The neuroendocrine response to surgical trauma is a complex set of hormonal and metabolic changes evoked by anxiety, blood loss, tissue damage, visceral handling, and also by the anaesthetic drugs and procedures (Traynor & Hall, 1981). A useful approach to understanding the surgery-induced stress syndrome is to individualize these stressful stimuli in order to explore the specific effects of anxiety, anaesthesia or surgery itself on the endocrine and metabolic responses that are observed altogether. The relative importance of each element contributing to surgical stress should be better characterized in order to provide the rationale for improving the management of surgical patients. For instance, it remains unclear whether the physiological alterations induced by surgical stress are a single syndrome arising from the addition of several stressors or comprise parallel responses to each stressor, with some convergent end-points.

The analysis of picomolar quantities of magnesium by electrothermal atomic absorption spectrophotometry (EAAS) was studied using a Perkin-Elmer-Zeeman 3030 spectrophotometer. The absorbance signal was not heavily dependent on the atomization temperature, but was greatly reduced when ashing temperatures in excess of 1200¡C were applied. The magnesium signal was significantly depressed in the presence of excess chloride in the sample matrix. However, use of NH4NO3 as a matrix modifier was sufficient to overcome this artefact. The analytical sensitivity was 0·15 absorbance units pmol-1 and the detection limit was 0·04 pmol. Using nanolitre constriction pipettes to dispense standards, the mean coefficient of variation was 5 %. Measurement of magnesium handling in the rat proximal convoluted tubule revealed a significant correlation between the tubular fluid-to-plasma ultrafiltrate (TF/UF) concentration ratio for magnesium and the tubular fluid-to-plasma (TF/P) concentration ratio for [3H]inulin (r2 = 0·56, n = 17). This indicated that magnesium is concentrated during its passage along the proximal tubule. In contrast, this was not the case for sodium (r2 = 0·11, n = 16). Mean (TF/UF)Mg (1·16 ± 0·07, n = 17) for random punctures was significantly greater than that for sodium ((TF/UF)Na = 1·02 ± 0·02, n = 16). Despite concentration of magnesium in the lumen, significant net reabsorption of magnesium was observed along the length of the tubule (fractional reabsorption, FRMg = 19·4 ± 3·0 %, n = 17). In conclusion, EAAS provides a highly sensitive, reproducible and technically simple method for measuring picomolar quantities of magnesium in renal tubular fluid.

Transmission electron microscopic techniques were used to carry out a quantitative analysis of the density of fenestration in the inner medullary vasa recta of the rat kidney. Measurements were made at 200 µm intervals from the tip to the base of the papilla (1800 µm from the tip). Fenestral diaphragms were estimated to be 65·4 ± 0·78 nm in diameter (mean ± S.E.M.), and were arranged in plaques with a mean interfenestral distance of 114·8 ± 2·6 nm. Near the tip of the papilla there was no correlation between vessel size and degree of fenestration; density of fenestration, however, began to decrease about 1400 µm from the tip. The ratio of fenestrated to non-fenestrated profiles of vasa recta was found to be linear with respect to distance from the tip (r = 0·991), with values ranging from about 40 : 1 near the tip to 2 : 1 near the base of the papilla. We have estimated the proportion of the total surface area of a fenestrated vasa recta occupied by fenestral diaphragms to be 0·057 at 1000 µm from the tip. The total potential conductance (K) of a 200 µm segment of fenestrated vessel at 1000 µm from the tip was calculated to be 0·319 µm3 s-1 cmH2O-1, giving a hydraulic conductivity (Lp) of 0·030 µm s-1 cmH2O-1. We have also examined the reverse question of the conductance of a single fenestra if all the fluid flux across the vessel wall occurred through the fenestrae and none via the intercellular clefts or water channels; single fenestral conductance was estimated to be 1·94 × 10-3 µm3 s-1 cmH2O-1.

