Lactate elimination and glycogen resynthesis after intense bicycling.

OBJECTIVE: Muscles break down glycogen to lactate during intense exercise, and in the recovery period, glycogen reappears while lactate disappears. The purpose of this study was to examine to what extent lactate is resynthesized to glycogen within the formerly active muscles themselves in man. MATERIAL AND METHODS: Fifteen healthy young men cycled for 2 min to exhaustion. Muscle biopsies were taken from the knee extensor muscle before the exercise, just after the ride, and again after 45 min of recovery. In addition, blood samples were taken from the femoral artery and vein, and the leg blood flow was measured using the ultrasound Doppler technique. The muscle biopsies were analysed for glycogen, lactate and other metabolites, and the blood samples were analysed for lactate and glucose. The exchanges of lactate and glucose of the leg were assessed by multiplying the measured arterio-venous (a-v) differences by the blood flow. RESULTS: During the exercise the muscles broke down 20+/-4 mmol glycogen kg(-1) wet muscle mass and produced 26+/-1 mmol lactate kg(-1). In the recovery period after 24+/-1 mmol lactate kg(-1) had disappeared, of which 48 % was released to the blood, 52 % disappeared within the muscle. An R-value of 0.62 across the leg suggests that none of the lactate was oxidized. Altogether, 10+/-3 mmol glycogen kg(-1) reappeared during recovery. Glucose uptake accounted for 2 mmol kg(-1) and glycolytic intermediates (G-6-P and free glucose) accounted for 4 mmol kg(-1); 4 mmol glycogen kg(-1) (42 %) reappeared from unknown sources. CONCLUSIONS: The present data are compatible with the idea that around half of the lactate produced during intense bicycling is resynthesized to glycogen within the working muscles themselves in the recovery period after the bicycling.

Arterio-venous differences of blood acid-base status and plasma sodium caused by intense bicycling.

After intense exercise muscle may give off hydrogen ions independently of lactate, perhaps by a mechanism involving sodium ions. To examine this possibility further five healthy young men cycled for 2 min to exhaustion. Blood was drawn from catheters in the femoral artery and vein during exercise and at 1-h intervals after exercise. The blood samples were analysed for pH, blood gases, lactate, haemoglobin, and plasma proteins and electrolytes. Base deficit was calculated directly without using common approximations. The leg blood flow was also measured, thus allowing calculations of the leg's exchange of metabolites. The arterial blood lactate concentration rose to 14.2 +/- 1.0 mmol L-1, the plasma pH fell to 7. 18 +/- 0.02, and the base deficit rose 22% more than the blood lactate concentration did. The femoral-venous minus arterial differences peaked at 1.8 +/- 0.2 mmol L-1 (lactate), -0.24 +/- 0.01 (pH), and 4.5 +/- 0.4 mmol L-1 (base deficit), and -2.5 +/- 0.7 mmol L-1 (plasma sodium concentration corrected for volume changes). Thus, near the end of the exercise and for the first 10 min of the recovery period the leg gave off more hydrogen ions than lactate ions to the blood, and sodium left plasma in proportion to the extra hydrogen ions appearing. The leg's integrated excess release of hydrogen ions of 0.88 +/- 0.45 mmol kg-1 body mass was 67% of the integrated lactate release. Base deficit calculated by the traditional approximate equations underestimated the true value, but the error was less than 10%. We conclude that intense exercise and lactic acidosis may lead to a muscle release of hydrogen ions independent of lactate release, possibly by a Na+,H+ exchange. Hydrogen ions were largely buffered in the red blood cells.

Hypertonic saline and dextran in normovolaemic and hypovolaemic healthy volunteers increases interstitial and intravascular fluid volumes.

