Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery of function after ischemia in the isolated perfused heart
Abstract
The aim of this study was to determine whether the transition from insulin resistance to hyperglycemia in a model of type 2 diabetes leads to intrinsic changes in the myocardium that increase the sensitivity to ischemic injury. Hearts from 6-, 12-, and 24-wk-old lean (Control) and obese Zucker diabetic fatty (ZDF) rats were isolated, perfused, and subjected to 30 min of low-flow ischemia (LFI) and 60 min of reperfusion. At 6 wk, ZDF animals were insulin resistant but not hyperglycemic. By 12 wk, the ZDF group was hyperglycemic and became progressively worse by 24 wk. In spontaneously beating hearts rate-pressure product (RPP) was depressed in the ZDF groups compared with age-matched Controls, primarily due to lower heart rate. Pacing significantly increased RPP in all ZDF groups; however, this was accompanied by a significant decrease in left ventricular developed pressure. There was also greater contracture during LFI in the ZDF groups compared with the Control group; surprisingly, however, functional recovery upon reperfusion was significantly higher in the diabetic 12- and 24-wk ZDF groups compared with age-matched Control groups and the 6-wk ZDF group. This improvement in recovery in the ZDF diabetic groups was independent of substrate availability, severity of ischemia, and duration of diabetes. These data demonstrate that, although the development of type 2 diabetes leads to progressive contractile and metabolic abnormalities during normoxia and LFI, it was not associated with increased susceptibility to ischemic injury.
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In fa/fa rats studied very shortly after the onset of hyperglycemia, ischemia was associated with increased ischemic contracture, but functional recovery following reperfusion was enhanced despite reduced baseline cardiac function.
“In fa/fa rats studied very shortly after the onset of hyperglycemia, ischemia was associated with increased ischemic contracture, but functional recovery following reperfusion was enhanced in the obese mice despite the fact that at baseline, cardiac function was reduced (369).”
From Cardiac remodeling in obesity (2008) · cites this paper as [369]
In Langendorff-perfused hearts from fa/fa (Zucker) rats prior to the onset of diabetes, cardiac function is depressed; after the onset of diabetes, increased FA utilization and decreased glucose and lactate utilization are observed.
“In Langendorff-perfused hearts from fa/fa (Zucker) rats prior to the onset of diabetes, cardiac function was also depressed (369), and in rats studied after the onset of diabetes, increased FA utilization and decreased glucose and lactate utilization were observed (370).”
From Cardiac remodeling in obesity (2008) · cites this paper as [369]
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References 48 · Cited by 81
- Authors
- Wang, P., & Chatham, J. C.
- Affiliations
- University of Alabama at Birmingham (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2004-05
- Volume
- 286
- Issue
- 5
- Pages
- E725-E736
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2097674872
- Cited by
- 81
- References
- 48
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1 · 2020: 1 · 2018: 3 · 2016: 2 · 2015: 2 · 2014: 2 · 2013: 8 · 2012: 1
- FWCI
- 5.97
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-48789, HL 67464, R01HL067464)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Keywords
- type 2 diabetes, Zucker diabetic fatty rats, myocardial ischemia, ischemia-reperfusion injury, functional recovery, insulin resistance, hyperglycemia, cardiac contractility, rate-pressure product, pacing, myocardial substrate metabolism, diabetic cardiomyopathy
- MeSH terms
- Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Disease Susceptibility, Hyperglycemia, Insulin Resistance, Male, Muscle Contraction, Myocardium, Obesity, Organ Culture Techniques, Rats, Zucker, Matched-Pair Analysis, Myocardial Ischemia, Disease Progression, Recovery of Function, Rats
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