Adrenomedullin in heart failure

Adrenomedullin in heart failure

90 Journal of Cardiac Failure Vol. 4 No. 3 Suppl. 2 1998 101 102 IODINE-123 METAIODOBOBEZYLGUANINE (MIBG) IMAGES AND NEUROHORMONAL ACTIVATION iN P...
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90

Journal of Cardiac Failure Vol. 4 No. 3 Suppl. 2 1998

101

102

IODINE-123 METAIODOBOBEZYLGUANINE (MIBG) IMAGES AND NEUROHORMONAL ACTIVATION iN PATIENTS WITH ASYMPTOMATIC CONGESTIVE HEART FAILURE Shinya Okamoto, Ryuuji Okamote, Kimimasa Saitou, Masatoshi Miyahara, Katutoshi Makino, Takakazu Kouji, Yoshiyuki Nemura*, Kann Takeda* Departmrnt of Intarnal Medicine, Matsusaka Central Hospital, Matusaka 515-0818, Japan. *Department of Radiology, Mie University, Tsu 514-8507, Japan. This study was undertaken to estimate the relationship between myocardial adrenergic nerve activity using iodine-123 metaiodobenzylguanidine (MIBG) and systemic neurohormonal activation in patients with asymptomatic chronic heart failure. Planner MIBG images were obtained from 21 patients with asymptomatic congestive heart failure, To evaluate the myocardial accumulation of MIBG, heart / mediastinal (H / M) activity ratio, myocardial MIBG washout rate (%Wo) defined as percent change in activity from the immediate (15 min) and delayed (4hr) images, and fractional myocardial uptake (MU) caluculated with Ishi-Maclntyre method were measured. To evaluate systemic neurohormonal activation in thease patients, plasma norepineprine (NE), atrial natriuretic peptide (ANP) and brain natriuretic peptide (SNP) were measured. Two-dementional echocardiography were performed and left ventricular ejection fraction (EF) was measured. The H / M ratio did not correlate with either any neurohormonal values or EF. I The %We correlated positively with ANP (r=0 61 p<0.01) and BNP (r=0.62 p<0.01). The MU correlated inversely with BNP (r=-o.41 p<0.05). The reduction of myocardial adrenergic nerve activity in patients with asymptomatic congestive heart failure was related to the abnormality of systemic neurohormonal activation. 800

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103 Cardiovascular and Renal Effects of Adrenomedullin in Rats With Heart F a i l u r e Noritoshi Nagaya, Toshio Nishikimi, Takeshi Horio, Fumiki Yoshihara, Hisayuki Matsuo, Kenji Kangawa National Cardiovascular Center, Osaka 565-8565, Japan Plasma adrenomedullin (AM), a novel vasorelaxant and natriuretic peptide, has been shown to be increased in heart failure (HF). This study sought to investigate the effects of AM on systemic and pulmonary circulation and renal function in HF rats produced by coronary artery ligation. Rat-AM at rates of 0.01 (low) and 0.05 (high) ,ug. kg body wt -1- min -1 was intravenously administered in HF and sham rats (Con). During the infusion of low-dose AM, systemic, pulmonary, and renal hemodynamics were unchanged, whereas urine flow (+21% in HF; +29% in Con) and urinary sodium excretion (+109% in HF; +123% in Con) were significantly increased. In contrast, the infusion of high-dose AM slightly decreased mean arterial pressure (-3% in HF; -5% in Con) and significantly increased cardiac output (+20% in HF; +12% in Con) in both groups. Interestingly, the infusion of high-dose AM resulted in significant decreases in right ventricular systolic pressure (-I 1%) and right atrial pressure (-28%) only in HF group and not in Con group. Furthermore, the infusion of high-dose AM significantly increased glomemlar filtration rate (+10% in HF; +16% in Con) and effective renal plasma flow (+25% in HF; +46% in Con) as well as urine flow (+26% in HF; +36% in Con) and urinary sodium excretion (+133% in HF; +160% in Con). AM infusion may exert diuresis and natriuresis at a low dose, and further may improve systemic, pulmonary, and renal hemodynamics at a high dose in rats with HF. Intravenous infusion of AM may be a new therapeutic approach to the treatment of HF.

