scholarly journals Reducing susceptibility to bacteremia after experimental burn injury: a role for selective decontamination of the digestive tract

2007 ◽  
Vol 102 (6) ◽  
pp. 2207-2216 ◽  
Author(s):  
Jureta W. Horton ◽  
David L. Maass ◽  
Jean White ◽  
Joseph P. Minei
Keyword(s):  
Digestive Tract ◽  
Cardiac Myocyte ◽  
Burn Injury ◽  
Inflammatory Responses ◽  
Left Ventricular ◽  
Selective Decontamination ◽  
Myocardial Inflammation ◽  
Oral Gavage ◽  
Experimental Burn ◽  
Tnf Α

We proposed that selective decontamination of the digestive tract (SDD) initiated after experimental burn injury would decrease myocardial inflammation and dysfunction after a second insult such as septic challenge. Rats were divided into eight experimental groups. Groups included sham burn plus sham sepsis, burn alone, sepsis alone, and burn plus sepsis given either water by oral gavage for 5 days after burn (or sham burn) or given oral antibiotics (polymyxin E, 15 mg; tobramycin, 6 mg; 5-flucytosin, 100 mg given by oral gavage, 2× daily for 5 days after burn or sham burn). Cardiac function and inflammation were studied 24 h after septic challenge. In the absence of SDD, burn alone, sepsis alone, or burn plus septic challenge promoted cardiac myocyte secretion of TNF-α (burn, 174 ± 11; sepsis, 269 ± 19; burn + sepsis, 453 ± 14 pg/ml), IL-1β (burn, 35 ± 2; sepsis, 29 ± 1; burn + sepsis, 48 ± 7 pg/ml), and IL-6 (burn, 143 ± 18; sepsis, 116 ± 3; burn + sepsis, 248 ± 12 pg/ml) compared with values measured in sham (TNF-α, 3 ± 1; IL-1β, 1 ± 0.4; IL-6, 6 ± 1.5 pg/ml) ( P < 0.05). Impaired ventricular contraction and relaxation responses were evident in the absence of SDD [burn + sepsis: left ventricular pressure (LVP), 65 ± 4 mmHg; rate of LVP rise (+dP/d t), 1,320 ± 131 mmHg/s compared with values measured in sham: LVP, 96 ± 4 mmHg; +dP/d t, 2,095 ± 99 mmHg/s, P < 0.05]. SDD treatment of experimental burn attenuated septic challenge-related inflammatory responses and improved myocardial contractile responses, producing cardiac TNF-α, IL-1β, and IL-6 levels, LVP, +dP/d t, and rate of LVP fall (−dP/d t) values that were significantly better ( P < 0.05) than values measured in burn plus sepsis in the absence of SDD. This work confirms that endogenous gut organisms contribute to sensitivity to subsequent infectious challenge.

Selective decontamination of the digestive tract attenuated the myocardial inflammation and dysfunction that occur with burn injury

2004 ◽  
Vol 287 (5) ◽  
pp. H2241-H2251 ◽  
Author(s):  
Jureta W. Horton ◽  
Jing Tan ◽  
D. Jean White ◽  
David L. Maass ◽  
James A. Thomas
Keyword(s):  
Digestive Tract ◽  
P38 Mapk ◽  
Nuclear Translocation ◽  
Burn Injury ◽  
Inflammatory Responses ◽  
Total Body Surface Area ◽  
Selective Decontamination ◽  
Cytokine Secretion ◽  
Myocardial Inflammation ◽  
Sprague Dawley

