Ketamine and magnesium association reduces morphine consumption after scoliosis surgery: prospective randomised double-blind study.

BACKGROUND: Scoliosis repair is a major orthopaedic surgery associated with severe post-operative pain. Ketamine and magnesium have an established efficacy as morphine-sparing agents. Our purpose was to evaluate the morphine-sparing effect of both magnesium and ketamine given simultaneously compared with ketamine alone during scoliosis surgery. METHODS: Fifty patients scheduled for posterior instrumentation were randomised in a prospective double-blind study. The Gr (K + Mg) received, after induction, an intravenous (IV) bolus of ketamine 0.2 mg/kg and magnesium 50 mg/kg, followed by continuous infusion of ketamine (0.15 mg/kg/h) and magnesium (8 mg/kg/h) until extubation. The Gr (K) received the same dose of ketamine associated with bolus and continuous infusion of normal saline. All patients received multimodal analgesia associated with IV morphine administered via patient-controlled analgesia pump. Morphine consumption, visual analogue scale (VAS) pain scores and occurrence of side effects were followed until 48 h post-operatively. Sleep quality and patient satisfaction were also followed. P < 0.05 was considered statistically significant. RESULTS: The average cumulative morphine consumption was significantly lower in the Gr (K + Mg) compared with the Gr (K) at post-operative hours 4, 8, 12, 18, 30, 36 and 48. The relative difference in the post-operative morphine consumption was 29.5%: Gr (K + Mg) 51.53 mg vs. Gr (K) 73.16 mg. VAS scores were not statistically different between the two groups. However, qualities of sleep and satisfaction scores on the first night were significantly better in the Gr (K + Mg) (P = 0.027 and P = 0.016, respectively). CONCLUSION: Ketamine and magnesium association reduces the post-operative morphine consumption after scoliosis surgery. It seems to provide a better sleep quality and improves patient satisfaction.

[Audit on preoperative cardiac evaluation before non-cardiac surgery: the importance of a pocket guide to improve the anaesthesist's adhesion to ACC/AHA guidelines]. / Audit sur l'évaluation cardiaque préopératoire avant une chirurgie non cardiaque : utilité d'un aide-mémoire pour améliorer l'adhésion des anesthésistes aux recommandations de l'American College of Cardiology/American Heart Association (ACC/AHA).

INTRODUCTION: The American College of Cardiology/American Heart Association (ACC/AHA) guidelines stratify perioperative cardiac risk according to clinical markers, functional capacity, and type of surgery. They help determining which patients are candidates for preoperative cardiac testing and optimizing the cost-effectiveness of the evaluation strategy. Auditing our preoperative anaesthetic screening practice revealed an exceedingly high rate of referrals to the cardiologists. A small pocket-size reminder was created in order to improve the adhesion of the anaesthesiologists to the recommendations of the ACC/AHA, and confirm or obviate the need for a formal preoperative specialized cardiology consultation. Another audit was conducted 1 year later in order to evaluate the effectiveness of this reminder. METHODS: The second audit was conducted over a period of 1 month. Recorded data included demographic characteristics, clinical predictors of cardiovascular risk, surgical risk, and the reasons for the cardiac evaluation by a cardiologist (as reported by the senior or junior anaesthesiologist). Results of this second audit were compared to those of the audit conducted a year earlier. RESULTS: During the first audit, a total of 654 patients were seen in the preoperative unit. Fifty-two patients were referred to a cardiologist during the study period (7.9%). Guidelines for cardiac assessment were respected in 7/52 patients (13.5%). During the second audit, 30 out of 787 patients (3.8%) screened in preoperative anaesthetic consultation unit were referred to the cardiologist. According to the ACC/AHA guidelines, 27/30 patients (90%) objectively needed a cardiology consultation due to the existence of a known previous heart disease. DISCUSSION: The use of the pocket reminder concerning the ACC/AHA recommendations significantly reduced both the total number of cardiology referrals, and the number of unjustified referrals. The use of a pocket guide may help in reducing both the cost and the postponement of scheduled surgery.

Correlation between central venous oxygen saturation and oxygen delivery changes following fluid therapy.