ADRENOMEDULLIN IN HEART FAILURE Toshio Nishikimi, Takeshi Horio, Fumiki Yoshihara, Noritoshi Nagaya, Hisayuki Matsuo, Kenji Kangawa National Cardiovascular Center, Osaka 565 8565, Japan [Object] We previously reported that plasma adrenomedullin (AM) levels are increased in proportion to the severity of the disease. In the present study, we investigated (1) whether cardiac myocytes (MC) or nonmyocytes (NMC) produce AM, (2) the effect of AM on the cAMP and cGMP levels in MC and NMC, (3) the effects of various peptides or cytokines on the AM production in MC and NMC, (4) the AM production in the heart in heart failure rats. [Methods and Results] (1) Neonatal cardiac MC and NMC were p r e p a r e d from the v e n t r i c l e of Wistar rats by the discontinuous Percoll gradient method. Not only MC, but also NMC secreted almost equal amount of AM into the media in a time- dependent manner. (2) Both AM and CGRP increased the cAMP levels, not the cGMP levels, both in the MC and NMC in a concentration- dependent manner. In MC, CGRP (8- 37), an antagonist for CGRP receptor, almost completely inhibited the AM and CGRP- induced cAMP formation. In the NMC, CGRP(8 37) completely inhibited the cAMP levels induced by AM and CGRP. Antagonistic effect of CGRP- (8- 37) was greater in NMC than in MC. (3) Interleukin- 1 /3 and TNF- a significantly increased AM secretion and production both in MC and NMC, however, its effects were greater in NMC than in MC. Endothelin, angietensin II, phenylephrine did not increase AM secretion both in MC or NMC. (4) We measured tissue AM peptide and mRNA levels in heart failure rats. Tissue AM levels and AM mRNA levels were increased in the heart of heart failure rats induced by aortocaval fistula. [Conclusion] These results suggest that production of AM in the failing heart is increased. [nterleukin- 1/3 and TNF- a may be one of the important stimulators to AM production in the failing heart. AM secreted in cardiac MC and NMC may be involved in the pathophysiology of failing heart by increasing cAMP levels as an autocrine and/or paracrine fashion.

104 PLASMA ATRIAL NATRIURETIC PEPTIDE, BRAIN NATRIURETIC PEPTIDE, AND ADRENOMEDULLIN IN PACEMAKER IMPLANTED PATIENTS Shigeko Watanabe, Koichi Kono, Teruo Higashi, Kazuyoshi Hara, N a o h i k o K o b a y a s h i , S h i g e o H o r i n a k a , Hiroaki Matsuoka Department of Medicine, Division of Hypertension and Cardiorenal Disease, Dokkyo University School of Medicine, Tochigi 321-02, Japan The aim of this study was to evaluate the effect of changes in the pacing mode on plasma Atrial Natriuretic Peptide (ANP), plasma Brain Natriuretic Peptide (BNP), plasma A d r e n o m e d u l l i n (AM) and cardiac function. The study included 9 patients with permanent physiological pacemakers (7 of DDD and 2 of VDD). At the baseline, ANP, BNP, AM and M-mode echocardiogram were evaluated. Then the pacing mode was turned to nonphysiological pacing (VVI) for 1 month and the same parameters were evaluated. After 1 month of VVI pacing, singnificant increase of ANP (from 72 -+21 pg/ml to 109_+30 pg/ml, p<0.05) and BNP (from 80:525 pg/ml to 225 _+91pg/ml, p<0.05) above the baseline were observed. However, VVI pacing did not cause a significant change of AM (from 243_+17 pg/ml to 261 +_15pg/ml). The left ventricular end-diastolic dimension increased (from 48_+ 2.1 mm to 5 3 + .9mm, p<0.05), and the left ventricular ejection fraction decreased (from 67+_ 1.5% to 55_+2.4%, p<0.05) significantly after VVI pacing. In conclusion, the use of ANP and BNP measurements are more useful than AM to select the best pacing mode in pacemaker implanted patients.