Hiroyuki Tachibana

Effects of size and shape (aspect ratio) on the hemodynamics of saccular aneurysms: A possible index for surgical treatment of intracranial aneurysms

OBJECTIVE The present study was undertaken to explore the relationship between the characteristic geometry of aneurysms prone to rupture and the blood flow patterns therein, using microsurgically produced aneurysms that simulated human middle cerebral artery aneurysms in scale and shape. METHODS We measured in vivo velocity profiles using our 20-MHz, 80-channel, Doppler ultrasound velocimeter. We produced small (< or =5 mm, 5 cases) and large (6-13 mm, 12 cases) aneurysms with round, dumbbell, or multilobular shapes. RESULTS The fundamental patterns of intra-aneurysmal flow were composed of inflow, circulating flow, and outflow. The inflow, which entered the aneurysm only during the systolic phase, was strongly influenced by the position and size of the neck and the flow ratio into the distal branches. The outflow was usually nonpulsatile and of low velocity. The circulating flow depended on the aspect ratio (depth/neck width). A single recirculation zone was observed in aneurysms with aspect ratios of less than 1.6. This circulation did not seem to extend to areas with aspect ratios greater than this value; in aneurysms with aspect ratios of more than 1.6, a much slower circulation was observed near the dome. Furthermore, in the dome of dumbbell-shaped aneurysms and daughter aneurysms, no flow was detected. Intra-aneurysmal flow was determined by the aspect ratio, rather than the aneurysm size. CONCLUSION The localized, extremely low-flow condition that was observed in the dome of aneurysms with aspect ratios of more than 1.6 is a common flow characteristic in the geometry of ruptured aneurysms, so great care should be taken for patients with unruptured intracranial aneurysms with aspect ratios of more than 1.6.

In vivo observations of the intramural arterioles and venules in beating canine hearts

1 To evaluate the effects of cardiac contraction on intramyocardial (midwall) microvessels, we measured the phasic diameter change of left ventricular intramural arterioles and venules using a novel needle‐probe videomicroscope with a CCD camera and compared it with the diameter change in subepicardial and subendocardial vessels. 2 The phasic diameter of the intramural arterioles decreased from 130 ± 79 μm in end‐diastole to 118 ± 72 μm (mean ± s.d.) in end‐systole by cardiac contraction (10 ± 6 %, P < 0.001, n= 21). 3 The phasic diameter in the intramural venules was almost unchanged from end‐diastole to end‐systole (85 ± 44 vs. 86 ± 42 μm, respectively, 2 ± 6 %, n. s., n= 14). 4 Compared with intramural vessels, the diameters of subendocardial arterioles and venules decreased by a similar extent (arterioles: 10 ± 8 %, P < 0.001; venules: 12 ± 10 %, P < 0.001) from end‐diastole to end‐systole, respectively, whereas the diameter of the subepicardial arterioles changed little during the cardiac cycle, and subepicardial venule diameter increased by 9 ± 8 % (P < 0.01) from end‐diastole to end‐systole. These findings are consistent with our previous report. 5 We suggest that the almost uniform distribution of the cardiac contractility effect and arteriolar transmural pressure between the subendocardium and the midmyocardium, which together constitute the systolic vascular compressive force, accounts for the similarity in the arteriolar diameter changes in both myocardial layers. The smaller intravascular pressure drop from deep to superficial myocardium relative to the larger intramyocardial pressure drop explains the difference in the phasic venular diameter changes across the myocardium.

Direct In Vivo Observation of Subendocardial Arteriolar Response During Reactive Hyperemia

