BACKGROUND

Postoperative atrial fibrillation (POAF) is the most common arrythmia to occur after cardiovascular surgery. Inflammation being pivotal in POAF perpetuation has been utilized as a therapeutic target. Owing to their anti-inflammatory and anti-oxidant effects, beta-blockers (BB) and N-acetylcysteine (NAC) became research interests in the pursuit for an effective POAF prevention strategy.

OBJECTIVE

To determine the efficacy of NAC plus BB versus BB alone in preventing POAF in cardiac surgery patients.

METHODOLOGY

A literature search using the following search engines: PubMed/Medline, Cochrane Review Central, Clinical Trials Registry, ResearchGate, Mendeley and Google Scholar for relevant randomized trials were conducted. Published and unpublished studies indexed from inception until 2023 were included. Three independent reviewers evaluated the randomized clinical trials (RCTs) for eligibility. The pooled estimates for POAF prevention as primary outcome and MACE, mortality, myocardial infarction, stroke, ICU LOS and hospital LOS as secondary outcomes were measured using the RStudio statistical software.

RESULTS

Seven eligible RCTs allocated 1069 cardiac surgery patients to NAC + BB (n=539) and BB alone (N = 530) treatment arms. The effect estimate using random effect model disclosed significantly reduced POAF events (RR 0.62, 95% CI [0.44, 0.86], p = 0.005) in those on NAC + BB. While no statistical difference between the study arms were demonstrated in reducing mortality (RR 0.63, 95% CI [0.23, 1.73], p = 0.37); myocardial infarction (RR 1.02, 95% CI [0.49, 2.13], p = 0.96); stroke (RR 0.95, 95% CI [0.24, 3.68], p = 0.94); ICU LOS (std. mean difference 0.14, 95% CI [-0.43, 0.70], p = 0.41), and hospital LOS (std. mean difference 0.08, 95% CI [-0.06, 0.21], p = 0.19).

CONCLUSION

Among cardiac surgery patients, the use of NAC in combination with BB compared with BB alone significantly reduced POAF.

Acetylcysteine ; Arrhythmias, Cardiac ; Atrial Fibrillation ; Myocardial Infarction ; Omega-chloroacetophenone

(R)-chlorprenaline, a selective activator of beta2 receptor and an effective drug for bronchitis and asthma, is industrially prepared from (R)-2'-chloro-1-phenyl-ethanol. In this communication, we describe (1) the identification of Saccharomyces cerevisiae B5 as an effective host for stereoselective reduction of 2'-chloroacetophenone to (R)-2'-chloro-1-phenyl-ethanol; (2) the presence of ethanol enhances the conversion; and (3) the biochemical factors that effect the yield of the product. Among the four yeast strains capable of reduction 2'-chloroacetophenone to (R)-2'-chloro-1-phenyl-ethanol we screened, Saccharomyces cerevisiae B5 showed the highest activity and stereoselectivity, and was used for the subsequent study. The effect of the presence of methanol, ethanol, 2-propanol, 1-butanol, glucose, glycerol and lactic acid was first investigated, as it was previously reported that they increased the yield and stereoselectivity of the reaction. The addition of the co-substrate methanol, ethanol, 2-propanol, 1-butanol, glucose and glycerol favored the formation of the 2'-chloroacetophenone to (R)-2'-chloro-1-phenyl-ethanol. Lactic acid inhibited the enzyme activity. Ethanol is the best co-substrate among the seven co-substrates and under the optimum concentration of 5% , the yield of (R)-2'-chloro-1-phenyl-ethanol was increased from 17% to 74%. The oxidation of ethanol regenerates NADH required for the reduction. The effects of the reaction time, pH, cell concentration, substrate concentration and temperature on the reduction were investigated next. The enantiometric excess of (R)-2'-chloro-1-phenyl-ethanol reached 100% under the optimal condition: pH8.0, 25 degrees C and 5% ethanol. The product yield went up with the increasing Saccharomyces cerevisiae B5 concentration and reached 100% when the cell dry weight was 10.75 mg/mL and 2'-chloroacetophenone was 6.47 mmol/L. The yield of (R)-2'-chloro-1-phenyl-ethanol decreased sharply with the increase of substrate concentration, as the high concentration of substrates is toxic to the cell and inhibits the activity of reductases. The aerobic cultivation of the yeast and shaking during the reaction increased the yield of (R)-2'-chloro-1-phenyl-ethanol. The yeast can be reused up to 15 times. This research paves the way for economical preparation of chiral 2'-chloroacetophenone to R-2'-chloro-1-phenylethanol.
Ethanol ; metabolism ; Hydrogen-Ion Concentration ; Oxidation-Reduction ; Phenylethyl Alcohol ; chemistry ; metabolism ; Saccharomyces cerevisiae ; metabolism ; Stereoisomerism ; omega-Chloroacetophenone ; chemistry ; metabolism

