Biomedical subjects

C T Kappagoda

Publications and source records attributed to C T Kappagoda.

At least 19 recordsLinked to original sources

PubMed1992

Effect of aging on the pharmacokinetics of acebutolol enantiomers.

Acebutolol (AC) is a chiral beta-blocker that is metabolized to an equipotent chiral metabolite, diacetolol (DC). A stereoselective disposition of AC and DC enantiomers has recently been reported in young healthy subjects. As many physiologic properties affecting drug disposition are progressively altered with increasing age, the effect of aging on the pharmacokinetics of AC and DC enantiomers were investigated in nine subjects ranging from 60 to 75 years after administration of an oral 200-mg dose of racemic AC. Increasing age resulted in a significant prolongation of the elimination t1/2s of R- (r = 0.913) and S-DC (r = 0.811). Also, the S:R ratios of AC urinary excretion (sigma Xu) of enantiomers was significantly correlated with age (r = 0.677). Contribution of declining renal function to age-associated pharmacokinetics changes was subsequently examined. Renal clearance and cumulative urinary excretion of both AC and DC enantiomers were positively correlated with creatinine clearance. In addition, declining creatinine clearance was associated with a subsequent decline in the enantiomer S:R ratio of AC in plasma (AUC S:R, r = 0.807) and urine (sigma Xu S:R r = 0.807). Similarly, a progressive decline in the S:R ratio of DC collected in urine was evident (r = 0.689). Age-related changes in the enantiomers ratios may suggest that an active stereoselective pathway such as renal tubular secretion or nonrenal excretion may be affected in the elderly.

Acebutolol↗

PubMed1992

The effect of concurrent administration of isradipine on the development of fatty streaks in the cholesterol-fed rabbit: a morphometric study.

Calcium antagonists attenuate the development of aortic lesions in cholesterol-fed rabbits. This study was undertaken to examine the influence of isradipine (dose: 0.3 mg/kg per day orally) on the histological components of these lesions in New Zealand White rabbits (age: 12 weeks, weight: 2-2.5 kg). Five groups of animals were fed standard chow with the following supplements for 3 weeks: Group 1, no supplements; Group 2, 40 g cholesterol; Group 3, 60 g cholesterol; Group 4, 40 g cholesterol + isradipine; Group 5, 60 g cholesterol + isradipine. After 3 weeks, the animals were killed and the aorta prepared for morphometry. The volume of intima/cm aorta was estimated and the volume fraction (Vv) of the intima occupied by components of the lesions was estimated by point counting. By integrating these two measurements the volume/unit length (mm3/cm) of the following components of the aorta were estimated: intima, non-cellular components, endothelial cells, myointimal cells, lipid accumulating myointimal cells and foam cells. Cholesterol feeding for 3 weeks was associated with significant increases in the volume of non-cellular components of the intima, endothelial cells, myointimal cells, lipid accumulating myointimal cells and foam cells. Administration of isradipine significantly reduced all these parameters. It is concluded that isradipine attenuates cellular hyperplasia and accumulation of non-cellular components of lesions in cholesterol fed rabbits.

Administration, Oral↗

PubMed1992

Responses of airway rapidly adapting receptors to bradykinin before and after administration of enalapril in rabbits.

1. The present study was performed in anaesthetized, artificially ventilated, open-chested rabbits to examine whether (a) the rapidly adapting receptors of the airways were stimulated by exogenously administered bradykinin, and (b) if this sensitivity could be enhanced by the angiotensin-converting-enzyme inhibitor, enalapril. 2. Rapidly adapting receptor activity (n = 8) was recorded from the cervical vagus. Bradykinin was injected intravenously (0.25-1.0 microgram/kg) and a dose-response curve relating receptor activity to bradykinin was elicited. In the control state, the threshold dose of bradykinin required for stimulation of rapidly adapting receptors was 0.53 +/- 0.11 microgram/kg. Five minutes after the administration of enalapril maleate (2 mg intravenously), the dose-response curve was shifted to the left significantly (P < 0.01). 3. In seven other rapidly adapting receptors, enalapril (2 mg) increased the resting activity significantly (P < 0.05) over a period of 60 min. This increase was significantly different from the spontaneous variation in neural activity of rapidly adapting receptors (n = 7) recorded over a period of 60 min. 4. Bradykinin either alone (0.25-1.0 microgram/kg) or in the presence of enalapril did not stimulate the slowly adapting receptors (n = 5) of the airways. 5. These results show that (a) exogenous bradykinin stimulates the rapidly adapting receptors, (b) the sensitivity of rapidly adapting receptors to bradykinin is enhanced by enalapril and (c) enalapril increases the resting activity of rapidly adapting receptors. It is suggested that the cough reported after the administration of enalapril may be due to stimulation of rapidly adapting receptors of the airways.

Action Potentials↗

PubMed1992

Responses of pulmonary C-fibre and rapidly adapting receptor afferents to pulmonary congestion and edema in dogs.