This study examined the effects of oral antibiotics to selectively decontaminate the digestive tract (SDD) on postburn myocardial signaling, inflammation, and function. We hypothesized that antibiotic therapy to eliminate pathogens from the gastrointestinal (GI) tract would reduce myocardial inflammatory responses and improve postburn myocardial performance. Sprague-Dawley rats received polymyxin E (15 mg), tobramycin (6 mg), and 5-flucytosin (100 mg) by oral gavage twice daily for 3 days preburn and 24 h postburn. Experimental groups included 1) sham burn given vehicle (3 ml water), 2) sham plus SDD, 3) burn over 40% total body surface area (TBSA) plus SDD, and 4) burn over 40% TBSA given vehicle. All burns received lactated Ringer solution (4 mg·kg−1·%burn−1); myocardial signaling (PKCε/p38 MAPK/NF-κB) was studied 2, 4, and 24 h postburn; and cytokine secretion (systemic and myocyte secreted cytokines, ELISA) and cardiac function were examined 24 h postburn. Vehicle-treated burn injury increased myocardial PKCε/p38 MAPK expression, promoted NF-κB nuclear translocation, promoted TNF-α, IL-1β, IL-6, and IL-10 secretion, and impaired myocardial function. SDD attenuated burn-related proinflammatory myocardial signaling, cytokine secretion, and myocardial contractile defects. Our data suggest that burn-related loss of GI barrier function and translocation of microbial products serve as upstream mediators of postburn myocardial inflammatory signaling and dysfunction.

scholarly journals Hypertonic saline dextran after burn injury decreases inflammatory cytokine responses to subsequent pneumonia-related sepsis

2006 ◽  
Vol 290 (4) ◽  
pp. H1642-H1650 ◽  
Author(s):  
Jureta W. Horton ◽  
David L. Maass ◽  
D. Jean White
Keyword(s):  
Hypertonic Saline ◽  
Burn Injury ◽  
Inflammatory Responses ◽  
Contractile Function ◽  
Total Body Surface Area ◽  
Isotonic Saline ◽  
Ringer Solution ◽  
Myocardial Inflammation ◽  
Adult Rats ◽  
Tnf Α

The present study examined the hypothesis that hypertonic saline dextran (HSD), given after an initial insult, attenuates exaggerated inflammation that occurs with a second insult. Adult rats ( n = 15 per group) were divided into groups 1 (sham burn), 2 [40% total body surface area burn + 4 ml/kg isotonic saline (IS) + 4 ml·kg−1·% burn−1 lactated Ringer solution (LR)], and 3 (burn + 4 ml/kg HSD + LR), all studied 24 h after burns. Groups 4 (sham burn), 5 (burn + IS + LR), and 6 (burns + HSD + LR) received intratracheal (IT) vehicle 7 days after burns; groups 7 (burn + IS + LR) and 8 (burn + HSD + LR) received IT Streptococcus pneumoniae (4 × 106 colony-forming units) 7 days after burn. Groups 4–8 were studied 8 days after burn and 24 h after IT septic challenge. When compared with sham burn, contractile defects occurred 24 h after burn in IS-treated but not HSD-treated burns. Cardiac inflammatory responses (pg/ml TNF-α) were evident with IS (170 ± 10) but not HSD (45 ± 5) treatment vs. sham treatment (80 ± 15). Pneumonia-related sepsis 8 days after IS-treated burns ( group 7) exacerbated TNF-α responses/contractile dysfunction vs. IS-treated burns in the absence of sepsis ( P < 0.05). Sepsis that occurred after HSD-treated burns ( group 8) had less myocyte TNF-α secretion/better contractile function than IS-treated burns given septic challenge ( group 7, P < 0.05). We conclude that an initial burn injury exacerbates myocardial inflammation/dysfunction occurring with a second insult; giving HSD after the initial insult attenuates myocardial inflammation/dysfunction associated with a second hit, suggesting that HSD reduces postinjury risk for infectious complications.

Role of interleukin-6 in cardiac inflammation and dysfunction after burn complicated by sepsis

2007 ◽  
Vol 292 (5) ◽  
pp. H2408-H2416 ◽  
Author(s):  
Hongchao Zhang ◽  
Huan-You Wang ◽  
Rhonda Bassel-Duby ◽  
David L. Maass ◽  
William E. Johnston ◽  
...  
Keyword(s):  
Interleukin 6 ◽  
Total Body Surface Area ◽  
Left Ventricular ◽  
Myocardial Inflammation ◽  
Contractile Dysfunction ◽  
Cardiac Inflammation ◽  
Tnf Α

