Diabetic cardiomyopathy in Zucker diabetic fatty rats: the forgotten right ventricle.
BACKGROUND
In patients with myocardial infarction or heart failure, right ventricular (RV) dysfunction is associated with death, shock and arrhythmias. In patients with type 2 diabetes mellitus, structural and functional alterations of the left ventricle (LV) are highly prevalent, however, little is known about the impact of diabetes on RV characteristics. The purpose of the present study was to investigate whether LV changes are paralleled by RV alterations in a rat model of diabetes.


METHODS
Zucker diabetic fatty (ZDF) and control (ZL) rats underwent echocardiography and positron emission tomography (PET) scanning using [18F]-2-fluoro-2-deoxy-D-glucose under hyperinsulinaemic euglycaemic clamp conditions. Glucose, insulin, triglycerides and fatty acids were assessed from trunk blood. Another group of rats received an insulin or saline injection to study RV insulin signaling.


RESULTS
ZDF rats developed hyperglycaemia, hyperinsulinaemia and dyslipidaemia (all p < 0.05). Echocardiography revealed depressed LV fractional shortening and tricuspid annular plane systolic excursion (TAPSE) in ZDF vs. ZL rats (both p < 0.05). A decrease in LV and RV insulin-mediated glucose utilisation was found in ZDF vs. ZL rats (both p < 0.05). LV associated with RV with respect to systolic function (r = 0.86, p < 0.05) and glucose utilisation (r = 0.74, p < 0.05). TAPSE associated with RV MRglu (r = 0.92, p < 0.05) and M-value (r = 0.91, p < 0.0001) and RV MRglu associated with M-value (r = 0.77, p < 0.05). Finally, reduced RV insulin-stimulated phosphorylation of Akt was found in ZDF vs. ZL (p < 0.05).


CONCLUSIONS
LV changes were paralleled by RV alterations in insulin-stimulated glucose utilisation and RV systolic function in a rat model of diabetes, which may be attributed to ventricular interdependence as well as to the uniform effect of diabetes. Since diabetic patients are prone to develop diabetic cardiomyopathy and myocardial ischaemia, it might be suggested that RV dysfunction plays a central role in cardiac abnormalities in this population.
van den Brom
Charissa E
CE
Department of Internal Medicine/Diabetes Centre, VU University Medical Centre, Amsterdam, the Netherlands. c.vandenbrom@vumc.nl
Bosmans
Joanna W A M
JW
Vlasblom
Ronald
R
Handoko
Louis M
LM
Huisman
Marc C
MC
Lubberink
Mark
M
Molthoff
Carla F M
CF
Lammertsma
Adriaan A
AA
Ouwens
Margriet D
MD
Diamant
Michaela
M
Boer
Christa
C
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D009202:Cardiomyopathies / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000209:etiology; D015150:Echocardiography, Doppler; D005227:Fatty Acids / Q000097:blood; D019788:Fluorodeoxyglucose F18; D015309:Glucose Clamp Technique; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism; D006946:Hyperinsulinism / Q000209:etiology; D007328:Insulin / Q000097:blood; D008297:Male; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019275:Radiopharmaceuticals; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000209:etiology; D018497:Ventricular Dysfunction, Right / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D016277:Ventricular Function, Left; D016278:Ventricular Function, Right
D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D019275:Radiopharmaceuticals; D014280:Triglycerides; D019788:Fluorodeoxyglucose F18; D051057:Proto-Oncogene Proteins c-akt