Recruitment Microcirculatory - Mitochondrial through a permissive systemic perfusion pressure combats microcirculatory - mitochondrial distress syndrome. Cases report (original) (raw)
Related papers
Microcirculation vs. Mitochondria—What to Target?
Frontiers in Medicine, 2020
Circulatory shock is associated with marked disturbances of the macro-and microcirculation and flow heterogeneities. Furthermore, a lack of tissue adenosine trisphosphate (ATP) and mitochondrial dysfunction are directly associated with organ failure and poor patient outcome. While it remains unclear if microcirculation-targeted resuscitation strategies can even abolish shock-induced flow heterogeneity, mitochondrial dysfunction and subsequently diminished ATP production could still lead to organ dysfunction and failure even if microcirculatory function is restored or maintained. Preserved mitochondrial function is clearly associated with better patient outcome. This review elucidates the role of the microcirculation and mitochondria during circulatory shock and patient management and will give a viewpoint on the advantages and disadvantages of tailoring resuscitation to microvascular or mitochondrial targets.
Mitochondrial dysfunction in chronic ischemia and peripheral vascular disease
Mitochondrion, 2004
In peripheral vascular disease, impaired muscle energy metabolism is assumed to be due mainly to defective vascular O 2 supply, the resulting cellular hypoxia inhibiting oxidative ATP synthesis. Older work suggested a compensatory increase in muscle aerobic enzymes, but more recent studies suggest a relative decrease in some mitochondrial components and an accumulation of damage in mitochondrial DNA, perhaps due to reactive oxygen species. However, to establish whether in vivo muscle mitochondria suffer from anything other than a low concentration of O 2 will require more knowledge of the mitochondrial behaviour at low PO 2 , and the actual cell PO 2 during exercise. q
PLOS ONE, 2022
Background Despite current resuscitation strategies, circulatory shock and organ injury after cardiac surgery occur in 25-40% of patients. Goal-directed resuscitation after cardiac surgery has generated significant interest, but clinical practice to normalize hemodynamic variables including mean arterial pressure, cardiac filling pressures, and cardiac output may not reverse microcirculation abnormalities and do not address cellular dysoxia. Recent advances in technology have made it possible to measure critical components of oxygen delivery and oxygen utilization systems in live human tissues and blood cells. The MicroRE-SUS study will be the first study to measure microcirculatory and mitochondrial function in patients with circulatory shock and link these findings with clinical outcomes. Methods and analysis This will be a prospective, observational study that includes patients undergoing elective cardiovascular surgery with cardiopulmonary bypass (CPB). Microcirculation will be
The Mitochondrial Permeability Transition: Role in Ischemia/Reperfusion Injury
Sepsis, 1999
The mitochondrial permeability transition (MPT) occurs when a non-speci~c pore opens in the inner mitochondrial membrane and converts the mitochondrion from an organelle whose ATP production sustains the normal function of the cell to an instrument of death. Conditions favouring the MPT including high [Ca 2ϩ ], oxidative stress and adenine nucleotide depletion, all of which occur when a tissue is reperfused following a period of ischemia. Cyclosporin A (CsA) and low pH (Ͻ7.0) are potent inhibitors of the MPT. Methods have been devised to demonstrate directly that the MPT pores open upon reperfusion but not during ischemia. The mechanism of the MPT appears to involve binding of mitochondrial cyclophilin (CyP) to the adenine nucleotide translocase (ANT) followed by a calcium-mediated conformational change that converts the ANT into a non-speci~c pore. Understanding the molecular mechanism has assisted in devising strategies that can be used to protect tissues from damage caused by reperfusion injury. These might also be of bene~t in the prevention of multiple organ failure for which reperfusion injury of the gut is thought to be the initial trigger. Protective regimes include the pretreatment of tissues prior to ischemia/reperfusion with CsA (binds to CyP), free radical scavengers that reduce oxidative stress (e.g., pyruvate and propofol) and agents that decrease pH i (e.g., pyruvate or amelioride derivatives). Reperfusion injury can produce both immediate cell death by necrosis or delayed apoptotic cell death and it appears that the mitochondria determine which route is taken. Prolonged opening leads to rapid cell death by necrosis, whilst transient opening leads to cytochrome c release and subsequent apoptosis hours or days later.
