PubMed Health⌕ Search

Biomedical subjects

E Patterson

Publications and source records attributed to E Patterson.

At least 73 records · Page 4Linked to original sources
PubMed1992

Electrophysiologic actions of clofilium and lidocaine in ischemically injured canine epicardium.

The electrophysiologic actions of the Class III antiarrhythmic drug, clofilium, and the Class IB antiarrhythmic drug, lidocaine, were examined in ischemically injured canine epicardium, 4 days after coronary artery occlusion. Experiments were performed utilizing 1) composite electrode recordings from the intact heart in the anesthetized dog and 2) intracellular and extracellular recordings from superfused canine epicardium. In intact hearts, both clofilium (2 mg/kg i.v.) and lidocaine (6 mg/kg i.v.) increased refractoriness (188 +/- 16 to 331 +/- 39 and 288 +/- 18 msec, respectively, P less than .01), and produced tachycardia-dependent conduction disorders in ischemically injured epicardium. For both drugs, slowing the sinus heart rate with vagus nerve stimulation (32 +/- 6/min) returned activation delays to predrug values. Unlike lidocaine, clofilium failed to increase maximal activation delays in ischemically injured epicardium preceding conduction block (116 +/- 14 msec vs. 71 +/- 7 msec and 147 +/- 16 msec for clofilium and lidocaine, respectively, P less than .01 for both drugs). In superfused epicardium, both clofilium (3 x 10(-7) M) and lidocaine (4 mg/l) prolonged refractoriness in ischemically injured epicardium (175 +/- 16 predrug vs. 273 +/- 33 msec, P less than .01) and (181 +/- 3 predrug vs. 216 +/- 10 msec, P less than .01), respectively, whereas only lidocaine reduced Vmax and prolonged local conduction times in the same tissue. The results demonstrate that 1) lidocaine increases refractoriness in ischemically injured tissue via a decrease in Vmax and conduction velocity and 2) clofilium increases refractoriness in ischemically injured tissue without altering action potential duration, Vmax or conduction velocity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites.

Camptothecin (CPT), a plant alkaloid with antitumor activity, is a specific inhibitor of eukaryotic DNA topoisomerase I. We have previously isolated and characterized a CPT-resistant topoisomerase I isolated from a CPT-resistant human leukemia cell line, CPT-K5. cDNA clones of topoisomerase I were isolated from the CPT-resistant and the parental CPT-sensitive cell lines, respectively. Sequencing of the clones identified two mutations in the cDNA isolated from the resistant cells, which cause amino acid changes from aspartic acid to glycine at residues 533 and 583 of the parental topoisomerase I. When the CPT-K5 topoisomerase I was expressed in E. coli as a fusion protein with Staphylococcal Protein A fragment, the activity was resistant to CPT at a dose level up to 125 microM, whereas the parental fusion protein was sensitive to CPT as low as 1 microM. The resistance index (greater than 125) of the CPT-K5 fusion topoisomerase I is similar to that of the native CPT-K5 topoisomerase I. These results indicate that either or both of the two amino acid changes identified in the mutant enzyme is responsible for the resistance to CPT.

Amino Acid Sequence↗
PubMed1991

The monophasic action potential in clinical cardiology.

For more than 30 years, the monophasic action potential has been used as an experimental tool for the study of myocardial repolarization. With recent improvements in catheter design, the utility of the tool as a means to identify the bases for ventricular arrhythmias in humans has been greatly improved. Abnormalities of repolarization leading to ventricular arrhythmia formation can be identified and specific pharmacologic therapies may be evaluated. Further evaluation of the technique by cardiac electrophysiologists may improve both the diagnosis and the treatment of ventricular arrhythmias dependent upon afterdepolarization formation (acquired and familial long QT syndromes).

Action Potentials↗
PubMed1991

Electrophysiological actions of BRB-I-28 in canine myocardial tissues.

