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Biomedical subjects

A V Robinson

Publications and source records attributed to A V Robinson.

At least 19 recordsLinked to original sources
PubMed2001

The use of the endothelin receptor antagonist, tezosentan, before or after renal ischemia protects renal function.

BACKGROUND: Utilization of organs subjected to ischemia/reperfusion (I/R) injury could expand the donor pool. Endothelin (ET) is implicated in renal I/R injury. Therefore, our study compared the effectiveness of pre- and postischemic administration of the ET receptor antagonist, Tezosentan, in preserving renal function. METHODS: In a rat model, a kidney was subjected to 45 min of ischemia along with a contralateral nephrectomy. After 24 hr of reperfusion, renal function was assessed by serum creatinine (Scr), inulin clearance (glomerular filtration rate; GFR), and histology. ET-1 peptide expression was localized using immunohistochemistry. Three groups were studied: I/R untreated (n=17), I/R pretreated (n=11), and I/R posttreated (n=13) with Tezosentan (15 mg/kg, i.v.). RESULTS: Tezosentan significantly decreased (P<0.05) the rise in Scr from I/R injury (2.0+/-0.4 mg/dl, before and 2.9+/-0.4 mg/dl, after treatment) compared with untreated animals (4.2+/-0.4 mg/dl). GFR was significantly increased (P<0.05) from 0.13+/-0.03 ml/min (untreated animals) to 0.74+/-0.16 and 0.47+/-0.14 ml/min (pre- and posttreated animals). Untreated animals had significant cortical acute tubular necrosis, which was almost completely prevented by pretreatment with Tezosentan and markedly reduced by posttreatment. Increased ET-1 peptide expression was noted in the renal vasculature and in the cortical tubular epithelium of kidneys exposed to I/R. CONCLUSIONS: The purpose of this study was to optimize the function of kidneys exposed to I/R injury. Pretreatment as well as posttreatment with Tezosentan successfully decreased Scr, increased GFR, and maintained renal architecture in kidneys after ischemia. Therefore, ET receptor antagonists may be useful to preserve renal function in the transplantation setting.

Animals↗
PubMed2001

Pneumoperitoneum upregulates preproendothelin-1 messenger RNA.

BACKGROUND: Laparoscopic pneumoperitoneum has been shown to decrease glomerular filtration rate (GFR) and urine volume (UV). Endothelin-1 (ET-1), a potent renal vasoconstrictor, has been implicated. The purpose of this study was to determine renal function, ET-1 gene expression, and peptide localization in kidneys subjected to CO2 pneumoperitoneum. METHODS: Experiments were performed in three groups of anesthetized Sprague-Dawley rats in which GFR and UV were measured before, during, and after insufflation. In the first group (n = 8), pneumoperitoneum (10 mmHg) was established for 30 min. The second group (n = 4) underwent a sham operation without pneumoperitoneum. In the final group (n = 4), kidneys were obtained from normal control animals without any prior surgical instrumentation. PreproET-1 (ppET-1) mRNA levels were measured by reverse transcription-polymerase chain reaction (RT-PCR). The ET-1 peptide was localized within kidneys by immunohistochemistry (IHC). RESULTS: Pneumoperitoneum caused a significant (p < 0.05) 87% decrease in GFR and a 79% decrease in UV from baseline, with a return to baseline values after desufflation. RT-PCR showed a significant (p < 0.05) increase in expression of ppET-1 mRNA in the laparoscopic group; it was 3.52 +/- 0.33 densitometric units (DU), as compared to 0.35 +/- 0.06 DU and 0.57 +/- 0.12 DU in the control and sham groups, respectively. IHC showed enhanced expression of the ET-1 peptide in the vascular endothelium and proximal tubular cells of the laparoscopic group compared to the control and sham groups. CONCLUSION: Pneumoperitoneum induces ET-1 gene and peptide upregulation in the kidney. Expression of ET-1 is increased in the renal vasculature and proximal tubular cells. The elevation of ET-1 and its localization may account for some of the renal dysfunction observed during pneumoperitoneum. This suggests that antagonism of ET-1 may be beneficial in patients with renal impairment undergoing prolonged laparoscopic procedures or in protecting allograft function during and after living donor nephrectomy.