BACKGROUND: Hypertonic saline (HS) is increasingly used for fluid resuscitation in hypovolaemic patients. Although the effects of HS have been investigated in animal models, controlled studies in healthy human individuals are few. AIM: The effects of i.v. hypertonic saline 75 mg.ml-1 in dextran 70, 60 mg.ml-1 (HSD) infusion on fluid shifts between the interstitial and intravascular fluid spaces, diuresis and haemodynamics were studied in normovolaemic and moderately hypovolaemic healthy volunteers. MATERIAL AND METHODS: Nine fasting subjects received 4 ml.kg-1 HSD as a 10-min infusion in a normovolaemic situation. Seven days later they served as their own controls in a hypovolaemic situation after 10% of the calculated blood volume had been withdrawn during a 15-min period. Before and after the HSD infusion, interstitial colloid osmotic pressure (COPi) and interstitial fluid hydrostatic pressure (Pi) were measured on the lateral part of the thorax. During the study, blood sampling and pressure measurements were performed through a radial artery cannula, and central venous pressure measured through a catheter in the cubital vein. RESULTS: In these awake and normovolaemic healthy volunteers, HSD infusion caused a transitory unpleasant sensation of headache and heat in the thorax up to the throat. A transitory haemodynamic effect was found with increased heart rate (HR), increased mean arterial pressure (MAP) from 77 +/- 5 mmHg to 92 +/- 13 mmHg (P < 0.05) and CVP increase from 5 +/- 1 mmHg to 8 +/- 1 mmHg (P < 0.05) after end of infusion. A haemodilution with increase in calculated blood volume lasting longer than the MAP increase was observed, with decreased COPi from 14.4 +/- 2.2 mmHg to 12.1 +/- 2.0 mmHg (P < 0.05). The diuresis measured at 180 min was higher in the normovolaemic than in the hypovolaemic situation. More pronounced effects of the infused fluid (HSD) on calculated blood volume, interstitial compartment and CVP were observed during moderate hypovolaemia. CONCLUSIONS: HSD infusion resulted in increased calculated blood volume with increased HR, MAP, and CVP. These effects were greater in a hypovolaemic situation. The haemodilution was most likely caused by fluid shifts from the intracellular compartment to the interstitial and vascular fluid spaces, eventually increasing diuresis.

Hypertonic saline and dextran after coronary artery surgery mobilises fluid excess and improves cardiorespiratory functions.

BACKGROUND: Extracorporeal circulation induces increased capillary permeability with fluid leakage into the interstitial space, resulting in positive fluid balance and intravascular hypovolaemia. Hypertonic saline 75 mg.ml-1 in dextran 70, 60 mg.ml-1 (HSD) seems to be of benefit in patients with impaired perfusion. The purpose of the study was to investigate the effects of HSD infusion on fluid balance and cardiorespiratory functions just after the end of cardiac surgery. MATERIAL AND METHODS: Twenty patients with 3-vessel coronary artery disease undergoing elective coronary artery bypass surgery were studied. A standard regimen for anaesthesia, extracorporeal circulation and monitoring was used. The patients were allocated to receive just after the end of surgery either HSD or isotonic saline (4 ml.kg-1 during 30 min) at random in a double-blind single infusion. Ringer's acetate solution was added as needed to stabilise haemodynamics postoperatively. RESULTS: HSD caused mobilisation of the retained intraoperative fluid excess, and increased diuresis. Despite reduced need for extra fluid and a decreased cumulative fluid balance, after HSD infusion patients had increased filling pressures of the heart and improved cardiac output. HSD infusion also induced reduced intrapulmonary venous admixture and improved PaO2 in the early postoperative period. CONCLUSIONS: The present study documents that infused hypertonic saline with dextran just after the end of cardiac surgery resulted in mobilisation of the intraoperative fluid excess with increased urine output in the early postoperative period and improved gas exchange. Despite reduced need for extra i.v. fluid and decreased cumulative fluid balance, after HSD infusion the patients had increased filling pressures of the heart with improved cardiac output.

Complement activation during and after open-heart surgery is only marginally affected by the choice of fluid for volume replacement.

Forty patients undergoing CPB for coronary artery surgery, using a standardized technical setting, were randomized to receive either Ringer's acetate, dextran 70 (Macrodex), polygeline (Haemaccel) or albumin 4% for volume replacement during and after surgery. The choice of fluid did not affect early complement activation (C3 activation products). Higher values of the terminal complement complex (TCC) were found only at the end of the operation in patients receiving polygeline. There were no differences between any two of the four groups during the postoperative course. The use of blood transfusion or autotransfusion and the degree of haemodilution and hypothermia did not affect complement activation. We conclude that complement activation in association with open-heart surgery is only marginally affected by the choice of fluid for volume replacement.