BACKGROUND: The rationale for using central venous oxygen saturation (ScvO(2)) in various clinical scenarios is that it reflects the balance between oxygen delivery (DO(2)) and demands. In this study, we evaluated the correlation between ScvO(2) and DO(2) changes (Delta Do(2), DeltaScvO(2)) in patients receiving fluid therapy following coronary surgery. We also correlated the changes of mean arterial pressure (Delta MAP) and central venous pressure (Delta CVP), with Delta DO(2). METHODS: Sixty consecutive sedated and mechanically ventilated adult patients, with cardiac index

[Spinal anaesthesia and Moya Moya disease]. / Rachianesthésie chez un patient connu avoir une maladie de Moya Moya.

Moya Moya is a rare disease of uncertain origin, characterised by stenosis of one or both of the internal carotid arteries and responsible of several neurological signs. We present the case of a boy with Moya Moya disease who was scheduled for an epiphisiodesis of the lateral malleola and had a spinal anaesthesia with hyperbaric bupivacaine 0.5% 10 mg without any perioperative complications. Any anaesthetic method could be used, provided special attention is given to avoid changes of capnea and blood pressure to preserve cerebral blood flow and palliate to cerebral flow steal.

[Bilateral ilioinguinal nerve block for ambulatory varicocele surgery]. / Bloc ilio-inguinal bilatéral et cure de varicocèle en ambulatoire.

OBJECTIVE: The aim of this study was to evaluate the effectiveness of bilateral ilioinguinal-iliohypogastric nerve blocks for pain relief following ambulatory bilateral varicocelectomy. STUDY DESIGN: Prospective and randomised. PATIENTS AND METHODS: Sixty adult men scheduled for bilateral varicocelectomy were included in this prospective study. All patients had a standardised general anesthesia. After surgical procedures, patients were randomized into two groups: patients in group I received a bilateral ilioinguinal nerve block with 15 ml x 2 of 0.25% bupivacaine; patients in group II received subcutaneously 1 mg kg-1 of tramadol. Visual analogue pain scores at rest and during mobilisation were recorded at 5 min and 1, 3, 5 postoperative hours. The side effects of analgesia and amounts of rescue analgesics were recorded. RESULTS: Pain scores at rest and during mobilisation, the incidence of postoperative nausea and vomiting and additional analgesics requirement were significantly reduced in group I. There was no complication. CONCLUSION: Ilioinguinal nerve block is effective in controlling pain after bilateral varicocelectomy in ambulatory surgery.

Role of carotid bodies in control of the neuroendocrine response to exercise.

This study was aimed at assessing the role of carotid body function in neuroendocrine and glucoregulatory responses to exercise. The carotid bodies and associated nerves were removed (CBR, n = 6) or left intact (Sham, n = 6) in anesthetized dogs >16 days before experiments, and infusion and sampling catheters were implanted. Conscious dogs were studied at rest and during 150 min of exercise. Isotopic dilution was used to assess glucose production (R(a)) and disappearance (R(d)). Arterial glucagon was reduced in CBR compared with Sham at rest (29 +/- 3 vs. 47 +/- 3 pg/ml). During exercise, glucagon increased more in Sham than in CBR (47 +/- 9 vs. 15 +/- 2 pg/ml). Cortisol and epinephrine levels were similar in the two groups at rest and during exercise. Basal norepinephrine was similar in CBR and Sham. During exercise, norepinephrine increased by 432 +/- 124 pg/ml in Sham, but by only 201 +/- 28 pg/ml in CBR. Basal arterial plasma glucose was 108 +/- 2 and 105 +/- 2 mg/dl in CBR and Sham, respectively. Arterial glucose dropped by 10 +/- 3 mg/dl at onset of exercise in CBR (P < 0.01) but was unchanged in Sham (decrease of 3 +/- 2 mg/dl, not significant). Basal glucose kinetics were equal in Sham and CBR. At onset of exercise, R(a) and R(d) were transiently uncoupled in CBR (i.e., R(d) > R(a)) but were closely matched in Sham. In steady-state exercise, R(a) and R(d) were closely matched in both groups. Insulin was equal in the basal period and decreased similarly during exercise. These studies suggest that input from the carotid bodies, or receptors anatomically close to them, 1) is important in control of basal glucagon and the exercise-induced increment in glucagon, 2) is involved in the sympathetic response to exercise, and 3) participates in the non-steady-state coupling of R(a) to R(d), but 4) is not essential to glucoregulation during sustained exercise.

Gastrointestinal tract, hepatic, hindlimb, and renal recovery of CO(2) in vivo.

