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Biomedical subjects

B Noe

Publications and source records attributed to B Noe.

12 recordsLinked to original sources

Phosphorylcholine coating of ePTFE grafts reduces neointimal hyperplasia in canine model.

This study attempts to prevent neointimal hyperplasia by coating the graft luminal surface with a derivative of phosphorylcholine (PC), thereby providing a biocompatible surface with the assumption of limiting pannus tissue ingrowth from the graft anastomoses. Bilateral carotid artery bypass grafts were placed in six dogs using expanded polytetrafluoroethylene (ePTFE). In each animal, one carotid arterial-arterial conduit was constructed using a graft having a PC coating over the entire luminal surface of the graft. On the contralateral side, uncoated graft served as a control. The processed specimens were analyzed for graft neointimal area and neointimal thickness. Cell proliferation was assessed by staining for bromodeoxyuridine (BrdU) incorporation. All grafts were patent except one control graft that was occluded at 4 weeks. There was a significant reduction in the anastomotic graft neointimal area between the treated and control groups (0.27 +/- 0.17 mm2 versus 0.53 +/- 0.13 mm2, respectively; p = 0.008). Furthermore, the BrdU labeling index in the graft neointimal tissues was significantly smaller (p < 0.001) in the treated group (2.64 +/- 0.77%) as compared with the control group (5.07 +/- 0.83%). These data demonstrate that PC coating of ePTFE significantly reduces graft neointimal hyperplasia and cell proliferation in a canine carotid artery bypass model. The application of PC within the ePTFE graft effectively blocks tissue ingrowth from the adjacent native vessel, thereby preserving the anastomosis luminal diameter.

Animals↗

Renal artery perfusion modifies ischemia/reperfusion injury.

Renal ischemic and reperfusion injury is a significant complication of major aortic and renovascular surgery. The delivery of a preservative agent just prior to reperfusion of an ischemic kidney may decrease the reperfusion injury. The purpose of this study was to evaluate the effects of renal artery perfusates delivered at the termination of an ischemic period. Five groups of rats were evaluated. All rats underwent left nephrectomy. The right kidney was made ischemic for 45 min by occlusion of the renal artery and vein. Ischemic control animals had no renal artery perfusion. Nonischemic control animals had no renal vessel occlusion or perfusion. The other three groups were perfused during the final 4 min of ischemia with one of the following: normal saline (NS), phosphate-buffered saline (PBS), or anti-ICAM-1-antibody (mAb). The blood urea nitrogen (BUN), serum creatinine (Cr), and renal histopathologic injury of each group were compared. The ischemic control group had significantly better renal function than the group perfused with NS or mAb at 72 hr. There was no significant difference between the ischemic control and PBS groups in renal function or morphologic injury. It is concluded that none of the perfusates in the study had protected the kidney from ischemic and reperfusion injury. NS delivered in this manner was injurious to the kidney.

Animals↗

Normothermic renal artery perfusion: a comparison of perfusates.

Hypothermia and preservative perfusates have been used to decrease ischemic renal injury. This study was performed to identify the preservative function of perfusates independent of the effects of hypothermia. Rats underwent 45 minutes of renal ischemia. Rectal and renal parenchyma temperatures were monitored and maintained within 1 degree C of normal. Perfusates were University of Wisconsin solution (UW), Euro-Collins solution, normal saline solution, and Ringer's lactate solution. A nonperfused ischemic control and a nonischemic control group were also evaluated. Parameters evaluated included serum creatinine and blood urea nitrogen levels, renal ischemic injury grade, renal weight, and gross appearance of the injured kidney. Rats treated with UW solution were found to have a significantly lower creatinine, blood urea nitrogen, and injury grade than the other three perfused groups. The external gross appearance of the UW-treated kidneys was normal, whereas that of the other groups demonstrated moderate to severe injury. Although the mean right/left renal weight difference of the UW-treated group was lower than that of the other three groups, this was not statistically significant. Under normothermic conditions in rats, UW solution affords significant renal protection from ischemia. Euro-Collins, normal saline, and Ringer's lactate solutions display no significant protective effect.

Adenosine↗

Anisoosmotic regulation of hepatic gene expression.

The effect of anisoosmolarity on the abundance of various mRNA species was examined in perfused rat liver and H4IIE rat hepatoma cells. Hyperosmotic exposure (385 mosmol/l) of isolated rat livers increased mRNA levels for tyrosine aminotransferase (TAT) by 246% and those for phosphoenolpyruvate carboxykinase (PEPCK) by 186%, whereas hypoosmotic exposure (225 mosmol/l) decreased their levels to 43% and 42%, respectively. mRNA levels for fructose-1,6-bisphosphatase (FBP), argininosuccinate lyase (ASL), argininosuccinate synthetase (ASS), glutamine synthetase (GS), glutaminase (GA) and glucokinase (GK) were largely unaffected. In H4IIE cells the modulation of TAT and PEPCK mRNA levels by anisoosmotic exposure was similar to that found in perfused rat liver. ASL and glutaminase mRNA levels were influenced in an opposite manner. The effects of anisoosmolarity on PEPCK mRNA levels in H4IIE cells were largely abolished in the presence of the protein kinase inhibitors H-7, H-89 and HA-1004. Other protein kinase inhibitors such as Go-6850, KN-62, Rp-8-CPT-cAMPS, rapamycin, wortmannin, genistein or herbimycin did not prevent the osmosensitivity of PEPCK mRNA levels. Also pertussis and cholera toxin, vanadate and colchicine did not affect the osmosensitivity of PEPCK mRNA levels. The data suggest that anisoosmotic exposure acts on the levels of some but not all mRNA species and that this action may involve changes in protein phosphorylation. They further indicate that the recently identified osmosensitive signal transduction pathway which involves a G-protein and tyrosine kinase dependent activation of mitogen-activated protein kinases is apparently not involved in the osmoregulation of PEPCK mRNA levels.

