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Biomedical subjects

R J Linden

Publications and source records attributed to R J Linden.

At least 19 recordsLinked to original sources

Indices for detection of changes in cardiorespiratory fitness during exercise training in man.

A decrease in the elevation of the linear relation of heart rate on oxygen consumption (HR/VO2) throughout submaximal exercise testing has previously been used in individuals as an index of improvement in cardiorespiratory fitness after a moderate intensity training programme. In the present investigation, changes in HR/VO2 elevation and its variability were quantified and compared with those of other similar indices. These comprised changes in the level of oxygen consumption or heart rate attained at respiratory exchange ratio (R) of unity (VO2/R=1 or HR/R=1. In a first trial in six healthy volunteers, the decrease in HR/VO2 elevation caused by 16 weeks of training significantly exceeded measurement variability, and was associated with increases and decreases respectively in VO2/R=1 and HR/R=1. In a second trial in eight healthy volunteers, the three indices were obtained at four stages during the course of the 16 weeks of training, to grade the improvement in fitness. There were progressive changes in the three indices, the magnitude of which was greatest in the case of the HR/VO2 index. The findings make it possible quantitatively to obtain a graded measure of improvement in fitness during exercise training as indicated by the magnitude of decreases in HR/VO2 elevation.

Adult

Coronary flow and left ventricular pressure during diastole in the anaesthetized dog.

There is controversy about the effect of left ventricular pressure on resistance of the intramyocardial coronary vessels. In anaesthetized dogs the effect of left ventricular pressure on coronary flow during diastole was studied using an extracorporeal circulation and allowing the heart to contract and relax isovolumically. At constant coronary perfusion pressure of about 45 mmHg with maximal coronary vasodilatation, produced by dipyridamole, increases in diastolic left ventricular pressure to 22 mmHg, producing a volume of 50 ml, did not affect diastolic coronary flow. It is suggested that in the intact animal over the physiological range of left ventricular diastolic pressure the resistance in the coronary vessels is not affected.

Anesthesia

Heart rate and hemodynamics.

Evidence is presented to show that cardiac output is little affected by changes in heart rate but the heart volumes, systolic and diastolic, are inversely related. Heart rate is controlled by changes in efferent nerves, sympathetic and vagal, which are in turn controlled from central and reflex sources. An argument is presented showing that reflexes from receptors in the atria control heart volumes by affecting, in the short term heart rate, and in the long term water intake (thirst) and urine flow, and therefore blood volume. Explanations of the mechanisms involved are presented.

Animals

Coronary response to transient increases in transmural pressure.

Previous studies have shown that transient increases in aortic blood pressure obtained by occlusion of the descending thoracic aorta, in anesthetized dogs with beta-blockade and vagal section, did not affect coronary vascular resistance apart from a non-significant increase just after release of the constriction. The present study examined whether this response also occurred in the normally innervated heart. Experiments were carried out in six anesthetized dogs, in which pressure in the aortic root and in the left ventricle, as well as flow in the left circumflex coronary artery, were recorded. Coronary vascular resistance was calculated as the ratio of the difference between aortic pressure and left ventricular pressure to coronary circumflex flow during the slow inflow phase. Before occlusion coronary vascular resistance was significantly lower than during the same period in the previous studies using animals with beta-blockade and vagal section. During the occlusion, in contrast with the previous investigation, the increase in aortic pressure caused a significant increase in coronary vascular resistance 10 seconds after the beginning of the occlusion. Coronary vascular resistance was further increased immediately after release of the occlusion, concomitantly with the decrease in aortic pressure, which fell abruptly below the control level. The increase immediately after the release of the constriction was qualitatively similar, but greater in extent, to that observed in the animals with vagal section and beta-blockade. These differences are assumed to depend on a lower vasomotor tone in the normally innervated hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The myogenic contribution to coronary autoregulation.