To examine the role of myocardial interleukin-6 (IL-6) in myocardial inflammation and dysfunction after burn complicated by sepsis, we performed 40% total body surface area contact burn followed by late (7 days) Streptococcus pneumoniae pneumonia sepsis in wild-type (WT) mice, IL-6 knockout (IL-6 KO) mice, and transgenic mice overexpressing IL-6 in the myocardium (TG). Twenty-four hours after sepsis was induced, isolated cardiomyocytes were harvested and cultured in vitro, and supernatant concentrations of IL-6 and tumor necrosis factor (TNF)-α were measured. Cardiomyocyte intracellular calcium ([Ca2+]i) and sodium ([Na+]i) concentrations were also determined. Separate mice in each group underwent in vivo global hemodynamic and cardiac function assessment by cannulation of the carotid artery and insertion of a left ventricular pressure volume conductance catheter. Hearts from these mice were collected for histopathological assessment of inflammatory response, fibrosis, and apoptosis. In the WT group, there was an increase in cardiomyocyte TNF-α, [Ca2+]i, and [Na+]i after burn plus sepsis, along with cardiac contractile dysfunction, inflammation, and apoptosis. These changes were attenuated in the IL-6 KO group but accentuated in the TG group. We conclude myocardial IL-6 mediates cardiac inflammation and contractile dysfunction after burn plus sepsis.

scholarly journals INDICATORS OF THE CARDIOMYOCYTES` CELLS CYCLE UNDER INFUSION OF BLOOD SUBSTITUTES AND IN THE CORRECTION OF EXPERIMENTAL BURN INJURY BY 0,9% NACL SOLUTION

2018 ◽  
Vol 24 (1) ◽  
pp. 62-68
Author(s):  
R.V. Radoga
Keyword(s):  
Cell Cycle ◽  
Burn Injury ◽  
Vena Cava ◽  
Left Ventricular ◽  
Blood Substitutes ◽  
The Body ◽  
Synthetic Activity ◽  
Myocardial Cells ◽  
Nacl Solution ◽  
Experimental Burn

According to the WHO, the thermal trauma is on the third place among other injuries. Burned injury is not only damage to the skin, but also the traumatization of all organs and systems of the body as a result of the stress response of the vascular system and the effects of toxic products coming from the area of burn injury. Firstly, such damages affect cardiomyocytes and the microcirculation vessels of the heart. The purpose of our study was to evaluate the changes in the cell cycle of myocardial cells in the left ventricle of rats under conditions of blood substitutes infusion and in the correction of experimental burn injury with a 0,9% solution of NaCl. The burn trauma was modeled using the Regas’ method and placed a catheter into the lower vena cava for intravenous infusion. The following solutions were used for infusion: 0,9% NaCl solution, lactoproteinum with sorbitol (Lactoproteinum-C) and colloidal-hyperosmolar HAES-LX-5% solution. Flow cytometry of the nuclear suspension of left ventricular cardiomyocytes was performed on the 1st, 3rd, and 7th days of the experiment. The statistical analysis of the results was carried out using the “STATISTICA 6.1” program package. The results of the performed study show a fairly stable picture of cell cycle parameters in myocardial cells of animals without burn injury with a predominance, on the one hand, of cells present in the G0G1 phase and the presence of a certain balance between the processes of creation of nuclear DNA synthesis and apoptosis. Changes in the phase of cardiac myocyte cell cycle against the background of the thermal injury of the skin throughout the observation time indicate a prolonged, uncorrected cell cycle disorder and a lack of effective normalization on the background of the physiological solution usage in the first 7 days after burning trauma of the skin. The protective effect of HAES-LX-5% prevents over-strain of cells, as evidenced by the lower synthetic activity of nuclei of cardiomyocytes at all times of the experiment.

scholarly journals Burn injury induces intestinal inflammatory response mediated by Th17 in burn-primed endotoxemic mice

2020 ◽  
Author(s):  
Kazuhiko Sekine ◽  
Takayuki Shibusawa ◽  
Seitaro Fujishima ◽  
Naoki Aikawa ◽  
Junichi Sasaki
Keyword(s):  
Lamina Propria ◽  
Mononuclear Cells ◽  
Burn Injury ◽  
Inflammatory Responses ◽  
Total Body Surface Area ◽  
Vital Role ◽  
Mice Model ◽  
Th17 Response ◽  
Lamina Propria Mononuclear Cells ◽  
Tnf Α

