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Biomedical subjects

G L Freeman

Publications and source records attributed to G L Freeman.

At least 73 records · Page 4Linked to original sources
PubMed1993

Pine pollen allergy in northern Arizona.

Allergy to pine trees is generally held to be rare and clinically insignificant. Skin test sensitivity to pine pollen antigen was found in 12 of approximately 826 (1.5%) atopic patients in a northern Arizona private allergy practice. There were five women and seven men and their ages ranged from 6 to 59 years. All were residents of the pine tree area for at least 2 years. All 12 reacted to the antigen of the predominant ponderosa pine and five also reacted, usually less strongly, to Colorado pinyon pine. Eight patients had spring season rhinoconjunctivitis and four others had perennial symptoms. Four of the 12 also had asthma. Some patients had clinical symptoms coinciding with pine pollen season.

Adolescent↗
PubMed1992

An evaluation of pulsus alternans in closed-chest dogs.

Pulsus alternans is a condition in which the arterial pressure generated by the heart oscillates between two levels on a beat-to-beat basis. We evaluated the onset of pulsus alternans in chronically instrumented dogs subjected to tachycardia and inferior vena caval occlusion. During pulsus alternans, the left ventricular (LV) end-diastolic volume (EDV) was larger before the strong beats (28.7 +/- 5.3 vs. 25.9 +/- 4.5 ml, P less than 0.001 by paired t test), suggesting that the Frank-Starling mechanism participates in the alternating difference in end-systolic pressure. In addition, however, the ratio of pressure to volume at end systole was greater in the strong beats (2.01 +/- 0.36 vs. 1.46 +/- 0.45, P less than 0.005 by paired t test), a difference that cannot be explained by the Frank-Starling mechanism alone. This indicates that there is also a difference in end-systolic inotropic states between strong and weak beats. These changes occurred without significant alterations in beat-to-beat levels of coronary flow. The time constant of isovolumic pressure fall (T) was faster for the strong beats (37.5 +/- 4.2 vs 61.1 +/- 12.7 ms, P less than 0.002 by paired t test). The onset of oscillation in T preceded the onset of changes in LVEDV and LV systolic pressure in every case by an average of seven beats (range 3-11), suggesting that abnormalities of intracellular calcium handling led to the occurrence of pulsus alternans.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Myocardial depression produced by sustained tachycardia in rabbits.

Much recent attention has been focused on the tachycardia-induced heart failure model. We hypothesized that sustained tachycardia would lead to myocardial depression in rabbits, as it does in dogs and swine. We evaluated the passive and active length-tension relations and postrest contraction behavior in right ventricular papillary muscles from 22 New Zealand White rabbits, 11 controls, and 11 subjected to ventricular pacing at a rate of 400 beats/min for 29.4 +/- 10.6 days. Studies were performed in oxygenated buffer at 22 degrees C. Active tension was significantly reduced at muscle lengths of 0.95.Lmax and above; at Lmax it was 4.7 +/- 0.2 g/mm2 for the control group and 3.3 +/- 0.2 g/mm2 for the paced group (P less than 0.005). Both groups showed increased force development when the concentration of calcium in the buffer was increased. There were no differences between the groups in the passive length-tension relations. Of note, postrest contraction data showed that the second postrest beat was smaller for the paced animals for rest intervals up to 2 min, suggesting that beat-to-beat trans-sarcolemmal calcium handling may differ from normal in this model. We conclude that sustained tachycardia will lead to myocardial depression in rabbits; the extension of this model to a small animal species may offer new ways to explore its causative mechanisms.

Animals↗
PubMed1992

Simple circuit for pacing hearts of experimental animals.

In this paper we describe a simple pacing circuit which can be used to drive the heart over a wide range of rates. The circuit is an astable multivibrator, based on an LM555 integrated circuit. It is powered by a 9-V battery and is small enough for use in rabbits. The circuit is easily constructed and inexpensive, making it attractive for numerous applications in cardiovascular research.

Animals↗
PubMed1992

Beneficial influence of vasoactive intestinal peptide on ventriculovascular coupling in closed-chest dogs.

