High fat diet-induced glucose intolerance impairs myocardial function, but not myocardial perfusion during hyperaemia: a pilot study

Abstract

BackgroundGlucose intolerance is a major health problem and is associated with increased risk of progression to type 2 diabetes mellitus and cardiovascular disease. However, whether glucose intolerance is related to impaired myocardial perfusion is not known. The purpose of the present study was to study the effect of diet-induced glucose intolerance on myocardial function and perfusion during baseline and pharmacological induced hyperaemia.MethodsMale Wistar rats were randomly exposed to a high fat diet (HFD) or control diet (CD) (n = 8 per group). After 4 weeks, rats underwent an oral glucose tolerance test. Subsequently, rats underwent (contrast) echocardiography to determine myocardial function and perfusion during baseline and dipyridamole-induced hyperaemia (20 mg/kg for 10 min).ResultsFour weeks of HFD feeding resulted in glucose intolerance compared to CD-feeding. Contractile function as represented by fractional shortening was not altered in HFD-fed rats compared to CD-fed rats under baseline conditions. However, dipyridamole increased fractional shortening in CD-fed rats, but not in HFD-fed rats. Basal myocardial perfusion, as measured by estimate of perfusion, was similar in CD- and HFD-fed rats, whereas dipyridamole increased estimate of perfusion in CD-fed rats, but not in HFD-fed rats. However, flow reserve was not different between CD- and HFD-fed rats.ConclusionsDiet-induced glucose intolerance is associated with impaired myocardial function during conditions of hyperaemia, but myocardial perfusion is maintained. These findings may result in new insights into the effect of glucose intolerance on myocardial function and perfusion during hyperaemia.

Body adiposity dictates different mechanisms of increased coronary reactivity related to improved in vivo cardiac function

“…Indeed, the ex vivo cardiac mechanical function was reduced by the HF diet, following the elevated adiposity of the animals irrespective of their body weight. That observation has already been presented in the literature after a HF diet period [9,31], after weight gain through post-natal overfeeding in the mouse [7] and in the rat [8] as well as in the ZDF rat [6]. This depressed ex vivo cardiac mechanical activity observed in this study could be related to changes in the cardiac metabolism related to the whole body glucose intolerance, the increased degree of saturation of the cardiac membranes as shown by the increase in the SFAs at the detriment of MUFAs [36] and the pro-inflammatory environment as indicated by the low ratio EPA/AA that predisposes to a balance of eicosanoids favoring platelet aggregation and inflammatory signaling [37,38].…”

Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet

“…Diet-induced obesity is associated with dyslipidemia, glucose intolerance and insulin resistance in rats [ 25 , 40 – 42 ]. In the present study, 6 weeks of HFD led to a marked increase in abdominal fat depots and a rise in serum total cholesterol levels, but not in a rise of serum triglyceride, insulin or glucose levels as measured under non-fasting conditions.…”

“…Intriguingly, at baseline the rate of LV volume change across the cardiac cycle (dV/dt) tended to be increased for HFD rats in both systole and diastole suggesting that, if anything, baseline cardiac function is enhanced, rather than reduced, after 6 weeks of HFD. In literature inconsistent findings have been reported as far as the effect of HFD on myocardial function is concerned, with some studies reporting reduced function [ 25 , 46 ], unchanged function [ 42 ] and improved function [ 21 ], respectively. In this context it is of note that one study reported that functional outcome was dependent on the exact composition of the HFD diet [ 42 ].…”

“…In mice with diet-induced obesity, microcirculatory glycocalyx dysfunction in skeletal muscle was observed [ 13 ]. To date information on whether the abnormalities in microvascular function in obese and insulin resistant subjects also involve the coronary microcirculation is scarce and often conflicting [ 19 – 25 ]. As far as the glycocalyx of the coronary circulation is concerned, it has been shown that the glycocalyx is shedded in case of highly injurious conditions like myocardial ischemia/reperfusion [ 26 ].…”

Diabetes, perioperative ischaemia and volatile anaesthetics: consequences of derangements in myocardial substrate metabolism

“…Whereas the metabolic undisturbed heart usually responds to injury by increasing myocardial glucose metabolism [22,24], this adaptive response is inhibited by insulin resistance, which is a characteristic of obesity and T2DM. This inhibition results in increased myocardial fatty acid metabolism [31,32], increased oxygen consumption, decreased cardiac efficiency [31] and altered myocardial perfusion [33]. In obese or T2DM animals subjected to myocardial ischaemia the findings are inconclusive.…”