Influence of the exercise protocol on hemodynamic, gas exchange, and neurohumoral responses to exercise in heart transplant recipients.

BACKGROUND: A gradual accommodation to increasing exercise loads has been recommended for exercise testing in denervated posttransplantation heart recipients. However, how the exercise protocol influence the hemodynamic, gas exchange, and hormonal response to exercise in this not been studied. METHODS: Nine heart transplant recipients tests incremental maximal bicycle ergometry tests in random order. Exercise stages of 1 and 3 minute durations were compared with matched work rate increments ranging between 30 and 40 W. Expiratory gas was measured continuously and arterial blood was sampled at each of the matched work rates. RESULTS: Total exercise duration was 6.4 +/- and 15.3 +/- 0.7 minutes for the 1-minute and 3-minute protocols, respectively. Maximal workload was significantly higher during the 1-minute versus the 3-minute protocol (238 +/- 9 versus 200 +/- 11 W, p < 0.001), but maximal oxygen uptake was not significantly different (25.5 +/- 1.1 versus 26.5 +/- 1.2 ml. min-1.kg-1). Hemodynamic, metabolic, and some hormonal parameters showed marked differences between the two protocols, with significantly higher responses observed during the 3-minute protocol for heart rate, ventilation, lactate, atrial natriuretic factor, and growth hormone. Catecholamine (epinephrine and norepinephrine) and insulin responses did not differ between the two tests. If expressed as a relative exercise intensity (percentage of maximal oxygen uptake) no differences in hormonal responses were observed between the two protocols, except for growth hormone response which remained higher during the 3-minute protocol. CONCLUSIONS: Although maximal oxygen uptake was independent of the exercise protocol in these heart transplant recipients, the exercise protocol has a major influence on the hormonal and metabolic response. The delayed response observed for oxygen uptake and hormonal responses suggests a significant physiologic lag time during the more rapidly incremental protocol. These differences should be taken into account when exercise is used as a method to evaluate the heart transplant recipient.

Cold and warm infusion of Ringer's acetate in healthy volunteers: the effects on haemodynamic parameters, transcapillary fluid balance, diuresis and atrial peptides.

The effects of Ringer's acetate (RAc) infusion with different temperatures, 18 degrees C compared to 36 degrees C, were studied in 20 healthy volunteers. An infusion volume of 20% of the estimated extracellular volume was given over 45 min. Before and after the RAc infusion, interstitial colloid osmotic pressure and interstitial fluid hydrostatic pressure were measured on the lateral part of the thorax and in the lower leg. Blood sampling and pressure measurements were performed through a cannula placed in the left radial artery, and arterial oxygen saturation was measured by pulse oximetry. Atrial peptides ANF (99-126) and ANF (1-98) in plasma were measured as indicators of volume loading. Cold RAc infusion increased mean arterial pressure from 82 (s.d. +/- 7) to 96 (s.d. +/- 9) mmHg (10.9-12.8 kPa) at the end of the infusion with a simultaneous fall in heart rate. Warm RAc infusion gave no changes in blood pressure or heart rate. The arterial oxygen saturation during the infusion of cold RAc was higher than during warm RAc infusion. Cold infusion produced the expected haemodilution with a fall in erythrocyte volume fraction (EVF) from 0.39 (+/- 0.03) to 0.33 (+/- 0.03) and a fall in plasma colloid osmotic pressure (COPp) from 21.7 (+/- 1.1) mmHg to 15.0 (+/- 1.3) mmHg (2.9-2.0 kPa). Warm infusion induced a nearly identical haemodilution. Interstitial colloid osmotic pressure fell from 11.6 (+/- 2.3) mmHg to 8.9 (+/- 2.7) mmHg (1.5-1.2 kPa) after warm infusion while cold infusion gave no changes. The changes in interstitial fluid hydrostatic pressure were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Colloid osmotic pressure of plasma replacement fluids.

