Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CLAMPS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed2006

Topical lidocaine effectively reduced the increase of systolic blood pressure after side-clamping of the aorta in off-pump cardiac surgery.

BACKGROUND: Side-clamping of the ascending aorta during off-pump coronary artery bypass surgery (OPCAB) may be associated with a significant increase in systemic blood pressure which may rarely result in aortic dissection. We evaluated whether topical application of lidocaine on the ascending aorta could reduce the rise in systemic blood pressure during side-clamping of the aorta in OPCAB. METHODS: Forty-four patients scheduled for OPCAB were randomly allocated to receive gauze soaked with 10 ml of 4% lidocaine (n = 22) or normal saline (n = 22) on the side-clamping site of the aorta. Sodium nitroprusside (SNP) was infused as necessary to maintain the systolic blood pressure at around 100 mmHg immediately prior to and during side-clamp of the aorta. The requirement and frequency of use of SNP, as well as haemodynamic variables, were recorded serially. RESULTS: The number of patients requiring an SNP infusion and the average amount of infused SNP were significantly less in the lidocaine group. Systolic blood pressure increased significantly during side-clamping in the control group, but not in the lidocaine group. CONCLUSION: Topical application of lidocaine on the surface of the aorta is a simple and effective method to reduce the risk of a sudden increase in systemic blood pressure during side-clamping of the aorta.

Administration, Topical↗
PubMed2005

Nephron-sparing surgery for renal tumours using selective renal parenchymal clamping.

OBJECTIVE: To describe a technical modification that facilitates nephron-sparing surgery (NSS) for renal tumours, without clamping the renal pedicle or promoting renal surface hypothermia. PATIENTS AND METHODS: Seventeen patients with renal tumours had NSS using the selective renal-parenchymal clamping technique. In 11 patients the tumour was polar and in six it was central. The mean (range) size of the tumours was 3.6 (2-6) cm. The technique was performed using one or two large Satinsky vascular clamps. Time was not limited as there was no clamping of the renal pedicle, or renal hypothermia. RESULTS: The mean (range) operative duration was 190 (120-300) min. Only one patient needed a blood transfusion. There were no complications in 13 patients after NSS. The mean (range) hospital stay was 5 (3-12) days. The pathological examination detected malignant tumours in 13 patients, and a microscopic examination showed adequate surgical margins in all. The mean (range) follow-up was 24.5 (4-60) months. No patients required haemodialysis immediately after surgery or later. CONCLUSIONS: Selective renal parenchymal clamping is a simple and efficient technical manoeuvre that facilitates NSS without dissection or clamping of the renal pedicle. Time is not limited as the ischaemia is limited to the tissue surrounding the tumour. The operative duration and blood loss are acceptable and the complications similar to those with the conventional technique. The size and position of the tumour could be limiting factors to this technique.

Adult↗
PubMed2006

The alcohol clamp: applications, challenges, and new directions--an RSA 2004 symposium summary.

This article summarizes the proceedings of a symposium organized and cochaired by Vijay Ramchandani and Sean O'Connor and presented at the 2004 Research Society on Alcoholism meeting in Vancouver, BC, Canada. The objectives of this symposium were: (1) to provide a rationale for the development and use of the alcohol clamp and the requirements for its use in alcohol challenge studies; (2) to highlight recent studies conducted using the alcohol clamp to identify sources of variation in the pharmacokinetics and pharmacodynamics of alcohol, as well as to address important research questions related to the relationship between the response to alcohol and the risk for alcoholism; and (3) to provide a perspective on progress, address limitations of the clamp, and identify new directions for alcohol challenge research. The symposium began with an introduction and overview of the alcohol clamp, by Vijay Ramchandani. This was followed by 4 presentations that highlighted recent studies conducted using the clamp including: (1) determination of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in a male Jewish population, by Yehuda Neumark; (2) examination of family history of alcoholism, recent drinking history, and levels and rates of administration as determinants of the response to alcohol and risk for alcoholism, by Sean O'Connor; (3) evaluation of the time course of ethanol intoxication on neuroendocrine function in humans, by Ulrich Zimmermann; and (4) a study of the effects of steady-state blood alcohol levels on auditory event-related potentials in rats, by Sandra Morzorati. Harriet de Wit summarized and discussed the research presented at the symposium and provided her perspective on future directions for research using the alcohol clamp.

