- Email: [email protected]
P1-30 PHYSIOLOGICAL CONCENTRATION OF 17β-ESTRADIOL ON SYMPATHETIC REINNERVATION IN OVARIECTOMIZED INFARCTED RATS
Abstract of the 16th Asian Pacific Congress of Cardiology, Taipei, Taiwan, 13–16 December, 2007
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of 1×106 ADSCs was compared to the injection of media alone. Animals were analyzed using Echocardiography at 2 weeks after transplantation, and then sacrificed for histologic assessment. Results: The FS and LVEF improved in ADSCs transplant group at 2 weeks to compare with control group (p<0.05). LVEDD in ADSCs transplant group compared to control group showed a little decrease from 4.65±0.63mm (control) to 4.14±0.53mm (ADSCs); but there was no statistical difference (p=0.072), whereas LVESD decreased significantly in cell ,significant difference between ADSCs transplant group and control group (media) in injury size, infarct area, wall thickness or scar formation at 2 weeks after AMI. In our study, ADSCs have been showed to migrate into the injured sites and to integrate into the scar areas. In addition, some of transplanted ADSCs were able to express endothelial marker. Conclusion: In present study, the cardiac function and remodeling of ventricle in ADSCs transplant group were improved better than that in control group on echocardiography and histological analysis. This suggests that ADSCs could be a good candidate as a novel source of cell therapy in cardiovascular disease. Keywords: myocardial infarction, adipose tissue, transplantation.
were given intraperitoneal injections of sinomenine 10 mg/kg. The vascular effect of sinomenine was then examined in isolated aortic rings of Wistar rats. We further investigated the effect of sinomenine on changes in intracellular Ca2+ concentrations ([Ca2+ ]i) in cultured aortic smooth muscle (A7r5) cells by using the Ca2+ -sensitive dye fura-2 as an indicator. Results: At 30 min, sinomenine decreased systolic blood pressure in a dosedependent manner from 2.5–10 mg/kg in the SHR but not in the WKY, whose systolic blood pressure did not change. Sinomenine produced concentrationdependent relaxation in the aortic rings precontracted with phenylephrine (10 nmol/l) or KCl (40 mmol/l). Glibenclamide, an inhibitor specific to adenosine triphosphatase (ATP)-sensitive K+ channel, but not other specific inhibitors for K+ channel attenuated the sinomenine-induced relaxation. Sinomenine decreased [Ca2+ ]i elicited by phenylephrine (1 µmol/l) or KCl (40 mmol/l) in a concentration-dependent manner from 0.1–10 µmol/l. Glibenclamide abated this effect. Conclusions: Sinomenine caused vascular relaxation by opening ATP-sensitive K+ channel and thus decreasing [Ca2+ ]i.
P1-28
P1-30
CELLULAR MECHANISMS RESPONSIBLE FOR THE ARRHYTHMOGENIC ACTIVITY IN XIN-DEFICIENT MURINE LEFT ATRIAL-PULMONARY VEINS MYOCARDIUM
PHYSIOLOGICAL CONCENTRATION OF 17β-ESTRADIOL ON SYMPATHETIC REINNERVATION IN OVARIECTOMIZED INFARCTED RATS
Y.J. Lai 1,2 , E.Y.K. Huang 1 , H.I. Yeh 2 , Y.L. Chen 1 , J.J. Lin 3 , C.T. Lin 1 . 1 Institutes of Life Sciences, Pharmacology & Physiology, National Defense Medical Center ([email protected]), 2 Mackay Memorial Hospital, Taipei, Taiwan and 3 Department of Biological Science, University of Iowa, Iowa City, USA.
Tsung-Ming Lee 1 , Mei-Shu Lin 2 , Nen-Chung Chang 3 . 1 Department of Medicine, Cardiology Section, Chi-Mei Medical Center, Tainan, Taiwan; 2 Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; 3 Department of Medicine, Cardiology Section, Taipei Medical University and Hospital, Taipei, Taiwan.
