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      Acetyl-l-Carnitine and Oxfenicine on Cardiac Pumping Mechanics in Streptozotocin-Induced Diabetes in Male Wistar Rats

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          Abstract

          Introduction

          In the treatment of patients with diabetes, one objective is an improvement of cardiac metabolism to alleviate the left ventricular (LV) function. For this study, we compared the effects of acetyl- l-carnitine (one of the carnitine derivatives) and of oxfenicine (a carnitine palmitoyltransferase-1 inhibitor) on cardiac pumping mechanics in streptozotocin-induced diabetes in male Wistar rats, with a particular focus on the pressure-flow-volume relationship.

          Methods

          Diabetes was induced by a single tail vein injection of 55 mg kg −1 streptozotocin. The diabetic animals were treated on a daily basis with either acetyl-L-carnitine (1 g L −1 in drinking water) or oxfenicine (150 mg kg −1 by oral gavage) for 8 wk. They were also compared with untreated age-matched diabetic controls. LV pressure and ascending aortic flow signals were recorded to calculate the maximal systolic elastance ( E max) and the theoretical maximum flow ( Q max). Physically, E max reflects the contractility of the myocardium as an intact heart, whereas Q max has an inverse relationship with the LV internal resistance.

          Results

          When comparing the diabetic rats with their age-matched controls, the cardiodynamic condition was characterized by a decline in E max associated with the unaltered Q max. Acetyl- l-carnitine (but not oxfenicine) had reduced cardiac levels of malondialdehyde in these insulin-deficient animals. However, treating with acetyl- l-carnitine or oxfenicine resulted in an increase in E max, which suggests that these 2 drugs may protect the contractile status from deteriorating in the diabetic heart. By contrast, Q max showed a significant fall after administration of oxfenicine, but not with acetyl-L-carnitine. The decrease in Q max corresponded to an increase in total vascular resistance when treated with oxfenicine.

          Conclusions

          Acetyl- l-carnitine, but not oxfencine, optimizes the integrative nature of cardiac pumping mechanics by preventing the diabetes-induced deterioration in myocardial intrinsic contractility associated with unaltered LV internal resistance.

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          Most cited references 34

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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                26 July 2013
                : 8
                : 7
                Affiliations
                [1 ]Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
                [2 ]Department of Surgery and Traumatology, National Taiwan University Hospital, Taipei, Taiwan
                [3 ]Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
                [4 ]Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan
                Medical University Innsbruck, Austria
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KCC CHW. Performed the experiments: CHW RWC. Analyzed the data: CYC RWC CHW. Contributed reagents/materials/analysis tools: SSW WJK YSC. Wrote the paper: KCC CHW.

                Article
                PONE-D-13-07327
                10.1371/journal.pone.0069977
                3724909
                23922880

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 11
                Funding
                This study was supported by grants from the National Science Council of Taiwan (NSC 97-2320-B-002-040-MY3) and National Taiwan University Hospital, Hsin-Chu Branch (HCH-100-02 and HCH-101-19). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Cardiovascular System
                Medicine
                Anatomy and Physiology
                Cardiovascular System
                Cardiovascular
                Cardiovascular Pharmacology
                Hemodynamics
                Peripheral Vascular Diseases
                Endocrinology
                Diabetic Endocrinology
                Diabetes Mellitus Type 1
                Diabetes Mellitus Type 2

                Uncategorized

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