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Biomedical subjects

J D Allen

Publications and source records attributed to J D Allen.

161 records · Page 9Linked to original sources
PubMed1972

The effect of Kö 1173, a new anticonvulsant agent on experimental cardiac arrhythmias.

1. The effects of the intravenous injection of Kö 1173, a new anticonvulsant drug, phenytoin and procainamide were studied on three types of cardiac arrhythmia in dogs.2. Ventricular ectopic beats produced by intravenous injection of adrenaline in anaesthetized dogs respired with halothane were abolished by Kö 1173, 0.6 +/- 0.1 mg/kg, phenytoin, 1.1 +/- 0.3 mg/kg and procainamide, 4.1 +/- 1.8 mg/kg.3. Ventricular tachycardia was produced in anaesthetized dogs by the intravenous injection of ouabain and the three drugs infused intravenously at 0.2 (mg/kg)/min until sinus rhythm returned. Kö 1173 was effective in 8 out of 9 dogs after a mean dose of 1.3 +/- 0.3 mg/kg; phenytoin in all 3 dogs after 2.7 +/- 0.6 mg/kg and procainamide in the 3 dogs tested after 16.6 +/- 1.3 mg/kg.4. The intravenous injection of Kö 1173, 8.0 mg/kg, greatly reduced the number of ventricular ectopic beats occurring in conscious dogs 18-44 h after ligation of the anterior descending branch of the left coronary artery, with a resultant increase in the number of sinus beats. Phenytoin, 8.0 mg/kg, had a similar effect but procainamide was much less effective.5. These results indicate that Kö 1173 is effective in abolishing experimental cardiac arrhythmias and suggest that its effects should be studied in patients.

Animals↗
PubMed1971

Effects of lignocaine and propranolol on experimental cardiac arrhythmias.

1. The effects of intravenous injection of lignocaine and propranolol were studied in dogs.2. Ventricular ectopic beats produced by intravenous injection of adrenaline in anaesthetized dogs respired with halothane were abolished in four out of six dogs by lignocaine. Propranolol was effective in all three dogs tested.3. Intravenous infusion of lignocaine at (0.2 and 1.0 mg/kg)/min to total doses of 3.0 +/- 1.0 and 2.2 +/- 0.5 mg/kg, respectively, abolished the ventricular tachycardia produced in anaesthetized dogs by ouabain. A similar effect was produced by infusion of propranolol at (0.2 mg/kg)/min to a total dose of 1.9 +/- 0.4 mg/kg. Intravenous injection of single doses of lignocaine (4.0-8.0 mg/kg) also abolished the arrhythmia.4. The frequency of the ventricular ectopic beats occurring in conscious dogs 20-44 h after ligation of the anterior descending branch of the left coronary artery was reduced, with an increase in the number of sinus beats, after intravenous injection of lignocaine (8.0 mg/kg). Larger doses produced excitement. Propranolol (4.0 mg/kg) had a greater effect than the same dose of lignocaine but after 8.0 mg/kg, three of the four dogs died.5. Propranolol was more effective than lignocaine in abolishing the three different types of arrhythmia.6. Dose-response curves showed that lignocaine was more active in abolishing the ouabain induced arrhythmia than the halothane-adrenaline arrhythmia and was least active on the arrhythmia caused by ligation of the coronary artery.

Animals↗
PubMed1971

Compound stimulus control by discriminative stimuli associated with high and moderate response rates.

Four rats received water on a fixed-ratio schedule for lever pressing in the presence of a tone (or light) stimulus and on a variable-interval schedule in the presence of a light (or tone) stimulus. Following stabilization of a high response rate during the fixed-ratio component and a moderate response rate during the variable-interval component, brief periods with the light and tone presented simultaneously but with no responses reinforced were inserted into the regular training schedule. Response rates during the compound stimuli were intermediate between the response rates controlled by the individual fixed-ratio and variable-interval associated stimuli.

Animals↗
PubMedDate not supplied

Inhaled nitric oxide in combination with volume resuscitation refines a porcine model of endotoxic shock.

BACKGROUND: Existing porcine models of endotoxic shock poorly represent the human situation. AIMS: To assess whether the cardiovascular profile of a porcine model could be improved by refining the protocol. METHODS: In 30 pigs, right and left heart pressures and cardiac output were measured. Lipopolysaccharide (LPS) was administered as a bolus (n=12), as a 30 minute infusion (n=6) or as a 30 minute infusion along with inhaled NO and volume resuscitation (n=6) and six sham-treated pigs received normal saline. Haemodynamic values were measured over three hours. RESULTS: LPS increased pulmonary vascular resistance (PVR) (13.3 +/- 1.4 to 37.0 +/- 3.9kPa/l per sec, p<0.05) and reduced cardiac output (6.0 +/- 0.6 to 4.8 +/- 0.41/min). Mortality was 50% within 30 minutes. Inhaled NO and volume resuscitation controlled pulmonary vascular resistance (PVR) and preserved CO. Systemic vascular resistance (SVR) declined in the first hour (118.4 +/- 11.8 to 65.8 +/- 8.2kPa/l per sec, p<0.05) and remained low. CONCLUSIONS: Porcine models of endotoxaemia based on LPS administration are a poor model of human septic shock, but can be improved by regulating PVR and supporting CO which may contribute to future studies of septic shock

Administration, Inhalation↗
PubMedDate not supplied

The effects of potassium-ATP channel modulation on ventricular fibrillation and defibrillation in the pig heart.