The effects of cardiogenic and noncardiogenic pulmonary edema on the activities of rapidly adapting receptors (RARs) and pulmonary C-fibre receptors were investigated in dogs anaesthetized with chloralose. Cardiogenic pulmonary edema was produced by elevating the mean left atrial pressure by 25 mmHg (1 mmHg = 133.32 Pa) above the control value for a period of 45 min, by partial obstruction of the mitral valve. Noncardiogenic pulmonary edema was produced by injecting alloxan (100 mg/kg) intravenously. The effect of the latter was examined on RARs alone. Cardiogenic edema activated RARs (n = 8) and the activity was greatest during the first few minutes after elevation of mean left atrial pressure. The pulmonary C-fibre receptors (n = 6) were also activated by cardiogenic edema, but these responses were variable. Noncardiogenic pulmonary edema also activated RAR (n = 6), and this response was maintained during the entire recording period (20 min). The extravascular lung water (%), measured 15 min (n = 5) and 45 min (n = 5) after the elevation of the mean left atrial pressure, was significantly elevated above control values. However, these two values were not significantly different from each other. The extravascular lung water increased significantly after the injection of alloxan also (n = 5). These results show that during pulmonary edema, there is significant stimulation of the RARs and the pulmonary C-fibre receptors. It is suggested that the reflex respiratory responses observed in pulmonary edema may be due to the activation of both the RARs and the pulmonary C-fibre receptors.

Afferent Pathways↗

PubMed1992

Changes in blood pressure and cardiac output during maximal isokinetic exercise.

This study was undertaken to determine the blood pressure (BP) and cardiac output (Qc) responses to maximal isokinetic exercise. The subjects (n = 5) performed unilateral knee extension/flexion exercise (knee exercise) and unilateral elbow extension/flexion exercise (elbow exercise) at 0.52, 1.57, and 2.62 rads.sec-1. The BP was monitored using a cannula placed in the radial artery. Heart rate (HR), stroke volume (SV), and Qc were measured by impedance cardiography. In response to isokinetic exercise, HR and Qc increased significantly (p less than .01), while the SV did not. The BP response was characterized by significant increases in systolic, diastolic, and mean arterial pressure (MAP) (p less than .01). The Qc and MAP, responses were not influenced by the exercise velocity. The adjustments in HR, MAP, and rate pressure product (RPP) to the elbow exercise were qualitatively similar to those seen during the knee exercise, but the absolute values achieved were smaller (p less than .05). Compared with maximal dynamic exercise, the HR and SV responses to the knee exercises were lower. The MAP response to isokinetic exercise equaled the highest value achieved during dynamic exercise. Findings from the present study suggest that the cardiovascular stress (the increase in HR, MAP, and RPP) associated with isokinetic exercise is independent of the velocity of movement and is proportional to the active muscle mass.

Adult↗

PubMed1990

A model for demonstration of reversal of impairment of endothelium-dependent relaxation in the cholesterol-fed rabbit.

This investigation was undertaken to determine whether it was possible to restore endothelium-dependent relaxation (EDR) in the cholesterol-fed rabbit model of atherosclerosis following discontinuation of the cholesterol. New Zealand white rabbits, approximately 8 weeks of age, were randomized into (i) control group (9 animals fed a standard rabbit diet) and (ii) experimental group (27 animals: fed the same diet supplemented with 2.5% cholesterol). The experimental animals were restored to the standard diet after 3 weeks. EDR to acetylcholine (-9.0 to -5.0 log mol/L) was examined in the experimental animals at 3, 7, and 15 weeks after commencement of the study (n = 9 at each stage) and the nine control animals examined after 7 weeks. At the end of 7 weeks, EDR to acetylcholine (-6.0 log mol/L) was significantly (p less than 0.05) impaired in the experimental group (34.3 +/- 3.8%) compared with that in the control group (79.8 +/- 3.0%). The loss of EDR was not apparent in the experimental group at 3 weeks (relaxation: 81.7 +/- 4.7%). At the end of 15 weeks, the EDR was significantly restored in the experimental group (relaxation: 63.6 +/- 5.1%). These findings demonstrate that it is possible to reverse the loss of EDR that occurs with cholesterol feeding in the rabbit by limiting the period of exposure to a high cholesterol diet.

Acetylcholine↗

PubMed1990

Morphology of presumptive rapidly adapting receptors in the rat bronchus.

The present investigation was undertaken in rats to determine whether sensory nerves exist in apposition to the bronchial microvessels which may function as rapidly adapting receptors (RAR). The primary and secondary bronchi on both sides were removed and processed for light and electron microscopy. Nerves were frequently found in relation to venules external to the muscle coat of bronchi. They comprised myelinated axons which ended individually as non-myelinated convoluted terminals enclosed within a loose capsule of attenuated cells. Serial sections showed that these terminals were not related to ganglion cells. Cervical vagal section and injection of HRP-WGA into the nodose ganglion provided corroborative evidence of the sensory nature of these terminals. Vagal section caused degenerative changes in the encapsulated nerve terminals in the bronchial walls and horseradish peroxidase labelling was demonstrable in such terminals. Moreover, immunocytochemical studies demonstrated the presence of calcitonin gene regulated peptide and substance P in these structures. It is suggested that they comprise the RAR. Encapsulated nerve terminals were not found in the epithelial layer, in the submucous coat or in the muscularis of bronchi.

Animals↗

PubMed1979

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↗

PubMed1979

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↗

PubMed1979

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↗

PubMed1979

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↗

PubMed1979

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↗

PubMed1979