Colloid osmotic pressure (COP) of some of the most frequently used plasma replacement fluids was measured with a colloid osmometer. COP of 4% human albumin solutions was only half that of normal human serum (13.6 +/- 0.6 vs. 27.5 +/- 2.7 mmHg (1.8 +/- 0.1 vs. 3.7 +/- 0.4 kPa)) (mean +/- s.d.), whereas COP of 20% human albumin solutions was eight times higher (196.0 +/- 12.3 mmHg (26.1 +/- 1.6 kPa)). Enhancing the protein concentration from 4% to 20% in the human albumin solutions increased COP 14-fold, reflecting the exponential relationship between protein concentration and COP of a solution. Fresh donor plasma furnished by the hospital blood-bank had a COP about 30% below normal human serum (18.1 +/- 1.3 mmHg (2.4 +/- 0.2 kPa)), due to dilution during preparation. Dextran 70 (6%) had a COP more than twice, and Ringer-Dextran 60 (3%) about 75% of that of normal human serum. Dextran 40 (10%) and gelatin (3.5%, Haemaccel) leaked markedly through the membrane of the colloid osmometer, making acceptable measurements impossible. Seven different hydroxyethyl starch (HES) solutions were measured, and the COP varied between half and 3 times that of normal human serum, depending on molecular weight and concentration of the HES.

Plasma concentrations of atrial peptides ANF(1-98) and ANF(99-126) after intravenous infusion: effect of infusate temperature.

Atrial peptides ANF(1-98) and ANF(99-126) were measured in plasma before and after infusion of Ringer-Acetate solution in healthy volunteers. The solution was infused over a 45 min period in an amount equal to 20 per cent of estimated extra-cellular volume. We found that the increase in atrial peptide immunoreactivity after infusion depended on the temperature of the infusate. The molar increase in ANF(1-98) was much larger than the increase in ANF(99-126). We speculate that plasma levels of ANF(1-98) may be a clinically useful parameter of atrial distension secondary to hypervolaemia.

[Treatment of hypovolemia with hypertonic saline solutions]. / Behandling av hypovolemi med hypertone saltløsninger.

Clinical and experimental studies indicate that intravenous infusion of small volumes of hypertonic saline may be beneficial in the treatment of acute hypovolemia. After infusion, cardiac output is increased and systemic vascular resistance is lowered. The effect is transient, however, but can be prolonged by adding a colloid solution. Infusion of small volumes of hypertonic saline (7.5% NaCl) does not significantly influence serum osmolality or serum sodium concentration.

Effects of leg activity and ambient barometric pressure on foot swelling and lower-limb skin temperature during 8 h of sitting.

Prolonged immobilization in an upright position often leads to discomfort and oedema in the feet of otherwise healthy subjects. To determine the significance of leg activity and ambient pressure on oedema formation, skin temperature (Tsk) and discomfort, 6 volunteers sat for 8 h with one leg immobilized and the other spontaneously active; one day at "sea level" (750 mmHg) and one day at reduced barometric pressure (540 mmHg). Foot swelling was measured by water plethysmography. Leg movements were continuously monitored by a Vitalog computer, and foot discomfort was estimated by analog-visual scales. The 8 hour swelling averaged 5.7% in the inactive foot, and 2.7% in the active foot (p less than 0.001). Tsk of the inactive foot levelled off towards ambient temperature (21 degrees C) within 4 h. For the active foot this fall was reduced by 2-3 degrees C (p less than 0.025). The increase in foot discomfort during the day was lowest in the active foot (p less than 0.005). High foot Tsk was associated with a high foot swelling rate. Reduced ambient barometric pressure had no effects on foot swelling or Tsk. It is concluded that modest leg activity during 8 h of sitting has several effects on the circulation in the feet: some effects promote and some prevent oedema formation. However, the net result is a reduction in foot swelling.

Measurement of colloid osmotic pressure in body fluids: errors caused by preheparinized glass capillaries and by CO2 loss.

