Effects of Spironolactone on Hypoxia-Inducible Factor-1α in the Patients Receiving Coronary Artery Bypass Grafting

Abstract

:We explored the protective effect of spironolactone on cardiac function in the patients undergoing coronary artery bypass grafting (CABG) by determining serum hypoxia-inducible factor-1α (HIF-1α) before and after CABG. We used the propensity score matching method retrospectively to select 174 patients undergoing CABG in our hospital from March 2018 to December 2019. Of the 174 patients, 87 patients taking spironolactone for more than 3 months before CABG were used as a test group and other 87 patients who were not taking spironolactone as a control group. In all patients, serum HIF-1α and troponin I levels were determined before as well as 24 hours and 7 days after CABG, serum N-terminal probrain natriuretic peptide (NT-proBNP) level was determined before as well as 12, 24, and 36 hours after CABG, and electrocardiographic monitoring was performed within 36 hours after CABG. The results indicated that there were no significant differences in the HIF-1α level between the test group and the control group before and 7 days after CABG, but the HIF-1α level was significantly lower in the test group than that in the control group 24 hours after CABG (P < 0.01). The 2 groups were not significantly different in the troponin I level at any time point. There was no significant difference in the serum NT-proBNP level between the test group and the control group before CABG, but NT-proBNP (BNP) levels were all significantly lower in the test group than those in the control group at postoperative 12, 24, and 36 hour time points (all P <0.05). The incidence of postoperative atrial fibrillation was also significantly lower in the test group than that in the control group (P = 0.035). Spironolactone protects cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling.

Vascular Endothelial Barrier Protection Prevents Atrial Fibrillation by Preserving Cardiac Nanostructure

“…Spironolactone was distinctly effective in reducing the risk of new-onset AF, mirroring levels of vascular leak-inducing cytokines, which are only elevated in early-stage AF patients 5,6,[26][27][28] , suggesting that it may be uniquely useful in treating early-stage AF. Thus, our results, along with those of the aforementioned clinical trials 12,[47][48][49] suggest that spironolactone and mefloquine merit consideration for antiarrhythmic therapy specifically in early stages of AF in a setting of elevated inflammation.…”

“…Similar antiarrhythmic effects were observed with clinically relevant small molecule alternatives, mefloquine and spironolactone, at doses selected to maximize inhibition while minimizing any off-target effects. Notably, others, who evaluated spironolactone in AF as an aldosterone antagonist, reported antiarrhythmic efficacy in early-stage 12,47,48 but not persistent/permanent 49 AF patients. This highlights the relevance of a targeted therapeutic approach based on logical, mechanistic understanding of the underlying drivers of AF.…”

“…During periods of stress, or in regions of injury, these non-specific channels remain open as part of the inflammatory response. Several studies have reported vasculoprotective effects with Cx43 HC and Panx1 channel inhibition in both cardiac [10][11][12][13] and non-cardiac tissues 14,15 . Thus, we investigated the potential of these inhibitors as antiarrhythmic therapies in our vascular leak-induced atrial arrhythmia model.…”