Animals↗
PubMed1999

Cold ischemia induces endothelin gene upregulation in the preserved kidney.

BACKGROUND: Prolonged cold ischemia time (CIT) can lead to posttransplant renal dysfunction; however, the pathophysiology remains unclear. Endothelin (ET), a potent vasoconstrictive peptide, may play a role in this injury. The purpose of this study was to determine if cold ischemia could induce renal ET-1 gene upregulation and to localize ET-1 peptide expression in the hypothermic kidney. MATERIALS AND METHODS: Kidneys from Lewis rats were perfused with Viaspan, harvested, and stored at 4 degrees C for varying periods of CIT: 0, 6, 24, and 48 h. Preproendothelin-1 (ppET-1) gene upregulation was measured using a reverse-transcription polymerase-chain reaction. ET-1 peptide expression was localized using immunohistochemistry. RESULTS: Control kidneys (0 h CIT) had 0. 56 +/- 0.22 DU of ppET-1 mRNA. After 6 h of CIT, a 2.3-fold increase in this level was noted. Following 24 h of CIT, ppET-1 mRNA was significantly upregulated to 1.96 +/- 0.38 DU (P < 0.05). Immunohistochemistry revealed typical vascular ET-1 staining in control kidneys. At 6 h of CIT, a significant increase in the expression of ET-1 was noted in the peritubular capillaries and vasa recta. After 24 h, intense staining for ET-1 was seen in the medullary collecting ducts. After 48 h of CIT, early cellular necrosis was present along with global decreases in ET-1 expression and ppET-1 mRNA levels. CONCLUSIONS: This study demonstrates that 24 h of cold preservation can induce significant upregulation of the renal ET-1 gene and increase expression of the ET-1 peptide localized to both vascular endothelial and tubular epithelial surfaces of the kidney. Consequently, prolonged cold ischemia prior to transplantation may lead to delayed renal function following revascularization via endothelin-induced vasoconstriction and/or tubular impairment.

Animals↗
PubMed1999

Endothelin up-regulation and localization following renal ischemia and reperfusion.

BACKGROUND: Endothelin (ET), a potent vasoconstrictor, is known to play a role in ischemic acute renal failure. Although preproET-1 (ppET-1) mRNA is known to be up-regulated following ischemia/reperfusion injury, it has not been determined which component of the injury (ischemia or reperfusion) leads to initial gene up-regulation. Likewise, although ET-1 peptide expression has been localized in the normal kidney, its expression pattern in the ischemic kidney has not been determined. Therefore, the purpose of this study was twofold: (a) to determine whether ischemia alone or ischemia plus reperfusion is required for the up-regulation of ppET-1 mRNA to occur, and (b) to localize ET-1 peptide expression following ischemia in the rat kidney to clarify better the role of ET in the pathophysiology of ischemia-induced acute renal failure. METHODS: Male Lewis rats underwent clamping of the right renal vascular pedicle for either 30 minutes of ischemia (group 1), 60 minutes of ischemia (group 2), 30 minutes of ischemia followed by 30 minutes of reperfusion (group 3), or 60 minutes of ischemia followed by three hours of reperfusion (group 4). The contralateral kidney acted as a control. ppET-1 mRNA up-regulation and ET-1 peptide expression were examined using the reverse transcription-polymerase chain reaction and immunohistochemistry, respectively. RESULTS: Reverse transcription-polymerase chain reaction yielded a control (nonischemic) value of 0.6 +/- 0.2 densitometric units (DU) of ppET-1 mRNA in the kidney. Group 1 levels (30 min of ischemia alone) were 1.8 +/- 0.4 DU, a threefold increase (P < 0.05). Group 2 levels (60 min of ischemia alone) increased almost six times above baseline, 3.5 +/- 0.2 DU (P < 0.01), whereas both group 3 and group 4 (ischemia plus reperfusion) did not experience any further significant increases in mRNA levels (1.9 +/- 0.4 DU and 2.8 +/- 0.6 DU, respectively) beyond levels in group 1 or 2 animals subjected to similar ischemic periods. ET-1 peptide expression in the ischemic kidneys was significantly increased over controls and was clearly localized to the endothelium of the peritubular capillary network of the kidney. CONCLUSIONS: Initial ET-1 gene up-regulation in the kidney occurs secondary to ischemia, but reperfusion most likely contributes to sustaining this up-regulation. The marked increase of ET-1 in the peritubular capillary network suggests that ET-induced vasoconstriction may have a pathophysiological role in ischemic acute tubular necrosis.

