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Biomedical subjects

I R Cameron

Publications and source records attributed to I R Cameron.

At least 19 recordsLinked to original sources

A comparison of the pharmacological and mechanical properties in vitro of large and small pulmonary arteries of the rat.

1. The mechanical and pharmacological properties of small pulmonary arteries (100-300 microns normalized lumen diameter) were directly compared with those of the left main pulmonary artery (1-2 mm) from the rat. The active and passive length-tension characteristics and responses to a variety of agonists and antagonists were dependent on arterial diameter. 2. Maximum contractile function was obtained in both groups of vessels when stretched so as to give an equivalent transmural pressure of 30 mmHg. This is substantially lower than that found for systemic vessels, and reflects the normal low pulmonary arterial pressure. 3. Noradrenaline was a powerful vasoconstrictor in large but not small pulmonary arteries (P less than 0.001). In contrast, bradykinin produced a significantly greater response in the small arteries (P less than 0.001). In comparison with large pulmonary arteries, small arteries were more sensitive to noradrenaline (P less than 0.05) and 5-hydroxytryptamine (P less than 0.001), less sensitive to endothelin-1 (P less than 0.001) and had the same sensitivity to prostaglandin F2 alpha. 4. The mechanism that maintains the low arterial tone of the pulmonary circulation is unknown, but it may involve the release of relaxing factors from the endothelium. In this preparation, basal resting tone could not be demonstrated in either large or small arteries. 5. Acetylcholine-induced relaxation of pre-contracted pulmonary arteries was reduced or absent in the small artery, despite histological evidence of an intact endothelium. In large arteries pre-contracted with prostaglandin F2 alpha, acetylcholine (100 mumol/l) caused 88.2% relaxation compared with 25.2% in the small artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

Portable liquid oxygen and exercise ability in severe respiratory disability.

BACKGROUND: The development of portable liquid oxygen systems, capable of delivering high flow rate oxygen for long periods, justifies reassessment of the value of supplemental oxygen to aid exercise tolerance in patients with chronic respiratory insufficiency. The type of exercise test and the low oxygen flow rates previously used may account for the variable and often poor responses to supplemental oxygen reported in earlier studies. METHODS: The walking tolerance of 30 patients with severe respiratory disability was measured while they were breathing air and increasing doses of supplemental oxygen (2, 4, 6 1/min) by using both the standard six minute walking test and an endurance walking test. To assess the initial learning effect and repeatability of the walking tests, three six minute walks and three endurance walks were performed on day 1 and a single walk of each type on days 2, 3, and 14. In addition, oxygen dosing studies were performed on days 2 and 3 after the initial baseline walking tests. Each dosing study comprised four endurance walking tests or four six minute walking tests with patients breathing either air at a flow rate of 4 1/min from a portable cylinder or supplemental oxygen at a flow rate of 2, 4 or 6 1/min from a portable liquid oxygen supply. The order of the tests was randomised. Walking distance with each flow rate of oxygen was compared with walking distance with patients carrying cylinder air and for the initial unburdened walks. Breathlessness was assessed by visual analogue scoring on completion of each walk. RESULTS: Exercise ability and breathlessness were significantly improved with supplemental oxygen and this benefit outweighed the reduction in performance resulting from carrying the portable device. Supplemental oxygen at flow rates of 2, 4, and 6 1/min increased mean endurance walking distances by 37.9%, 67.7% and 85.0% and six minute walking distances by 19.2%, 34.5%, and 36.3% by comparison with distances when the patient was carrying air with a flow rate of 4 1/min. The additional work of carrying the portable gas supply reduced endurance walking distance by 22.2% and six minute walking distance by 14.1% by comparison with a baseline unburdened walk. Comparison of supplemental oxygen at 2, 4, and 6 1/min with the baseline unburdened performance showed increased endurance walking distances of 7.3%, 30.4%, and 43.9% and six minute walking distances of 2.3%, 15.5%, and 17.0%. Walking distance was increased by more than 50% by comparison with an unburdened walk in seven patients with the endurance walking test but in only three patients with the six minute walking test. The benefit was similar in patients with obstructive and with interstitial lung disease. Individual responses were variable and only desaturation during the baseline walk in patients with obstructive lung disease had any predictive value for benefit with oxygen. CONCLUSION: As there was no clear relation between response to oxygen therapy and the patients' characteristics, assessment for supplemental oxygen therapy will depend on exercise testing. It is suggested that portable oxygen should be considered only if a patient shows a 50% improvement in exercise ability with high flow rate oxygen (4-6 1/min) by comparison with an unburdened walk.

