Northwestern University Medical School.
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Curriculum↗
Biomedical subjects
J X Thomas
Publications and source records attributed to J X Thomas.
Teaching medical faculty how to apply continuous quality improvement to medical education.
BACKGROUND: An eight-hour workshop was conducted at a professional meeting in 1996 to introduce medical faculty to the principles of continuous quality improvement (CQI) as they relate to change in medical education and to provide participants with opportunities to use specific tools for applications to education. Four two-hour sessions focused on an introduction to CQI, understanding and mapping processes, identifying change ideas, and testing a change for improvement. TESTING A CHANGE FOR IMPROVEMENT: The goals of the final session were to plan a pilot test of an improvement, identify the steps of the plan-do-study-act (PDSA) cycle, and consider change for improvement in the context of one's own organization. Working in small groups, participants chose a specific change one might try in the following example: improving student performance in a neuroscience course. POSTSESSION EVALUATION AND FOLLOW-UP: Immediately following the workshop sessions, participants represented by administrators in medical education and clinical and basic science teaching faculty completed evaluations on the usefulness and likelihood of their using CQI tools. One year later, of the 32 workshop registrants who were mailed surveys, 15 respondents rated their change in understanding of CQI and their use of CQI techniques. More than 60% of the respondents reported application of CQI principles at their organizations. CQI methods used most frequently included structured team meetings, prioritizing opportunities, and brainstorming. CONCLUSION: The significant application of CQI principles and methods reported by participants one year after a brief intervention supports a need and utility for CQI principles and tools in medical education.
Curriculum↗
Effect of chronic tocolytic therapy on maternal ventricular function in pregnant rabbits.
OBJECTIVE: Our purpose was to determine whether peripartum cardiomyopathy may be associated with chronic beta-mimetic tocolytic therapy. STUDY DESIGN: On gestational day 20 (term 31 days), two 200 microliter Alzet miniosmotic pumps were implanted in the subcutaneous tissue of pregnant New Zealand White rabbits. Each pump was filled with terbutaline (20 micrograms/microliter, n = 7) or saline solution (0.9%, n = 7) and infused continuously for 7 days. The rabbits were killed on the twenty-eighth gestational day. Maternal hearts were placed on a Langendorff (nonejecting) perfusion apparatus for assessment of cardiac function. At a constant perfusion pressure and heart rate left ventricular diastolic pressure was varied while left ventricular developed pressure and left ventricular +/- rate of pressure rise, index values of left ventricular contractility and relaxation, were continuously recorded. Comparisons between groups at each preload were made by analysis of variance. RESULTS: Hearts taken from terbutaline-treated rabbits exhibited periodic arrhythmias and mechanical alternans in five of seven hearts versus one of seven in the saline solution group. At a preload of 0 mm Hg both left ventricular developed pressure (88.0 vs 48.4 mm Hg, p < 0.001) and left ventricular rate of pressure rise (1406 vs 653 mm Hg/sec, p < 0.001) were less in terbutaline-treated rabbits. At a preload of 10 mm Hg left ventricular developed pressure (104.4 vs 56.7 mm Hg, p < 0.01) and rate of pressure rise (1424 vs 694 mm Hg/sec, p < 0.001) were also significantly less in terbutaline-treated rabbits. Left ventricular relaxation was also impaired at all preloads. CONCLUSIONS: In this model chronic administration of terbutaline during late pregnancy significantly depresses global maternal cardiac function.
Animals↗
Ventricular dysfunction in norepinephrine-induced cardiomyopathy.
Cardiac dysfunction resulting from norepinephrine-induced cardiomyopathy has not been fully investigated. This study evaluates acute and chronic changes in systolic and diastolic function at three levels of norepinephrine (NE)-induced injury. Rabbits were infused with saline or 2, 4, or 6 micrograms/kg/min NE for 90 min. Ventricular function was assessed immediately after infusion or at 48 hr using the isolated non-ejecting heart preparation. Hearts were perfused at 10 ml/min/g with Krebs-Henseleit buffer. After baseline measurements, hearts were perfused with NE (10(-10) to 10(-7) M). Steady state left ventricular pressure (LVP), +dP/dt, and -dP/dt were recorded at baseline and each NE concentration. NE infusion acutely depressed baseline LV systolic function. Decreases in LVP and +dP/dt were inversely related to dose of infused NE. By 48 hr, LVP and +dP/dt improved slightly in all NE groups but improvement was significant only in hearts from rabbits infused with 4 micrograms NE. Systolic function of hearts from animals infused with 6 micrograms NE remained depressed. Diastolic (-dP/dt) function was impaired following NE infusion when compared to saline treated hearts and did not improve within 48 hr. Although baseline function is depressed, myopathic hearts increased ventricular function the same amount as normal hearts at 10(-7) M NE. These findings demonstrate a) impairment in LV systolic and diastolic function acutely after NE infusion, b) improvement in systolic function within 48 hr, c) ability to increase contractility in response to NE is not impaired, and d) recovery of systolic function precedes improvement in diastolic function.
