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Biomedical subjects

E Patterson

Publications and source records attributed to E Patterson.

At least 91 records · Page 5Linked to original sources
PubMed1985

Antiarrhythmic and electrophysiologic actions of clofilium in experimental canine models.

Clofilium was studied in three experimental models. In non-ischemic and chronically infarcted canine hearts, clofilium (0.5-2 mg/kg) produced a dose-dependent increase in electrical ventricular fibrillation threshold (VFT), but prolonged the effective refractory period (ERP) of normal myocardium in only the non-ischemic heart. When chronically infarcted hearts were subjected to programmed electrical stimulation, 1 mg/kg of clofilium inhibited the re-induction of either ventricular tachycardia or ventricular fibrillation in 5 of 6 animals and slowed the rate of the induced tachycardia in the sixth. Clofilium, however, failed to alter ventricular refractory periods of normal myocardium at either twice diastolic threshold current (176 +/- 5 ms control vs. 187 +/- 9 ms post-clofilium, P greater than 0.05) or at 10 mA (134 +/- 6 ms control vs. 137 +/- 13 ms post-clofilium, P greater than 0.05). In addition, chronic administration of clofilium (2 mg/kg, i.v., followed by 1 mg/kg every 12 h) was ineffective in decreasing mortality in a canine model of sudden coronary death. Of 10 saline-treated conscious animals subjected to an electrically-induced intimal lesion of the left circumflex coronary artery in the presence of a previous ischemic insult, all 10 died suddenly of ventricular fibrillation within 173 +/- 45 min after current application. Under similar conditions, 7 clofilium-treated animals died suddenly within 249 +/- 88 min (P greater than 0.05) after current application while 3 animals survived (P greater than 0.10). Clofilium did, however, elevate the effective refractory period in these animals (150 +/- 3 ms saline-treated vs. 195 +/- 7 ms clofilium-treated). It is concluded from our data that there is little relationship between clofilium's electrophysiologic actions in normal myocardium and antiarrhythmic effects. Furthermore, simple prolongation of refractoriness in normal non-ischemic myocardium may be insufficient for the prevention of ventricular fibrillation which develops in response to a transient ischemic event superimposed on a chronically injured myocardium.

Animals↗
PubMed1984

Sympathetic ophthalmia. Histopathologic and fluorescein angiographic correlation.

Sympathetic ophthalmia was found 15 months after cataract extraction in a previously traumatized eye. Histopathologic examination disclosed numerous Dalen-Fuchs nodules with underlying choroidal granulomas causing obliteration of the choriocapillaris and disruption of Bruch's membrane. Prominent Dalen-Fuchs nodules were also observed clinically in the sympathizing eye, and the angiographic findings of initial hypofluorescence followed by late hyperfluorescence correlated with the pathologic findings in the sympathogenic eye. Only ten cases of sympathetic ophthalmia with fluorescein angiography have been reported previously. This is the fifth case accompanied by a histopathologic description of the exciting eye. The finding of breaks in Bruch's membrane has not been previously reported, to the best of our knowledge. This article compares the angiographic and pathologic appearances with those described in previous reports.

Aged↗
PubMed1984

Antidysrhythmic actions of meobentine sulfate.

The antiarrhythmic efficacy of meobentine sulfate, a bethanidine derivative lacking inhibitory effects on adrenergic neuronal function, was assessed in three canine models. Intravenous meobentine sulfate, administered in dosages of 5.0, 10,0, and 20.0 mg/kg, produced a dose-related increase in the ventricular fibrillation threshold (VFT) under nonischemic conditions (7.6 +/- 1.8 mA vs 37.8 +/- 8.6 mA) (20 mg/kg; p less than 0.05) and during regional myocardial ischemia (5.6 +/- 1.5 mA vs 41.8 +/- 9.1 mA) (20 mg/kg; p less than 0.05). The VFT was also increased in the presence of chronic ischemic injury (6.4 +/- 1 mA to 31 +/- 10 mA) (20 mg/kg; p 0.05). In the conscious dog, 4 days after an anterior myocardial infarction, programmed electrical stimulation (PES) produced nonsustained ventricular tachycardia (VT) in five dogs. After meobentine sulfate administration, eight of nine animals had sustained VT and one animal developed ventricular fibrillation (VF). At a dose of 20 mg/kg, there was prolongation of the cycle length of the VT (169 +/- 11 msec to 237 +/- 20 msec), prolongation of the QRS duration (58 +/- 2.6 msec to 71 +/- 3.7 msec), and prolongation of the delay in epicardial activation. There was an enhanced potential after meobentine administration for programmed stimulation to produce ventricular arrhythmias with the introduction of fewer premature impulses. In the third canine model, conscious dogs with a previous anterior myocardial infarction developed VF in response to electrically induced left circumflex coronary artery injury. Meobentine (20 mg/kg) failed to prevent VF in eight of eight dogs. These results suggest that while meobentine sulfate significantly increases the electrical VFT, it does not protect the conscious canine from the induction of ventricular tachyarrhythmias in response to PES, and it does not prevent VF in a conscious canine model of sudden coronary death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Antifibrillatory properties of the beta-adrenergic receptor antagonists, nadolol, sotalol, atenolol and propranolol, in the anesthetized dog.

