METFORMIN IMPROVES CARDIAC-FUNCTION IN ISOLATED STREPTOZOTOCIN-DIABETIC RAT HEARTS

The effects of metformin administration were studied in isolated perfu sed working hearts from control and diabetic rats. Control and strepto zotocin-treated diabetic rats were treated for 8 wk with metformin hyd rochloride. Treatment was initiated at 350 mg.kg(-1).day(-1) and was g radually increased to a dose of 650 mg.kg(-1) day(-1), which was maint ained over a 6-wk period. Isolated heart performance was assessed unde r conditions of increasing preload to evaluate the performance of each heart to ''stress.'' Hearts from untreated diabetic rats exhibited a depressed response to increases in left atrial filling pressures from 17.5 to 22.5 cmH(2)O in terms of left ventricular developed pressure, ventricular contractility, and ventricular relaxation compared with ag e-matched untreated controls. The diabetic hearts also exhibited a del ayed half time to relaxation at filling pressures from 15 to 22.5 cmH( 2)O. The function curves were performed at-a constant heart rate of 30 0 beats/min. These responses were restored to control values in diabet ic rats treated with metformin. Metformin treatment did not affect the ventricular responses in control rats. Metformin reduced plasma gluco se levels in the diabetic rats from 24.3 to 14.4 mM without any increa se in the plasma insulin levels. The diabetic group had higher triglyc erides than age-matched untreated control rats, and metformin administ ration in diabetic rats reduced triglyceride levels to control values but had no effect in control rats. In conclusion, metformin administra tion improves cardiac performance in streptozotocin-diabetic rats unde r conditions of increasing preload.