Whole body oxidative rates of labeled substrates are often measured by collecting expired air and determining the amount of labeled CO(2) that is produced. However, the CO(2) produced may not be completely recovered under all circumstances, and there is a wide variation in values reported under different experimental conditions ( approximately 50-100%). The potential contribution of specific organs to this variation has not been defined. In vivo studies using healthy, postabsorptive, multicatheterized conscious canines were conducted to determine gastrointestinal tract, hepatic, hindlimb, and renal recoveries of NaH(14)CO(3) during a 180-min constant infusion [0.022+/-0.002 (SE) microCi x kg(-1) x min(-1)]. Before the constant infusion period, a bolus infusion of NaH(14)CO(3) (1.76+/-0.16 microCi/kg) was given, and the rate of decay in blood was measured over a 15-min period to determine pool size. The pool size for the distribution of (14)CO(2) was approximately 80% of the total body pool (16.0+/-1.7 liters). Whole body recovery was 97.2+/-6.7%. The recoveries across the liver, gut, leg, and kidney were 99.9+/-1.3, 98.0 +/-1.4, 96.7+/-2.6, and 99.9+/-2.1%, respectively. In conclusion, hepatic, gastrointestinal tract, hindlimb, and renal recoveries of CO(2) in vivo were near 100%, suggesting that CO(2) loss is not greater in gluconeogenic organs and that corrections for incomplete recovery of CO(2), when measuring oxidation of substrates across these organs under normal postabsorptive conditions, would be very minor.

Evidence that carotid bodies play an important role in glucoregulation in vivo.

The carotid bodies are sensitive to glucose in vitro and can be stimulated to cause hyperglycemia in vivo. The aim of this study was to determine if the carotid bodies are involved in basal glucoregulation or the counterregulatory response to an insulin-induced decrement in arterial glucose in vivo. Dogs were surgically prepared >16 days before the experiment. The carotid bodies and their associated nerves were removed (carotid body resected [CBR]) or left intact (Sham), and infusion and sampling catheters were implanted. Removal of carotid bodies was verified by the absence of a ventilatory response to NaCN. Experiments were performed in 18-h fasted conscious dogs and consisted of a tracer ([3-3H]glucose) equilibration period (-120 to -40 min), a basal period (-40 to 0 min), and an insulin infusion (1 mU x kg(-1) x min(-1)) period (0-150 min) during which glucose was infused as needed to clamp at mildly hypoglycemic (65 mg/dl) or euglycemic (105 mg/dl) levels. Basal (8 microU/ml) and clamp (40 microU/ml) insulin levels were similar in both groups. Basal arterial glucagon was reduced in CBR compared with Sham (30 + 2 vs. 40 +/- 2 pg/ml) and remained reduced in CBR during hypoglycemia (peak levels of 36 +/- 3 vs. 52 +/- 7 pg/ml). Cortisol levels were not significantly different between the 2 groups in the basal state, but were reduced during the hypoglycemic clamp in CBR. Catecholamine levels were not significantly different between the 2 groups in the basal and hypoglycemic periods. The glucose infusion rate required to clamp glucose at 65 mg/dl was 2.5-fold greater in CBR compared with Sham (4.0 +/- 0.4 vs. 1.6 +/- 0.4 mg x kg(-1) x min(-1)). Basal endogenous glucose appearance (R(a)) was equal in CBR and Sham (2.5 +/- 0.1 vs. 2.5 +/- 0.2 mg x kg(-1) x min(-1)). During the hypoglycemic clamp, insulin suppressed R(a) in CBR but not Sham (1.1 +/- 0.2 vs. 2.5 +/- 0.2 mg x kg(-1) x min(-1) during the last 30 min of the clamp), reflecting impaired counterregulation. Glucose disappearance (R(d)) in the basal state was similar in CBR and Sham, whereas it was elevated in CBR during the hypoglycemic clamp (4.8 +/- 0.1 vs. 3.9 +/- 0.1 mg x kg(-1) x min(-1) during the last 30 min of the clamp). R(d) was also elevated in euglycemic clamp studies, indicating an effect of carotid body resection independent of hypoglycemia. There were no other measured systematic endocrine or metabolic effects of carotid body resection during euglycemic clamps. In conclusion, we found that the carotid bodies (or receptors anatomically close by) play an important role in the insulin-induced counterregulatory response to mild hypoglycemia.

Zonation of acetate labeling across the liver: implications for studies of lipogenesis by MIDA.

