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PubMed2005

Insulin sensitivity by oral glucose minimal models: validation against clamp.

Measuring insulin sensitivity in the presence of physiological changes in glucose and insulin concentrations, e.g., during a meal or OGTT, is important to better understand insulin resistance in a variety of metabolic conditions. Recently, two oral minimal models have been proposed to measure overall insulin sensitivity (S(I)) and its selective effect on glucose disposal (S(I)*) from oral tests. S(I) and S(I)* have been successfully validated against multiple tracer meal estimates, but validation against euglycemic hyperinsulinemic clamp estimates is lacking. Here, we do so in 21 subjects who underwent both a multiple-tracer OGTT and a labeled euglycemic hyperinsulinemic clamp. Correlation between minimal-model S(I), S(I) and corresponding clamp estimates S(I)(*clamp), S(I)(*clamp) was satisfactory, respectively r = 0.81, P < 0.001, and r = 0.71, P < 0.001. S(I) was significantly lower than S(I)(clamp) (8.08 +/- 0.89 vs. 13.66 +/- 1.69 10(-4) dl.kg(-1).min(-1) per microU/ml, P = 0.0002), whereas S(I) and S(I)(*clamp) were very similar (8.17 +/- 1.59 vs. 8.84 +/- 1.39 10(-4) dl.kg(-1).min(-1) per microU/ml, P = 0.52). These results add credibility to the oral minimal-model method as a simple and reliable physiological tool to estimate S(I) and S(I)*, also in large-scale clinical trials.

Adult↗
PubMed2003

Activation of alpha2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men.

The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic alpha2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 +/- 0.9 yr; body mass index: 23.8 +/- 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 microM) or epinephrine (1 and 10 microM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 microM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 microM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 microM phentolamine (a nonselective alpha-AR antagonist), the inhibition of epinephrine (10 microM)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the beta-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by alpha2-ARs.

Adipose Tissue↗
PubMed2000

Active dendritic membrane properties of Xenopus larval spinal neurons analyzed with a whole cell soma voltage clamp.

Voltage- and current-clamp measurements of inwardly directed currents were made from the somatic regions of Xenopus laevis spinal neurons. Current-voltage (I-V) curves determined under voltage clamp, but not current clamp, were able to indicate a negative slope conductance in neurons that showed strong accommodating action potential responses to a constant current stimulation. Voltage-clamp I-V curves from repetitive firing neurons did not have a net negative slope conductance and had identical I-V plots under current clamp. Frequency domain responses indicate negative slope conductances with different properties with or without tetrodotoxin, suggesting that both sodium and calcium currents are present in these spinal neurons. The currents obtained from a voltage clamp of the somatic region were analyzed in terms of spatially controlled soma membrane currents and additional currents from dendritic potential responses. Linearized frequency domain analysis in combination with both voltage- and current-clamp responses over a range of membrane potentials was essential for an accurate determination of consistent neuronal model behavior. In essence, the data obtained at resting or hyperpolarized membrane potentials in the frequency domain were used to determine the electrotonic structure, while both the frequency and time domain data at depolarized potentials were required to characterize the voltage-dependent channels. Finally, the dendritic and somatic membrane properties were used to reconstruct the action potential behavior and quantitatively predict the dependence of neuronal firing properties on electrotonic structure. The reconstructed action potentials reproduced the behavior of two broad distributions of interneurons characterized by their degree of accommodation. These studies suggest that in addition to the ionic conductances, electrotonic structure is correlated with the action potential behavior of larval neurons.

Action Potentials↗
PubMed1988

Reduction of insulin clearance during hyperglycemic clamp. Dose-response study in normal humans.

