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Biomedical subjects

M J Curtis

Publications and source records attributed to M J Curtis.

At least 91 records · Page 5Linked to original sources
PubMed1987

Effects of (-), (+/- ), and (+) verapamil on coronary occlusion-induced mortality and infarct size.

In a blind and randomised study, (-), (+/- ), and (+) verapamil were compared for their abilities to reduce mortality induced by occlusion of the left anterior descending coronary artery in conscious rats. In addition, effects on infarct size were also measured. In a separate experiment, the ability of an observer to detect ventricular fibrillation (VF) on the basis of changes in behaviour alone was established; (+/- ) verapamil statistically significantly reduced total mortality compared with controls, while (-) verapamil produced a similar, but non-statistically significant reduction. Both (+/- ) and (-) verapamil reduced mortality caused by VF; (-) verapamil was more effective than (+/- ) verapamil. Neither (-), (+/- ), nor (+) verapamil reduced infarct size in 24-h survivors; (-) verapamil produced the highest incidence of morbidity and associated cardiovascular depression (hypotension, bradycardia, and P-R interval prolongation), whereas (+) verapamil produced the least. Since (-) verapamil is a more potent calcium antagonist than (+) verapamil, the results of this study support the hypothesis that calcium antagonism was responsible for the observed antiarrhythmic actions.

Animals↗
PubMed1986

Identification of chicken major histocompatibility complex (B) haplotypes by an immunoblot technique.

A means of identifying the major histocompatibility complex (MHC) phenotype of chickens has been developed using solubilised extracts of cell membranes. The proteins from the solubilised membranes are separated by gel electrophoresis, applied to nitrocellulose membranes and detected using specific alloantisera followed by biotin-conjugated secondary antisera and avidin-glucose oxidase complex. This procedure allows samples to be stored frozen for at least 2 years before analysis and in conjunction with Western blotting allows characterisation of the class of MHC-encoded protein identified by the antisera.

Animals↗
PubMed1986

An improved perfusion apparatus for small animal hearts.

A perfusion apparatus for mechanical and electrophysiological studies in small animal (e.g., rat, guinea pig) hearts is described. The apparatus consists of a number of individual perfusion chambers connected to the aortic perfusion cannula of a Langendorff perfused heart. The aortic root perfusion pressure is controlled by the oxygenating gas (usually 5% CO2 in O2) at a range of 0-200 mmHg. Different solutions can be placed in different individual chambers. Pressure in the left ventricle is monitored by means of a special compliant, but nonelastic, balloon while special atraumatic electrodes allow high-voltage, noise-free ECG recordings to be made from all parts of the epicardium. The apparatus keeps hearts beating for hours while the multichamber allows multiple drug applications to be made rapidly. Thus, the apparatus can be used for all types of pharmacodynamic analysis.

Animals↗
PubMed1986

Actions of the verapamil analogues, anipamil and ronipamil, against ischaemia-induced arrhythmias in conscious rats.

Two analogues of verapamil, ronipamil and anipamil, were tested for their ability to reduce arrhythmias induced by occlusion of the left anterior descending coronary artery in conscious rats. Only anipamil (50 and 150 mg kg-1 orally) produced a statistically significant reduction in arrhythmias; it was most effective against ventricular fibrillation. Ronipamil at the same doses had limited antiarrhythmic actions. Only anipamil delayed the development of ECG signs of ischaemia, while both drugs reduced the magnitude of such changes. Anipamil has a more favourable ratio of antiarrhythmic to hypotensive effects when compared with verapamil.

Animals↗
PubMed1986

The mechanism of action of the optical enantiomers of verapamil against ischaemia-induced arrhythmias in the conscious rat.

