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PubMed2003

Accurate control of the superficial and deep dorsal veins during radical retropubic prostatectomy: the Münster clamp technique.

OBJECTIVE: To better control the superficial and deep dorsal veins during radical retropubic prostatectomy and, thus, to reduce blood loss. PATIENTS AND METHODS: A surgical technique is described which introduces a modified Babcock clamp to fully encompass all tissue above the prostatic capsule. In a prospective protocol, 30 consecutive patients (median age 64.5, range 57-76 years) were randomly assigned to either the standard technique or the Münster clamp method. Blood loss was estimated for the entire phase from teasing away the periprostatic fat until the apex had been mobilized. RESULTS: Median hemorrhage was 950 (range 300-2,100) ml for the standard technique and 800 (range 200-1,750) ml for the clamp procedure (Wilcoxon rank sum test, p = 0.17). CONCLUSIONS: The Münster clamp technique can reduce hemorrhage during radical retropubic prostatectomy. This method is easy to apply and is also suitable for cystoprostatectomy.

Hemostasis, Surgical↗

PubMed2003

Early cord clamping protects at-risk neonates from polycythemia.

UNLABELLED: Neonatal polycythemia is a potentially lethal, multi-organ disease. We have performed a prospective, open-label study to test the hypothesis that an early cord clamping proximally to the neonate's abdomen could avert from the neonatal circulation a blood volume critical to the occurrence of polycythemia in at-risk neonates. Newborns were divided into group 1 (clamping time within 10 s) and group 2 (clamping time 11-120 s). Group 1 had statistically significant more blood volume sequestered in the cord and less manifestations of polycythemia. CONCLUSION: An early cord clamping is an effective and zero-cost way to prevent polycythemia in at-risk neonates.

Blood Volume↗

PubMed1986

Influence of mannitol and dopamine on renal function during elective infrarenal aortic clamping in man.

The impact of elective infrarenal aortic clamping on parameters of renal function was evaluated in 27 extracellular fluid volume expanded patients. Significant transient decreases (p less than 0.05) in glomerular filtration rate were observed in all three groups either in the early or late post-clamp release period, despite maintenance of hemodynamic stability. This study documents transient decreases in glomerular filtration rate which occurred following release of the infrarenal aortic cross-clamp. No clinically important benefit from the use of mannitol and dopamine over extracellular fluid volume expansion with saline alone was demonstrated in the prevention of the changes in renal function associated with aortic cross-clamping.

Adult↗

PubMed1997

Insulin sensitivity, vascular reactivity, and clamp-induced vasodilatation in essential hypertension.

BACKGROUND: Insulin resistance and vascular abnormalities have both been described in patients with essential hypertension. Whether these defects are associated with one another in the same individual has not been established. METHODS AND RESULTS: Whole-body insulin sensitivity (by the insulin clamp technique), forearm minimal vascular resistances, and the dose-response curve to acetylcholine, sodium-nitroprusside, and norepinephrine were measured in a group of 29 male patients with untreated essential hypertension. When the patients were divided into tertiles according to their level of insulin sensitivity, resistant and sensitive hypertensives were matched on several potential confounders of insulin action and vascular function. These subgroups showed similar minimal vascular resistances (2.5+/-0.2 versus 3.2+/-0.6 mm Hg per mL x min(-1) x dL(-1)) and superimposable responses to graded intraarterial infusions of acetylcholine, sodium-nitroprusside, and norepinephrine. No correlation was found between the vascular parameters (slope of the curve or maximal response) and insulin-mediated glucose uptake in the whole group. During the clamp, insulin sensitive patients tended to have greater increments in forearm blood flow when compared to their insulin resistant counterparts (+53+/-21 versus +9+/-7%, P=.06); in the whole group, clamp-induced vasodilatation was weakly related to insulin-mediated glucose uptake (r=.44, P<.02) as well as to the slope of the acetylcholine dose-response curve (r=.40, P<.04). Together, these two responses explained 30% (multiple r=.55, P<.01) of the variability in insulin-induced vasodilatation. CONCLUSIONS: Metabolic insulin resistance in essential hypertension is not associated with abnormalities in vascular structure, acetylcholine or nitroprusside-induced vasodilatation, or vascular adrenergic reactivity. Degree of insulin sensitivity and acetylcholine sensitivity explain a small portion of the variability of the clamp-induced vasodilatation in hypertensive patients.

