Comparative investigation of the left ventricular pressure-volume relationship in rat models of type 1 and type 2 diabetes mellitus

Abstract

Diabetes mellitus (DM) is associated with characteristic structural and functional changes of the myocardium, termed diabetic cardiomyopathy. As a distinct entity independent of coronary atherosclerosis, diabetic cardiomyopathy is an increasingly recognized cause of heart failure. A detailed understanding of diabetic cardiac dysfunction, using relevant animal models, is required for the effective prevention and treatment of cardiovascular complications in diabetic patients. We investigated and compared cardiac performance in rat models of type 1 DM (streptozotocin induced) and type 2 DM (Zucker diabetic fatty rats) using a pressure-volume (P-V) conductance catheter system. Left ventricular (LV) systolic and diastolic function was evaluated in vivo at different preloads, including the slope of the end-systolic P-V relation (ESPVR) and end-diastolic P-V relationship (EDPVR), preload recruitable stroke work (PRSW), maximal slope of the systolic pressure increment (dP/dt(max)), and its relation to end-diastolic volume (dP/dt(max)-EDV) as well as the time constant of LV relaxation and maximal slope of the diastolic pressure decrement. Type 1 DM was associated with decreased LV systolic pressure, dP/dt(max), slope of ESPVR and dP/dt(max)-EDV, PRSW, ejection fraction, and cardiac and stroke work indexes, indicating marked systolic dysfunction. In type 2 DM rats, systolic indexes were altered only to a lower extent and the increase of LV stiffness was more pronounced, as indicated by the higher slopes of EDPVR. Our data suggest that DM is characterized by decreased systolic performance and delayed relaxation (mainly in type 1 DM), accompanied by increased diastolic stiffness of the heart (more remarkably in type 2 DM). Based on the sophisticated method of P-V analysis, different characteristics of type 1 and type 2 diabetic cardiac dysfunction can be demonstrated.

Structural lesions and changing pattern of expression of genes encoding cardiac muscle proteins are associated with ventricular myocyte dysfunction in type 2 diabetic Goto-Kakizaki rats fed a high-fat diet

“…The GK rats fed LFD, with elevated non-fasting blood glucose, displayed prolonged t peak and t 1 /2 relaxation of shortening compared with GK rats fed HFD. Previous studies have variously demonstrated increased collagen deposition and increased ventricular stiffness in different experimental models of type 2 diabetes, including diet-induced diabetic rats and Zucker diabetic fatty rats, which in turn were associated with altered kinetics of myocardial contraction (Patel et al 2009;Radovits et al 2009;Rickman et al 2010;Patel et al 2011).…”

Strain and strain rate by speckle-tracking echocardiography correlate with pressure-volume loop-derived contractility indices in a rat model of athlete's heart

“…A polyethylene catheter was inserted into the left external jugular vein for fluid administration. P-V analysis was performed as described previously (22). A 2-Fr pressureconductance catheter (SPR-838; Millar Instruments, Houston, TX) was introduced into the right carotid artery and advanced into the LV.…”

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2

“…Hyperglycemia is a common feature in all animal models of diabetes, but plasma levels of insulin and lipids are different in T1DM and T2DM and also in models of T2DM (28,44). In addition, characteristics of LV pressurevolume relationship are different in T1DM and T2DM (25), indicating a possible difference in modifications of excitationcontraction coupling between the two types of DM.…”