Acute Kidney Injury↗
PubMed1997

Cholescintigraphy in the diagnosis of bile leak after laparoscopic cholecystectomy.

Bile leaks are a recognized complication of laparoscopic cholecystectomy (LC). Different diagnostic approaches have been employed when this condition is suspected. We present our experience with cholescintigraphy as a primary imaging technique for the detection of bile leaks. The medical records of all patients who had cholescintigraphy after LC during a 58-month period were reviewed. Patients were selected for cholescintigraphy if fever unusual abdominal pain, nausea, vomiting, or jaundice were present beyond 36 hours after LC. Bile leaks were suspected in 25 out of 744 patients (3.36%). The nuclear imaging study was true positive in 7 cases and true negative in 18 cases, for a 100 per cent sensitivity, specificity, and accuracy in the detection of bile leaks. Five patients were treated by endoscopic retrograde cholangiopancreatography with stent and/or sphincterotomy, and two patients underwent exploratory laparotomy. None of the patients who underwent endoscopic retrograde cholangiopancreatography required peritoneal drainage. We conclude that cholescintigraphy is sensitive and accurate in the diagnosis of bile leaks. Its use along with a high index of suspicion of a bile leak may prevent the development of bile peritonitis.

Adult↗
PubMed1996

Laparoscopic surgery in a small animal model. A simplified technique of retroperitoneal dissection in the rat.

BACKGROUND: An adequate laparoscopic small-animal model would benefit surgical oncologic research. Immunobiologic data and reagents available for the rodent make them an ideal species. We developed a simple, inexpensive, reproducible technique for laparoscopic surgery in rodents. METHODS: Carbon dioxide pneumoperitoneum is achieved in anesthetized animals. Through a 0.5-cm midline incision a 4.8-mm bronchofiberscope is inserted into the peritoneal cavity and secured with a purse-string suture (PSS). Three additional PSSs are made to introduce the dissectors. Under fiberscopic vision, a blunt dissection of the retroperitoneum exposes the inferior vena cava and aorta. Necropsy 24 h after verifies the adequacy of dissection. RESULTS: Eighteen animals survived. The only death resulted from bleeding. Mortality was 5.26%. Surgical time was 24.72 +/- 8.93 min with all animals active 2 h postlaparoscopy. CONCLUSIONS: Laparoscopic surgery (LS) can be done inexpensively without sophisticated equipment. The rodent is ideal for examining the immunologic consequences of laparoscopic surgery and pneumoperitoneum.

Animals↗
PubMed1996

Open versus laparoscopic surgery: a comparison of natural antitumoral cellular immunity in a small animal model.

The scope of laparoscopic surgery has extended to the treatment of cancer. The immunological impact of laparoscopic surgery as compared with open surgery has not been well characterized. A paucity of information is available about differences or similarities of these two methods regarding natural antitumoral cellular immunity, namely, natural killer cell cytotoxicity. This study compared the activity of natural killer cells in rats subjected to pneumoperitoneum, open dissection of the retroperitoneum, and laparoscopic dissection of the retroperitoneum. When compared to control animals, rats subjected to pneumoperitoneum did not show any change in natural killer cell activity. Conversely, the groups of open surgery and laparoscopic surgery revealed significantly decreased natural killer cell cytotoxicity compared with controls (P < 0.0167). When the laparoscopic and the open surgical groups were compared to each other, no difference was found. In this study, both open and laparoscopic surgery had a suppressive effect upon the natural antitumoral cellular immunity. Pneumoperitoneum did not have an immune suppressive effect on natural killer cell activity. In this model, the advantages of laparoscopic surgery do not apply to natural antitumoral cellular immunity.

Animals↗
PubMed1995

Prostaglandin E1 attenuation of ischemic renal reperfusion injury in the rat.