Introduction: In our previous studies we have shown that left atrial-pulmonary vein (LA-PV) from 30% of wild-type (mXin?+/+) but none in Xinα-deficient (mXin?-/-) could generate re-entrant arrhythmias. This observation prompts us to further investigate the conduction velocity (CV) and the arrhythmogenic activity in mXin?+/+ vs. mXin?-/- murine LA-PV tissues. Methods and Results: Extra-cellular recording of electrical activities and CVs were determined in LA-PV by means of a MED64 system. Conventional microelectrode techniques revealed a +40% longer APD90 (driven at 4 Hz) and presence of automatic rhythms in 2/6 of mXin?-/- LA-PV preparations but none in mXin +/+ preparations. In the presence of 1 µM isoproterenol (ISO), automatic rhythms occurred in all 6 mXin but only in 1/6 mXin LA-PV preparations. The CVs were significantly faster in mXin?+/+ than in mXin?-/- LA-PV. In mXin?+/+ right atrial (RA)-LA-PV preparations, the incidence of atrial fibrillation (AF) after pacing under combined cardio-active drugs treatment (ISO + 10 µM strophanthidin + 0.1 µM atropine) was significantly higher as compared to that of mXin?-/- mice. Whole-cell current clamp experiments on LA-PV cardiomyocytes revealed a less negative maximum diastolic potential but no significant differences in diastolic slope and threshold potential in mXin?-/- vs. mXin?+/+ LA-PV cardiomyocytes. Conclusion: The incidence of AF in RA-LA-PV of mXin?-/- mice was significantly lower than that of mXin?+/+ after rapid pacing and drugs treatment. Results of tissue and cellular studies revealed a prolonged APD90 , a slower CV and a less negative diastolic potential in cardiac cells of mXin-deficient LA-PV.
Purpose of introduction/Background: Epidemiological studies showed that a lower mortality rate of sudden cardiac death among women than among men may depend in part on the action of female sex hormones. 17β-estradiol (E2) has been shown to exert antiarrhythmic effect after myocardial infarction; however, the mechanisms remain unclear. This study was performed to determine whether E2 exerts beneficial effects through attenuated sympathetic hyperreinnervation after infarction. Methods: Two weeks after ovariectomy, female Wistar rats were randomly assigned to coronary artery ligation or sham-operation. Twenty-four hours after operation, rats underwent one of four treatments: 1) subcutaneous vehicle treatment, 2) subcutaneous E2 treatment (0.5 mg 17β-estradiol pellet), 3) subcutaneous E2 treatment + tamoxifen (a potent estrogen receptor antagonist), or 4) bosentan (an endothelin receptor blocker) and followed for 4 weeks. Results: Myocardial endothelin-1 and norepinephrine levels in the remote zone revealed a significant elevation in vehicle-treated infarcted rats compared with sham-operated rats, which is consistent with sympathetic hyperinnervation after infarction. Sympathetic hyperinnervation was blunted after giving the rats either E2 or bosentan, assessed by immunohistochemical analysis of tyrosine hydroxylase, growth associated protein 43 and neurofilament, and Western blotting and real-time quantitative RT-PCR of nerve growth factor. Arrhythmic scores during programmed stimulation in E2-treated infarcted rats were significantly lower than in vehicle-treated infarcted rats. The beneficial effect of E2 on sympathetic hyperinnervation was abolished by tamoxifen. Conclusions: Our data indicated that E2 has a role for sympathetic hyperinnervation after infarction probably through an endothelin-1-depedent pathway. Chronic administration of E2 after infarction may attenuate the arrhythmogenic response to programmed electrical stimulation.
P1-29 VASODILATATION INDUCED BY SINOMENINE TO LOWER THE BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS
Ping-Ying Lee 1 , Wency Chen 2 , I-Min Liu 3 , Juei-Tang Cheng 4 . 1 Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan; 2 Department of Internal Medicine, E-Da Hospital, I-Shou University, Yan-Chau Shiang, Kaohsiung County, Taiwan; 3 Department of Pharmacy, Tajen University, Yanpu Shiang, Ping Tung Shien, Taiwan; 4 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan Introduction: Sinomenine is an alkaloid with wide range of pharmacologic actions. We investigated the effect of sinomenine on blood pressure and its possible mechanisms. Methods: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY)
P1-31 ASSOCIATION BETWEEN PPAR ALPHA GENE POLYMORPHISM AND COMPONENTS OF METABOLIC SYNDROME
Sir-Chen Lin 1 , Chun-Hsiung Wang 1 , Shen-Tien Chang 2 , Fu-Tien Chiang 3 . 1 Section of Cardiology, Taipei City Hospital, Renai Branch, Taipei, Taiwan. 2 Section of Cardiology, Min-Sheng General Hospital, Tao-Tuan, Taiwan; 3 Section of Cardiology, National Taiwan University Hospital, Taipei, Taiwan Introduction: Peroxisome proliferator-activated receptors (PPARs) are nuclear proteins that belong to the superfamily of nuclear hormone receptors. PPARs are ligand-induced transcription factors that regulate the transcription of target
69
of 1×106 ADSCs was compared to the injection of media alone. Animals were analyzed using Echocardiography at 2 weeks after transplantation, and then sacrificed for histologic assessment. Results: The FS and LVEF improved in ADSCs transplant group at 2 weeks to compare with control group (p<0.05). LVEDD in ADSCs transplant group compared to control group showed a little decrease from 4.65±0.63mm (control) to 4.14±0.53mm (ADSCs); but there was no statistical difference (p=0.072), whereas LVESD decreased significantly in cell ,significant difference between ADSCs transplant group and control group (media) in injury size, infarct area, wall thickness or scar formation at 2 weeks after AMI. In our study, ADSCs have been showed to migrate into the injured sites and to integrate into the scar areas. In addition, some of transplanted ADSCs were able to express endothelial marker. Conclusion: In present study, the cardiac function and remodeling of ventricle in ADSCs transplant group were improved better than that in control group on echocardiography and histological analysis. This suggests that ADSCs could be a good candidate as a novel source of cell therapy in cardiovascular disease. Keywords: myocardial infarction, adipose tissue, transplantation.