Animals↗
Dietary fish oil supplementation reduces myocardial infarct size in a canine model of ischemia and reperfusion.
OBJECTIVES: This study was conducted to determine whether the long-term administration of fish oil attenuates myocardial necrosis in an occlusion-reperfusion model of myocardial ischemia. BACKGROUND: Omega-3 fatty acids found in fish oil have various biologic properties that may modify myocardial injury caused by severe ischemia and reperfusion. METHODS: Of 21 dogs fed an identical diet, 10 were given supplemental fish oil containing 0.06 g/kg per day of eicosapentaenoic acid for 6 weeks. Under anesthesia and open chest conditions, the left circumflex coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Regional myocardial blood flow was measured with 15-microns spheres before and during occlusion and during reperfusion. The area at risk and infarct size were measured using standard staining techniques. RESULTS: In the dogs receiving supplemental fish oil, the platelet cell membrane content of eicosapentaenoic acid increased from 0.9 +/- 0.56% to 7.1 +/- 4.0% (p < 0.001). Infarct size was 29 +/- 7% in the control group and 13 +/- 3% in the fish oil group (p < 0.05). There was no significant difference in the myocardial area at risk or rate-pressure product between the control and fish oil groups. There was no difference in regional myocardial blood flow between the groups at baseline study or during coronary occlusion and reperfusion. CONCLUSIONS: Dietary fish oil supplementation significantly reduced myocardial infarct size in this model. The difference in infarct size did not appear to be related to dissimilarities in regional myocardial blood flow or determinants of oxygen consumption. Further investigation is needed to determine the nature of the protective mechanisms of omega-3 fatty acids on myocardial infarct size.
Animals↗
Intracellular recordings from canine intracardiac ganglion cells.
Stable transmembrane potentials were recorded from 60 canine intracardiac ganglion cells taken from 10 dogs, which had intact synaptic connections: mean resting membrane potential, input resistance and time constant were 61.5 mV, 70 M omega and 3.3 ms. Action potentials could be evoked by intrasomal current injection and by orthodromic and antidromic stimulation of interganglionic nerves. Orthodromic action potentials were initiated by excitatory postsynaptic potentials and mediated by nicotinic receptors. All action potentials could be blocked by tetrodotoxin. Intracellular labeling revealed large cell bodies and long dendritic and axonal processes. Thus, the functional and anatomical properties of canine cardiac ganglion cells and their synaptic connections can be elucidated using this preparation.
Action Potentials↗
Topical organization of the cardiac sympathetic nervous system.
A thorough understanding of the innervation pathways to the heart is requisite for studying the effects of the sympathetic nervous system. Knowledge of these pathways and how to selectively activate or eliminate them allows for the production of unique animal models for further investigation about the interaction between the cardiac sympathetics and the heart during ischemia.
Animals↗
Effects of selective cardiac denervation on collateral blood flow after coronary artery occlusion in conscious dogs.
The extent to which cardiac nerves regulate responses to myocardial ischemia remains controversial. Our data in conscious dogs indicate that neither selective posterior left ventricular (LV) wall denervation nor selective ventricular denervation, leaving the atria intact, modifies the effects of coronary artery occlusion (for 24 h) on regional myocardial function and infarct size as compared to normally innervated dogs. Since hemodynamic changes were similar among the three groups after coronary artery occlusion, it is possible to speculate that responses of collateral blood flow to the ischemic zone were also not modified by chronic selective cardiac denervation. To address this, individual samples were selected and included in either the infarcted (TTC negative) or salvaged (TTC positive) group. The infarcted and salvaged samples were paired according to blood flow levels of 0.1-0.2, 0.2-0.3, or 0.3-0.4 ml/min/g at either 5 min, 1 h, 3 h, or 6 h after coronary artery occlusion. The results demonstrated similar patterns of myocardial blood flow in tissue samples within the area at risk after coronary artery occlusion in the animals, regardless of whether the ischemic zone was innervated or denervated. While blood flow rose in ischemic tissue that ultimately was salvaged, and tended not to rise over the 24 h monitoring period in tissue samples that became necrotic, no differences could be discerned on the basis of intact or absent innervation of the ischemic zone. Thus, chronic absence of cardiac nerves does not affect regulation of ischemic zone blood flow following coronary artery occlusion in conscious dogs.