To study the vasodilatory capacity of subendocardial (ENDO) arterioles, we evaluated the reactive hyperemic responses of ENDO as well as subepicardial (EPI) arterioles in 40 dogs by our needle-probe intravital microscope. We also examined the individual and combined effects of an ATP-sensitive K+ channel blocker (glibenclamide, 200 micrograms/kg), an inhibitor of nitric oxide synthase (NG-monomethyl-L-arginine [L-NMMA], 2 mumol/min, 20 minutes), and an adenosine-receptor antagonist (8-phenyltheophylline [8PT], 0.75 mumol/min, 15 minutes). The percent increase in end-diastolic diameter of ENDO arterioles was larger (P < .01) than that of EPI arterioles during reactive hyperemia, especially for the arterioles larger than 120 microns (P < .01). The diastolic-to-systolic vascular pulsation amplitude at the peak flow was greater in ENDO than EPI arterioles (25% versus 6%, P < .05). Compared with control conditions, the presence of both glibenclamide and L-NMMA suppressed the vasodilation responses of ENDO arterioles (P < .01 for both) and EPI arterioles (P < .05 for both). The effect of L-NMMA was greater in ENDO arterioles (P < .01), but that of glibenclamide was not different between ENDO and EPI arterioles. 8PT influenced the hyperemic response, although statistical significance was found only in the flow response. The effect of combined infusion of L-NMMA and glibenclamide with or without 8PT was greater than that of individual infusions in both ENDO and EPI arterioles. Conclusions are as follows: (1) The vasodilatory response of ENDO arterioles was even larger than that of EPI arterioles. Thus, the smaller flow reserve of ENDO arterioles may be caused by other factors, including the greater effects of myocardial compression and nitric oxide on the ENDO arterioles. (2) The vascular responses of ENDO and EPI arterioles were modulated by both endothelium-independent and -dependent vasodilative factors, and the effect of each factor including adenosine was associated with the effects of others.

Effects of intraaortic balloon pumping on septal arterial blood flow velocity waveform during severe left main coronary artery stenosis

OBJECTIVES We sought to evaluate the effect of intraaortic balloon pumping on the phasic blood velocity waveform into myocardium with severe coronary artery stenosis. BACKGROUND In the presence of severe coronary artery stenosis, it is not clear whether intraaortic balloon pumping augments intramyocardial inflow during diastole or changes systolic retrograde blood flow from the myocardium to the extramural coronary arteries. METHODS Using anesthetized open chest dogs (n=7), we introduced severe stenosis in the left main coronary artery to reduce the poststenotic pressure to approximately 60 mm Hg (>90% diameter stenosis). Septal arterial blood flow velocities were measured with a 20-MHz, 80-channel ultrasound pulsed Doppler velocimeter. Left anterior descending arterial flow, aortic pressure and poststenotic distal coronary pressure were measured simultaneously. The diastolic anterograde flow integral and systolic retrograde flow integral were compared in the presence and absence of intraaortic balloon pumping. RESULTS Although intraaortic balloon pumping augmented diastolic aortic pressure, this pressure increase was not effectively transmitted through stenosis. Septal arterial diastolic flow velocity was not augmented, and left anterior descending arterial flow was unchanged during intraaortic balloon pumping. CONCLUSIONS In the presence of severe coronary artery stenosis, intraaortic balloon pumping failed to increase diastolic inflow in the myocardium and did not enhance systolic retrograde flow from the myocardium to the extramural coronary artery. Thus, the major effect of intraaortic balloon pumping on the ischemic heart with severe coronary artery stenosis may be achieved by reducing oxygen demand by systolic unloading.

Transmural microcirculatory blood flow distribution in right and left ventricular free walls of rabbits.

Within-layer regional myocardial flows in the left and right ventricles (LV, RV) and in LV with increased myocardial workload (β1-adrenoceptor stimulation) were studied transmurally in anesthetized rabbits. Myocardial flow distribution was visualized with resolutions between 0.1 × 0.1- and 1 × 1-mm2 pixels, using digital radiography combined with the3H-labeled desmethylimipramine deposition technique. The spatial pattern of flow distribution was quantitated by the coefficient of variation of regional flows (CV, related to global flow heterogeneity) and the correlation between adjacent regional flows (CA, inversely related to local flow randomness). CV was lower in LV than in RV [ P < 0.05, nonparametric 2-way analysis of variance (NANOVA)]. When resolution was lowered from 0.1 × 0.1- to 1 × 1-mm2 pixels, CV decreased by 70% in both LV and RV. CA was higher in LV than in RV ( P < 0.05, NANOVA); the interventricular difference in CA was large over the resolutions between 0.4 × 0.4- and 1 × 1-mm2 pixels. In LV, both CV and CA increased with depth of myocardium ( P < 0.05, NANOVA); in subendocardium CV was high comparable with CV in RV ( P = 0.47, NANOVA). The enhancement of myocardial workload decreased CV and tended to decrease CA in LV subendocardium ( P < 0.05, P = 0.06, respectively; NANOVA). We conclude that 1) microregional flow distribution is less heterogeneous and less random in LV than in RV; 2) transmurally, in LV subendocardium global flow heterogeneity was the highest whereas local flow randomness was the lowest, so that clusters of low- or high-flow regions exist in this LV layer; and 3) global flow heterogeneity decreased and local flow randomness tended to increase (flow homogenizing occurred) in LV subendocardium with increasing myocardial workload. Thus the distributed pattern of myocardial microregional flows may be adaptable to local myocardial metabolic change.