It seems now, mainly from the results of the experiments carried out in the Department of Human Anatomy and Physiology of the University of Turin, Italy, that there is an active myogenic response in the coronary vessels. In response to changes in the transmural pressure, both increases and decreases, in the coronary vessels transient contractions and relaxations (respectively) of the smooth muscle wall can be demonstrated. Although this suggested mechanism can not be fully integrated into a hypothesis explaining autoregulation of blood flow in the coronary vessels it does seem a strong possibility that it takes part; but further investigation will be necessary to clarify all aspects of this kind of regulation.

Animals

The relationship between left atrial pressure and atrial receptor discharge in dogs and cats with different body weights.

The diuretic response to distension of a large balloon in the left atrium and the increase in discharge of atrial receptors for a given increment in left atrial pressure have been found to be greater in dogs with a high blood volume than in dogs with a low blood volume. To determine whether atrial size may influence atrial receptor discharge, a group of cats and two groups of dogs with different body weights were examined under anaesthesia with alpha-chloralose. The relationship between atrial receptor discharge and left atrial pressure was determined in twenty-six fibres from seven cats, thirty-seven fibres from eight small dogs weighing less than 15 kg and twenty-five fibres from five large dogs weighing more than 25 kg. The slope of the relationship between the increase in atrial receptor activity and increments in left atrial pressure was shown to be significantly greater in the large dogs than in the small dogs, and the slopes in dogs were greater than in cats. The size of the atria was greater in larger dogs than small, and both those groups had atria larger than those of the cats. These findings indicate that the response of an increase in atrial receptor discharge to the same increment in left atrial pressure was greater in large animals than small and that this difference is possibly due to the different atrial size.

Animals

Coronary myogenic responses to abrupt changes in aortic blood pressure in anaesthetized dogs.

A transient increase in coronary transmural pressure was produced in anaesthetized dogs by occlusion of the descending thoracic aorta. Aortic blood pressure (ABP), left ventricular pressure and coronary flow were measured; coronary vascular resistance (CVR) was calculated. Results were similar in innervated and denervated hearts. Occlusion for 10 and 20 s resulted in no change in CVR for 15 s, followed by a metabolic dilatation attributable to enhanced oxygen demand; after release the fall in ABP resulted in an immediate increase in CVR, caused by vascular elastic recoil, followed by hyperaemia.

Anesthesia

Effect of the cessation of an infusion of vasopressin in acutely hypophysectomized anaesthetized dogs.

Stimulation of left atrial receptors in dogs anaesthetized with chloralose results in a reflex diuresis and a small decrease in the plasma concentration of vasopressin. It has been suggested that this diuretic response is solely mediated by the antidiuretic hormone, vasopressin (Gauer & Henry, 1976; Ledsome, 1985). The present investigation was designed to determine how these anaesthetized dogs, which are thought to be insensitive to changes in plasma vasopressin, respond to small decreases in plasma vasopressin similar to those observed during stimulation of left atrial receptors. In the event it was shown for the first time that it is possible to obtain a water diuresis in an anaesthetized animal in response to a small fall in the concentration of plasma vasopressin. In order to produce changes in plasma vasopressin similar to those seen during stimulation of left atrial receptors the pituitary gland was removed and an intravenous infusion of arginine vasopressin was given in eleven dogs anaesthetized with chloralose; a small decrease in plasma vasopressin was then produced by replacing the vasopressin with an infusion of saline for 30 min. A decrease in the plasma concentration of 1.29 pg cm-3 from a control concentration of 1.85 pg cm-3 resulted in a 96.7% increase in urine flow. The fall in concentration of vasopressin consequent upon stimulation of atrial receptors could, therefore, explain the water diuresis in the anaesthetized dog preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia

The effect of indoramin on exercise performance in mild hypertension.

