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Biomedical subjects

I R Cameron

Publications and source records attributed to I R Cameron.

At least 37 records · Page 2Linked to original sources
PubMed1987

Effect of verapamil on polycythaemia secondary to hypoxia in rats.

1. Polycythaemia occurs in man secondary to chronic hypoxaemia, and may lead to morbidity from hyperviscosity of the blood. Hypoxaemic rats develop similar changes. We have investigated the effect of the calcium antagonist verapamil upon the polycythaemic response to hypoxia in rats. 2. Control groups of 10 male rats breathed air in an environmental chamber for 28 days. Hypoxic groups breathed a normobaric atmosphere of 10% oxygen for 6 h each day, and air for the remaining 18 h. Control and hypoxic groups were treated with intraperitoneal or subcutaneous water, or with intraperitoneal or subcutaneous water plus verapamil. 3. On day 28, packed cell volume (PCV) was measured by a microhaematocrit technique and red cell mass (RCM) by dilution of injected 51Cr-labelled rat erythrocytes. 4. PCV and RCM were significantly higher in all the hypoxic groups compared with the control groups (P less than 0.01 in each case). 5. PCV and RCM were significantly lower in the hypoxic groups treated with intraperitoneal or subcutaneous verapamil than in the hypoxic groups treated with intraperitoneal or subcutaneous water (P less than 0.01). There were no significant differences between PCV and RCM in verapamil- and water-treated normoxic control groups. Verapamil had no effect on the shift of the oxygen/haemoglobin dissociation curve produced by hypoxia. 6. Verapamil reduces the polycythaemic response to repeated intermittent hypoxia in rats. Venesection is usually performed for excessive secondary polycythaemia in man. Our results suggest a possible therapeutic role for verapamil in such individuals.

Animals↗
PubMed1987

The acute haemodynamic effects of intravenous verapamil in patients with chronic obstructive airways disease.

The haemodynamic effects of a single intravenous dose of verapamil have been investigated in patients with chronic obstructive airways disease both during an acute exacerbation and when in a stable clinical condition and compared with the effects of oxygen administered by nasal cannulae. In five patients studied during an episode of acute on chronic hypoxaemia (mean PaO2 = 5.4 kPa) there was a significant fall in pulmonary vascular resistance (p less than 0.03) following intravenous verapamil (10 mg) without any reduction in PaO2, cardiac index or oxygen delivery. Subsequent administration of oxygen by nasal cannulae at 2 l/min for 30 min produced similar pulmonary haemodynamic changes: pulmonary vascular resistance fell by 17 +/- 3 per cent following oxygen and by 22 +/- 4 per cent following verapamil. In a similar group of five patients in a stable clinical condition (mean PaO2 = 7.3 kPa) neither oxygen nor verapamil administered during acute exacerbations produced any significant changes in pulmonary vascular resistance, cardiac index or oxygen delivery.

Acute Disease↗
PubMed1986

Intermittent hypoxia in patients with unexplained polycythaemia.

The aetiology of polycythaemia is unclear in up to 30% of patients. Twenty patients with unexplained polycythaemia were investigated to see whether they had an intermittent hypoxic stimulus to erythropoiesis that was undetected by conventional investigations for hypoxic secondary polycythaemia. Overnight polygraphic sleep studies showed that five patients had prolonged nocturnal hypoxaemia. Their arterial oxygen saturation was below 92%, the level at which appreciable hypoxic stimulation of erythropoiesis occurs, for 26-68% of the time for which they were studied. Considerable evidence is accumulating that intermittent hypoxia is a potent stimulus to erythropoiesis, and clinicians should consider the possibility of nocturnal hypoxia in patients with unexplained polycythaemia. Appropriate investigation will lead to the correct diagnosis of polycythaemia secondary to hypoxia in some cases previously regarded as idiopathic, and treatment may then be planned accordingly.

Adult↗
PubMed1986

Effects of PCO2, pH and extracellular calcium on contraction of airway smooth muscle from rats.

