| Cardiac hypertrophy was an absolute and dangerous factor that affected mortality and morbidit of cardiovascular diseases. Left ventricular weight rise in patients with cardiac hypertrophy. Cardiac hypertrophy was not only a pathophysiological process, but olso a discompensatory change that affected short-term and long-term prognosis. Nowdays drugs for curing cardiac hypertrophy mostly have angiotensin coverting enzyme inhibitors and calcium channel blockers. Some calcium channel blockers had satisfactory anti-hypertrophy effect. It would have wide clinical significance and provide academic basis for clinical application to develop a new type calcium antagonist. Dipfluzine (Dip), a novel derivative of diphenylpiperazines with similar stucture to flunarizine, was synthesized by Hebei Medical University. The previous studies showed that Dip could markedly shorten duration of action potential, and decrease action potential amplitude (APA) and maximal rate of depolarization in phase 0 (Vmax) of partially depolarized papillary muscles. Furthermore, it could decrease Vmax and APA of sinoatrial pacemaker cell of rabbits and human atrial fibers. Dip could attenuate or postponed the occurrence of isoprenaline-induced EADs and TA in guinea pig papillary muscles. Dip could inhibit Ca2+ influx through L-type Ca2+ channel. But it was not known whether Dip had protective effects on myocytes. In this study, the model of cardiac hypertrophy was made through partial ligation of abdominal aorta in rats. The effects of Dip on cardiac hypertrophy were observed and the mechanism of action was studied. 1 Effects of Dip on cardiac hypertrophy Objective: To study the effects of Dip on blood pressure, the functions of contraction and diastole of left ventricle, heart weight index, left ventricular weight index and microstructure. Methods: Models were made through partial ligation of abdominal aorta. SD rats (weighing 180-220g, male, healthy) were randomly divided into 6 groups: (1) Sham operation control group; (2) Solvent control group; (3) Flunarizine 10mg/kg group; (4) Dip 30mg/kg group; (5) Dip 10mg/kg group; (6) Dip 3mg/kg group. Rats in sham operation control group only underwent operating procedure. Drugs were administered by ig for four weeks after operation (1ml/100g). Rats were anaesthetized, right carotid artery was separated and a cardiac catheter was inserted into the left ventricular cavity via the right carotid artery and connected with MS2000 media mix signal analysis system. The SBP, DBP, MBP, LVSP, LVEDP and ±dp/dtmax were recorded, and HW/BW and LVW/BW were calculated. Specimen of left ventricle was fixed, embedded in paraffin, cranked out 5 micron thick common section, HEstained. MFD was measured by microscope. Results: (1)Blood pressure (BP): SBP, DBP and MBP in sham operation control group were 20.3±2.4kpa, 16.3±1.8kpa and 17.6±1.9kpa respectively; those in solvent control group were 31.2±3.9kpa, 21.0±2.4kpa and 25.4±3.2kpa respectively, which were significantly higher than those in the sham operation control group (p<0.01). Dip 10mg/kg could markedly reduced SBP (p<0.05), Dip 30mg/kg could significantly decrease SBP and MBP (p<0.05), but Dip 3mg/kg had no obvious effect on BP. (2)Functions of contraction and diastole of left ventricle: LVSP, LVEDP, +dp/dtmax and -dp/dtmax in sham operation control group were 20.8±1.7 kpa, -0.04±0.09 kpa, 1324±90 kpa/s and 1151±113 kpa/s respectively. Those in solvent control group were 22.7±1.1 kpa, 1.89±0.74 kpa, 1116±99 kpa/s and 935±120 kpa/s respectively. The LVSP and LVEDP in solvent control group were higher than those in sham operation control group (p<0.05), and +dp/dtmax and -dp/dtmax were lower than those in sham operation control group (p<0.01). Compared with solvent control group, All doses of Dip could decrease LVEDP (p<0.01). Dip 10 and 30mg/kg could obviously increase ±dp/dtmax (p<0.01). (3)HMI and LVMI: The values of HW/BW and LVW/BW in sham operation control group were 2.74±0.22 and 1.92±0.10 respectively. Those in solvent control group w...
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