Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock

Garcia, Bruno; Su, Fang; Dewachter, Laurence; Favory, Raphaël; Khaldi, Amina; Moiroux-Sahraoui, Alexander; Annoni, Filippo; Vasques‐Nóvoa, Francisco; Rocha-Oliveira, Estela; Roncon‐Albuquerque, Roberto; Hubesch, G.; Njimi, Hassane; Vincent, Jean‐Louis; Taccone, Fabio Silvio; Créteur, Jacques; Herpain, Antoine

doi:10.1186/s13054-022-04161-3

Cited by 13 publications

(10 citation statements)

References 60 publications

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“…1 and Table 1 ). However, due to species differences with humans, normal lactate levels are usually observed in swine septic shock 35 despite developing all the criteria for a septic shock and tissular hypoperfusion 36 . According to the surviving sepsis campaign guidelines from 2013 25 , which were the only available at the time this protocol was designed, severe sepsis was defined as sepsis plus sepsis-induced organ dysfunction or tissue hypoperfusion; our porcine sepsis phenotype is therefore compatible with this definition.…”

Section: Resultsmentioning

confidence: 99%

Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment

Carrara

Antenucci

Liu

et al. 2022

Sci Rep

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Autonomic and vascular failures are common phenotypes of sepsis, typically characterized by tachycardia despite corrected hypotension/hypovolemia, vasopressor resistance, increased arterial stiffness and decreased peripheral vascular resistance. In a 5-day swine experiment of polymicrobial sepsis we aimed at characterizing arterial properties and autonomic mechanisms responsible for cardiovascular homeostasis regulation, with the final goal to verify whether the resuscitation therapy in agreement with standard guidelines was successful in restoring a physiological condition of hemodynamic profile, cardiovascular interactions and autonomic control. Twenty pigs were randomized to polymicrobial sepsis and protocol-based resuscitation or to prolonged mechanical ventilation and sedation without sepsis. The animals were studied at baseline, after sepsis development, and every 24 h during the 3-days resuscitation period. Beat-to-beat carotid blood pressure (BP), carotid blood flow, and central venous pressure were continuously recorded. The two-element Windkessel model was adopted to study carotid arterial compliance, systemic vascular resistance and characteristic time constant τ. Effective arterial elastance was calculated as a simple estimate of total arterial load. Cardiac baroreflex sensitivity (BRS) and low frequency (LF) spectral power of diastolic BP were computed to assess autonomic activity. Sepsis induced significant vascular and autonomic alterations, manifested as increased arterial stiffness, decreased vascular resistance and τ constant, reduced BRS and LF power, higher arterial afterload and elevated heart rate in septic pigs compared to sham animals. This compromised condition was persistent until the end of the experiment, despite achievement of recommended resuscitation goals by administered vasopressors and fluids. Vascular and autonomic alterations persist 3 days after goal-directed resuscitation in a clinically relevant sepsis model. We hypothesize that the addition of these variables to standard clinical markers may better profile patients’ response to treatment and this could drive a more tailored therapy which could have a potential impact on long-term outcomes.

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Section: Resultsmentioning

confidence: 99%

Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment

Carrara

Antenucci

Liu

et al. 2022

Sci Rep

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“…Clinical parameters measured at the timepoint just before euthanizing are summarized in Table 1 . A more comprehensive description of the model severity and the response to resuscitation care can be found in the princeps study publication [ 17 ].…”

Section: Resultsmentioning

confidence: 99%

“…The collaborative study reported here is an example. Liver biopsies and plasma were isolated from septic shock pigs that were also used in a study on the myocardial effects of vasopressors [ 17 ]. Due to logistical reasons, we were, however, not able to quantify FFA β-oxidation ex vivo in the pig samples, so conclusive proof of the link between PPARα resistance on the one hand and FFA increase and lipotoxicity on the other is lacking in pigs.…”

Section: Discussionmentioning

confidence: 99%

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Hepatic Peroxisome Proliferator-Activated Receptor Alpha Dysfunction in Porcine Septic Shock