The alpha 1-adrenoceptor antagonist indoramin is proposed to reduce arterial blood pressure without a concomitantly significant increase in heart rate (HR). The present study involves assessment of the effect of alpha 1-adrenoceptor antagonism in patients with mild hypertension on the HR/oxygen consumption (Vo2) relationship, which has previously been shown to indicate improvement in cardiorespiratory fitness following exercise training. A total of 16 patients with a systolic blood pressure of 140-200 mm Hg and diastolic blood pressure of 95-110 mm Hg were examined. A double-blind, placebo-controlled study design was utilized. Following initial observations, the patients were randomized into one group (a) of seven patients who were given a placebo, indoramin, and finally placebo, and a second group (b) of nine patients who were given the two agents in the reverse order, i.e., indoramin, placebo, indoramin; each intervention lasted for 2 weeks and indoramin was given in a dose of 75 mg/day. Indoramin caused a reduction in the elevation of the computed regression line relating HR to Vo2 (a shift to the right), such that at the same HR a greater Vo2 was attained in 11 of the 16 patients in comparison with the baseline exercise test. Pooled results showed a shift of the HR/Vo2 regression line to the right when indoramin was compared with baseline (p less than 0.05) or placebo. In the same patients, indoramin caused a decrease in arterial blood pressure during exercise relative to baseline or placebo periods, and a decrease in the HR during exercise relative to baseline period, but not when compared with placebo periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic

Atrial reflexes and renal function.

Distension of small balloons in the venous-atrial junctions results in an increase in heart rate, urinary flow and sodium excretion. Two types of atrial receptors are described: one type, histologically known, discharging into myelinated fibers, and a second type, discharging into nonmyelinated ("C") fibers. These responses are mediated by the myelinated fibers. Experiments have shown that simulation of receptors discharging into the large myelinated vagal fibers is responsible for a reflex increase in heart rate mediated only by sympathetic nerves and for an increase in urinary flow. The efferent pathway of the diuretic response is shown to be nervous and hormonal. Stimulation of atrial receptors causes (1) a reduction of activity in nerves to the kidney, causing an increase in both urinary volume and sodium excretion, and (2) the release of a blood-borne agent, possibly diuretic, that increases urinary volume but does not affect sodium excretion.

Afferent Pathways

Diagnostic value of routine exercise testing in hospital patients with angina pectoris.

A group of patients with angina pectoris were investigated prospectively using a simple and well-recognised exercise test protocol, and S-T segment displacements during exercise were correlated with the results of coronary arteriography. Definitive exercise results in 100 patients correlated well with findings on coronary angiograms: 69 out of 70 patients with positive exercise test results had significant coronary disease on angiography, while 23 out of 30 with negative exercise test results had no significant coronary disease. In six patients a period of physical training changed indeterminate initial tests to definitive ones after the training. These results show that the use of a widely available exercise test and a light physical training programme, with rigid adherence to the protocol, can reduce the overall demand on coronary arteriography.

Adult

Effect of exercise in hypertension controlled with metoprolol or methyldopa.

1. The adequacy of the control of essential hypertension during exercise was studied in patients whose resting blood pressure had been controlled for 1 year with either metoprolol or methyldopa. 2. Systolic blood pressure increased with exercise in both groups, the increase being significantly less in the metoprolol group than in the methyldopa group.

Adult

Effect of the Canadian Air Force training programme on a submaximal exercise test.

Validation of the submaximal heart rate/oxygen consumption relationship as an index of 'cardiorespiratory fitness' requires the demonstration of systematic alterations in this relationship concomitant with interventions designed to alter physical fitness. To fulfil those criteria a longitudinal training/de-training study was undertaken. Previously sedentary adult subjects undertook the Canadian Airforce 5BX-XBX exercise programme. Submaximal exercise tests were performed before and after training, and following several weeks cessation of training. A regression line of submaximal heart rate on submaximal oxygen consumption was calculated from the data of each submaximal exercise test. Alterations in the regression lines were examined for each subject individually by testing statistically for difference in slope and elevation between any pair of lines. Subjects who undertook the training/de-training study demonstrated significant systematic alterations in the elevation of the regression lines concomitant with periods of training and de-training. The reproducibility of the submaximal heart rate/oxygen consumption relationship was examined in two additional groups of subjects. Group A repeated a submaximal test on 3 or 4 successive days; Group B were tested before and after 16 weeks of normal activity. Subjects in Group A demonstrated non significant, random alterations in the regression lines on repeated testing and subjects in Group B demonstrated random, though on occasion significant, alterations in the regression lines. The elevation of the submaximal heart rate/oxygen consumption relationship is therefore a valid index for detecting sequential changes in 'cardiorespiratory fitness' in individual subjects.