Insulin secretion and clearance were studied in eight normal subjects who underwent hyperglycemic clamp studies at plasma glucose levels of 120, 225, and 300 mg/dl on three occasions. Insulin secretion rates were calculated during a 1-h baseline period and during 3 h of glucose clamping from a two-compartmental analysis of peripheral C-peptide concentrations with individual kinetic parameters derived after intravenous bolus injections of biosynthetic human C-peptide. At the 300-mg/dl clamp level, the insulin secretion rate increased to a value 9.9 +/- 0.7 times that of basal at the end of the clamp (mean +/- SE), whereas over the same period, the peripheral insulin concentrations increased to a greater extent, reaching a value 15.4 +/- 1.2 times that of basal (P = .002). This greater relative increase in the insulin concentration in comparison with the corresponding insulin secretion rate suggests a reduction in the clearance of endogenous insulin. A similar trend was seen at the 225-mg/dl clamp level, but the relative increase in the insulin concentration (9.9 +/- 1.5 times that of basal) was not significantly higher than the relative increase in the insulin secretion rate (8.1 +/- 0.5 times that of basal, P = .17). At the 120-mg/dl clamp level, the relative increases in the insulin secretion rate (2.7 +/- 0.2 times that of basal) and the insulin concentration (2.4 +/- 0.2 times that of basal) were similar (P = .26), indicating no reduction in endogenous insulin clearance during moderate stimulation of insulin secretion. In conclusion, a reduction in endogenous insulin clearance occurs during greater stimulation of insulin secretion at higher glucose-clamp levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Comparison of estimates of insulin sensitivity from minimal model analysis of the insulin-modified frequently sampled intravenous glucose tolerance test and the isoglycemic hyperinsulinemic clamp in subjects with NIDDM.

Minimal model (MINMOD) analysis of the frequently sampled intravenous glucose tolerance test (FSIVGTT) is dependent on an adequate insulin response to the glucose load. As this is characteristically deficient in subjects with non-insulin-dependent diabetes mellitus (NIDDM), the technique has been modified by the use of an intravenous bolus of insulin. Previous validation of this modification in humans has relied on agreement between insulin sensitivity indexes (SI) estimated from tolbutamide- and insulin-modified tests and not on direct comparison with estimates derived from the isoglycemic glucose clamp. We have compared estimates of insulin sensitivity derived from minimal modeling of a 4-h insulin-modified FSIVGTT and the glucose clamp in subjects with NIDDM. Twelve subjects underwent an insulin-modified FSIVGTT and an isoglycemic hyperinsulinemic clamp in random order 2-4 weeks apart. Fasting plasma glucose (8.4 vs. 9.0 mmol/l) and immunoreactive insulin (IRI) concentrations (104.5 vs. 101.5 pmol/l) were not different between the 2 study days. SI(clamp) was derived from the steady-state glucose infusion rate during the 3rd h of the clamp, corrected for the ambient insulin and glucose concentrations. SI(ivgtt) was derived using MINMOD. SI(ivgtt) was 1.06 +/- 0.18 min-1.mU-1.ml x 10(4), and mean SI(clamp) was 4.97 +/- 0.69 l.min-1/pmol.l-1 x 10(4) (mean +/- SE). SI(ivgtt) was positively correlated with SI(clamp) (r = 0.73, P = 0.004) and negatively correlated with body mass index (r = -0.7, P = 0.005) and fasting IRI(ivgtt) (r = -0.64, P = 0.008). In summary, MINMOD analysis of the insulin-modified FSIVGTT provides a valid measure of insulin sensitivity in subjects with NIDDM.

Blood Glucose↗
PubMed2003

Determination of reference range values indicative of glucose metabolism and insulin resistance by use of glucose clamp techniques in horses and ponies.