The effect of changes in PCO2 on airway smooth muscle was studied in acetylcholine-induced contractions of isolated rat trachea. Elevation of superfusate PCO2 from control PCO2, 38 mm Hg (pH 7.49), to 168 mm Hg (pH 6.74) decreased tension to 68% of control tension; reduction of PCO2 to 19 mm Hg (pH 7.84) increased tension to 104%. Similar effects on tension occurred when pH was altered by varying superfusate bicarbonate concentration at constant PCO2. Modification of the response to changes in PCO2 by varying extracellular calcium (Ca2+) concentration and also by verapamil indicated that changes in PCO2 and pH may alter Ca2+ uptake by the smooth muscle. Calcium uptake was measured by 45Ca2+ and the lanthanum method. At control pH 7.49, net Ca2+ uptake was 5.34 mmol Ca2+/kg trachea 60 min after the onset of contraction; this decreased to 4.26 at pH 6.88, and increased to 6.58 at pH 7.85. The results suggest that the mechanism whereby changes in PCO2 affect airway smooth muscle contraction is a pH-dependent alteration of Ca2+ uptake.

Animals↗
PubMed1985

Ventilatory control in normal man following five minutes' exposure to hypoxia.

Ventilatory control was studied in normal subjects following brief (5 min) exposure to hypoxia (inhalation 7-8% O2). The ventilatory response to rebreathing CO2 (hyperoxic) was assessed 20 min before and after 5 min exposure to (a) 7-8% O2, (b) 7-8% O2 rebreathing CO2, (c) rebreathing CO2 during hyperoxia, and (d) 10% O2, normocapnic. The slope of the V-PCO2 response (S) was increased for up to 40 min following (a) and (b) by 25-34%, but was unchanged following (c) and (d). Resting ventilation was unchanged throughout. The ventilatory response to normocapnic progressive hypoxia was measured as the slope of the V-Hb% SaO2 relationship (H); this was increased by 26%. The mechanism underlying this change in ventilatory control in man is unknown; it may relate to the process of acclimatization to hypoxia whereby chronic hypoxia is a greater stimulus to ventilation than acute hypoxia.

Acclimatization↗
PubMed1985

Alterations to potassium fluxes in the heart during chronic dietary potassium depletion.

Dietary K+ depletion in rabbits causes a loss of cellular K+ from skeletal muscle but not from cardiac muscle, and it has been suggested that this is due to a specific protective mechanism in the heart. Net uptake and efflux of 42K was investigated in the interventricular septum of the rabbit. Acute reductions in extracellular [K+] caused a loss of K+ from tissue of both normal and K+ depleted animals. In the K+ depleted group the relationship between [K+]e and net uptake was altered, so that the maximum rate of uptake was increased, and this was obtained at a lower [K+]e. There were no significant changes in K+ efflux. These results would be consistent with an adaptive change to the cardiac cell Na+ pump during chronic K+ depletion.

Animals↗
PubMed1985

The effect of verapamil and inspired CO2 on the bronchoconstriction provoked by hyperventilation in normal humans.

Two groups of eight normal subjects were investigated in separate studies to demonstrate the effects of changes in end-tidal PCO2, and of pretreatment with the calcium antagonist drug verapamil, on bronchoconstriction provoked by voluntary hyperventilation. Total respiratory resistance (Ros) was measured by the forced oscillation technique before and after 90 s voluntary hyperventilation. End-tidal PCO2 during hyperventilation was varied by altering inspired CO2 concentration. When end-tidal PCO2 fell during hyperventilation, there was a rise in Ros. This did not occur if end-tidal PCO2 was controlled at a normal resting level during hyperventilation. Specific conductance (sGaw) was measured before and after 90 s voluntary hyperventilation of air. Subjects were treated with oral verapamil or placebo for 2 1/2 days and the effect of hyperventilation on sGaw was reassessed. Verapamil reduced significantly the fall in sGaw caused by hyperventilation. Placebo had no effect. In normal humans, bronchoconstriction provoked by hyperventilating air at ambient temperature and humidity is mediated by the fall in PCO2, and is also reduced by verapamil.

Adult↗
PubMed1985

Right ventricular hypertrophy and polycythaemia in rats after intermittent exposure to hypoxia.