The antifibrillatory and electrophysiologic actions of the beta-adrenergic receptor antagonists, d,l-sotalol, d,l-nadolol, d,l-atenolol and d,l-propranolol were examined in anesthetized dogs. All four drugs were equally effective in increasing the electrical threshold for induction of ventricular fibrillation, but efficacy failed to correlate with reported beta-blocking efficacy. The d-isomers of the respective beta-adrenergic receptor blocking agents, sotalol and propranolol, were equipotent and equally effective at increasing the fibrillation threshold compared to their respective racemates. The ability of beta-adrenergic antagonists to increase the fibrillation threshold could not be attributed to changes in intraventricular conduction, ventricular refractoriness, or ventricular excitability in common with all four drugs. The antifibrillatory actions of the beta-adrenergic receptor blocking drugs could not be attributed solely to either beta-adrenergic blockade or specific alterations in the membrane properties of the cardiac cell.

Adrenergic beta-Antagonists↗
PubMed1984

Antiarrhythmic and antifibrillatory actions of the beta adrenergic receptor antagonist, dl-sotalol.

The antiarrhythmic and antifibrillatory actions of the beta adrenergic receptor antagonist, dl-sotalol, were examined in the canine heart subjected to myocardial ischemic injury. Programmed electrical stimulation of the heart was done 4 to 7 days after a 2-hr occlusion followed by reperfusion of the left anterior descending coronary artery. The resulting dysrhythmias consisted of nonsustained ventricular tachycardia (n = 1), sustained ventricular tachycardia (n = 5) or polymorphous ventricular tachycardia degenerating to ventricular fibrillation (n = 3). After dl-sotalol (8 mg/kg), programmed stimulation failed to produce ventricular arrhythmias in five animals with only nonsustained ventricular tachycardia observed in the other animals. Epicardial activation delays produced in ischemically injured myocardium by premature ventricular stimuli were not altered by treatment with sotalol. However, the increase in ventricular refractoriness (156 +/- 5 msec predrug vs. 191 +/- 7 msec post 8 mg/kg of sotalol, P less than .01) prevented the introduction of premature ventricular stimuli at coupling intervals previously producing ventricular tachyarrhythmias despite the presence of continuous diastolic electrical activity recorded with epicardial composite electrodes over the region of chronic myocardial injury. In a conscious canine model which spontaneously develops ventricular fibrillation, dl-sotalol (2 mg/kg, n = 7; 8 mg/kg, n = 13) decreased the incidence of ventricular fibrillation and increased survival at 24 hr (13 of 20, 65% vs. control, 1 of 15, 7%; P less than .001). Composite electrograms recorded from the anterior and posteriorlateral surfaces of the heart demonstrated the rapid development of activation delays on the posteriorlateral surface with the appearance of ischemic ST segment changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Cardiac electrophysiologic actions of KB-944 (Fostedil), a new calcium antagonist, in the anesthetized dog.