Alcohol Dehydrogenase↗
PubMed1990

Force production following transient potential changes in voltage-clamped myocardium.

Inter-relationships between force, membrane voltage and currents were studied in ferret and guinea-pig papillary muscles using the single sucrose gap technique (37 degrees C). The preparations were held at -90 or -40 mV and depolarized (excited) to 0 mV for 180 ms at 1.0 Hz. At regular intervals the shape of a single clamp pulse (called '1') was varied and its effects were investigated during the same test cycle and in two subsequent test cycles ('2' and '3'). Peak force of contraction 1 (F1) increased with the duration of the test clamp up to 90 ms and was constant thereafter. F1 increased with clamp amplitude (V1) between -30 and 10 mV and decreased at greater amplitudes. This relation was similar to the relation between peak second inward current (I1) and V1. The peak force of contractions 2 and 3 rose with the clamp duration and clamp amplitudes of cycle 1. The relation between F3 and F2 was linear (slope 0.40), except at the lowest and highest F2 values where there was a small deviation. There was an inverse relation between I2 and F2. The results support the idea that increased duration or amplitude of the voltage clamp pulse leads to a greater calcium entry which is manifested in the following potentiated contraction. The relation between F3 and F2 implies that about 40% of calcium recirculates between the contractions. The inverse relationship between F2 and I2 indicates that the second inward current is regulated by release from the sarcoplasmic reticulum via negative feedback.

Animals↗
PubMed1977

Measurement of transmembrane potential and current in cardiac muscle: a new voltage clamp method.

1. A single sucrose gap voltage clamp technique was developed to correct for artifacts of 'leakage' corrent and extracellular resistance making possible improved measurement of membrane current and membrane potential in cardiac muscle. 2. A fourth compartment termed 'guard gap' was added to the sucrose gap. The guard gap is maintained at the same potential as the Reinger pool, so that no extracellular leakage current can flow into the Ringer pool. Comparison of experimental results with the predictions of an idealized cable model indicates that the guard gap is effective in trapping leakage current. 3. The slow charging of membrane capacitance due to extracellular series resistance was accelerated by applying a 'pre-pulse' of the command potential past the final voltage clamp value. 4. A second technique, termed 'chopped current pulse clamp', was used to compensate for the extracellular resistance throughout the voltage clamp step. The applied current was turned on and off at a frequency of 0-5-2 kHz. The membrane potential sampled during the zero current phase was fed back through the clamp loop. 5. With either of these compensation techniques, the voltage and current traces settle to effectively constant values within 2-4 msec after initiation of a hyperpolarizing voltage clamp step from rest. 6. The membrane conductance measured by the prepulse and chopped current-pulse technique are equal and confirm a higher conductance at rest than during the plateau of the action potential. 7. The 'instantaneous' current-voltage relation of the membrane is linear during the plateau of the frog ventricular action potential.

Action Potentials↗
PubMed1980

Voltage clamp of cat motoneurone somata: properties of the fast inward current.

