S5-02 Caution: as dietary calcium is raised to prevent osteoporosis, increase magnesium intake for cardiovascular health

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Abstracts/International Journal of Cardiology 97 SuppL 2 (2004) S 1 ~ 7 5

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Vascular Biology $4-01 I N VIVO E V A L U A T I O N O F S I G N A L I N G M O L E C U L E : D E V E L O P M E N T OF C A T H E T E R - T Y P E N I T R I C O X I D E S E N S O R

M asarrd Goto 1, Yoji Neishi 2, Seiichi Mochizuki 1, Takehiro Miyasaka3, Renan S ulOlmwan2, Yasuo Ogasawara1, Furrdhiko Kajiya3, Takashi Akasaka2, Kiyoshi Yoshida 2. 2Dept. of Medical Engineering and

Systems Cardiology; 2Diu of Cardiovascular Medicine, Kawasaki Medical School, Dept. of Cardiovascular Physiology, s Okayama University Graduate School of Medicine and Dentistry, Japan I n t r o d u c t i o n : Nitric oxide (NO) is a key signaling molecule in the regulation of coronary blood flow and vascular integrity. However, lack of technology to measure NO in the coronary circulation has been preventing us fiom the understanding of the kinetics of NO in the coronary circulation, remaining many uncertainties in coronary vascular biology. Thus, we developed a catheter type NO sensor for coronary sinus. M e t h o d : An NO sensitive electrode was located and fixed in a 4 Fr catheter with a soft tip for protection of vascular wall. After calibrating with an NO saturated pine water, the catheter type NO sensor was located in the coronary sinus in anesthetized dogs ( n ~ ) . The coronary flow velocity (CFV) was also measured with a Doppler guide wire in the left anterior descending artery (LAD). We a&~linistrated saline, acethylcholine (ACh) and isosorbide dinitrate into the LAD. Administration of ACh was repeated after the infusion of N ~ methyl L arginine (L NAME). Results: Saline Wansiently increased NO concenWation with CFV. ACh further increased NO concentration and CFV. L NAME decreased basal NO concentration and suppressed the NO synthesis by ACh. ISDN also increased NO concentration and CFV. C o n c l u s i o n : We conclude that 1) NO produced in the coronary circu lation persists in the coronary venous blood at a measurable level and 2) the newly developed catheter type NO sensor for coronary sinus is useful to evaluate the endothelium derived flow and agonisbinduced NO production and phamlacokinetics of NO donor in the coronary circulation.

$4-02 EXERCISE IMPROVES ENDOTHELIUM-DEPENDENT VASCULAR FUNCTIONS

Chauying J. Jen, Hsiun Ing Chen. Department of Physiology, College of

Medicine, National Cheng Kung University, Taincvt, Taiwan Despite the cleat- association between exercise and a reduced risk of cardiovascular disease, the precise mechanisms responsible for this asso ciation remain unclear. It is intriguing to examine whether exercise exerts direct effects on vascular functions. As the endothelium not only plays a pivotal role in controlling vascular tone but exerts several important anti atherosclerotic functions, such as preventing platelets and ii~lamma tory cells fiom adhering to the vascular surface, could the exercise effects on vascular functions be mediated by this vascular lining? Our early animal studies conducted a decade ago have provided the first conclusive evidence that physical conditioning modulates endothelium dependent va sorelaxation, instead of altering the relaxing response in vascular smooth muscle. More recently, we have developed a tissue flow chamber that allows simultaneous measurements of endothelial calcium signaling and vascular contraction/relaxation in dissected vessel segments. Using this tissue flow chamber, we have shown that exercise improves vascular endothelial functions in various aninml models. Interestingly, many ben eficial effects of exercise are more pronounced in diseased animals than in controls. In recent years, it has also become apparent that exercise in humans directly affects the functional activity of the vascular endothe lium. Based on studies using model aninmls and human subjects, exercise improves endothelium dependent vascular functions via multiple mecha nisms, including at least the modulation of surface receptors and adhesion

molecules, intracellular calcium signaling, NO synthase expression and Akbdependent NO synthase phospho~Nlation.

