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      Therapeutic Hypothermia Reduces Peritoneal Dialysis Induced Myocardial Blood Flow Heterogeneity and Arrhythmia

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          Abstract

          Background: Moderate therapeutic hypothermia (TH) is a well-recognized cardio-protective strategy. The instillation of fluid into the peritoneum provides an opportunity to deliver moderate hypothermia as primary prevention against cardiovascular events. We aimed to to investigate both cardiac perfusion consequences (overall blood flow and detailed assessment of perfusion heterogeneity) and subsequently simulate the associated arrhythmic risk for patients undergoing peritoneal dialysis (PD) induced TH.

          Methods: Patients underwent high resolution myocardial perfusion scanning using high resolution 256 slice CT scanning, at rest and with adenosine stress. The first visit using the patient's usual PD regimen, on the second visit the same regime was utilized but with cooled peritoneal dialysate at 32°C. Myocardial blood flow (MBF) was quantified from generated perfusion maps, reconstructed in 3D. MBF heterogeneity was assessed by fractal dimension (FD) measurement on the 3D left ventricular reconstruction. Arrhythmogenicity was quantified from a sophisticated computational simulation using a multi-scale human 3D ventricle wedge electrophysiological computational model.

          Results: We studied 7 PD patients, mean age of 60 ± 7 and mean vintage dialysis of 23.6 ± 17.6 months. There were no significant different in overall segmental MBF between normothermic condition (NT) and TH. MBF heterogeneity was significantly decreased (−14%, p = 0.03) at rest and after stress (−14%, p = 0.03) when cooling was applied. Computational simulation showed that TH allowed a normalization of action potential, QT duration and T wave.

          Conclusion: TH-PD results in moderate hypothermia leading to a reduction in perfusion heterogeneity and simulated risk of non-terminating malignant ventricular arrhythmias.

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          Most cited references35

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          Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart. A statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association.

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            Cold-inducible proteins CIRP and RBM3, a unique couple with activities far beyond the cold

            Cold-inducible RNA-binding protein (CIRP) and RNA-binding motif protein 3 (RBM3) are two evolutionarily conserved RNA-binding proteins that are transcriptionally upregulated in response to low temperature. Featuring an RNA-recognition motif (RRM) and an arginine–glycine-rich (RGG) domain, these proteins display many similarities and specific disparities in the regulation of numerous molecular and cellular events. The resistance to serum withdrawal, endoplasmic reticulum stress, or other harsh conditions conferred by RBM3 has led to its reputation as a survival gene. Once CIRP protein is released from cells, it appears to bolster inflammation, contributing to poor prognosis in septic patients. A variety of human tumor specimens have been analyzed for CIRP and RBM3 expression. Surprisingly, RBM3 expression was primarily found to be positively associated with the survival of chemotherapy-treated patients, while CIRP expression was inversely linked to patient survival. In this comprehensive review, we summarize the evolutionary conservation of CIRP and RBM3 across species as well as their molecular interactions, cellular functions, and roles in diverse physiological and pathological processes, including circadian rhythm, inflammation, neural plasticity, stem cell properties, and cancer development.
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              Global trends in rates of peritoneal dialysis.

              Although there is a perception that the use of peritoneal dialysis is declining worldwide, compilations of global data are unavailable to test this hypothesis. We assessed longitudinal trends in the use of peritoneal dialysis from 1997 to 2008 in 130 countries. The preferred data sources were renal registries, followed by nephrology societies, health ministries, academic centers, national experts, and industry affiliates. In 2008, there were approximately 196,000 peritoneal dialysis patients worldwide, representing 11% of the dialysis population. In total, 59% were treated in developing countries and 41% in developed countries. Over 12 years, the number of peritoneal dialysis patients increased in developing countries by 24.9 patients per million population and in developed countries by 21.8 per million population. The proportion of all dialysis patients treated with peritoneal dialysis did not change in developing countries but significantly declined in developed countries by 5.3%. The use of automated peritoneal dialysis increased by 14.5% in developing countries and by 30.3% in developed countries. In summary, the number of patients treated with peritoneal dialysis rose worldwide from 1997 to 2008, with a 2.5-fold increase in the prevalence of peritoneal dialysis patients in developing countries. The proportion of all dialysis patients treated with this modality continues to decline in developed countries.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                30 July 2021
                2021
                : 8
                : 700824
                Affiliations
                [1] 1Kidney Clinical Research Unit, Lawson's Health Research Institute, Victoria Hospital , London, ON, Canada
                [2] 2Department of Medical Biophysics, Schulich School of Medicine and Dentistry, University of Western Ontario , London, ON, Canada
                [3] 3Imaging Program, Lawson Health Research Institute , London, ON, Canada
                Author notes

                Edited by: Pasqual Barretti, São Paulo State University, Brazil

                Reviewed by: Mark Dominik Alscher, Robert Bosch Hospital, Germany; Jong Hyun Jhee, Yonsei University, South Korea

                *Correspondence: Christopher W. McIntyre cmcint48@ 123456uwo.ca

                This article was submitted to Nephrology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2021.700824
                8362929
                34395480
                beb961dc-166e-4de1-b558-fc4e1f031a72
                Copyright © 2021 Kharche, Lemoine, Tamasi, Hur, So and McIntyre.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 26 April 2021
                : 30 June 2021
                Page count
                Figures: 5, Tables: 3, Equations: 0, References: 36, Pages: 9, Words: 5907
                Funding
                Funded by: Heart and Stroke Foundation of Canada 10.13039/501100000222
                Categories
                Medicine
                Original Research

                peritoneal dialysis,therapeutic hypothermia,computed tomography imaging,computational cardiology,arrhythmia

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