1. The soma membrane of cat spinal motoneurones was voltage clamped using separate intracellular voltage and current electrodes directed into the same motoneurone with a new guide system. 2. Antidromic stimulation of the motoneurone's axon or small depolarizing voltage clamp steps (10-20 mV from the resting potential) evoked a small (30-80 nA) all-or-none action potential current, which was shown by occlusion experiments to originate from the initial segment of the axon. Except for this axonal current spike, there was no indication of active (voltage-dependent) conductance changes in membrane regions not under good voltage clamp control. Calculations based on motoneuronal geometry, and electrophysiological recordings from spinal cord neurones in tissue culture, indicate that the proximal portions of dendritic membranes were also under good voltage clamp control. 3. Clamp depolarizations greater than 20 mV activated a fast, transient inward current, which increased in a smoothly graded manner with depolarization between 20 and 40 mV from the resting potential, reaching a peak magnitude of up to 450 nA, and then decreased smoothly for larger depolarizations. Extrapolation of the current-voltage relationship for this current indicated a reversal potential about 80-116 mV positive to the resting potential. 4. This transient inward current is blocked by tetrodotoxin. After a depolarizing voltage clamp step the conductance system controlling this current first activates with fast, non-linear kinetics, and then inactivates with first-order kinetics. These properties are similar to those of the Na conductance system in squid and frog axons. 5. Conditioning-testing experiments showed that the time constant of inactivation ranges from 1.0-1.3 msec at potentials slightly negative to the resting potential to 0.1-0.3 msec for depolarizations 60 mV from the resting potential. The degree of steady-state inactivation also varied with membrane potential, ranging from total inactivation at depolarizations greater than 30 mV from the resting potential, to minimal inactivation at potentials more than 10 mV negative to the resting potential.

Action Potentials↗
PubMed1985

Calcium entry into voltage-clamped presynaptic terminals of squid.

Voltage-clamp measurements of Ca current and Arsenazo III measurements of intracellular Ca concentration were used to assess Ca ion entry into voltage-clamped presynaptic terminals of squid 'giant' synapses. Depolarization of voltage-clamped terminals filled with Arsenazo III produced absorbance changes consistent with intracellular accumulation of Ca ions. These intracellular Ca transients had a bell-shaped dependence on presynaptic potential and were maximal at approximately -10 mV. Arsenazo III signals recorded from the proximal portion of voltage-clamped presynaptic terminals had a dependence on command potential which was shifted relative to signals recorded from other presynaptic regions. Micro-electrode measurements of presynaptic membrane potential showed that during voltage-clamp depolarizations the proximal region was less depolarized than the rest of the presynaptic terminal. This indicates that voltage-clamped presynaptic terminals may be poorly controlled at their proximal region due to current flow into the adjacent axon. This poor control can cause heterogeneous Ca entry into the presynaptic terminal and thus heterogeneous release of transmitter along the terminal. Application of Ca ions from an extracellular pipette positioned near the distal end of the presynaptic terminal was used to restrict Ca entry to this well-controlled region. Local Ca application decreased the contribution of release from the poorly controlled proximal region to synaptic transfer curves. Presynaptic Ca currents were derived by correcting membrane currents for leakage and capacitive currents and other currents measured in the absence of Ca application. Ca currents measured in this way activated along a sigmoidal time course and did not inactivate for depolarizations as long as 25 ms. Peak Ca currents occurred at approximately -10 mV and inward Ca currents had an apparent 'reversal potential' near +60 mV. Ca channel activation, assessed with tail current measurements, was half-maximal at -13 mV and maximal at +20 mV. Simultaneous measurements of presynaptic Ca currents and Arsenazo III transients revealed a quantitative correspondence between Ca current integrals and Arsenazo III signal amplitude. This suggests that both methods provide reliable measures of Ca ion entry into presynaptic terminals under these conditions.

Action Potentials↗
PubMed1998

Efficiency and frequency of translational coupling between the bacteriophage T4 clamp loader genes.

The bacteriophage T4 DNA polymerase holoenzyme is composed of the core polymerase, gene product 43 (gp43), in association with the "sliding clamp" of the T4 system, gp45. Sliding clamps are the processivity factors of DNA replication systems. The T4 sliding clamp comes to encircle DNA via the "clamp loader" activity inherent in two other T4 proteins: 44 and 62. These proteins assemble into a pentameric complex with a precise 4:1 stoichiometry of proteins 44 and 62. Previous work established that T4 genes 44 and 62, which are directly adjacent on polycistronic mRNA molecules, are-to some degree-translationally coupled. In the present study, measurement of the levels (monomers/cell) of the clamp loader subunits during the course of various T4 infections in different host cell backgrounds was accomplished by quantitative immunoblotting. The efficiency of translational coupling was obtained by determining the in vivo levels of gp62 that were synthesized when its translation was either coupled to or uncoupled from the upstream translation of gene 44. Levels of gp44 were also measured to determine the relative stoichiometry of synthesis and the percentage of gp44 translation that was transmitted across the intercistronic junction (coupling frequency). The results indicated a coupling efficiency of approximately 85% and a coupling frequency of approximately 25% between the 44-62 gene pair during the course of infection. Thus, translational coupling is the major factor in maintaining the 4:1 stoichiometry of synthesis of the clamp loader subunits. However, coupling does not appear to be an absolute requirement for the synthesis of gp62.

