Effect of streptomycin on electrophysiological changes caused by rising of left ventricular afterload in rabbits

AIM: The aim of this study was to study the changes of rabbit heart electrophysiological properties caused by increasing left ventricular afterload, and to assess the effects of streptomycin or verapamil on these changes. METHODS: The rabbit heart preparation in situ was used, and the afterload of left ventricle was increased by clipping in part the root of ascending aorta. The changes of heart electrophysiological parameters including relative refractory period (RRP), effective refractory period (ERP), monophasic action potential duration (MAPD₉₀) and ventricular fibrillation threshold(VFT) were observed before and after altering the afterload of left ventricle and were compared in the absence and presence of streptomycin or verapamil. RESULTS: The rising of left ventricular afterload led to shortening of RRP, ERP and MAPD₉₀, and to descent of VFT (P＜0.01). Streptomycin inhibited these changes of heart electrophysiological parameters caused by elevation of left ventricular afterload. In contrast, verapamil had no effects on the afterload-related changes of RRP, ERP and MAPD₉₀ (P＞0.05) except increasing of VFT (P＜0.01). CONCLUSION: The electrophysilogical effect of streptomycin appears consistent with inhibition of stretch-activated ion channels, suggesting that the stretch-activated ion channels might be involved in the afterload-related changes of heart electrophysiological properties.     

Effects of catestatin on ventricular arrhythmia in isolated rat hearts with chronic heart failure

AIM:To determine the effects of catestatin (CST) on ventricular arrhythmia (VA) in isolated rat hearts with chronic heart failure (CHF). METHODS:Fifty-one male rats were randomly divided into 2 groups: control (CTL) group (n=17) and CHF group (n=34), which were injected with 0.9% normal saline (1 mL·kg-1·d-1, ip) and isoproterenol (ISO, 5 mg·kg-1·d-1, ip) for 7 d,respectively. The echocardiography was used to assess the cardiac functions 2 weeks after the end of modeling in both groups. The CHF rats were divided into non-treatment group (n=17) and CST treatment group (CST group, n=17). The rats in CST group was given CST (2 nmol·kg-1·d-1, ip) for 3 weeks, while 0.9% normal saline (1 mL·kg-1·d-1, ip) was applied to the rats in non-treatment group. To all the whole Langendorff-perfused hearts, the monophasic action potential (MAP) and the ventricular effective refractory period (VERP) were recorded and measured in left anterior free wall (LAF). The programmed electrical stimulation and burst pacing were used to induce action potential duration (APD) alternans (ALT) and VA in the LAF, respectively. The car-diac myocytes of LAF were enzymatically isolated and the technique of whole-cell patch clamp was used to record L-type Ca2+ current (ICa-L). RESULTS:Compared with CTL group, the peak ICa-L density, 90% of MAP duration (MAPD90), VERP, median of maximum pacing cycle length (PCLmax) inducing APD-ALT and incidence of VA (83.33% vs 1667%) were significantly increased in non-treatment group (all P<0.01). Compared with non-treatment group, the peak ICa-L density, MAPD90, VERP, median of PCLmax inducing APD-ALT and incidence of VA were significantly decreased in CST group (all P<0.05). CONCLUSION: Treatment with CST reduces the incidence of VA in CHF rats, which might be associated with the inhibition of ICa-L.     

Effects of non-excitatory electric stimulation on cardiac function in normal and infarcted heart rabbits and it's regional effect on myocardium

AIM: To investigate the influences of electric stimulation applied during the absolute refractory period (ARP) on the cardiac function of normal rabbits and rabbits after myocardial infarction (MI) and to observe the regional effects of this electric stimulation. METHODS: 64 rabbits were randomly assigned to normal and MI groups and each group was then divided into the anterior and posterior groups. A thoracotomy was performed 4 weeks after MI in rabbits. One set of electrodes was inserted into the anterior and posterior wall of left ventricle of the anterior and posterior groups, respectively. Current pulses were delivered during the ARP (called CCM) during sinus rhythm in rabbits. The left ventricular systolic pressure (LVSP) and the left ventricular end diastolic pressure(LVEDP) as well as maximum positive and negative left ventricular pressure change (±dp/dt_max) were observed. RESULTS: In the normal and MI groups, LVSP, +dp/dt_max significantly increased, and LVEDP, -dp/dt_max were reduced during CCM stimulation compared with the baseline (P<0.05). In the normal rabbits, electric stimulation in the anterior group improved the cardiac function more significantly than that in the posterior group (P<0.05). In the MI rabbits, there was no difference between the anterior and the posterior groups (P>0.05). CONCLUSION: Electric stimulation delivered during the ARP significantly enhances the contractility and the relaxation of myocardium in normal rabbits and rabbits after MI, and the effects of CCM stimulation on heart are regional.     

