Beneficial effect of hydroxyfasudil, a specific Rho-kinase inhibitor, on ischemia/reperfusion injury in canine coronary microcirculation in vivo.

Objectives: We examined whether hydroxyfasudil, a specific Rho-kinase inhibitor, exerts cardioprotective effect on coronary ischemia/reperfusion (I/R) injury and, if so, whether nitric oxide (NO) is involved.

Background: Recent studies have demonstrated that Rho-kinase is substantially involved in the pathogenesis of cardiovascular diseases; however, it remains to be examined whether it is also involved in ischemia/reperfusion (I/R) injury.

Methods: Canine subepicardial small arteries (SA, >or=100 microm) and arterioles (A, <100 microm) were observed by a charge-coupled device intravital microscope during I/R.

Effect of nicorandil, a K+ATP -channel opener, on coronary capillary architecture and volume after early myocardial ischemia-reperfusion--a 3-dimensional confocal laser microscopic study--.

Background: Previous experimental and clinical studies have reported that nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts a beneficial effect on microvascular function and clinical outcome after myocardial ischemia. The present study assessed whether intravenous administration of nicorandil affects the 3-dimensional (3-D) architectural characteristics of capillaries and their volume after early myocardial reperfusion.

Methods And Results: Using the hearts of open-chest anesthetized rats, the left anterior descending artery was occluded for 7 min followed by reperfusion.

Exogenous NO suppresses flow-induced endothelium-derived NO production because of depletion of tetrahydrobiopterin.

Exogenous nitric oxide (NO) suppresses endothelium-derived NO production. We were interested in determining whether this is also the case in flow-induced endothelium-derived NO production. If so, then is the mechanism because of intracellular depletion of tetrahydrobiopterin [BH4; a cofactor of NO synthase (NOS)], which results in superoxide production by uncoupled NOS? Isolated canine femoral arteries were perfused with 100 microM S-nitroso-N-acetylpenicillamine (SNAP; an NO donor) and/or 64 microM BH4.

Direct observation of epicardial coronary capillary hemodynamics during reactive hyperemia and during adenosine administration by intravital video microscopy.

Using high-resolution intravital charge-coupled device video microscopy, we visualized the epicardial capillary network of the beating canine heart in vivo to elucidate its functional role under control conditions, during reactive hyperemia (RH), and during intracoronary adenosine administration. The pencil-lens video-microscope probe was placed over capillaries fed by the left anterior descending artery in atrioventricular-blocked hearts of open-chest, anesthetized dogs paced at 60-90 beats/min (n = 17). In individual capillaries under control conditions, red blood cell flow was predominant during systole or diastole, indicating that the watershed between diastolic arterial and systolic venous flows is located within the capillaries.

Three-dimensional microstructural abnormality of the coronary capillary network after myocardial reperfusion--comparison between 'reflow' and 'no-reflow'.

Background: The 3-dimensional (D) structural abnormalities of the coronary capillary network and capillary volume changes after myocardial reperfusion were investigated using confocal laser scanning microscopy.

Methods And Results: Using open-chest anesthetized rats' hearts, the left anterior descending artery (LAD) was occluded for 7 min followed by reperfusion. The hearts were divided into 2 groups: (1) reperfused area stained well by intravenous indocyanine green after reperfusion (Reflow), and (2) lack of staining in the reperfused area (No-reflow).

Global heterogeneity of glomerular volume distribution in early diabetic nephropathy.

Background: Morphologic characteristics in early stage of nephropathy of noninsulin-dependent diabetes mellitus (NIDDM) have not been determined despite the fact thatdiagnosis in this stage of the disease is important for the prognosis. We hypothesized that heterogeneity in glomerular volume-distribution may be a sensitive index of early stage of diabetic nephropathy in NIDDM.

Methods: In spontaneous diabetic rats [Otsuka Long-Evans Tokushima Fatty (OLETF) rat (N= 5)] of 27 to 28 weeks, an experimental model of early diabetic nephropathy in human NIDDDM and age-matched control rats [Long Evans Tokushima Lean (LETO) rat (N= 5)], we completely filled the kidney with contrast medium.

Role of hyaluronic acid glycosaminoglycans in shear-induced endothelium-derived nitric oxide release.

Endothelium-derived nitric oxide (NO) is synthesized in response to chemical and physical stimuli. Here, we investigated a possible role of the endothelial cell glycocalyx as a biomechanical sensor that triggers endothelial NO production by transmitting flow-related shear forces to the endothelial membrane. Isolated canine femoral arteries were perfused with a Krebs-Henseleit solution at a wide range of perfusion rates with and without pretreatment with hyaluronidase to degrade hyaluronic acid glycosaminoglycans within the glycocalyx layer.

Hydrogen peroxide, an endogenous endothelium-derived hyperpolarizing factor, plays an important role in coronary autoregulation in vivo.

Background: Recent studies in vitro have demonstrated that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) in animals and humans. The aim of this study was to evaluate our hypothesis that endothelium-derived H2O2 is an EDHF in vivo and plays an important role in coronary autoregulation.

Methods And Results: To test this hypothesis, we evaluated vasodilator responses of canine (n=41) subepicardial small coronary arteries (> or =100 microm) and arterioles (<100 microm) with an intravital microscope in response to acetylcholine and to a stepwise reduction in coronary perfusion pressure (from 100 to 30 mm Hg) before and after inhibition of NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA).

Dynamic changes in three-dimensional architecture and vascular volume of transmural coronary microvasculature between diastolic- and systolic-arrested rat hearts.

Background: The phase difference of coronary arterial and venous flows indicates the importance of intramyocardial capacitance vessels in storing diastolic flow and in discharging volume in systole. However, the anatomic and functional characteristics of the capacitance vessels are unclear. We aimed to clarify those characteristics with their transmural difference by 3D visualization of transmural microvessels under diastole and systole.