We investigated the tolerance of the insulin-resistant diabetic heart to ischemic injury in the male Goto-Kakizaki (GK) rat, a model of type 2 diabetes. Changes in energy metabolism, nitric oxide (NO) pathway, and cardiac function were assessed in the presence of physiological substrates. Age-matched control Wistar (n = 19) and GK (n = 18) isolated rat hearts were perfused with 0.4 mM palmitate, 3% albumin, 11 mM glucose, 3 U/l insulin, 0.2 mM pyruvate, and 0.8 mM lactate for 24 min before switching to 1.2 mM palmitate (11 rats/group) during 32 min low-flow (0.5 ml·min(-1)·g wet wt(-1)) ischemia. Next, flow was restored with 0.4 mM palmitate buffer for 32 min. A subset of hearts from each group (n = 8 for control and n = 7 for GK groups) were freeze-clamped for determining baseline values after the initial perfusion of 24 min. ATP, phosphocreatine (PCr), and intracellular pH (pH(i)) were followed using (31)P magnetic resonance spectroscopy with simultaneous measurement of contractile function. The NO pathway was determined by nitric oxide synthase (NOS) isoform expression and total nitrate concentration (NOx) in hearts. We found that coronary flow was 26% lower (P < 0.05) during baseline conditions and 61% lower (P < 0.05) during reperfusion in GK vs. control rat hearts. Rate pressure product was lower during reperfusion in GK vs. control rat hearts (P < 0.05). ATP, PCr, and pH(i) during ischemia-reperfusion were similar in both groups. Endothelial NOS expression was increased in GK rat hearts during baseline conditions (P < 0.05). NOx was increased during baseline conditions (P < 0.05) and after reperfusion (P < 0.05) in GK rat hearts. We report increased susceptibility of type 2 diabetic GK rat heart to ischemic injury that is not associated with impaired energy metabolism. Reduced coronary flow, upregulation of eNOS expression, and increased total NOx levels confirm NO pathway modifications in this model, presumably related to increased oxidative stress. Modifications in the NO pathway may play a major role in ischemia-reperfusion injury of the type 2 diabetic GK rat heart.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2993220 | PMC |
| http://dx.doi.org/10.1152/ajpheart.00998.2009 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Puerarin Protects Myocardium From Ischaemia/Reperfusion Injury by Inhibiting Ferroptosis Through Downregulation of VDAC1.
J Cell Mol Med
December 2024
Institute of Cardiovascular Surgical Diseases, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Despite improvements in interventional techniques leading to faster myocardial reperfusion postmyocardial infarction, there has been a significant rise in the occurrence of myocardial ischaemia/reperfusion injury (MI/RI). A deeper understanding of the underlying mechanisms of MI/RI could offer a crucial approach to reducing myocardial damage and enhancing patient outcomes. This study examined the myocardial protective properties of puerarin (PUE) in the context of MI/RI using hypoxia/reoxygenation (H/R) or ischaemia/reperfusion (I/R) injury models were employed in H9c2 cells and C57BL/6 mice.
View Article and Find Full Text PDFSafety assessment on CBD-rich hemp extract in sub-chronic cross-sex study with rats.
Toxicol Appl Pharmacol
December 2024
Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic. Electronic address:
Cannabidiol (CBD) is a phytocannabinoid from Cannabis sativa L., in which there is currently growing interest for medicinal use. Here, we focused on the safety and pharmacokinetics of a CBD-rich (77 %, w/w) full-spectrum hemp extract in male and female rats.
View Article and Find Full Text PDFEvaluation of a Miniature, Injectable, Wireless Stimulator to Treat Obstructive Sleep Apnea.
Neuromodulation
December 2024
StimAire Corporation, Tucson, AZ, USA.
Introduction: Moderate-to-severe obstructive sleep apnea (OSA) affects a large segment of the US population and is characterized by repetitive and reversible obstruction of the upper airway during sleep. Untreated OSA is associated with increased incidence of heart attack, stroke, and motor vehicle accidents due to sleepiness. Continuous positive airway pressure is often prescribed, but most patients with OSA are nonadherent.
View Article and Find Full Text PDFAntihypertensive Effect of Perla and Esmeralda Barley ( L.) Sprouts in an Induction Model with L-NAME In Vivo.
Metabolites
December 2024
Academic Area of Medicine, Institute of Health Sciences, Autonomous University of the State of Hidalgo, Eliseo Ramírez Ulloa 400, Doctores Pachuca, Pachuca 42090, Hidalgo, Mexico.
Hypertension is one of the leading causes of premature death worldwide. Despite advances in conventional treatments, there remains a significant need for more effective and natural alternatives to control hypertension. In this context, sprouted barley extracts have emerged as a potential therapeutic option.
View Article and Find Full Text PDFElucidating Early Radiation-Induced Cardiotoxicity Markers in Preclinical Genetic Models Through Advanced Machine Learning and Cardiac MRI.
J Imaging
December 2024
Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Radiation therapy (RT) is widely used to treat thoracic cancers but carries a risk of radiation-induced heart disease (RIHD). This study aimed to detect early markers of RIHD using machine learning (ML) techniques and cardiac MRI in a rat model. SS.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!