Effect of β3-adrenoceptor activation on ventricle fibrillation threshold and effective refractory period in rats with heart failure

AIM: To observe the effect of β₃-adrenoceptor (AR) on ventricle fibrillation threshold (VFT) and effective refractory period (ERP) in rats with heart failure.METHODS: Rats were randomized into control group and heart failure group. The expression of β₃- AR mRNA was detected with RT-PCR. The VFT, ERP, left ventricle end-systolic pressure(LVESP)，left ventricle end-diastolic pressure(LVEDP), +dp/dtmax and -dp/dtmax were measured at the same time with administration of BRL37344 (β₃-AR agonist).RESULTS: ① Both the expression of β₃-AR mRNA and the proportion (β₃/β₁+β₂+β₃) were increased in failure rats comparied with those in control rats (0.028 vs 0.011 and 5.4% vs 1.2%, P<0.05). ② ERP was longer in rats with heart failure than that in control group (70.5 ms±5.5 ms vs 59.5 ms±6.4 ms, P<0.05). No difference in ERP in rats with heart failure was observed before and after administration of BRL37344 (73.0 ms±4.8 ms vs 70.5 ms±5.5 ms, P>0.05). ③ VFT was lower in rats with heart failure than that in control group (10.9 mV±0.8 mV vs 30.5 mV±1.3 mV, P<0.05) and decreased obviously in rats with heart failure after administration of BRL37344 (7.1 mV±0.6 mV vs 10.9 mV±0.8 mV, P<0.05). The decrease in VFT correlated with the effect of LVESP, +dp/dtmax, -dp/dtmax with BRL37344 and the expression of β₃-AR mRNA (correlation coefficient: 0.788, 0.708, 0.759, 0.787; P<0.05). CONCLUSION: The expression of β₃-AR mRNA in left ventricle is obviously increased in rats with heart failure. The activation of β₃-AR has no effect on ERP but can decrease VFT which correlates with the effect of β₃-AR on LVESP, +dp/dtmax, -dp/dtmax and the expression of β₃-AR mRNA.     

Inhibitory effect of aerobic exercise on left ventricular remodeling and sympathetic neural remodeling in rats with heart failure after myocardial infarction

AIM: To investigate the effects of long-term aerobic exercise on the heart and sympathetic neural remodeling (structure and function remodeling) in heart failure rats induced by myocardial infarction. METHODS: Heart failure model after myocardial infarction was performed by ligating anterior descending coronary artery in the Wistar rats. Four weeks after operation, the rats were randomly divided into sham operation sedentary (S) group, heart failure sedentary (H) group and heart failure exercise (HE) group. The animals in HE group underwent 10-week treadmill running, while those in S group and H group were sustained in a resting state. The cardiac structure and function including left ventricular internal diameter at diastole (LVIDd), left ventricular internal diameter at systole (LVIDs), left ventricular anterior wall diameter at diastole (LVAWDd), left ventricular anterior wall diameter at systole (LVAWDs), left ventricular posterior wall diameter at diastole (LVPWDd) and left ventricular posterior wall diameter at systole (LVPWDs), and cardiac function parameters including fractional shortening (FS) and left ventricular ejection fraction (LVEF) were measured by echocardiography. The myocardium was collected for histopathological observation with Masson staining, and the collagen volume fraction (CVF) was determined. The concentrations of norepinephrine (NE) in the myocardium and plasma were measured by high-pressure liquid chromatography. The frequency domain analysis was applied for determining the heart rate variability (HRV) via subcutaneous recording electrode involving total power (TP), normalized low power (LFn), normalized high power (HFn) and LF/HF ratio. The mRNA expression of collagen type I (Col-I), collagen type III (Col-III), atrial natriuretic factor (ANF), α-myosin heavy chain (α-MHC), β-myosin heavy chain (β-MHC), sarcoplasmic endoplasmic reticulum Ca²⁺-ATPase (SERCA2a) was detected by real-time PCR. The protein levels of nerve growth factor (NGF) and its receptor (TrkA), and tyrosine hydroxylase (TH) were measured by Western blotting. RESULTS: (1) Compared with S group, body weight (BW), LVIDd, FS, LVEF, TP, HFn, the mRNA expression of α-MHC and SERCA2a, and the protein levels of NGF, TrkA and TH decreased (P<0.05). Left ventricular weight (LVW), left ventricular mass index (LVMI), LVAWDd, LVAWDs, LVPWDd, LVPWDs, CVF, plasma and myocardial NE content, LFn, LF/HF, and the mRNA expression of ANF, β-MHC, Col-I and Col-III increased (P<0.05) in H group. (2) Compared with H group, LVW, LVMI, LVIDd, FS, LVEF, TP, HFn, the mRNA expression of α-MHC and SERCA2a, and the protein levels of NGF, TrkA and TH were raised (P<0.05), while CVF, plasma and myocardial NE content, LFn, LF/HF, and the mRNA expression of ANF, β-MHC, Col-I and Col-III decreased (P<0.05) in HE group. CONCLUSION: Long-term aerobic exercise training leads to inhibition of heart and sympathetic neural remodeling and improvement of cardiac function and autonomic modulation in the rats after myocardial infarction.     