Objective: This study aimed to elucidate the mechanism underlying the susceptibility to infection-related acute lung injury by focusing on the role of gut mucosal T-helper (Th) 17 cells that preferentially produce IL-17 with probiotics in a burn-primed endotoxemic mice model. Methods: Mice were subjected to a 15% total body surface area third-degree burn. Survival from lethal lipopolysaccharide (LPS) administration (3 mg/kg) on 11th day post burn was assessed in mice fed by chow with or without 1.2% Lactobacillus powder after burn injury. Lamina propria mononuclear cells were enzymatically isolated from the ileum removed on 11th day post burn and incubated along with 1 μg/mL LPS or 10 μg/mL anti-CD3 antibody for 24 h; subsequently, the following seven cytokines were analyzed in the supernatant: IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, and IL-17. Results: Lactobacillus treatment post-burn injury markedly improved survival after lethal endotoxemia in burn-primed mice (64.3% vs. 21.4%, p = 0.03). The production of proinflammatory cytokines such as TNF-α, IL-6, and IL-17 by lamina propria mononuclear T-lymphocytes and macrophages including Th17 response was augmented by burn injury but decreased with Lactobacillus treatment after burn injury. Conclusions: Th17- and Th17-mediated inflammatory responses in the gut mucosa may play a vital role, which could be attenuated by Lactobacillus treatment, in survival of lethal endotoxemia in burn-primed mice.

scholarly journals Positive effects of renal denervation on markers of cardiovascular inflammation and left ventricular mass. 24-months follow-up

2021 ◽  
Vol 20 (2) ◽  
Author(s):  
E. S. Sitkova ◽  
V. F. Mordovin ◽  
S. E. Pekarskiy ◽  
T. M. Ripp ◽  
T. R. Ryabova ◽  
...  
Keyword(s):  
Left Ventricular Mass ◽  
Inflammatory Markers ◽  
Renal Denervation ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Myocardial Inflammation ◽  
Positive Effects ◽  
Ventricular Mass ◽  
Tnf Α

Aim. To study the long-term effect of renal denervation (RDN) on left ventricular mass (LVM) and inflammatory markers in resistant hypertensive patients.Material and methods. Forty-one patients with resistant hypertension and 24-h blood pressure (BP) 158,7±15,8/87,3+14,6 mmHg, aged 56,6+10,2 years, were enrolled in the study and undergone RDN. Mean 24-h BP, left ventricular mass (transthoracic echocardiography), high sensitivity C-reactive protein (hsCRP), interleukin- 1β (IL­1β), IL-6, IL-10) and tumor necrosis factor alpha (TNF- α) were assessed at baseline and 2 years after the RDN.Results. A baseline prevalence of left ventricular hypertrophy (LVH) was 90,2%. Two years after RDN LVM and interventricular septum (IVS) decreased significantly (p<0.05 for both). Decrease in myocardial mass (∆LVM >0 g) was documented in 24 patients. The regression of LVM was accompanied by a significant decrease in levels of inflammatory markers — hsCRP by 38,3% (p=0,031), TNF-α by 60,7% (p=0,009), IL- 1β — by 71,1% (p=0,001), and IL-10 by 58,2% (p=0,001). In patients in the absence of LVM regression only TNF-α decreased significantly (-68,8%, p=0,001). There was no correlation between changes of LVM and the inflammatory markers at 24 months after RDN.Conclusion. The RDN in RH patients may have long-term cardioprotective effect in terms of significant regress of LVH, which may be partly attributed to the regress in systemic or myocardial inflammation.

scholarly journals Amlexanox and Forskolin Prevents Isoproterenol-Induced Cardiomyopathy by Subduing Cardiomyocyte Hypertrophy and Maladaptive Inflammatory Responses

2021 ◽  
Vol 9 ◽  
Author(s):  
Gabriel Komla Adzika ◽  
Hongjian Hou ◽  
Adebayo Oluwafemi Adekunle ◽  
Ruqayya Rizvi ◽  
Seyram Yao Adzraku ◽  
...  
Keyword(s):  
Cardiac Hypertrophy ◽  
Troponin I ◽  
Inflammatory Responses ◽  
Myocardial Hypertrophy ◽  
Left Ventricular ◽  
Cardiomyocyte Hypertrophy ◽  
Myocardial Inflammation ◽  
Treatment Interventions ◽  
Pathological Cardiac Hypertrophy