BACKGROUND: Prostaglandin E1 (PGE1), a vasodilating prostaglandin, has been shown to protect against renal ischemic-reperfusion injury in acute experiments. The purpose of this study was to determine whether or not delayed administration of PGE1 would also be effective, as it has been suggested to be, in ischemic hepatic injury. STUDY DESIGN: In a chronic model, rats underwent 60 minutes of total renal ischemia followed by either NaCl or PGE1 therapy delivered at either time 0, 30, or 60 minutes after reperfusion. Serum creatinine and renal histology were evaluated for seven days. In an isolated perfused kidney model, kidneys were similarly treated but were removed and perfused in order to measure renal vascular resistance (VR). RESULTS: Prostaglandin E1 administration at time 0 resulted in lower creatinine values when compared with controls at both day 2 (2.1 +/- 0.4 compared with 4.2 +/- 0.9 mg/dL) and day 7 (0.9 +/- 0.1 compared with 2.3 +/- 0.8 mg/dL). Conversely, no improvement was observed when PGE1 was delayed for either 30 or 60 minutes. Renal morphology at seven days was essentially intact in PGE1-treated rats (time 0) whereas changes characteristic of acute tubular necrosis were observed in control kidneys. Ischemia caused a twofold increase in VR compared with nonischemic controls (6.18 +/- 1.12 compared with 3.45 +/- 0.66 mm Hg/mL/min/g at 20 minutes of perfusion). Prostaglandin E1-treated kidneys (time 0) had a VR that was unchanged from that calculated for nonischemic controls (3.28 +/- 0.63 compared with 3.45 +/- 0.66 mm Hg/mL/min/g at 20 minutes). CONCLUSIONS: These data demonstrate that after total renal ischemia, PGE1 administration at reperfusion ameliorates the expected injury, whereas delayed treatment is ineffective. Decreased vascular resistance may be responsible for this protective effect.

Alprostadil↗
PubMed1994

Captopril amelioration of renal reperfusion injury.

The purpose of this study was to determine whether angiotensin converting enzyme inhibition could ameliorate renal ischemic injury. Both a chronic rat model and a rat isolated perfused kidney (IPK) model were used. Adult rats were subjected to 60 min of left hilar crossclamping and right nephrectomy. Captopril (1 mg/kg) was given intravenously 5-10 min prior to clamping (CAP-pre, n = 5), at reperfusion (CAP-post, n = 5), or 30 min after reperfusion (CAP-30 min post, n = 5). Other groups of rats received enalapril (0.8 mg/kg iv) in the same manner (ENAL-pre, n = 5; ENAL-post, n = 5; ENAL-30 min post, n = 4). Serum creatinine in the treated groups was compared to ischemic control (NS, n = 7) for 7 days. In the IPK experiments, kidneys were similarly treated with CAP or ENAL. Vascular resistance (VR) and oxygen consumption (O2 CON) were determined from pressure, flow, and oxygen tension data for 60 min after initial equilibration. In the chronic model, Day 2 serum creatinine was significantly lower in all treated groups vs ischemic control. By Day 7, serum creatinine remained significantly lower in all ENAL-treated groups and in the CAP-30 min post group, although other CAP-treated groups had appreciably, although not significantly, lower creatinines, too. Histologic examination of CAP-pre kidney revealed intact morphology compared to ischemic control where acute tubular necrosis was observed. In the IPK experiments, CAP- and ENAL-treated kidneys had VR values that were significantly lower than those of ischemic controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Multiple pathways in the rejection of skin grafts.

