Yuichi Tsunoda

Ongoing myocardial damage relates to cardiac sympathetic nervous disintegrity in patients with heart failure

Iodine-123-metaiodobenzylguanidine (123I-MIBG) has been used to assess the integrity and function of the cardiac sympathetic nervous system in patients with heart failure. Heart-type fatty acid binding protein (H-FABP) is released into the circulation when the myocardium is injured, and H-FABP has been recently used as a novel marker for the diagnosis of ongoing myocardial damage.ObjectiveThe aim of the present study was to compare cardiac sympathetic nervous activity assessed by123I-MIBG imaging with serum levels of H-FABP in patients with heart failure.MethodsFifty patients with chronic heart failure were studied.123I-MIBG imaging was carried out at 30 min (early) and 240 min (delayed) after the tracer injection. We measured serum levels of H-FABP using a sandwich enzyme linked immunosorbent assay.ResultsHeart to mediastinum (H/M) ratios of123I-MIBG decreased and washout rate increased with higher New York Heart Association (NYHA) functional class. H-FABP, norepinephrine and brain natriuretic peptide (BNP) levels increased as the severity of NYHA class advanced. Delayed H/M ratio was significantly correlated with H-FABP (r = -0.296, p = 0.029) and BNP (r = -0.335, p = 0.0213). Myocardial washout rate of123I-MIBG was also correlated with H-FABP (r = 0.469, p < 0.001), norepinephrine (r = 0.433, p = 0.005), and BNP (r = 0.465, p = 0.001).ConclusionsThese data suggest that cardiac sympathetic nervous activation was associated with ongoing cardiomyocyte damage characterized by an elevated serum level of H-FABP in patients with heart failure.123I-MIBG imaging is an appropriate approach to evaluate non-invasively not only cardiac sympathetic nervous activity, but also latent ongoing myocardial damage in the failing heart.

Long-term treatment with angiotensin II type 1 receptor antagonist, CV-11974, restores β-catenin mRNA expression in volume-overloaded rabbit hearts

Abstract. This study aimed to search genes altered in expression after long-term treatment with the angiotensin II type 1 receptor (AT1) antagonist, CV-11974, in volume-overloaded hearts. Arteriovenous shunt was made between the common carotid artery and jugular vein in Japanese White rabbits. Shunt-operated rabbits were randomly treated with CV-11974 or vehicle for 6 weeks, starting 6 weeks after surgery. As controls, sham-operated rabbits were given vehicle. Total RNA was prepared from each left ventricular myocardium. Using differential display, we screened one cDNA encoding human β-catenin, in which the expression was upregulated after CV-11974 administration in shunt rabbit hearts. β-Catenin is a molecule that exists in the intercalated disks and also works in cytoplasm as a major component of Wnt signaling. We then examined mRNA expressions of β-catenin and connexin43 by semiquantitative reverse transcriptase–polymerase chain reaction (RT-PCR). The mRNA expressions of β-catenin and connexin43 were markedly depressed in shunt-operated animals given vehicle compared with sham-operated animals (P < 0.01). These results suggest that downregulation of β-catenin and connexin43 expression might be involved in the process of ventricular remodeling by volume overload. The RT-PCR also demonstrated that β-catenin mRNA expression was significantly higher in shunt rabbits treated with CV-11974 than in those given vehicle (P < 0.05). These data suggest that volume overload may downregulate β-catenin expression by an AT1 receptor-mediated pathway.

Effects of long-term treatment with nonselective endothelin receptor antagonist, TAK-044, on remodeling of cardiovascular system with sustained volume overload.

To assess the role of endothelin-1 (ET-1) on cardiovascular remodeling, nonselective endothelin-receptor antagonist TAK-044 was administered for the long term to rabbits with or without arteriovenous (A-V) shunt formation. Six weeks after sham operation (n = 12) or carotid-jugular shunt formation (n = 21), TAK-044 (30 mg/day) or saline was infused subcutaneously using osmotic mini pumps for another 6 weeks. Twelve weeks after operation, left ventricular (LV) diameter was enlarged with the presence of an A-V shunt; however, the levels of LV diameter and arterial pressure or the postmortem weight of LVs of shunt rabbits were similar between saline and TAK-044 groups. A linear relation of the luminal diameter and the medial cross-sectional area of the left and right carotid arteries was similar between shunt + saline and shunt + TAK-044 groups. In saline groups, myocardial ET-1 levels were higher in shunt than in sham rabbits (217+/-22 vs. 136+/-19 pg/g tissue; p < 0.01 between rabbit groups) without changes in plasma ET-1 concentrations during saline infusion for 6 weeks. Differences in plasma ET-1 levels before and 6 weeks after the administration of TAK-044 were 0.32+/-0.78 and 0.16+/-0.28 pg/ml (NS between periods) in shunt and sham groups, respectively. In TAK-044 groups, myocardial ET-I levels 12 weeks after operation were similarly lower in both sham (105+/-7.4 pg/g tissue) and shunt rabbits (126+/-9.2 pg/g tissue) than in those with saline administration; however, the plasma ET-1 concentrations were increased significantly 6 weeks after TAK-044 administration by 5.0+/-0.6-fold and 3.5 +/-0.3-fold (p < 0.01) of the levels 6 weeks after operation in shunt and sham groups (NS between groups), respectively. Accordingly, myocardial but not plasma ET-1 levels were increased by a long-term burden of volume overload and were attenuated by a long-term administration of TAK-044 without altering drastically the hemodynamics or vascular remodeling. These results suggest that endogenous ET-1 does not play a major role in the compensatory stage of cardiovascular remodeling in the present volume-overload model.

Successful Revascularization to Right Coronary Artery by Percutaneous Coronary Intervention after Endovascular Therapy for Leriche Syndrome

A 69-year-old man with effort angina was admitted to our institution. Echocardiography showed poor left ventricular systolic function with akinesis of the anterior wall and severe hypokinesis of the inferior wall. We performed coronary angiography, which revealed two diseased vessels including chronic total occlusion in the left anterior descending artery and severe stenosis in the right coronary artery (RCA). In addition, aortography revealed aortoiliac occlusive disease known as Leriche syndrome. As the patients symptom was stable, we first planned to perform endovascular therapy (EVT) for Leriche syndrome to make a route for intra-aortic balloon pumping. We prepared a bi-directional approach from bi-femoral arteries and a left brachial artery. The guidewire was passed through the occlusive area using the retrograde approach. The self-expanding stents were deployed by a kissing technique. At one week after EVT, a 6Fr sheath was inserted from the right radial artery and an intra-aortic balloon pump was successfully inserted through the right femoral artery for percutaneous coronary intervention (PCI) to the RCA. Two drug-eluting stents were successfully deployed to RCA after using an atherectomy device (rotablator). We reported the case as a successfully performed PCI to the RCA after EVT for Leriche syndrome.