Acetylcholine↗

PubMed1995

Stimulation of endogenous nitric oxide pathway by L-arginine reduces declamp mortality and attenuates hypertension associated with aortic cross-clamp-induced hindlimb ischemia in rats.

We tested the hypotheses that maintaining the activity of nitric oxide by L-arginine infusion would counteract the release of an endogenous nitric oxide synthase inhibitor, improve survival, and decrease intraoperative hypertension after infrarenal aortic cross-clamp surgery. Hindlimb ischemia was generated by infrarenal aortic cross-clamping and tying of the left femoral artery for 5 hours in rats with bilateral femoral and sciatic nerves cut. Mean blood pressure significantly increased during the 5-hour ischemic period in ischemic rats (no drug treatment). Baroreceptor function was inhibited in ischemic rats assessed by intravenous dose response to phenylephrine and nitroprusside after 5 hours of ischemia, suggesting baroreceptor resetting. In ischemic rats infused with L-arginine the intraoperative hypertension was prevented during the 5-hour period, suggesting that this hypertension may be mediated by nitric oxide inhibition. The rates of survival and arrhythmias 2 hours after declamping were 50% in ischemic rats and 100% in ischemic rats treated with N omega-nitro-L-arginine (a nitric oxide synthase inhibitor) 10 minutes before declamping. In ischemic rats infused with L-arginine the survival rate was significantly increased to 100% and the arrhythmic rate was inhibited. We conclude that L-arginine prevents hypertension during cross-clamping and decreases the mortality rate and arrhythmias after declamping by maintaining nitric oxide synthesis. These results suggest that humoral factors released from the ischemic hindlimb may inhibit endogenous nitric oxide production, thus contributing to intraoperative hypertension, arrhythmias, and high mortality rate after aortic cross-clamp surgery.

Animals↗

PubMed2006

Delayed umbilical cord clamping for reducing anaemia in low birthweight infants: implications for developing countries.

BACKGROUND: Cheap and effective interventions are needed to reduce the risk of infant anaemia in developing countries. Delayed cord clamping (DCC) has been shown to be a simple, safe and cost-free delivery procedure that augments red cell mass in appropriate-for-gestational-age term and preterm infants. It is not known, however, whether DCC is similarly safe and effective in small-for-gestational-age (SGA) infants. We analysed the available evidence to generate a balanced inference on the use of DCC in developing countries. OBJECTIVES: To examine the short- and long-term effects in SGA infants of DCC compared with immediate clamping, and to assess the relationship between time of clamping and the potential postnatal haematological complications of DCC in SGA infants. SEARCH STRATEGY: PubMed (1966 to January 2006), EMBASE (1988 to January 2006) and The Cochrane Library (Issue 1, 2006) were searched. Reference lists of published trials were examined and major journals of perinatal and tropical medicine were hand-searched. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing delayed with immediate cord clamping in infants born between 30 and 42 completed weeks of gestation and which included a proportion of SGA infants. DATA COLLECTION AND ANALYSIS: Three reviewers assessed eligibility and trial quality. MAIN RESULTS: To date, no trials have specifically reported the effects of DCC in SGA infants. Three trials were included, of 190 term and 40 preterm infants, a proportion of whom were SGA. DCC was associated with higher haemoglobin levels in term infants at follow-up [two trials, 127 infants, weighted mean difference (WMD) 9.17 g/L, 95% confidence interval (CI) 5.94-12.40]. In preterm infants, the proportion who required a blood transfusion in the 1st 6 weeks after birth was lower after DCC (one trial, 38 infants, RR 0.56, 95% CI 0.34-0.94). It was not possible to infer from the available data whether SGA infants were at greater risk of adverse effects in the early neonatal period. CONCLUSIONS: DCC in a group that contains both AGA and SGA infants was associated with higher haemoglobin levels at 2-3 months of age in term infants and a reduction in the number of blood transfusions needed in the 1st 4- 6 weeks of life in preterm infants. No reliable conclusions could be drawn about the potential adverse effects of DCC. The paucity of information on DCC in SGA infants justifies further research, especially in developing countries where the baseline risk for polycythaemia-hyperviscosity syndrome is likely to be lower than in industrialised countries.

