Impact of transient decrease in mixed venous oxygen saturation on prognosis in off-pump coronary artery bypass surgery: a retrospective cohort study.

BACKGROUND: The prognostic consequences of transient hemodynamic deterioration due to cardiac displacement, which is most severe during left circumflex artery (LCX) grafting in off-pump coronary artery bypass surgery (OPCAB) are unknown. This study aimed to investigate the association between mixed venous oxygen saturation (SvO2) < 60% during LCX grafting and the occurrence of composite of morbidity endpoints. METHODS: Data of patients who underwent elective OPCAB between January 2010 and December 2019 were reviewed. Logistic regression analysis was performed to detect risk factors for the composite of morbidity endpoints, defined as 30-day or in-hospital mortality, postoperative myocardial infarction, prolonged mechanical ventilation > 24 h, cerebrovascular accident, and acute kidney injury. RESULTS: Among 1,071 patients, the composite of morbidity endpoints occurred in 303 (28%) patients. SvO2 < 60% during LCX grafting was significantly associated with the composite of morbidity (OR: 2.72, 95% CI [1.60, 4.61], P < 0.001) along with advanced age, chronic kidney disease, ratio of early mitral inflow velocity to mitral annular early diastolic velocity, and EuroSCORE II. Other major hemodynamic variables including the cardiac index were not associated with the outcome. Additional regression analysis revealed pre-operative anemia as a predictor of SvO2 < 60% during LCX grafting (OR: 2.09, 95% CI [1.33, 3.29], P = 0.001). CONCLUSIONS: A decrease in SvO2 < 60%, albeit confined to the period of cardiac displacement, was associated with a 2.7-fold increased risk of detrimental outcomes after OPCAB, implying the prognostic importance of this transient deterioration in oxygen supply-demand balance.

Age-Related Difference in the Effect of Acute Hyperglycemia on Myocardial Ischemia-Reperfusion Injury.

Age and acute hyperglycemia are known risk factors of myocardial ischemia-reperfusion injury. We investigated age-related difference in the effect of acute hyperglycemia on myocardial ischemia-reperfusion injury in Sprague-Dawley rats (young, 3 months; middle-aged, 10-12 months; and old, 22-24 months). The rats received 1.2 g/kg dextrose or normal saline and were subjected to coronary artery occlusion for 45 minutes followed by reperfusion for 240 minutes. Infarct size and ejection fraction were measured. The levels of apoptosis-related proteins (C-PARP, Bcl-2, Bax, and cytochrome c) and autophagy-related proteins (Bnip3, Beclin-1, Atg5, and LC3B-II) were evaluated. Infarct size increased with acute hyperglycemia in young and middle-aged rats but not in old rats, whereas the reduction of ejection fraction after ischemia-reperfusion was aggravated by acute hyperglycemia in all age groups. Acute hyperglycemia increased Bnip3 and Beclin-1 expressions after ischemia-reperfusion in young and middle-aged rats but not in old rats, whereas it increased the expression of Bax, cytochrome c, Atg5, and LC3B-II only in young or middle-aged rats. Conclusively, acute hyperglycemia does not aggravate myocardial ischemia-reperfusion injury in old rats, unlike in young and middle-aged rats. This heterogeneity may be due to attenuated changes in protein signaling after ischemia-reperfusion injury under acute hyperglycemia in old rats.

Apoptosis Signal-regulating Kinase 1 Silencing on Astroglial Inflammasomes in an Experimental Model of Ischemic Stroke.

Activation of the inflammasome complex contributes to the inflammatory response and cell death under pathologic conditions. The nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 2 (NLRP2) inflammasome is activated in astrocytes after cerebral ischemia, which can aggravate ischemic damage. Apoptosis signal-regulating kinase 1 (ASK1) is an early activator and immune-regulator after ischemic injury, that can lead to cell death. The objective of the present study was to evaluate the role of ASK1 in controlling NLRP2 inflammasomes in astrocytes after cerebral ischemia. In a mouse model of ischemic stroke, the levels of NLRP2 inflammasome components, and interleukin (IL)-1ß and IL-18, were quantified in different brain regions. In addition, an astrocyte cell line was subjected to oxygen-glucose deprivation and reperfusion (OGD/R) injury, and the levels of NLRP2 inflammasome factors, IL-1ß and IL-18 were evaluated. Ischemic brain injury activated astrocytes. The levels of NLRP2 inflammasome components, IL-1ß and IL-18 productions, and cell death increased in the cortex and striatum after ischemic injury. In cultured astrocytes, NLRP2 inflammasome components, IL-1ß and IL-18 levels were upregulated after OGD/R. ASK1 silencing or inhibition efficiently reduced NLRP2 inflammasome components and pro-inflammatory cytokine levels in mice and cultured astrocytes. Our findings identify a key role for ASK1 in regulating astroglial inflammasomes after cerebral ischemia. We suggest ASK1 as one of the main targets for astroglial inflammasomes in ischemic stroke.