Search PubMed⌕ Search

Biomedical subjects

R J Linden

Publications and source records attributed to R J Linden.

At least 37 records · Page 2Linked to original sources

Diuresis from atrial receptors after hypophysectomy and local ablation with no changes in plasma vasopressin.

Stimulation of the left atrial receptors in dogs anaesthetized with chloralose results in a reflex diuresis and natriuresis. The efferent limb of this reflex is though to have at least three components: nervous, haemodynamic and humoral. The present study was designed to investigate the humoral component in dogs anaesthetized with chloralose; to determine whether a humoral agent, other than vasopressin, might be causative in this reflex diuresis. The nervous and haemodynamic components were prevented by pharmacological denervation. Any possible contribution to the diuresis by a decrease in the plasma concentration of vasopressin was prevented by the removal of the pituitary gland. In animals in which a spontaneous diuresis followed hypophysectomy, an infusion of arginine vasopressin sufficient to maintain urine flow in the normal range for these dogs anaesthetized with chloralose was given. Distension of small balloons at the pulmonary vein-atrial junctions and in the left atrial appendage discretely to stimulate the atrial receptors in eleven dogs anaesthetized with chloralose resulted in a significant diuresis. It was concluded that a blood-borne agent other than vasopressin was responsible for the observed diuresis. At the moment it is not known whether vasopressin or the diuretic agent, or both, are involved in the diuresis accompanying the stimulation of atrial receptors.

Animals↗

Involvement of the reflex increase in heart rate in the differences in urinary responses to stimulation of atrial receptors in dogs with different blood volumes.

The effect of increasing heart rate by increasing the rate of atrial pacing in the absence of any reflex effects from atrial receptors, by cooling the vagi to 12 degrees C, was studied in two groups of dogs with different blood volumes. In one group of nine dogs with a high blood volume increasing heart rate, by an amount similar to that reflexly obtained in response to stimulation of atrial receptors, resulted in significant increases in urine flow and sodium excretion; in another group of eight dogs with a low blood volume similar increases in heart rate did not result in a diuresis or natriuresis. The findings suggest that the effects of an increase in heart rate in combination with differences in blood volume could contribute to the previously reported differences in the urinary responses that result from stimulation of atrial receptors in dogs with different blood volumes.

Animals↗

Assessment of the effect of nifedipine on myocardial ischaemia by using the ST segment/heart rate slope.

Nifedipine is used in patients with stable angina of effort and any resulting change in symptoms is attributed to several effects of nifedipine. However, there have been indications in such patients that one effect of nifedipine could be an increase in the severity of myocardial ischaemia, and the present report involves a trial the results of which could explain this effect. In the present trial, the effect of nifedipine on myocardial ischaemia was assessed by using the maximal ST/heart rate slope. This slope was used as an index of myocardial ischaemia because, in our hands in patients with angina, an increase or a decrease in the value of the slope respectively indicated an increase or a decrease in the severity of myocardial ischaemia as assessed by coronary arteriography. The maximal ST/heart rate slope was obtained at least twice in each of 23 patients with stable angina, with and without nifedipine; two patients were examined twice and three other patients were examined after an increased dose. Nifedipine resulted in an increase in the slope in 24 of the 28 comparisons, no change in three and a decrease in one comparison; there was a statistically significant (P less than 0.005; n = 28; paired t-test) increase in the maximal ST/heart rate slope. A further increase in the slope was obtained by increasing the dose of nifedipine in two out of three patients. The increase in the maximal ST/heart rate slope occurred in the absence of any effect of nifedipine on the initial level of ST segment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

Does stimulation of the left atrial receptors affect the activity in efferent vagal nerves to the heart in decerebrate dogs?

In anaesthetized dogs with an intact neuraxis, distension of small balloons at the pulmonary vein--atrial junctions to stimulate atrial receptors with myelinated vagal afferent nerves causes an increase in heart rate but does not influence the activity in efferent vagal cardiac nerves. However, it has been suggested from experiments performed in decerebrate dogs that stimulation of atrial receptors causes a tachycardia partly mediated by a decrease in activity in efferent vagal nerves. In the present study in chloralose-anaesthetized dogs, following total decerebration (four dogs) or partial decerebration (four dogs) at the level of the mid-brain, distension of the small balloons caused an increase in heart rate but did not affect the activity in efferent vagal nerve fibres which responded by an increase in activity to stimulation of carotid baroreceptors and chemoreceptors. These results show that stimulation of the left atrial receptors in totally or partially decerebrate dogs causes an increase in heart rate but does not influence the activity in efferent vagal cardiac nerves.