Diameters of subendocardial arterioles and venules during prolonged diastole in canine left ventricles.

Using a needle-probe videomicroscope with a charge-coupled device (CCD) camera, we measured the diameter of subendocardial arterioles and venules during prolonged diastole beyond the time point at which coronary blood flow reached zero. In seven open-chest heart-blocked dogs, a sheathed needle probe with a doughnut-shaped balloon was introduced from the left atrial appendage and advanced into the left ventricle through the mitral valve. The tip of the probe was placed gently on the endocardial surface. Diameters of arterioles (n = 16) and venules (n = 16) at the beginning of long diastole ranged from 40 to 126 microns and from 32 to 192 microns, respectively. After cardiac arrest, the arteriolar diameter gradually declined with aortic pressure. Arteriolar diameters at zero flow decreased by 28 +/- 9% (mean +/- SD) compared with the initial diameter (P < .01). However, none of the subendocardial arterioles collapsed at zero flow or at 12 seconds after the beginning of prolonged diastole (8 to 9 seconds after zero flow) in an additional experiment (n = 5). In contrast to arteriolar diameter, venular diameter increased during prolonged diastole. Venular diameter at zero flow increased by 14 +/- 12% compared with the initial diameter (P < .01). We conclude that during prolonged diastole, when coronary arterial inflow ceases, subendocardial arteriolar diameter decreases without any visible collapse, whereas venular diameter increases.

Role of NO and K ATP + channels in adenosine-induced vasodilation on in vivo canine subendocardial arterioles

Adenosine (Ado) plays an important role in regulation of coronary vascular tone with nitric oxide (NO) and ATP-sensitive K+ [Formula: see text]) channels. In vitro, it was reported that subendocardial (Endo) arterioles are more sensitive to Ado than subepicardial (Epi) arterioles. The purpose of this study was to observe enhanced vasodilation of Endo arterioles directly and to evaluate possible roles of [Formula: see text] channels and NO in the different responses of Endo and Epi arterioles to Ado-induced vasodilation. We evaluated dilation of Endo and Epi arterioles (<120 μm) of beating canine hearts ( n = 19) by Ado (20 and 50 μg ⋅ kg-1 ⋅ min-1ic) before and after [Formula: see text] channel blockade (glibenclamide; 200 μg/kg ic), inhibition of NO synthase [ N G-nitro-l-arginine methyl ester (l-NAME); 30 μg ⋅ kg-1 ⋅ min-1, 20 min ic], or glibenclamide +l-NAME using a novel needle-probe CCD intravital microscope. Ado induced dose-dependent vasodilation in both Epi and Endo arterioles, but vasodilation was greater in Endo arterioles, i.e., increase at 120 s (maximum dilation) after Ado (50 μg ⋅ kg-1 ⋅ min-1) was 17% in Endo and 13% in Epi arterioles ( P < 0.01). Endo arteriole dilation was attenuated by blockade of [Formula: see text]channels from 18% (Ado) to 9% (Ado+glibenclamide) increase ( P < 0.001) and by inhibition of NO synthase from 17% (Ado) to 9% (Ado+l-NAME) ( P < 0.005). Epi arteriole vasodilation was attenuated by blockade of[Formula: see text] channels from 15 to 9% ( P < 0.005) and inhibition of NO from 16 to 10% ( P < 0.005). Suppression of vascular response was additive (Endo, 14 to -1%; Epi, 12 to 3%) with glibenclamide +l-NAME. We conclude that 1) the degree of Ado-induced vasodilation was greater in Endo than in Epi arterioles, with higher sensitivity of smaller arterioles in both layers and 2) transmural difference of arteriolar sensitivity to adenosine was abolished or reversed by[Formula: see text] channel blockade and/or by NO synthase inhibition, indicating crucial involvement of[Formula: see text] and NO in transmural sensitivity difference.