Ambulatory Care

Tandem integration of complete and defective SV40 genomes in mouse-human somatic cell hybrids.

We have analyzed the arrangement of SV40 DNA sequences integrated in human chromosome 7 in two lines of mouse-human somatic cell hybrids: one containing only one human chromosome 7 per cell and the other containing an average of about three. We found that the integration site differs in both the viral and host sequences in the two clones. However, the sites of integration into the several copies of human chromosome 7 of one clone are identical. Each chromosome 7 in both clones carries approximately six viral genomes tandemly linked. Some of these genomes lack about 20% of the DNA from the late region, including the Eco RI site.

Animals

Role of Pco2 oscillations and chemoreceptors in ventilatory response to inhaled and infused CO2.

We have previously shown in the anaesthetized rabbit that the ventilatory response to an increase in Paco2 is greater if that increase is produced by intravenous infusion of hypercapnic blood than by inhalation of CO2 (Linton et al., 1976). The present set of experiments was designed to investigate the reason for this. It was found that the difference in ventilatory response observed in the intact rabbit was abolished by cutting the carotid sinus nerves or by eliminating the pH/Paco2 oscillations in the carotid blood flow. It is concluded that the normally greater ventilatory response to intravenous infusion of hypercapnic blood compared with inhalation of CO2 is due to a respiratory signal derived from Paco2 oscillations and carried in the carotid sinus nerves.

Animals

The effect of chronic frusemide administration on intracellular potassium, sodium and pH of cardiac and skeletal muscle.

1. Chronic administration of frusemide in large doses of 4 mg day-1 kg-1 for 3 weeks caused a significant reduction of cell water in rabbit cardiac and skeletal muscle. Intracellular Na+ concentration, intracellular pH and extracellular space was unchanged in both tissues. Intracellular K+ concentration increased slightly in both cardiac and skeletal muscle. 2. It is concluded that frusemide does not reduce intracellular K+ concentration in cardiac or skeletal muscle of normal animals receiving a normal oral potassium intake.

Animals

Ventilatory response to CO2 inhalation and intravenous infusion of hypercapnic blood.

The ventilatory responses to intravenous infusion of hypercapnic blood (equilibrated with 80% CO2: 20% O2) and inhaled CO2 (1.5-2.0% CO2) have been compared in anaesthetized rabbits. A control infusion of blood equilibrated with 4% CO2: 21% O2 produced no change in V, PaCO2 or PaO2. The ventilatory response to a given rise in PaCO2, deltaV - (delta PaCO2)-1, was greater during infusion of hypercapnic blood (69 +/- 33 ml-min-1-mm Hg-1, mean +/- SD) than during CO2 inhalation (28 +/- 16 ml-min-1-min Hg-1, P less than 0.01). There was no difference between the rates at which the final levels of ventilation were reached during inhalation of CO2 or infusion of hypercapnic blood. It is suggested that the difference between the responses may be accounted for by differences in the pattern of PaCO2 oscillations in the two situations.

Animals

The effect of local changes in potassium and bicarbonate concentration on hypothalamic blood flow in the rabbit.

