Pathological Responses of Cardiac Mitochondria to Burn Trauma

Wang, Meijing; Scott, Sue; Koniaris, Leonidas G.; Zimmers, Teresa A.

doi:10.3390/ijms21186655

Cited by 10 publications

(11 citation statements)

References 171 publications

(247 reference statements)

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“…Mitochondria play a crucial role in the regulation of metabolism via ATP production, reduction of oxidative stress and calcium homeostasis. After burn injury, the interaction of increased oxidative stress, apoptosis and a disruption in respiratory activity and functionality can lead to cardiac dysfunction [ 23 ]. In a 2020 in vivo rat model, Wen et al .…”

Section: Resultsmentioning

confidence: 99%

Current understanding of thermo(dys)regulation in severe burn injury and the pathophysiological influence of hypermetabolism, adrenergic stress and hypothalamic regulation—a systematic review

et al. 2022

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Background In this systematic review, we summarize the aetiology as well as the current knowledge regarding thermo(dys)regulation and hypothermia after severe burn trauma and aim to present key concepts of pathophysiology and treatment options. Severe burn injuries with >20% total body surface area (TBSA) affected commonly leave the patient requiring several surgical procedures, prolonged hospital stays and cause substantial changes to body composition and metabolism in the acute and long-term phase. Particularly in severely burned patients, the loss of intact skin and the dysregulation of peripheral and central thermoregulatory processes may lead to substantial complications. Methods A systematic and protocol-based search for suitable publications was conducted following the PRISMA guidelines. Articles were screened and included if deemed eligible. This encompasses animal-based in vivo studies as well as clinical studies examining the control-loops of thermoregulation and metabolic stability within burn patients Results Both experimental animal studies and clinical studies examining thermoregulation and metabolic functions within burn patients have produced a general understanding of core concepts which are, nonetheless, lacking in detail. We describe the wide range of pathophysiological alterations observed after severe burn trauma and highlight the association between thermoregulation and hypermetabolism as well as the interactions between nearly all organ systems. Lastly, the current clinical standards of mitigating the negative effects of thermodysregulation and hypothermia are summarized, as a comprehensive understanding and implementation of the key concepts is critical for patient survival and long-term well-being. Conclusions The available in vivo animal models have provided many insights into the interwoven pathophysiology of severe burn injury, especially concerning thermoregulation. We offer an outlook on concepts of altered central thermoregulation from non-burn research as potential areas of future research interest and aim to provide an overview of the clinical implications of temperature management in burn patients.

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Section: Resultsmentioning

confidence: 99%

Current understanding of thermo(dys)regulation in severe burn injury and the pathophysiological influence of hypermetabolism, adrenergic stress and hypothalamic regulation—a systematic review

et al. 2022

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“…These stressors can lead to cardiac dysfunction (both right and left) with resultant failure. [5][6][7][8][9] In the acute burn setting, Howard et al noted cardiac dysfunction in 65% of their 26 studied pediatric burn patients, unaffected by the number of surgeries received or presence of inhalation injury. Systolic dysfunction was associated with longer ventilator day requirements and length of stay.…”

Section: Discussionmentioning

confidence: 99%

Is the Use of Routine Echocardiograms Warranted in Large Pediatric Burns?