Microcirculation-driven mitochondrion dysfunction during the progression of experimental sepsis
Scientific reports, 2024
Sepsis is accompanied by a less-known mismatch between hemodynamics and mitochondrial respiration. We aimed to characterize the relationship and time dependency of microcirculatory and mitochondrial functions in a rodent model of intraabdominal sepsis. Fecal peritonitis was induced in rats, and multi-organ failure (MOF) was evaluated 12, 16, 20, 24 or 28 h later (n = 8/group, each) using rat-specific organ failure assessment (ROFA) scores. Ileal microcirculation (proportion of perfused microvessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI)) was monitored by intravital video microscopy, and mitochondrial respiration (OxPhos) and outer membrane (mtOM) damage were measured with high-resolution respirometry. MOF progression was evidenced by increased ROFA scores; microcirculatory parameters followed a parallel time course from the 16th to 28th h. Mitochondrial dysfunction commenced with a 4-h time lag with signs of mtOM damage, which correlated significantly with PPV, while no correlation was found between HI and OxPhos. High diagnostic value was demonstrated for PPV, mtOM damage and lactate levels for predicting MOF. Our findings indicate insufficient splanchnic microcirculation to be a possible predictor for MOF that develops before the start of mitochondrial dysfunction. The adequate subcellular compensatory capacity suggests the presence of mitochondrial subpopulations with differing sensitivity to septic insults.
Endothelial dysfunction and increased oxidative stress in mitochondrial diseases
Clinical Science, 2012
MDs (mitochondrial diseases) are a clinically heterogeneous group of disorders characterized by impairment of the respiratory chain function with altered oxidative phosphorylation. We tested the hypothesis that the function of vascular endothelium is affected by increased oxidative stress in MDs. A total of 12 patients with MDs and pair-matched controls were studied. Endothelial function was assessed by measuring FMD (flow-mediated vasodilation) of brachial and common femoral arteries. The test was repeated after vitamin C (500 mg, twice a day) and E (400 mg, once a day) supplementation for 30 days and 90 days after vitamin withdrawal. FMD was reduced in patients compared with controls [AUC/τ (time-averaged area under the curve) for the brachial artery, 1.05±0.24 compared with 4.19±0.59% respectively, P<0.001; AUC/τ for the femoral artery, 0.98±0.19 compared with 2.36±0.29% respectively, P=0.001; values are means±S.E.M.] and correlated (brachial artery) with plasma lactate (r=−0....
Monitoring of mitochondrial oxygenation during perioperative blood loss
BMJ Case Reports, 2021
One of the challenges in the management of acute blood loss is to differentiate whether blood transfusion is required or not. The sole use of haemoglobin values might lead to unnecessary transfusion in individual cases. The suggestion is that mitochondrial oxygen tension can be used as an additional monitoring technique to determine when blood transfusion is required. In this case report, we report mitochondrial oxygen measurements in a patient with perioperative blood loss requiring blood transfusion.
Current Opinion in Critical Care
Purpose of review To fully exploit the concept of hemodynamic coherence in resuscitating critically ill one should preferably take into account information about the state of parenchymal cells. Monitoring of mitochondrial oxygen tension (mitoPO 2) has emerged as a clinical means to assess information of oxygen delivery and oxygen utilization at the mitochondrial level. This review will outline the basics of the technique, summarize its development and describe the rationale of measuring oxygen at the mitochondrial level. Recent findings Mitochondrial oxygen tension can be measured by means of the protoporphyrin IX-Triplet State Lifetime Technique (PpIX-TSLT). After validation and use in preclinical animal models, the technique has recently become commercially available in the form of a clinical measuring system. This system has now been used in a number of healthy volunteer studies and is currently being evaluated in studies in perioperative and intensive care patients in several European university hospitals. Summary PpIX-TSLT is a noninvasive and well tolerated method to assess aspects of mitochondrial function at the bedside. It allows doctors to look beyond the macrocirculation and microcirculation and to take the oxygen balance at the cellular level into account in treatment strategies.
2021
Sepsis is a potentially life-threatening condition caused by a dysregulated host response to infection. Along with its progression, regulatory failure is frequently associated with a mismatch between oxygen delivery (DO2), oxygen consumption (VO2) and a deficit in oxygen extraction (ExO2) at the cellular level. The poorly functioning microvasculature reduces delivery of oxygen to the tissue, while the mitochondrial electron transport system (ETS) is deficient, being unable to use oxygen efficiently. These processes are closely linked and ultimately lead to microcirculatory and mitochondrial distress syndrome (MMDS), which is thought to mediate end organ damage. Given this background, the major goal of this thesis was to find a novel, clinically applicable maneuver for microcirculatory recruitment and mitochondrial resuscitation to minimize the energy deficit of the organs in experimental sepsis. In our studies Sprague Dawley rats were subjected to fecal peritonitis or a sham operati...