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Antioxidants and Cardiovascular D i s e a s e $5-01 ANTI-THROMBOTIC PROPERTIES OF FRUITS AND V E G E T A B L E S : F R O M IN V I T R O S T U D I E S TO H U M A N T R I A L S

Asim K. Duttaroy. Dept. of Nutrition, University of Oslo, Norway Activation of blood platelets plays a crucial role not only in haemostasis but also in pathological development of several arterial disorders, including strokes and myocardial infarction. There is increasing evidence that acute clinical manifestations of coronary atherosclerotic disease are caused by plaque disruption and subsequent platelet tllrombus fomlation. Thus platelet activity may play a major role in the development of disease as well as in the stability of atherosclerotic plaques. In support of the pathophysiologicalrole of platelets, platelet inhibito~N ddrugssuch as aspirin reduce the incidence of myocardial infarction, stroke and death from cardiovascular disease in secondary prevention trials. Epidemiological investigations have shown that the incidence of myocardial infarction is much lower in Naples, Italy compared to Bristol, UK. After adjusting for dietat-y and classical risk factors, the authors concluded that the intake of tomatoes and olive oils in the Naples group might account for the differences. Tomatoes are rich source of antioxidants such as beta carotene, folic acid, potassium, vitamin C, vitamin E, fl avonoids and lycopene, which have been postulated to have a beneficial effect on cardiovascular disease. However, despite an inverse association of cardiovascular disease with high intakes of tomato based products, dietat-y lycopene was not strongly associated with a lower risk of CVD. Thisindicates that other unidentified compounds in tomatoes may have cat-dioprotective effects. In 2000, we identified potent anti platelet factors in tomatoes, which inhibit platelet aggregation in response to ADR collagen, and tllrombin An extract with high anti platelet activity was isolated from the yellow juice concenWated around the seeds in intact tomatoes. On investigation the extract was found to be a complex mixture of low molecular weight (<1000 Da) water soluble compounds. Recently we have concluded several human trials using tomato extracts either in encapsulated form or mixed with orange juice.Along with these results, I will surrmaarise the recent trials involving fl-ults and vegetables and their overall effects on CVD, specifically platelet function in human volunteers.

$5-02 CAUTION: A S D I E T A R Y C A L C I U M IS R A I S E D TO P R E V E N T OSTEOPOROSIS, I N C R E A S E M A G N E S I U M I N T A K E F O R CARDIOVASCULAR HEALTH

Mildred S. Seelig. Master of Am Coil of Nutr, Decatur, Georgia, USA Altering dietary intakes in Asian countries, so that they resemble Wesb ern (i.e. American) foods, may well contribute to increasing prevalence of cardiovascular- diseases in Asia that have long been predominantly a problem of the West. Ischemic heart disease, arrhythmias and other cardiovascular disorders, and predisposing conditions: Type 2 diabetes, essential hypertension, obesity and other aspects of the metabolic syn ddrome are common in America and other Western countries, and are increasing in Japan where American type foods have become popular. The current official American recommendation for high intakes of calcium (Ca), despite marginal intakes of magnesitml (Mg) which results in Ca/Mg intake ratios of over 4/1 was adopted in 1997, stemming largely fiom the intent to protect against osteoporosis, by increasing consump tion of nutrients that increase bone mineralization. Rarely considered is the growing evidence of cardiovascular damage, as well as metabolic

Abstracts/International Journal of Cardiology 97 SuppL 2 (2004) S1~75 disturbances associated with high Ca/Mg ratios in the body both extra cellular and intracellular, An early clue to damage associated with dietary CaLVlg imbalance is the finding that the peak in ischemic heart disease mortality in American and Canadian men occurred early in the sixth decade of the 20 th century, by which time the Ca/Mg intake had risen from the earlier 211 ratio to an over 311 ratio. Might the even higher Ca/Mg intake ratio in the United States of ~ecent years have contributed to the failure of the Women's Health Initiative (WHI)? That was a large controlled double blind test of the controversial value of postmenopausal hormone replacement therapy in reducing risks of bone, cardiovascular, and mental diseases of aging women. The disappointing results most caused by thromboembolic events could have been contributed to by estrogen induced enhancement of coagulation, that might well have been abetted by high plasma Ca/Mg levels, in view of increasing Ca dependent steps in the coagulation cascade and platelet aggregation, reactions that are inhibited by Mg, Elevated intracellular Ca/Mg has been shown to be characteristic of patients with the metabolic syndrome (insulin resistance syndrome or syndrome X), Current interest in nutritional antioxidants as adjuvant treatment for cardiac patients should call attention to observations that marginal and low Mg intakes increase release of free oxygen radicals, and additionally increase formation of proinflammatory agents another condition suspected to play a role in cardiovascular disease.