Animals↗

The effect of the coronary vascular wall on the changes in the coronary vascular resistance during a sudden reduction and recovery of the aortic blood pressure.

To demonstrate the effect of elastic and myogenic properties of the vessel wall on the mean coronary vascular resistance during ventricular diastole (m.d.c.r.), this resistance was assessed in twenty dogs anaesthetized with sodium pentobarbitone during a 10 s period of arterial haemorrhage and 20 s of recovery from this haemorrhage. In a first stage of the study ten dogs were investigated following sectioning of the vagal nerves in the neck, beta-blockade, and ligation of the carotid arteries. During haemorrhage and reduction in aortic blood pressure (A.B.P.) in these dogs, there was an initial rise (at 2 s after the start of the haemorrhage) in m.d.c.r. which quickly decreased to a value similar to that obtained during the control period. After the abrupt cessation of haemorrhage, and a rise in A.B.P., there was an initial decrease in m.d.c.r. which eventually increased to the control levels. In the second stage of study identical patterns of changes were obtained in a group of five dogs in which the cervical vagi were not sectioned and beta-blocking agents not given. In another group of five dogs, during infusion of dipyridamole to force maximal coronary vasodilation, the increase in m.d.c.r. was maintained throughout the period of haemorrhage and reduction in A.B.P., and m.d.c.r. did not decrease below the control values following the abrupt cessation of haemorrhage and a rise in A.B.P. The findings in the dogs without dipyridamole infusion suggested that the pattern of changes in m.d.c.r. was due to changes in the perfusion pressure and their effect on the elasticity and myogenic properties of the coronary vascular wall. This suggestion was supported in the second stage of the study, when the reductions in m.d.c.r. were abolished by forcing coronary vasodilation using the infusion of dipyridamole.

Animals↗

Evidence against ANP as a natriuretic hormone during atrial distension.

To determine whether natriuresis attributable to atrial natriuretic peptides (ANP) is obtained in response to atrial stretch after blockade of the afferent input and reflex diuresis from atrial receptors, urine flow and sodium excretion were measured in response to distension of a balloon in the left atrium with the vagi at 37 and 9 degrees C. It is known that during such a distension ANP plasma concentration is increased by the same amount whether or not the afferent vagal fibres are intact. In 11 chloralose anaesthetized dogs 22 distensions with the vagi at 37 degrees C increased urine flow 117.5% and increased sodium excretion 28.7%. In 11 distensions with the vagi at 9 degrees C, urine flow did not change but sodium excretion decreased significantly (-20.9%). Thus natriuresis could not be demonstrated in response to atrial stretch in anaesthetised dogs after blockade of the atrial receptor reflex. These results imply that under these conditions, in which ANP is reportedly released into plasma, ANP is not acting as a hormone. The results must call into question the suggestion that ANP is released into plasma in a concentration capable of causing a natriuresis as its normal physiological function.

Animals↗

The causative agent in atrial receptor diuresis in the dog is a low molecular weight, lipophilic and weakly acidic substance.

Stimulation of atrial receptors by distension of a balloon in the left atrium of anaesthetized dogs results in a reflex diuresis mediated by a humoral agent of unknown identity. In previous investigations, a substance was recovered in a low molecular weight fraction from Bio-Gel P-2 (100-1800 daltons) and shown to be related to the reflex diuresis. In this investigation, the active Bio-Gel P-2 fraction was partitioned with ethyl acetate at pH 11.0, with subsequent partition of the aqueous phase with ethyl acetate at pH 7.4; the activity of the humoral agent was soluble in ethyl acetate at pH 7.4. These investigations suggest that the humoral agent is a low molecular weight, lipophilic and weakly acidic substance. The substance is not antidiuretic hormone (ADH) as vasopressin is insoluble in ethyl acetate at pH 7.4.

Acetates↗

The effects of long-term physical training in patients with coronary heart disease.