To obtain a better understanding of the possible electrophysiological bases of the antiarrhythmic actions of 7-benzyl-3-thia-7-azabicyclo[3.3.1]nonane hydroperchlorate (BRB-I-28), microelectrode recordings of myocardial electrical activity were obtained in canine Purkinje and ventricular tissue, and in isolated canine ventricular myocytes. BRB-I-28 (1.0 and 3.2 mg/l) reduced Vmax, action potential amplitude, overshoot potential and conduction velocity in Purkinje tissues without altering action potential duration or spontaneous automaticity. Vmax and conduction velocity were reduced only at paced cycle lengths of 500 msec or less. BRB-I-28 (3.2 and 10 mg/l) also reduced Vmax, action potential amplitude and overshoot potential in subendocardial and epicardial ventricular muscle, with Vmax reduced only at cycle lengths of 500 msec or less. Recovery half-times for Vmax estimated in canine subendocardium were 330 +/- 28 and 336 +/- 25 msec at BRB-I-28 concentrations of 3.2 and 10 mg/l, respectively. In epicardium, conduction velocity longitudinal to fiber orientation was depressed more than conduction velocity transverse to fiber orientation, despite similar changes in Vmax. In both epicardial and subendocardial ventricular muscle, a reduction in Vmax is observed in the absence of alterations in action potential duration. Experiments using myocytes isolated from canine epicardial tissue demonstrated similar rate-dependent changes in Vmax as ventricular epicardium. The data demonstrate a rate-dependent depression of Vmax by BRB-I-28 in canine ventricular tissues. The depression of conduction occurs only at rapid paced rates and occurs in the absence of changes in Purkinje cell automaticity or action potential duration.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Seasonal variation in sudden cardiac death after experimental myocardial infarction.

The authors studied the incidence of sudden death by monitoring the ECG after ligation of the left anterior descending coronary artery in 184 dogs. A significant number of sudden deaths (46 dogs) occurred in the cold weather months, November-February (42%), compared to the summer months, July and August (6%). All deaths resulted from ventricular tachyarrhythmias (greater than or equal to 300/min) and occurred between 13 and 22 hours after coronary artery ligation. The survivors (138 dogs) were subjected to electrophysiological study, during which a significantly higher number showed induced sustained monomorphic ventricular tachycardia (VT) (heart rate greater than or equal to 300/min) during the winter months than during the summer months. Heart weight and infarct mass were not significantly different throughout the year. Higher sympathetic tone or catecholamine levels may account for the seasonal variation in sudden death during evolving myocardial infarction.

Animals↗
PubMed1990

Early and delayed afterdepolarizations associated with cesium chloride-induced arrhythmias in the dog.

Monophasic action potentials (MAPs) were utilized to examine the basis for cesium-induced arrhythmia in the dog. Cesium chloride (1 mmol/kg i.v.) produced an immediate prolongation of MAP (250 +/- 11 to 396 +/- 34 ms, p less than 0.05). Coupled premature ventricular beats (345 +/- 46 ms) and polymorphic ventricular tachycardia developed in association with early afterdepolarizations during the first 1-3 min after cesium administration. A slowing of the sinus heart rate with vagus nerve stimulation exacerbated the arrhythmia. During the subsequent 7 min, the MAP duration decreased from 396 +/- 34 to 316 +/- 19 ms. At 8-10 min, the premature ventricular beats were associated with delayed afterdepolarizations in the MAP recordings. However, there was no change in the coupling intervals of the premature ventricular beats (351 +/- 29 ms). Ventricular arrhythmias and delayed afterdepolarizations during this phase were exacerbated by increasing the heart rate with atrial pacing. T wave alternans and U wave formation in the ECG were associated with early or delayed afterdepolarizations in MAP. Cesium chloride (1 mmol) injected into the left anterior descending coronary artery produced local MAP prolongation and ventricular bigeminy. Although the MAP duration returned to predrug values after intracoronary cesium injection, the severity of ventricular arrhythmia increased with succeeding doses. These data suggest that early and delayed afterdepolarizations, T wave alterations, and ventricular beats can be dissociated from the initial action potential prolongation with cesium and closely resemble altered calcium transients observed in vitro.

Action Potentials↗
PubMed1990

Accelerated thrombolysis and reperfusion in a canine model of myocardial infarction by liposomal encapsulation of streptokinase.

The aim of thrombolytic therapy for acute myocardial infarction with plasminogen activators such as streptokinase is to lyse the coronary thrombus and reestablish blood flow as quickly as possible so that heart tissue loss is minimized and mortality rates are improved. Streptokinase has been encapsulated in large unilamellar phospholipid vesicles and tested in an animal model of acute myocardial infarction. The time required to restore vessel patency has been reduced more than 50% when compared with findings for free streptokinase. The total dosage of streptokinase required was lower, and smaller remnant thrombi were observed with the encapsulated agent. Results from this initial unoptimized study may have significant implications for further reduction in mortality from heart attacks by therapy with plasminogen activators.

Animals↗
PubMed1989

RNA sequence analysis of a perinatal lethal osteogenesis imperfecta mutation.