Animals↗

Modulation of phosphoenolpyruvate carboxykinase mRNA levels by the hepatocellular hydration state.

Exposure of isolated perfused rat livers to hypo-osmotic (225 mosmol/l) perfusion media for 3 h led to a decrease of about 60% in mRNA levels for phosphoenolpyruvate carboxy-kinase (PEPCK) compared with normo-osmotic (305 mosmol/l) perfusions. Conversely, PEPCK mRNA levels increased about 3-fold during hyperosmotic (385 mosmol/l) perfusions. The anisotonicity effects were not explained by changes in the intracellular cyclic AMP (cAMP) concentration or by changes of the extracellular Na+ or Cl- activity. Similar effects of aniso-osmolarity on PEPCK mRNA levels were found in cultured rat hepatoma H4IIE.C3 cells, the experimental system used for further characterization of the effect. Whereas during the first hour of anisotonic exposure no effects on PEPCK mRNA levels were detectable, near-maximal aniso-osmolarity effects were observed within the next 2-3 h. PEPCK mRNA levels increased sigmoidally with the osmolarity of the medium, and the anisotonicity effects were most pronounced upon modulation of osmolarity between 250 and 350 mosmol/l. The aniso-osmolarity effects on PEPCK mRNA were not affected in presence of Gö 6850, protein kinase C inhibitor. cAMP increased the PEPCK mRNA levels about 2.3-fold in normo-osmotic media, whereas insulin lowered the PEPCK mRNA levels to about 8%. The effects of cAMP and insulin were also observed during hypo-osmotic and hyperosmotic exposure, respectively, but the anisotonicity effects were not abolished in presence of the hormones. The data suggest that hepatocellular hydration affects hepatic carbohydrate metabolism also over a longer term by modulating PEPCK mRNA levels. This is apparently unrelated to protein kinase C or alterations of cAMP levels. The data strengthen the view that cellular hydration is an important determinant for cell metabolic function by extending its regulatory role in carbohydrate metabolism to the level of mRNA.

Animals↗

Volumetric and functional liver blood flow are both increased in the human transplanted liver.

This study measured volumetric liver blood flow and galactose clearance concurrently during orthotopic liver transplant in human subjects. Ultrasound transit time flowmeters measured hepatic artery and portal vein flow 1-3 h after reperfusion. Galactose (100 mg/min) was infused over 45-60 min to steady state for calculation of clearance. Mean +/- S.D. total volumetric flow was 1966 +/- 831 ml/min with portal flow contributing 86%. Mean galactose clearance was 1988 +/- 641 ml/min. There was a significant correlation (p < 0.05, r = 0.61) between volumetric total liver blood flow and galactose clearance. The data show that: (i) the newly transplanted liver is capable of metabolizing galactose within 1-3 h of reperfusion; and (ii) liver blood flow is high in the newly implanted liver. The clinical importance of this observation is that there is increased clearance of high first pass substances by the transplanted liver which may be of importance in patient management.

Blood Volume↗

Increased galactose clearance after liver transplantation: a measure of increased blood flow through the denervated liver?

This study measured the liver blood flow-dependent index of galactose clearance in patients after liver transplantation, to test the hypothesis that liver blood flow is increased in the denervated liver. Eight normal subjects and 16 patients 1 to 8 months after liver transplant were studied. All patients were stable with no evidence of severe rejection at the time of study. Galactose clearance was measured at steady state during continuous infusion of 75 mg per min of 5% galactose. The results show a statistically significant (p less than 0.01) higher average galactose clearance in the transplant patients (1,187 +/- 316 ml per min per m2) compared to the control group (709 +/- 121 ml per min per m2). The major limiting factor in galactose clearance at low concentrations is liver blood flow, and we interpret these data as evidence for increased blood flow in the transplanted liver. Possible mechanisms for the increased galactose clearance are (i) loss of normal vasomotor tone in the denervated liver, or (ii) persistence of abnormal systemic hemodynamics after transplantation. Elucidation of these mechanisms awaits further study.

Adult↗

Fluorometric determination of indocyanine green in plasma.

With this fluorometric method for measuring indocyanine green (ICG) in biological fluids, the limit of detection is an order of magnitude lower than for the traditional spectrophotometric procedure. The excitation and emission maxima are 780 and 810 nm, respectively. Agreement was excellent (r = 0.998) between direct results by this method and those by a liquid-chromatographic procedure with spectrophotometric detection. ICG breaks down in aqueous solution; the degradation products can be detected with liquid-chromatographic/spectrophotometric methods, but because the metabolites are not fluorescent, they do not interfere in the method present here. The increased specificity and sensitivity of this method should permit much more complete analysis of the kinetics of ICG disposition.

Chromatography, High Pressure Liquid↗