During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to afailure in heart function with decreased cardiac output....During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to afailure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the followup progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.展开更多
Inotropic agents are indicated to treat ventricular dysfunction that frequently found post-CABG surgery. However, the use of inotropic isn’t free from disadvantageous side effects and is related to higher morbidity a...Inotropic agents are indicated to treat ventricular dysfunction that frequently found post-CABG surgery. However, the use of inotropic isn’t free from disadvantageous side effects and is related to higher morbidity and mortality in post-CABG surgery patients. Several risk factors are known to affect higher need for inotropic agents’?post-CABG surgery. This study aims to discover the inotropic?requirement in patients undergoing CABG surgery based on age, sex, preoperative left ventricular ejection?fraction?(LVEF),?comorbidities,?cross clamping time (CCT), and cardiopulmonary bypass (CPB) duration in Hasan Sadikin General Hospital Bandung in 2014-2016. This study is a descriptive cross-sectional study done retrospectively through medical records. This study found the inotropic?requirement?post-CABG surgery was?130 patients (74.3%). The inotropic?requirement?based on age was?28 patients (80.0%) > 65 years old,?112 patients (75.7%) were?male, 18 patients (66.7%) were?female, 19 patients (100%) with ?LVEF, 41?patients (85.4%) with DM, 20 patients (90.9%) with CKD, 44?patients (93.6%) with >90 minute CCT, 37?patients (90.2%) with >120 minute duration CPB. In conclusion, there was a higher inotropic?requirement in?patients with age > 65 years?old,?preoperative LVEF??comorbidities,?CPB duration > 120 minutes and CCT > 90 minutes.展开更多
Systemic inflammatory response syndrome (SIRS) is one of the key accompanied states that worsens severity of congestive heart failure (CHF) and leads refractory CHF to conventional therapy. We investigated whether the...Systemic inflammatory response syndrome (SIRS) is one of the key accompanied states that worsens severity of congestive heart failure (CHF) and leads refractory CHF to conventional therapy. We investigated whether the cessation of the symptoms and signs of SIRS prevents the progression of the CHF caused by chronic aortic stenosis in rabbits. 8 weeks after induced CHF by left descending coronary artery stenosis, all animals were randomly assigned into 3 groups: control (CG)—without therapy (infusion of 0.9% NaCl);main I— receive mg/kg of Adenocin®dissolved in water for injection i.v., once daily and main II—animals receive 0.25 mg/kg enalapril i.m, furosemide 1.0 mg/kg i.v. (bolus) and pimobendan 0.1 mg/kg i.v. once daily. All animals were euthanized after 14 days of the beginning of treatment. Long-term aortic stenosis leads to a simultaneously developing of CHF, diagnosed by developing cardiac hypertrophy, increased level of BNP and myocardial oedema and SIRS, confirmed by increasing markers and symptoms of endotoxemia, tissue dysoxia and decreasing reserve ability of intrinsic defense systems. Restoration of myocardium redox-potential and level of NAD under treatment with Adenocin®leads unlike combined treatment with enalapril, furosemide and pimobendan to restoration, the regulatory pathways of TNF-α synthesis, cessation of the hypoxic/ischemic, lysosomal dysfunction and free radical-induced damage in myocardium and symptoms of CHF. Potential important link between cellular metabolism (hypoxia/ischemia), endotoxemia and disturbances in intrinsic defense system is the level of redox-potentail, NAD/NADH in myocardium. Influence of oxidized form of NAD-containing positive inotropic drug Adenocin®leads to the decreasing symptoms of CHF and beneficial action occurs on all the key links of SIRS.展开更多