The ketoreductase (KR) domain in the first extending module of the polyketide synthase (PKS) catalyzes the reductions of both an α-keto group and a β-keto group in the biosynthesis of bacillaene, suggesting the intrinsic substrate promiscuity. In order to further investigate the substrate specificity, the KR domain (BacKR1) was heterologously overexpressed in Escherichia coli. In vitro enzymatic analysis showed that only one of the four diastereomers was formed in the reduction of the racemic (±)-2-methyl-3-oxopentanoyl-N-acetylcysteamine thioester catalyzed by BacKR1. In addition, BacKR1 was revealed to catalyze the reductions of cyclohexanone and p-chloroacetophenone, indicating the potential of KR domians of PKSs as biocatalysts.
Bacterial Proteins ; genetics ; metabolism ; Catalysis ; Cyclohexanones ; metabolism ; Escherichia coli ; enzymology ; Polyketide Synthases ; genetics ; metabolism ; Protein Structure, Tertiary ; Substrate Specificity ; omega-Chloroacetophenone ; metabolism

BACKGROUND: Coronary microcirculation impairment with sequential decrease in cardiac function is reflected by abnormal left ventricular ejection fraction reserve (LVEFR),which precedes diagnostic evidence of myocardial insult. However, prognostic utility of LVEFR is less, if not least explored. The aim of this study was to evaluate the clinical utility of LVEFR in predicting major cardiac events (MACE) among patients with and suspected coronary artery disease (CAD).
MATERIALS AND METHODS: A retrospective cohort study of 245 patients who underwent stress thallium-201 myocardial perfusion scan (MPS) was conducted. The patients were categorized as having normal or abnormal perfusion scan. Each group was subdivided into normal and abnormal LVEFR groups. All subjects were followed up for any major adverse cardiac events 36 months after MPS through review of hospital records.
RESULTS: There was an overall increase in the likelihood of cardiac events with abnormal LVEFR (i.e., odds ratio of 2.99,p=<0.01). Majority of subjects with abnormal MPS also had abnormal LVEFR showing a significantly lower mean LVEFR (1.17± 7.30 vs. 3.02 ± 7.36p =<0.01).
CONCLUSION: Abnormal LVEFR can be used as an independent predictor of cardiac events which can be observed in subjects with normal and abnormal perfusion scans alike.

Human ; Male ; Female ; Middle Aged ; Adult ; Coronary Artery Disease ; Thallium ; Omega-chloroacetophenone ; Microcirculation ; Stroke Volume ; Heart ; Thallium Radioisotopes ; Myocardium ; Perfusion Imaging

BACKGROUND: Coronary microcirculation impairment with sequential decrease in cardiac function is reflected by abnormal left ventricular ejection fraction reserve (LVEFR),which precedes diagnostic evidence of myocardial insult. However, prognostic utility of LVEFR is less, if not least explored. The aim of this study was to evaluate the clinical utility of LVEFR in predicting major cardiac events (MACE) among patients with and suspected coronary artery disease (CAD).
MATERIALS AND METHODS: A retrospective cohort study of 245 patients who underwent stress thallium-201 myocardial perfusion scan (MPS) was conducted. The patients were categorized as having normal or abnormal perfusion scan. Each group was subdivided into normal and abnormal LVEFR groups. All subjects were followed up for any major adverse cardiac events 36 months after MPS through review of hospital records.
RESULTS: There was an overall increase in the likelihood of cardiac events with abnormal LVEFR (i.e., odds ratio of 2.99,p=<0.01). Majority of subjects with abnormal MPS also had abnormal LVEFR showing a significantly lower mean LVEFR (1.17± 7.30 vs. 3.02 ± 7.36p =<0.01).
CONCLUSION: Abnormal LVEFR can be used as an independent predictor of cardiac events which can be observed in subjects with normal and abnormal perfusion scans alike.

Human ; Male ; Female ; Middle Aged ; Adult ; Coronary Artery Disease ; Thallium ; Omega-chloroacetophenone ; Microcirculation ; Stroke Volume ; Heart ; Thallium Radioisotopes ; Myocardium ; Perfusion Imaging