Measurement of fractional lipogenesis by mass isotopomer distribution analysis (MIDA) of fatty acids or cholesterol labeled from [(13)C]acetate assumes constant enrichment of lipogenic acetyl-CoA in all hepatocytes. This would not be the case if uptake and release of acetate by the liver resulted in transhepatic gradients of acetyl-CoA enrichment. Conscious dogs, prefitted with transhepatic catheters, were infused with glucose and [1, 2-(13)C(2)]acetate. Stable concentrations and enrichments of acetate were measured in artery (17 microM, 36%), portal vein (61 microM, 5. 4%), and hepatic vein (17 microM, 1.0%) and were computed for mixed blood entering the liver (53 microM, 7.4%). We also measured balances of propionate and butyrate across gut and liver. All gut release of propionate and butyrate is taken up by the liver. The threefold decrease in acetate concentration and the sevenfold decrease in acetate enrichment across the liver strongly suggest that the enrichment of lipogenic acetyl-CoA decreases across the liver. Thus fractional hepatic lipogenesis measured in vivo by MIDA may be underestimated.

Comparison of arcuate-legged clipped versus sutured hepatic artery, portal vein, and bile duct anastomoses.

Attempts at improving anastomoses have included the development of stapling techniques. Our purpose was to evaluate arcuate-legged clipped versus standard sutured anastomoses of the hepatic artery (HA), portal vein (PV), and bile duct in a porcine liver transplantation model. Two groups of pigs were studied intraoperatively and 1 day after liver transplantation. A control group underwent sutured anastomosis of PV and HA with polypropylene and of bile duct with polydioxanone (n = 8). An experimental group underwent anastomoses with arcuate-legged clips (n = 8). We analyzed the time to perform anastomosis and flows before and at various time points after anastomosis. In addition, patency and histology of the anastomoses were evaluated 1 day after operation, including a fibrin-thrombosis score, medial injury, and inflammation score. Times to complete HA and PV anastomoses were not different between clipped and sutured groups. However, the time was shorter to complete bile duct anastomosis with clips than with sutures (6.3 +/- 1.1 minutes and 13.3 +/- 2.0 minutes, respectively). Flows through HA anastomoses were not different between groups, but flow through the PV was higher in clipped compared with sutured anastomosis (P = 0.06). Patency was 100 per cent with no leaks for all three anastomoses in both groups. Histologic data were similar between vascular anastomotic groups. Sutured bile duct anastomoses revealed mild smooth muscle injury in 75 per cent whereas clipped bile duct anastomoses displayed no smooth muscle injury. We conclude that arcuate-legged clipped anastomosis represents a viable option to sutured anastomoses of the PV, HA, and bile duct anastomoses. Bile duct anastomoses were completed in less than half the time and with less tissue damage documented histologically.

The effect of nutritional and hormonal supplementation on protein synthesis immediately after liver transplantation.

We have previously shown that immediately after liver transplantation (LT) the porcine recipient exhibits elevated plasma glucagon, increased fractional synthetic rate (FSR) of fibrinogen, and decreased FSR of fixed or structural liver proteins. The purpose of this study was to evaluate the effect of nutritional and hormonal supplementation on these observations 24 h after LT. Two groups of nine pigs were studied 1 day after LT using radioisotopic and arteriovenous difference techniques. A control group underwent LT with saline infusion and a supplemented group underwent LT with infusion of glucose, amino acids (6 and 1.06 mg/kg. min, respectively), and intraportal insulin (0.6 mU/kg. min) and glucagon (1.3 ng/kg. min). Primed constant infusions of [3H]leucine were used to determine leucine flux, an estimate of whole body protein breakdown, and fractional synthetic rates (FSR). The following changes were noted with supplementation: elevated plasma insulin (6 +/- 1 versus 29 +/- 4 microU/ml, control versus supplemented, respectively, P < 0.05), decreased glucagon to normal levels (323 +/- 65 versus 102 +/- 12 pg/ml, P < 0.05), decreased fibrinogen FSR (108 +/- 15 versus 70 +/- 6%/day, P < 0.025), and increased fixed liver protein FSR (8 +/- 1 versus 13 +/- 2%/day, P < 0.05, respectively). Albumin FSR was unaltered by supplementation (8 +/- 2 versus 6 +/- 1%/day, respectively). Nutritional and hormonal supplementation immediately after LT restored the measured protein synthesis in the allograft to near normal levels 1 day after transplantation.