Chronic catecholamine stress (CCS) induces the occurrence of cardiomyopathy—pathological cardiac hypertrophy (PCH), which is characterized by left ventricular systolic dysfunction (LVSD). Recently, mounting evidence has implicated myocardial inflammation in the exacerbation of pathological cardiac remodeling. However, there are currently no well-defined treatment interventions or regimes targeted at both the attenuation of maladaptive myocardial hypertrophy and inflammation during CCS to prevent PCH. G protein-coupled receptor kinase 5 (GRK5) and adenylyl cyclases (ACs)-cAMP mediates both cardiac and inflammatory responses. Also, GRK5 and ACs are implicated in stress-induced LVSD. Herein, we aimed at preventing PCH during CCS via modulating adaptive cardiac and inflammatory responses by inhibiting GRK5 and/or stimulating ACs. Isoproterenol-induced cardiomyopathy (ICM) was modeled using 0.5 mg/100 g/day isoproterenol injections for 40 days. Alterations in cardiac and inflammatory responses were assessed from the myocardia. Similarities in the immunogenicity of cardiac troponin I (cTnI) and lipopolysaccharide under CCS were assessed, and Amlexanox (35 μM/ml) and/or Forskolin (10 μM/ml) were then employed in vitro to modulate adaptive inflammatory responses by inhibiting GRK5 or activating ACs-cAMP, respectively. Subsequently, Amlexanox (2.5 mg/100 g/day) and/or Forskolin (0.5 mg/100 g/day) were then translated into in vivo during CCS to modulate adaptive cardiac and inflammatory responses. The effects of Amlexanox and Forskolin on regulating myocardial systolic functions and inflammatory responses during CCS were ascertained afterward. PCH mice had excessive myocardial hypertrophy, fibrosis, and aggravated LVSD, which were accompanied by massive CD68+ inflammatory cell infiltrations. In vitro, Forskolin-AC/cAMP was effective than Amlexanox-GRK5 at downregulating proinflammatory responses during stress; nonetheless, Amlexanox and Forskolin combination demonstrated the most efficacy in modulating adaptive inflammatory responses. Individually, the translated Amlexanox and Forskolin treatment interventions were ineffective at subduing the pathological remodeling and sustaining cardiac function during CCS. However, their combination was potent at preventing LVSD during CCS by attenuating maladaptive myocardial hypertrophy, fibrosis, and inflammatory responses. The treatment intervention attained its potency mainly via Forskolin-ACs/cAMP-mediated modulation of cardiac and inflammatory responses, coupled with Amlexanox inhibition of GRK5 mediated maladaptive cascades. Taken together, our findings highlight the Amlexanox and Forskolin combination as a potential therapeutic intervention for preventing the occurrence of pathological cardiac hypertrophy during chronic stress.

Bactericidal/permeability increasing protein attenuates the myocardial inflammation/dysfunction that occurs with burn complicated by subsequent infection

2007 ◽  
Vol 103 (3) ◽  
pp. 948-958 ◽  
Author(s):  
Jureta W. Horton ◽  
David L. Maass ◽  
D. Jean White ◽  
Joseph P. Minei
Keyword(s):  
Contractile Function ◽  
Total Body Surface Area ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cytokine Secretion ◽  
Myocardial Inflammation ◽  
Susceptibility To Infection ◽  
Tnf Α ◽  
Total Body ◽  
T Values

