Search PubMed⌕ Search

Biomedical subjects

J M Loeb

Publications and source records attributed to J M Loeb.

At least 37 records · Page 2Linked to original sources
PubMed1989

Human vs animal rights. In defense of animal research.

For centuries, opposition has been directed against the use of animals for the benefit of humans. For more than four centuries in Europe, and for more than a century in the United States, this opposition has targeted scientific research that involves animals. More recent movements in support of animal rights have arisen in an attempt to impede, if not prohibit, the use of animals in scientific experimentation. These movements employ various means that range from information and media campaigns to destruction of property and threats against investigators. The latter efforts have resulted in the identification of more militant animal rights bands as terrorist groups. The American Medical Association has long been a defender of humane research that employs animals, and it is very concerned about the efforts of animal rights and welfare groups to interfere with research. Recently, the Association prepared a detailed analysis of the controversy over the use of animals in research, and the consequences for research and clinical medicine if the philosophy of animal rights activists were to prevail in society. This article is a condensation of the Association's analysis.

American Medical Association↗
PubMed1989

Refractory ascites due to POEMS syndrome.

A 52-yr-old woman developed exudative ascites 2 yr after the onset of peripheral neuropathy. Extensive evaluation revealed that the patient had no underlying liver disease, malignancy, infection, or cardiac or renal disease. The ascites initially responded to high-dose corticosteroid therapy. The patient had many clinical features of the recently described POEMS syndrome, including a persistent IgA lambda-paraprotein. Initially, her ascites responded to treatment with steroids. This is characteristic of the syndrome and should be considered in patients with POEMS syndrome and refractory ascites.

Ascites↗
PubMed1988

Phasic influences of vagal stimulation on atrioventricular conduction.

The beat-by-beat changes in atrioventricular (AV) conduction evoked by constant frequency and phase-coupled vagal stimulation were examined both qualitatively and quantitatively in 13 anesthetized dogs. The effects of pacing cycle length and sympathetic activity on the vagally induced phasic changes in AV conduction were also characterized. When the vagal stimulus interval was nearly equal to the pacing cycle length and the vagal stimulus moved progressively through the cardiac cycle, AV interval oscillated in a rhythmic fashion. The rhythmicity of the vagally induced AV interval oscillations was altered substantially by changes in either the vagal stimulus interval or the pacing cycle length. The vagally induced AV interval oscillations were abolished during phase-coupled vagal stimulation; however, the magnitude of the resultant steady-state AV interval depended on the time relative to the phase of the cardiac cycle that the vagal stimulus was delivered. In the presence or absence of sympathetic stimulation, a vagal stimulus falling approximately 200 ms prior to atrial depolarization evoked the greatest prolongation in AV interval, regardless of the pacing cycle length. Additionally, the effects of combined sympathetic and phase-dependent vagal stimulation on the AV interval were additive. These data confirm that the influence of a vagal stimulus on AV interval can be predicted from the phase in the cardiac cycle that the vagal stimulus is delivered. Moreover, this phase dependency of vagal effects evokes marked qualitative variations in AV interval response patterns when either the vagal stimulus interval or the pacing cycle length is altered.

Animals↗
PubMed1988

Integration of heart rate and sympathetic neural effects on AV conduction.

Sympathetic activation increases heart rate (HR) and reduces atrioventricular interval (AVI), whereas atrial pacing alone increases AVI. We sought to differentiate the direct effects of sympathetic activation on atrioventricular (AV) conduction time from the indirect changes associated with concurrent alterations in HR. We recorded electrocardiograms, blood pressure (BP), and intracardiac electrograms from chloralose-anesthetized autonomically decentralized dogs. Beat-by-beat HR and AVI data were collected continuously. Sympathetic stimulation (0.25-2.5 Hz; mean 0.81 Hz) resulted in a HR change of +60 beats/min after 60 s. This tachycardia was associated with a mean decrease in AVI of 22 ms. Computer-driven atrial pacing to reproduce the HR associated with control sympathetic stimulation caused a mean AVI increase of 10 ms. Propranolol (200 micrograms) was then administered via the sinoatrial node artery and sympathetic stimulation repeated. Although HR remained constant, AVI decreased by 14.8 ms. The AVIs associated with an identical HR achieved by two different mechanisms (sympathetic stimulation and atrial pacing) were significantly different. Although removal of the contribution of sympathetically induced HR changes on AV conduction might be expected to result in potentiation of neural effects at the AV node, none was evident. Thus sympathetic activity restricted to the AV node is less effective in influencing AV conduction than the response that occurs when HR changes occur concurrently. Therefore, the opposing actions of HR and sympathetic tone on AV conduction may not be predicted by a simple linear relationship.

Animals↗
PubMed1987

Atrioventricular nodal accommodation: rate- and time-dependent effects.

