Xanthine oxidase (XO) is increased in human and rat left ventricular (LV) myocytes with volume overload (VO) of mitral regurgitation and aortocaval fistula (ACF). In the setting of increased ATP demand, XO-mediated ROS can decrease mitochondrial respiration and contractile function. Thus, we tested the hypothesis that XO inhibition improves cardiomyocyte bioenergetics and LV function in chronic ACF in the rat. Sprague-Dawley rats were randomized to either sham or ACF ± allopurinol (100 mg·kg(-1)·day(-1), n ≥7 rats/group). Echocardiography at 8 wk demonstrated a similar 37% increase in LV end-diastolic dimension (P < 0.001), a twofold increase in LV end-diastolic pressure/wall stress (P < 0.05), and a twofold increase in lung weight (P < 0.05) in treated and untreated ACF groups versus the sham group. LV ejection fraction, velocity of circumferential shortening, maximal systolic elastance, and contractile efficiency were significantly depressed in ACF and significantly improved in ACF + allopurinol rats, all of which occurred in the absence of changes in the maximum O2 consumption rate measured in isolated cardiomyocytes using the extracellular flux analyzer. However, the improvement in contractile function is not paralleled by any attenuation in LV dilatation, LV end-diastolic pressure/wall stress, and lung weight. In conclusion, allopurinol improves LV contractile function and efficiency possibly by diminishing the known XO-mediated ROS effects on myofilament Ca(2+) sensitivity. However, LV remodeling and diastolic properties are not improved, which may explain the failure of XO inhibition to improve symptoms and hospitalizations in patients with severe heart failure.
Pharmacology, Toxicology and Pharmaceutical Science
3
10%
Biochemistry, Genetics and Molecular Biology
3
10%
Engineering
2
7%
Other
2
7%
Unknown
3
10%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 12 September 2013.
All research outputs
#28,131,172
of 34,844,563 outputs
Outputs from American Journal of Physiology: Heart & Circulatory Physiology
#6,634
of 7,508 outputs
Outputs of similar age
#189,863
of 242,697 outputs
Outputs of similar age from American Journal of Physiology: Heart & Circulatory Physiology
#29
of 38 outputs
Altmetric has tracked 34,844,563 research outputs across all sources so far. This one is in the 16th percentile – i.e., 16% of other outputs scored the same or lower than it.
So far Altmetric has tracked 7,508 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one is in the 9th percentile – i.e., 9% of its peers scored the same or lower than it.
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