title: Evaluation of the relationship between hyperinsulinaemia and myocardial ischaemia/reperfusion injury in a rat model of depression.
abstract: Major depression is associated with medical co-morbidity, such as ischaemic heart disease and diabetes, but the underlying pathophysiological mechanisms remain unclear. The FSL (Flinders Sensitive Line) rat is a genetic animal model of depression exhibiting features similar to those of depressed individuals. The aim of the present study was to compare the myocardial responsiveness to I/R (ischaemia/reperfusion) injury and the effects of IPC (ischaemic preconditioning) in hearts from FSL rats using SD (Sprague-Dawley) rats as controls and to characterize differences in glucose metabolism and insulin sensitivity between FSL and SD rats. Hearts were perfused in a Langendorff model and were subjected or not to IPC before 40 min of global ischaemia, followed by 120 min of reperfusion. Myocardial infarct size was found to be significantly larger in the FSL rats than in the SD rats following I/R injury (62.4+/-4.2 compared with 46.9+/-2.9%; P<0.05). IPC reduced the infarct size (P<0.01) and improved haemodynamic function (P<0.01) in both FSL and SD rats. No significant difference was found in blood glucose levels between the two groups measured after 12 h of fasting, but fasting plasma insulin (70.1+/-8.9 compared with 40.9+/-4.7 pmol/l; P<0.05) and the HOMA (homoeostatic model assessment) index (P<0.01) were significantly higher in FSL rats compared with SD rats. In conclusion, FSL rats had larger infarct sizes following I/R injury and were found to be hyperinsulinaemic compared with SD rats, but appeared to have a maintained cardioprotective mechanism against I/R injury, as IPC reduced infarct size in these rats. This animal model may be useful in future studies when examining the mechanisms that contribute to the cardiovascular complications associated with depression.
authors: Institute of Pharmacology, Aarhus University, DK-8000 Aarhus C, Denmark. solskov@dadlnet.dk
authors: Lasse
authors: L
authors: Solskov
authors: Bo
authors: B
authors: Løfgren
authors: Rasmus
authors: R
authors: Pold
authors: Steen B
authors: SB
authors: Kristiansen
authors: Torsten T
authors: TT
authors: Nielsen
authors: David H
authors: DH
authors: Overstreet
authors: Ole
authors: O
authors: Schmitz
authors: Hans Erik
authors: HE
authors: Bøtker
authors: Sten
authors: S
authors: Lund
authors: Gregers
authors: G
authors: Wegener
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003326:Coronary Circulation / Q000502:physiology; D003866:Depressive Disorder / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000209:etiology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009043:Motor Activity; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D015425:Myocardial Reperfusion / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose