Bio-effects of salusins on isolated rat heart and neonatal cardiomyocytes

AIM: To investigate the bio-effects of salusins on rat heart and cardiomyocytes. METHODS: The cardiac function was determined by multipurpose polygraph in isolated rat heart treated with various concentrations of salusin-α or salusin-β.[⁴⁵Ca²⁺] and[³H]-Leu incorporation were determined in cultured neonatal rat cardiomyocytes with β-liquid scintillation counter. RESULTS: 10^-12-10^-7mol/L salusin-α and salusin-β had no effects on isolated rat cardiac function. However, salusin-α and salusin-β stimulated uptake and[³H]-Leu incorporation. The [⁴⁵Ca²⁺] uptake induced by salusins were inhibited by nicardipine, and were synergistically increased by endothelin-1. The[³H]-Leu incorporation induced by salusin-α and salusin-β was inhibited by nicardipine, FK506 (a special inhibitor of carcineulin), PD₉₈₀₅₉ (inhibitor of MAPK) and chelerthine (inhibitor of PKC). The effects of salusin-β[⁴⁵Ca²⁺] on uptake was stronger than those of salusin-α. But there were no statistical difference in[³H]-Leu incorporation between salusin-α and salusin-β. CONCLUSIONS: Salusin-α and salusin-β did not affect directly cardiac function in rat hearts. But salusins improved calcium uptake and protein synthesize in neonatal rat cardiomyocytes. Those effects of salusins were related with calcium channel, carcinuelin, MAPK and PKC signal pathways. Salusins may be the regulatory factors for myocardium growth and hypertrophy.     

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.     

Quantitative perfusion parameters of dynamic contrast-enhanced magne-tic resonance imaging in patients with rectal cancer: estimation of the microvascular perfusion and permeability

AIM: To investigate the perfusion parameters using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rectal cancer patients so as to explore its potential value in estimating the microvascular condition including perfusion and permeability. METHODS: The data of 38 rectal cancer patients examined with DCE-MRI was retrospectively analyzed. The perfusion parameters of carcinoma and normal rectal wall in each case were calculated, including volume transfer constant (K^trans), rate constant of back flux (K_ep), extravascular extracellular space fractional volume (V_e) and initial area under curve (iAUC). The mean values of tumor and normal rectal wall, mucinous and nonmucinous carcinoma, poorly and moderately-to-well differentiated carcinoma, case with or without lymph node metastasis were compared. RESULTS: All the parameters of rectal cancer were higher than normal rectal wall (P<0.01). No significant difference was found between poorly and moderately-to-well differentiated carcinoma in terms of K^trans, K_ep and V_e, neither was the case with or without lymph node metastasis. The cases with lymph node metastasis had lower iAUC than those without (P<0.05). CONCLUSION: Quantitative perfusion DCE-MRI answered the microvascular perfusion and permeability change of rectal cancer compared with normal rectal wall, besides it could be used to distinguish between mucinous and nonmucinous carcinoma, which demonstrated its value in the evaluation of rectal cancer. However, it should not be recommended to predict the degrees of tumor cell differentiation and lymph node metastasis just according to the perfusion parameters.     

Application of laser scanning confocal microscope in the study of ischemic heart disease

This article reviewed the characteristics of the laser scanning confocal microscope and its application in the research of the ischemic heart disease, including the morphology, apoptosis and necrosis of the myocardium, the express of the adhesion molecule, and the Ca²⁺ ion in the myocardium.     

A simple and effective auxiliary device for detection of physiologic function on isolated sciatic nerve and gastrocnemius in toads

AIM: To design a simple and effective auxiliary device for detection of the compound action potential (CAP) and the force on the isolated sciatic nerve and gastrocnemius in toads, and to investigate its practicability. METHODS: A simple "L" shape device (L tube), which was composed of a nerve chamber and an organ bath, was made for fixing the isolated sciatic nerve and gastrocnemius. After fixing, the sciatic CAP and the gastrocnemius force were detected by BL-420S data acquisition and analysis system. The specimens were radomly divided into control group, and the lidocaine nerve and muscle groups. The sciatic nerve or gastrocnemius of each lidocaine group was firstly treated with the corresponding concentration of lidocaine, and then washed out with Ringer's solution, and its reversible anesthetic action on nerve conduction and muscle force was analyzed to verify the practicability of the L tube device. RESULTS: The CAP and the force of the sciatic-gastrocnemius specimens were detected concurrently by fixing the specimens in the L tube, and the liquid in the nerve chamber and organ bath was changed easily. Compared with the control, lidocaine at 0.05 and 0.2 g/L significantly increased the sciatic threshold stimulus voltage and maximal stimulus voltage (P<0.05), prolonged the absolute refractory period (P<0.01), and slowed down the conduction velocity (P<0.01). Lidocaine at 1 g/L completely blocked the sciatic conduction. The rest tension of the gastrocnemius was increased, and the maximal twitch force was decreased significantly by 1 g/L lidocaine (P<0.01), but the threshold and maximal stimulus voltage did not show statistic difference. The parameters of the sicatic nerve and gastrocnemius completely or partially recovered to the control level after washing out.CONCLUSION: As an auxiliary device, L tube makes the detection of CAP and force on the isolated sciatic nerve and gastrocnemius in toads more conveniently.     

Role of calcium activated potassium channel in cardioprotection induced by anoxic postconditioning in isolated rat heart

AIM:To investigate whether calcium activated potassium channel (KCa) and mitochondrial permeability transition pore (mPTP) contribute to cardioprotective effect elicited by anoxic postconditioning.METHODS:The isolated perfused hearts of male Sprague-Dawley rats were subjected to 30 min global anoxic followed by 120 min reoxygenation. Formazan content of myocardium was measured at 490 nm spectrophotometrically,and the level of lactate dehydrogenase (LDH) in the coronary effluent was detected. The absorbance of isolated heart mitochondria at 520 nm was determined. RESULTS:Anoxic postconditioning increased formazan content,reduced LDH release,improved the hemodynamic parameters of the left ventricular developed pressure,maximal rise/fall rate of left ventricular pressure,left ventricular end-diastolic pressure and rate pressure product and attenuated the decrease of coronary flow during reperfusion. Pretreatment with paxilline (1 μmol/L) inhibited the effect of anoxic postconditioning. The opening of mPTP was suppressed in the mitochondria isolated from A/R hearts treated with anoxic postconditioning.CONCLUSION:The findings indicate that in the isolated rat heart,anoxic postconditioning protects myocardium against anoxic/reoxygenation injury via inhibiting KCa and the mPTP opening.     

Effect of changing left ventricular afterload and isolated perfused rabbit heart on ventricular refractory period measured by subthreshold conditioning train stimulation

AIM: To study the effect of changing left ventricular afterload and isolated perfused rabbit heart on ventricular refractory period measured by subthreshold conditioning train stimulation (S_t). METHODS: Ventricular refractory period strength-interval relation was measured by S_t method under the condition of changing left ventricular afterload and eliminating action of nervous and body fluid. RESULTS: Reducing left ventricular afterload pro- longed ventricular refractory period measured by S_t method (P＜0.05, P＜0.01). and S_t (200 Hz,100 ms) and S_t (50 ms,100 Hz) caused maximal prolongation of ventricular refractory period (P＜0.05, P＜0.01). CONCLUSION: Changing left ventricular afterload and eliminating action of nervous and body fluid could cause alteration of characteristic of ventricular refractory period strength-interval relation measured by S_t method.     

Role of cytokines in the pathogenesis of heart failure

Previous reports have shown that cytokines and cytokine receptors are independent predictors of mortality in patients with advanced heart failure. Recent studies demonstrate that cytokines, such as tumor necrosis factor, interleukin 1 and interleukin 6, play an important role in the pathogenesis of heart dysfunction in patients with heart failure. In this review, we summarized the importance, expression and mechanism of cytokines in the development and progression of heart failure.     

Effect of scutellarin on resuscitating rat NHBMD livers with extracorporeal liver perfusion in vitro

AIM: To investigate the effect of scutellarin on resuscitating rat non-heart-beating marginal donor (NHBMD) livers with extracorporeal liver perfusion in vitro. METHODS: Twenty-four male Wistar rats were randomly divided into 3 groups: group A (n=8), the livers were subject to 15~20 min of warm ischemia; group B (n=8) and group C (n=8), the livers were subject to 45 min of warm ischemia. All the livers were treated by extracorporeal liver perfusion (ECLP), and scutellarin solution was add to the perfusion fluid in group C with the intervals of 1 h. The data of bile production and the markers of hepatocyte reperfusion injury of the livers,alanine aminotransferase (ALT) and endothelin-1 (ET-1), in each group were tested. The liver tissues in each group were obtained before perfusion and 1 h, 3 h and 6 h after perfusion, and then observed under transmission electron microscope to investigate the changes of ultrastructures. RESULTS: With the time of perfusion went on, the livers in group B and group C demonstrated recovery of synthe-tic function after 3 h and 6 h of perfusion, and the production of bile in group B and group C was not significantly different from that in group A after 6 h of perfusion (P>0.05). The levels of ALT and ET-1 in group B and group C were significantly higher than those in group A after 1 h, 3 h and 6 h of perfusion (P<0.05), and those in group C was significantly lower than those in group B after 3 h and 6 h of perfusion (P<0.05). The ultrastructural destruction of the liver cells in both group B and group C was more serious than that in group A. After 3 h and 6 h of perfusion, the destruction of the liver cells was partly recovered, and the recovery degree in group C was more obvious than that in group B. CONCLUSION: Scutellarin may play a significant role in resuscitating rat NHBMD livers with extracorporeal liver perfusion in vitro.     

Experimental study on how brain-dead state affects the heart structure and function of Ba-Ma mini pigs and the mechanism

AIM:To investigate how brain-dead state affects the heart structure and function and the effect of PKC-α in BA-Ma mini pigs.METHODS:Ten Ba-Ma mini pigs were randomized into 2 groups: brain-dead group (n=5),and control group (n=5). The brain-dead model was made by increasing intracranial pressure,while the control group was maintained anesthesia for 24 h. The concentrations of cTnT,TNF-α,IL-1β and IL-6 in serum were determined at 6,12 and 24 h after brain death. At 24 h,heart tissues were observed by HE staining and electron microscope. The expression of PKC-α was detected by immunohistochemistry and RT-PCR.RESULTS:(1) Histological changes of myocardium: flaky bleeding under endocardium and dissolution of myocardium were found in optical microscope. In electron microscope dropsical mitochondria and confluent muscle fiber were found. (2) Changes of serum cTnT: serum cTnT for brain-dead group began to increase gradually since 6 h,and were significantly higher at each time point than those in control group (P<0.05). (3) Changes of inflammatory factors: IL-1β,IL-6,and TNF-α in brain-dead group began to increase gradually since 6 h,and were significantly higher at each time point than those in control group (P<0.05). (4) Changes of PKC-α expression: PKC-α mRNA and protein expressions in brain-dead group increased significantly at 24 h (P<0.05).CONCLUSION:Brain death may evoke heart structure and functional injury,and increase the levels of inflammatory factors and PKC-α. The activation of PKC-α may participate in the process of heart injury.     

Dendranthema morifolium attenuated the reduction of contraction of isolated heart and cardiomyocytes induced by ischemia/reperfusion

AIM: To investigate the effect of Dendranthema morifolium (Ramat) Tzvel (DM) on isolated rat heart and ventricular myocytes during ischemia/anoxia and reperfusion/reoxygenation.METHODS: The Langendorff perfused rat hearts were used to measure intraventricular pressure and coronary flow. The cell contraction and intracellular calcium transient in enzymatically isolated ventricular myocytes were determined. RESULTS: (1) DM (0.5 g/L) significantly attenuated the inhibitory effects induced by ischemia/reperfusion on left ventricular developed pressure (LVDP), ±dp/dt_max, coronary flow and LVDP×HR, meanwhile increased the content of SOD and decreased the content of MDA in the myocardium; (2) DM (0.5 g/L) attenuated the inhibitory effects of anoxia and reoxygenation on i transient and cell contraction in isolated ventricular myocytes. CONCLUSION: DM attenuated the effects on contractility and intracellular calcium induced by ischemia/anoxia and reperfusion/reoxygenation in the isolated rat heart and the ventricular myocytes. The mechanism might be related to increase in SOD activity and maintaining [Ca]i homeostasis.     

Adaptive changes in heart during acclimation to hypoxia in the rat

AIM:To study the changes in myocardial blood flow (MBF), capillarization and cardiac function in the rat during acclimation to hypoxia. METHODS:Myocardial capillary density (CD) and capillary/myocyte ratio (C/M) was assayed by alkaline phosphatase histochemistry. Biomicrosphere method was used to determine MBF in the rat after 5, 15 or 30 days hypobaric hypoxic exposure (5 000 m). RESULTS:In the course of hypoxia, MBF and cardiac function increased in the right ventricle. However, in the left ventricle, acute hypoxia caused an increase in MBF and a decrease in cardiac function. Both returned to the control level on continued hypoxic exposure. Neovascularization occurred after 15 day or 30 day of hypoxic exposure in both ventricles, judged from the significant increment of C/M ratio albeit the CD remained unchanged in the right ventricle. CONCLUSION:Our findings indicate that adaptive changes in rat heart during acclimation to hypoxia include: ① persistent increase in MBF, hypertrophy associated with increase in capillarity and enhanced cardiac function of the right ventricle; ② increase in MBF and depression of cardiac function at first, then followed by recovery of MBF and increase in capillarity accompanied with recovery of left ventricular function.     

Effects of cardiac contractility modulation applied to different locations of heart on cardiac functions in rabbits with heart failure

AIM: To investigate the effects of cardiac contractility modulation (CCM) applied to different locations of the heart on cardiac functions and cardiac dys-synchrony in the rabbits with chronic heart failure, and to explore the best pattern of CCM.METHODS: Forty rabbits were divided into 4 groups according to the location of receiving CCM: heart failure (HF) group, left ventricular anterior wall (LVAW-CCM) group, left ventricular posterior lateral wall (LVPLW-CCM) group and right ventricular apex (RVA-CCM) group. The model of chronic heart failure was made by ligating ascending aortic root of the rabbits. After 12 weeks, the electrical stimulations during the absolute refractory period were delivered in different locations of the heart, lasting 6 h everyday for 7 days. The changes of cardiac functions and cardiac dys-synchrony were observed by cardiac ultrasonic cardiogram before and after CCM stimulation. The plasma level of brain natriuretic peptide (BNP) was detected by ABC-ELISA method. Pulsed-wave Doppler was used to acquire aortic pre-ejection interval (APEI) and pulmonary pre-ejection internal (PPEI), and inter-ventricular mechanical delay (IVMD) was calculated to evaluate the cardiac dys-synchrony.RESULTS: Compared with HF group, left ventricular end-systolic dimension (LVESD) and left ventricular end-diastolic dimension (LVEDD) in LVAW-CCM group, LVPLW-CCM group and RVA-CCM group were significantly decreased (P<0.05), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were significantly increased (P<0.05), especially in LVAW-CCM group. Interventricular septal thickness (IVS) and left ventricular posterior wall thickness (LVPW) were similar among groups. No significant difference of plasma BNP level before CCM delivery among the 4 groups was observed. However, the plasma BNP level in control group was the highest, followed by LVPLW-CCM group and RVA-CCM group, and LVAW-CCM group was the lowest after CCM delivery. No change of IVMD was observed among groups before and after CCM delivery.CONCLUSION: The effect of CCM applied to different locations of the heart on cardiac functions is different.The optimal site of CCM delivery is left ventricular anterior wall. No influence of interventricular dys-synchrony was observed during application of CCM.     

Effects of meglumine cycle adenylate phosphate combined with transplantation of mesenchymal stem cells on heart functions in rat model of heart failure

AIM: To investigate the therapeutic effects of recombinant meglumine cycle adenylate phosphate (MCA) and bone marrow mesenchymal stem cells (BMSCs) on the enhancement of the cell survival and improvement of the cardiac functions in the rat model of adriamycin-induced cardiomyopathic heart failure. METHODS: BMSCs were isolated and expanded using the pre-plating method. Doxorubicin was used by intraperitoneal injection into the Wistar rats to establish the model of cardiomyopathic heart failure. The model animals randomly received the injection of PBS, MCA, BMSCs or MCA+BMSCs respectively, and normal controls were without any treatment. Four weeks after injection, the cardiac functions were determined by echocardiography and multichannel physiological recorder. The levels of brain natriuretic peptide (BNP) were measured by ELISA. The positive rate of BrdU-labeled BMSCs in the myocardium was analyzed by the method of immunohistochemistry. The expression of myocardium-specific protein, GATA-4, connexin 43(Cx43) and cardiac troponin 1(cTNI), was detected by Western blotting. Myocardial fibrosis was observed with Masson's staining. RESULTS: Compared with other groups, the results of echocardiography and hemodynamic showed that the left ventricular functions in BMSCs+MCA group improved significantly (P<0.05). The BMSCs numbers in the myocardium in BMSCs+MCA group were significantly higher than those in BMSCs group (P<0.05). The level of BNP was significantly lower in BMSCs+MCA group than that in BMSCs group (P<0.05). Compared with other groups, the expression of GATA-4, Cx43 and cTNI was significantly increased in BMSCs+MCA group. CONCLUSION: Combination of MCA with BMSCs transplantation improves the cardiac functions, possibly due to the enhancement of BMSCs survival and the increase in the protein expression of GATA-4.     

Effects of different ages on ventricular remodeling after ischemic heart failure in mice

AIM: To observe ventricular remodeling induced by ischemic heart failure in the mice at different ages.METHODS: Three-month-old (young group, n=50) and 18-month-old (old group, n=50) male C57BL/6J mice were selected in the study. Forty mice underwent ligation of left coronary artery with certain infarct size, and 10 were sham-operated for control. Echocardiography was performed after 8 weeks of infarction. All mice were killed and the hearts were collected for examinations. Masson trichrome staining was used to detect myocardial fibrosis. The expression of type I and type Ⅲ collagens was measured by the method of immunohistochemistry.RESULTS: The incidences of cardiac rupture (18% vs 10%, P<0.05) and heart failure (22% vs 10%, P<0.05) were significantly higher in aged mice than those in young mice. The degrees of left ventricular dilation, contractile dysfunction and heart rate were significantly higher in aged mice than those in young mice (P<0.05). The left ventricular mass index, collagen volume fraction, the expression of type I collagen and ratio of type Ⅰ/Ⅲ collagens were significantly increased in aged mice as compared with young mice (P<0.05).CONCLUSION: After heart failure, aged mice show abnormal collagen distribution, and suffer from worse cardiac functions and more serious ventricular remodeling.     

Effects of Qili Qiangxin capsule on serum concentration of adiponectin and heart function in patients with coronary heart disease combined with congestive heart failure

AIM：To investigate the effects of Qili Qiangxin capsule on serum adiponectin (APN), serum N-terminal pro-brain natriuretic peptide (NT-proBNP) and heart function in the patients of coronary heart disease combined with congestive heart failure. METHODS：One hundred and twenty patients were randomly divided into treatment group and control group, and both groups were given anti-failure routine therapy. The patients in treatment group were treated with Qili Qiangxin capsule and the patients in control group were treated with placebo. The patients in the 2 groups were given a certain dose of the drugs for 6 months. The New York Heart Association (NYHA) heart function classification, left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD),left ventricular ejection fraction (LVEF), and 6-min walking test (6-MWT) were observed before and after treatment. The levels of APN, NT-proBNP were measured by ELISA before and after treatment. RESULTS：With the increase in the class of NYHA heart function, the serum concentrations of APN and NT-proBNP in the heart failure cases increased significantly. After 6-month treatment, the effective rate in experimental group was 91.7% and that in control group was 75.0%. A significant difference was found between the 2 groups (P<0.01). After treatment, LVEDD and LVESD in both groups were decreased significantly, and LVEF in both groups was increased significantly. The serum concentrations of APN and NT-proBNP decreased significantly (P<0.05). 6-MWT result was improved significantly. Compared with control group, more obvious effect was observed in experimental group (P<0.05). CONCLUSION：Treatment with Qili Qiangxin capsule reduces the levels of APN and NT-proBNP in the patients with coronary heart disease combined with congestive heart failure.     

Effects of human urotensin II on ischemia/reperfusion injury in isolated perfused rat hearts

AIM: To investigate the effects of human urotensin II (hUII) on ischemia/reperfusion (I/R) injury in isolated rat hearts. METHODS: In the ischemia/reperfusion (I/R) model of isolated perfused rat hearts, the effects of hUII pretreatment on cardiac function was monitored with cardiac function software of MFL Lab200. ATP, total calcium, and malondialdehyde (MDA) content in myocardium were detected. The coronary perfusion flow (CPF) and lactate dehydrogenase (LDH) activity in coronary effluent were measured during reperfusion. RESULTS: In the hUII pretreated group, the release of LDH from myocardium was lower [(78.3±18.1)U/L] than I/R group [(109.3±23.9) U/L, P< 0.05], with decreased contents of MDA and calcium in myocardium (decreased by 24% and 27%, respectively, P< 0.05) and an increased myocardial ATP content [(3.8±0.4)μmol/g dw vs (2.2±0.4)μmol/g dw, P< 0.05)]. At the same time, hUII pretreatment increased CPF [(5.4±0.7) mL/min vs (3.8±0.8) mL/min in I/R group, P< 0.05], reduced left ventricular end-diastolic pressure (LVEDP) by 20% ( P< 0.05) with increased±d p /d t max [(217±38) kPa/s and (119±18) kPa/s vs (173±29) kPa/s and (82±25) kPa/s in I/R groups, respectively, P< 0.05]. hUII pretreatment also increased natrite/natrate (NO₂^-/NO₃^-) content in coronary effluent [(52.2±12.0)μmol/L vs (32.1±10.2)μmol/L in I/R group, P< 0.05)]. CONCLUSION: hUII pretreatment attenuated I/R injury in isolated perfused rat hearts. The protective mechanism might be associated with NO-mediated coronary vasodilation.     

Expression of calcium handling protein in diastolic heart failure

AIM:To elucidate molecular mechanisms underlying calcium handling protein in diastolic heart failure (DHF) from mRNA level and protein expression, including calcium adenosine triphosphatase (Ca²⁺-ATPase), phospholamban, ryanodine receptor, calsequestrin and L-type calcium channel.METHODS:The mRNA of these calcium handling genes were detected by RT-PCR, and the protein levels were analyzed by Western blot analysis.RESULTS:Compared with sham-operated rabbits, the steady-state levels of mRNA encoding the SR Ca²⁺-ATPase and cardiac L-type calcium channel were decreased significantly in rabbits with DHF, and protein level of SR Ca²⁺-ATPase was greatly reduced, whereas the mRNA and protein levels of other calcium handling protein were unchanged.CONCLUSION:L-type calcium channel and the sarcoplasmic reticular Ca²⁺-ATPase were down regulated in DHF. These changes may be a contributory factor for DHF.     

Changes in the expression of endothelin system in rats with chronic heart failing

AIM: To study the changes of endothelin system during chronic heart failure (CHF) and imply the relationship between endothelin system and the course of CHF by observing the mRNA expression of endothelin receptors (ET_AR and ET_BR) and PreproET₁ in early stage and later stage of CHF caused by left coronary artery ligation. METHODS: The mRNA expression of ET_A, ET_B receptors and PreproET₁ were detected by RT-PCR technique. The plasma concentrations of ET₁ and ANP were determined by RIA method. RESULTS: The plasma concentrations of ET₁ and ANP, and the mRNA expression of ET receptors and PreproET₁ in the lefe ventricle increased significantly in early stage (myocardial infarction 10 d). While the plasma concentrations of ET₁ and ANP in later stage (myocardial infarction 70 d) were higher than those in the early stage. However, the mRNA expression of ET_AR, ET_BR and PreproET₁ decreased significantly. The mRNA expression of ET_AR in myocardial infarction (MI) 70 d rats had no difference with those in sham-operated rats and the mRNA expression of ET_BR and PreproET₁ in MI 70 d rats was lower significantly than those in MI 10 d rats, but significantly higher than those in sham-operated rats. CONCLUSION: The changes of ET receptors and PreproET₁ mRNA expression are involved in the cardiac function modulation during the different stages in chronic heart failure.