A previous trial was completed in 24 patients with coronary heart disease, randomly assigned to a group who undertook a 6-month exercise training programme (5BX/XBX) and a control (no training) group. It was shown that the patients in the training group were able to achieve during exercise a higher heart rate at ST segment depression of 0.1 mV (HR/ST threshold) and that the patients in the control group showed a reduction in the threshold as well as symptomatic deterioration; the results indicated that the training programme had resulted in a reduction in the severity of myocardial ischaemia. In the present trial 9 patients of the previous training group were followed up to examine the effect of long-term maintenance training (up to 4.5 years). The same methods were used to examine the effect of maintenance training in a further group of 8 patients with coronary heart disease, 6 of whom were on beta-blocker therapy. By the end of the study, the heart rate achieved during exercise in the 17 patients was still significantly greater (P less than 0.0004) by 12.1 +/- 2.85 beats/min (mean +/- SEM) than that at the beginning of the trial; similar results were obtained in the 6 patients on beta-blocker therapy. Therefore a maintenance exercise training programme in patients with coronary heart disease can result in a sustained improvement in the form of a reduction in the severity of myocardial ischaemia, and this can occur in patients on beta-blocker therapy.

Adrenergic beta-Antagonists↗

The atrial receptors responsible for the decrease in plasma vasopressin caused by distension of the left atrium in the dog.

In dogs anaesthetized with chloralose, the effects of cooling the cervical vagi on the reflex decrease in plasma concentration of vasopressin, caused by distension of a large balloon in the lumen of the left atrium, were examined. Distension of the balloon in ten dogs with the vagi at 37 degrees C resulted in a decrease in plasma concentration of vasopressin and, as before, an increase in urine flow. The responses were not significantly affected by cooling to 16-18 degrees C but were abolished at 9 degrees C. At 16-18 degrees C the increase in activity in myelinated vagal afferent fibres is largely unchanged and at 9 degrees C is abolished (Kappagoda, Linden & Sivananthan, 1979; Sivananthan, Kappagoda & Linden, 1981). It is concluded that the decrease in plasma concentration of vasopressin during distension of the left atrium is mediated by the Paintal-type atrial receptors with myelinated vagal afferent fibres.

Afferent Pathways↗

Use of the exercise maximal ST segment/heart rate slope in assessing the results of coronary angioplasty.

A new exercise test was used to assess the effects of coronary angioplasty in 22 patients. Twenty five angioplasty procedures were performed and the exercise maximal ST segment/heart rate slope was measured before and after operation on 23 occasions; in two patients treated for unstable angina the slope was measured only after the two procedures. Successful angioplasty (23 of the 25 procedures) resulted in a significant reduction of the maximal ST/HR slope, usually falling by the equivalent of single vessel disease according to previously published criteria. When angioplasty produced little angiographic change (two of the 25 procedures) the maximal ST/HR slope was not significantly altered. A second, and successful, angioplasty for these two patients led to a significant reduction of the maximal ST/HR slope. Twelve patients were restudied by coronary angiography and exercise testing approximately six months after angioplasty. Of these, six had experienced recurrent chest pain, and the exercise test successfully identified the three who had restenoses and the three who did not. Thus the maximal ST/HR slope was useful as a non-invasive and accurate method for following the progress of individual patients after coronary angioplasty.

Adult↗

Assessment of aortocoronary bypass grafting using exercise ST segment/heart rate relation.

The maximal rate of progression of ST segment depression relative to increases in heart rate (maximal ST/HR slope) has recently been shown to be an accurate index of the presence and the severity of coronary heart disease in patients with angina. The value of this new exercise test was assessed in patients undergoing aortocoronary bypass. The maximal ST/HR slope and the results of coronary angiography were obtained in each of 46 patients before aortocoronary bypass surgery and in 26 of the 46 patients six months after the operation. At each stage of the investigation the maximal ST/HR slope detected without false results the absence and the number of significantly diseased vessels as shown by angiocardiography. As in previous findings the ranges of the maximal ST/HR slope showed no overlap between the four groups of patients: those with no significant disease and those with single, double, or triple vessel disease. In each of the 46 patients in whom the maximal ST/HR slope was determined before operation and three months afterwards the slope was lower after operation than before, indicating improvement. Follow up examinations showed that the maximal ST/HR slopes accurately detected the number of patent grafts used to bypass significantly diseased coronary arteries. Furthermore, the development of a significant narrowing or occlusion in any vein graft caused an increase in the maximal ST/HR slope which was equivalent to the value of single vessel disease. It is suggested that the maximal ST/HR slope may be used reliably in individual patients to indicate restoration of adequate blood supply to the myocardium after successfully aortorcoronary bypass surgery and the to detect in the period of six months after the operation the degree of severity of coronary heart disease whether it is caused by occlusion of the graft of significant disease of the coronary arteries.