Intubation and mechanical ventilation after burn contribute to pneumonia-related infection. Although postburn presence or absence of endotoxin has been described, inactivation of Toll-like receptor 4 signaling has been shown to improve postburn organ function, suggesting that LPS participates in burn-related susceptibility to infection. We hypothesized that bactericidal/permeability-increasing protein (rBPI) given postburn would attenuate myocardial inflammation/dysfunction associated with postburn septic challenge given 7 days postburn. Rats were given burn over 40% total body surface area, lactated Ringer 4 ml·kg−1·% burn−1; burns received either vehicle or rBPI, 1 mg·kg−1·h−1for 48 h postburn. Postburn day 7, subgroups of burns and shams were given intratracheal Klebsiella pneumoniae, 4 × 106CFU to produce burn complicated by sepsis; additional sham and burn subgroups received intratracheal vehicle to produce sham sepsis. Vehicle-treated groups: 1) sham burn + sham sepsis 2) sham burn + sepsis, 3) burn + sham sepsis, 4) burn + sepsis. rBPI-treated groups: 5) sham burn + sham sepsis, 6) sham burn + sepsis, 7) burn + sham sepsis, 8) burn + sepsis. Cardiomyocyte cytokine secretion and myocardial function were studied 24 h after septic challenge, postburn day 8. Pneumonia-related infection 8 days after vehicle-treated burn produced myocyte cytokine secretion (pg/ml), indicated by increased myocyte TNF-α, 549 ± 46; IL-1β, 50 ± 8; IL-6, 286 ± 3 levels compared with levels in sham myocytes (TNF-α, 88 ± 11; IL-1β, 7 ± 1; IL-6, 74 ± 10; P < 0.05). Contractile dysfunction was evident from lower left ventricular pressure ±dP/d t values in this group compared with sham. rBPI attenuated myocyte cytokine responses to septic challenge and improved contractile function, suggesting that burn-related mobilization of microbial-like products contribute to postburn susceptibility to infection.

Role of cytosolic vs. mitochondrial Ca2+ accumulation in burn injury-related myocardial inflammation and function

2005 ◽  
Vol 288 (2) ◽  
pp. H744-H751 ◽  
Author(s):  
David L. Maass ◽  
Jean White ◽  
Billy Sanders ◽  
Jureta W. Horton
Keyword(s):  
Room Temperature ◽  
Burn Injury ◽  
Imaging System ◽  
Total Body Surface Area ◽  
Myocardial Inflammation ◽  
Adult Rats ◽  
Burn Trauma ◽  
Fura 2 ◽  
Tnf Α

This study was designed to examine the role of mitochondrial Ca2+ homeostasis in burn-related myocardial inflammation. We hypothesized that mitochondrial Ca2+ is a primary modulator of cardiomyocyte TNF-α, IL-1β, and IL-6 responses to injury and infection. Ventricular myocytes were prepared by Langendorff perfusion of hearts from adult rats subjected to sham burn or burn injury over 40% of total body surface area to produce enzymatic (collagenase) digestion. Isolated cardiomyocytes were suspended in MEM, cell number was determined, and aliquots of myocytes from each experimental group were loaded with fura 2-AM (2 μg/ml) for 1) 45 min at room temperature to measure total cellular Ca2+, 2) 45 min at 30°C followed by incubation at 37°C for 2 h to eliminate cytosolic fluorescence, and 3) 20 min at 37°C in MnCl2 (200 μM)-containing buffer to quench cytosolic fura 2-AM signal. In vitro studies included preparation of myocytes from control hearts and challenge of myocytes with LPS or burn serum (BS), which have been shown to increase cytosolic Ca2+. Additional aliquots of myocytes were challenged with LPS or BS with or without a selective inhibitor of mitochondrial Ca2+, ruthenium red (RR). All cells were examined on a stage-inverted microscope that was interfaced with the InCyt Im2 fluorescence imaging system. Heat treatment or MnCl2 challenge eliminated myocyte cytosolic fluorescence, whereas cells maintained at room temperature retained 95% of their initial fluorescence. Compared with Ca2+ levels measured in sham myocytes, burn trauma increased cytosolic Ca2+ from 90 ± 3 to 293 ± 6 nM ( P < 0.05) and mitochondrial Ca2+ from 24 ± 1 to 75 ± 2 nM ( P < 0.05). LPS (25 μg/5 × 104 cells) or BS (10% by volume) challenge for 18 h increased cardiomyocyte cytosolic and mitochondrial Ca2+ and promoted myocyte secretion of TNF-α, IL-1β, and IL-6. RR pretreatment decreased LPS- and BS-related rise in mitochondrial Ca2+ and cytokine secretion but had no effect on cytosolic Ca2+. BS challenge in perfused control hearts impaired myocardial contraction/relaxation, and RR pretreatment of hearts prevented BS-related myocardial contractile dysfunction. Our data suggest that a rise in mitochondrial Ca2+ is one modulator of myocardial inflammation and dysfunction in injury states such as sepsis and burn trauma.

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