were given intraperitoneal injections of sinomenine 10 mg/kg. The vascular effect of sinomenine was then examined in isolated aortic rings of Wistar rats. We further investigated the effect of sinomenine on changes in intracellular Ca2+ concentrations ([Ca2+ ]i) in cultured aortic smooth muscle (A7r5) cells by using the Ca2+ -sensitive dye fura-2 as an indicator. Results: At 30 min, sinomenine decreased systolic blood pressure in a dosedependent manner from 2.5–10 mg/kg in the SHR but not in the WKY, whose systolic blood pressure did not change. Sinomenine produced concentrationdependent relaxation in the aortic rings precontracted with phenylephrine (10 nmol/l) or KCl (40 mmol/l). Glibenclamide, an inhibitor specific to adenosine triphosphatase (ATP)-sensitive K+ channel, but not other specific inhibitors for K+ channel attenuated the sinomenine-induced relaxation. Sinomenine decreased [Ca2+ ]i elicited by phenylephrine (1 µmol/l) or KCl (40 mmol/l) in a concentration-dependent manner from 0.1–10 µmol/l. Glibenclamide abated this effect. Conclusions: Sinomenine caused vascular relaxation by opening ATP-sensitive K+ channel and thus decreasing [Ca2+ ]i.
P1-28
P1-30
CELLULAR MECHANISMS RESPONSIBLE FOR THE ARRHYTHMOGENIC ACTIVITY IN XIN-DEFICIENT MURINE LEFT ATRIAL-PULMONARY VEINS MYOCARDIUM
PHYSIOLOGICAL CONCENTRATION OF 17β-ESTRADIOL ON SYMPATHETIC REINNERVATION IN OVARIECTOMIZED INFARCTED RATS
Y.J. Lai 1,2 , E.Y.K. Huang 1 , H.I. Yeh 2 , Y.L. Chen 1 , J.J. Lin 3 , C.T. Lin 1 . 1 Institutes of Life Sciences, Pharmacology & Physiology, National Defense Medical Center ([email protected]), 2 Mackay Memorial Hospital, Taipei, Taiwan and 3 Department of Biological Science, University of Iowa, Iowa City, USA.
Tsung-Ming Lee 1 , Mei-Shu Lin 2 , Nen-Chung Chang 3 . 1 Department of Medicine, Cardiology Section, Chi-Mei Medical Center, Tainan, Taiwan; 2 Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan; 3 Department of Medicine, Cardiology Section, Taipei Medical University and Hospital, Taipei, Taiwan.