The relative contribution of intraluminal versus peritubular factors in mediating glomerulo-tubular balance (GTB) is still controversial. We modulated the load of tubular fluid to the proximal tubule of single nephrons of rats by injecting oil into the efferent arteries (EAO). In fifty nephrons the changes in reabsorption induced by obstruction occurred in the same direction as, and were significantly correlated with, the simultaneous changes in single nephron glomerular filtration rate (SNGFR) (y = -0·54 + 0·92x, R = 0·91, P < 0·0001). In an additional set of thirty-nine nephrons the load of tubular fluid was changed, during EAO, by partial collection from Bowman's space or from the early proximal convolution. Thus, the rate of tubular fluid delivery along the proximal tubule was changed in an experimental situation that prevented any modification in the oncotic pressure of peritubular capillaries. The changes in proximal deliveries during this experimental condition were significantly correlated with those during reabsorption (y = -2·87 + 0·71x, R = 0·82, P < 0·0001). These data demonstrate that GTB is fully expressed even when the native peritubular environment is kept constant while the rate of perfusion of proximal tubular segments with native tubular fluid is changed.

We have investigated the effect of temperature upon the rate-dependent decrease in the L-type Ca2+ current (iCa) in isolated rat ventricular myocytes. Increasing the rate of stimulation from 0·5 to 3·0 Hz for 30 s induced a reversible decrease in iCa which was temperature dependent. Compared to control (0·5 Hz), the first beat at 3 Hz was decreased by 38 ± 7 % at 22¡C and by 9 ± 1 % at 37¡C (mean ± S.E.M., n = 5, P < 0·05) and, after 30 s of 3 Hz stimulation, iCa was reduced by a further 26 ± 4 and 21 ± 2 % at 22 and 37¡C, respectively. The magnitude of this secondary decline was not significantly different at the two temperatures (P = 0·29). Corroboratory results were obtained from cell-attached patches which also illustrated that the rate-dependent decrease in iCa resulted from a reduction of open channel probability. Paired pulse experiments showed that the greater initial rate-dependent decrease in iCa at 22¡C occurred as a result of slower recovery from fast inactivation processes at 22 than at 37¡C. Recovery of the channel from fast inactivation was very temperature sensitive with a Q10 of 5·6. In contrast, the secondary, progressive decrease in iCa, which results from incomplete recovery from ultra-slow voltage-dependent inactivation, was similar at the two temperatures and appears to be much less temperature dependent.

The aim of this study was to determine the ouabain receptor density, Na+,K+-ATPase function and contractile properties of cardiac muscle in insulin-dependent and non-insulin-dependent rat diabetes mellitus (IDDM and NIDDM, respectively) and the reversibility of the diabetes-induced changes by insulin or thyroxin substitution. IDDM and NIDDM were induced in Wistar rats by streptozotocin injection. Contractile parameters were measured in isolated left ventricular trabeculae. [3H]Ouabain binding to myocardium was measured in right and left ventricular strips obtained from diabetic animals and their age-matched controls. Both the maximum [3H]ouabain binding capacity (Bmax) and the Kd for [3H]ouabain binding, as well as maximum 86Rb+ uptake and rate of contraction, were decreased in IDDM myocardium compared with controls. Insulin or thyroxin substitution reversed the reduction in Bmax and contraction rate, but not the decrease in Kd. In young, but not old, control animals, both Bmax and maximum 86Rb+ uptake were higher in the right ventricular myocardium than in the left one. In contrast to changes observed in IDDM, both Bmax and Kd for [3H]ouabain binding were increased in the left but not in the right ventricle of NIDDM animals. NIDDM caused no alterations in contractile properties. Prominent differences were observed in [3H]ouabain binding characteristics and myocardial contractility between young and old control animals. Bmax of [3H]ouabain binding and rate of contraction were inversely proportional in all preparations studied. It is concluded that IDDM and NIDDM induce different alterations in myocardial Na+,K+-ATPase, and these changes may influence the contractile properties of cardiac muscle.