The actions of (-)-verapamil (0.2-6 mg kg-1) and (+)-verapamil (0.4-12 mg kg-1) against arrhythmias induced by coronary artery occlusion were studied in conscious rats. Intravenously administered (-)- and (+)-verapamil dose-dependently reduced ventricular arrhythmias. (-)-Verapamil was consistently 4 times more potent than (+)-verapamil. In the same animals, (-)-verapamil was approximately 4 times more potent than (+)-verapamil for effects on heart rate and blood pressure. Both enantiomers prolonged P-R interval, but had no effect on QRS interval. In separate groups of conscious rats, neither enantiomer influenced the threshold voltage and pulse width required to elicit fibrillo-flutter, or altered the maximum following frequency, during electrical stimulation of the left ventricle. In isolated, paced, Langendorff-perfused ventricles of the rat, both enantiomers dose-dependently reduced contractility, (-)-verapamil being 8-21 times more potent than (+)-verapamil; both absolute and relative potencies were dependent on potassium concentration. These results are compatible with the hypothesis that calcium antagonism in the ischaemic ventricular myocardium is antiarrhythmic during acute myocardial ischaemia.

Animals↗
PubMed1986

Lanthanum as a surrogate for calcium in transmitter release at mouse motor nerve terminals.

The mechanism by which lanthanum (La3+) causes an increased frequency of miniature end-plate potentials (m.e.p.p.s) was studied at the mouse neuromuscular junction. At concentrations as low as 0.25 microM, La3+ caused a progressive rise in m.e.p.p. frequency, to a maximum of several hundred per second. 'Washing' with solution containing EDTA arrested the rise, but did not substantially reduce the raised m.e.p.p. frequency. At partially 'lanthanized' junctions high frequencies of m.e.p.p.s were maintained indefinitely, even in 0 Ca2+/EDTA solutions. The rate of development of high m.e.p.p. frequency was increased by repetitive nerve stimulation or by depolarization of the nerve terminal (high K+ or focally applied current), and appeared to be proportional to the concentration of La3+ over the range of 0.25-5 microM. At low concentrations of La3+ the rise of m.e.p.p. frequency depended upon the co-presence of a small amount of Ca2+ (greater than 10 microM) and was slowed and partially blocked by Cd2+, or by Ca2+ at about 10 microM. The quantal content of end-plate potentials was usually reduced in the presence of La3+, but was increased over control values after removal of La3+ by 'washing' with solution containing EDTA, once a raised m.e.p.p. frequency had developed. At partially lanthanized junctions the absolute increases in m.e.p.p. frequency produced by Ca2+ (in raised K+), ethanol, or by nerve stimulation in the presence of Ba2+, were greater than at control junctions, but in each case the increases in the logarithm of m.e.p.p. frequency were less than at control junctions. It is concluded that La3+ causes transmitter release only after entry into the nerve terminal via voltage-sensitive channels, probably those that normally admit Ca2+, that La3+ and Ca2+ may co-operate at internal sites to induce transmitter release, and that these ions both co-operate and compete at external sites that regulate their entry into the nerve terminal.

Action Potentials↗
PubMed1985

The actions of felodipine on arrhythmias and other responses to myocardial ischaemia in conscious rats.

The antiarrhythmic activity of felodipine was investigated in conscious chronically prepared rats subjected to coronary artery occlusion. By deliberate high or low placement of an occluder, either large or small occluded zones were produced. In rats with small occluded zones (SOZ), felodipine i.v. (0.2 mumol/kg slow injection + 0.01 mumol/kg per min infusion, and 12.2 mumol/kg slow injection) possessed slight antiarrhythmic activity. In rats with large occluded zones (LOZ), similar doses of felodipine had little antiarrhythmic activity. Felodipine produced a dose-dependent reduction in blood-pressure and delayed the development of ECG signs of ischaemia (ST elevation). The occluded zone size was not reduced by felodipine, although some myocardial salvage (8-17%) may have occurred in SOZ rats. It is concluded that felodipine, at doses producing severe hypotension associated with vasodilatation, possesses little antiarrhythmic activity.

Animals↗
PubMed1985

The effects of ablations in the central nervous system on arrhythmias induced by coronary occlusion in the rat.

