1. The haemodynamic response to acute central hypovolaemia consists of two phases. During phase I, arterial pressure is well maintained in the face of falling cardiac output (CO) by baroreceptor-mediated reflex vasoconstriction and cardio-acceleration. Phase II commences once CO has fallen to a critical level of 50-60% of its resting value, equivalent to loss of approximately 30% of blood volume. 2. During phase II, sympathetic vasoconstrictor and cardiac drive fall abruptly and cardiac vagal drive increases. In humans, this response is invariably associated with fainting and has been termed vasovagal syncope. 3. In both experimental animals and in humans, the responses to acute central hypovolaemia are greatly affected by anaesthetic agents, in that the compensatory responses during phase I (e.g. halothane) or their failure during phase II (e.g. alfentanil) are blunted or abolished. 4. Therefore, our present knowledge of the neurochemical basis of the response to hypovolaemia depends chiefly on the results of experiments in conscious animals. Use of techniques for simulating haemorrhage has greatly enhanced this research effort, by allowing the effects of multiple treatments on the response to acute central hypovolaemia to be tested in the same animal. 5. The results of such experiments indicate that phase II of the response to hypovolaemia is triggered, at least in part, by a signal from cardiac vagal afferents. There is also strong evidence that phase II depends on brainstem delta-opioid receptor and nitrergic mechanisms and can potentially be modulated by circulating or neuronally released adrenocorticotropic hormone, brainstem serotonergic pathways operating through 5-HT1A receptors and opioids acting through mu- and kappa-opioid receptors in the brainstem. 6. Phase II also appears to require input from supramedullary brain centres. Future studies should determine how these neurotransmitter systems interact and their precise neuroanatomical arrangements.

Animals↗

PubMedDate not supplied

Statistics in physiology and pharmacology: a slow and erratic learning curve.

1. Learning how to apply statistical analyses to the results of experimental or clinical studies may take a lifetime of trial (and sometimes error), as it has done in the author's case. There is no evidence that biomedical investigators of the present generation are on a steeper learning curve. Gross misunderstandings of the purpose and functions of statistical analysis are apparent in applications to research grant-giving bodies and ethics committees, in manuscripts submitted to journals and sometimes in published papers. 2. Although estimation of minimal group (sample) size for a given power is an essential step in planning clinical studies, it seems to be used rarely in laboratory experimental work. This is despite exhortations to restrict the number of animals used to a minimum. 3. Most investigators use hypothesis testing to analyse their results, but their understanding of the meaning of the resultant P-values is slight. 4. A flaw found almost universally in biomedical manuscripts is to make multiple inferences from the results of a single study. The goal of statistical analysis is to maintain the familywise type I error rate (risk of false-positive inference) at a predetermined level (usually 5%). But, when multiple inferences are made from the same experiment, the risk of false-positive error is inflated. There are two solutions to this problem: (i) use a multiple comparison procedure to control the familywise type I error rate; and (ii) test a single, global hypothesis. 5. Biomedical investigators have been quick to acquire computer statistics software and to use it to analyse their experiments. However, they have been slow to recognize the limitations of this software. These include: (i) inadequate documentation of routines, so that neither the user nor the reader of published papers can be sure how the tests have been executed; (ii) flawed algorithms for the execution of statistical procedures; and (iii) failure to recognize that the best software for their purposes is that which takes them just beyond their statistical horizons. 6. The obvious solution to these difficulties is to recruit a biomedical statistician into every research group, at a relatively trivial cost. However, properly qualified biostatisticians are in desperately short supply in Australia. It follows that research groups, national grant-giving agencies and academic institutions must make provision for the proper training and subsequent employment of biostatisticians.

Data Interpretation, Statistical↗

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Haemodynamic effects of isometric handgrip exercise in patients convalescent from myocardial infarction.