OBJECTIVES: To acquire reference range values indicative of glucose metabolism by use of the hyperglycemic clamp technique in healthy horses and evaluate the usefulness of the euglycemic hyperinsulinemic clamp technique in healthy horses and ponies. ANIMALS: Dutch Warmblood horses and 4 Shetland ponies. PROCEDURE: The hyperglycemic clamp technique was used for quantification of the sensitivity of beta cells to exogenous glucose infusion in horses. The euglycemic hyperinsulinemic clamp technique was used to determine the sensitivity and responsiveness of tissues to exogenous insulin in horses and ponies. RESULTS: During the hyperglycemic clamp technique, the mean amount of glucose metabolized (M) in horses was 0.011 +/- 0.0045 mmol/kg x min(-1) (95% confidence interval [CI], 0.0018 to 0.020 mmol/kg x min(-1); range, 0.000035 to 0.021 mmol/kg x min(-1)) and the mean M value-to-plasma insulin concentration (I) ratio (ie, mmol of glucose/kg x min(-1) per pmol of insulin/L x 100) was 0.017 +/- 0.016 (95% CI, -0.014 to 0.049; range, 0.000025 to 0.055). During the euglycemic hyperinsulinemic clamp technique, the mean M value was 0.014 +/- 0.0055 mmol/kg x min(-1) (95% CI, 0.0026 to 0.025 mmol/kg x min(-1); range, 0.0042 to 0.023 mmol/kg x min(-1)) in horses and 0.0073 +/- 0.0020 mmol/kg x min(-1) (95% CI, 0.0034 to 0.011 mmol/kg x min(-1); range, 0.0049 to 0.011 mmol/kg x min(-1)) in ponies. The M value was significantly lower in ponies than in horses, whereas the M:I ratios were not significantly different between horses and ponies. CONCLUSION AND CLINICAL RELEVANCE: Glucose clamp techniques offer good methods to investigate glucose metabolism in horses and ponies. A higher degree of insulin resistance was found in ponies, compared with Dutch Warmblood horses.

Animals↗
PubMed2001

Randomized comparison of ultrasonic vs clamp transection of the liver.

HYPOTHESIS: Hepatic parenchymal transection is a technical priority in liver surgery. The use of an ultrasonic dissector for hepatectomy may result in less blood loss than conventional clamp crushing. DESIGN: Randomized controlled trial. SETTING: University teaching hospital. PATIENTS: The 132 patients scheduled to undergo partial hepatectomies were randomly assigned to receive hepatic transection by ultrasonic dissector or by clamp crushing (66 patients by each method). INTERVENTIONS: All resections were performed with inflow occlusion and were guided ultrasonographically. Hepatectomies were graded according to a predefined system based on 6 criteria (blood loss, transection time, technical error, surgical margin, landmark appearance, and postoperative morbidity), each with 3 scores (lower scores indicating higher quality). MAIN OUTCOME MEASURES: Blood loss and hepatectomy grade. RESULTS: No difference was found between the ultrasonic and clamp groups in median blood loss (515 mL [range, 15-2527 mL] vs 452 mL [range, 17-1912 mL]; P =.63), transection time (61 minutes [range, 16-177 minutes] vs 54 minutes [range, 7-205 minutes]; P =.58), or transection speed (1.1 cm(2)/min [range, 0.4-4.0 cm(2)/min] vs 1.0 cm(2)/min [range, 0.4-3.0 cm(2)/min]; P =.90). Ultrasonic dissection caused more frequent histologically proven tumor exposure at the surgical margin (9 vs 3 patients; P =.09), incomplete appearance of landmark hepatic veins on the cut surface after anatomical resection (12 vs 4 patients; P =.03), and postoperative morbidity (20 vs 14 patients; P =.32) than did clamp crushing. The hepatectomies with clamp crushing had significantly higher grades than those with ultrasonic dissection (P =.05), as indicated by the lower median sum score (4.0 [range, 0-12] vs 5.0 [range, 0-19]; 95% confidence interval for difference, -2.0 to 0; P =.03). The transection method independently influenced hepatectomy grade (adjusted odds ratio = 3.06; 95% confidence interval, 1.35-6.92; P =.01). CONCLUSIONS: Ultrasonic dissection offers no reduction in blood loss compared with clamp crushing for transection of the liver. Clamp crushing results in a higher quality of hepatectomy and is therefore the option of choice.

Adult↗
PubMed1992

The effect of suprarenal cross-clamping on abdominal aortic aneurysm repair.

Two hundred five patients who underwent elective abdominal aortic aneurysm repair were divided into two groups: those who underwent infrarenal cross-clamping alone (n = 166) and those who underwent suprarenal cross-clamping alone or combined with infrarenal cross-clamping (n = 39). Mortality was comparable between groups (1.2% for infrarenal cross-clamping vs 2.6% for suprarenal cross-clamping). Transient renal insufficiency was more frequent in the suprarenal group than in the infrarenal group (28% vs 10%), but dialysis rates (3% for suprarenal vs 2% for infrarenal) were similar. Cardiac morbidity was comparable between groups as well. Operating room data reflected the technical challenge of complex aneurysm repairs. The retroperitoneal approach was the preferred exposure in the suprarenal group since better access to the suprarenal aorta may be achieved with this technique. While abdominal aortic aneurysm repairs requiring suprarenal cross-clamping remain a technical challenge, the risks are not formidable and suprarenal cross-clamping should be considered when confronted with difficult periaortic dissection.