Endothelium-derived nitric oxide enhances the effect of intraaortic balloon pumping on diastolic coronary flow

BACKGROUND High shear rate with pulsation is one of the major stimuli for the release of endothelium-derived nitric oxide leading to coronary arteriolar dilation. Intraaortic balloon pumping mechanically enhances shear rate and diastolic-to-systolic flow oscillation. We aimed to evaluate whether or not coronary blood flow augmentation during intraaortic balloon pumping is mediated by coronary arteriolar dilation through endothelium-derived nitric oxide release. METHODS Using a charge-coupled device intravital videomicroscope, we observed epicardial coronary arterioles (40 to 220 microm in diameter) in anesthetized open-chest dogs (n = 10) during 2:1 mode of intraaortic balloon pumping. Endothelium-derived nitric oxide-mediated vasodilatory effects of intraaortic balloon pumping were evaluated by comparing end-diastolic arteriolar diameters between the coupled beats of on and off intraaortic balloon pumping before and after intracoronary endothelium-derived nitric oxide synthesis inhibition with Nomega-nitro-L-arginine (L-NNA, 2 micromol/min) administration. RESULTS Intraaortic balloon pumping increased coronary arteriolar diameters and coronary blood flow by 11.4%+/-1.8% (p < 0.0001) and 33.4%+/-4.1% (p < 0.001), respectively. Vasodilation was greater in small arterioles (<110 microm; 15.4%+/-2.2%) than in large arterioles (> or =110 microm; 4.2%+/-1.2%, p < 0.0001). L-NNA attenuated the intraaortic balloon pumping-induced vasodilation and augmentation of coronary blood flow to 4.6%+/-1.0% (p < 0.001) and to 20.8%+/-2.1%, (p < 0.05), respectively. Attenuation of vasodilatory effect by L-NNA was observed mainly in small arterioles (from 15.4%+/-2.2% to 5.9%+/-1.2%). CONCLUSIONS Intraaortic balloon pumping augmented coronary blood flow by dilating coronary arterioles in diastole, more significantly in small arterioles than in large arterioles. Endothelium-derived nitric oxide inhibition markedly attenuated these effects. We conclude that, in a canine model, endothelium-derived nitric oxide contributes to mechanical enhancement of the coronary blood flow with diastolic arteriolar vasodilation during intraaortic balloon pumping.

The relationship between cardiac contraction and intramyocardial hemodynamics

Since coronary venous flow is squeezed out from the myocardial vascular bed by the extravascular compressive force of heart muscle, the coronary venous system provides a suitable model to investigate the relationship between cardiac contraction and intramyocardial hemodynamics. To investigate coronary venous flow velocity in more detail, we previously developed a laser Doppler velocimeter (LDV) with an optical fiber. Furthermore, we have recently developed a needle probe charge-coupled device (CCD) videomicroscope to visualize intramyocardial microvessels. In this article, we report I) blood flow velocity waveforms in the epicardial small veins of the left ventricle and 2) subendocardial venular diameter changes during a cardiac cycle.

Direct measurement of nipradilol-derived nitric oxide in the vascular wall of canine femoral arteries

Nipradilol (NP: 3,4-dihydro-8-[2-hydroxy-3-isopropylamino]propoxy-3-nitroxy-2H-1-benzopyran) shows not only β-adrenoreceptor-blocking effects but also nitroglycerin-like vasodilatory action. We aimed to directly measure NP-derived nitric oxide (NO) in the vascular wall. An NO-sensitive microelectrode was inserted into the vascular media (the vasodilatory action site of NO) of isolated perfused canine femoral arteries. Each vessel was perfused with 15 µM NP in the presence or absence of 1 mM N-ethylmaleimide (NEM; a thiol alkylator). Intravascular-wall NO concentration increased 181 ± 34 nM during NP perfusion (P < 0.001 vs basal, n = 10) with an average base-to-peak reaction time of 1.5 ± 0.1 min (P < 0.0001, n = 8). Concomitant perfusion of NEM with NP attenuated the intravascular-wall NO production significantly (P < 0.0001 vs NP only). It is concluded that NP is metabolized to NO in the vascular wall of an isolated canine femoral artery in large part through a metabolic process involving thiols with a base-to-peak reaction time of about 1.5 min.