The perinatal lethal form of osteogenesis imperfecta often results from mutations which disrupt stable assembly, delay secretion, and cause excessive posttranslational modification of type I procollagen molecules. One such mutation was efficiently characterized by an indirect method of RNA sequence analysis. The mutation initially was localized in procollagen by mapping the distribution of abnormal posttranslational modification within the triple helical domain of mutant molecules. Total RNA was isolated from osteogenesis imperfecta cells in culture, cDNA was synthesized using alpha 1(I) and alpha 2(I) specific primers, and fragments of cDNA suspected to harbor the mutation were amplified by the polymerase chain reaction technique and then cloned in M13 vectors. Sequence analysis of the amplified cDNA revealed a new, heterozygous Gly----Val substitution at residue 256 of the triple helical domain of alpha 1(I) chains produced by the perinatal lethal osteogenesis imperfecta cells. The nature and location of the mutation were confirmed by sequence analysis of amplified genomic DNA. A Gly----Val substitution has not previously been associated with the lethal form of osteogenesis imperfecta, and this mutation has the most amino-terminal location within the alpha 1(I) chain triple helical domain reported to date.

Alleles↗
PubMed1989

Treatment of breast cancer with segmental mastectomy alone or segmental mastectomy plus radiation.

A retrospective review of the outcome of treatment for primary, Stage I and II breast cancer with segmental mastectomy (SGM) alone or segmental mastectomy plus postoperative irradiation (SGM + RT) at four Rochester, New York, city hospitals is reported. Between January 1971 and March 1984, 99 women were treated with SGM and 146 with SGM + RT. Groups were similar regarding significant clinical and histologic prognostic factors; they differed, however, in that the SGM group was considerably older (means = 72) than the SGM + RT group (means = 56). Among SGM patients, local and total locoregional failure was 26.44 and 35.2%, respectively. Local and total locoregional failure (7.6 and 12.4%, respectively) was significantly reduced among patients treated with SGM + RT (p less than 0.0001). Among SGM patients, there was scant advantage in enlarging the extent of resection from local excision (29.5% local failure) to wide local excision (27.3%) to quadrantectomy (22.2%). Among women receiving SGM + RT, similar rates of local failure occurred among patients receiving local excision (15.5%) and wide local excision (12.5%). By contrast, only 2.8% of those receiving quadrantectomy failed. Results are viewed as supportive of findings of NSABP-B06. Findings suggest that SGM constitutes inadequate treatment of Stage I and II breast cancer. Locoregional failure rates of 30-40% may be reduced to around 10% with postoperative irradiation.

Adult↗
PubMed1988

Electrophysiologic and antiarrhythmic actions of nadolol: acute ischemia in the presence of previous myocardial infarction.

The actions of the beta-adrenergic receptor antagonist, d,l-nadolol, were examined in anesthetized dogs subjected to circumflex coronary artery ligation in the presence of previous anterior myocardial infarction. With circumflex ligation, control dogs (N = 18) developed premature ventricular beats and ventricular tachycardia, followed by ventricular fibrillation (N = 16, 89%). Immediate arrhythmias (2 to 5 minutes) were accompanied by activation delays and continuous diastolic electrical activity in acutely ischemic epicardial tissue. Delayed arrhythmias (6 to 12 minutes) were accompanied by delayed activation and continuous diastolic electrical activity in acutely ischemic mid-myocardium. Nadolol (8 mg/kg, intravenously) (N = 10) reduced ventricular arrhythmias during both phases of arrhythmia development and increased survival (70%, p = 0.001 vs control). Nadolol failed to after activation in acutely ischemic epicardium, but prevented beat-to-beat changes in epicardial and mid-myocardial activation. Atrial pacing of nadolol-treated animals at heart rates comparable with those of the control group reversed the beneficial effects of nadolol on the development of ventricular arrhythmias and ventricular fibrillation (70%; p = 0.07 vs nadolol; p = 0.21 vs control, respectively). The beneficial effects of nadolol could not be attributed to reduced epicardial delays, but were associated with the suppression of beat-to-beat conduction abnormalities that preceded ventricular fibrillation.

Animals↗
PubMed1988

Antiarrhythmic and arrhythmogenic actions of methyl lidocaine during the recovery phase after canine myocardial infarction.