Adult↗

Diuresis from stimulation of left atrial receptors in dogs: further purification of the causative agent from plasma.

Stimulation of atrial receptors by distension of a balloon in the left atrium of anaesthetized dogs results in a reflex diuresis mediated by an unknown humoral agent. This paper reports the further purification from plasma of acetone extracts of the humoral agent which may mediate the diuretic response. Activity of the humoral agent was detected using the Malpighian tubules of Rhodnius prolixus. Gel filtration of the acetone extracts on Sephadex G-25 and G-100, followed by dialysis of the fraction from Sephadex G-100 that contained the humoral agent, showed that the activity of the agent was associated with a high molecular weight fraction (greater than 30000). Acetone extracts of the humoral agent were also shown to be stable to treatment with HCl for 1 h at 25 degrees C. After this acid treatment, gel filtration on Sephadex gels and Bio-Gel P-2 showed that the agent was of low molecular weight (less than 1800). It is concluded that the activity of the humoral agent, as detected by the Malpighian tubule preparation, is associated with a molecule of low molecular weight which may be bound to a larger molecule from which it can be dissociated by acid treatment.

Animals↗

Abolition of atrial receptor diuresis and of release of humoral agent by cooling the vagal nerves.

Stimulation of atrial receptors in anaesthetized dogs results in a reflex increase in urine flow mediated by vagal myelinated fibres and, in part, by a humoral agent of unknown identity. The humoral agent has been detected by an in vitro preparation of the Malpighian tubules of Rhodnius prolixus. The purpose of this investigation was to determine whether the present extract of plasma purporting to contain the humoral agent is also related to the reflex diuresis. In nine chloralose anaesthetized dogs atrial receptors were stimulated by distension of a balloon in the left atrium. Plasma samples collected before and during distension of the balloon, respectively, were precipitated with acetone, acid-treated and fractionated on Bio-Gel P-2. The purified samples were tested for the activity of the humoral agent on the Malpighian tubule preparation. In each dog, distensions of the balloon were performed with the cervical vagal nerves at 9 and 37 degrees C. Cooling the vagal nerves to 9 degrees C abolished the reflex diuresis and abolished the activity of the humoral agent recovered from a Bio-Gel P-2 fraction (molecular weight range 100-1800) which elutes between the void volume and the salt fraction. It was concluded that the substance recovered from Bio-Gel P-2 is associated with the diuresis in response to stimulation of atrial receptors; it is suggested that its presence is dependent on the integrity of the afferent limb of the atrial receptor reflex.

Animals↗

The effect of stimulation of atrial receptors on the plasma concentration of vasopressin.

The effect of stimulation of the left atrial receptors on plasma concentration of vasopressin and urine flow was studied in dogs anaesthetized with chloralose. Distending a large balloon in the left atrium, so as to occlude the mitral valve and increase left atrial pressure, consistently resulted in a decrease in plasma vasopressin and an increase in urine flow. Discrete stimulation of the left atrial receptors, by distending small balloons in the pulmonary vein - left atrial junctions and in the left atrial appendage, consistently resulted in a decrease in plasma vasopressin and an increase in urine flow. The left atrial receptors were stimulated discretely in dogs in which bretylium tosylate, atropine and atenolol had been administered. In these dogs distension of the small balloons was not associated with significant changes in heart rate, left atrial pressure or arterial blood pressure and consistently resulted in a decrease in plasma vasopressin and an increase in urine flow. It is concluded that this decrease in the plasma concentration of vasopressin is a direct result of discrete stimulation of the atrial receptors and is not secondary to any haemodynamic changes. The exact role of this decrease in plasma concentrations of vasopressin in the diuretic response to stimulation of the left atrial receptors remains to be established.

Animals↗