Parenteral glutamine infusion alters insulin-mediated glucose metabolism.

BACKGROUND: Glutamine is a conditionally essential amino acid that is critical for many basic cellular processes. Its supplementation has been found to be beneficial during several critical illnesses. This study examines the effects of increased glutamine availability on insulin-mediated glucose homeostasis in vivo in multicatheterized conscious canines (n = 5). METHODS: Two weeks before the study, catheters were placed in the femoral artery and the portal, hepatic, femoral, and renal veins for blood sampling and in the splenic vein for intraportal infusion of insulin and glucagon. Doppler probes were placed to measure blood flow. The metabolic study consisted of equilibration, basal, and experimental periods during which [3-3H]glucose was infused to measure glucose kinetics. During the 5-hour experimental period, a hyperinsulinemic-euglycemic clamp was performed by infusing somatostatin, basal glucagon, fivefold basal insulin, and glucose to maintain euglycemia. The experimental period was divided evenly into two subperiods performed in random order: (1) i.v. glutamine infusion (0.72 mmol kg(-1) h(-1)) and (2) i.v. saline infusion. RESULTS: With glutamine, the glucose required to maintain euglycemia was increased 46% over saline (6.8 +/- 1.0 to 9.9 +/- 1.7 mg kg(-1) min(-1). In addition, whole-body glucose production and utilization were increased by 1.4 and 4.6 mg kg(-1) min(-1), respectively. Finally, the increase in whole-body glucose utilization was manifested by increased hepatic and hindlimb glucose utilization. CONCLUSIONS: Increased glutamine availability blunted insulin's action on glucose production and enhanced insulin-mediated glucose utilization with the changes in utilization being threefold greater than the changes in production. Thus parenteral glutamine has potential benefit as a nutrient adjuvant during clinical situations associated with insulin resistance.

Net hepatic glucose output is normal on postoperative day 1 after liver transplantation.

The liver plays a central role in carbohydrate metabolism and glucose homeostasis; therefore, the rapid recovery of glucose homeostasis after liver transplantation (LT) is important. The purpose of this study was to evaluate hepatic and whole-body glucose production (WBGP) on postoperative day 1 after LT using a combination of arteriovenous differences and radioisotope techniques. Two groups of female commercially bred pigs with an average body weight of 31.9 +/- 1.4 kg were studied. A control group (n = 6) underwent laparotomy. A transplanted group (n = 6) was submitted to LT. All pigs were instrumented with catheters placed in the carotid artery and the hepatic, portal, and jugular vein, and flow probes were placed around the hepatic artery and portal vein. WBGP was measured by a primed constant infusion of 3-[3H]glucose 1 day postoperatively. Plasma glucose was 89 +/- 6 versus 98 +/- 7 mg/dL in the control and transplanted groups, respectively. WBGP was increased by 42 per cent in the transplanted group (2.54 +/- 0.17 vs 3.62 +/- 0.39 mg/kg.min), but the net hepatic glucose output was not different between the control and the transplanted groups (1.53 +/- 0.28 vs 1.68 +/- 0.31 mg/kg.min). These results demonstrate that net hepatic glucose output was not different between the control and transplanted pigs, suggesting that LT does not compromise the ability of the liver to produce glucose. However, the WBGP was increased by 42 per cent in the transplanted group, suggesting either a significant contribution from another organ or a significant intrahepatic utilization of glucose.

Hepatic uptake of amino acids immediately after liver transplantation is well preserved despite altered plasma profiles.

