Effects of Individual and Coexisting Diabetes and Cardiomyopathy on Diastolic Function in Rats (Rattus norvegicus domestica)

The goal of this study was to evaluate diastolic intraventricular pressure gradients (IVPG) and 2-dimensional tissue tracking (2DTT) patterns during diabetes and cardiomyopathy. Rats (n = 60) were induced to become diabetic (DM group, n = 15) by using streptozotocin, to become cardiomyopathic (CM group, n = 15) by using isoproterenol, and to become both diabetic and cardiomyopathic (DMCM group, n = 15); control rats (CT group, n = 15) were injected with saline. Two months after induction, all rats underwent conventional echocardiography, IVPG, and 2DTT and then were euthanized for microscopic examination of cardiac fibrosis. Compared with the controls, all 3 treated groups showed diastolic dysfunction and delayed cardiac relaxation. DMCM rats showed the most pronounced cardiac abnormalities. In addition, CM and DMCM groups had showed decreased middle IVPG, whereas DMCM rats had decreased midapical IVPG. Although the overall IVPG of the CM group was normal, the middle segment was significantly decreased. 2DTT results showed that the DMCM group had a delay in relaxation compared with other groups. IVPG and 2DTT can be used to overcome the limitation of conventional echocardiographic methods and reveal diastolic dysfunction. DM worsened diastolic function during cardiac disease.

Diabetes mellitus (DM) is a chronic disease identified by hyperglycemia.¹ DM and associated insulin abnormalities result in hypertension, cardiovascular disease, and multiple organ dysfunction.¹⁸ Diabetic cardiomyopathy is defined as abnormal myocardial structure and performance in the absence of other cardiac risk factors, such as coronary artery disease, hypertension, and significant valvular disease, in patients with DM.³ A previous study showed that diastolic dysfunction could result from DM; and cardiac fibrosis in the interstitial and perivascular areas was a hallmark of long-term DM.²³ Cardiac fibrosis in DM rats results from myocardial infarction.Cardiomyopathy can be induced in rats by using isoproterenol.¹⁷ Cardiomyopathy refers to the cardiac disorder in which myocardial abnormalities result from myocyte injury. Cardiomyopathy has several etiologies, including chronic hypertension, valvular abnormality, and toxin.¹⁵ Both DM and cardiomyopathy are fibrotic heart diseases, but their pathogenesis differs. Moreover, DM and CM cause fibrosis in different heart locations.The diastolic function of the left ventricle (LV) can be defined as the pull of blood into the LV under low filling pressure. Two groups have described the pressure differences that pull the blood through the mitral valve into the ventricle during diastole.^6,16 The difference of pressure between the LV and aorta during systole and the importance of regional pressure differences within the ventricle during relaxation has recently gained attention.^9,29 The diastolic intraventricular pressure gradient (IVPG) in the LV is closely related to LV relaxation. Deterioration of the IVPG is associated with abnormal LV blood flow patterns.²2D tissue tracking (2DTT) echocardiography is a promising technique that quantifies myocardial deformation by tracking the ultrasonographic speckle pattern of the cardiac cycle.¹³ Because of the importance of measuring diastolic function, we used conventional echocardiography, IVPG and 2DTT to evaluate the diastolic impairment without altering systolic function. We studied the relationship between mild (DM rats) and moderate (CM rats) cardiac fibrosis due to myocardial injury and infarction together with the severe fibrosis that develops due to the combination of DM and cardiomyopathy.Streptozotocin and isoproterenol were used to induce DM and cardiomyopathy, respectively. Both cause cardiac fibrosis, but the pathogenesis and affected location are different. Our study was designed to evaluate diastolic IVPG and 2DTT as diastolic indices. Our goal was to delineate IVPG and 2DTT patterns in DM, CM, and very severe fibrotic heart disease induced by combining DM and cardiomyopathy.