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Biomedical subjects

J J Lynch

Publications and source records attributed to J J Lynch.

At least 145 records · Page 8Linked to original sources

Components of occupational health information systems.

Occupational health information systems continue to evolve and mature. Consistent throughout this evolution is the linkage of four data bases: job history, work site exposure, environmental agents, and health and safety. A review of the literature cites common elements within these data bases and characteristics of successful systems. Among the factors of successful systems is the role of key staff members. The medical record practitioner can be a significant contributor in the design of such systems. The profession should explore further the opportunities that exist in the occupational health setting.

Environmental Pollutants↗

The effects of calcium entry blockade on the vulnerability of infarcted canine myocardium toward ventricular fibrillation.

The effects of the calcium entry blockers diltiazem, KB-944 [diethyl 4-(benzothiazol-2-yl)benzylphosphonate] and bepridil on the vulnerability of ischemically injured myocardium toward fibrillation were determined in urethane-anesthetized dogs 4 to 7 days after anterior myocardial infarction. Diltiazem (3.0-30.0 micrograms/kg/min X 30 min), KB-944 (0.3-3.0 mg/kg) and bepridil (1.0-10.0 mg/kg) were administered i.v. to produce equivalent increases in atrioventricular nodal effective and functional refractory periods as a measure of slow calcium channel blockade. At dosages producing equivalent increases in atrioventricular nodal refractoriness, diltiazem and KB-944 failed to increase the electrical current threshold required to produce ventricular fibrillation, whereas bepridil elevated the fibrillation threshold from 4.2 +/- 0.5 mA predrug to 14.7 +/- 2.2 mA postdrug (P less than .01). Increases in atrial (128 +/- 6-185 +/- 29 msec, P less than .01) and ventricular (156 +/- 4-175 +/- 6 msec, P less than .05) refractory periods accompanied the increase in fibrillation threshold with bepridil. These findings suggest that calcium entry blockade per se does not reduce ventricular vulnerability toward fibrillation in the setting of recent myocardial infarction.

Animals↗

Preclinical assessment of antiarrhythmic drugs.

The morbidity statistics for the United States alone would suggest that there are 400,000 victims each year who succumb to sudden coronary death, which suggests that there is a need for the development of pharmacological interventions capable of preventing ventricular fibrillation (VF) in patients identified as being at high risk. A major deficiency in this area of experimental investigation is the lack of an animal model that would permit preclinical studies to identify potentially useful therapeutic agents. We have developed an experimental canine model of sudden coronary death in which VF occurs in the chronically injured heart that is subjected to a period of transient ischemia in a coronary region remote from the site of a previous myocardial infarction. The experimental model is subject to the induction of ventricular tachyarrhythmias in response to programmed electrical stimulation, thereby permitting the investigator to correlate the effectiveness of a pharmacological agent in preventing electrically induced arrhythmias with its potential to prevent the development of VF in response to ischemia at a site remote from a previous infarct. Thus, acute myocardial ischemia at a site distant from a previous myocardial infarction enhances the likelihood of primary VF in the conscious dog. This model of sudden coronary death may stimulate more closely the clinical state in humans and might serve as an appropriate model for the study of electrophysiological mechanisms associated with the development of VF and for the evaluation of potential antifibrillatory drugs.

Animals↗

Role conflict and role ambiguity among middle managers in general acute care hospitals.

One hundred ninety-three middle managers in general acute care hospitals participated in a study to measure role conflict and role ambiguity. Middle managers of both direct patient care and supporting services departments reported low levels of role conflict. Nonetheless, role overload and role conflict were significantly higher for managers of patient care departments than service departments. In addition, managers of both types of departments most often experienced intersender role conflict. Direct patient care and supporting services managers also reported low levels of role ambiguity, with no significant differences reported between the two types of departments. The relationship of role conflict and role ambiguity to demographic factors such as the manager's sex, educational level, years of managerial experience, and hospital size was also explored.

Conflict, Psychological↗

Cardiac electrophysiologic actions of SCH 19927 (Dilevalol), the R,R-isomer of labetalol.

