Takafumi Sekka

Synchrotron microangiography reveals configurational changes and to-and-fro flow in intramyocardial vessels

In 8 dogs, in situ microangiography using synchrotron radiation visualized penetrating transmural arteries (PTAs) with a diameter of >60 μm and allowed quantitation of vessel diameters of >140 μm. Myocardial contraction reduced the vascular short-axial diameters to 87 ± 17% ( n = 62, P < 0.001, paired t-test) of the end-diastolic values and increased the longitudinal dimension to 129 ± 5% ( n = 45, P < 0.001). The diameter reduction in the subendocardial PTA segments was significantly more marked than that in the subepicardial PTA segments (60 ± 12 vs. 88 ± 12%, n=13, P < 0.001, paired t-test). Intracoronary administration of dobutamine (0.1 μg ⋅ kg-1 ⋅ min-1) increased, and in contrast, partial clamping of the coronary artery (ischemia) decreased, the configurational changes. To-and-fro blood flow was clearly observed in PTAs with visual identification of capacitive backflow, resistive forward flow during ischemia on coronary arteriography, and even under baseline conditions in coronary venography. Thus this method advances our understanding of mechanical influences on the coronary circulation.

Coronary vasoconstrictive effects of neuropeptide Y and their modulation by the ATP-sensitive potassium channel in anesthetized dogs.

OBJECTIVES This study examined the coronary vasoconstrictive action of endogenous neuropeptide Y (NPY) during sympathetic nerve stimulation and its modulation by the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel in vivo. BACKGROUND Exogenous NPY was characterized by its potent vasoconstrictive effect. However, endogenous NPY has failed to show any vasoconstrictive activity in vivo. METHODS We studied 70 anesthetized dogs with vagotomy under beta-adrenergic blockade. Ansae subclaviae stimulation and intracoronary administration of the neurotransmitters (NPY and norepinephrine) were done with or without alpha-adrenergic blockade, NPY antagonist BIBP3226 or KATP channel acting agents. We measured coronary vascular resistance (CVR) and the neurotransmitter levels in systemic arteries and the great cardiac vein, and the amount of overflow (venoarterial difference times myocardial blood flow). RESULTS During nerve stimulation, NPY levels correlated significantly with CVR at the highest r value (r = 0.850, p < 0.0001) obtained for the venous level under alpha-blockade, but norepinephrine showed no correlation. Treatment with BIBP3226 abolished the correlation between NPY level and CVR under alpha-blockade. Without alpha-blockade, norepinephrine levels correlated significantly with CVR; however, NPY showed no correlation. The amount of NPY overflow during the stimulation was nearly 1,000-fold lower than norepinephrine overflow. Exogenous NPY had a 100-fold more potent coronary vasoconstrictive action than that of norepinephrine. The KATP channel antagonist glibenclamide enhanced vasoconstriction of NPY, and the agonist pinacidil suppressed it with a predominant effect in the subepicardial region. CONCLUSIONS During sympathetic nerve stimulation, the vasoconstrictive actions of NPY are masked by norepinephrine under intact alpha-adrenoceptor conditions, manifest during alpha-blockade and modulated by KATP channel activity.

Branching patterns of intramural coronary vessels determined by microangiography using synchrotron radiation

The intramural coronary artery (IMCA) with a diameter of 50-500 μm is critical for blood supply to the inner layers of heart muscle. We introduced digital measurement to microangiography using monochromatic synchrotron radiation and quantified branching patterns of the IMCA, the epicardial coronary artery (EPCA), and the distal ileal artery (DIA). The pre- and postbranching diameters were measured (95-1,275 μm) in seven dogs. A typical arterial segment divided into two nearly equivalent branches, and a regression line of daughter-to-mother diameter plots was almost identical among the EPCA ( y = 0.838 x - 16.7 in μm), IMCA ( y = 0.737 x- 2.18), and DIA ( y = 0.755 x + 8.63). However, a considerable difference was present at a segment where a proximal IMCA branched off from an EPCA ( y = 0.182 x + 90.2). Moreover, a proximal IMCA diameter had no relationship to the branching order from an EPCA. The precision of this method was confirmed by the good correlation of diameter measurements between two independent observers ( r = 0.999, y = 1.02 x - 1.07). In conclusion, using digital microangiography we demonstrated that the self-similar branching pattern of coronary arteries was discrete at the connection between the IMCA and EPCA.

Visualization, quantification and therapeutic evaluation of angiogenic vessels in cancer by synchrotron microangiography

The usefulness of a synchrotron microangiography system for depicting, quantitating and therapeutically evaluating angiogenic vessels in cancer is illustrated. In 20 mice transplanted with murine colon cancer, sequential changes in the angiogenic vessels were determined by using synchrotron microangiography, using changes in tumor volume for reference. This system allowed the depiction and quantification of angiogenic vessels in the period from one to four weeks after transplantation. The effects of antiangiogenic therapy were evaluated by using a neutralizing antibody against vascular endothelial growth factor. The neutralizing antibody partially suppressed angiogenesis and tumor growth. Synchrotron microangiography is shown to be useful for the depiction, quantification and evaluation of angiogenic vessels in cancer.

2 Long Term Survival Cases of Small Pancreatic Cancers Performed Middle Pancreatectomy

われわれは, 膵中央切除術を施行し5年生存が得られた小膵癌2例を経験した. 症例1: 72歳の女性で, 心窩部痛で来院し超音波検査で膵体部腫瘤が指摘された. 精査の結果, 小膵癌と診断, 膵中央切除術を施行. 病理診断は中分化型管状腺癌, stage Iであった. 術後5年7か月無再発生存中である. 症例2: 68歳の男性で, 無症状にて検診超音波検査で膵管拡張と膵腫瘍が指摘され来院した. 精査の結果. 膵体部小膵癌と診断, 膵中央切除術を施行, 病理診断は中分化型管状腺癌, stage IV aであったが術後5年3か月無再発生存中である. 従来, 予後不良な膵管癌では, 脈管侵襲, 膵外進展および転移率の高さから, 小膵癌でも拡大手術を求める傾向があるが, 縮小手術でも長期生存する症例もある. TSP-1, EGFRなどの癌増殖転移関連因子の発現の有無を検討することは, 拡大手術を避け, 縮小手術の可能性を示唆するものと考えられた.