EDITOR—The debate about whether we can learn from animals is far more subtle than the rapid responses to Roberts et al's systematic review of fluid resuscitation after haemorrhage suggest. 1 2 It depends on the problem and on the species of the animal; the lessons of comparative medicine are most useful when the model has sufficient similarities to suggest its relevance and enough differences to make it informative. Blanket assertions that we cannot learn from animals are naive, …
# ABC shows absence of evidence in measuring blood pressure during pregnancy {#article-title-2} EDITOR—In the short ABC on blood pressure measurement Beevers et al made several references to problems with measurement in pregnancy that have been discussed for many years without satisfactory resolution.1 There are four main points. 1. Interestingly, the vascular sounds that are caused by vibration of the vessel wall are clearly modulated by consistent changes in patterns of flow in the brachial artery in pregnancy (figure).2 Sequence of vascular sounds in normotensive pregnancy. Vascular sounds were recorded with microphone over brachial artery (Toshiba HSM-05B), with concomitant Doppler recording of brachial artery waveform (Toshiba PLF703ST)
Glomerular filtration rate (GFR) and extracellular volume (ECFV) were measured before, during and after treadmill exercise in 5 trained Thoroughbred horses (mean weight 483 kg). GFR/ECFV was determined by plasma disappearance of Tc-DTPA and ECFV was measured independently as thiocyanate space. Resting GFR averaged 1.6 l/min (3.3 ml/kg/min) and fell by over 40% during exercise, moreover the fall was severe even during the first walk, prior to trotting. The results suggest that rather than being protected, GFR is allowed to fall, even with mild exercise and that this is probably an adaptation to allow greater perfusion of muscle and skin. In man, GFR appears to be more resistant to the effects of exercise but it is hard to compare intensity of exercise between such different species.
Measurement of renal function in horses poses a particular challenge because plasma creatinine is influenced by muscle mass which is highly developed and variable between individuals, while conventional clearance methods involve potentially daunting problems, particularly urine collection and bladder washout. This paper provides data which enable technetium-diethyleneaminopentacetic acid (Tc-DTPA) clearance to be used to calculate glomerular filtration rate (GFR)/extracellular fluid volume (ECFV) as an expression of GFR in horses, as previously validated in humans, dogs and calves. Apart from being arguably a more physiological expression of GFR than using derivatives of body weight, the use of GFR/ECFV eliminates a source of delay and error, namely measurement of the injected dose, and offers the convenience of requiring only three blood samples. It therefore has advantages for both research and clinical applications.
This paper examines the possibility that treatment of diarrhoea with conventional oral rehydration solutions (ORSs) may be detrimental to villus structure by imposing nutrient deprivation and that such detrimental effects may be reduced or avoided by using a nutrient ORS. A conventional WHO-type ORS (W) was compared with two nutrient solutions (N and G) both containing high glucose concentrations and the latter containing glutamine; their effects on enteric structure were assessed by morphometric analysis of samples obtained from diarrhoeic calves after 96 h treatment. Comparisons were also made with samples from controls and diarrhoeic calves at the stage where oral rehydration would have begun in the treated groups. As in our previous ORS studies, diarrhoea was induced with enterotoxigenic Escherichia coli (09:K30:K99). We measured villus length and width, crypt depth and width and calculated villus surface area in proximal, mid and distal small intestine (PSI, MSI, DSI), using standard morphometric techniques. Proximal and distal spiral colon samples (PC, DC) were examined for crypt depth and width; mitoses per crypt were counted in samples from all regions. Non-diarrhoeic calves showed the expected gradient of villus length through PSI, MSI and DSI, hence data for each region are normalized as a percentage of the control value for that region. PSI showed the greatest loss of villus length and surface area (50%) with diarrhoea. In MSI and DSI the villus loss was greater with solution W and N or G, as were increased mitoses and crypt depth. Crypt depth and mitoses also increased in the colon with solution W. Colonic crypt width increased with diarrhoea and conventional oral rehydration but less so with G; there is reason to believe that such changes have functional significance. Crypt changes in colon, MSI and DSI were least with solution G. The changes developing in diarrhoeic calves prior to treatment were thus less apparent in those treated with a nutritional ORS, particularly if it contained glutamine.
Changes in plasma urea, creatinine and glomerular filtration rate (GFR) were measured in calves before and after development of diarrhoea and during treatment with a conventional (WHO-type) or a nutritional oral rehydration solution (ORS). Changes in urea and creatinine failed to represent the extent of pre-renal failure. The two ORSs differed in their impact on GFR with the nutritional ORS improving GFR whereas with the WHO-type solution it deteriorated further.
To be clinically reliable, blood pressure readings taken in quiet surroundings with good technique from healthy, unstressed subjects accustomed to the procedure, should be reasonably constant between occasions. Apart from changes attributable to age or stress, sustained rises suggest hypertension. Yet it is increasingly realised that arterial pressure shows great short-term lability. Despite this, ‘tracking’ occurs in groups of humans, i.e. when ranked by blood pressure they tend to maintain their rank order. This paper examines month-on-month variability of arterial pressure, measured by non-invasive oscillometry (Dinamap) in both pet dogs and kennel populations. ‘Tracking’ occurred and there was also evidence of ‘white coat’ effects. Heart rate was more variable than arterial pressure and should not be used to reject pressure readings unless changes are extreme. There was further evidence that canine blood pressure rises with age.
