Sumihisa Abe

SYNERGISTIC EFFECT OF EPINEPHRINE AND SHEARING ON PLATELET ACTIVATION

Platelet activation mediated through the interaction between von Willebrand factor (vWF) and platelet glycoprotein (GP) Ib is known to occur under high shear rate. We have demonstrated that low concentration of epinephrine could reduce the threshold level of shear rate necessary to cause platelet activation with purified system devoid of the effect of plasma proteins other than vWF. Both the extent of platelet aggregation and [Ca2+]i were continuously measured with optically modified cone-and-plate viscometer. No aggregation with no change in [Ca2+]i occurred under shear rate less than 7,200 s-1 in the absence of exogeneously added epinephrine. Epinephrine enhanced platelet aggregation under moderate level of shear rate (7,200 s-1) in a dose dependent manner. Significant aggregation with rise in [Ca2+]i was demonstrated even under the low shear rate of 1,200 s-1 when exogeneously added low concentration of epinephrine (0.05 microM) which did not cause platelet activation by itself was present. Aggregation and rise in [Ca2+]i under low shear in the presence of epinephrine was abolished by monoclonal antibodies against A1 domain of vWF or GP Ib, like aggregation and the rise in [Ca2+]i occurred under high shear rate (10,800 s-1), alpha 2-receptor blockade yohimbine completely antagonized the enhancing effects of epinephrine. Our findings suggested that epinephrine and shearing synergistically activated platelets through vWF interaction to GP Ib, which might suggest the role of sympathetic stimulation for the onset of acute arterial thrombosis.

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.

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.

Examination of the Direct Effects of Nicorandil, Verapamil, Propranolol, and Nitroglycerin on the Hypoxic Canine Myocardium

Effects of intracoronary administration of verapamil (VER), nitroglycerin (TNG), propranolol (PRO), and nicorandil (NIC) on regional hypoxia were examined in 39 open-chest dogs. Distal left anterior descending coronary artery was perfused for 5 min with deoxygenated Krebs-Henseleit solution (KHS) in group 1 (n = 9), VER-containing (1.3 mg/dl) KHS in group 2 (n = 9), TNG-containing (0.5 mg/dl) KHS in group 3 (n = 7), PRO-containing (0.4 or 0.8 mg/dl) KHS in group 4 (n = 7), and NIC-containing (0.5 or 2.5 mg/dl) KHS in group 5 (n = 7). Transmural biopsy at 5 min revealed a less severe metabolic deterioration in the hypoxic myocardium in groups 2, 4, and 5, as evidenced by higher ATP content (2.99 ± 0.73, 2.81 ± 0.35, and 3.14 ± 1.20 μmol/g in groups 2,4, and 5, respectively) and lower lactate accumulation (5.16 ± 0.59, 5.62 ± 1.44, and 5.05 ± 1.12 μmol/g in groups 2, 4, and 5, respectively) compared with those in group 1 (2.09 ± 0.45 μmol/g in ATP and 8.77 ± 2.34 μmol/g in lactate). Metabolic preservation by VER, PRO, and NIC were not mediated by changes in hemodynamics and regional myocardial contraction. On the other hand, any significant protective effects were not noted in group 3, despite a significant reduction in rate-pressure products. Under an aerobic condition these agents affected regional myocardial contraction in a different manner from each other.

Synchrotron Radiation Micro-angiography using an Avalanche-type High-definition Video Camera

We improved the originally reported synchrotron radiation (SR) micro-angiographic system by applying avalanche-type high-definition (HD) video camera. The New Super Harp HDTV (NHK, Tokyo) with high contrast resolution and effective quantum ratio of 640 allowed precise assessment of configuration of small vessels (less than 100 mm after digital processing) in heart, brain, and the other organs. The originally used image-intensifier-video camera system could not delineate small vessels well. Conventional HD video system using CCD could not reveal small vessels of heart and brain in situ. This system would allow us clinical evaluation of small vessel -diseases in heart, brain, and the other organs and also visualization of newly developed small vessels due to angiogenesis in malignant tumor and circulatory disorders.