The effect of vasoactive intestinal peptide (VIP) on ventriculovascular coupling in the intact cardiovascular system has not been defined. We studied seven dogs chronically instrumented with left ventricular (LV) pressure manometers and three sets of diameter gauges before and after infusions of 0.02, 0.05, and 0.10 microgram.kg-1.min-1 VIP. The dogs were studied after autonomic blockade, anesthesia, and intubation, with a fixed heart rate of 160 beats/min. Contractility was assessed using LV elastance at end systole (Ees) and the slope of the stroke work-end-diastolic volume relation. The vascular influence of VIP was quantified by determining effective arterial elastance (Ea) under steady-state conditions. The overall effect on ventriculovascular coupling was assessed using the transfer of mechanical energy from LV to the arterial system (TransPVA) quantified as the percentage of pressure-volume area (PVA) expressed as stroke work. LV relaxation was measured using the time constant of LV pressure decay. The results showed that VIP increased contractility (Ees increased to 129, 156, and 181% of control; P < 0.01 for all vs. control) and decreased effective arterial elastance (Ea fell to 84, 68, and 64% of control; P < 0.0155 vs. control for the two higher doses). VIP had no consistent effects on LV relaxation. Thus, in addition to its positive ventricular effects (increased contractility), VIP has beneficial vascular effects (reduced Ea). These properties combine to improve ventriculovascular coupling, such that VIP enhances delivery of mechanical energy from the LV to the circulatory bed.

Animals↗
PubMed1992

Kinetics of restitution of left ventricular relaxation.

Although the kinetics of cardiac systolic force restitution have been well described, the restitution kinetics of left ventricular relaxation have not been examined. To define relaxation restitution behavior, we studied seven dogs chronically instrumented with left ventricular high-fidelity micromanometers and piezoelectric dimension crystals. After a priming period at a basic cycle length of 375 msec, test extrastimuli were introduced after a range of extrasystolic intervals (ESIs). Relaxation behavior of control and extrasystolic beats was characterized by the time constant of isovolumic relaxation, tau. Relaxation restitution can be described by two concatenated monoexponential curves, an early phase described by a rapid time constant and a late phase described by a slower time constant (TC1, 36.21 +/- 7.90 msec; TC2, 75.94 +/- 10.65 msec; p less than 0.05). The first phase of relaxation restitution parallels systolic force restitution over the same range and displays faster recovery (TCs, 58.93 +/- 10.01 msec, p less than 0.05). Postextrasystolic restitution of test pulses after beats at fixed ESIs depends on the initial ESI. Relaxation recovery of postextrasystolic beats proceeds faster with smaller initial ESIs (TC1 for ESI of 300 msec, 13.27 +/- 4.05 msec; TC1 for ESI of 450 msec, 72.85 +/- 21.72 msec; p less than 0.0001). The monoexponential pattern of restitution was seen with model-independent descriptors of relaxation as well as with tau.

Analysis of Variance↗
PubMed1990

Immune responses during human Schistosoma mansoni. XVII. Recognition by monoclonal anti-idiotypic antibodies of several idiotopes on a monoclonal anti-soluble schistosomal egg antigen antibody and anti-soluble schistosomal egg antigen antibodies from patients with different clinical forms of infection.

A monoclonal human anti-soluble schistosomal egg Ag(SEA) antibody (E5) that stimulates anti-Id T cells and is idiotypically represented in pools of immunoaffinity-purified human anti-SEA antibodies from chronic, generally asymptomatic, intestinal (INT) patients (AM1 and AM5) was used to raise several monoclonal anti-Id: 1C2, 1C6, 4A8, 4F9, and 2A7. Cross-inhibition between these anti-Id identified distinct idiotopes on E5. Anti-SEA preparations from schistosomiasis patients (AM1, AM5, and others) were tested for their inhibition of the E5/monoclonal anti-Id reactions, in competitive ELISA. In either the E5/4A8 or E5/1C6 ELISA system, anti-SEA from INT (AM1 or AM5) or hepatointestinal (HI) (AM7) patients were able to inhibit these reactions. However, anti-SEA antibodies from acute (AM9) or hepatosplenic (HS) (AM3 or AM8) patients did not express Id that were inhibitory in these systems. These results suggest that a relatively high proportion of INT and HI anti-SEA antibodies express a dominant cross-reactive idiotope (CRI) recognized by 1C6/4A8. This CRI is also easily detected in plasmas from individual INT patients. Anti-Id 1C2 reacted strongly with an Id in AM1, AM5, or AM7, but one which also occurred, to a lesser extent, in AM3, AM8, and AM9. Monoclonal anti-Id 4F9 and 2A7 reacted weakly with idiotopes expressed by antibodies from all patients, regardless of the clinical form of their infection. These observations indicate that anti-SEA antibodies from INT and HI, but not acute or HS patients express dominant, CRI that are identified by 1C6, 4A8, or 1C2 and are also expressed on the INT-derived anti-SEA mAb E5.