Anemia↗

PubMed1985

Presentation of a new method for specific measurement of in vivo insulin-stimulated glucose disposal in humans: comparison of this approach with the insulin clamp and minimal model techniques.

This study was initiated to compare the abilities of two alternative approaches to the measurement of insulin-dependent glucose disposal in normal humans. The ability of insulin to stimulate glucose disposal was measured in 12 normal subjects by determining glucose disposal rates during insulin clamp studies carried out at both basal insulin concentrations (approximately 6 microU/ml) and during a period of sustained hyperinsulinemia (approximately 60 microU/ml). The increment in glucose disposal was defined as insulin-dependent disposal and compared to estimates of insulin action generated by both the conventional insulin clamp approach and the minimal model technique. The results documented an extremely close correlation (r = 0.99; P less than 0.001) between the direct determination of insulin-dependent glucose disposal and insulin-stimulated glucose disposal as estimated by the insulin clamp technique. In contrast, there was a poor correlation (r = 0.44; P = NS) between insulin sensitivity as estimated by the minimal model technique and insulin-dependent glucose disposal. These results indicate that the value of glucose disposal determined by the insulin clamp approach, which includes both insulin-independent and insulin-dependent glucose disposal, provides an excellent estimate of insulin-dependent glucose disposal in subjects with normal glucose tolerance. Unfortunately, this does not appear to be true of the minimal model technique. However, it must be emphasized that these conclusions are only applicable to normal humans, and may not apply to normal subjects of other species or to humans under different physiological or pathological situations.

Administration, Oral↗

PubMed1992

Mechanisms of renal hemodynamic impairment during infrarenal aortic cross-clamping.

Infrarenal aortic cross-clamping is associated with impairment of renal hemodynamics due to vasoconstriction, the mechanism of which remains under debate. To assess the renal effect of two potent renal vasodilators (enalapril, a converting enzyme inhibitor, and nicardipine, a calcium antagonist), 24 patients scheduled for reconstructive aortic surgery were randomly allocated to one of three treatment groups (n = 8 each) and received either a placebo, nicardipine, or enalapril. Anesthesia consisted of flunitrazepam, fentanyl, pancuronium, and, occasionally, droperidol. Although aortic cross-clamping was associated with no change in mean arterial blood pressure, decreased cardiac output and increased systemic vascular resistance occurred in control patients (33% and 43%, respectively, both P less than 0.05 versus baseline) and nicardipine-treated patients (51.7% and 67.7%, respectively, both P less than 0.05 versus baseline); however, changes in cardiac output and systemic vascular resistance failed to reach significance in enalapril-treated patients. Glomerular filtration rate (technetium 99-diethylenetriaminepentacetic acid clearance) and effective renal plasma flow (iodo-Hippuran 131 clearance) decreased for the duration of aortic cross-clamping in control patients (42.9% and 18.5%, respectively, both P less than 0.05 versus baseline) and enalapril-treated patients (34.0% and 38.1%, respectively, both P less than 0.05 versus baseline), but no change was observed in nicardipine-treated patients. These results suggest that the reninangiotensin system is not an important determinant of the renal vasoconstriction associated with aortic cross-clamping. In contrast, renal dysfunction may be alleviated by the dihydropyridine derivative nicardipine, which probably acts at the level of the preglomerular resistance vessels.

