Local VEGF administration enhances healing of colonic anastomoses in a rabbit model.

BACKGROUND/AIMS: Many studies report the role of vascular endothelial growth factor (VEGF) in wound healing, but few describe local VEGF administration to the digestive tract. Leakage from colonic anastomoses, including those due to ischemia, represents a major complication causing increased mortality and morbidity. Angiogenesis is crucial to anastomotic healing and restoration of blood supply, and VEGF is a potent angiogenic factor showing improved healing in various models of reconstruction and anastomosis. Here, we examine the effects of local VEGF-A(165) administration on postoperative rabbit colon anastomosis. METHODS: Two colotomies per animal were made in the sinistral colon on opposite sides of the mesentery. Randomly assigned VEGF (10 microg/0.1 ml) or saline (0.1 ml) was injected into the muscularis propria on both sides of each colonic anastomosis before closing the access laparotomy using single-layer sutures. On postoperative days 3, 4 and 7, the bursting pressure of partially healed anastomoses was measured. On postoperative day 4, anastomotic tissues were examined for the following: hydroxyproline; histopathologically for inflammatory infiltrate and tissue organization and immunohistochemically for capillary proliferation and density; vessel density of midzone collaterals around anastomoses by microangiography. RESULTS: Compared to saline, VEGF administration significantly improved bursting pressure (p = 0.014, paired t test) and increased hydroxyproline (p = 0.027, paired t test) on postoperative day 4. Inflammatory cell infiltration and fibroblast proliferation were prominent, and submucosal capillary vascular counts were significantly higher for VEGF. CONCLUSIONS: Administration of VEGF to colonic anastomosis accelerates wound healing and strengthens the anastomosis by increased angiogenesis.

Transmyocardial revascularization aggravates myocardial ischemia around the channels in the immediate phase.

We examined whether transmyocardial revascularization (TMR) relieves myocardial ischemia by increasing regional perfusion via the transmural channels in acute canine experiments. Regional blood flow during transient coronary ligation (2 min) was compared before and 30 min after TMR, and at the third transient ischemia the mid-left ventricle (LV) was cut and immediately frozen along the short axis for the analysis of NADH fluorescence in the regions around the TMR channels. In low-resolution analysis (2-4 g tissue or 2-3 cm(2) area), regional perfusion was not significantly altered after TMR, and NADH fluorescence was observed throughout the ischemic region without significant spatial variation. High-resolution analysis (2.8 mg, 1 mm x 1 mm) revealed that the flow after TMR was lower, and NADH fluorescence was higher in the regions close to the channels (1-2 mm) than in the regions 3-4 mm away from them. Creating TMR channels did not improve the regional perfusion and rather aggravated the local ischemia in the vicinity of the channels in the immediate phase.

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.

Digitized cerebral synchrotron radiation angiography: quantitative evaluation of the canine circle of Willis and its large and small branches.

BACKGROUND AND PURPOSE: Conventional X-ray angiography lacks the sensitivity and spatial resolution needed to detect small amounts of iodinated contrast material and to quantitate diameters of the small vessels in the brain. The purpose of this study was to ascertain whether digitized synchrotron radiation microangiography, with the use of a high-definition TV camera system, can accurately show small cerebral vessels. METHODS: Six anesthetized dogs were exposed to monochromatic synchrotron radiation with an energy level of 33.3 keV optimized for iodine detection while iodinated contrast material was injected into the brachiocephalic and vertebral arteries. The images were detected with a high-definition TV camera system with a spatial resolution of 30 microm. In all, 26 cerebral angiograms of the circle of Willis with its branches were obtained, and the images were digitized at a workstation. RESULTS: The small branches of the circle of Willis were clearly visible on all images. Vasodilatation of the circle of Willis and its large and small branches induced by CO2 inhalation was quantitatively confirmed on the images: for example, the diameter of one small branch was increased from 0.24 +/- 0.04 mm to 0.38 +/- 0.12 mm. Temporal subtraction improved the image quality. CONCLUSION: The synchrotron radiation angiographic system is useful for visualizing large and small vessels deep in the brain as well as for quantitating their diameters.

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

The intramural coronary artery (IMCA) with a diameter of 50-500 micrometers 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 micrometers) 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 = 0.838x - 16.7 in micrometers), IMCA (y = 0.737x - 2.18), and DIA (y = 0.755x + 8.63). However, a considerable difference was present at a segment where a proximal IMCA branched off from an EPCA (y = 0.182x + 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 = 1.02x - 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.

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 micrometers and allowed quantitation of vessel diameters of >140 micrometers. 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 micrograms. 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.

Small-vessel radiography in situ with monochromatic synchrotron radiation.

PURPOSE: To evaluate the usefulness of a radiographic system with monochromatic synchrotron radiation to depict small vessels and peripheral secretory ducts. MATERIALS AND METHODS: Radiography of various organs was tested in 14 anesthetized dogs and pancreatography was performed in an excised human pancreas by using the following system: monochromatic synchrotron radiation with an energy level just above the k absorption edge of iodine as an x-ray source and a high-definition TV system with a high-light-sensitivity image pick-up tube camera coupled with a fluorescent screen as a detector. RESULTS: This system allowed depiction of small vessels (diameter < 50-100 microns) of the heart (penetrating transmural artery), brain (perforating arteries that arise directly in the circle of Willis), and intestinal organs (vasa recta and their submucosal communications) and of small branches (down to the fifth order) of the pancreatic duct. CONCLUSION: The synchrotron radiation system may be useful for evaluating microcirculatory disorders and early-stage malignant tumors in various human organs.

Acute emphysematous cholecystitis associated with pneumobilia: a case report.

This report describes a rare case of acute emphysematous cholecystitis with pneumobilia in the common bile duct. The patient was a 66-year-old woman with a part history of diabetes mellitus, and operations for gastric and breast carcinoma. The chief complaint was pain in the right hypochondrium with severe right hypochondrial tenderness and distention of the gallbladder detected on examination. Laboratory tests showed leukocytosis, marked elevation of CRP, jaundice, liver dysfunction, and hyperglycemia. Gas was detected in the gallbladder on plain abdominal X-rays and CT scans of the abdomen, and a small amount of gas was also observed in the common bile duct. On the day of admission, percutaneous transhepatic gallbladder drainage (PTGBD) was carried out under ultrasound guidance, and Clostridium perfingens and E. coli were detected in the bile. Imaging after PTGBD showed no cystic duct obstruction. On the 12th day after PTGBD, cholecystectomy and choledochotomy with primary closure were performed. The postoperative course was good and the patient was discharged on the 15th day after surgery.