Academic Medical Centers↗
PubMed1996

Structural recovery of small arteries following clamp injury: a light and electron microscopic investigation in the rat.

Endothelial injuries were induced in the left common iliac arteries (1 mm in diameter) of rats, by the placement of 1 mm Scovell-Lewis microvascular clamps for 5 minutes, to create a lesion in which to quantitate the rate and degree of cellular regeneration. The left (clamp-injured) and right (control) iliac arteries from the 15 rats used in this study were viewed with the electron microscope at 2, 7, and 14 days after clamping, and the clamp sites were analysed morphometrically. At 2 days there was only minimal denudation of the endothelium; most cells were disoriented and showed some signs of traumatic injury. By 7 days there was a completely continuous endothelial lining, but there was also evidence of increased cytoplasmic activity in these cells, as well as a statistically significant simplification in their intercellular junctional morphology. These changes persisted at 14 days after injury, but they were less pronounced. Smooth muscle cells in the media were relatively unaffected by the trauma in the first 2 days after clamping. However, they exhibited a change of phenotype from contractile to synthetic by 7 days after injury. By 14 days most smooth muscle cells had reverted back to the contractile phenotype, with little evidence of residual damage. These studies reveal that the reconstitution and regeneration of the endothelium is very rapid following clamp injury, but that significant residual ultrastructural changes in the interendothelial junctions persist for at least 14 days after injury. These findings indicate that there is potential for subsequent pathological changes in sites of vascular clamp injury.

Animals↗
PubMed2006

Randomized clinical trial of liver resection with and without hepatic pedicle clamping.

BACKGROUND: The purpose of this study was to compare the perioperative outcome of liver resection with and without intermittent hepatic pedicle clamping. METHODS: Between June 2002 and June 2004, 126 consecutive patients with resectable liver tumours were randomized to undergo resection with (63 patients) or without (63 patients) intermittent hepatic pedicle clamping. RESULTS: The transection time was significantly higher in the group without hepatic pedicle clamping. The blood loss per cm(2) was similar in the two groups: 2.7 ml/cm(2) in the group with versus 3.2 ml/cm(2) in group without hepatic pedicle clamping (P = 0.425). In the subset of patients with an abnormal liver, there were no differences in blood loss per transection surface: 3.1 ml/cm(2) in the group with versus 2.9 ml/cm(2) in the group without clamping (P = 0.829). The rate of blood transfusions was not higher in the non-clamping group. No differences were observed in the postoperative liver enzyme serum levels, the in-hospital mortality (one patient in each group) or the number of complications. CONCLUSION: This study showed clearly that liver resection without hepatic pedicle clamping is safe, even in patients with a diseased liver.

Aged↗
PubMed2006

Efficient sequence-specific purification of Listeria innocua mRNA species by triplex affinity capture with parallel tail-clamps.

Parallel clamps can interact in a sequence-specific manner with homopyrimidine DNA and RNA oligonucleotides to form triplexes. For longer nucleic acids, we have previously demonstrated the inhibitory effect of DNA-target secondary structures on triplex formation. We further designed a modification of these molecules-that is, tail-clamps formed by addition of a tail sequence to the parallel clamp-and proved efficient binding of the molecules with structured single-stranded DNA targets. Here we explore the possible application of the tail-clamp strategy for triplex formation with RNA targets, which are typically found as strongly folded single-stranded molecules. Efficient and specific binding of a tail-clamp designed to form a parallel triplex with Listeria innocua iap mRNA sequences has been verified by UV melting curves and triplex affinity capture techniques. Furthermore, we show for the first time the formation of stable complexes of mRNA with tail-clamps not only under acidic but also under neutral and slightly basic pH conditions. These results signify a further step towards the possible applications of triplexes with mRNA molecules; research, analytical, and therapeutic uses can be envisaged. As an example, our tail-clamp-based triplex affinity capture assay allowed the specific capture and recovery of iap mRNA molecules from an L. innocua total RNA solution with 45 % yield.