Bacteriophage T4↗
PubMed1989

Cyclosporin A pharmacokinetics in liver transplant recipients in relation to biliary T-tube clamping and liver dysfunction.

Cyclosporin A pharmacokinetics were studied after oral (4-14 mg/kg body weight) and intravenous dosing (1.5-3.5 mg/kg) in 13 orthotopic liver transplant recipients before and after permanent clamping of the biliary T-tube. After T-tube clamping, cyclosporin A absorption was faster and more complete with the mean time of peak concentration, tmax, reduced to around three hours from around six hours and mean bioavailability rising from only 16.6% (n = 13) to 30% in the entire group (n = 11 after clamping) or to 35% after excluding two patients who developed severe cholestasis after the preclamping study. Bioavailability in these two patients fell below 8% and to around 1% in a further patient with severe graft dysfunction. Clamping reduced the metabolic clearance of cyclosporin A by only 25% from a mean before clamping of 2.9 ml/min/kg to 2.3 ml/min/kg (n = 11). Oral cyclosporin A becomes a reliable means of maintaining therapeutic drug concentrations only after bioavailability increases in association with T-tube clamping and in the absence of severe liver dysfunction or cholestasis.

Absorption↗
PubMed1995

Effect of sodium nitroprusside on cardiac output during cross-clamping of the descending thoracic aorta in pigs.

Sodium nitroprusside (SNP) is used to control proximal hypertension during cross-clamping of the descending thoracic aorta (XC). To assess the haemodynamic effects of SNP on cardiac output (CO) during XC, 21 pigs were anaesthetized with ketamine and fentanyl. In the control group (n = 11), no vasodilating therapy was given. In the investigation group (SNP group), 2 animals died during the surgical preparation and were excluded, leaving 8 animals in the group (n = 8). In these animals, SNP was infused in order to keep the mean arterial pressure (MAP) at about 100 mm Hg during cross-clamping. In both groups, aorta was cross-clamped for 30 min, and cardiac output (CO) was measured by the thermodilution technique. Following cross-clamping, CO increased 107% in the control group and 96% in the SNP group. There was an increase in heart rate (HR) of 77% in the control group and of 110% in the SNP group, and a reduction in systemic vascular resistance of 41% in the SNP group. Stroke volume (SV) was unchanged in both groups. MAP increased 83% in the control-group. No differences were observed between the two groups regarding central venous pressure or pulmonary artery pressure. Four animals in the SNP group died 5-10 min after release of the aortic clamp. In conclusion, we found equal increase in CO in both groups. The increase in CO was related predominantly to increased HR, whereas SV was largely unaltered. Vasodilation with SNP increased the mortality following clamp removal in this experimental model.

Animals↗
PubMed1994

Cerebral emboli detected during bypass surgery are associated with clamp removal.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasonography detects embolic signals during coronary artery bypass surgery. The relationship between embolization and specific events of bypass surgery is unclear. METHODS: With this technique, 20 patients undergoing bypass surgery were continuously monitored from inception to discontinuation of bypass. RESULTS: Embolic signals were detected in all patients. Of all embolic signals, 34% were detected as aortic cross-clamps were removed, and another 24% as aortic partial occlusion clamps were removed. Only 5% were detected at inception of bypass. Rates for embolization were 15.15 embolic signals per minute at cross-clamp removal, 10.9 embolic signals per minute at partial occlusion clamp removal, and fewer than 3 embolic signals per minute at other times. Correlation was found between the number of emboli, severity of aortic atheromatosis, and neurocognitive deterioration. CONCLUSIONS: The majority of emboli detected during coronary artery bypass grafting are associated with the release of clamps. Clamp manipulation may lead to release of aortic atheromatous debris. These emboli may be relevant to neurocognitive outcome.

