Cardioprotective effect of hyperkalemic cardioplegia in an aquaporin 7-deficient murine heart
- 44 Downloads
Hyperkalemic cardioplegia using St. Thomas’ Hospital solution No. 2 (STH2) is commonly used to protect the myocardium during surgery. Mice deficient in the myocyte channel aquaporin 7 (AQP7) show significantly reduced glycerol and ATP contents and develop obesity; however, the influence of AQP7 on cardioplegia effectiveness remains unclear.
After determining the influence of ischemic duration on cardiac function, isolated hearts of male wild-type (WT) and AQP7-knockout (KO) mice (> 13 weeks old) were aerobically Langendorff-perfused with bicarbonate buffer, and randomly allocated to the control group (25 min of global ischemia) and STH2 group (5 min of STH2 infusion before 20 min of global ischemia, followed by 60 min of reperfusion).
Final recovery of left ventricular developed pressure (LVDP) of WT and AQP7-KO hearts in the control group was 24.5 ± 12.4% and 20.6 ± 8.4%, respectively, which were significantly lower than those of the STH2 group (96.4 ± 12.7% and 92.9 ± 27.6%). Troponin T levels of WT and AQP-KO hearts significantly decreased in the STH2 groups (142.9 ± 27.2 and 219.9 ± 197.3) compared to those of the control (1725.0 ± 768.6 and 1710 ± 819.9).
AQP7 was not involved in the protective efficacy of STH2 in this mouse model, suggesting its clinical utility even in complications of metabolic disease.
KeywordsMouse Aquaporin 7 Cardioplegia Ischemia–reperfusion Cardioprotection
The authors wish to thank Dr. Norikazu Maeda, Dr. Tohru Funabashi, and Dr. Iichiro Shimomura (Department of Internal Medicine and Molecular Science, Osaka University, Osaka, Japan) for providing the AQP7-KO mice. We also would like to thank Dr. Kazutora Mizukami (PhD in Statistical Science, President of Medical Data Management, Fukuoka, Japan) for statistical assistance, Dr. Toshio Akimoto (PhD in Veterinary Medicine, Laboratory Animal Science, Nippon Medical School) for assistance with genotyping analysis, and Ms. Akina Kimura for assistance with the experiments. We are grateful to Dr. David J. Chambers (Cardiac Surgical Research, The Rayne Institute, St Thomas’ Hospital, London, UK) for academic advice. We would also like to thank Editage (www.editage.com) for English language editing.
This work was supported by JSPS KAKENHI Grant Number JP17K10740.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
- 3.Ferguson TB Jr, Hammill BG, Peterson ED, DeLong ER, Grover FL. STS National Database Committee. A decade of change–risk profiles and outcomes for isolated coronary artery bypass grafting procedures, 1990–1999: a report from the STS National Database Committee and the Duke Clinical Research Institute. Society of Thoracic Surgeons. Ann Thorac Surg. 2002;73:480–9.CrossRefGoogle Scholar
- 15.Yeh JI, Charrier V, Paulo J, Hou L, Darbon E, Claiborne A, et al. Structures of enterococcal glycerol kinase in the absence and presence of glycerol: correlation of conformation to substrate binding and a mechanism of activation by phosphorylation. Biochemistry. 2004;43:362–73.CrossRefGoogle Scholar