1. Cardiac performance in response to 30% maximal isometric handgrip exercise was studied in fourteen patients convalescing uneventfully from a first myocardial infarction. In each patient, heart rate, mean arterial blood pressure and cardiac index were measured, and total peripheral resistance was calculated. The covariance of changes in the mean arterial blood pressure and cardiac index in these patients was matched against tolerance limits calculated from published data for normal subjects. 2. All patients had normal haemodynamic values at rest, and showed the usual rise of heart rate and mean arterial pressure during handgrip exercise. However, in six patients (group 1) the rise in mean arterial pressure was, as in normal subjects, accounted for mainly by a rise in cardiac index, with no consistent change in peripheral resistance. In eight patients (group 2), the mean arterial pressure rose to the same level as in group 1, but with a consistent increase in peripheral resistance and a smaller rise in the cardiac index. 3. It is suggested that in a substantial proportion of patients who are making a seemingly uncomplicated recovery from myocardial infarction, it may be possible to unmask an impairment of left ventricular function by means of isometric handgrip exercise.

Adult↗

PubMedDate not supplied

Comparison of methods for eliciting the baroreceptor-heart rate reflex in conscious rabbits.

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Animals↗

PubMedDate not supplied

Does the baroreceptor-heart rate reflex indicate the capacity of the arterial baroreceptors to control blood pressure?

1. We have examined the question asked in the title by studying: the carotid baroreceptor reflex in man with a variable-pressure neck chamber; the carotid baroreceptor reflex in conscious rabbits with a variable-pressure capsule around the carotid bifurcation; and the barorecptor-heart rate reflex. 2. At rest, the association between the sensitivities of the carotid baroreceptor-blood pressure and -heart rate reflexes, and of these with the baroreceptor-heart rate reflex, is weak. Exercise causes dissociation between control of blood pressure and heart rate. In hypertension, depression of the baroreceptor-heart rate reflex does not reflect the altered characterisitics of the carotid sinus-blood pressure reflex.

Animals↗

PubMedDate not supplied

Static versus dynamic techniques for characterizing the carotid sinus baroreceptor reflex in conscious rabbits.

1. We have studied in conscious rabbits the dynamic (AC) characteristics of the carotid sinus baroreceptor reflex by effecting sinusoidal pressure changes across the all of the carotid sinus of 28, 55 and 103 mmHg amplitude at frequencies of 0.005, 0.01 and 0.01 Hz. 2. The amplitudes of the reflex oscillations of blood pressure and heart rate were dependent on both input frequency and amplitude. The output amplitude for blood pressure was maximal at 0.005 Hz, for heart rate at 0.02 Hz: i.e. blood pressure output exhibited frequency attenuation, heart rate output frequency amplification. 3. AC gain was similarly dependent on input frequency, and was inversely associated, for both blood pressure and heart rate, with input amplitude. 4. Phase lag for heart rate behind carotid transmural pressure was small (3-4 degrees), suggesting that vagal efferent mechanisms predominated. For blood pressure it was positively associated with input frequency, and was much larger (30 degrees, 19 degrees and 12 degrees). 5. The reflex was also elicited by intermittent static (DC) input. The AC and DC output amplitudes were similar at high input amplitudes, but DC gain was always greater than AC except for the case of heart rate at high input frequency and low input amplitude. 6. The AC characteristics of the reflex were satisfactorily reproducible over 2-15 days. AC output amplitude provides a measure of the performance limits of the reflex, AC gain of its capacity to buffer rapidly changing disturbances, while phase lag reflects the inertia of the reflex.

Animals↗

PubMedDate not supplied

Comparison of the reflex effects of arterial baroreceptors and cardiac receptors on the heart rate of conscious rabbits.