To characterize intrinsic rate- and time-dependent properties of the atrioventricular (AV) node, we examined whether AV interval (AVI) would be comparable at identical heart rates (HR) reached using different types of stimulation paradigms. We compared changes in AVI during five consecutive 30-s, 20 beat/min increases in HR from control with AVI changes induced by 30-s single-step protocols to each of the same levels. In addition, HR was maintained at each level for 30, 60, 90, 120, and 150 s to control for the influences of time. Chloralose-anesthetized dogs (n = 16) were autonomically decentralized and instrumented to record electrocardiogram, blood pressure, and multiple intracardiac electrograms. Computer-generated HR steps were begun 20 beats/min above control, while continuously recording AVI. The beat-by-beat changes in AVI within each step were quantitated for all protocols. Differences between AVI during single- and multiple-step protocols were most pronounced during the first 15 s of atrial pacing. Accommodation in AVI (change in AV conduction time associated with an increased but constant heart rate) was evident during both protocols. The degree of accommodation during multiple-step protocols was modulated by the cumulative effects of earlier HR; however, a similar degree of accommodation occurred at higher HR irrespective of protocol used. Finally, the time to onset of loss of 1:1 AV conduction was significantly shorter when HR was increased using a multiple-step protocol. Thus the intrinsic response of the AV node to HR change is dependent on absolute level of HR, duration of rate change, and the potential cumulative effects of any earlier HR steps.

Animals↗
PubMed1987

Reflex regulation of atrioventricular conduction.

We evaluated the time course of baroreflex modulation of atrioventricular (AV) nodal conduction in anesthetized dogs (n = 28). Beat-by-beat changes in heart rate (HR) and AV interval (AVI) evoked by transient alterations in arterial pressure (AP) were recorded in the intact state, after vagotomy, and following stellectomy. Under each experimental condition, alterations in AP induced parallel changes in HR and AVI with maximum HR and AVI responses occurring simultaneously. In three animals, AP alterations elicited pacemaker shifts that markedly altered AVI. Reflex changes in AVI were also examined during atrial pacing. When pacing at a low (120 beats/min) versus a high (190 beats/min) level of heart rate, reductions in AP decreased AVI to a significantly lower absolute value in the intact state, after vagotomy, and following stellectomy. However, under each experimental condition, decreases in AP elicited marked changes in AVI at either level of pacing. We conclude that baroreflex-induced changes in sympathetic and parasympathetic activity influence the sinoatrial and AV nodes simultaneously, predominate over the effects of changes in HR at the AV node, and may induce pacemaker shifts that influence the measurement of AVI.

Animals↗
PubMed1987

Postpacing tachycardia: autonomic involvement.

The cessation of pacing from the sinus node region is followed by a transient sinus tachycardia or postpacing tachycardia (PPT). We sought to characterize autonomic involvement in PPT. We used alpha-chloralose-anesthetized dogs and recorded electrocardiograms, blood pressure, and electrograms from the sinus node, right atrium, right ventricle, and His bundle. Both vagi and both stellate ganglia were transected. PPT developed immediately after either linear or stepped heart rate changes. PPT followed pacing from the rostral but not the caudal region of the sulcus terminalis. Independent manipulation of absolute level of heart rate (+33, +66, and +100 beats/min above control) and duration of atrial pacing (10, 20, and 30 s) revealed that PPT is dependent predominantly on the duration of pacing and less on level of heart rate. During pacing in the control state, a 1:1 atrial capture was maintained. After atropine administration (0.2 mg/kg iv), PPT increased significantly in magnitude, time to peak PPT was shortened significantly, and loss of 1:1 atrial capture during pacing was evident at pacing rates of from 10 to 60 beats above control. In contrast, propranolol significantly attenuated PPT. We conclude that acetylcholine, released during pacing from the sinus node region, suppresses inherent sinus node acceleration induced by the concurrent release of intramural catecholamines. During pacing, acetylcholine release is essential for the maintenance of 1:1 atrial capture and significantly modulates both the latency and magnitude of PPT.

Animals↗
PubMed1986

Beat-by-beat modulation of AV conduction. I. Heart rate and respiratory influences.