Introduction: In our previous studies we have shown that left atrial-pulmonary vein (LA-PV) from 30% of wild-type (mXin?+/+) but none in Xinα-deficient (mXin?-/-) could generate re-entrant arrhythmias. This observation prompts us to further investigate the conduction velocity (CV) and the arrhythmogenic activity in mXin?+/+ vs. mXin?-/- murine LA-PV tissues. Methods and Results: Extra-cellular recording of electrical activities and CVs were determined in LA-PV by means of a MED64 system. Conventional microelectrode techniques revealed a +40% longer APD90 (driven at 4 Hz) and presence of automatic rhythms in 2/6 of mXin?-/- LA-PV preparations but none in mXin +/+ preparations. In the presence of 1 µM isoproterenol (ISO), automatic rhythms occurred in all 6 mXin but only in 1/6 mXin LA-PV preparations. The CVs were significantly faster in mXin?+/+ than in mXin?-/- LA-PV. In mXin?+/+ right atrial (RA)-LA-PV preparations, the incidence of atrial fibrillation (AF) after pacing under combined cardio-active drugs treatment (ISO + 10 µM strophanthidin + 0.1 µM atropine) was significantly higher as compared to that of mXin?-/- mice. Whole-cell current clamp experiments on LA-PV cardiomyocytes revealed a less negative maximum diastolic potential but no significant differences in diastolic slope and threshold potential in mXin?-/- vs. mXin?+/+ LA-PV cardiomyocytes. Conclusion: The incidence of AF in RA-LA-PV of mXin?-/- mice was significantly lower than that of mXin?+/+ after rapid pacing and drugs treatment. Results of tissue and cellular studies revealed a prolonged APD90 , a slower CV and a less negative diastolic potential in cardiac cells of mXin-deficient LA-PV.
Purpose of introduction/Background: Epidemiological studies showed that a lower mortality rate of sudden cardiac death among women than among men may depend in part on the action of female sex hormones. 17β-estradiol (E2) has been shown to exert antiarrhythmic effect after myocardial infarction; however, the mechanisms remain unclear. This study was performed to determine whether E2 exerts beneficial effects through attenuated sympathetic hyperreinnervation after infarction. Methods: Two weeks after ovariectomy, female Wistar rats were randomly assigned to coronary artery ligation or sham-operation. Twenty-four hours after operation, rats underwent one of four treatments: 1) subcutaneous vehicle treatment, 2) subcutaneous E2 treatment (0.5 mg 17β-estradiol pellet), 3) subcutaneous E2 treatment + tamoxifen (a potent estrogen receptor antagonist), or 4) bosentan (an endothelin receptor blocker) and followed for 4 weeks. Results: Myocardial endothelin-1 and norepinephrine levels in the remote zone revealed a significant elevation in vehicle-treated infarcted rats compared with sham-operated rats, which is consistent with sympathetic hyperinnervation after infarction. Sympathetic hyperinnervation was blunted after giving the rats either E2 or bosentan, assessed by immunohistochemical analysis of tyrosine hydroxylase, growth associated protein 43 and neurofilament, and Western blotting and real-time quantitative RT-PCR of nerve growth factor. Arrhythmic scores during programmed stimulation in E2-treated infarcted rats were significantly lower than in vehicle-treated infarcted rats. The beneficial effect of E2 on sympathetic hyperinnervation was abolished by tamoxifen. Conclusions: Our data indicated that E2 has a role for sympathetic hyperinnervation after infarction probably through an endothelin-1-depedent pathway. Chronic administration of E2 after infarction may attenuate the arrhythmogenic response to programmed electrical stimulation.
P1-29 VASODILATATION INDUCED BY SINOMENINE TO LOWER THE BLOOD PRESSURE IN SPONTANEOUSLY HYPERTENSIVE RATS
Ping-Ying Lee 1 , Wency Chen 2 , I-Min Liu 3 , Juei-Tang Cheng 4 . 1 Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medicine, Nursing and Management College, Taipei, Taiwan; 2 Department of Internal Medicine, E-Da Hospital, I-Shou University, Yan-Chau Shiang, Kaohsiung County, Taiwan; 3 Department of Pharmacy, Tajen University, Yanpu Shiang, Ping Tung Shien, Taiwan; 4 Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan Introduction: Sinomenine is an alkaloid with wide range of pharmacologic actions. We investigated the effect of sinomenine on blood pressure and its possible mechanisms. Methods: Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY)
P1-31 ASSOCIATION BETWEEN PPAR ALPHA GENE POLYMORPHISM AND COMPONENTS OF METABOLIC SYNDROME
Sir-Chen Lin 1 , Chun-Hsiung Wang 1 , Shen-Tien Chang 2 , Fu-Tien Chiang 3 . 1 Section of Cardiology, Taipei City Hospital, Renai Branch, Taipei, Taiwan. 2 Section of Cardiology, Min-Sheng General Hospital, Tao-Tuan, Taiwan; 3 Section of Cardiology, National Taiwan University Hospital, Taipei, Taiwan Introduction: Peroxisome proliferator-activated receptors (PPARs) are nuclear proteins that belong to the superfamily of nuclear hormone receptors. PPARs are ligand-induced transcription factors that regulate the transcription of target