The cardiac electrophysiologic, hypotensive and antiadrenergic actions of SCH 19927, the R,R-isomer of labetalol, were evaluated in urethane-anesthetized dogs. The cumulative administration of 0.3, 1.0 and 3.0 mg/kg i.v. decreased mean arterial pressure by 18 to 26 mm Hg from a pretreatment value of 106 +/- 6 mm Hg and slightly enhanced atrioventricular nodal conduction. After 3.0 mg/kg of SCH 19927, sinoatrial (SA) conduction times were decreased, whereas intraventricular conduction was depressed slightly. SCH 19927, 10.0 mg/kg, reduced mean arterial pressure by 39 mm Hg and enhanced SA nodal conduction and recovery after overdrive pacing (decreased SA conduction time and corrected sinus node recovery times), whereas intraventricular conduction times and the rate-corrected QTc interval were prolonged. Sinus heart rate, atrial, ventricular and atrioventricular nodal functional and effective refractory periods were unaltered by SCH 19927, 0.3 to 10.0 mg/kg. The administration of SCH 19927 produced significant beta adrenergic receptor blockade, as determined by inhibition of the positive chronotropic and peripheral vasodilatory response to isoproterenol, but did not alter the alpha-1 adrenergic receptor-mediated vasopressor response to phenylephrine. The results indicate that SCH 19927, in beta adrenergic receptor blocking and hypotensive dosages, does not depress SA nodal or atrioventricular nodal function, thus suggesting an electrophysiologic spectrum of activity different from that of other beta adrenergic receptor antagonists.

Animals↗

Antifibrillatory actions of bepridil and butyl-MDI, two intracellular calcium antagonists.

The antifibrillatory and electrophysiologic actions of bepridil and butyl-methylenedioxyindene (BU-MDI), two intracellular calcium antagonists, were examined in anesthetized dogs. The administration of bepridil (1.0-10.0 mg/kg i.v.) significantly increased the electrical threshold for ventricular fibrillation determined during unobstructed coronary flow, and was associated with a significant decrease in ventricular excitability and a progressive depression in ventricular myocardial conduction. BU-MDI (3.0-30.0 mg/kg i.v.) did not significantly alter ventricular fibrillation thresholds during unobstructed coronary flow, nor did it significantly alter electrophysiologic properties such as ventricular excitability, conduction or refractoriness. The administration of either bepridil (10 mg/kg i.v.) or BU-MDI (30 mg/kg i.v.), however, resulted in significant increases in the ventricular fibrillation thresholds determined during transient myocardial ischemia, restoring the threshold values to corresponding non-ischemic levels. These results suggest that an inhibition of the action and/or availability of intracellular calcium may play a role in the antifibrillatory actions of BU-MDI and bepridil during transient ischemia.

Animals↗

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

The antiarrhythmic and antifibrillatory actions of the dextrorotatory isomer of sotalol, administered in a multiple-dose regimen, were evaluated in conscious dogs 3 to 5 days after anterior myocardial infarction. The intravenous administration of d-sotalol, four 8 mg/kg doses over a 24-hour treatment period, suppressed the induction of ventricular tachycardia by programmed electrical stimulation in six of nine dogs tested, slowed the rate of the induced tachyarrhythmia in two of the remaining three dogs, and provided significant protection (5 of 8 d-sotalol vs 0 of 8 vehicle control) against the development of ventricular fibrillation in response to ischemia at a site distant to a previous myocardial infarction. Increases in ventricular myocardial refractoriness and in QTc and paced QT intervals suggest that class III electrophysiologic actions contribute to the antiarrhythmic properties of dextrorotatory sotalol in this animal model. The degree of beta-adrenergic receptor blockade produced by d-sotalol in this dose regimen was negligible. These findings suggest the potential utility of d-sotalol in the prevention of ventricular tachycardia and ventricular fibrillation in the setting of myocardial infarction, particularly when beta-adrenergic receptor blockade is undesirable or contraindicated.

Animals↗

Postinfarction sudden death: significance of inducible ventricular tachycardia and infarct size in a conscious canine model.

The relationship between inducible ventricular tachycardia in the convalescent phase of myocardial infarction and subsequent spontaneous ventricular fibrillation is uncertain. Thirty conscious instrumented dogs underwent programmed ventricular stimulation 5 days after anterior infarction; 15 had inducible ventricular tachycardia and 15 were noninducible. Following programmed ventricular stimulation, the application of a 150 uA current to the intima of the proximal circumflex artery initiated intimal damage, thrombosis, and acute ischemia of the posterolateral wall. After 20 minutes of ischemia, 73% inducible and 15% noninducible animals developed ventricular fibrillation (p less than 0.005) without previous hypotension. At 24 hours, 7% inducible and 85% noninducible animals survived (p less than 0.001). Anterior infarct size (percentage of left ventricular mass) was much larger in inducible (24.7 +/- 1.7%) than in noninducible (5.3 +/- 1.1%) (p less than 0.001) animals. Inducible ventricular tachycardia following infarction was highly predictive of spontaneous ventricular fibrillation during a later ischemic episode in this model. The mass of previously injured myocardium was a critical determinant of both.

Animals↗

Purification and Partial Characterization of Ribulose Bisphosphate Carboxylase Holoenzyme and Its Subunits from Chlorella sorokiniana and Use of Its Antigen Affinity-Purified Antibodies in Specific Immunoprecipitation and Immunoadsorption Procedures.