Animals↗
Calcitonin gene-related peptide increases coronary flow and decreases coronary resistance.
Calcitonin gene-related peptide (CGRP) is a potent vasodilator, but its effects on in situ ventricular function are unknown. We studied effects of intracoronary CGRP (100, 200, and 600 pmole/min, for 10 min) in 21 open-chest chloralose-anesthetized dogs. Systemic, pulmonary, left ventricular (LVP), central venous, and pulmonary capillary wedge pressures were continuously monitored. Left ventricular wall thickness (WT) and circumflex coronary blood flow were also measured. CGRP was infused into the proximal circumflex artery. During CGRP infusion there were no changes in heart rate, cardiac index, pulmonary artery pressure, or systemic vascular resistance, no percentage change in ventricular WT, and no changes in dWT/dt, peak dP/dt, or the slope of end-systolic points on WT/LVP loops. But there were significant changes in coronary flow (CQ), coronary resistance (CRES) and mean arterial blood pressure (MAP) from control (C)* (P less than 0.05). (table; see text) CGRP is a potent coronary artery vasodilator causing notable dose-dependent decreases in coronary resistance and a rise in myocardial flow, despite a decreased MAP (all P less than 0.05). CGRP does not affect ventricular contractility in vivo.
Animals↗
Effect of inosine in the normal and reperfused rat heart.
Inosine is a positive inotropic agent and dilates coronary blood vessels. During ischemia, inosine infusion increases blood flow, resulting in decreased myocardial damage. We wished (a) to determine inosine's effect in isolated rat hearts and (b) to determine if inosine attenuates myocardial dysfunction after transient global ischemia. Developed left ventricular pressure (LVP), LV dP/dt, and coronary perfusion pressure were monitored in hearts receiving Krebs-Henseleit buffer (KHB) (n = 10) or KHB + 2 mM inosine (n = 4). KHB + 2 mM inosine significantly reduced coronary perfusion pressure by 21% but had no effect on developed LVP or LV dP/dt. Hearts receiving KHB (n = 6) or KHB + 2 mM inosine (n = 5) were subjected to 15-min global ischemia followed by 30-min reperfusion with KHB. Recovery of LVP, LV dP/dt, the incidence of arrhythmias, and the time to peak recovery of developed LVP was not different between groups. In two additional hearts, KHB + 2 mM inosine administered during reperfusion had no effect on developed LVP, LV dP/dt, or coronary perfusion pressure. Thus, unlike other preparations, inosine pretreatment did not significantly affect the time course of postischemic functional recovery of rat myocardium.
Animals↗
Relative roles of cardiac receptors and arterial baroreceptors during hemorrhage in conscious dogs.
To determine the relative roles of cardiac receptors and arterial baroreceptors during blood loss, the effects of acute hemorrhage on measurements of mean arterial pressure, cardiac output, stroke volume, total peripheral resistance, and heart rate were examined in chronically instrumented, conscious dogs with all nerves intact (n = 15) and following either cardiac denervation (CD, n = 14), sinoaortic denervation alone (SAD, n = 11), or combined sinoaortic denervation plus cardiac denervation (SAD + CD, n = 8). Hemorrhage at a constant rate (0.5 ml/kg/min) was continued until mean arterial pressure fell to 40 mm Hg or 30 ml/kg of blood was withdrawn. Hemorrhage (20 ml/kg) decreased mean arterial pressure similarly in the intact group (-15 +/- 3.3 mm Hg) and CD group (-17 +/- 3.2 mm Hg), but to a greater extent in the SAD (-53 +/- 3.4 mm Hg) and SAD + CD (-49 +/- 2.9 mm Hg) groups. Total peripheral resistance increased similarly in the intact (20.4 +/- 3.0 mm Hg/l/min) and CD (22.4 +/- 2.4 mm Hg/l/min) groups, but did not increase in SAD and SAD + CD groups. Acute cardiac denervation induced with intrapericardial lidocaine in either the intact or SAD groups resulted in similar responses of mean arterial pressure to hemorrhage as those observed in the chronic CD and chronic SAD + CD groups, respectively. Thus, dogs with cardiac denervation withstand hemorrhage and increase total peripheral resistance to a similar extent as intact dogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of interleukin 2 on cardiac function in the isolated rat heart.
