Zhengyuan Xia

Background. Pretreatment with the angiotensin‐converting inhibitor captopril or volatile anesthetic isoflurane has, respectively, been shown to attenuate myocardial ischemia reperfusion (MI/R) injury in rodents and in patients. It is unknown whether or not captopril pretreatment and isoflurane preconditioning (Iso) may additively or synergistically attenuate MI/R injury. Methods and Results. Patients selected for heart valve replacement surgery were randomly assigned to five groups: untreated control (Control), captopril pretreatment for 3 days (Cap3d), or single dose captopril (Cap1hr, 1 hour) before surgery with or without Iso (Cap3d+Iso and Cap1hr+Iso). Rabbit MI/R model was induced by occluding coronary artery for 30 min followed by 2‐hour reperfusion. Rabbits were randomized to receive sham operation (Sham), MI/R (I/R), captopril (Cap, 24 hours before MI/R), Iso, or the combination of captopril and Iso (Iso+Cap). In patients, Cap3d+Iso but not Cap1hr+Iso additively reduced postischemic myocardial injury and attenuated postischemic myocardial inflammation. In rabbits, Cap or Iso significantly reduced postischemic myocardial infarction. Iso+Cap additively reduced cellular injury that was associated with improved postischemic myocardial functional recovery and reduced myocardial apoptosis and attenuated oxidative stress. Conclusion. A joint use of 3‐day captopril treatment and isoflurane preconditioning additively attenuated MI/R by reducing oxidative stress and inflammation.

Inhalation anesthetic isoflurane inhibits hypoxia pulmonary vasoconstriction (HPV), while dexmedetomidine (Dex) could reduce the dose of isoflurane inhalation and potentiate HPV, but the mechanism is unclear. Inhibition of reactive oxygen species (ROS) production can favor HPV during one‐lung ventilation (OLV). Similarly, nitric oxide (NO), an important endothelium‐derived vasodilator in lung circulation, can decrease the regional pulmonary vascular resistance of ventilated lung and reduce intrapulmonary shunting. We hypothesized that Dex may augment HPV and improve oxygenation during OLV through inhibiting oxidative stress and increasing NO release. Patients undergoing OLV during elective thoracic surgery were randomly allocated to either isoflurane + saline (NISO, n = 24) or isoflurane + dexmedetomidine (DISO, n = 25) group. Anesthesia was maintained with intravenous remifentanil and inhalational isoflurane (1.0–2.0%), with concomitant infusion of dexmedetomidine 0.7 μgkg⁻¹h⁻¹ in DISO and saline 0.25 mL kg⁻¹h⁻¹ in NISO group. Hemodynamic variables or depth of anesthesia did not significantly differ between groups. Administration of Dex significantly reduced Qs/Qt and increased PaO₂ after OLV, accompanied with reduced lipid peroxidation product malondialdehyde and higher levels of SOD activity as well as serum NO (all P < 0.05 DISO versus NISO). In conclusion, reducing oxidative stress and increasing NO release during OLV may represent a mechanism whereby Dex potentiates HPV.

Lei S, et al. Yonsei Med J. 2012 Mar;53(2):294-303. https://doi.org/10.3349/ymj.2012.53.2.294

This study was to explore whether repeated non-invasive limb ischemic pre-conditioning (NLIP) can confer an equivalent cardioprotection against myocardial ischemia-reperfusion (I/R) injury in acute diabetic rats to the extent of conventional myocardial ischemic pre-conditioning (MIP) and whether or not the delayed protection of NLIP is mediated by reducing myocardial oxidative stress after ischemia-reperfusion. Streptozotocin-induced diabetic rats were randomized to four groups: Sham group, the I/R group, the MIP group and the NLIP group. Compared with the I/R group, both the NLIP and MIP groups showed an amelioration of ventricular arrhythmia, reduced myocardial infarct size, increased activities of total superoxide dismutase (SOD), manganese-SOD and glutathione peroxidase, increased expression of manganese-SOD mRNA and decreased xanthine oxidase activity and malondialdehyde concentration (All p < 0.05 vs I/R group). It is concluded that non-invasive limb ischemic pre-conditioning reduces oxidative stress and attenuates myocardium ischemia-reperfusion injury in diabetic rats.

The circulatory inflammatory cytokine tumor necrosis factor alpha (TNF-α) is increased in pathologic conditions that initiate or exacerbate vascular endothelial injury, such as diabetes. Protein kinase C (PKC) has been shown to play a critical role in TNF-α-induced human endothelial cell apoptosis. However, the relative roles played by specific isoforms of PKC in TNF-α-induced human endothelial cell apoptosis have not been addressed. We investigated the effects of a selective PKCβ₂inhibitor (CGP53353) on TNF-α-induced apoptosis in human vascular endothelial cells (cell line ECV304) and on the production of reactive oxygen species and nitric oxide, and compared its effects with rottlerin, a reagent that has been shown to reduce PKCδ protein levels. Cultured human vascular endothelial cells (ECV304) were treated for 24 h with one of 4 regimes: 40 ng/mL TNF-α alone (TNF-α), TNF-α with 10 µmol/L rottlerin (T+rottlerin), TNF-α with 1 µmol/L CGP53353 (T+CGP), or untreated (control). Cell viability was measured by MTT assay, and cell apoptosis was assessed by flow cytometry. TNF-α-induced endothelial cell apoptosis was associated with dramatic increases in production of intracellular hydrogen peroxide (approximately 20 times greater than control) and superoxide (approximately 16 times greater than control), as measured by dichlorofluorescein and dihydroethidium fluorescent staining, respectively. This increase was accompanied by reduced activity of superoxide dismutase and glutathione peroxidase and, subsequently, an increase in the lipid peroxidation product malondialdehyde. CGP53353, but not rottlerin, abolished or attenuated all these changes. We conclude that PKCβ₂plays a major role in TNF-α-induced human vascular endothelial cell apoptosis.

To the Editor:— I read with great interest the recently published article by Nakahata et al. ,1 “Propofol Restores Brain Microvascular Function Impaired by High Glucose via the Decrease in Oxidative Stress.” In this study, the authors observed that propofol, at potentially clinically relevant concentrations, dose-dependently attenuated or abolished rat brain microvascular dysfunction induced by high glucose, and that the protection of propofol, similar to that of the superoxide dismutase mimetic Tempol, is attributable to its inhibition of superoxide production induced by high glucose. Further, the authors found that nicotinamide adenine dinucleotide phosphate oxidase, but not xanthine oxidase, is the major source of superoxide production in the brain microvascular arteriolar wall after high glucose stimulation.1 This is an interesting finding because nicotinamide adenine dinucleotide phosphate oxidase has also be reported as a major source of superoxide production in the diabetic heart2 that is complicated by hypertrophic cardiomyopathy in the rat.3 Therefore, theoretically, propofol may provide protection against oxidative injury of the diabetic heart through superoxide scavenging.