Wilmot

Chang

Fowler

et al. 2021

Journal of Burn Care &Amp; Research

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Cardiac dysfunction can develop in large pediatric burns during the acute and recovery phase. When occurring in this population, the cardiac abnormality appears as left ventricular dysfunction or dilated cardiomyopathy. Recent studies have demonstrated perioperative and long-term cardiac dysfunction resulting in longer hospital stays for patients over 40% total body surface area. The objective of this study was to assess if early use of echocardiograms in large burns would allow for early recognition of patients at risk for cardiac dysfunction. Pediatric burn patients ages 0 to 18 years who sustained a burn injury of 30% TBSA or more or developed cardiac dysfunction during hospital course were evaluated. Echocardiograms were obtained upon admission with monthly repeats until three normal studies were attained or the patient was discharged and when symptomatic. Of the 130 acute burn patients admitted during 7/2017 to 10/2018, 10 patients met criteria for enrollment in this study. The average age was 5 years (0.8–10 years), 70% were males and 90% sustained flame injuries.Total TBSA average was 45% (24–70%) with average full-thickness burns of 33% (0–67%). Twenty echocardiogram studies were obtained. One patient with 25% TBSA burn, demonstrated severe left ventricular dysfunction with an ejection fraction (EF) of 25% from post-arrest myocardial stunning. Repeat echocardiogram studies demonstrated full recovery with normal EF. The remaining patients, despite large TBSA injuries, did not exhibit any abnormalities on echocardiogram examinations. No cardiac interventions were required. Use of echocardiograms is best performed on symptomatic burn patient populations.

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“…Therefore, these results do not firmly imply calpain 1 as a therapeutic target in burn patients. (2) Calpain is a superfamily encoded by 16 genes, alluding to its functional diversity (25). Unfortunately, we used MDL28170, a nonselective inhibitor of calpain subtypes (24,25), to evaluate the role of calpain 1 in the event of burn injury.…”

Section: Limitationsmentioning

confidence: 99%

“…Severe burn injury, which is defined as burns greater than 30% of the total body surface area, is a critical care problem in clinics. Patients experiencing severe burn injury experience depression of cardiac contractility and output as early as 1 h after the injury, and the severity of heart dysfunction is closely correlated with hospital stays and mortality ( 1 , 2 ). Severe burn results in increased capillary permeability, which reduces venous return and blood supply to the heart.…”

Section: Introductionmentioning

confidence: 99%

Severe burn-induced mitochondrial recruitment of calpain causes aberrant mitochondrial dynamics and heart dysfunction

Ranran

Zhang

Qiao

et al. 2023

Shock

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Mitochondrial damage is an important cause of heart dysfunction after severe burn injury. However, the pathophysiological process remains unclear. This study aims to examine the mitochondrial dynamics in the heart and the role of μ-calpain, a cysteine protease, in this scenario. Rats were subjected to severe burn injury treatment, and the calpain inhibitor MDL28170 was administered intravenously 1 h before or after burn injury. Rats in the burn group displayed weakened heart performance and decreased mean arterial pressure, which was accompanied by a diminishment of mitochondrial function. The animals also exhibited higher levels of calpain in mitochondria, as reflected by immunofluorescence staining and activity tests. In contrast, treatment with MDL28170 before any severe burn diminished these responses to a severe burn. Burn injury decreased the abundance of mitochondria and resulted in a lower percentage of small mitochondria and a higher percentage of large mitochondria. Furthermore, burn injury caused an increase in the fission protein DRP1 in the mitochondria and a decrease in the inner membrane fusion protein OPA1. Similarly, these alterations were also blocked by MDL28170. Of note, inhibition of calpain yielded the emergence of more elongated mitochondria along with membrane invagination in the middle of the longitude, which is an indicator of the fission process. Finally, MDL28170, administered 1 h after burn injury, preserved mitochondrial function and heart performance, and increased the survival rate. Overall, these results provided the first evidence that mitochondrial recruitment of calpain confers heart dysfunction after severe burn injury, which involves aberrant mitochondrial dynamics.

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Pathological Responses of Cardiac Mitochondria to Burn Trauma

Cited by 10 publications

References 171 publications

Current understanding of thermo(dys)regulation in severe burn injury and the pathophysiological influence of hypermetabolism, adrenergic stress and hypothalamic regulation—a systematic review

Current understanding of thermo(dys)regulation in severe burn injury and the pathophysiological influence of hypermetabolism, adrenergic stress and hypothalamic regulation—a systematic review

Is the Use of Routine Echocardiograms Warranted in Large Pediatric Burns?

Severe burn-induced mitochondrial recruitment of calpain causes aberrant mitochondrial dynamics and heart dysfunction

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