Chlorella sorokiniana ribulose-1,5-bisphosphate carboxylase (RuBPCase) was purified to homogeneity with yields of 35 to 40%. Molecular weights of the holoenzyme and its large subunit (LS) and small subunit (SS) were estimated to be 562,000, 55,000, and 15,800, respectively. Amino acid compositions of LS from C. sorokiniana and spinach were similar, whereas the compositions of their SS were very different. Antisera prepared against holoenzyme, LS, and SS were purified by antigen-affinity column chromatography. Purified anti-holoenzyme immunoglobulin G (IgG) and anti-LS IgG cross-reacted with holoenzyme and LS but not with SS. Anti-SS IgG reacted neither with holoenzyme nor with LS. Because purified anti-holoenzyme IgG or the anti-LS IgG inhibited RuBPCase activity, antibody preparations were titered by the amount of (35)S-labeled RuBPCase immunoprecipitated. Approximately 40% of the total RuBPCase activity in cell homogenates was tightly particulate-bound and was solubilized with 0.5% Nonidet P-40 without inhibition of enzyme activity. Direct-immunoprecipitation and indirect-immunoadsorption procedures, with affinity-purified anti-holoenzyme IgG, gave specific and quantitative recovery of (35)S-labeled RuBPCase from cell extracts containing Nonidet P-40. Affinity-purified anti-LS IgG and anti-SS IgG were used to immunoprecipitate either the LS or SS antigens synthesized in vitro in a mRNA-dependent in vitro translation assay system. Rocket immunoelectrophoresis was used to quantify as little as 50 nanograms of RuBPCase antigen in cell extracts.

Journal Article↗

Antiarrhythmic and electrophysiologic effects of bepridil in chronically infarcted conscious dogs.

The antiarrhythmic and antifibrillatory actions of bepridil, an antianginal agent with cardiac fast and slow channel-blocking activities, were evaluated in conscious dogs 3 to 7 days after anterior myocardial infarction. The i.v. administration of 5.0 mg/kg of bepridil prevented the initiation of ventricular tachycardia in four of 12 postinfarction dogs tested and slightly but significantly prolonged the effective refractory period determined at the right ventricular outflow tract. The i.v. administration of 10.0 mg/kg of bepridil prevented ventricular tachycardia induction in seven of 13 dogs tested and significantly reduced the rate of the induced tachycardia in the remaining six dogs. Significant increases in ventricular activation times measured in both normal and infarcted areas of myocardium, as well as a modest prolongation in ventricular refractoriness, accompanied administration of 10.0 mg/kg of bepridil. Acute pretreatment with 5.0 and 10.0 mg/kg of bepridil produced a dose-dependent and significant (10.0 mg/kg) delay in the development of ventricular fibrillation in response to ischemia at a site remote from previous myocardial infarction, as well as suggestive increases in survival 24 hr after the development of ischemia. These results suggest that bepridil may possess antiarrhythmic properties useful in the management of recurrent ventricular tachycardia in the setting of myocardial infarction and in the suppression of early ischemia-mediated ventricular fibrillation in the presence of previous myocardial injury.

Animals↗

Changes in nurses' blood pressure and heart rate while communicating.

Cardiovascular responses of nurses were measured during two communication tasks. In the first experiment 40 nurses' blood pressures and heart rates were taken pre, during, and post change-of-shift report. In the second experiment, 30 nurses spoke to an individual nurse and to a group of nurses. Blood pressures and heart rates were recorded pre, during, and post speech in both conditions. Analyses of variances showed that speaking levels of all cardiovascular parameters were higher (p less than .001) than resting levels in both experiments. Blood pressures and heart rates were higher (p less than .0001) in front of a group than in front of an individual. These findings extend previous work that has shown communication alters blood pressure.

Adult↗

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↗

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↗

Comparison of the characteristics of the negative inotropic actions of dinitrophenol, rotenone, antimycin A and the intracellular calcium antagonist, propyl-methylenedioxyindene.

The characteristics of the reversal of the comparable negative inotropic actions of 10(-4) M propyl-methylenedioxyindene (an intracellular calcium antagonist), 3 X 10(-5) M dinitrophenol (an uncoupler of mitochondrial oxidative phosphorylation), 10(-6) M rotenone (a site I mitochondrial respiratory chain poison) and 3 X 10(-6) M antimycin A (a site II mitochondrial respiratory chain poison) were studied in the isolated, electrically-paced guinea-pig left atrium. The negative inotropic effect of propyl-methylenedioxyindene was more sensitive to reversal by 5 mM calcium and 10(-9)-10(-7) M isoproterenol than were the comparable negative inotropic effects of dinitrophenol, rotenone and antimycin A. These results indicate that the negative inotropic effect of propyl-methylenedioxyindene is not exerted through inhibition of mitochondrial electron transport nor through uncoupling of mitochondrial oxidative phosphorylation.

Animals↗