is an important factor that causes poor prognosis in sepsis patients and is an important pathophysiological basis for the occurrence and development of sepsis.DATA RESOURCES: PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched from inception to August 1, 2021. The search was limited to the English language only. Two reviewers independently identified studies related to intestinal microcirculation dysfunction in sepsis. Exclusion criteria were duplicate articles according to multiple search criteria.RESULTS: Fifty articles were included, and most of them were animal studies. These studies reported pathogenesis, including endothelial dysfunction, leukocyte recruitment and adhesion, microthrombus formation, microcirculation hypoperfusion, and redistribution of intestinal wall blood flow. The monitoring methods of intestinal microcirculation were also diverse, including handheld microscopes, intravital microscopy (IVM), laser Doppler blood flow instruments, laser speckle contrast imaging, tissue refl ectance spectrophotometry, biochemical markers of intestinal ischemia, and histopathological examination. In view of the related pathogenesis of intestinal microcirculation disorder in sepsis, existing studies also have diff erent opinions on its treatment.CONCLUSIONS: Limited by monitoring, there are few clinical studies on intestinal microcirculation dysfunction in sepsis. Related research mainly focuses on basic research, but some progress has also been made. Therefore, this review may provide a reference for future research on intestinal microcirculation dysfunction in sepsis.

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Tetrahydrobiopterin improves microcirculation in experimental sepsis

Abstract: This study demonstrates that BH4 improves capillary density and inflammation in two separate models of sepsis. BH4 may represent a novel adjunct in the treatment of sepsis and septic shock in clinical practice. Further dose-finding studies and clinical trials are warranted.

Cited by 12 publications

References 31 publications

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Gases in Sepsis: Novel Mediators and Therapeutic Targets

Microcirculation during surgery

Intestinal microcirculation dysfunction in sepsis: pathophysiology, clinical monitoring, and therapeutic interventions

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