Adult↗

PubMed1993

Electrical stimulation as a substitute for the tail clamp in the determination of minimum alveolar concentration.

Circumstances may preclude the use of standard stimuli, namely tail clamp or surgical incision, to determine minimum alveolar concentration. In rats anesthesized with isoflurane, an alternative stimulus, electrical currents (10, 15, 20, or 40 V; biphasic pulses of 6.5 ms duration; 50 Hz), gave results comparable to those obtained with the tail clamp and the results did not change with repeated measurements if care was taken to avoid desensitization by exhaustion of a particular set of electrodes. The 40 V stimulation gave slightly higher values (4%; P < 0.006) than tail clamp, but the difference was too small to be of experimental significance. More importantly, the higher voltages produced desensitization after fewer attempts at stimulation. In addition to these results with isoflurane, we found that 15 V stimulation and tail clamp produced comparable minimum alveolar concentration values for halothane and for desflurane.

Anesthesia, Inhalation↗

PubMed1994

Blood volume redistribution during cross-clamping of the descending aorta.

We tested the hypothesis that occlusion of the descending aorta is associated with blood volume redistribution resulting in a relative hypervolemia in organs and tissues proximal to the level of occlusion. The study was performed on splenectomized dogs anesthetized with pentobarbital. Whole body scintigraphy with a Sophy DSX rectangular large field of view gamma-camera equipped with a high resolution collimator was used; Tc99m was used to label plasma albumin. The aorta was occluded at diaphragmatic and suprarenal levels in random order. The activity was counted during different stages of the experiments in the following regions of interest: brain, left and right ventricles, left and right lungs, left and right deltoid muscles, the liver, and intestines. Cross-clamping at the suprarenal level was not associated with significant changes in blood volume in any region of interest. The aortic cross-clamping at diaphragmatic level was associated with significant increases in the gamma-emission in all organs and tissues above the level of aortic occlusion by 8%-38%. Thus, the present study supports the hypothesis by demonstrating that cross-clamping of the aorta at diaphragmatic level is associated with an increase in blood volume in the organs and tissues proximal to the level of cross-clamping. Such an increase might represent the mechanism for well-documented increases in preload and blood flow above aortic occlusion, resulting in an additional (in addition to an increase in afterload) burden to the heart.

Animals↗

PubMed2005

Both milrinone and colforsin daropate attenuate the sustained pial arteriolar constriction seen after unclamping of an abdominal aortic cross-clamp in rabbits.

We previously reported that unclamping of an abdominal aortic cross-clamp causes initial dilation of pial arteries followed by sustained constriction. Both milrinone and colforsin daropate have a vasodilator action, and both have been used in such critical conditions as abdominal aortic aneurysmectomy. We measured cerebral pial arteriolar diameters using a rabbit closed cranial window preparation before (baseline) and 15 min after the start of an IV infusion of 0.9% saline (control group), milrinone, or colforsin daropate (0.05 and 0.5 microg . /kg(-1) . min(-1)) (pre-clamp), just after aortic clamping, 20 min after clamping, and at 0 to 60 min after unclamping. In the control group, a significant decrease in diameter persisted for at least 60 min after unclamping (maximum, -15% for large and -26% for small arterioles versus baseline). These values were significantly smaller after both doses of milrinone and the larger dose of colforsin daropate (-5% and -8%, 10% and 12%, and -2% and -5%, respectively vs baseline, at 60 min). In a second experiment, changes in regional cerebral blood flow and tissue oxygen tension reflected changes in vascular variables. Thus, sustained cerebral pial arteriolar constriction induced by aortic unclamping can be attenuated by IV milrinone or colforsin daropate.

Animals↗

PubMed2006

A comparison of fenoldopam with dopamine and sodium nitroprusside in patients undergoing cross-clamping of the abdominal aorta.