Listeria↗
PubMed1998

Decreased survival in rat liver transplantation with extended cold preservation: role of portal vein clamping time.

Primary liver graft dysfunction is currently related to cold ischemia-reperfusion injury, although a wide survival range has been reported using 24-hour preservation in cold University of Wisconsin (UW) solution. We hypothesized that the portal vein clamping time (PVCT) played a more important role than cold preservation injury in the postoperative outcome. Rat liver transplantation was performed using different clamping times after 24-hour cold ischemia in the UW solution. Survival rates, plasma tumor necrosis factor (TNF), and nitrate/nitrite levels were examined. Subsequently, the effect of clamping time was evaluated on hepatocyte and sinusoidal endothelial cell (SEC) function using isolated perfused livers. Survival rate was directly related to clamping time length. Marked increases in TNF and nitrate/nitrite levels were found after surgery, particularly after long clamping times. In perfusion studies, the SEC function was already markedly altered after preservation alone and was not further modified by transplantation. By contrast, the hepatocyte function was moderately altered after transplantation, irrespective of clamping times, even when rats operated with long clamping times were in terminal conditions. In rats, 24-hour preservation in cold UW solution is not a severely compromising condition leading to primary liver nonfunction. Long PVCTs are associated with an endotoxemia-like syndrome more related to a warm intestinal ischemia than to cold ischemia injury of the liver.

Animals↗
PubMed2007

Safety evaluation of large external fixation clamps and frames in a magnetic resonance environment.

Large orthopedic external fixation clamps and related components were evaluated for force, torque, and heating response when subjected to the strong electromagnetic fields of magnetic-resonance (MR) imaging devices. Forces induced by a 3-Tesla (T) MR scanner were compiled for newly designed nonmagnetic clamps and older clamps that contained ferromagnetic components. Heating trials were performed in a 1.5 and in a 3 T MR scanner with two assembled external fixation frames. Forces of the newly designed clamps were more than a factor 2 lower as the gravitational force on the device whereas, magnetic forces on the older devices showed over 10 times the force induced by earth acceleration of gravity. No torque effects could be found for the newly designed clamps. Temperature measurements at the tips of Schanz screws in the 1.5 T MR scanner showed a rise of 0.7 degrees C for a pelvic frame and of 2.1 degrees C for a diamond knee bridge frame when normalized to a specific absorption rate (SAR) of 2 W/kg. The normalized temperature increases in the 3 T MR scanner were 0.9 degrees C for the pelvic frame and 1.1 degrees C for the knee bridge frame. Large external fixation frames assembled with the newly designed clamps (390 Series Clamps), carbon fiber reinforced rods, and implant quality 316L stainless steel Schanz screws met prevailing force and torque limits when tested in a 3-T field, and demonstrated temperature increase that met IEC-60601 guidelines for extremities. The influence of frame-induced eddy currents on the risk of peripheral nerve stimulation was not investigated.

External Fixators↗
PubMed2004

Pedicle clamping with ischemic preconditioning in liver resection.

Hepatic pedicle clamping (HPC) is widely used to control intraoperative bleeding during hepatectomy; intermittent HPC is better tolerated but is associated with blood loss during each period of reperfusion. Recently, it has been shown that ischemic preconditioning (IP) reduces the ischemia-reperfusion damage for up to 30 minutes of continuous clamping in healthy liver. We evaluated the safety of IP for more prolonged periods of continuous clamping in 42 consecutive patients with healthy liver submitted to hepatectomy. IP was used in 21 patients (group A); mean +/- SD of liver ischemia was 54 +/- 19 minutes (range, 27-110; in 7 cases >60 minutes). In the other 21 patients, continuous clamping alone was used (Group B); liver ischemia lasted 36 +/- 14 minutes (range, 13-70; in 2 cases >60 minutes). Two patients in Group A (9.5%) and 3 in Group B (14.2%) received blood transfusions. In spite of the longer duration of ischemia (P=.001), patients with IP had lower aspartate aminotransferase (AST; P=.03) and alanine aminotransferase (ALT; P=not significant) at postoperative day 1, with a similar trend at postoperative day 3. This was reconfirmed by multiple regression analysis, which showed that although postoperative transaminases increased with increasing duration of ischemia and of the operation in both groups, the increases were significantly smaller (P<.001) with the use of preconditioning. In conclusion, the present study confirms that IP is safe and effective for liver resection in healthy liver and is also better tolerated than continuous clamping alone for prolonged periods of ischemia. This technique should be preferred to continuous clamping alone in healthy liver. Additional studies are needed to assess the role of IP in cirrhotic liver and to compare IP with intermittent clamping.