Aged↗
PubMedDate not supplied

Cerebral oximetry monitoring during carotid endarterectomy: effect of carotid clamping and shunting.

Cerebral oximetry is a simple method of measuring regional cerebral oxygen saturation (rSO(2)). One promising application is its use during carotid endarterectomy (CEA) to help minimize the risk of perioperative stroke. The authors used the INVOS-4100 cerebral oximeter at several steps during CEA to measure the effect of carotid clamping and shunting on rSO(2). The authors prospectively evaluated 42 consecutive CEAs in 40 patients. All had CEA under general anesthesia with the routine use of a Javid shunt. The INVOS-4100 oximeter was used to measure rSO(2) before clamping (t1), after clamping but before shunting (t2), 5 minutes after shunt insertion (t3), and after patch closure with reestablished flow (t4). The Wilcoxon signed-rank and rank-sum tests were used for analysis. Clamping of the internal carotid artery (t1 vs t2) resulted in a drop of ipsilateral rSO(2) by -12.3% (p < 0.001). Shunt insertion (t2 vs t3) increased rSO(2) by 10.9% (p < 0.001). Contralateral rSO(2) for the same time periods was insignificant. Patients with preoperative neurologic symptoms had a greater decrease in rSO(2) after clamping (-18.4%) compared with a decrease of -10.4% in asymptomatic patients (p = 0.037). Cerebral oximetry monitoring is simple and inexpensive. The study showed statistically significant changes in rSO(2) as a result of clamping and shunting of the carotid artery. Symptomatic patients had a greater drop in rSO(2).

Aged↗
PubMed2004

Late umbilical cord-clamping as an intervention for reducing iron deficiency anaemia in term infants in developing and industrialised countries: a systematic review.

This review evaluates the potential of delayed cord-clamping for improving iron status and reducing anaemia in term infants and for increasing the risk of polycythaemia and hyperbilirubinaemia. We applied a strict search protocol to identify controlled trials of early vs late cord-clamping. Four trials from developing and four from industrialised countries were finally assessed. Two of the four studies from developing countries found a significant difference in infant haemoglobin levels at 2-3 months of age in favour of delayed cord-clamping. This difference was more marked when mothers were anaemic. Three of four studies from industrialised countries showed a significant difference in haematocrit levels in favour of delayed clamping. Although meta-analysis showed an increased risk for hyperbilirubinaemia of 12%, no studies reported the need to apply phototherapy or perform exchange transfusion. We conclude that delayed cord-clamping in term infants, especially those with anaemic mothers, increases haemoglobin concentration in infants at 2-3 months of age and reduces the risk of anaemia, without an associated increased risk of perinatal complications. In developing countries where fetal anaemia is common, the advantages of delayed cord-clamping might be especially beneficial.

Anemia, Iron-Deficiency↗
PubMed2002

Acute changes of bone turnover and PTH induced by insulin and glucose: euglycemic and hypoglycemic hyperinsulinemic clamp studies.

