Preserved endothelium-dependent dilatation of the coronary microvasculature at the early phase of diabetes mellitus despite the increased oxidative stress and depressed cardiac mechanical function ex vivo

Abstract

BackgroundThere has been accumulating evidence associating diabetes mellitus and cardiovascular dysfunctions. However, most of the studies are focused on the late stages of diabetes and on the function of large arteries. This study aimed at characterizing the effects of the early phase of diabetes mellitus on the cardiac and vascular function with focus on the intact coronary microvasculature and the oxidative stress involved.Materials and methodsZucker diabetic fatty rats and their lean littermates fed with standard diet A04 (Safe) were studied at the 11th week of age. Biochemical parameters such as glucose, insulin and triglycerides levels as well as their oxidative stress status were measured. Their hearts were perfused ex vivo according to Langendorff and their cardiac activity and coronary microvascular reactivity were evaluated.ResultsZucker fatty rats already exhibited a diabetic state at this age as demonstrated by the elevated levels of plasma glucose, insulin, glycated hemoglobin and triglycerides. The ex vivo perfusion of their hearts revealed a decreased cardiac mechanical function and coronary flow. This was accompanied by an increase in the overall oxidative stress of the organs. However, estimation of the active form of endothelial nitric oxide synthase and coronary reactivity indicated a preserved function of the coronary microvessels at this phase of the disease. Diabetes affected also the cardiac membrane phospholipid fatty acid composition by increasing the arachidonic acid and n-3 polyunsaturated fatty acids levels.ConclusionsThe presence of diabetes, even at its beginning, significantly increased the overall oxidative stress of the organs resulting to decreased cardiac mechanical activity ex vivo. However, adaptations were adopted at this early phase of the disease regarding the preserved coronary microvascular reactivity and the associated cardiac phospholipid composition in order to provide a certain protection to the heart.

Increased Abdominal Adiposity Exacerbates Ex-Vivo Cardiac Reperfusion Injury through Augmented Mitochondrial Oxidative Stress

“…This confirms the effect of IAA in different ex-vivo models, including in Western diet-fed rats [5,7], ZDF animals [13,14,45] and mice subjected to ON [11]. This phenomenon was associated with lower coronary flow and cardiac metabolic efficiency.…”

“…Subtilisin action was stopped by adding complex activities were also measured in homogenates from the reperfused myocardium, as previously described [40]. Proteins were measured using the bicinchoninic acid method (Thermo Scientific, Rockford, IL) [45].…”

Early sepsis does not stimulate reactive oxygen species production and does not reduce cardiac function despite an increased inflammation status

“…Several parameters of the oxidative stress (protein thiol residues, total antioxidant defenses (FRAP), glutathione peroxidase activity, GSH and GSSG) were determined as already described previously (Mourmoura et al. 2013). …”

Evolution from increased cardiac mechanical function towards cardiomyopathy in the obese rat due to unbalanced high fat and abundant equilibrated diets

“…The measurement of the mitochondrial oxidative stress in that situation indicated a strong HF-and ZDF-induced increase in that parameter. This probably reduced Krebs cycle activity through inhibition of aconitase, decreased energy production and negatively affected inotropy (Mourmoura et al, 2013). We thus decided to utilize a second perfusion model in which the coronary flow was determined soon after the beginning of perfusion and maintained constant throughout it by means of a peristaltic pump.…”

“…The coronary reactivity was evaluated in the ex vivo situation as previously described (Mourmoura et al, 2013). After 30 min of fixed flow perfusion, the coronary flow was maintained constant by means of a peristaltic pump and the coronary pressure was artificially increased for 20 min by infusion of a thromboxane A2 analog (U46619, 30 nM).…”