Optical metabolic imaging of irradiated rat heart exposed to ischemia-reperfusion injury. J Biomed Opt 2018 Jan;23(1):1-9
Date
01/21/2018Pubmed ID
29352564Pubmed Central ID
PMC5774173DOI
10.1117/1.JBO.23.1.016011Scopus ID
2-s2.0-85040834320 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
Whole thoracic irradiation (WTI) is known to cause deterioration in cardiac function. Whether irradiation predisposes the heart to further ischemia and reperfusion (IR) injury is not well known. The aim of this study is to examine the susceptibility of rat hearts to IR injury following a single fraction of 15 Gy WTI and to investigate the role of mitochondrial metabolism in the differential susceptibility to IR injury. After day 35 of irradiation, ex vivo hearts from irradiated and nonirradiated rats (controls) were exposed to 25-min global ischemia followed by 60-min IR, or hearts were perfused without IR for the same protocol duration [time controls (TC)]. Online fluorometry of metabolic indices [redox state: reduced nicotinamide adenine dinucleotide (NADH), oxidized flavin adenine dinucleotide (FAD), and NADH/FAD redox ratio] and functional variables [systolic left ventricular pressure (LVP), diastolic LVP (diaLVP), coronary flow (CF), and heart rate were recorded in the beating heart; developed LVP (dLVP) and rate pressure product (RPP)] were derived. At the end of each experimental protocol, hearts were immediately snap frozen in liquid N2 for later three-dimensional imaging of the mitochondrial redox state using optical cryoimaging. Irradiation caused a delay in recovery of dLVP and RPP after IR when compared to nonirradiated hearts but recovered to the same level at the end of reperfusion. CF in the irradiated hearts recovered better than the control hearts after IR injury. Both fluorometry and 3-D cryoimaging showed that in WTI and control hearts, the redox ratio increased during ischemia (reduced) and decreased on reperfusion (oxidized) when compared to their respective TCs; however, there was no significant difference in the redox state between WTI and controls. In conclusion, our results show that although irradiation of rat hearts compromised baseline cardiovascular function, it did not alter cardiac mitochondrial redox state and induce greater susceptibility of these hearts to IR injury.
Author List
la Cour MF, Mehrvar S, Heisner JS, Motlagh MM, Medhora M, Ranji M, Camara AKSAuthor
Amadou K. Camara PhD Professor in the Anesthesiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsFemale
Flavin-Adenine Dinucleotide
Heart
Imaging, Three-Dimensional
Myocardium
NAD
Optical Imaging
Oxidation-Reduction
Rats
Rats, Wistar
Reperfusion Injury