Cardioprotection, attenuated systemic inflammation, and survival benefit of β1-adrenoceptor blockade in severe sepsis in rats*

Ackland, Gareth L.; Yao, Song T.; Rudiger, Alain; Dyson, Alex; Stidwill, R; Poputnikov, Dmitry M; Singer, Mervyn; Gourine, Alexander V.

doi:10.1097/ccm.0b013e3181c03dfa

Cited by 128 publications

(131 citation statements)

References 41 publications

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“…However, they failed to provide any supporting data, and one may argue that anti-inflammatory effects would unlikely have occurred this swiftly, i.e., after only four hours of treatment (12)(13)(14)(15).…”

Section: Study Design and Findingsmentioning

confidence: 99%

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

Kimmoun¹,

Wei

Lévy³

et al. 2016

J. Thorac. Dis.

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Section: Study Design and Findingsmentioning

confidence: 99%

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

Kimmoun¹,

Wei

Lévy³

et al. 2016

J. Thorac. Dis.

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“…In septic animals, β-blockers reduced heart rate though stroke volume was preserved [81,141]. The longer duration of diastole may perhaps allow better diastolic filling.…”

Section: Beta-blockers In Sepsismentioning

confidence: 99%

“…The heart in sepsis of pro-inflammatory cytokines such as TNF-α and IL-6 [81,141,144]. In rats with fecal peritonitis, an esmolol infusion reduced the local inflammatory response as well as bacterial translocation from the gut into mesenteric lymph nodes [145].…”

Section: Beta-blockers In Sepsismentioning

confidence: 99%

“…In rats with fecal peritonitis, an esmolol infusion reduced the local inflammatory response as well as bacterial translocation from the gut into mesenteric lymph nodes [145]. Survival times of septic animals have been prolonged in several animal studies [141,145,146]. Small clinical studies in septic patients revealed similar haemodynamic and inflammatory results with β-blockers [147][148][149].…”

Section: Beta-blockers In Sepsismentioning

confidence: 99%

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The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Rudiger¹,

Singer²

2013

Current Vascular Pharmacology

Self Cite

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Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown. Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors. Its mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium trafficking and blunted calcium sensitivity of contractile proteins. All these changes are mediated by cytokines. Treatment includes preload optimization with sufficient fluids. However, excessive volume loading is harmful. The first line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for those not responding to catecholamines. During early sepsis, cardiac output can be increased by dobutamine. While early administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might be harmful. Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice. While early administration of catecholamines might be necessary to restore adequate organ perfusion and pressure, prolonged administration might be harmful.Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine will reduce myocardial oxygen expenditure and ameliorate diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. However, all these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice.-3 -Alain Rudiger & Mervyn Singer: The heart in sepsis

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“…Peripheral (i.p.) 1-AR blockade prior to endotoxemia increases survival time, reduces hepatic expression of proinflammatory cytokines, decreases protein expression of cardiac dysfunction markers, and preserves arterial blood pressure and left ventricular contractility (Ackland et al, 2010). Surprisingly, few studies report overall mortality in the published -blocker trials in sepsis.…”

Section: Reflex Control Of Inflammation: Part I -Brain-to-immune Commmentioning

confidence: 99%

Neural Reflex Control of Inflammation During Sepsis Syndromes

Fernández¹,

Acuña-Castillo²

2012

Sepsis - An Ongoing and Significant Challenge

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Cardioprotection, attenuated systemic inflammation, and survival benefit of β1-adrenoceptor blockade in severe sepsis in rats*

Abstract: Peripheral beta1-adrenoceptor blockade offers anti-inflammatory and cardioprotective effects, with mortality reduction if commenced before a septic insult. Its role in sepsis should be explored further.

Cited by 128 publications

References 41 publications

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

Heart rate reduction may be a major determinant of vascular tone in esmolol-treated septic shock patients—although still remains to be confirmed!

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Neural Reflex Control of Inflammation During Sepsis Syndromes

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