Vandewalle

Garcia

Timmermans

et al. 2022

Cells

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Despite decades of research, sepsis remains one of the most urgent unmet medical needs. Mechanistic investigations into sepsis have mainly focused on targeting inflammatory pathways; however, recent data indicate that sepsis should also be seen as a metabolic disease. Targeting metabolic dysregulations that take place in sepsis might uncover novel therapeutic opportunities. The role of peroxisome proliferator-activated receptor alpha (PPARɑ) in liver dysfunction during sepsis has recently been described, and restoring PPARɑ signaling has proven to be successful in mouse polymicrobial sepsis. To confirm that such therapy might be translated to septic patients, we analyzed metabolic perturbations in the liver of a porcine fecal peritonitis model. Resuscitation with fluids, vasopressor, antimicrobial therapy and abdominal lavage were applied to the pigs in order to mimic human clinical care. By using RNA-seq, we detected downregulated PPARɑ signaling in the livers of septic pigs and that reduced PPARɑ levels correlated well with disease severity. As PPARɑ regulates the expression of many genes involved in fatty acid oxidation, the reduced expression of these target genes, concomitant with increased free fatty acids in plasma and ectopic lipid deposition in the liver, was observed. The results obtained with pigs are in agreement with earlier observations seen in mice and support the potential of targeting defective PPARɑ signaling in clinical research.

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“…Of note, the progressive loss of ACE2 in COVID-19 shifts the system to an overall higher angiotensin level due to the impaired ability of ACE2 to degrade it, which may explain the hemodynamic stability during the initial stages of the disease [ 64 ]. Moreover, recent experimental evidence suggests that angiotensin-II administration is associated with a similar level of cardiovascular resuscitation, less myocardial oxygen consumption, and less inflammation compared to norepinephrine [ 65 ]. Taking into consideration the characteristics of angiotensin-II, more research is needed to evaluate its potent effects in COVID-19-related shock.…”

Section: Discussionmentioning

confidence: 99%

Association of vasopressors with mortality in critically ill patients with COVID-19: a systematic review and meta-analysis

Mermiri

Mavrovounis

Laou

et al. 2023

APS

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Exogenous catecholamines may have pronounced side effects and affect physiological cascades. The aim of this study was to investigate the effect of vasopressors on mortality of critically ill patients with coronavirus disease 2019 (COVID-19). A systematic search of PubMed, Scopus, and ClinicalTrials.gov was conducted for relevant articles until December 2022. Eligibility criteria were randomized controlled and non-randomized trials. The primary outcome was in-hospital and 30-day mortality. The quality of studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) tool, while paired meta-analysis was used to estimate the pooled risk ratios (RR) along with their 95% Confidence Interval (95% CI). Analyses of 22 studies (n = 8034) revealed that vasopressor use is associated with mortality compared to no vasopressor therapy [RR (95%CI): 4.30 (3.21, 5.75); p < 0.001]. In-hospital and 30-day mortality are significantly higher in patients who receive vasopressors [RR (95%CI): 4.60 (2.47, 8.55); p < 0.001 and RR (95%CI): 2.97 (1.72, 5.14); p < 0.001, respectively]. Also, analyses of data from 10 studies (n = 3519) revealed that vasopressor use is associated with acute kidney injury [RR (95%CI): 3.17 (2.21, 4.54); p < 0.001]. In conclusion, current use of vasopressors in critically ill patients with COVID-19 may be associated with higher in-hospital mortality, 30-day mortality, and incidence rate of acute kidney injury. Further research is required to estimate the correlation of specific vasopressor characteristics (type, timing, dose, combination) with adverse effects and mortality in this population. Graphical Abstract

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Myocardial effects of angiotensin II compared to norepinephrine in an animal model of septic shock

Cited by 13 publications

References 60 publications

Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment

Autonomic and circulatory alterations persist despite adequate resuscitation in a 5-day sepsis swine experiment

Hepatic Peroxisome Proliferator-Activated Receptor Alpha Dysfunction in Porcine Septic Shock

Association of vasopressors with mortality in critically ill patients with COVID-19: a systematic review and meta-analysis

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