The effect on colloid osmotic pressure (COP) of heparinizing body fluids was estimated with a low compliant osmometer, using Diaflo PM-30 or PM-10 membranes (Amicon, Lexington, Mass., USA). It was found that collecting and storing samples in preheparinized glass capillaries may increase COP by up to 4.0 mmHg. Measurements on heparin and protein solutions, separately and mixed, show that these macromolecules have a mutually potentiating effect on COP, probably by excluding part of the water as distribution space for the other molecular species. While this 'heparin error' varies among various types and batches of capillaries (Vitrex, Modulohm I/S), the content of heparin in some batches appears to be two to three times greater than the declared minimum. Alternatively, the excess COP may result from addition of other water-soluble macromolecules in the heparinization process. Even if some batches do not give appreciable error, we recommend to avoid preheparinized capillaries for measurement of COP. Both defibrination, and the amount of heparin needed to anticoagulate macro blood samples, have insignificant effect on COP. Loss of CO2 by diffusion from separated plasma may increase pH towards 9.5. Concomitantly, COP increased by 2.1 mmHg per pH-unit. If plasma or serum samples are capped within some minutes after separation, they may be stored for weeks at 4 degrees C in polyethylene tubes without appreciable change of COP.

Transcapillary fluid dynamics during the menstrual cycle.

Transcapillary fluid dynamics in the follicular and luteal phase in women without symptoms of premenstrual syndrome were studied. Interstitial colloid osmotic pressure was measured by the "wick" method and interstitial hydrostatic pressure by the "wick-in-needle" method in subcutaneous tissue on the thorax and ankle. From follicular to luteal phase, the following changes were observed: Colloid osmotic pressures were significantly reduced, both in plasma (mean 2.5 mm Hg) and in the interstitium (thorax mean 1.9 mm Hg and ankle mean 2.0 mm Hg). The interstitial hydrostatic pressures did not change. There were no significant changes in serum albumin, hemoglobin, or hematocrit. A slight, but significant, weight gain was observed (mean 0.7 kg). The reduced plasma and interstitial colloid osmotic pressures in the luteal phase may be due to water retention, but the observed reductions in colloid osmotic pressures are probably not fully explained by simple dilution. A reduction in total protein mass in the luteal phase is suggested.

Transcapillary fluid balance in pre-eclampsia.

The fluid transport between the plasma and interstitial fluid compartment is governed by the Starling forces, i.e. the capillary pressure (Pc), interstitial fluid hydrostatic pressure (Pi) and colloid osmotic pressure in plasma (COPp) and interstitial fluid (COPi). Interstitial fluid was collected from subcutaneous tissue on the thorax and ankle by implanted wicks and Pi was measured using the 'wick-in-needle' technique. In pre-eclampsia, COPp is reduced due to hypoproteinaemia and this predisposes towards loss of fluid from the vascular compartment. An important oedema-preventing mechanism is reduction of COPi, which serves as a homeostatic buffer against increased capillary filtration. This mechanism works in moderate, but not in severe pre-eclampsia. A higher COPi was found both at the thorax (8.3 vs 7.0 mmHg) and ankle (5.9 vs 3.9 mmHg) in the group with severe pre-eclampsia compared with the group moderate pre-eclampsia, in spite of a significant reduction in COPp (15.5 vs 19.9 mmHg). These findings suggest that an increased microvascular permeability of plasma proteins to subcutaneous tissue contributes to COPp reduction in severe pre-eclampsia.

Proteinuria in fighter pilots after high +Gz exposure.

Exposure to high gravitational forces acting along the body axis towards the feet (+Gz) causes considerable strain on several organ systems, including the kidneys. During +Gz tolerance studies without anti-G suits, significant amounts of protein and hyaline casts were found in 17 of 20 fighter pilots after centrifugation. The G load alternated between 3.5 and 5.5 G. Mean time in the centrifuge was 15 min. For comparison we examined another group of 19 fighter pilots after air combat maneuver training with anti-G suits. None showed proteinuria. The proteinuria most likely indicates a severely depressed renal blood flow during centrifugation.

Turnover rate of interstitial albumin in rat skin and skeletal muscle. Effects of limb movements and motor activity.