This study sought to investigate whether low dose dobutamine MRI can detect residual myocardial viability in patients with chronic myocardial infarction and left ventricular dysfunction. Methods. Eleven patients with ...This study sought to investigate whether low dose dobutamine MRI can detect residual myocardial viability in patients with chronic myocardial infarction and left ventricular dysfunction. Methods. Eleven patients with chronic myocardial infarction and left ventricular dysfunction were employed for identification of viable myocardium by cine MRI during dobutamine infusion. All patients underwent coronary angiography and left ventriculography, 18 FDG PET, MRI at rest and stress.The systolic wall thickening measured at rest and during stress was compared with the results of 18 FDG PET, respectively. Results. A significant difference of either dobutamine induced systolic wall thickening (SWth stress ) or dobutamine induced contractile reserve (ΔSWth= SWth stress - SWth rest ) was present between viable and scar regions (1 0±0 3 versus -0 3 ±0 1, P<0 01; 1 0±0 3 versus -0 2±0 2, P<0 01). Conclusions. Dobutamine induced contractile reserve can be predicted in the regions of akinesia or dyskinesia at rest when systolic wall thickening was 1 0 mm during dobutamine stimulation.展开更多
In an attempt to search for more potent positive inotropic agents, a series of 1-（benzylamino）-3-（4,5-dihydro[ 1,2,4]trizaolo[4,3- a]quinolin-7-yloxy）propan-2-ol derivatives was synthesized in four steps using 6-h...In an attempt to search for more potent positive inotropic agents, a series of 1-（benzylamino）-3-（4,5-dihydro[ 1,2,4]trizaolo[4,3- a]quinolin-7-yloxy）propan-2-ol derivatives was synthesized in four steps using 6-hydroxy-3,4-dihydro-2（1H）-quinolinone as a starting material, and their positive inotropic activities were evaluated by measuring the coronary blood flow （CBF） and the left ventricular pressure （LVP） followed by calculating the rate of pressure development （dp/dtmax values） in the preparation of rat Langendorff＇s heart. Three compounds （5d, 5g, 5j） showed favorable activities, among which 5g was shown the most potent with dp/dtmax value of 9.7% and CBF value of 17.8% at a concentration of 1×10^-5 mol/L in our in vitro study.展开更多
There is scarce information about the effects of danazol and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of danazol at the cardiovascular level is very confu...There is scarce information about the effects of danazol and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of danazol at the cardiovascular level is very confusing. In order to clarify those phenomena in this study, a danazol derivative was synthesized with the objective of evaluating its activity on perfusion pressure and coronary resistance and comparing this phenomenon with the effect exerted by danazol. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in the absence or presence of danazol and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by danazol derivative was evaluated by measuring left ventricular pressure in the absence or presence of following compounds;flutamide, prazosin, metoprolol, indomethacin and nifedipine. The results showed that danazol derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and danazol. Additionally, other data indicate that the danazol derivative increases left ventricular pressure in a dose-dependent manner;nevertheless, this phenomenon was significantly inhibited by flutamide. These data suggest that danazol derivative induces positive inotropic activity through of the activation androgen receptor.展开更多
AIM: To explore the role of mammalian target of rapamycin(m TOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition.METHODS: Male albino Wistar rats wei...AIM: To explore the role of mammalian target of rapamycin(m TOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition.METHODS: Male albino Wistar rats weighing 100-120 g were treated with tetrachloride carbon(CCl_4) for 8 wk to induce cirrhosis. Subsequently, animals were administered rapamycin(2 mg/kg per day). The QT_c intervals were calculated in a 5-min electrocardiogram. Then, the left ventricular papillary muscles wereisolated to examine inotropic responsiveness to β-adrenergic stimulation using a standard organ bath equipped by Powerlab system. Phosphorylated-m TOR localization in left ventricles was immunohistochemically assessed, and ventricular tumor necrosis factor(TNF)-α was measured. Western blot was used to measure levels of ventricular phosphorylated-m TOR protein.RESULTS: Cirrhosis was confirmed by hematoxylin and eosin staining of liver tissues, visual observation of lethargy, weight loss, jaundice, brown urine, ascites, liver stiffness, and a significant increase of spleen weight(P < 0.001). A significant prolongation in QTc intervals occurred in cirrhotic rats exposed to CCl_4(P < 0.001), while this prolongation was decreased with rapamycin treatment(P < 0.01). CCl_4-induced cirrhosis caused a significant decrease of contractile responsiveness to isoproterenol stimulation and a significant increase in cardiac TNF-α. These findings were correlated with data from western blot and immunohistochemical studies on phosphorylated-m TOR expression in left ventricles. Phosphorylated-m TOR was significantly enhanced in cirrhotic rats, especially in the endothelium, compared to controls. Rapamycin treatment significantly increased contractile force and myocardial localization of phosphorylated-m TOR and decreased cardiac TNF-α concentration compared to cirrhotic rats with no treatment. CONCLUSION: In this study, we demonstrated a potential role for cardiac m TOR in the pathophysiology of cirrhotic cardiomyopathy. Rapamycin normalized the i展开更多