BACKGROUND: The liver is one of the principal organs responsible for the uptake and release of amino acids in the body. The ability of the transplanted liver to clear plasma amino acids is associated with a functioning allograft. However, clinical assessment is limited by the inability to access the portal vein postoperatively. Therefore, using a porcine liver transplant model, we examined (1) the plasma levels of amino acids presented to the new hepatic allograft and (2) the capacity of the new allograft to clear these amino acids from the circulation. MATERIALS AND METHODS: Two groups of commercially bred pigs were studied: a control group (n = 8) underwent laparotomy and a transplanted group (n = 6) underwent orthotopic liver transplantation (LT) using veno-venous bypass. All pigs had catheters placed in the carotid artery and portal and hepatic veins and ultrasonic transit time flow probes placed around the hepatic artery and portal vein. Plasma profiles of 23 amino acids were analyzed by high-pressure liquid chromatography. Hepatic balances of amino acids, using arteriovenous difference techniques coupled with hepatic blood flows, were also analyzed on postoperative day 1. RESULTS: Neither portal vein blood flow (703 +/- 74 ml/min vs 666 +/- 82 ml/min) nor hepatic artery blood flow (322 +/- 43 ml/min vs 209 +/- 59 ml/min) was significantly different between the control and the transplanted groups, respectively. The transplanted group had significantly increased plasma levels of alanine (135 +/- 13 mumol/l vs 382 +/- 72 mumol/l), hydroxyproline (30 +/- 5 mumol/l vs 60 +/- 9 mumol/l), methionine (25 +/- 2 mumol/l vs 55 +/- 10 mumol/l), ornithine (36 +/- 5 mumol/l vs 141 +/- 33 mumol/l), phenylalanine (84 +/- 5 mumol/l vs 120 +/- 12 mumol/l), threonine (75 +/- 9 mumol/l vs 159 +/- 27 mumol/l), and tryptophan (17 +/- 2 mumol/l vs 31 +/- 4 mumol/l). The transplanted group also had significantly decreased plasma levels of isoleucine (122 +/- 12 mumol/l vs 85 +/- 8 mumol/l) and taurine (71 +/- 7 mumol/l vs 35 +/- 7 mumol/l). These individual amino acid changes were not accompanied by impairment in the net hepatic amino acid balance or the hepatic fractional extraction of amino acids between the two groups. CONCLUSION: These results suggest that the circumstances associated with liver transplantation alter the fasting amino acid profile immediately postoperatively. However, liver transplantation does not impair the normal hepatic allograft uptake of most plasma amino acids. Thus, the changes observed in the circulating levels of amino acids may represent alterations in nonhepatic production and/or utilization. Furthermore, altered plasma amino acid profiles following liver transplantation are not necessarily indicative of impaired hepatic allograft amino acid metabolism.

Mechanisms of hyperinsulinemia and hyperglucagonemia after liver transplantation.

These studies were undertaken to evaluate the mechanisms for changes in plasma insulin and glucagon levels observed post-liver transplantation. Two groups of pigs were studied: a control group (n = 8) underwent laparotomy and catheter placement in the carotid artery and portal and hepatic veins. Hepatic blood flow was measured by ultrasonic flow probes placed around the hepatic artery and portal vein. An experimental group (n = 8) underwent orthotopic liver transplantation and similar instrumentation. On Day 1 after surgery, an estimate of insulin and glucagon secretion and hepatic extraction was determined using arteriovenous difference techniques. Serum assays were performed for markers of hepatic and renal function. Plasma insulin levels of the transplanted pigs were higher in the carotid artery (4 +/- 1 microU/ml vs 7 +/- 1 microU/ml), but not in the hepatic vein (5 +/- 1 microU/ml vs 7 +/- 1 microU/ml) and in the portal vein (10 +/- 2 microU/ml vs 12 +/- 2 microU/ml). Arterial plasma C-peptide was significantly greater in the transplanted group (0.23 +/- 0.02 ng/ml vs 0.42 +/- 0.03 ng/ml); however, the molar ratio of C-peptide and insulin was not different between the two groups (3.6 +/- 0.9 vs 3.4 +/- 0.4). Plasma glucagon levels of the transplanted pigs were significantly elevated in the carotid artery (111 +/- 11 pg/ml vs 323 +/- 65 pg/ml), portal vein (221 +/- 27 pg/ml vs 495 +/- 69 pg/ml), and hepatic vein (142 +/- 15 pg/ml vs 395 +/- 58 pg/ml). The estimate of pancreatic secretion of insulin (115 +/- 28 microU/kg.min) vs 71 +/- 21 microU/kg.min) and glucagon (2.0 +/- 0.4 ng/kg.min vs 2.7 +/- 0.7 ng/kg.min) and the fractional hepatic extraction rate of insulin (35 +/- 8% vs 32 +/- 5%) were not different between the two groups. However, the hepatic fractional extraction rate of glucagon was significantly decreased in the transplanted group (25 +/- 5% vs 11 +/- 3%). Therefore, the hyperglucagonemia observed 24 hr following liver transplantation is partly due to reduced hepatic fractional extraction of glucagon while the hyperinsulinemia is mainly due to the nonhepatic clearance of insulin. We speculate that decreased renal function may contribute to the hyperinsulinemia, elevated C-peptide concentrations, and hyperglucagonemia.