Change of Gq-phosphoinositide signaling pathway in left ventricular tissue in rats with chronic heart failure and reverse effect of benazepril on it

AIM: To investigate the changes of Gq-phosphoinositide pathway in left ventricular tissue of rats with chronic heart failure in order to assess the role of this signal pathway in the formation of heart failure. METHODS: Male Sprague-Dawle rats were divided into three groups: control, chronic heart failure and benazepril therapy group. Chronic heart failure was induced with adriamycin. Rats in benazepril group received benazepril 10 mg·kg-1·d-1 and adriamycin at the same time. Hemodynamic measurement was carried out after 4 weeks. The expression of Gα q/11 protein in left ventricle was detected by Western blotting analysis and activity of phospholipase C was measured by the method of hydrolysis of nuclear substrate. RESULTS: Compared with control group, the ±dp/dtmax in chronic heart failure group significantly decreased, and protein Gα q/11 expression, basic and stimulated phospholipase C activity significantly increased (P<0.01). The ±dp/dtmax in benazepril group was significantly lower than that in control but obviously higher than that in chronic heart failure group (P<0.05). Gα q/11 expression, basic and stimulated phospholipase C activity in benazepril group were significantly higher than those in control but obviously lower than those in heart failure group (P<0.01). CONCLUSION: Gq-phosphoinositide signaling pathway may play a role in the formation of chronic heart failure. Benazepril partialy attenuates the activation of phosphoinositide signaling pathway.     

Effect of pressure phase plane derived τ and K on evaluation of left ventricular diastolic function in isolated rat heart during ischemia/reperfusion

AIM: To analyze and compare the changes of pressure phase plane (PPP) derived τ and K on isolated rat heart during ischemia/reperfusion, and to explore the value of PPP derived τ and K for evaluation of left ventricular diastolic dysfunction. METHODS: LVEDP, -(dp/dt)_max, τ and K were measured and calculated during ischemia/reperfusion in Sprague-Dawley rat hearts. Meanwhile, the level of lactate dehydrogenase (LDH) in the coronary effluent was measured, and the ultrastructure changes in myocardium were observed under electron microscope. RESULTS: Compared with control group, τ increased and K reduced significantly in each ischemic group in a time dependent manner (P<0.05). With prolonged ischemia, τ was even higher and K was even lower (P<0.05). Compared with control group, except ischemia 15 min, LDH in other groups increased significantly at 10 min and 20 min after reperfusion (P<0.05). Compared with ischemia 30 min, LDH of ischemia 45 min and ischemia 60 min were even higher at 10 min and 20 min after reperfusion (P<0.05). With prolonged ischemia, the abnormal changes of the myocardial ultrastructure were observed. CONCLUSION: PPP derived τ and K may be promising indexes for quantitative assessment of left ventricular diastolic function on isolated rat heart during ischemia/reperfusion, and indication of the severity of ischemia/reperfusion injury.