The carduc effects of THB were studied in uolated rught and left atrual prepa-rations from guinea pigs.In spontaneously beating right atrua,TH B(1-56.3μmal/L caused brady-card ia,which was not prevented by atropine(1...The carduc effects of THB were studied in uolated rught and left atrual prepa-rations from guinea pigs.In spontaneously beating right atrua,TH B(1-56.3μmal/L caused brady-card ia,which was not prevented by atropine(1μmol/L).The time-effect curve of right atria on 4 mmul/L CaClz was markedly decreased by TIB.Tl B shifted the concentratwn-effect curve of iso to the right,and the maximum effect of Iso was clearly reduced.The PD2'was 5.32.For this reasun,the bradycard iae effect of TlI B mught be related to antogonism to Ca'+transport and non-competitme,block ofβ-adrenoceptur.Tll B pruduced negative inotropu effect.A decrease in trans membrane influz of Ca²+and inhibution of intracelluar calcium release mrght contribute to this action.展开更多
基金Supported by Grants from Fondo de Investigaciones Sanitarias(FIS 06/1082,in part)
文摘During the course of cirrhosis, there is a progressive deterioration of cardiac function manifested by the disappearance of the hyperdynamic circulation due to afailure in heart function with decreased cardiac output. This is due to a deterioration in inotropic and chronotropic function which takes place in parallel with a diastolic dysfunction and cardiac hypertrophy in the absence of other known cardiac disease. Other findings of this specific cardiomyopathy include impaired contractile responsiveness to stress stimuli and electrophysiological abnormalities with prolonged QT interval. The pathogenic mechanisms of cirrhotic cardiomyopathy include impairment of the b-adrenergic receptor signalling, abnormal cardiomyocyte membrane lipid composition and biophysical properties, ion channel defects and overactivity of humoral cardiodepressant factors. Cirrhotic cardiomyopathy may be difficult to determine due to the lack of a specific diagnosis test. However, an echocardiogram allows the detection of the diastolic dysfunction and the E/e′ ratio may be used in the followup progression of the illness. Cirrhotic cardiomyopathy plays an important role in the pathogenesis of the impairment of effective arterial blood volume and correlates with the degree of liver failure. A clinical consequence of cardiac dysfunction is an inadequate cardiac response in the setting of vascular stress that may result in renal hypoperfusion leading to renal failure. The prognosis is difficult to establish but the severity of diastolic dysfunction may be a marker of mortality risk. Treatment is non-specific and liver transplantation may normalize the cardiac function.
文摘Inotropic agents are indicated to treat ventricular dysfunction that frequently found post-CABG surgery. However, the use of inotropic isn’t free from disadvantageous side effects and is related to higher morbidity and mortality in post-CABG surgery patients. Several risk factors are known to affect higher need for inotropic agents’?post-CABG surgery. This study aims to discover the inotropic?requirement in patients undergoing CABG surgery based on age, sex, preoperative left ventricular ejection?fraction?(LVEF),?comorbidities,?cross clamping time (CCT), and cardiopulmonary bypass (CPB) duration in Hasan Sadikin General Hospital Bandung in 2014-2016. This study is a descriptive cross-sectional study done retrospectively through medical records. This study found the inotropic?requirement?post-CABG surgery was?130 patients (74.3%). The inotropic?requirement?based on age was?28 patients (80.0%) > 65 years old,?112 patients (75.7%) were?male, 18 patients (66.7%) were?female, 19 patients (100%) with ?LVEF, 41?patients (85.4%) with DM, 20 patients (90.9%) with CKD, 44?patients (93.6%) with >90 minute CCT, 37?patients (90.2%) with >120 minute duration CPB. In conclusion, there was a higher inotropic?requirement in?patients with age > 65 years?old,?preoperative LVEF??comorbidities,?CPB duration > 120 minutes and CCT > 90 minutes.