We have analyzed the ability of CD4+ and CD8+ T cells to cause rejection of skin grafts in an Ir gene high responder strain. (DA.RT1u x DA.RT1c)F1 B rats (thymectomized, lethally irradiated, reconstituted with fetal liver cells) were grafted with ear skin of the recombinant strain, DA.RT1rl. The only allogeneic difference was a single class I MHC antigen. The B rats, which do not reject these grafts due to the absence of T cells, were reconstituted at various time intervals after skin grafting with either unsorted lymph node cells (LNCs), CD4+, CD8+ or CD4+ and CD8+ T cells. Unsorted LNCs given any time after graft placement always caused rejection (MST = 15d). CD4+ cells alone never caused rejection (MST greater than 60d, n = 8). CD8+ cells alone caused rejection if given within 3 weeks of graft placement. Thereafter, CD8+ cells alone lost their ability to cause rejection (MST greater than 60d, n = 6). B rats with grafts in place more than 3 weeks, when CD8+ cells alone were ineffective, rejected their skin grafts when given both CD8+ and CD4+ cells. These data suggest that there may be two T cell pathways in skin graft rejection. The first requires only CD8+ cells and causes rejection of a recently placed graft. The second pathway requires both CD4+ and CD8+ cells to reject long-standing grafts in which donor antigen-presenting cells have been putatively depleted and, therefore, may be dependent on host antigen-presenting cells.

Animals↗
PubMed1990

Postischemic renal dysfunction: the limited role of xanthine oxidase-generated oxygen free radicals.

Oxygen free radicals (OFRs) generated during reperfusion are putative mediators of postischemic renal dysfunction. To address this issue, the renal response to ischemia and reperfusion was compared to the response to OFR generation without ischemia. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with an asanguinous modified Krebs' buffer. Kidneys were subjected to 30 min of ischemia followed by reperfusion or to OFRs generated by combining 25 mumole hypoxanthine with 1 unit xanthine oxidase. Both insults caused a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and an 80% reduction in glomerular filtration and urine flow rates. The OFR scavengers, superoxide dismutase (SOD, 250 units/ml) and catalase (CAT, 500 units/ml), prevented these alterations after OFR generation but not after 30 min of ischemia and reperfusion. SOD and CAT also afforded no protection against the less severe dysfunction observed after 10 or 20 min of ischemia and reperfusion. OFRs do not appear to be prominent mediators of postischemic renal dysfunction; other factors, probably associated with ischemia must be primarily responsible.

Animals↗
PubMed1989

Oxygen free radical mediated renal dysfunction.

Postischemic renal dysfunction (PIRD) is characterized by a reduction in glomerular filtration and tubular reabsorption of solute. The relative contribution of oxygen free radicals (OFRs) generated during reperfusion remains unclear. This study characterized the renal response to OFRs--independent of an ischemic insult. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with a modified Krebs' buffer. Hypoxanthine (25 mumole) and xanthine oxidase (1 unit) were combined and infused proximal to the kidney. There was a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and a 70% reduction in glomerular filtration rate. There was also a significant reduction in urine flow rate and oxygen consumption. The percentage reabsorption of filtered water and sodium by the renal tubules was not diminished, however. This pattern was not observed when the xanthine oxidase was inactivated or when the perfusate was pretreated with superoxide dismutase (250 units/ml) and catalase (500 units/ml). The generation of OFRs, independent of an ischemic insult, causes a decrease in glomerular filtration out of proportion to the decrease in renal flow similar to that observed with PIRD. OFRs may contribute to the hemodynamic and glomerular alterations seen with PIRD. Factors other than OFRs, probably associated with ischemia, must be responsible for the tubular dysfunction.

Animals↗
PubMed1988

A model of hypoxic renal failure.

Models of ischemic acute renal failure (ARF) must consider the combination of tissue hypoxia, insufficient nutrient flow, and anaerobic waste product accumulation. This study utilized isolated perfused rat kidneys to characterize the renal response to a graded hypoxic insult while maintaining flow. Kidneys were perfused at 37 degrees C with an asanguineous Krebs-buffered saline. After a 40-min baseline period, 10 or 30 min of hypoxia was rapidly achieved by reducing perfusate oxygen tension from approximately 550 to 50 mm Hg. Ten minutes of hypoxia resulted in tubular dysfunction evidenced by a 50% increase in urine flow (UV) and a 10% decrease in percent sodium reabsorption (%Na). Glomerular filtration rate (GFR) decreased by 40% during 10 min of hypoxia and returned to control levels after reoxygenation. Thirty minutes of hypoxia caused an irreversible 85% decrease in GFR accompanied by a 50% decrease in UV. This insult also caused more severe tubular dysfunction evidenced by a 20% decrease in %Na and a 35% decrease in oxygen consumption. These results demonstrate a spectrum of renal dysfunction that corresponds to the clinical spectrum from nonoliguric to oliguric ARF. This model of hypoxic ARF allows more specific investigation into the hypoxic component of postischemic renal dysfunction.

