Insulin resistance modifies plasma fatty acid distribution and decreases cardiac tolerance to in vivo ischaemia/reperfusion in rats.

1. The early stage of insulin resistance, also termed the 'prediabetic state', is characterized by the development of hyperinsulinaemia, which maintains normoglycaemia under fasting conditions. The metabolic disorders induced in myocardial cells during this stage of the disease may constitute a basis for an alteration of the tolerance of the heart to ischaemia and reperfusion. 2. To test this hypothesis, male Wistar rats were fed a 66% fructose diet for 4 weeks, inducing a prediabetic state. Rats were then subjected to in vivo left coronary artery ligation followed by reperfusion. Blood samples were collected for plasma lipid profile determination. 3. The prediabetic state significantly increased the severity of ischaemia-induced arrhythmias (arrhythmia score 1.4 +/- 0.2 vs 2.0 +/- 0.0 in control and fructose-fed rats, respectively; P < 0.05) and the size of infarction (infarct size 41.2 +/- 3.0 vs 56.0 +/- 2.0% in control and fructose-fed rats, respectively; P < 0.01). This alteration of the tolerance to in vivo ischaemia/reperfusion may be the consequence of an increase in mono-unsaturated fatty acids and a decrease in omega3 polyunsaturated fatty acids in fructose-fed-rats. 4. In conclusion, because it is known that the prediabetic state increases the incidence of cardiovascular diseases by promoting coronaropathy, our study suggests that this metabolic disorder may also affect the prognosis of heart disease by decreasing the tolerance of cardiomyocytes to ischaemic insults.