文摘Systemic inflammatory response syndrome (SIRS) is one of the key accompanied states that worsens severity of congestive heart failure (CHF) and leads refractory CHF to conventional therapy. We investigated whether the cessation of the symptoms and signs of SIRS prevents the progression of the CHF caused by chronic aortic stenosis in rabbits. 8 weeks after induced CHF by left descending coronary artery stenosis, all animals were randomly assigned into 3 groups: control (CG)—without therapy (infusion of 0.9% NaCl);main I— receive mg/kg of Adenocin®dissolved in water for injection i.v., once daily and main II—animals receive 0.25 mg/kg enalapril i.m, furosemide 1.0 mg/kg i.v. (bolus) and pimobendan 0.1 mg/kg i.v. once daily. All animals were euthanized after 14 days of the beginning of treatment. Long-term aortic stenosis leads to a simultaneously developing of CHF, diagnosed by developing cardiac hypertrophy, increased level of BNP and myocardial oedema and SIRS, confirmed by increasing markers and symptoms of endotoxemia, tissue dysoxia and decreasing reserve ability of intrinsic defense systems. Restoration of myocardium redox-potential and level of NAD under treatment with Adenocin®leads unlike combined treatment with enalapril, furosemide and pimobendan to restoration, the regulatory pathways of TNF-α synthesis, cessation of the hypoxic/ischemic, lysosomal dysfunction and free radical-induced damage in myocardium and symptoms of CHF. Potential important link between cellular metabolism (hypoxia/ischemia), endotoxemia and disturbances in intrinsic defense system is the level of redox-potentail, NAD/NADH in myocardium. Influence of oxidized form of NAD-containing positive inotropic drug Adenocin®leads to the decreasing symptoms of CHF and beneficial action occurs on all the key links of SIRS.
文摘This study sought to investigate whether low dose dobutamine MRI can detect residual myocardial viability in patients with chronic myocardial infarction and left ventricular dysfunction. Methods. Eleven patients with chronic myocardial infarction and left ventricular dysfunction were employed for identification of viable myocardium by cine MRI during dobutamine infusion. All patients underwent coronary angiography and left ventriculography, 18 FDG PET, MRI at rest and stress.The systolic wall thickening measured at rest and during stress was compared with the results of 18 FDG PET, respectively. Results. A significant difference of either dobutamine induced systolic wall thickening (SWth stress ) or dobutamine induced contractile reserve (ΔSWth= SWth stress - SWth rest ) was present between viable and scar regions (1 0±0 3 versus -0 3 ±0 1, P<0 01; 1 0±0 3 versus -0 2±0 2, P<0 01). Conclusions. Dobutamine induced contractile reserve can be predicted in the regions of akinesia or dyskinesia at rest when systolic wall thickening was 1 0 mm during dobutamine stimulation.
基金supported by the National Natural Science Foundation of China(No.30560177)the Natural Science Foundation of Jilin Province of China(No.20060567).
文摘In an attempt to search for more potent positive inotropic agents, a series of 1-（benzylamino）-3-（4,5-dihydro[ 1,2,4]trizaolo[4,3- a]quinolin-7-yloxy）propan-2-ol derivatives was synthesized in four steps using 6-hydroxy-3,4-dihydro-2（1H）-quinolinone as a starting material, and their positive inotropic activities were evaluated by measuring the coronary blood flow （CBF） and the left ventricular pressure （LVP） followed by calculating the rate of pressure development （dp/dtmax values） in the preparation of rat Langendorff＇s heart. Three compounds （5d, 5g, 5j） showed favorable activities, among which 5g was shown the most potent with dp/dtmax value of 9.7% and CBF value of 17.8% at a concentration of 1×10^-5 mol/L in our in vitro study.