We examined the integration of heart rate and neural influences at the atrioventricular (AV) node in conscious dogs. Animals were anesthetized and, under sterile conditions, instrumented to chronically record atrial and ventricular electrograms and blood pressure. In the conscious state, electrocardiogram (ECG), respiration, blood pressure, and electrograms were recorded on a beat-by-beat basis, and heart rate and AV interval were plotted graphically as a function of time. Resting animals exhibited both respiratory sinus arrhythmia and marked oscillations in AV conduction time associated with respiration. During inspiration AV interval was shortened, and during expiration AV interval was prolonged. To obviate the effect of cyclic changes in heart rate, atrial pacing was used to increase heart rate over a wide range both abruptly and linearly. Regardless of the pattern of heart rate change, AV interval oscillated at the respiratory frequency at pacing rates 10-100 beats/min above control. Higher levels of atrial pacing resulted in AV conduction patterns that were correlated with changes in blood pressure. Thus in the conscious dog variations in AV conduction time occur on a beat-by-beat basis in conjunction with respiration; oscillatory activity of AV conduction is not dependent on simultaneous changes in heart rate; and during atrial pacing, autonomic neural activity associated with respiration and blood pressure appears to dynamically modulate AV conduction with respiratory effects predominating at low heart rates and blood pressure effects at high heart rates.

Animals↗
PubMed1986

Beat-by-beat modulation of AV conduction. II. Autonomic neural mechanisms.

We examined the mechanism by which autonomic neural activity associated with respiration and blood pressure modulates atrioventricular (AV) conduction in conscious dogs. Mongrel dogs were anesthetized and instrumented under sterile conditions to record atrial and ventricular electrograms and blood pressure. In the conscious state, electrocardiogram (ECG), respiration, blood pressure, and electrograms were recorded continuously, and heart rate and AV interval were plotted graphically as a function of time. To delineate the role(s) of sympathetic and parasympathetic activity, AV conduction was studied during abrupt and linear changes in heart rate after administration of atropine, propranolol, or both. In the basal state and after propranolol, AV interval oscillated with respiration both in the absence of atrial pacing and at pacing rates 10-100 beats/min above control. Following atropine, oscillations in AV interval associated with respiration were abolished; however, linear and abrupt heart rate increases resulted in AV conduction changes that were associated with fluctuations in blood pressure. In contrast, after both atropine and propranolol, alterations in blood pressure or respiration did not influence AV conduction and rate-dependent prolongation of AV conduction occurred. We conclude that in the basal state, AV conduction is influenced predominately by changes in parasympathetic activity which is the major determinant of respiratory-related AV interval oscillations; after atropine, sympathetic activity produces fluctuations in both AV conduction and blood pressure; and intrinsic rate-dependent properties of the AV node are modulated continually by both divisions of the autonomic nervous system.

Animals↗
PubMed1985

Endocardial activation mapping and endocardial pace-mapping using a balloon apparatus.

The relation between endocardial activation mapping and endocardial pace-mapping was evaluated in 8 dogs while they were on cardiopulmonary bypass. Pacing or recording was accomplished by using a balloon apparatus (with 32 bipolar electrodes) inserted through a left apical ventriculotomy. Ventricular tachycardia (VT) was produced by occlusion followed by reperfusion of the left anterior descending coronary artery. During each VT, activation mapping was performed and early sites determined. Pace-map correlates (sites at which endocardial pacing produced a similar QRS morphology to that of the VT) were also determined. Isochronous maps were constructed for activation mapping and pace-mapping. There was a total of 29 morphologically distinct VTs. Groups were delineated according to correlations between activation mapping and pace-mapping. In 14 episodes of VT (group 1), pace-mapping confirmed the findings of activation mapping with all early sites being pace-map correlates (total number of early sites (tES) = 19; total number of pace-map correlates (tPMC) = 88; tES same as tPMC = 19). In 9 episodes of VT (group 2), there was a partial correlation between pace-mapping and activation mapping, such that pace-mapping when used with activation mapping appeared to further delineate the region of arrhythmogenesis (tES = 31; tPMC = 59; tES same as tPMC = 14). In 6 episodes of VT (group 3), there was no correlation between pace-mapping and activation mapping (tES = 15; tPMC = 0). With the balloon apparatus, endocardial activation mapping can be performed without the need for sustained monomorphic VT, and endocardial pace-maps may be generated easily.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effect of perfusion rate of cholinergic agonist on sinus node automaticity.

Recent evidence supports a complex relationship between pressure in the sinus node artery and heart rate. In addition, it has been suggested that acetylcholine effects vary depending upon the pressure at which the drug is injected. We examined the cardiac chronotropic responses to acetylcholine, delivered via the sinus node artery using a constant flow perfusion technique. Dogs were anesthetized with chloralose and prepared to record ECG, arterial pressure and bipolar electrograms from the sinus node, sulcus terminalis, right atrium, right ventricle and His bundle. The sinus node artery was catheterized, distribution verified and autologously perfused via the femoral artery. Both vagi and both stellate ganglia were transected. Analog data were processed by computer for each cycle length during perfusion with normal Tyrode solution or Tyrode solution containing acetylcholine. Perfusion of normal Tyrode solution (1-4ml/min) resulted in prolongation in cycle length which was greater at higher flow rates but rapidly dissipated at all flow rates. Beyond mechanically-induced bradycardia, acetylcholine initially prolonged cycle length but cycle length prolongation faded with time. Delivery of acetylcholine at higher flow rates resulted in significantly greater prolongation of cycle length. Cycle length always returned back toward control although perfusion of acetylcholine continued. Thus, responses to acetylcholine are influenced not only by drug concentration but also by the flow rate at which the drug is delivered. This suggests a coupling of mechanical and pharmacologic components of chronotropic influences at the sinus node.