Adoptive immunotherapy with IL 2 is associated with severe cardiovascular toxicities including peripheral and pulmonary edema, hypotension decreased systemic vascular resistance, increased heart rate, and an increased cardiac index. The purpose of this investigation was to determine whether IL 2 alone or in combination with lymphokine-activated killer cells (LAK) cells depress cardiac function using the isolated, perfused, working rat heart preparation. Male Sprague-Dawley rats (250-350 g) were anesthetized and the hearts were removed and placed on the perfusion apparatus. Hearts were perfused with oxygenated Krebs-Henseleit buffer (KHB), or oxygenated KHB containing IL 2 alone, IL 2-Media (cell culture media supplemented with 1,500 U IL 2/ml), LYMPH (cell culture media from cultured mononuclear cells from healthy volunteers), or LAK (cell culture media from cultured lymphocytes harvested from patients receiving IL 2/LAK in the presence of 1,500 U/ml IL 2). The cells were removed before perfusion (n = 9). Cardiac output and coronary flow were measured at 20-min intervals with preload constant (afterload varied or afterload constant (preload varied). The results indicate a significant depression in cardiac function in hearts treated with LAK. This depression was evident at 20 min and was more pronounced at 60 min. Washout of the KHB plus LAK reversed this depression. Thus, IL 2-stimulated/cultured human mononuclear cells produce a soluble factor that produces a reversible severe depression of cardiac function.
Animals↗
Bifurcations and intrinsic chaotic and 1/f dynamics in an isolated perfused rat heart.
The application of the theory of chaotic dynamical systems has gradually evolved from computer simulations to assessment of erratic behavior of physical, chemical, and biological systems. Whereas physical and chemical systems lend themselves to fairly good experimental control, biologic systems, because of their inherent complexity, are limited in this respect. This has not, however, prevented a number of investigators from attempting to understand many biologic periodicities. This has been especially true regarding cardiac dynamics: the spontaneous beating of coupled and non-coupled cardiac pacemakers provides a convenient comparison to the dynamics of oscillating systems of the physical sciences. One potentially important hypothesis regarding cardiac dynamics put forth by Goldberger and colleagues, is that normal heart beat fluctuations are chaotic, and are characterized by a 1/f-like power spectrum. To evaluate these conjectures, we studied the heart beat intervals (R wave to R wave of the electrocardiogram) of isolated, perfused rat hearts and their response to a variety of external perturbations. The results indicate bifurcations between complex patterns, states with positive dynamical entropies, and low values of fractal dimensions frequently seen in physical, chemical and cellular systems, as well as power law scaling of the spectrum. Additionally, these dynamics can be modeled by a simple, discrete map, which has been used to describe the dynamics of the Belousov-Zhabotinsky reaction.
Animals↗
Progressive change in collateral blood flow after coronary occlusion in conscious dogs.
This study used a retrospective analysis of infarcted and salvaged tissue samples to determine the patterns of blood flow changes (radioactive microsphere technique) that occur within the area at risk during the first 24 h after coronary artery occlusion (CAO) in conscious dogs. With the triphenyl tetrazolium chloride (TTC) technique, individual samples were selected and included in either the infarcted (TTC-negative) or salvaged (TTC-positive) group. The infarcted and salvaged samples were paired according to blood flow levels of 0.1-0.2, 0.2-0.3, or 0.3-0.4 ml.min-1.g-1 at either 5 min, 1 h, 3 h, or 6 h after CAO. In tissue samples that were salvaged, blood flow rose progressively, i.e., from 5 min to 1 h, from 1 to 3 h, from 3 to 6 h, and from 6 to 24 h. Blood flow to infarcted tissue rose only in the longest interval, from 6 to 24 h after CAO. When blood flow levels were less than 0.1 ml.min-1.g-1, virtually all the samples were infarcted, whereas corresponding lesser amounts of infarction were observed with increasing blood flow levels after CAO. Thus, in the conscious dog, blood flow rises progressively to salvaged but not infarcted tissue within the area at risk. Except for myocardium with blood flow levels less than 0.1 ml.min-1.g-1, the blood flow levels at any of the time points after CAO could not be used to predict necrosis.
Animals↗
Increased myocardial infarct size because of reduced coronary collateral blood flow in beagles.
