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MacDonald 2011 Am J Physiol Cell Physiol

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MacDonald JR, Oellermann M, Rynbeck S, Chang G, Ruggiero K, Cooper GJ, Hickey AJ (2011) Transmural differences in respiratory capacity across the rat left ventricle in health, aging, and streptozotocin-induced diabetes mellitus: evidence that mitochondrial dysfunction begins in the subepicardium. Am J Physiol Cell Physiol 300:C246-55.

ยป PMID: 21084644 Open Access

MacDonald JR, Oellermann M, Rynbeck S, Chang G, Ruggiero K, Cooper GJ, Hickey AJ (2011) Am J Physiol Cell Physiol

Abstract: In diabetic cardiomyopathy, ventricular dysfunction occurs in the absence of hypertension or atherosclerosis and is accompanied by altered myocardial substrate utilization and depressed mitochondrial respiration. It is not known if mitochondrial function differs across the left ventricular (LV) wall in diabetes. In the healthy heart, the inner subendocardial region demonstrates higher rates of blood flow, oxygen consumption, and ATP turnover compared with the outer subepicardial region, but published transmural respirometric measurements have not demonstrated differences. We aim to measure mitochondrial function in Wistar rat LV to determine the effects of age, streptozotocin-diabetes, and LV layer. High-resolution respirometry measured indexes of respiration in saponin-skinned fibers dissected from the LV subendocardium and subepicardium of 3-mo-old rats after 1 mo of streptozotocin-induced diabetes and 4-mo-old rats following 2 mo of diabetes. Heart rate and heartbeat duration were measured under isoflurane-anesthesia using a fetal-Doppler, and transmission electron microscopy was employed to observe ultrastructural differences. Heart rate decreased with age and diabetes, whereas heartbeat duration increased with diabetes. While there were no transmural respirational differences in young healthy rat hearts, both myocardial layers showed a respiratory depression with age (30-40%). In 1-mo diabetic rat hearts only subepicardial respiration was depressed, whereas after 2 mo diabetes, respiration in subendocardial and subepicardial layers was depressed and showed elevated leak (state 2) respiration. These data provide evidence that mitochondrial dysfunction is first detectable in the subepicardium of diabetic rat LV, whereas there are measureable changes in LV mitochondria after only 4 mo of aging. โ€ข Keywords: Permeabilized heart fibers, Mitochondria, Subendocardium

โ€ข O2k-Network Lab: NZ Auckland Hickey AJ

Labels: Pathology: Diabetes 

Organism: Rat  Tissue;cell: Heart  Preparation: Permeabilized tissue 

HRR: Oxygraph-2k 


An Oroboros Oxygraph-2k was used in this publication, whereas the Anton Paar/Oroboros Oxygraph was the first-generation instrument for high-resolution respirometry, which was replaced by the Oxygraph-2k in 2002.