The reflex effects on heart rate (HR) of presumptive cardiac receptors have been differentiated from those of the arterial baroreceptors in conscious rabbits by inflating cuffs on the ascending aorta, descending aorta, inferior vena cava and pulmonary artery. When the outflow from the right ventricle was progressively impeded the accompanying increase in HR was entirely explicable by unloading of the arterial baroreceptors. As the outflow from the left ventricle was progressively impeded there was an initial increase in HR due to unloading of the arterial baroreceptors, followed by a progressive decline. This decline was attributed to a reflex arising from vagally-innervated receptors in the left side of the heart. The threshold of this cardiac receptor-HR reflex occurred at a higher level of mean aortic pressure than that at which the effects of the arterial baroreceptors on HR were maximal. Cholinergic (vagal) efferent nerves were responsible for two-thirds of the decline in HR caused by the reflex. The properties of the cardiac receptor-HR reflex were altered by drugs that affect myocardial contractility. Isoprenaline raised the mean aortic pressure at which the threshold occurred, but lowered the corresponding level of left ventricular end-diastolic pressure. Propranolol virtually abolished the reflex, even though left ventricular end-diastolic pressure reached a high level. It is concluded that in the conscious rabbit the arterial baroreceptor reflexes normally prevent the threshold of the cardiac receptor-HR reflex from being attained.

Animals↗

PubMedDate not supplied

Concern about gain: is this the best measure of performance of cardiovascular reflexes?

Open-loop gain is commonly used as a measure of the effectiveness of cardiovascular reflex control systems. There is no evidence that directly measured baroreflex gain for heart rate gives useful information about blood pressure control in human or experimental hypertension. Calculation of open-loop gain for blood pressure from closed-loop observations requires many assumptions to be made. Calculation of the independent and interactive effects of reflex inputs by factorial analysis may be more versatile, and give a more useful expression of the actions and interactions of cardiovascular reflexes in response to physiological disturbances, than does the calculation of gain.

Animals↗

PubMedDate not supplied

Haemodynamic and metabolic responses of laboratory rabbits to near-maximal treadmill exercise.

1. The haemodynamic and metabolic responses of four laboratory rabbits to horizontal treadmill exercise at 8, 12, 16 and 20 m/min were studied. The primary haemodynamic variables measured were heart rate, cardiac output and arterial pressure. The metabolic variables measured were arteriovenous oxygen difference, whole-body oxygen consumption and central venous plasma lactate concentration. 2. Only at 8 m/min did the haemodynamic and metabolic variables reach an approximate steady state. This was the greatest speed at which aerobic exercise could be sustained for 4 min in all rabbits. 3. As the speed of the treadmill was increased the rabbits showed signs of exhaustion after progressively shorter periods of exercise. Exhaustion was associated with steep rises in central venous plasma lactate concentration. Exhaustion was also usually associated with secondary rises in systemic vascular resistance and arterial pressure, especially at 20 m/min. 4. The asymptotic (maximal) values for heart rate, cardiac index and O2 consumption were 386 beats/min, 263 ml/kg per min and 21.7 ml/kg per min, respectively. heart do not permit it to run continuously at other than a slow rate. Exhaustion is associated with increasing oxygen debt and, especially at near-maximal rates of exercise, with intense vasoconstriction in as yet unidentified vascular beds.

Animals↗

PubMedDate not supplied

Update: microcomputer statistics packages. A personal view.

1. There have been a number of recent commercial developments and new versions of microcomputer statistical software packages since the last review in December 1995. 2. New versions for Windows have been released: SPSS 7.0 (Windows 95), SYSTAT 6.0 (Windows 3.11, 95, NT) and MINITAB 11.0 (Windows 3.11, 95, NT). 3. The minimum requirements of microcomputer hardware to run the statistical packages under Windows now include 486 or Pentium processors and 16 Mb of RAM. 4. It is now clear to the reviewer that no package that operates under Windows can be recommended unless it is possible to execute analyses by commands as well as by menus. 5. The Internet is an important medium for disseminating information about forthcoming new versions of statistical software packages and about flaws in recently released versions of such packages.

Computer Communication Networks↗

PubMedDate not supplied

A new school of surgery in Australia.

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Australia↗