Blood flow has been measured locally in the hypothalamus of anaesthetized rabbits by measuring the clearance of small volumes (5-20 mul.) of a mock cerebrospinal fluid solution containing 133Xe. The effect of varying the [K+] or [HCO-3] of the 133Xe-containing solution on local hypothalamic blood flow has been investigated. 2. There was an increase in local hypothalamic blood flow if the 133Xe-containing solution was HCO3--free; raising the [HCO--3,] of the solution to 40 mM caused a fall in local blood flow. 3. There was an increase in local hypothalamic blood flow when 133Xe was injectedin a mock cerebrospinal fluid containing 10 or 20 mM-[K+]. There was no significant change in blood flow if a K+-free or a 40 mM [K+] solution was used. 4. The decrease in hypothalamic blood flow caused by injecting a 40 mM-[HCO3] solution could be reversed by the addition of 20 mM [K+] to the solution. There was no further increase in blood flow if 20 mM-[K+] was added to a HCO3--free solution. 5. It is concluded that local blood flow in the hypothalamus changes as a result of variation in local [K+] as well as local [HCO-3]. The changes in blood flow in the brain which accompany neuronal activity could be mediated by variation in local [K+].

Animals

Small airways in fibrosing alveolitis.

Pulmonary function, including lung elastic recoil, was measured in 9 subjects with fibrosing alveolitis. Closing volume and upstream conductance were studied to assess small airway function. Lung volumes, diffusing capacity, and transfer coefficient were decreased. Peak expiratory flow and the ratio of 1-sec forced expiratory volume to forced vital capacity were normal, whereas total lung resistance was low, suggesting that large airways were not narrowed. Lung elastic recoil was increased, but the changes could be accounted for by the loss of lung volume. Closing volume and closing capacity were increased when expressed as a percentage of vital capacity and total lung capacity, respectively; but again, this could be accounted for by the decrease in lung volume, because the absolute lung volume at which airway closure occurred was normal. Upstream conductance was not reduced. We conclude that there is no evidence of narrowing of functional small airways in ventilated parts of the lung. The mechanical findings are compatible with the patchy involvement seen pathologically in fibrosing alveolitis.

Adult

ECS, intracellular pH, and electrolytes of cardiac and skeletal muscle.

The extracellular space (ECS) of muscle from each ventricle of the heart (RV and LV), the atria, diaphragm, and quadriceps was estimated in the anesthetized rabbit from the distribution volumes of [14C]insulin, [14C]sucrose, [51Cr]EDTA, and C1--. Whole-tissue electrolytes were measured and intracellular electrolytes calculated. The ECS of the tissues varied, increasing in the order quadriceps less than LV less than RV less than atria. The volume of distribution of [14C]inulin was always less than that of either [14C]sucrose or [51Cr]EDTA which agreed closely, whereas that of C1-- was always greater. There was no difference in intracellular K+ in muscle from each of the cardiac chambers, whereas intracellular Na+ and C1-- varied, increasing in the order quadriceps less than LV less than RV less than atria. Intracellular pH, measured with [14C]DMO did not differ in any of the tissues studied. It is concluded that, in vivo, the estimated ECS incardiac muscle is lower than that reported in vitro, that [51Cr]EDTA is a satisfactory ECS marker, and that differences in intracellular Na+ and C1-- but not K+ or pH exist between muscle from the cardiac chambers.

Animals

Intracellular pH and K+ of cardiac and skeletal muscle in acidosis and alkalosis.

The effects of a metabolic and respiratory acidosis and alkalosis on intracellular pH (pHi) and K+ have been compared in cardiac and skeletal muscle from the anesthetized rabbit. The extracellular space and pHi were calculated from the distribution volumes of [51Cr] EDTA and [14C]DMO, respectively. When pHe was varied by altering PCO2, the slope of the line relating pHi to the extracellular pH (pHe) was greater (P less than 0.05--0.001) than that obtained during metabolic changes of pHe in right and left ventricles, atria, diaphragm, and quadriceps. During metabolic acidosis and alkalosis, the slope of pHi/pHe line did not vary between tissues. During respiratory acidosis, there was no difference in slope between cardiac tissues, but it was less in left ventricle than quadriceps (P less than 0.001). In left ventricle intracellular K+ increased in a metabolic (P less than 0.05) or respiratory acidosis (P less than 0.02), whereas in diaphragm it decreased (P less than 0.02). Intracellular K+ correlated with pHe and pHE-PHi. Changes in pHi but not intracellular K+ could explain known differences in myocardial function in respiratory and metabolic acidosis.

Acidosis