Acetylcholine↗
PubMed1985

Dynamic interactions between heart rate and atrioventricular conduction.

We examined the beat-by-beat alterations in atrioventricular (AV) conduction time that accompany both linear and abrupt changes in heart rate (HR). We used alpha-chloralose-anesthetized and autonomically decentralized dogs (n = 10) and recorded electrocardiogram (ECG), arterial pressure, and electrograms from sinus node, right ventricle, and His bundle. Abrupt or linear HR changes of known slope were generated by computer and displayed graphically with AV interval as a function of time. HR was increased linearly from 10 to 110 beats/min above control over 15, 30, and 60 s and then decreased in a linear fashion. AV interval was dependent on direction of HR change with marked asymmetry between increases and decreases in HR. Similar data were apparent irrespective of whether the decrease followed the increase or vice versa. To study determinants of 1:1 conduction, HR was increased linearly by 200 beats/min above control over 15, 30, and 60 s. As rate of change of HR increased, 1:1 conduction continued to a higher HR; however, the last conducted AV interval was negatively correlated with rate of change of HR. Abrupt sustained increases in HR of 25, 50, 75, and 100% above control resulted in marked accommodation of AV interval only at higher levels of HR. Thus in the absence of autonomic neural tone, 1) cardiac cycle length is not associated with a fixed AV interval but is dependent on magnitude and direction of HR change; and 2) the HR at which 1:1 AV conduction fails is significantly altered by the rate of change of HR.

Animals↗
PubMed1984

Maintained prolongation of AV conduction time by acetylcholine.

Although chronotropic responses to maintained cholinergic activation have been reported to fade during tonic vagal stimulation, discrepancy exists as to whether AV conduction behaves similarly. Since previous studies have examined only low grade AV block, we sought to more fully characterize the dromotropic responses to different degrees of maintained cholinergic activation. We used anesthetized mongrel dogs in which the nutrient artery supplying the AV node region was cannulated and perfused with either autologous blood or oxygenated Tyrode solution containing various concentrations of acetylcholine. Electrograms were recorded from the SA node, atrium, ventricle and His bundle. In ten of eleven animals, perfusion with high concentrations of acetylcholine for five min resulted in the production of complete heart block which was sustained for the duration of the infusion. Moderate concentrations of acetylcholine, perfused via the AV node artery, resulted in maintained second degree AV block in five of eight animals and oscillation between first and second degree block in the other three. Perfusion with lower concentrations of acetylcholine resulted in maintained prolongation of the AH interval, which appeared however, to be dependent upon continuous uninterrupted perfusion of the AV node artery with acetylcholine. These results suggest that, irrespective of the magnitude of the dromotropic response during acetylcholine perfusion, fading is not characteristic of AV conduction during maintained cholinergic activation. Thus acetylcholine affects chronotropic and dromotropic responses differently.

Acetylcholine↗
PubMed1984

Acetylcholine-calcium interactions in the canine atrium and sinus node.

Although the enhancement of acetylcholine release by extracellular calcium is well recognized, the potential arrhythmogenicity of vagal-calcium interactions has not been studied. We used anesthetized mongrel dogs and recorded: ECG, arterial pressure, and electrograms from the sinus node, sulcus terminalis, right atrium, right ventricle, and His bundle. All animals were autonomically decentralized. The sinus node artery was catheterized, its distribution was verified, and it was autologously perfused via the femoral artery. Vagal stimulation was carried out during autologous blood perfusion of the sinus node artery and again during perfusion with oxygenated Tyrode solution, with calcium concentrations ranging from 1.8 to 16.2 mmol. Vagal slowing of rate was accentuated in the presence of calcium concentrations as low as 2.7 mmol. Further increments in calcium concentration resulted in vagally-induced atrial fibrillation. Fibrillation was characterized by rapid, regular repetitive activity which was superceded by chaotic atrial rhythm at about 10 seconds and blocked by atropine. Elevations in calcium alone (5.4 to 16.2 mmol) resulted in atrial fibrillation which was chaotic in appearance and not blocked by atropine. We conclude that increases in calcium concentration within the distribution of the sinus node artery are arrhythmogenic alone, and also enhance vagally-induced changes in atrial rhythmicity.

Acetylcholine↗