Protocol for the MicroRESUS study: The impact of circulatory shock and resuscitation on microcirculatory function and mitochondrial respiration after cardiovascular surgery

Greenwood, John C.; Talebi, Fatima M; Jang, David H.; Spelde, Audrey E.; Kilbaugh, Todd J.; Shofer, Frances S.; Acker, Michael A.; Augoustides, John; Bakker, Jan; Meyer, Nuala J.; Brenner, J.; Muzykantov, Vladimir R.; Abella, Benjamin S.

doi:10.1371/journal.pone.0273349

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…The prognosis of postoperative patients with ATAAD may be impacted by AKI, which could result in a substantially worse outcome than a single ATAAD. Surgery after CPB negatively affects the microcirculatory system [ 22 ], and platelet counts following surgery have recently been associated with reduced sublingual microcirculation [ 23 ]. As a result, AKI may result from reduced microvascular flow in the kidneys.…”

Section: Discussionmentioning

confidence: 99%

Postoperative thrombocytopenia and subsequent consequences in acute type A aortic dissection

Tang,

Shao

2023

Annals of Medicine

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Objectives To ascertain if postoperative thrombocytopenia following open aortic surgery with a median sternotomy can predict early- and intermediate-term morbidity and mortality. Methods From January 2018 to December 2022, a comparison was made between patients who had and didn’t have postoperative thrombocytopenia (defined as a nadir < 75 × 103/μL after 72 h of open aortic surgery with median sternotomy). Intermediate-term mortality during follow-up was the main result, with cerebrovascular accident and acute renal injury requiring dialysis as secondary events. Inverse probability treatment weighting (IPTW) was used to account for selection bias between groups. The Kaplan-Meier method with the log-rank test was used to assess intermediate-term survivals following IPTW modification. To identify the nonlinear link between platelet nadir and mortality probability, a generalized additive mix model was applied. To help increase power in testing for the overall effect of platelet nadir on outcomes in the generalized additive mix model, the hazard ratios and 95% CIs for each subgroup and their interactions were examined. Results The study included 457 patients, 347 male (75.9%), with mean age of 54 ± 12 years. The last follow-up was done on April 14 th , 2023 and the median follow-up time was 16 (6-31) months. Following IPTW, patient characteristics were balanced among cohorts. Platelet nadir was found to be significantly inversely related to early-term mortality (IPTW-adjusted hazard ratio = 0.968 (0.960, 0.977), p < 0.001), and AKI requiring dialysis (IPTW-adjusted hazard ratio = 0.979 (0.971, 0.986), p < 0.001). A nonlinear relationship between platelet nadir and mortality risk probability during follow-up visually showed that the likelihood of mortality decreased with platelet nadir increased. In confounder-adjusted survival (‘postoperative thrombocytopenia not acquired’ vs ‘postoperative thrombocytopenia’; HR: 0.086 [95% CI: 0.045-0.163]; p < 0.01) analysis, non-acquired postoperative thrombocytopenia was associated with a lower risk of mortality, and the treatment benefit was validated in IPTW-adjusted analysis, which showed an HR of 0.067. Conclusions Early postoperative thrombocytopenia following type A aortic dissection surgery is a risk factor for morbidity and mortality. Because postoperative thrombocytopenia can indicate a poor prognosis, monitoring early postoperative platelets helps identify individuals who may develop late postoperative problems, which is performed by this affordable biomarker.

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Section: Discussionmentioning

confidence: 99%

Postoperative thrombocytopenia and subsequent consequences in acute type A aortic dissection

Tang,

Shao

2023

Annals of Medicine

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“…829765 on August 3, 2020), registered with ClinicalTrials.gov (NCT05330676), and performed in accordance with the ethical standards of the Helsinki Declaration of 1975. The full study protocol has been previously published, which includes a more detailed description of clinical, imaging, and laboratory collection time points (9).…”

Section: Methodsmentioning

confidence: 99%

“…A sample of PBMCs were obtained from the plasma buffy coat within 1-hour of blood draw and used to measure mitochondrial respiration as previously described (9, 14). Briefly, between 4 and 5 × 10 6 PBMC cells were suspended in a MiR05 buffer followed by exposure to a substrate-uncoupler-inhibitor titration (SUIT) protocol using an Oroboros O2k FluoRespirometer (Oroboros Instruments, Innsbruck, Austria).…”

Section: Methodsmentioning

confidence: 99%

Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass*

Greenwood,

Talebi,

Jang

et al. 2024

Critical Care Medicine

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Objectives: Quantify the relationship between perioperative anaerobic lactate production, microcirculatory blood flow, and mitochondrial respiration in patients after cardiovascular surgery with cardiopulmonary bypass. Design: Serial measurements of lactate-pyruvate ratio (LPR), microcirculatory blood flow, plasma tricarboxylic acid cycle cycle intermediates, and mitochondrial respiration were compared between patients with a normal peak lactate (≤ 2 mmol/L) and a high peak lactate (≥ 4 mmol/L) in the first 6 hours after surgery. Regression analysis was performed to quantify the relationship between clinically relevant hemodynamic variables, lactate, LPR, and microcirculatory blood flow. Setting: This was a single-center, prospective observational study conducted in an academic cardiovascular ICU. Patients: One hundred thirty-two patients undergoing elective cardiovascular surgery with cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Patients with a high postoperative lactate were found to have a higher LPR compared with patients with a normal postoperative lactate (14.4 ± 2.5 vs. 11.7 ± 3.4; p = 0.005). Linear regression analysis found a significant, negative relationship between LPR and microcirculatory flow index (r = –0.225; β = –0.037; p = 0.001 and proportion of perfused vessels: r = –0.17; β = –0.468; p = 0.009). There was not a significant relationship between absolute plasma lactate and microcirculation variables. Last, mitochondrial complex I and complex II oxidative phosphorylation were reduced in patients with high postoperative lactate levels compared with patients with normal lactate (22.6 ± 6.2 vs. 14.5 ± 7.4 pmol O2/s/106 cells; p = 0.002). Conclusions: Increased anaerobic lactate production, estimated by LPR, has a negative relationship with microcirculatory blood flow after cardiovascular surgery. This relationship does not persist when measuring lactate alone. In addition, decreased mitochondrial respiration is associated with increased lactate after cardiovascular surgery. These findings suggest that high lactate levels after cardiovascular surgery, even in the setting of normal hemodynamics, are not simply a type B phenomenon as previously suggested.

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“…Repeated measurements will be obtained at defined time points after ROSC. To ensure only vessels contributing to tissue gas exchange are included, only vessels < 20 μm in diameter will be included in IDF analysis [42][43][44][45].…”

Section: Cortical Microcirculation Imaging and Cerebral Blood Flow Me...mentioning

confidence: 99%

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol

Greenwood,

Morgan,

Abella

et al. 2024

PLoS ONE

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Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50–80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

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Protocol for the MicroRESUS study: The impact of circulatory shock and resuscitation on microcirculatory function and mitochondrial respiration after cardiovascular surgery

Cited by 7 publications

References 25 publications

Postoperative thrombocytopenia and subsequent consequences in acute type A aortic dissection

Postoperative thrombocytopenia and subsequent consequences in acute type A aortic dissection

Anaerobic Lactate Production Is Associated With Decreased Microcirculatory Blood Flow and Decreased Mitochondrial Respiration Following Cardiovascular Surgery With Cardiopulmonary Bypass*

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol

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