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Preventing Myocardial Injury Following Non-Cardiac Surgery: A Potential Role for Preoperative Antioxidant Therapy with Ubiquinone.

ABSTRACT: Over 240 million non-cardiac operations occur each year and are associated with a 15-20% incidence of adverse perioperative cardiovascular events. Unfortunately, preoperative therapies that have been useful for chronic ischemic heart diseases, such as coronary artery revascularization, antiplatelet agents, and beta-blockers have failed to improve outcomes. In a pre-clinical swine model of ischemic heart disease, we showed that daily administration of ubiquinone (coenzyme Q₁₀, CoQ₁₀) enhances the antioxidant status of mitochondria within chronically ischemic heart tissue, potentially via a PGC1?-dependent mechanism. In a randomized controlled trial, among high-risk patients undergoing elective vascular surgery, we showed that NT Pro-BNP levels are an important means of risk-stratification during the perioperative period and can be lowered with administration of CoQ₁₀ (400 mg/day) for 3 days prior to surgery. The review provides background information for the role of oxidant stress and inflammation during high-risk operations and the potential novel application of ubiquinone as a preoperative antioxidant therapy that might reduce perioperative adverse cardiovascular outcomes.

SUBMITTER: Chen Q

PROVIDER: S-EPMC7916807 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Preventing Myocardial Injury Following Non-Cardiac Surgery: A Potential Role for Preoperative Antioxidant Therapy with Ubiquinone.

Chen Qun Q Qi Steven S Hocum-Stone Laura L Lesnefsky Edward E Kelly Rosemary F RF McFalls Edward O EO

Antioxidants (Basel, Switzerland) 20210210 2

Over 240 million non-cardiac operations occur each year and are associated with a 15-20% incidence of adverse perioperative cardiovascular events. Unfortunately, preoperative therapies that have been useful for chronic ischemic heart diseases, such as coronary artery revascularization, antiplatelet agents, and beta-blockers have failed to improve outcomes. In a pre-clinical swine model of ischemic heart disease, we showed that daily administration of ubiquinone (coenzyme Q<sub>10</sub>, CoQ<sub> ...[more]

PMID: 33579045

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Project description:BACKGROUND:Myocardial injury after non-cardiac surgery (MINS) is the most common perioperative cardiovascular complication and is independently associated with 30-day mortality. We aimed to assess the association between preoperative glucose concentration and postoperative MINS and mortality. METHODS:The VISION study is a prospective cohort study done at 12 centres in eight countries. Patients aged 45 years or older who required at least one overnight hospital admission for non-cardiac surgery were enrolled from Aug 6, 2007, to Jan 11, 2011. In the GlucoVISION analysis, we assessed the relations between preoperative casual or fasting glucose concentration and MINS within 3 days after surgery using logistic regression, and 30-day mortality using Cox proportional regression, in people with and without diabetes. FINDINGS:11?954 patients were included in this analysis, of whom 2809 (23%) had diabetes. Within the first three postoperative days, MINS occurred in 813 (7%) patients. 249 (2%) patients died by day 30. More patients with diabetes had MINS (odds ratio [OR] 1·98 [95% CI 1·70-2·30]; p<0·0001), and died (OR 1·41 [1·08-1·86]; p=0·016) than did patients without diabetes. Casual glucose concentrations were associated with MINS in all patients (adjusted OR 1·06 [1·04-1·09] per 1 mmol/L increment in glucose; p=0·0003), and with death in patients without diabetes (adjusted hazard ratio [HR] 1·13 [95% CI 1·05-1·23] per mmol/L; p=0·002). We noted a progressive relation between unadjusted fasting glucose concentration and both MINS (OR 1·14 [1·08-1·20] per mmol/L; p<0·0001), driven by the effect in the subgroup without previous diabetes (pinteraction=0·025), and 30-day mortality (HR 1·10 [1·02-1·19] per mmol/L; p=0·013). For patients without diabetes, casual glucose of more than 6·86 mmol/L and fasting glucose of more than 6·41 mmol/L predicted MINS (OR 1·71 [1·36-2·15]; p<0·0001, and OR 2·71 [1·85-3·98]; p<0·0001, respectively). For patients with diabetes, only casual glucose concentration more than 7·92 mmol/L predicted MINS (OR 1·47 [1·10-1·96]; p=0·0096). INTERPRETATION:Preoperative glucose concentration, particularly casual glucose concentration, predicts risk for postoperative cardiovascular outcomes, especially in patients without diabetes. FUNDING:Full funding sources listed at the end of the paper (see Acknowledgments).