Force (and power)-velocity characteristics were determined at different stimulation frequencies in in situ rat muscle with nerve stimulation at 36¡C. In isometric contractions (duration, 150 ms), maximal force is generated at ~120 Hz. In contrast, in the high velocity (250 mm s-1) shortening contractions, frequencies of ~400 Hz were needed to obtain maximal dynamic force, while 120 Hz elicited only ~26 % of the maximum. At the highest velocity measured, power production was significantly different (P < 0·05) among frequencies of 80, 120, 200 and 400 Hz, suggesting that maximal shortening velocity should be assessed using very high stimulation frequencies. However, the results further indicate that lower frequencies may be adequate in exercise studies that investigate fatigue and changes in power output during series of repetitive contractions.

In patients following myocardial infarction (MI), exercise tolerance and muscular strength are often markedly reduced. The purpose of this investigation was to determine if calcium (Ca2+) uptake and release by skeletal muscle sarcoplasmic reticulum (SR) are altered following MI and if such changes are associated with diminished muscular performance. SR vesicles were isolated from rat gastrocnemius muscle at 6 and 12 weeks following MI (via left coronary artery ligation) or sham surgery. At both post-surgery intervals, the rates of Ca2+ uptake (measured using fura-2) were 35 % greater in the MI group. In addition, the rates of Ca2+ release were increased in the MI group by 10 and 30 % at 6 and 12 weeks, respectively. At 12 weeks post-surgery, animals of the MI group showed significant reductions in in situ twitch and tetanic forces and significant elevations in the rates of tension increase and decrease. These data indicate that SR Ca2+ exchange is altered following MI. In addition, changes in SR function are associated with changes in force production by the whole muscle.

The purpose of this study was to quantify the possible reduction in ventilation that could be attributed to changes in cerebral blood flow (CBF) with hypoxia to determine whether it could be of sufficient magnitude to underlie hypoxic ventilatory decline (HVD). Six subjects underwent 20 min of isocapnic hypoxia (end-tidal PO2, 50 mmHg). An index of CBF was obtained using transcranial Doppler ultrasound of the middle cerebral artery. The CBF sensitivities to hypoxia and hypercapnia were obtained from the percentage changes in CBF between the last 3 min of the hypoxic or hypercapnic exposure and the 3 min period prior to the exposure. The magnitude of HVD during hypoxia was estimated by fitting a simple model of the ventilatory response to the hypoxic stimulus. The predicted fall in expiratory ventilation ([Vdot]E) due to a reduction in brain PCO2 generated by the increase in CBF with hypoxia in all subjects was less than the measured magnitude of HVD (33 %). Thus, the results from this study suggest that, in awake humans, changes in CBF during acute isocapnic hypoxia are quantitatively insufficient to underlie HVD in humans.

We compared the kinetics of oxygen uptake ([Vdot]O2) and phosphocreatine (PCr) during the adjustment to and recovery from plantar flexion exercise in moderately active older (n = 10, 66·9 years) and younger (n = 10, 27·5 years) individuals. [Vdot]O2 kinetics were similar in the two groups, with time constants ([tau]) averaging 46·3 ± 10·2 s (younger, on-transient), 38·1 ± 14·4 s (younger, off-transient), 46·3 ± 17·8 (older, on-transient) and 40·7 ± 19·2 s (older, off-transient). These were similar to corresponding PCr kinetics, measured by 31P nuclear magnetic resonance spectroscopy, which averaged 50·6 ± 24·0 s (younger, on-transient), 42·0 ± 16·1 s (younger, off-transient), 39·8 ± 22·0 s (older, on-transient) and 37·6 ± 21·6 s (older, off-transient). On-transient [tau] values for [Vdot]O2and PCr were correlated, for combined groups (r = 0·53; P = 0·015). We conclude that: (1) [Vdot]O2 and PCr kinetics during exercise of a muscle group accustomed to daily activity are not compromised in physically active older humans, and (2) PCr kinetics reflect the kinetics of muscle O2 consumption, and are expressed at the lung ([Vdot]O2 kinetics) after a transit delay.