Absorption↗
PubMed1988

Effect of hypoxia on renal flow.

The isolated perfused rat kidney was used to characterize the renal response to hypoxia while flow was maintained. Hypoxia resulted in an 85% reduction in glomerular filtration rate (GFR) without any change in total renal vascular resistance. There was an initial 85% increase in urine flow rate (UV) and a 45% decrease in percent sodium reabsorption due to hypoxic metabolic inhibition of solute reabsorption. As GFR decreased, UV declined to 50% of control. GFR did not increase on reoxygenation. These results suggest that an intrinsic protective tubuloglomerular feedback mechanism is activated during hypoxia that redistributes intrarenal flow to reduce the filtered load and to reduce oxygen demand for solute reabsorption. Delivery of oxygen to the hypoxia-sensitive medulla would also be improved. Decreases in GFR observed with ischemic models of acute renal failure may reflect this protective mechanism in addition to the effects of ischemic injury.

Animals↗
PubMed1988

The contribution of hypoxia to postischemic renal dysfunction.

Renal ischemia is a multifactorial insult consisting of both hypoxia and stagnation of blood flow. This study compared the renal response with hypoxia alone versus ischemia (hypoxia and stagnation of flow). Isolated rat kidneys were perfused at 90 to 110 mm Hg and 37 degrees C with an asanguinous modified Krebs' buffer. Perfusate flow rate, vascular resistance, urine flow rate, glomerular filtration rate (GFR), percent sodium reabsorption, and oxygen consumption were measured. Five groups were examined: 10-minute hypoxia (HYP10), 30-minute hypoxia (HYP30), 10-minute ischemia (ISC10), 30-minute ischemia (ISC30), and time-matched controls. HYP10 resulted in isolated tubular dysfunction, as evidenced by an increase in urine flow rate and a decrease in percent sodium reabsorption. ISC10 caused decreased GFR, oliguria, and more severe tubular dysfunction. The pattern of glomerular and tubular dysfunction after HYP30 was similar to that after ISC30. Glomerular dysfunction was associated with a decrease in perfusate flow rate and an increase in vascular resistance only after ISC30. This suggests that the decrease in GFR seen with postischemic renal dysfunction is not a primary result of decreased flow. Furthermore, hypoxia does not account for the entire reduction in renal function after ischemia of similar duration. The more severe dysfunction after ischemia may be a consequence of the stagnation of renal flow (anaerobic waste product accumulation and inadequate nutrient supply).

Animals↗
PubMed1983

31P NMR studies of energy metabolism in perfused rat kidney.

Conventional biochemical analyses have demonstrated significant alterations in high-energy phosphate metabolism during shock, but the time course of these changes cannot be followed in individual animals because these analyses are invasive and destructive. This study sought to evaluate the utility of 31P NMR as a means of following phosphorus metabolites under various conditions, including those designed to model the shocked state. Twenty adult albino rats were subject to a modified Wiggers' model of hemorrhagic shock lasting from 5 to 140 min. ATP was determined on extracts of the kidneys of each animal both by a biochemical assay and by integration of 31P NMR resonance signals. The equation for renal ATP content plotted versus time for enzymatically determined ATP was 1.79 - 0.0097x (r = 0.83, P less than 0.01) as compared to 1.76 - 0.0093x (r = 0.69, P less than 0.01) for NMR-determined ATP. Isolated, normal rat kidneys perfused with oxygenated, modified Krebs' solution while in the NMR spectrometer maintained normal ATP levels for several hours. ATP/ADP ratios were greater than those observed by conventional enzymatic analysis. Temporary anoxia, induced by substituting 100% N2 for 95% O2:5% CO2, resulted in decreases in ATP content, which reverted to normal with reinstitution of oxygenation. Intracellular pH changed in accordance with perfusate pH during anoxia. It is concluded that 31P NMR studies of the perfused rat kidney have immediate application for the nondestructive study of energy metabolism in shock and ischemia.

Adenosine Diphosphate↗