Adult↗
PubMed1994

Delayed onset hypertension with infrarenal aortic cross-clamping in dogs.

The time course and mechanism of systemic hypertension associated with infrarenal aortic cross-clamping were investigated in 31 chloralose-anesthetized dogs after ligating the tail artery, the paired infrarenal lumbar arteries, and the circumflex iliac arteries bilaterally. Cardiac output, renal blood flow, and suprarenal and infrarenal mean arterial blood pressure were continuously monitored. Infrarenal aortic clamping (90 min) in the standard group (n = 6) consistently decreased infrarenal blood pressure from 90 +/- 6 to 13 +/- 1 mm Hg within 1 min, while suprarenal blood pressure gradually increased over 20-30 min from 88 +/- 7 to 144 +/- 8 mm Hg, where it remained until declamp. The SHAM group (identical operation and instrumentation, without aortic clamping) (n = 5) showed no statistically significant changes. After 90 min of clamp total peripheral and renal resistance nearly doubled but no statistically significant changes in cardiac output, heart rate, central venous pressure, renal blood flow, renin, or glomerular filtration rate were detected. Upon declamping, pressures returned to control levels within 20 min. Groups with bilateral nephrectomy (n = 9) or unilateral iliac artery clamping (n = 7) produced similar time courses and patterns of hemodynamic change. Ablation of afferent nerves from the left hind limb (n = 4) eliminated the hypertension produced by left iliac artery clamping. The substantial delay (20-30 min) to the onset and full development of suprarenal hypertension, with near immediate infrarenal hypotension, is not consistent with a direct mechanical impedance effect. Hypertension in the presence of a bilateral nephrectomy or unilateral iliac artery clamping combined with its full reversal by nerve section strongly suggests that this is a reflex hypertension. This reflex mechanism of hypertension development has implications for intra- or perioperative events associated with hypertension management.

Animals↗
PubMed1996

Decrease in internal jugular endothelin levels after carotid cross-clamping during human carotid revascularization procedures.

Endothelin-1 (ETL-1), a peptide recently isolated from vascular endothelial cells, acts in cerebral arteries in vitro as a potent and long-lasting vasoconstrictor and has been implicated in the development of cerebral vasospasm. To ascertain whether this new vasoconstrictor has any effect on regulation of the cerebral circulation, we measured plasma ETL-1 concentrations in patients undergoing carotid revascularization and attempted to correlate the variations of venous and arterial plasma ETL-1 with the characteristics of the procedure, including cerebral vasospasm. We prospectively studied 11 patients undergoing a total of 14 carotid surgical revascularization procedures (12 endarterectomies, 2 polytetrafluoroethylene bypass grafts from the common to the internal carotid arteries). Before carotid cross-clamping, blood samples were drawn from the internal jugular vein and the healthy common carotid artery proximal to the occlusive lesion to be treated. After endarterectomy, blood samples were withdrawn from the internal, external, and common carotid arteries. After the release of the last clamp, a final aliquot of blood was withdrawn from the internal jugular vein. After plasma extraction on a C2-ethyl microcolumn, plasma endothelin-like immunoreactivity was measured by means of radioimmunoassay with a polyclonal antibody. In 9 of the 11 patients, internal jugular vein ETL-1 concentration decreased statistically significantly after carotid artery cross-clamping (4.2 +/- 1.4 pg/ml vs. 3.9 +/- 1.1 pg/ml; p < 0.05). In the 2 patients in whom ETL-1 levels failed to drop, a shunt was used during the procedure in 1, and the other was the only patient who had an ipsilateral ischemic postoperative stroke. The decrease in internal jugular vein ETL-1 concentration failed to correlate with any of the cross-clamping times. The level of arterial blood ETL-1 remained steady in the common carotid artery before and after cross-clamping (4.5 +/- 1.5 pg/ml vs. 4.6 +/- 0.9 pg/ml). A small, nonsignificant decrease in ETL-1 level was noted in the external and internal carotid arteries after cross-clamping. The decrease in internal jugular vein ETL-1 levels may in part reflect a compensatory response to carotid artery cross-clamping, which could limit the reduction of local cerebral blood flow.