Fenoldopam, a selective dopamine-1-receptor agonist, decreases arterial blood pressure rapidly, with a brief duration of action similar to sodium nitroprusside (SNP), but in contrast to SNP, it increases renal blood flow. We compared the hemodynamic and renal effects of fenoldopam in patients undergoing abdominal aortic surgery requiring cross-clamping of the aorta with another therapeutic option, dopamine and SNP. Fenoldopam or 2 mcg x kg(-1) x min(-1) of dopamine and SNP was infused before incision in 60 randomly selected patients in a double-blind fashion. Hemodynamic variables were recorded before incision, immediately before clamping the aorta, 5 min after cross-clamp release and upon completion of surgery. Urine output, serum creatinine, and creatinine clearance were measured intraoperatively and postoperatively. Characteristics were compared between groups using two-sample rank sum test for continuous variables and Fisher's exact test for discrete variables. The occurrence of severe hypotension, maximum systolic blood pressure, and need for additional antihypertensive drugs were not different between the groups. Most intraoperative hemodynamic variables and all indices of renal function did not differ according to treatment. Therefore, fenoldopam has no therapeutic advantage compared with similar therapies in patients undergoing major vascular surgery involving cross-clamping of the aorta.

Aged↗

PubMed1995

The patch clamp technique.

The introduction of the patch clamp technique less than two decades ago revolutionized the study of cellular physiology by providing a high-resolution method of observing the function of individual ionic channels in a variety of normal and pathological cell types. By the use of variations of the basic recording methodology, cellular function and regulation can be studied at a molecular level by observing currents through individual ionic channels. At a cellular level, processes such as signaling, secretion, and synaptic transmission can be examined. In addition, by combining the information from high-resolution electrophysiological recordings obtained by the patch clamp method with modern molecular biological techniques, further insight can be gained into the gene expression and protein structure of ionic channels. Given the ubiquity and importance of ionic channels, it is not surprising that their study has led to a new understanding of the mechanisms of certain disease processes and has given insight into treatments for these diseases. This review gives an historical perspective of the development of the patch clamp technique and an overview of the methodologies currently in use. Examples are shown to illustrate typical uses of the patch clamp technique with emphasis on the variety of recording configurations available and the advantages and drawbacks of each method.

Animals↗

PubMed1993

Voltage-clamp frequency domain analysis of NMDA-activated neurons.

1. Voltage and current-clamp steps were added to a sum of sine waves to measure the tetrodotoxin-insensitive membrane properties of neurons in the intact lamprey spinal cord. A systems analysis in the frequency domain was carried out on two types of cells that have very different morphologies in order to investigate the structural dependence of their electrophysiological properties. The method explicitly takes into account the geometrical shapes of (i) nearly spherical dorsal cells with one or two processes and (ii) motoneurons and interneurons that have branched dendritic structures. Impedance functions were analysed to obtain the cable properties of these in situ neurons. These measurements show that branched neurons are not isopotential and, therefore, a conventional voltage-clamp analysis is not valid. 2. The electrophysiological data from branched neurons were curve-fitted with a lumped soma-equivalent cylinder model consisting of eight equal compartments coupled to an isopotential cell body to obtain membrane parameters for both passive and active properties. The analysis provides a quantitative description of both the passive electrical properties imposed by the geometrical structure of neurons and the voltage-dependent ionic conductances determined by ion channel kinetics. The model fitting of dorsal cells was dominated by a one-compartment resistance and capacitance in parallel (RC) corresponding to the spherical, non-branched shape of these cells. Branched neurons required a model that contained both an RC compartment and a cable that reflected the structure of the cells. At rest, the electrotonic length of the cable was about two. Uniformly distributed voltage-dependent ionic conductance sites were adequate to describe the data at different membrane potentials. 3. The frequency domain admittance method in conjunction with a step voltage clamp was used to control and measure the oscillatory behavior induced by N-methyl-D-aspartate (NMDA) on lamprey spinal cord neurons. Voltage-clamp currents and impedance functions were measured at different membrane potentials. The impedance functions had a voltage-dependent resonance and phase shift characteristic of a negative conductance. These measurements provide a quantitative analysis of the conductances induced by NMDA in central neurons of the lamprey spinal cord and directly establish the basis of the non-linear oscillatory behavior previously observed in the presence of NMDA. NMDA was shown specifically to activate a negative and a positive conductance, both of which were markedly affected by the membrane potential. It is shown that the net current in the presence of NMDA must be considered as the algebraic sum of currents in opposite directions.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