Six groups of 20 male adult rats were maintained in an environmental chamber, each group for a period of 28 days. One group breathed air throughout its experimental period, and a second group breathed a normobaric atmosphere of 12% oxygen. The other four groups were exposed to this hypoxic atmosphere for only a proportion of each 24 h cycle: 2, 4 and 12 h daily, and eight periods of 30 min daily. After 28 days, measurement was made, in each rat, of right ventricule (RV) weight and of red cell mass (RCM) by using 51Cr-labelled rat erythrocytes. In the normoxic control group, RV weight corrected for log body weight in grams was 63.2 +/- 1 mg/log body wt. and RCM was 2.02 +/- 0.05 ml/100 g body wt. This was significantly less than in the group hypoxic for only 2 h each day for 28 days: RV weight 66.6 +/- 0.8 mg/log body wt. (P less than 0.05) and RCM 2.27 +/- 0.05 ml/100 g body wt. (P less than 0.05). Greater increases compared with control were observed in all the other hypoxic groups. There was no significant difference in the increases in RV weight and RCM produced by daily hypoxia in a 4 h continuous period and daily hypoxia in eight 30 min periods. The possible role of intermittent hypoxia in producing polycythaemia and pulmonary hypertension has been the subject of much speculation. Our results show that intermittent hypoxia is a potent stimulus to erythropoiesis and to pulmonary hypertension, reflected in RV hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Herpes simplex virus sequences involved in the initiation of oncogenic morphological transformation of rat cells are not required for maintenance of the transformed state.

We have determined the herpes simplex virus (HSV) type 2 DNA sequences responsible for the initiation of morphological transformation and have investigated the retention and expression of these sequences in morphologically transformed cells and in tumours derived from these cells. All the transformed cells analysed were selected by a focus formation assay and are oncogenic in the inbred host rat. Cloned HindIII and Bg/II fragments from the HSV-2 genome were assayed for the ability to initiate morphological transformation of rat embryo cells. Only the HindIII a (map units 0.52 to 0.72) and the Bg/II n (0.582 to 0.612) clones gave transformed foci. This shows that the Bg/II n region is responsible for initiation of transformation. Southern blot analysis of DNA extracted from these transformed cells and from tumours derived from these transformed cells revealed that neither the Bg/II n fragment nor fragments of 500 bp mapping within it are detected at the level of one copy per cell and therefore need not be retained in the cell to maintain the oncogenic phenotype. In addition there was no evidence of expression of the HSV-specified ribonucleotide reductase activity which is partially encoded within the Bg/II n fragment of HSV-2. We also analysed DNA from rat embryo cells transformed by ts mutants of HSV-2 (HG52) or HSV-1 (HFEM or 17) at non-permissive temperature or by virus at supraoptimal temperature or by sheared virus DNA and DNA from tumours derived from lines of these transformed cells. In addition, we cloned both transformed and tumour cell lines and analysed these similarly. In no case could we detect HSV DNA sequences at the level of one copy per cell.

Animals↗
PubMed1984

Adaptation of the cardiac muscle sodium pump to chronic potassium deficiency.

During chronic dietary K+ depletion in rabbits there is a significant reduction of intracellular K+ concentration [( K+]i) in skeletal muscle, but not in the heart. After 1 week of subsequent K+ repletion both plasma [K+] and skeletal muscle [K+]i had returned to control levels. Cardiac muscle on the other hand showed a significant increase in [K+]i above control. It has been suggested that the heart is protected during K+ depletion by some modification to the sarcolemmal Na+ pump. The Na+ pump density was estimated in membrane preparations from normal and K+ depleted rabbits by the specific binding of 3H-ouabain. 3H-ouabain binding in cardiac muscle preparations was increased significantly after 2 weeks of K+ depletion, and remained so for a further 2 weeks of depletion. There was no significant change in 3H-ouabain binding to skeletal muscle preparations after 4 weeks of K+ depletion. After 1 week of subsequent K+ repletion 3H-ouabain binding was still increased in cardiac muscle preparations, corresponding to the overshoot in cardiac muscle [K+]i. These results support the hypothesis that cardiac muscle is protected against K+ loss during chronic K+ depletion by an adaptive increase in Na+ pump density.

Adaptation, Physiological↗
PubMed1984

Treatment of asthma in a general practice.

We examined the general practice treatment of 67 patients diagnosed as asthmatic. Compliance with treatment was poor in one-third of patients with severe asthma. Inhaled steroids were under-prescribed and our findings suggest that some severe asthmatics are receiving less than adequate therapy.

Adolescent↗