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an important role in the pathogenesis of CHF by mediating the cell cell interactions of the immune response. However, clinical data about the prognostic value of sCAMs are sparse, The purpose of this study is to deteffnine whether various sCAMs can provide prognostic infomlation in patients with CHF. Methods: We measured circulating levels of three sCAMs (vascular cell adhesion molecule 1 [sVCAM 1], intercellular adhesion molecule 1 [sICAM 1], and sP selectin) in 74 patients with symptomatic chronic CHF and left ventricular ejection fraction (LVEF) <50%. We compared these levels with those of a group of 19 age matched control subjects. Major adverse cardiac events (death, heart transplantation or hospitalization with worsening CHF) during a median follow up period of 240 days were determined. Results: The concentrations of the 3 sCAMs in the 74 patients with CHF were significantly associated with one another. Their levels were higher than those of the control subjects and increased with the severity of CHF. Significantly higher sCAM levels were noted in those patients who had major adverse cardiac events during the follow up period. There were significant negative correlations between LVEF and sCAMs, However; only high levels of sP selectin were found to be an independent significant predictor of CHF by Cox proportional hazards analysis. Conclusions: These findings indicate that the levels of these 3 sCAMs increase with the severity of CHF and are related to clinical outcomes. Among them, high levels of sP selectin can provide prognostic information independently in patients with CHE

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Hypertension II $6-01 N E W G U I D E L I N E S IN T H E M A N A G E M E N T O F H Y P E R T E N S I O N Philip Y u A n Ding, Division of Cardiolog~ Taipei Veterans General

Hospital, National Yang-Ming Universit~ Taipei, Taiwan Cardiovascular disease (CVD) is responsible for one third of global deaths and is a leading and increasing contributor to the global disease burden. Importantly, CVD is eminently preventable. In order to achieve significant reductions in the avoidable CVD burden, a combination of population bsed and high risk strategies is necessary. These sWategies should target lifestyle related risk factors such as unhealthy diet, physical inactivity, and tobacco use, as well as the intermediate manifestations of these lifestyles; hypertension, glucose intolerance, and hyperlipidemia, In addition, strategies aimed at improving management of those already affected by CVD should be an integral component of a comprehensive approach for the prevention and control of CVD, Hypertension, one of the commonest diagnoses in the clinic, contributes substantially to the morbidity and mortality of CVD, However, despite well ~ecognized as an important risk factor of CVD, management of hypertension remained unsatisfactory, since only about 30 percent of hypertensive patients were well treated, In latest two years, there were 3 guidelines for treatment of hypertension published: (1) 2003 JNC 7 guidelines; (2) 2003 WHO/ISH guidelines; (3) 2004 BHS IV guidelines, In this speech, I will address the highlight in these guidelines and give a brief summary,

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Basic Study of Heart Failure $7-01 T H E P R O G N O S T I C V A L U E O F SOLUBLE CELLULAR A D H E S I O N M O L E C U L E S IN PATIENTS W I T H C H R O N I C C O N G E S T I V E HEART FAILURE Wei Hsian Yin, Cheng Hsin Rehabilitation Medical Center Background: Circulating soluble (s) cell adhesion molecules (CAMs) are elevated in patients with congestive heart failure (CHF) and may play

$7-02 U S I N G Z E B R A F I S H TO E S T A B L I S H AN ANIMAL M O D E L OF H E A R T FAILURE: M Y O C A R D I A L F U N C T I O N A L A S S A Y IN CARDIAC TROPONIN C ANTI-SENSE ZEBRAFISH Yi Lwun Ho, Section of Cardiology, Department of Internal Medicine,

National Taiwan University Hospital, Taipei, Taiwan The zebrafish (Danio rerio) is a new animal model for cardiac researches. The zebrafish heart contains 4 components (sinus venosus, atrium, ventricle and bulbus arteriosus), Although it has a prototypic vertebrate heart, the studies of genetic control for zebrafish development can reveal some hints to solve human problems. On the other hand, the zebrafish mutations which principally disturb cardiac contractility fall into two broad phenotypic categories, 'dilated' and 'hypertrophic'. These correspond to the two primary types of heart failure in humans. The disorders of cardiac function provided candidate genes to be examined in complex hmnan heart diseases, including an-hytlmrias and heart failure). Using cardiac myosin light chain 2 as a promoter, we have specifically set up a "tet on system" in heart of zebrafish, After adding doxycycline to zebrafish 12 hours post fertilization, cardiac troponin42 (cTnC) anti sense mRNA and g~een fluorescent protein will be expressed in zebrafish hearts. The heart rate significantly reduced in cTnC anti sense zebrafish (150 vs 193 beats/min at 6 days; 128 vs 168 beats/min at 12 days). The prevalence of abnormal end diastolic volume, end systolic volume and ejection fi-action were15%, 39% and 46% in cTnC anti sense zebrafish at 6 days post fertilization. The prevalence of abnormal end diastolic volmne, end systolic volmne and ejection fraction were 60%, 50% and 90% in cTnC anti sense zebrafish at 12 days post fertilization. In addition to bradycardia, there were also 1,3% of cTnC anti sense zebrafish with att~o ventricular block. cTnC anti sense zebrafish offers a new animal model for researches of heart failure,