PubMed2006

Is single or double aortic clamping safer in terms of cerebral outcome during coronary bypass surgery?

The purpose of the present study was to investigate retrospectively which aortic clamping technique, the single clamp technique (SCT) or double clamping technique (DCT), is safer in terms of cerebral functions in patients who have undergone coronary bypass surgery. We evaluated 1100 patients who underwent coronary artery bypass graft surgery at our institute from 1998 to 2004. The two groups, SCT (n = 550, 50%) and DCT (n = 550, 50%), were comparable with respect to smoking, hypertension, hypercholesterolemia, diabetes mellitus, chronic obstructive pulmonary disease, peripheral arterial disease, history of neurological events, creatinine levels, and existence of a carotid lesion. No significant differences between the SCT and DCT groups were observed in terms of cardiac and cerebral complications perioperatively and postoperatively. Both single and double clamping techniques have advantages and disadvantages in patients undergoing coronary bypass surgery.

Aged↗

PubMedDate not supplied

Supraceliac clamping in the surgical treatment of abdominal aortic aneurysm. An experimental study in dogs.

Previous reports have suggested the use of supraceliac aortic clamping in the surgical treatment of abdominal aortic aneurysm of difficult approach. The objective of the present report was to study the hepatic and renal metabolic changes of three groups of dogs submitted to temporary clamping (30 minutes) of the abdominal aorta at three different levels: below the renal arteries, infrarenal group (8 dogs); above the renal arteries, suprarenal group (9 dogs); above the celiac artery, supraceliac group (9 dogs). Blood bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen, and creatinine levels were measured before clamping and 5 minutes and 24 hours after reperfusion of the aorta. Bilirubin levels remained unchanged 5 minutes and 24 hours after reperfusion in all three groups. Alkaline phosphatase levels were significantly increased in all three groups 24 hours after reperfusion. ALT levels increased significantly in the supraceliac group and AST levels increased significantly in the infrarenal and supraceliac groups 24 hours after reperfusion of the aorta. However, despite these significant increases after reperfusion, the levels of these hepatic enzymes were still within the normal range for dogs. Urea nitrogen and creatinine levels showed that renal function did not change in any of the three groups. We conclude that supraceliac, infrarenal or suprarenal aortic clamping for 30 minutes do not promote any important changes in the hepatic or renal function of dogs.

Alanine Transaminase↗

PubMed1998

Nitric oxide release as an essential mitigating step in tubuloglomerular feedback: observations during intrarenal nitric oxide clamp.

