Original articleCardiovascularDiazoxide Provides Maximal KATP Channels Independent Protection if Present Throughout Hypoxia
Section snippets
Material and Methods
The experiments were performed on right atrial trabeculae obtained from patients undergoing elective coronary artery surgery (Table 1). Specimens acquired from diabetic patients were excluded. The Local Bioethics Committee approval for the use of human tissue was obtained and individual patient consent was waived.
The tissue was transferred in ice-cold Krebs-Henseleit solution to the laboratory. The single trabecula less than 1 mm in diameter was mounted in the organ chamber (Schuler Organbath;
Results
The recovery of contraction force at 10 minutes of reoxygenation after 90-minute hypoxia was on average 30% ± 2.7% in control. It was significantly enhanced by adding 100 μΜ diazoxide to the tissue bath. When diazoxide was present throughout hypoxia, the 10-minute recovery was 65% ± 4.3% (p < 0.001); and when it was added 10 minutes before and present throughout hypoxia, it reached 82% ± 10.5% (p < 0.001). Diazoxide pretreatment also conferred some protective effect with the contraction force
Comment
The important findings of our study are as follows: (1) diazoxide presence in tissue bath during hypoxia allows for significantly stronger myocardial protection than its use as a “pharmacologic preconditioning” signal as assessed by both functional recovery and troponin I release; (2) diazoxide presence in the tissue bath throughout hypoxia prevents development of ischemic contracture; (3) the functional recovery correlates significantly with the degree of ischemic contracture at the end of
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Cited by (15)
Cardioprotective benefits of adenosine triphosphate-sensitive potassium channel opener diazoxide are lost with administration after the onset of stress in mouse and human myocytes
2014, Journal of the American College of SurgeonsCitation Excerpt :This is in contrast to previous work (with a shorter stress period) in which a statistically significant decline in contractility was demonstrated in the cardioplegia group after stress.1 The presence of DZX during the re-exposure to TYR period provided no additional benefit to contractility, similar to the work of other investigators.13 As stated above, intrinsic reparative mechanisms other than the presence of DZX during the re-exposure period were likely responsible for the observations noted in this study.
Myocardial remote ischemic preconditioning: From pathophysiology to clinical application
2013, Revista Portuguesa de CardiologiaDiazoxide protects myocardial mitochondria, metabolism, and function during cardiac surgery: A double-blind randomized feasibility study of diazoxide-supplemented cardioplegia
2009, Journal of Thoracic and Cardiovascular SurgeryCitation Excerpt :The current study failed to find significant differences in CK-MB and troponin I levels in the postoperative period between the groups. Most experimental studies show that diazoxide significantly protects against ischemia-induced myocardial necrosis.1,8,9,15,17 However, many of these tested diazoxide-mediated protection against no protection.
Maintenance of Myocyte Volume Homeostasis During Stress by Diazoxide is Cardioprotective
2007, Annals of Thoracic SurgeryCitation Excerpt :In the present study, the addition of 5HD (mitochondrial KATP-channel blocker) or HMR 1098 (sarcolemmal KATP-channel blocker) did not reverse the beneficial effect observed by diazoxide after metabolic inhibition. These findings are consistent with our previous work in which HMR 1098 did not inhibit the beneficial effects of diazoxide or pinacidil in animal and human myocytes [2; unpublished data] and the work of others who have found that 5HD does not inhibit the protective effects of diazoxide [18]. However, these results are not consistent with other reports documenting a reversal or a partial reversal of diazoxide’s cardioprotection with the use of 5HD [14, 17, 19, 20].
Diazoxide provides maximal K<inf>ATP</inf> channels independent protection if present throughout hypoxia: Invited commentary
2006, Annals of Thoracic SurgeryCan human myocardium be remotely preconditioned? the results of a randomized controlled trial
2019, European Journal of Cardio-thoracic Surgery