Bone turnover is acutely suppressed after feeding or oral glucose. Insulin infusion suppresses bone turnover and might mediate this effect, but this is confounded by a possible direct effect of hypoglycemia. We examined the effect of euglycemic hyperinsulinemia and hypoglycemic hyperinsulinemia on bone turnover using an insulin clamp. Sixteen men participated in this double-blind crossover study. Clamp induction involved infusion of insulin (80 mU/m(2).min) while maintaining euglycemia (5 mmol/liter) for 40 min with a variable rate dextrose infusion. Glucose was lowered to 2.5 mmol/liter (hypoglycemic clamp) or maintained at 5 mmol/liter (euglycemic clamp) for a further 105 min. Nine controls received a matched saline infusion. Measurements included serum C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide, osteocalcin, and PTH. Induction of hyperinsulinemia resulted in a reduction in PTH (27% +/- 5; P < 0.01), but no significant change in bone turnover from baseline. Hypoglycemic clamp resulted in suppression of serum C-terminal telopeptide of type I collagen by 34% +/- 3, procollagen type I N-terminal propeptide by 15% +/- 1, osteocalcin by 5% +/- 1, and PTH by a further 12% +/- 5 (all P < 0.05). By contrast, there was no significant change in any marker of bone turnover during euglycemic clamp. Postprandial hyperinsulinemia is unlikely to explain the acute suppression of bone turnover with feeding. The reduction in bone turnover during hypoglycemia may be related to hypoglycemia itself, acute changes in PTH, or other hormones released in response to hypoglycemia.

Adult↗
PubMedDate not supplied

Cardiovascular responses to clamping of the aorta during epidural and general anesthesia.

The cardiovascular responses of aortic cross-clamping and declamping with normal and high ventricular filling pressures were compared during epidural and nitrous oxide-morphine anesthesia in 32 male patients undergoing reconstructive aortic surgery. The patients were divided into four groups. Groups I and II had lumbar epidural blocks with bupivacaine and received nitrous oxide in oxygen to breathe; groups III and IV were anesthetized with morphine (2 mg/kg) and nitrous oxide. During aortic occlusion groups I and III received Ringer's lactate at a rate which maintained mean pulmonary capillary wedge pressure (PCWP) 3 to 4 torr above pre-anesthetic values whereas groups II and IV were given Ringer's lactate rates which kept PCWP similar to pre-anesthetic values. Prior to cross-clamping mean arterial blood pressure and systemic vascular resistance were lower in groups I and II than in groups III and IV but cardiac output, PCWP, and pulmonary vascular resistance were similar in the four gropus. Cross-clamping of the aorta produced no significant change in any cardiovascular variable measured in any group. Declamping did not significantly alter any variable in groups I and III but produced moderate hypotension in group IV and severe hypotension in group II as well as significant decreases in PCWP in both groups. Our data demonstrate that aortic cross-clamping and release result in little change in cardiovascular dynamics in patients anesthetized with epidural or morphine-nitrous oxide and given balanced salt solutions intravenously in amounts adequate to increase left ventricular filling pressures prior to release of the aortic cross-clamp. Our findings also indicate that hypotension can occur in patients in whom left ventricular filling pressures are maintained at normal levels prior to cross-clamp release, especially in patients given epidural anesthesia.

Aged↗
PubMed1995

Detachable clamps for minimal access surgery.

A detachable clamp and applicator have been developed for use in minimal access surgical operations involving hollow visceral transection and anastomosis. The clamp has parallel jaws which ensure uniform distribution of the occlusive force. Following application on the bowel, the clamp is released from the applicator, thus freeing the access port. On completion of the anastomosis, the clamp is docked to the applicator, its jaws opened for release from the bowel and then closed prior to removal. The jaws of the clamp are kept closed by a pseudoelastic nickel-titanium (NiTi) alloy spring which imparts advantageous force characteristics when compared to stainless steel. The excellent holding and atraumatic characteristics of the detachable clamp have been confirmed by use in laparoscopic and thoracoscopic surgery on the gastrointestinal tract.

Colectomy↗
PubMed1982

A minimal-model-based glucose clamp yielding insulin sensitivity independent of glycemia.