Programmed electrical stimulation was used to evaluate the electrophysiologic and antiarrhythmic actions of methyl lidocaine in both conscious and anesthetized dogs, 4-7 days after myocardial infarction. When administered to animals demonstrating sustained ventricular tachycardia (n = 6), methyl lidocaine (5 and 10 mg/kg i.v.) prevented the induction of the original ventricular tachycardia in 2 dogs, and in the remaining 4 dogs slowed the tachycardia (cycle length 163 +/- 18 ms vs. 198 +/- 11 and 219 +/- 11 ms, respectively, p less than 0.05). New morphologic forms of sustained tachycardia were observed after drug administration in 4 of 6 experiments. When administered to animals developing only nonsustained ventricular tachycardia or no arrhythmias with programmed stimulation, methyl lidocaine administration enabled programmed stimulation to produce monomorphic sustained ventricular tachycardia in 10 of 13 experiments. The drug increased activation delays in both normal and ischemically injured epicardium, with larger activation delays always observed in ischemically injured tissue. The drug increased refractoriness in ischemically injured myocardium without altering refractoriness in normal tissue. The data suggest that the depression of conduction and prolonged refractoriness produced by methyl lidocaine in ischemically injured tissue may extinguish or slow some forms of ventricular arrhythmia while promoting the formation of new reentry pathways.

Animals↗
PubMed1987

Electrophysiologic and antiarrhythmic actions of sulphinpyrazone and its sulfide metabolite G25671.

In anesthetized dogs, the cumulative intravenous administration of 1.0-40.0 mg/kg sulphinpyrazone failed to alter the ventricular excitation threshold, ventricular refractory period and ventricular fibrillation threshold determined during nonobstructed coronary blood flow. Sulphinpyrazone, however, did attenuate the reduction in the ventricular fibrillation threshold occurring during transient myocardial ischemia. G25671, the sulfide metabolite of sulphinpyrazone, failed to alter ventricular refractoriness and 'nonischemic' ventricular fibrillation thresholds, and was minimally effective in reducing the decrease in 'ischemic' fibrillation thresholds when administered in cumulative intravenous doses of 5.0-20.0 mg/kg. In conscious dogs in the subacute phase of anterior myocardial infarction, the administration of a cumulative 10.0-40.0 mg/kg sulphinpyrazone failed to alter the mode of induction, rate or morphology of ventricular tachyarrhythmias initiated by programmed ventricular stimulation. These data suggest that neither sulphinpyrazone nor its sulfide metabolite possess primary electrophysiologic properties which might contribute directly to significant antiarrhythmic or antifibrillatory activity.

Animals↗
PubMed1987

Changes in cardiac muscle function and biochemistry produced by long-term amiodarone and amiodarone + triiodothyronine administration in the rabbit.

Cardiac muscle function and biochemistry were examined after long-term amiodarone administration in the rabbit (20 mg/kg/day for 28 days). Isolated cardiac muscle preparations were obtained from control and amiodarone-treated rabbits, and were studied in vitro. Amiodarone treatment did not alter the magnitude of force development in isolated atrial and papillary muscle preparations, but depressed the rate of force development (dF/dt). The muscle preparations responded similarly to inotropic and chronotropic stimulation with isoproterenol, histamine, and tyramine, although the intrinsic rate of right atrial preparations from the drug-treated animals was reduced. Na+-K+ ATPase activity in crude ventricular homogenates was increased in the amiodarone-treated group. Mitochondrial respiratory function in amiodarone-treated left ventricular tissue was depressed for glutamate, malate, and glutamate + malate. The reduction in respiratory function occurred without uncoupling oxidative phosphorylation or altering respiratory function for succinate. The pharmacologic effects of amiodarone observed in the present study were not observed with the simultaneous administration of triiodothyronine (5 micrograms/day). No difference in ATP-dependent calcium uptake or in calcium-dependent ATPase activity were observed in sarcoplasmic reticulum preparations from control, amiodarone, and amiodarone + T3 groups. The pharmacologic effects of amiodarone in rabbit hearts resemble those previously reported with hypothyroidism and are not observed after triiodothyronine administration.

Adenosine Triphosphatases↗
PubMed1986

Mechanism of prevention of sudden death by nadolol: differential actions on arrhythmia triggers and substrate after myocardial infarction in the dog.