Fractional removal rate (FRR) of radioactive-labelled human serum albumin (I-HSA) injected subcutaneously or intramuscularly was determined by external gamma-detecting equipment. Radioactivity over the injection site fell monoexponentially during registration periods up to 6 h. The FRR was calculated as the turnover rate constant of the radioactivity removal. The FRR fell into one of two ranges: in anaesthetized rats FRR was 0.02-0.03 h-1, and in awake and freely moving rats FRR was 0.08-0.11 h-1. In awake rats, FRR was similar during day and night (spontaneous motor activity is four times higher during the night). Passive limb movements at 1 Hz in anaesthesia increased FRR in skin to that in awake rats, while FRR in skeletal muscle was unchanged. Immobilization resulted in FRR similar to that in anaesthesia. Interstitial albumin mass did not change during 6 h of anaesthesia. It is concluded that the observed FRR reflects steady state changes in albumin turnover. In the awake and freely moving rats at least 3/4 of the removal of albumin is by the lymphatics. Calculated lymph flow was 10 microliters g-1 h-1 and 40 microliters g-1 h-1 in skeletal muscle and skin respectively with corresponding figures during anaesthesia of 3 microliters g-1 h-1 and 10 microliters g-1 h-1 respectively.

Oedema-preventing mechanisms in subcutaneous tissue of normal pregnant women.

Fluid transport between the plasma and interstitial fluid compartment is governed by the Starling forces, i.e. the capillary pressure (Pc), interstitial fluid hydrostatic pressure (Pi) and colloid osmotic pressure in plasma (COPp) and interstitial fluid (COPi). The COPp, COPi and Pi were measured in 10 normal pregnant women in the first and 10 women in the third trimester of pregnancy. Interstitial fluid was collected from subcutaneous tissue by implanted wicks and Pi was measured by the 'wick-in-needle' technique. The COPp was reduced from 23.2 mmHg in the first trimester to 21.1 mmHg in the third trimester. Concomitantly, COPi decreased from 13.1 to 8.4 mmHg on the thorax and from 9.6 to 5.5 mmHg at the ankle. Only small changes in Pi were observed. The more marked fall in COPi than in COPp indicates that a rise in Pc, in addition to hypoproteinaemia, contributes to increased capillary fluid filtration in pregnancy. The reduction in COPi opposes the increased filtration and thereby prevents a rise in interstitial fluid volume and oedema formation. These physiological changes imply a reduced safety margin against oedema formation in late pregnancy.

An evaluation of ultrafiltration as treatment of diuretic-resistant oedema in nephrotic syndrome.

Plasma volume, plasma colloid osmotic pressure, creatinine clearance and sodium excretion were measured before and after ultrafiltration treatment in six patients with diuretic-resistant nephrotic syndrome. The mean total ultrafiltrate volume in two sessions on two successive days was 7460 ml, the mean ultrafiltration rate was 22.0 ml/min and the calculated plasma refilling rate was 19.9 ml/min. Plasma volume and creatinine clearance were unchanged and sodium excretion was reduced after treatment. A short-lasting drop in blood pressure was seen in 3 of the 12 treatment sessions. No other complications were noted. Ultrafiltration is a safe and useful alternative in the treatment of the few patients with massive oedema due to nephrotic syndrome not responding to conventional therapy.

Interstitial fluid volume, plasma volume and colloid osmotic pressure in patients with nephrotic syndrome.

Colloid osmotic pressure in plasma (IIp) and in subcutaneous interstitial fluid (IIi) (wick technique), plasma volume (PV) and interstitial fluid volume (IFV) were measured in nephrotic patients (n = 11) and in healthy controls. Six of the patients were treated with ultrafiltration and the parameters were measured before and after withdrawal of mean 7460 ml (total ultrafiltrate in two sessions). In the nephrotic patients mean IIp was 11.6 mmHg and IIi was 3.9 mmHg compared to 28.6 mmHg and 15.8 mmHg, respectively, in healthy controls. PV was in the normal-to-high range and IFV was increased to 150% of the valued in controls. No statistically significant change in PV, IIp or IIi was found after ultrafiltration, and IFV was reduced by 20%. The results indicate that reduction in IIi is an important oedema-preventing factor and that the reduction in interstitial protein mass is more than proportional compared to the degree of hypoproteinaemia. Ultrafiltration in the rate and magnitude we have used, leads to reduction in IFV, but small changes in PV, IIp or IIi.