A new technique is introduced for automatic control of the blood sugar ("glucose clamp") at basal (euglycemic) or elevated (hyperglycemic) levels during variable insulin infusion. A minimal mathematical model of glucose kinetics is implemented on a laboratory minicomputer during clamp experiments. From the measured time course of plasma glucose concentration, the computer estimates the fractional disappearance rate of glucose (X) and calculates the rate of exogenous infusion required to match the desired concentration (M). Eight clamp experiments were performed on three conscious dogs. Euglycemic (N = 4): insulin was infused at 8, 40, and 150 microU/min for sequential 2.5-h periods )I, II, and III); hyperglycemic (N = 4): following the establishment of 140 mg/dl hyperglycemia (period I), insulin was infused at 30 and 120 mU/min for 2.5 h each (periods II and III). Plasma insulin levels [range: 21 +/- 9 (basal) to 1729 +/- 209 microunits/ml] were matched in comparable periods in the two types of experiments [P greater than 0.8 (I); P greater than 0.5 (II), P greater than 0.2 (III)]. Glucose was successfully clamped for all periods at euglycemia (99.6 +/- 0.7% of desired value) and hyperglycemia (100.0 +/- 1.1% desired 140-mg/dl value). Glucose infusion rates necessary to achieve stable glycemia were greater at elevated than basal glucose (P less than 0.001) despite comparable insulinemia during the three insulin infusion periods. Thus, the glucose infusion rate versus insulin level (M/I) was glycemia-dependent, and therefore not a direct measure of insulin sensitivity. In contrast, the insulin-induced increases in fractional glucose disappearance (delta X), also provided by our clamp technique during experiments, were highly correlated within insulin (r = 0.08 to r = 0.99, P less than 0.01) and independent of glycemia (P greater than 0.7). The ratio delta X/delta I (increase in glucose fractional disappearance rate/incremental insulin level) was a measure of insulin sensitivity independent of glycemia, and could successfully differentiate insulin-resistant from normal animals (P less than 0.001; delta X/delta I in three animals: 6.9 X 10(-4), 5.5 X 10(-4), and 1.4 X 10(-4) min-1 microunits/ml). Thus, this model-dependent glucose clamp technique provides a direct measurement of insulin sensitivity independent of glycemia.

Animals↗
PubMed1988

Modeling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps.

We previously demonstrated that conventional tracer methods applied to euglycemic-hyperinsulinemic glucose clamps result in substantially negative estimates for the rate of endogenous glucose production, particularly during the first half of 180-min clamps. We also showed that addition of tracer to the exogenous glucose infusate resulted in nonnegative endogenous glucose production (Ra) estimates. In this study, we investigated the underlying cause of negative estimates of Ra from conventional clamp/tracer methods and the reason for the difference in estimates when tracer is added to the exogenous glucose infusate. We performed euglycemic-hyperinsulinemic (300-microU/ml) clamps in normal dogs without (cold GINF protocol, n = 6) or with (hot GINF protocol, n = 6) tracer (D-[3-3H]glucose) added to the exogenous glucose infusate. In the hot GINF protocol, sufficient tracer was added to the exogenous glucose infusate such that arterial plasma specific activity (SAa) did not change from basal through the clamp period (P greater than .05). In the cold GINF studies, plasma SAa fell 81 +/- 2% from the basal level by the 3rd h of clamping. We observed a significant, transient, positive venous-arterial difference in specific activity (SAv-SAa difference) during the cold GINF studies. The SAv-SAa difference reached a peak of 27 +/- 6% at 30 min and diminished to a plateau of 7 +/- 1% between 70 and 180 min. We also observed a positive but constant SAv-SAa difference (4.6 +/- 0.2% between 10 and 180 min) during the hot GINF studies. The observations of a difference between hot and cold GINF endogenous Ra estimates and a positive but transient SAv-SAa difference during the cold GINF studies are consistent with the interpretation that a portion of the underestimation of Ra is due to insufficient mixing of endogenous and exogenous glucose for the one-compartment, fixed-pool volume model to be applicable. Alternatively, our results suggest that the one-compartment, fixed-pool volume model of glucose kinetics is insufficient to account for the complex dynamics of labeled and unlabeled glucose during euglycemic-hyperinsulinemic clamps. Improved mixing through addition of tracer to the exogenous glucose infusate or improved modeling by allowing for a variable-pool volume appears to improve the accuracy of the tracer methods; however, these approaches remain to be validated. The constant positive SAv-SAa difference observed during the hot GINF studies is consistent with the interpretation that an additional contributor to underestimation of endogenous Ra is apparent isotope discrimination.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