The role of the central nervous system (CNS) in arrhythmogenesis in the 4 h period following occlusion of a coronary artery was investigated in rats by use of CNS ablations and other procedures. Ablations in the CNS included pithing, spinalization and decerebration combined with acute and chronic surgical preparation and noradrenaline/adrenaline infusions. All procedures involving acute surgery reduced the incidence and severity of the arrhythmias induced by occlusion. Such reductions were most marked in the second (0.5-4 h post-occlusion) arrhythmic period. The observed reductions in arrhythmias could not be explained in terms of involvement of the CNS or adrenoceptor activation. When circulating leucocytes, platelets and serum potassium were measured in a group of pithed rats before and after occlusion, reduced levels (20-50%) of both leucocytes and platelets occurred while serum potassium levels rose by 50-100%. Arrhythmias following coronary occlusion may depend in part on factors in the blood such as leucocytes, platelets and serum potassium and these factors may be altered by acute surgery.

Animals↗
PubMed1984

Antiarrhythmic actions of verapamil against ischaemic arrhythmias in the rat.

The actions of intravenous verapamil against arrhythmias induced by occlusion of a coronary artery were investigated in conscious rats. Verapamil (2-20 mg kg-1, i.v. given pre-occlusion) dose-dependently reduced arrhythmias in rats with either large or small occluded zones at an ED50 of 6 mg kg-1. This dose was effective when given immediately post-occlusion. Severe arrhythmias, as opposed to PVC, were preferentially reduced. In conscious, and pentobarbitone-anaesthetized rats, verapamil (6 mg kg-1) had different effects on electrically-induced arrhythmias, and the ECG, from an equi-effective anti-arrhythmic dose of quinidine (20 mg kg-1, i.v.). Quinidine decreased following frequency, but increased threshold current and pulse width, whereas verapamil did not. Both drugs increased P-R interval, but only quinidine increased QRS and Q-T intervals. Thirty minutes post-occlusion, the verapamil content of tissue and blood was determined after a 6 mg kg-1 dose given pre- or post-occlusion. Measurable levels of verapamil were found in both normal and ischaemic myocardium. Plasma and plasma water concentrations were 3.6 +/- 0.8 mumol l-1 and 0.6 +/- 0.1 mumol l-1 (mean +/- s.e. mean), respectively following post-occlusion administration vs. 2.7 +/- 1.2 and 0.24 +/- 0.04 for pre-occlusion administration. Plasma water concentrations were close to IC50 values for inhibition of contractility in rat atria and ventricles. Similar concentrations depressed slow action potentials induced in rat ventricles by raised K+ We suggest that the ability of verapamil to prevent severe ventricular arrhythmias following myocardial ischaemia in the conscious rat is largely due to the calcium antagonist effects of the drug.

Action Potentials↗
PubMed1981

The influence of Escherichia coli O78 endotoxin on carbohydrate metabolism in the domestic fowl.

The injection of endotoxin isolated from a pathogenic avian strain of Escherichia coli (1 mg/kg intravenously) accelerated the depletion of liver glycogen in fasting nine- to 10-week-old chickens within the first hour and concurrently reduced their plasma inorganic phosphate levels. These changes were attributed to increased glycogenolysis and were followed by hypoglycaemia and a large increase in the lactate content of the plasma which appeared to be caused by enhanced glucose oxidation and reduced gluconeogenesis. The plasma glucose level returned to normal within three hours and simultaneous changes in the plasma urate and albumin content indicated that glucose was being synthesised from amino acids and that albumin was being catabolised to provide them.

Animals↗
PubMed1981

Bacterial endotoxins and the pathogenesis of fatty liver--haemorrhagic syndrome in the laying hen.

A high energy maize diet produced a higher incidence of fatty liver-haemorrhagic syndrome than a low energy barley diet when the diets were fed during the summer. The triglyceride content of the liver increased with the liver haemorrhage score and in hens with the highest scores there was evidence of hepatic hyperplasia. They also had high activities of aspartate transaminase and cholinesterase in the plasma and a low activity of sorbitol dehydrogenase. There was no increase in plasma endotoxin levels as the syndrome developed or any significant variation in these levels with the haemorrhage score, the triglyceride content of the liver or plasma enzyme activities. It was concluded that the steatosis does not impair the ability of the liver to inactivate endotoxins of enteric bacteria and that these toxins are not involved in the pathogenesis of the syndrome.

