Skeletal Muscle Microvascular Dysfunction Manifests Early in Diabetic Cardiomyopathy.

Autor: Loai S; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada., Zhou YQ; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada., Vollett KDW; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada., Cheng HM; Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada.; Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada.; The Edward S. Rogers Sr. Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada.
Jazyk: angličtina
Zdroj: Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2021 Jul 20; Vol. 8, pp. 715400. Date of Electronic Publication: 2021 Jul 20 (Print Publication: 2021).
DOI: 10.3389/fcvm.2021.715400
Abstrakt: Aim: To perform a deep cardiac phenotyping of type II diabetes in a rat model, with the goal of gaining new insight into the temporality of microvascular dysfunction, cardiac dysfunction, and exercise intolerance at different stages of diabetes. Methods and Results: Diabetes was reproduced using a non-obese, diet-based, low-dose streptozotocin model in male rats (29 diabetic, 11 control). Time-course monitoring over 10 months was performed using echocardiography, treadmill exercise, photoacoustic perfusion imaging in myocardial and leg skeletal muscle, flow-mediated dilation, blood panel, and histology. Diabetic rats maintained a normal weight throughout. At early times (4 months), a non-significant reduction (30%) emerged in skeletal muscle perfusion and in exercise tolerance. At the same time, diabetic rats had a normal, slightly lower ejection fraction (63 vs. 71% control, p < 0.01), grade 1 diastolic dysfunction (E/A = 1.1 vs. 1.5, isovolumetric relaxation time = 34 vs. 27 ms; p < 0.01), mild systolic dysfunction (ejection time = 69 vs. 57 ms, isovolumetric contraction time = 21 vs. 17 ms; p < 0.01), and slightly enlarged left ventricle (8.3 vs. 7.6 mm diastole; p < 0.01). Diastolic dysfunction entered grade 3 at Month 8 (E/A = 1.7 vs. 1.3, p < 0.05). Exercise tolerance remained low in diabetic rats, with running distance declining by 60%; in contrast, control rats ran 60% farther by Month 5 ( p < 0.05) and always remained above baseline. Leg muscle perfusion remained low in diabetic rats, becoming significantly lower than control by Month 10 (33% SO 2 vs. 57% SO 2 , p < 0.01). Myocardial perfusion remained normal throughout. Femoral arterial reactivity was normal, but baseline velocity was 25% lower than control ( p < 0.05). High blood pressure appeared late in diabetes (8 months). Histology confirmed absence of interstitial fibrosis, cardiomyocyte hypertrophy, or microvascular rarefaction in the diabetic heart. Rarefaction was also absent in leg skeletal muscle. Conclusion: Reduced skeletal muscle perfusion from microvascular dysfunction emerged early in diabetic rats, but myocardial perfusion remained normal throughout the study. At the same time, diabetic rats exhibited exercise intolerance and early cardiac dysfunction, in which changes related to heart failure with preserved ejection fraction (HFpEF) were seen. Importantly, skeletal muscle microvascular constriction advanced significantly before the late appearance of hypertension. HFpEF phenotypes such as cardiac hypertrophy, fibrosis, and rarefaction, which are typically associated with hypertension, were absent over the 10 month time-course of diabetes-related heart failure.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Loai, Zhou, Vollett and Cheng.)
Databáze: MEDLINE
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