BACKGROUND: Drugs acting on the cardiac ATP-sensitive potassium (K-ATP) channels may modulate responses to ischaemia and arrhythmogenesis. We investigated the effects of K-ATP channel modulation on frequency patterns of ventricular fibrillation (VF) and on defibrillation threshold (DFT). METHODS AND RESULTS: Each group of 24 pigs randomly received intravenous levcromakalim (LKM) 40 microgram/kg (K-ATP agonist), glibenclamide (Glib) 20 mg/kg (K-ATP antagonist), saline or vehicle. Firstly, QTc interval was measured before and after drug. VF was then induced by endocardial stimulation and its power spectra and dominant frequencies over 15 min determined by fast Fourier transformation. Secondly, transthoracic DFT was determined (step-up/step-down protocol) before and after each drug. LKM reduced QTc interval (e.g., lead II, 354-321 ms, P<0.05) and increased the dominant VF frequency between 6 and 8 min (9.5+/-0.5 Hz at 6.5 min compared with 7.2+/-0.6 Hz (saline), 7.4+/-0.8 Hz (vehicle), 6.8+/-0.5 Hz (Glib), P=0.03). LKM reduced (to 57.2+/-2.1 mmHg) and Glib increased (to 107.8+/-6.1) mean arterial BP compared with saline (80.3+/-5.6) and vehicle (87. 6+/-7.1; P<0.01). There was no significant difference in defibrillation threshold energy, current or voltage, after any drug. CONCLUSIONS: Activation of K-ATP channels reduced blood pressure and QTc interval. The lack of major effect on VF dominant frequency and DFT of either LKM or Glib suggests that prior administration of similar drugs to patients should not prejudice outcome from VF cardiac arrest.

Analysis of Variance↗
PubMedDate not supplied

Effect of alinidine on experimental cardiac arrhythmias.

Alinidine (2.9 +/- 0.7 mg/kg) prevented an adrenaline-induced ventricular arrhythmia in dogs respired with halothane. In ouabain-induced ventricular tachycardia, a cumulative dose of alinidine (15.5 mg/kg) reduced the number of ventricular beats by 91.6 +/- 1.9%. The drug was much less effective in abolishing the ventricular tachycardia 24 h after ligation of a coronary artery, with only a 36 +/- 15% reduction in ventricular ectopic beats after 15.5 mg/kg. The administration of alinidine (0.5-1.0 mg/kg) to anaesthetized dogs with no cardiac arrhythmia reduced sinus node rate with little effect on the response of the node to vagal stimulation.

Animals↗
PubMedDate not supplied

Antiarrhythmic and cardiovascular effects of MP 115.

We studied the effects on experimental cardiac arrhythmias of MP 115, a tertiary amine, in dogs anaesthetised with pentobarbitone sodium. Low doses of the drug (0.2-2.1 mg/kg i.v.) abolished ventricular tachycardia resulting from cardiotoxic doses of ouabain in 12 of 15 experiments. The ventricular arrhythmic response to the intravenous administration of adrenaline was prevented in dogs respired with 1% halothane in room air. Higher doses given intravenously to conscious dogs by sequential injections or infusion abolished the ventricular tachycardia 1 day after ligation of the anterior descending branch of the left coronary artery (effective plasma concentration, 5.0 +/- 1.6 micrograms/ml). Studies in normal dogs anaesthetised with pentobarbitone sodium (30 mg/kg) showed that the drug (0.1-1.0 mg/kg) caused reductions in arterial blood pressure and peripheral resistance. In isolated rabbit ear arteries perfused at a constant flow rate, MP 115 (1-10 microM) competitively antagonised the vasoconstrictor response to noradrenaline and had a more potent effect on the responses to 5-hydroxytryptamine. The vasoconstrictor responses to histamine, barium, and potassium were only reduced at higher concentrations. Poor oral absorption and central nervous system toxicity limit further development of this compound.

Animals↗
PubMedDate not supplied

The effects of encainide and its major metabolites, O-demethyl encainide and 3-methoxy-O-demethyl encainide, on experimental cardiac arrhythmias in dogs.

Encainide (E) is a class I antiarrhythmic agent which is metabolised in humans, with the formation in the majority of patients of O-demethyl encainide (ODE) and 3-methoxy-O-demethyl encainide (MODE). As it has been suggested that these metabolites may contribute to the antiarrhythmic effect of E in humans, we have investigated the effects of E, ODE, and MODE on ventricular arrhythmias produced by ouabain and by coronary artery ligation. In the ouabain model, E restored sinus rhythm (SR) in eight of 13 dogs after a mean dose of 0.81 +/- 0.19 mg/kg (mean +/- SEM). ODE returned SR in five of 10 dogs after 0.30 +/- 0.06 mg/kg, and MODE returned SR in two of nine dogs after doses of 0.40 and 0.68 mg/kg, respectively. For comparison, mexiletine returned SR in six of six dogs after 3.50 +/- 1.02 mg/kg. In conscious dogs with ventricular arrhythmias 24 h after two-stage coronary artery ligation E restored SR in four of four dogs after 2.38 +/- 0.50 mg/kg. ODE restored SR in four of four dogs after 0.63 +/- 0.14 mg/kg, and MODE restored SR in four of four dogs after 1.39 +/- 0.30 mg/kg. Thus, ODE and MODE have antiarrhythmic activity which may contribute to the effects of E in patients with cardiac arrhythmias.

Anilides↗