文摘There is scarce information about the effects of danazol and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of danazol at the cardiovascular level is very confusing. In order to clarify those phenomena in this study, a danazol derivative was synthesized with the objective of evaluating its activity on perfusion pressure and coronary resistance and comparing this phenomenon with the effect exerted by danazol. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in the absence or presence of danazol and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by danazol derivative was evaluated by measuring left ventricular pressure in the absence or presence of following compounds;flutamide, prazosin, metoprolol, indomethacin and nifedipine. The results showed that danazol derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and danazol. Additionally, other data indicate that the danazol derivative increases left ventricular pressure in a dose-dependent manner;nevertheless, this phenomenon was significantly inhibited by flutamide. These data suggest that danazol derivative induces positive inotropic activity through of the activation androgen receptor.
基金Supported by Tehran University of Medical Sciences and Health Services grant,No.92033024196
文摘AIM: To explore the role of mammalian target of rapamycin(m TOR) in the pathogenesis of cirrhotic cardiomyopathy and the potential of rapamycin to improve this pathologic condition.METHODS: Male albino Wistar rats weighing 100-120 g were treated with tetrachloride carbon(CCl_4) for 8 wk to induce cirrhosis. Subsequently, animals were administered rapamycin(2 mg/kg per day). The QT_c intervals were calculated in a 5-min electrocardiogram. Then, the left ventricular papillary muscles wereisolated to examine inotropic responsiveness to β-adrenergic stimulation using a standard organ bath equipped by Powerlab system. Phosphorylated-m TOR localization in left ventricles was immunohistochemically assessed, and ventricular tumor necrosis factor(TNF)-α was measured. Western blot was used to measure levels of ventricular phosphorylated-m TOR protein.RESULTS: Cirrhosis was confirmed by hematoxylin and eosin staining of liver tissues, visual observation of lethargy, weight loss, jaundice, brown urine, ascites, liver stiffness, and a significant increase of spleen weight(P < 0.001). A significant prolongation in QTc intervals occurred in cirrhotic rats exposed to CCl_4(P < 0.001), while this prolongation was decreased with rapamycin treatment(P < 0.01). CCl_4-induced cirrhosis caused a significant decrease of contractile responsiveness to isoproterenol stimulation and a significant increase in cardiac TNF-α. These findings were correlated with data from western blot and immunohistochemical studies on phosphorylated-m TOR expression in left ventricles. Phosphorylated-m TOR was significantly enhanced in cirrhotic rats, especially in the endothelium, compared to controls. Rapamycin treatment significantly increased contractile force and myocardial localization of phosphorylated-m TOR and decreased cardiac TNF-α concentration compared to cirrhotic rats with no treatment. CONCLUSION: In this study, we demonstrated a potential role for cardiac m TOR in the pathophysiology of cirrhotic cardiomyopathy. Rapamycin normalized the i
文摘The carduc effects of THB were studied in uolated rught and left atrual prepa-rations from guinea pigs.In spontaneously beating right atrua,TH B(1-56.3μmal/L caused brady-card ia,which was not prevented by atropine(1μmol/L).The time-effect curve of right atria on 4 mmul/L CaClz was markedly decreased by TIB.Tl B shifted the concentratwn-effect curve of iso to the right,and the maximum effect of Iso was clearly reduced.The PD2'was 5.32.For this reasun,the bradycard iae effect of TlI B mught be related to antogonism to Ca'+transport and non-competitme,block ofβ-adrenoceptur.Tll B pruduced negative inotropu effect.A decrease in trans membrane influz of Ca²+and inhibution of intracelluar calcium release mrght contribute to this action.