Effects of permanent left circumflex coronary artery occlusion (CAO) were examined in conscious purebred beagles and mongrel dogs, instrumented with miniature left ventricular (LV) pressure gauges, wall thickness gauges in the ischemic zone, catheters in left atrium and aorta, and snares around the left circumflex coronary artery. Blood flow was measured using the radioactive microsphere technique before CAO and at 5 min, 1, 3, and 24 h after CAO. Although CAO reduced myocardial blood flow similarly in beagles and mongrels, significantly less (P less than 0.05) recovery of myocardial blood flow was observed over the following 24-h period in beagles. Infarct size, as determined by triphenyltetrazolium chloride and expressed as percentage of area at risk, was larger (P less than 0.05) in beagles (62.0 +/- 5.1%) than mongrels (42.5 +/- 4.2%). Thus beagles do not tolerate ischemia as well as mongrel dogs and possess fewer functional coronary collaterals resulting in larger infarcts after CAO.
Animals↗
Differential effects of acute endotoxin shock on myocardial contractility and performance.
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Animals↗
The hemodynamic effects of treatment with interleukin-2 and lymphokine-activated killer cells.
STUDY OBJECTIVE: To determine the hemodynamic alterations occurring during therapy with the maximally tolerated doses of interleukin-2 and lymphokine-activated killer cells. DESIGN: Case series. SETTING: Referal-based inpatient oncology service at a university medical center. PATIENTS: A sequential sample of 13 patients with metastatic colon carcinoma, malignant melanoma, or hypernephroma who were receiving treatment with interleukin-2 and lymphokine-activated killer cells in the maximally tolerated doses. MEASUREMENTS AND MAIN RESULTS: Pretreatment variables of mean arterial pressure, systemic vascular resistance, heart rate, pulmonary capillary wedge pressure, and cardiac index were compared with the same variables measured either immediately before the eighth dose of interleukin-2 or immediately before the initiation of pressor support with dopamine hydrochloride. When these values were compared with the pretreatment values, patients showed a significant decrease in mean arterial pressure (92 mm Hg compared with 75 mm Hg; P less than 0.0001), and systemic vascular resistance (15.1 compared with 8.5 mm Hg/L . min; P less than 0.0001), but an increase in heart rate (73 compared with 110 beats/min; P less than 0.0001) and cardiac index (3.1 compared with 4.7 L/min . m2 body surface area; P less than 0.0001). No significant change was noted in pulmonary capillary wedge pressure. Low systemic vascular resistance persisted throughout interleukin-2 therapy. Although blood pressure normalized in 24 hours, the systemic vascular resistance remained below baseline levels 6 days after interluekin therapy had been stopped. INTERVENTIONS: Blood pressure was successfully supported at greater than 90 mm Hg with dopamine hydrochloride or phenylephrine hydrochloride, or both. CONCLUSIONS: Therapy with high doses of interleukin-2 induces hemodynamic changes consistent with a high-output and low-resistance state similar to changes noted during the early phase of septic shock.
Hemodynamics↗
Influence of selective parasympathectomy of the A-V nodal region on atrioventricular conduction in conscious dogs.
The maximum atrial paced rate with 1:1 atrioventricular conduction (Rmax) was compared before and after selective parasympathectomy of the atrioventricular nodal region (AVNR). Each animal was instrumented with right atrial and right ventricular bipolar electrodes. Rmax was determined (1) under quietly resting, control conditions, (2) following beta-adrenergic blockade, (3) following muscarinic blockade, and (4) following combined beta-adrenergic and muscarinic blockade. During a second surgical procedure approximately two weeks later, parasympathectomy was achieved by dissection and topical application of phenol to the fat pad and underlying epicardium at the inferior left atrial junction with the inferior vena cava; completeness of AVNR parasympathectomy was tested at surgery by supramaximal stimulation of right and left cervical vagi, with and without rapid atrial pacing. AVNR sympathetic innervation remained intact. All studies were conducted while the animals were conscious and quietly resting. Before parasympathectomy, Rmax under control conditions averaged 136 +/- b4 beats per minute (bpm). Following beta-blockade, Rmax was 126 +/- 5 bpm; while with muscarinic blockade, Rmax averaged 373 +/- 4 bpm (P less than 0.001, with control). With combined beta- and muscarinic blockade, Rmax was 300 +/- 14. After AVNR parasympathectomy, although the resting heart rate was unchanged, the Rmax under control conditions was 342 +/- 10 bpm. beta-Blockade reduced this significantly (P less than 0.001) to 278 +/- 15 bpm. With muscarinic blockade, Rmax averaged 346 +/- 11 bpm, which was not different from the control Rmax after AVNR parasympathectomy. Combined beta- and muscarinic blockade produced an Rmax of 280 +/- 14 bpm.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenergic alpha-Antagonists↗