The cardiac electrophysiologic actions of a novel calcium antagonist, KB-944 [Fostedil, Abbott-53986, diethyl 4-(benzothiazol-2-yl) benzylphosphonate], were examined in anesthetized dogs. Cumulative doses of 0.5, 2.5 and 12.5 mg/kg i.v. produced dose-dependent increases in atrioventricular (AV) nodal refractoriness and conduction time (AH interval), although failing to alter atrial or ventricular refractoriness. Intra-atrial, infranodal and intraventricular conduction (PA, HV and H-EG intervals, respectively) were unchanged. In three of nine dogs, 2.5 to 12.5 mg/kg of KB-944 produced third degree AV blockade. Pretreatment with propranolol (0.1 mg/kg) was accompanied by sinoatrial blockade in three of five dogs who later received 12.5 mg/kg of KB-944. Glucagon (4 micrograms/kg) reversed the electrophysiologic changes associated with administration of KB-944 alone or in conjunction with propranolol. An examination of the temporal profiles of the cardiac electrophysiologic effects of KB-944 indicated selective alterations in AV nodal conduction and refractoriness for durations of approximately 60, 120 and 180 to 240 min after administration of 0.3, 1.0 or 3.0 mg/kg i.v. These results suggest that KB-944 may be an effective agent for treatment of supraventricular tachyarrhythmias via selective depression of the AV nodal conduction system.

Animals↗
PubMed1983

Ventricular fibrillation in a conscious canine model--its prevention by UM-272.

The antifibrillatory properties of UM-272 (dimethylpropranolol; Pranolium) were evaluated in a conscious canine model of sudden coronary death. The initial preparation of the animal model was carried out under surgical anesthesia and involved the intraluminal implantation of a Teflon-coated silver wire into the circumflex coronary artery so that 3 mm of the bared electrode was in contact with the endothelial surface. The left anterior descending coronary artery then was occluded for a period of 90 min and reperfused in the presence of a critical stenosis. Three days after myocardial infarction, they were randomized into two groups. One group (n = 10) served as controls and received saline. The second group (n = 10) received UM-272 in a dose of 5 mg/kg every 6 h. On day 4, a 150 microA current was applied to the intimal surface of the left circumflex coronary artery, resulting in transient or permanent alterations in circumflex coronary blood flow accompanied by electrocardiographic evidence of regional myocardial ischemia. The time to onset of ST-segment changes in the saline control group was 99 +/- 34 min and was followed by the appearance of premature ventricular complexes (111 +/- 34 min) and subsequent ventricular tachycardia (131 +/- 37 min) which terminated in ventricular fibrillation in each of the 10 dogs. Animals treated with UM-272 likewise developed ST-segment changes (156 +/- 28 min) and premature ventricular complexes (168 +/- 29 min), but 4 of 10 animals failed to develop ventricular fibrillation (P less than 0.05 vs. saline). These results demonstrate that UM-272, the dimethyl quaternary analog of propranolol, is effective in reducing the incidence of ventricular fibrillation in a conscious canine model in which the superimposition of a transient ischemic event upon an already jeopardized heart leads to the development of sudden death.

Animals↗
PubMed1983

Prevention of ventricular fibrillation by bretylium in a conscious canine model of sudden coronary death.

In anesthetized dogs, a silver wire electrode was inserted into the lumen of the circumflex coronary artery (LCX) and myocardial infarction was produced by a temporary 90-minute occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. Four days later while in the ambulatory state, a 150 microA current was applied to the intimal surface of the LCX of saline (n = 10) and bretylium (n = 10) treated animals. Intimal injury and coronary thrombosis produced ST segment changes at 138 +/- 39 minutes (chi +/- SEM), followed by premature ventricular beats (at 142 +/- 37 minutes), ventricular tachycardia (at 156 +/- 49 minutes), and ventricular fibrillation (at 163 +/- 51 minutes) in 9 of 10 saline-treated animals. In bretylium-treated animals, ST segment changes appeared at 128 +/- 35 minutes, with six animals surviving for 24 hours (p less than 0.03 vs saline). LAD infarction was present in both saline (14.1 +/- 2.3%) and bretylium (15.1 +/- 2.1% of left ventricle) treated animals with only bretylium-treated animals developing LCX infarcts (16.1 +/- 2.1%). Bretylium prevents ventricular fibrillation (VF) resulting from ischemia at a site distant to prior myocardial infarction in the conscious dog and deserves further attention as a potential antifibrillatory agent for prevention of sudden coronary death in man.

Animals↗
PubMed1983

Sublingual absorption of the quaternary ammonium antiarrhythmic agent, UM-272.

UM-272 (N,N-dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain-induced ventricular tachycardias. Both anti-arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM-272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4-12 times greater than for oral drug, suggesting the existence of an absorption-limiting process in the intestine, and providing an alternate form of administration for quaternary drugs.

Animals↗
PubMed1983

Effects of diltiazem upon experimental ventricular dysrhythmias.