Electrocardiographic monitoring and provocative ventricular pacing were used to evaluate control and nadolol treatment groups 6 to 24 hours after left anterior descending coronary artery ligation in the dog. During the 6 to 24 hour period, the control group (n = 20) developed ventricular triplets at rates exceeding 270/min. Seven dogs spontaneously developed sustained monomorphic ventricular tachycardia (421 +/- 12 beats/min) at 13 +/- 2 hours. Sustained monomorphic ventricular tachycardia was present for 38 +/- 8 seconds before ventricular fibrillation developed. One dog developed recurrent monomorphic ventricular tachycardia, with six episodes lasting from 8 to 72 seconds (375 to 425 beats/min). At 24 hours, ventricular pacing produced sustained monomorphic ventricular tachycardia (378 +/- 12 beats/min) in 9 of 13 surviving animals. Nadolol administration 6 hours after coronary artery ligation (n = 19) lowered both the rate (241 +/- 8 versus 328 +/- 8 beats/min; p = 0.001) and the incidence (8 +/- 6 versus 198 +/- 61 per hour; p = 0.004) of rapid ventricular triplets and prevented sudden arrhythmic death (0%; p = 0.005). Nadolol failed to prevent sustained monomorphic ventricular tachycardia (88%; 365 +/- 12 beats/min) produced by ventricular pacing. The data suggest that nadolol prevents spontaneous sustained monomorphic ventricular tachycardia by selectively suppressing the arrhythmia trigger (rapid ventricular triplets) without altering the underlying arrhythmia substrate.

Animals↗
PubMed1986

Electrophysiologic, antiarrhythmic and cardiovascular actions of UM301, a quaternary ammonium compound.

The electrophysiologic, antiarrhythmic and cardiovascular actions of UM301 were evaluated in a variety of animal models. UM301 (range, 4.5-10 mg/kg i.v.) converted ouabain-induced ventricular tachycardia to normal sinus rhythm in the anesthetized dog. UM301 (10 mg/kg i.v.) suppressed the ventricular arrhythmias observed in a modified 2 day postinfarction dog preparation; normal sinus rhythm was maintained in excess of 120 min in these conscious animals. The ventricular fibrillation threshold was elevated in four animals after pretreatment with UM301 (5 and 10 mg/kg i.v.) without interfering with electrical cardioversion. In one animal, the spontaneous conversion of ventricular fibrillation to normal sinus rhythm was observed after pretreatment with UM301. In anesthetized dogs, 2 to 8 days after myocardial infarction, UM301 (5 and 10 mg/kg i.v.) prevented the reinduction of re-entrant ventricular tachyarrhythmias using programmed pacing techniques. The antiarrhythmic and antifibrillatory actions of the therapeutic doses of UM301 (i.e., 5 mg/kg i.v.) were associated with significant increases in the refractoriness of atrial, ventricular and atrioventricular conducting tissue. Higher doses of UM301 (10 mg/kg i.v.) progressively increased refractoriness, and the highest dose of UM301 tested (20 mg/kg i.v.) increased refractoriness further and depressed cardiac conduction in these tissues. Acute cardiovascular studies in anesthetized dogs showed that only the highest dose of UM301 tested (20 mg/kg i.v.) produced a significant decrease in the right ventricular force of contraction, cardiac output and arterial pressure. These data demonstrate that UM301, a quaternary ammonium compound, possesses both antiarrhythmic and antifibrillatory properties in various experimental animal models. The antiarrhythmic efficacy of UM301 can be observed in the absence of depressant cardiovascular actions.

Animals↗
PubMed1986

Cardiac electrophysiologic effects of acute and chronic amiodarone administration in the isolated perfused rabbit heart: altered thyroid hormone metabolism.

The electrophysiologic changes produced by amiodarone were examined in the isolated buffer-perfused rabbit heart. Long-term amiodarone administration (20 mg/kg/day for 28 days) depressed the intrinsic sinus heart rate and prolonged the PR and QT intervals of the electrocardiogram (P less than .05 vs. control). Ventricular refractoriness and the AH interval of the His-bundle electrogram were prolonged (P less than .05 vs. control) without a prolongation of the HV or QRS intervals. The electrophysiologic actions observed with long-term amiodarone treatment were reversed by the simultaneous administration of triiodothyronine (T3). No differences were noted in the electrophysiologic parameters measured in hearts removed from control and long-term amiodarone- plus T3-treated rabbits. The perfusion of the normal rabbit hearts with a buffer solution containing 1 microgram/ml of amiodarone hydrochloride failed to mimic the electrophysiologic changes produced by long-term amiodarone administration. Only a prolongation of the AH and PR intervals occurred with acute drug administration. The long-term administration of amiodarone was accompanied by decreased plasma T3 concentrations and increased concentrations of the less active thyroxine and reverse T3 species. The present data demonstrate the reversal of the electrophysiologic effects of long-term amiodarone administration by T3 administration. The data also suggest that the electrophysiologic actions of long-term amiodarone administration may be due in part to an antagonism of the actions of thyroid hormones.

Amiodarone↗