Blood Vessel Prosthesis↗
PubMed1990

Increased therapeutic effect on metastatic liver tumors in rats of two-route chemotherapy using cis-diamminedichloroplatinum (II) and its antidote, sodium thiosulfate, with temporary clamping of the abdominal aorta.

To improve the therapeutic effects of conventional "two-route chemotherapy" (TRC) comprising cis-diamminedichloroplatinum(II) (CDDP) given via the hepatic artery plus simultaneous i.v. sodium thiosulfate (STS) on metastatic liver tumors in rats, we combined TRC with aortic clamping at the supraceliac level. Treatments were evaluated in Wistar-King-Aptekman (WKA) rats bearing metastatic liver tumors 7 days after the inoculation of 10(6) syngenic RBT-1 (transitional-cell carcinoma) cells via the mesenteric vein. When 15 mg/kg CDDP was injected i.a. over 5 min, immediately followed by STS 1,580 mg/kg (200-fold the molar equivalent of 15 mg/kg CDDP) given i.v. over a further 5 min, the antitumor activity, evaluated by the number of tumor nodules present 12 days after treatment, was superior to that of conventional TRC (15 mg/kg i.a. CDDP plus simultaneous administration of 1,580 mg/kg i.v. STS), but the blood urea nitrogen (BUN) level was highly elevated (63.6 mg/dl). With aortic clamping for 7.5 min during CDDP administration and the first half of STS treatment, the TRC consisting of CDDP plus delayed STS (modified TRC) exhibited a further improvement in antitumor activity, with no nephrotoxicity (BUN, 17.1 mg/dl). Although the antitumor activity of 3 or 5 mg/kg i.a. CDDP was also increased by aortic clamping, in animals with normal BUN levels the survival of those treated with modified TRC was greater than that of rodents given 3 mg/kg i.a. CDDP with aortic clamping; however, the former was the same as that of animals given 5 mg/kg i.a. CDDP with aortic clamping whose BUN levels were elevated (31.2 mg/dl). Loss of body weight, the decrease in WBC counts, and changes in the serum transaminase levels in rats given modified TRC were tolerable. The improved therapeutic effect of modified TRC can be explained as follows: during aortic clamping, (a) CDDP delivery to the kidney decreased by 96% and made feasible the delay in STS administration after CDDP without nephrotoxicity, and (b) CDDP retention in the liver was increased by 366%, as aortic clamping decreased the portal blood flow, thereby inhibiting the washout of CDDP from the liver.

Animals↗
PubMed2000

Postoperative renal function after an abdominal aortic aneurysm repair requiring a suprarenal aortic cross-clamp.

We describe herein the postoperative renal functions of patients who required a suprarenal aortic cross-clamp during abdominal aortic surgery. Seven patients required a unilateral suprarenal aortic cross-clamp (group A) and six patients required a bilateral suprarenal clamp (group B). Eighty-three patients who required an infrarenal aortic clamp were assigned to group C. Renal hypothermia with renal perfusion or topical cooling during suprarenal clamp was not performed. No hospital deaths were encountered. In group B, the postoperative creatinine and blood urea nitrogen (BUN) levels remained statistically significantly higher than that of group C until the seventh postoperative day. The postoperative renal dysfunction (serum creatinine level >2.0 mg/dl) was 28.6% in group A and 50% in group B, while it was only 8.4% in group C, although no patient required either temporary or permanent hemodialysis. The postoperative peak BUN over 30 min suprarenal clamp was significantly higher than that within 30 min. In summary, the postoperative renal function was impaired after an extended bilateral suprarenal clamp. These findings suggest that if prolonged renal ischemia is thus expected, then renal preservation should be considered.

Aged↗