Adolescent

A comparison of the oxygen consumption/body weight relationship obtained during submaximal exercise on a bicycle ergometer and on a treadmill.

It is widely accepted that the relationship between oxygen consumption and body weight obtained during exercise on a bicycle ergometer differs from that obtained during treadmill walking. Experimental evidence to support this claim is lacking. To examine this difference a group of subjects (body weight 41--81 kg) undertook a predetermined level of submaximal exercise on a bicycle ergometer and a treadmill. Oxygen consumption was measured in a steady state at rest (i.e. sitting on the bicycle ergometer and standing on the treadmill) and during the two modes of exercise. A significant positive correlation between oxygen consumption and body weight was obtained under all four conditions of measurement. At rest the two regression lines did not differ in slope or elevation. During exercise the slope and the elevation of the line obtain from treadmill walking were significantly greater than from bicycle ergometer exercise. The 'metabolic cost' of bicycle ergometer exercise, (Vo2 during exercise--V02 at rest), showed no significant correlation with body weight. In contrast, there was a significant positive correlation during walking. It is suggested that these differences have arisen due to a different proportion of the total body weight supported by the subject in the two forms of exercise.

Adult

Diuresis from left atrial receptors: effect of plasma on the secretion of the Malpighian tubules of Rhodnius prolixus.

1. Stimulation of left atrial receptors by distension of a balloon in the lumen of the left atrium of anaesthetized dogs was shown to result in an increase in urine flow. Plasma samples obtained from these dogs during control periods and during periods of stimulation were applied to the Malpighian tubules of Rhodnius prolixus. 2. It was found that the tubules suspended in test plasma secreted at a significantly lower rate than those suspended in control plasma. 3. These differences were also evident in extracts of plasma prepared using the solvent n-butanol. 4. Cutting or cooling the cervical vagi abolished these differences along with the increase in urine flow. It is argued that this preparation of the Malpighian tubule of Rhodnius prolixus could be used as a means of detecting the diuretic agent responsible for the increase in urine flow.

Animals

The nature of the atrial receptors responsible for a reflex increase in heart rate in the dog.

1. In dogs anaesthetized with chloralose, small latex balloons were positioned at the left pulmonary vein-atrial junctions so as to stretch this region. By recording action potentials from slips of the cervical vagi it was established that distension of these balloons stimulated receptor endings in the atrial endocardium which discharged into the myelinated branches of the vagi i.e. Paintal type A, type B and Intermediate type receptors. 2. In other dogs, cooling the cervical vagus in steps of 2 degrees C reduced this response in vagal myelinated fibres. With twelve receptors the response to distension was reduced by 30% when the vagus was cooled to 16 degrees C, by 70% when cooled to 12 degrees C and abolished at 8--12 degrees C. 3. In a third group of dogs, distension of balloons at the pulmonary vein-atrial junctions resulted in a reflex increase in heart rate. Cooling the cervical vagi in these dogs in stages to 8 degrees C reduced this increase in heart rate. In nine dogs the response was reduced by 20% when the vagi was cooled to 16 degrees C, by 70% when cooled to 12 degrees C and abolished between 12 and 8 degrees C. 4. In a fourth group of dogs, distension of balloons at the pulmonary vein-atrial junctions was shown also to activate receptor endings in the atria which discharged into non-myelinated branches of the Vagi. In twelve receptors, cooling the cervical vagus in steps of 2 degrees C reduced this evoked increase in activity in non-myelinated fibres. These responses were abolished over a wide range of temperature unlike the responses observed above. 5. It is concluded that the increase in heart rate which follows distension of balloons at the pulmonary vein-atrial junctions is mediated solely by the Paintal-type receptors which discharge into the myelinated fibres in the vagi.

Action Potentials