Project description:Acute kidney injury is a frequent complication of cardiac surgery and increases morbidity and mortality. As preoperative biomarkers predicting the development of acute kidney injury are not available, we have tested the hypothesis that preoperative plasma levels of endogenous ouabain may function as this type of biomarker.Endogenous ouabain is an adrenal stress hormone associated with adverse cardiovascular outcomes. Its involvement in acute kidney injury is unknown. With studies in patients and animal settings, including isolated podocytes, we tested the above mentioned hypothesis.Preoperative endogenous ouabain was measured in 407 patients admitted for elective cardiac surgery and in a validation population of 219 other patients. We also studied the effect of prolonged elevations of circulating exogenous ouabain on renal parameters in rats and the influence of ouabain on podocyte proteins both "in vivo" and "in vitro."In the first group of patients, acute kidney injury (2.8%, 8.3%, 20.3%, p < 0.001) and ICU stay (1.4±0.38, 1.7±0.41, 2.4±0.59 days, p = 0.014) increased with each incremental preoperative endogenous ouabain tertile. In a linear regression analysis, the circulating endogenous ouabain value before surgery was the strongest predictor of acute kidney injury. In the validation cohort, acute kidney injury (0%, 5.9%, 8.2%, p < 0.0001) and ICU stay (1.2±0.09, 1.4±0.23, 2.2±0.77 days, p = 0.003) increased with the preoperative endogenous ouabain tertile. Values for preoperative endogenous ouabain significantly improved (area under curve: 0.85) risk prediction over the clinical score alone as measured by integrate discrimination improvement and net reclassification improvement. Finally, in the rat model, elevated circulating ouabain reduced creatinine clearance (-18%, p < 0.05), increased urinary protein excretion (+ 54%, p < 0.05), and reduced expression of podocyte nephrin (-29%, p < 0.01). This last finding was replicated ex vivo by incubating podocyte primary cell cultures with low-dose ouabain.Preoperative plasma endogenous ouabain levels are powerful biomarkers of acute kidney injury and postoperative complications and may be a direct cause of podocyte damage.

Project description:Acute kidney injury (AKI) after cardiac surgery is a common and serious complication. Although lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration in patients with chronic kidney injury, it is not well-known whether preoperative low serum bicarbonate levels are associated with the development of AKI in patients who undergo cardiac surgery. Therefore, the clinical implication of preoperative serum bicarbonate levels on AKI occurrence after cardiac surgery was investigated. Patients who underwent coronary artery bypass or valve surgery at Yonsei University Health System from January 2013 to December 2014 were enrolled. The patients were divided into 3 groups based on preoperative serum bicarbonate levels, which represented group 1 (below normal levels) <23?mEq/L; group 2 (normal levels) 23 to 24?mEq/L; and group 3 (elevated levels) >24?mEq/L. The primary outcome was the predicated incidence of AKI 48?hours after cardiac surgery. AKI was defined according to Acute Kidney Injury Network criteria. Among 875 patients, 228 (26.1%) developed AKI within 48?hours after cardiac surgery. The incidence of AKI was higher in group 1 (40.9%) than in group 2 (26.5%) and group 3 (19.5%) (P?<?0.001). In addition, the duration of postoperative stay in a hospital intensive care unit (ICU) was longer for AKI patients and for those in the low-preoperative-serum-bicarbonate-level groups. A multivariate logistic regression analysis showed that low preoperative serum bicarbonate levels were significantly associated with AKI even after adjustment for age, sex, hypertension, diabetes mellitus, operation type, preoperative hemoglobin, and estimated glomerular filtration rate. In conclusion, low serum bicarbonate levels were associated with higher incidence of AKI and prolonged ICU stay. Further studies are needed to clarify whether strict correction of bicarbonate levels close to normal limits may have a protective role in preventing further AKI development.

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Preventing Myocardial Injury Following Non-Cardiac Surgery: A Potential Role for Preoperative Antioxidant Therapy with Ubiquinone.

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Preventing Myocardial Injury Following Non-Cardiac Surgery: A Potential Role for Preoperative Antioxidant Therapy with Ubiquinone.

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