The antidysrhythmic and antifibrillatory actions of the calcium entry blocker diltiazem were examined in three experimental canine models: 1) ventricular fibrillation thresholds in the anesthetized dog; 2) programmed electrical stimulation in the conscious dog during the subacute phase of myocardial infarction; and 3) a conscious canine model of sudden coronary death wherein ventricular fibrillation was produced by acute myocardial ischemia in the presence of previous anterior myocardial infarction. Diltiazem administration failed to alter ventricular fibrillation thresholds determined under normal physiologic conditions and during acute occlusion of the distal left anterior descending coronary artery. Diltiazem did not prevent ventricular tachyarrhythmias produced by programmed electrical stimulation in the subacute phase of myocardial infarction. The coupling intervals of premature beats producing ventricular tachycardia and the cycle length of the ventricular tachycardias were unchanged by diltiazem administration. In a conscious canine model of sudden coronary death, left circumflex coronary artery thrombosis was produced in the presence of previous anterior myocardial infarction. Acute myocardial ischemia as evidenced by ST-segment changes in saline-treated animals (145 +/- 26 min) was followed by the development of premature ventricular beats (150 +/- 27 min) and ventricular tachycardia (154 +/- 26 min). Ventricular fibrillation occurred in 9 of 10 animals at 156 +/- 28 min. Diltiazem administration did not affect the time to development of ST-segment changes (196 +/- 38 min), premature ventricular beats (202 +/- 37 min) or ventricular tachycardia (209 +/- 37 min). Although the development of ventricular fibrillation was not prevented by diltiazem (9 of 10 animals developed ventricular fibrillation), the time to onset of the fatal arrhythmia was delayed significantly (P less than .01). These data fail to suggest a protective action for the calcium entry blocker diltiazem.

Acute Disease↗
PubMed1982

Long-term intravenous infusion of antiarrhythmic drugs using a totally implanted drug delivery system.

In vitro and in vivo testing was performed to establish the feasibility of a totally implantable pump system to deliver antiarrhythmic agents. In vitro flow characteristics suggested predictable day to day delivery with acceptably small variations in flow with changes in reservoir volume or temperature. During 3 months of in vitro testing, procainamide and bretylium were found suitable for long-term delivery. Delivery of lidocaine was limited by high viscosity and corrosion of steel elements within the pump. The pump was implanted in a subcutaneous pocket in four dogs. Procainamide (0.5 g/ml), delivered at 4 ml/day (70 mg/kg body weight per day), provided a mean steady state drug concentration of 5.3 micrograms/ml. Bretylium (50 mg/ml), delivered at 8 ml/day (13 mg/kg per day), provided a steady state concentration of 0.8 micrograms/ml (range 0.4 to 1.4). Long-term intravenous administration of therapeutic doses of bretylium and procainamide with this delivery system has been demonstrated in dogs and appears to be feasible in human subjects.

Animals↗
PubMed1981

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate induces ornithine decarboxylase in proliferating basal cells but not in differentiating cells from mouse epidermis.

The cultivation of mouse epidermal cells in medium of reduced calcium concentration (0.02--0.1 mM) selects for basal cell growth. Elevation of medium calcium levels above 0.1 mM results in rapid and well defined differentiative changes. This model was utilized to determine which cell type in mouse epidermis responds to the phorbol ester tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), by an induction of the enzyme ornithine decarboxylase (ODC). Previous data had shown that TPA induces ODC in primary mouse epidermal cells only during the first 36 hr after plating in medium containing 1.44 mM Ca2+. In contrast, the induction in cells grown in low calcium medium was 2--10-fold greater, and inducibility persisted for at least 4 weeks. The greater inducibility of ODC in low calcium cells is not paralleled by increased thymidine incorporation after TPA treatment, probably because these cells are already proliferating at a maximum rate. When low calcium cells grown in 0.07 mM Ca2+ medium were switched to 1.2 mM Ca2+, there was a rapid loss of ODC inducibility. These results strongly suggest that the basal cells of the epidermis constitute the major target cells for the induction of ODC by TPA. The induction of ODC by ultraviolet light was not enhanced by growth of cells in low calcium medium, indicating that extracellular calcium concentration per se does not determine ODC inducibility. When epidermal cells grown in 1.2 mM or 0.07 mM Ca2+ medium were exposed to both UV light and TPA, there was a significant synergistic effect of combined treatment over the sum of each individual response, suggesting that factors in addition to differentiation determine the extent of ODC induction.

Animals↗