Animals↗
PubMed1980

The effect of Escherichia coli endotoxins on the concentrations of corticosterone and growth hormone in the plasma of the domestic fowl.

The intravenous injection of chickens aged six to 11 weeks with Escherichia coli endotoxins (serogroups O111 and O78) produced a large increase in the plasma corticosterone concentration which was maximal (five to 10-fold) after 1 h and still evident after 8 h. It did not vary with the dose over the range 0.1 to 2 mg/kg and was smaller than that produced by adrenocorticotrophic hormone (ACTH) (20 iu/kg). A decrease in growth hormone concentration was detected between 1 and 2 h after endotoxin administration in six- to seven-week-old birds, this change being opposite to that which occurs in man.

Adrenocorticotropic Hormone↗
PubMed1980

The effect of Escherichia coli endotoxins and adrenocortical hormones on plasma enzyme activities in the domestic fowl.

The intravenous injection of endotoxins isolated from Escherichia coli serogroups O111 and O78 (2 mg/kg) increased the activities of aspartate transaminase and lactate and sorbitol dehydrogenases in the plasma of six- to 11-week-old chickens during the next 24 h. These changes were compared with those produced by adrenocorticotrophic hormone and beta-methasone and were attributed to tissue damage involving the liver followed by increased enzyme synthesis which may have been induced partly by adrenocortical hormones. Further evidence of liver damage was provided by a fall in the activity of cholinesterase. The alkaline phosphatase activity gave no indication of cholestasis.

Adrenocorticotropic Hormone↗
PubMed1980

Response of caeruloplasmin to Escherichia coli endotoxins and adrenal hormones in the domestic fowl.

The injection of chickens with Escherichia coli endotoxins immediately produced a 50 per cent rise in plasma caeruloplasmin activity which was attributed to the release of the protein from liver cell. This was followed by a fall in activity, which was probably due to a fall in activity, which was probably due to a stabilising effect of adrenocortical hormones on the cell membranes, and then by a five-fold increase. The results of experiments with cycloheximide, adrenocorticotrophin, beta-methasone and reserpine indicated that the third phase of the response reflected increased synthesis in the liver which was partly induced by adrenal hormones. It increased with the dose and was not elicited by the particulate nature of the toxin preparation or by its lipid and polysaccharide components.

Adrenal Cortex Hormones↗
PubMed1980

Effect of Escherichia coli O78 endotoxin on plasma lipids in the domestic fowl.

The injection of fasting nine- to 10-week-old chickens with endotoxin from a pathogenic avian strain of Escherichia coli (1 mg/kg iv) reduced the triglyceride, cholesterol and phospholipid content of the plasma 2 to 5 h afterwards. This effect was similar to that of an E coli infection and opposite to that produced in mammals. There was a transient rise in the cholesterol level within the first hour.

Animals↗
PubMed1980

Bacterial endotoxins and liver haemorrhage in the oestrogenised chicken.

Hepatic steatosis and haemorrhage in oestrogenised chickens were not associated with any increase in the endotoxin content of the plasma. The haemorrhage was not ameliorated by suppressing enteric bacteria with neomycin or exacerbated by the repeated injection of Escherichia coli O111 endotoxin and there were no relevant changes in plasma enzyme activities that are indicators of liver damage. These results therefore do not support the hypothesis that, as in the choline deficient rat, hepatic steatosis impairs the ability of the oestrogenised chicken to dispose of bacterial endotoxins and that these then damage the liver.

Animals↗
PubMed1977

Escherichia coli endotoxin as a stressor in the domestic fowl.

During 24 h after the injection of fowls (aged eight to 11 weeks) with Escherichia coli endotoxin (1 to 3 mg/kg) isolated from a pathogenic strain (O78) there were changes in the ascorbate content of the adrenal gland and increases in the plasma free fatty acid levels, indicating that the toxin behaves as a mild stressor.

Adrenal Glands↗