Maintaining muscle protein anabolism after a metabolic stress: role of dextrose vs. amino acid availability.

The effect of chronic hypocaloric parenteral infusions of amino acids (AA) vs. dextrose (D) on protein homeostasis after a generalized metabolic stress was examined. Multicatheterized mongrel dogs were metabolically challenged by a 4-day fast and then administered a 4-day intravenous infusion of saline (S, n = 8), D (n = 8), or isocaloric AA (n = 7). Although nitrogen balance (g.kg.1.day-1) was similarly negative with S (-0.37 +/- 0.05), D (-0.28 +/- 0.03), and AA (-0.37 +/- 0.04) during the fasting period, it was less negative (P < or = 0.05) with AA (-0.06 +/- 0.04) than with D (-0.20 +/- 0.03) or S (-0.23 +/- 0.04) during nutrient infusion. AA resulted in net hindlimb uptake and D in net hindlimb release of essential AA (570 +/- 261 vs. -248 +/- 59 nmol.kg-1.min-1). Whereas S and D infusions led to net hindlimb muscle protein loss (-37 +/- 24 and -89 +/- 33 micrograms.kg-1.min-1, respectively, P < or = 0.05 vs. AA), parenteral AA resulted in net deposition (169 +/- 62 micrograms.kg-1.min-1) as measured using L-[ring-2H5]phenylalanine. Thus hypocaloric parenteral D infusion after a metabolic stress does not favor nitrogen conservation, because net whole body nitrogen loss, skeletal muscle protein catabolism, and hindlimb AA release were not blunted compared with S infusion. Conversely, hypocaloric AA infusion preserves whole body and muscle protein stores.

Effect of acute ethanol intoxication on glucoregulation during prolonged insulin-induced hypoglycemia.

This study examined the interaction of acute ethanol administration on glucose homeostasis during insulin-induced hypoglycemia (IIH). Glucose kinetics and net hepatic balances of alanine, glycerol, and lactate were estimated in three groups of dogs: group I underwent 3 h of IIH; group II received a continuous ethanol infusion in addition to IIH; group III received ethanol for 3 h. In group I, IIH resulted in a sustained twofold increase in glucose rate of appearance (Ra) and net hepatic uptake (NHU) of glycerol and lactate but no change in NHU of alanine. In group II, glucose Ra rose transiently, NHU of alanine and glycerol increased two- and fivefold, respectively, whereas NHU of lactate dropped 60%. In group III, no alterations in plasma glucose levels, glucose Ra, and NHU of alanine and glycerol were observed, but NHU of lactate switched to a net output. These results demonstrate that ethanol alone or with IIH exclusively inhibited NHU of lactate, and this was responsible, in a stoichiometric fashion, for the failure of the delayed increase in glucose Ra during IIH.

Comparison of the cardiodynamic and metabolic effects of dobutamine with those of norepinephrine and dopamine in the dog isolated heart.

A comparative study of the cardiodynamic and metabolic effects of norepinephrine, dopamine and dobutamine was carried out on the isolated heart-lung preparation from dogs, modified to measure coronary outflow and myocardial oxygen consumption. Infusions of the three sympathomimetic drugs which increased myocardial contractility, as reflected by maximal rate of rise of left ventricular pressure, dp/dt, by 24%, produced comparable increases in heart rate of 5 to 7% with the three drugs, comparable increases in myocardial oxygen consumption of 11% with dopamine and 19% with dobutamine and a decrease in mechanical efficiency of 13% with dobutamine. At higher doses which increased dp/dt by an average of 68%, heart rate increased by 9%, 19% and 26% following norepinephrine, dopamine and dobutamine, respectively, the increase produced by dobutamine being significantly higher than that produced by norepinephrine. Myocardial oxygen consumption increased significantly following dopamine by 39% and dobutamine by 46% but not following norepinephrine. Mechanical efficiency decreased following dobutamine by 24%. At average increases in dp/dt of 123% and 166%, there were further increases in heart rate and myocardial oxygen consumption and decreases in mechanical efficiency, the changes in each parameter being similar for all three drugs. The increase in coronary outflow was compared with the spontaneous increase which is regularly observed with time in the isolated heart-lung preparation. Only dobutamine was found to increase coronary outflow by 49%, 117% and 137% at increases in dp/dt of 71%, 118% and 173%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)