Dogs have provided classic models of induced hypertension. This paper shows that despite being susceptible to hypertension, they are naturally resistant to its development even when renal function is severely compromised. The proportion of hypertensive dogs was almost as low among those with reduced glomerular filtration rate (GFR) (9%) as those with normal GFR (6%). Dogs with GFR less than 33% of the normal lower limit (with an average GFR equivalent to 10 mL min-1 in a 70-kg patient) had arterial pressures not significantly above normal. Only dogs with a GFR 33-75% of the lower limit of normal had significantly elevated systolic pressure, though none was actually hypertensive. Since there was no correlation between arterial pressure and GFR below 33% of lower limit, the dogs in the 33-75% range may be showing an effect of increased pressure, rather than a cause. In humans with GFR less than 33% of normal, the majority are hypertensive. Since various aspects of canine cardiovascular and renal function are comparable with humans, the question is why dogs, despite being capable of developing hypertension, are resistant to it, even when they have chronic renal insufficiency.
The essential constituents of a conventional oral rehydration solution (ORS) are sodium, glucose and a bicarbonate precursor. The glucose promotes sodium uptake but because these solutions are isotonic, it is insufficient to sustain calorie requirements. This paper examines the performance of a novel ORS with over three times the conventional glucose concentration, by comparing it with two leading commercial ORSs in calves with induced Escherichia coli diarrhoea. This solution showed greater ability than the current market-leading ORS to repair extracellular fluid and plasma volume and to correct both hyponatraemia and metabolic acidosis, especially in more severely affected calves. In acidotic calves it was more effective in correcting hyperkalaemia, probably by supplying glucose to promote cellular potassium uptake as well as by correcting the acidosis. It therefore appears possible to depart from the traditional isotonic formulations for calf ORSs and gain significant nutritional support while retaining effective rehydration and correction of acid-base and electrolyte disturbances. This seems especially important in young animals where energy deprivation imposes a particular penalty; the use of hypertonic ORSs should not, however, be extended to other species without further research.
Oscillometric measurements of arterial blood pressure were compared with direct measurements made on seven dogs fitted with catheters. Tail and limb cuff sites were used while the dogs were gently restrained either standing or in lateral recumbency. The accuracy of the readings for the various cuff sites was compared with the direct (gold standard) readings. The accuracy of the indirect readings was improved by using mean values from a series of readings rather than individual values and when the dogs were in lateral recumbency rather than standing. The differences between the direct and indirect values were greatest with high pressures, and with systolic rather than diastolic values. In standing dogs, the proximal forelimb readings (when obtainable) correlated most closely with the direct readings. The tail cuff readings correlated significantly with the direct readings, though less closely. The tail cuff readings were the most easily recorded in the standing dogs. In the laterally recumbent dogs, the readings from all the cuff sites correlated closely with the direct values except for diastolic readings from the distal hindlimb.
There is an engagingly simple explanation for the renal involvement in edema. Occasionally, when the glomeruli leak sufficient protein to reduce plasma albumin, the kidney is the primary cause. Whatever the cause, however, edema formation involves the expansion of the extracellular fluid (ECF) as a whole, with the major compartment (the interstitial fluid, ISF) expanding at the expense of the minor compartment, plasma. This is only feasible because the kidney responds, as with any other cause of hypovolemia, by conserving sodium (and water) in defense of plasma volume. In that sense, edema is an "underfill" phenomenon and the kidney is always its enabling cause. In various circumstances, however, edema fluid accumulates as a consequence of overexpansion of plasma volume, and suspicion then arises that the kidney is its primary cause, i.e., that it is an "overfill" phenomenon. The intervening shades of grey arise from the realization that abnormal escape of intravascular markers of plasma volume could make it appear falsely elevated; moreover, engorgement, for example ofportal capillaries, could increase measured plasma volume without increasing the functional
As part of an assessment of stress during the training of guide dogs for the blind, blood pressures have been monitored in their main breeds. For this article a population of 227 Labradors, between 9 and 24 months of age, had indirect arterial blood pressures measured and means taken of five readings. They were ranked according to their pressures. Prior to the measurements, their character was independently assessed as "stress-prone" or "non-stress-prone" by their highly experienced and trained handlers. The pressure data distribution of stress-prone animals in the ranking was analysed; they were significantly more likely to be found at the high end of the blood pressure range for that population.
The contrast medium iohexol can be used as a marker for the measurement of glomerular filtration rate. It has the advantages of sample stability and the availability of a simple, automated (though expensive) analyser. The clearance of iohexol was compared with the clearance of Tc-DTPA in 24 dogs with known or suspected renal impairment. The results were comparable but fractionally lower with iohexol. The correction factors developed for human beings were found to be satisfactory in the dogs, thus validating the software routines used in the automated analyser with the canine samples.
It is often said that the success of oral rehydration in humans depends on the adequacy of the improvement in the composition and volume of extracellular fluid, not reduction of faecal output. Indeed, the latter may increase initially. Such increases do not prevent the treatment from being effective but they may, falsely, undermine its acceptability to patients or those caring for them. This paper provides data to show that standard oral rehydration solutions used to treat experimentally induced calf diarrhoea procure identical improvements in plasma volume during the first 48 h, whether faeces improve or not, and those calves whose faecal consistency improved actually showed greater deterioration of extracellular fluid volume. While it is important for this to be appreciated by clinicians and explained to owners, it is absolutely imperative that those responsible for the approval of new therapeutic products for registration understand and accept that faecal consistency offers no reliable insight into the effectiveness of oral rehydration therapy for calf diarrhoea. It was, however, interesting that there was some relationship with correction of acidosis-perhaps because some of the contributing factors arise from colonic dysfunction.