Perioperative Implications of Vascular Endothelial Dysfunction: Current Understanding of this Critical Sensor-Effector Organ

Riedel, Bernhard; Rafat, Neysan; Browne, Kim; Burbury, Kate; Schier, Robert

doi:10.1007/s40140-013-0024-7

Cited by 8 publications

(8 citation statements)

References 92 publications

(119 reference statements)

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“…DAMPs from damaged mitochondria exacerbate CNS injury, cardiovascular dysfunction and secondary injury ( 143 – 145 ). According to SHOT, improving CNS protection and CNS-cardiovascular-endothelium coupling will improve tissue perfusion and protect mitochondrial integrity ( 146 ) ( Figure 3 ).…”

Section: Third Pillar: Mitochondrial Integritymentioning

confidence: 99%

Immune dysfunction following severe trauma: A systems failure from the central nervous system to mitochondria

Dobson

Morris²,

Letson³

2022

Front. Med.

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When a traumatic injury exceeds the body’s internal tolerances, the innate immune and inflammatory systems are rapidly activated, and if not contained early, increase morbidity and mortality. Early deaths after hospital admission are mostly from central nervous system (CNS) trauma, hemorrhage and circulatory collapse (30%), and later deaths from hyperinflammation, immunosuppression, infection, sepsis, acute respiratory distress, and multiple organ failure (20%). The molecular drivers of secondary injury include damage associated molecular patterns (DAMPs), pathogen associated molecular patterns (PAMPs) and other immune-modifying agents that activate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic stress response. Despite a number of drugs targeting specific anti-inflammatory and immune pathways showing promise in animal models, the majority have failed to translate. Reasons for failure include difficulty to replicate the heterogeneity of humans, poorly designed trials, inappropriate use of specific pathogen-free (SPF) animals, ignoring sex-specific differences, and the flawed practice of single-nodal targeting. Systems interconnectedness is a major overlooked factor. We argue that if the CNS is protected early after major trauma and control of cardiovascular function is maintained, the endothelial-glycocalyx will be protected, sufficient oxygen will be delivered, mitochondrial energetics will be maintained, inflammation will be resolved and immune dysfunction will be minimized. The current challenge is to develop new systems-based drugs that target the CNS coupling of whole-body function.

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Section: Third Pillar: Mitochondrial Integritymentioning

confidence: 99%

Immune dysfunction following severe trauma: A systems failure from the central nervous system to mitochondria

Dobson

Morris²,

Letson³

2022

Front. Med.

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“… There is increasing recognition that targeting the endothelium and maximizing inherent physiological function in the perioperative period may improve postoperative outcomes. Riedel and colleagues (2013) [ 98 ]p151…”

Section: A Working Hypothesis To Reduce Surgical Stressmentioning

confidence: 99%

Trauma of major surgery: A global problem that is not going away

Dobson

2020

International Journal of Surgery

149

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Globally, a staggering 310 million major surgeries are performed each year; around 40 to 50 million in USA and 20 million in Europe. It is estimated that 1–4% of these patients will die, up to 15% will have serious postoperative morbidity, and 5–15% will be readmitted within 30 days. An annual global mortality of around 8 million patients places major surgery comparable with the leading causes of death from cardiovascular disease and stroke, cancer and injury. If surgical complications were classified as a pandemic, like HIV/AIDS or coronavirus (COVID-19), developed countries would work together and devise an immediate action plan and allocate resources to address it. Seeking to reduce preventable deaths and post-surgical complications would save billions of dollars in healthcare costs. Part of the global problem resides in differences in institutional practice patterns in high- and low-income countries, and part from a lack of effective perioperative drug therapies to protect the patient from surgical stress. We briefly review the history of surgical stress and provide a path forward from a systems-based approach. Key to progress is recognizing that the anesthetized brain is still physiologically ‘awake’ and responsive to the sterile stressors of surgery. New intravenous drug therapies are urgently required after anesthesia and before the first incision to prevent the brain from switching to sympathetic overdrive and activating secondary injury progression such as hyperinflammation, coagulopathy, immune activation and metabolic dysfunction. A systems-based approach targeting central nervous system-mitochondrial coupling may help drive research to improve outcomes following major surgery in civilian and military medicine.

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“…47,48 There are several causes for perioperative endothelial damage, many of which result from activation of inflammatory pathways and could manifest as increased energy loss in biomechanical evaluation of aortic tissue (both in vivo and ex vivo ). 6,19,20,48,73 A single anesthetic agent can have opposite effects on smooth muscle tone and endothelial function, acting simultaneously to both improve and impair vascular function (table 2). The summation of these effects should result in dominant mechanism(s) that determine the overall impact of administering anesthetic agents on aortic biomechanics, and it is reasonable to assume that agents known to clinically result in peripheral vasodilation would most likely lead to reduced aortic stiffness as well.…”

Section: Clinical Applications Of Aortic Biomechanicsmentioning

confidence: 99%