Nitric oxide synthase inhibition in the kidney enhances tubuloglomerular feedback (TGF) responsiveness. This may reflect either the effect of reduced basal nitric oxide (NO) availability or the effect of impaired NO release that is physiologically induced by TGF activation. However, it is unknown whether the latter actually takes place. In this study, it was hypothesized that NO is released (from macula densa cells or endothelium) as part of the normal TGF loop, and mitigates the TGF response. In Sprague Dawley rats, TGF responsiveness was assessed (fall in tubular stop flow pressure, deltaSFP, upon switching loop of Henle perfusion rates from 0 to 40 nl/min) during an intrarenal NO clamp (systemic infusion of nitro-L-arginine, 10 microg/kg per min, followed by intrarenal nitroprusside infusion adjusted to restore renal blood flow [RBF]). This maneuver was presumed to fix intrarenal NO impact at a physiologic level. To validate the approach, TGF responsiveness during an intrarenal angiotensin II (AngII) clamp (systemic infusion of enalaprilat 0.2 mg/kg per min, followed by intrarenal AngII infusion) was also studied. AngII is presumed to modulate but not mediate, TGF, thus not to increase as part of the TGF loop. In untreated animals, RBF was 7.4 +/- 0.4 ml/min, and deltaSFP was 5.7 +/- 1.6 mmHg. Nitro-L-arginine infusion alone reduced RBF to 5.3 +/- 0.5 ml/min (P < 0.05); with nitroprusside infusion, RBF was restored to 8.3 +/- 0.7 ml/min. In this condition (NO clamp), deltaSFP was markedly increased to 19.6 +/- 3.2 mmHg (P < 0.05). By contrast, deltaSFP, which was virtually abolished during enalaprilat alone (0.2 +/- 0.3 mmHg), was not significantly different from controls during AngII clamp (8.2 +/- 1.0 mmHg). These data suggest that NO may well be released upon TGF activation. By contrast, AngII is not dynamically involved in TGF activation, but may modulate the TGF response. Thus, dynamic release of NO during TGF activation mitigates the TGF response, so that it will offset the action of a primary, as yet undefined, vasoconstrictor mediator. The source of this NO, macula densa or endothelium, remains to be elucidated.

Analysis of Variance↗

PubMed1985

Insulin action during pregnancy. Studies with the euglycemic clamp technique.

To assess the mechanisms responsible for the insulin resistance associated with both normal human pregnancy and gestational-onset diabetes, we have measured exogenous glucose disposal using sequential insulin infusions with the euglycemic glucose clamp technique and erythrocyte insulin binding. Three groups of women were studied: nonpregnant women with normal glucose tolerance (N = 7, mean age 32.9 +/- 2.1 yr), pregnant women with normal glucose tolerance (N = 5, mean age 24.8 +/- 3.5 yr), and pregnant women with gestational-onset diabetes (N = 5, mean age 34.6 +/- 2.6 yr). Despite normal plasma glucose levels obtained during a 100-g oral glucose tolerance test, plasma insulin levels were significantly elevated in the pregnant women compared with the nonpregnant control subjects, suggesting a state of insulin resistance. Insulin binding to erythrocytes was similar in all three groups (maximum specific binding being 5.0 +/- 0.6%, 5.5 +/- 1.1%, and 6.0 +/- 0.7% in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively). In vivo peripheral insulin action was measured using the euglycemic glucose clamp technique during an insulin infusion of 40 mU/m2 X min, with blood glucose clamped at a concentration of 75 mg/dl using a variable glucose infusion. Glucose infusion rates were 213 +/- 11 mg/m2 X min, 143 +/- 23 mg/m2 X min, and 57 +/- 18 mg/m2 X min in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively. This demonstrates that pregnant subjects display a state of insulin resistance, and that this appears to be more marked in gestational-onset diabetic subjects. To further define the possible mechanism of insulin resistance during pregnancy, the insulin infusion rate was increased to 240 mU/m2 X min and further euglycemic clamp measurements performed. Glucose infusion rates were 372 +/- 11 mg/m2 X min, 270 +/- 31 mg/m2 X min, and 157 +/- 26 mg/m2 X min, in nonpregnant, nondiabetic pregnant, and gestational-onset diabetic women, respectively. This demonstrates a shift to the right of the dose-response curve of insulin action and suggests that the insulin resistance of pregnancy may include a decrease in presumed "maximum" insulin responsivity. In four subjects, studies were repeated in the postpartum period, and these demonstrated that the insulin resistance of pregnancy is ameliorated shortly after delivery. These studies suggest that the insulin resistance of pregnancy results from a target cell defect in insulin action beyond the initial step of insulin binding to cellular receptors, a postreceptor (or postbinding) defect in insulin action.

Adult↗