Animals↗
PubMed1990

Expression of cross-reactive, shared idiotypes on anti-SEA antibodies from humans and mice with schistosomiasis.

Immunoaffinity-purified antibodies against Schistosoma mansoni soluble egg Ag (SEA) from infected patients' sera differ idiotypically according to the donor's clinical form of the disease. The Id differ both by their ability to stimulate proliferation of anti-Id T cells and their recognition by anti-Id-specific sera. Also, mice infected with S. mansoni develop anti-Id T and B cell responses against mouse anti-SEA antibodies. We now show that anti-SEA antibodies from serum pools of chronic, but asymptomatic patients (AM1 and AM5) stimulate proliferation of spleen cells from mice infected with S. mansoni. However, AM8, anti-SEA antibodies from hepatosplenic patients, did not stimulate these spleen cells. The murine responses directly parallel patient studies where AM1 and AM5 Id-stimulated human PBMC, but AM8 Id did not. In competitive ELISA, using AM1 or AM-5-specific rabbit antisera or human anti-SEA mAb E5-specific rabbit antiserum, sera from mice infected for 8 and 16 wk (but not from uninfected mice) compete with AM1, AM5, or E5. These sera do not compete in the AM8/anti-AM8 competitive ELISA. Sera from 8-wk-infected mice inhibit more against AM1, AM5, and E5 than do sera from later infections, and anti-SEA immunoaffinity-purified antibodies from 8-wk-infected mice stimulate spleen cells from infected mice more than anti-SEA antibodies from sera of mice late in infection. However, spleen cells from more chronically infected mice are more responsive to either the murine or human anti-SEA antibody preparations than cells from mice with earlier infections. Both the ELISA data and lymphocyte responses indicate that anti-SEA antibodies from mice infected with S. mansoni for 8 wk bear Id cross-reactive with those expressed on anti-SEA antibodies from humans with chronic, asymptomatic schistosomiasis, but not those from hepatosplenic patients.

Animals↗
PubMed1990

Influence of adenosine on left ventricular performance in conscious dogs.

Adenosine, a potent vasodilator of both the peripheral and coronary vasculature, is increasingly used to produce controlled hypotension in the clinical and experimental setting. To define the influence of adenosine on left ventricular (LV) performance in conscious closed-chest dogs were studied six chronically instrumented autonomically blocked animals before and after the administration of 0.3, 0.6, and 1.2 microM.kg-1.min-1 infusions of adenosine. Systolic performance was quantified by the end-systolic pressure-volume (Pes-Ves) and stroke work end-diastolic volume (SW-EDV) relations. Active diastolic performance was quantified by the time constant of LV relaxation (T), whereas passive diastolic properties were assessed by comparing LV pressures at a common LV volume. Despite a decrease of mean arterial pressure of 51 mmHg, adenosine did not change the slope of the Pes-Ves relation or the end-systolic volume at a pressure of 100 mmHg. The slope of the SW-EDV relation was also unchanged, and its volume axis intercept was slightly reduced. There were no differences in T or in the diastolic pressure at a common LV volume. Thus adenosine appears to have little influence on systolic or diastolic LV performance aside from its marked affect on afterload, indicating it is a useful agent for producing controlled hypotension.

Adenosine↗
PubMed1990

Effects of increased afterload on left ventricular function in closed-chest dogs.

Mechanical response of the left ventricle (LV) in an intact circulatory system to steady-state increases in afterload may differ from that of an isolated LV, because secondary hemodynamic changes cannot be independently manipulated when the circulation is intact. To evaluate the integrated response of the LV in closed-chest dogs to sustained increases in afterload, six animals chronically instrumented with three orthogonal diameter gauges and LV manometers were studied after autonomic blockade and fentanyl-droperidol anesthesia. End-systolic pressure-volume (PES-VES) and stroke work end-diastolic volume (SW-EDV) relations and the relations between pressure-volume area (PVA, area bounded by PV loop and PES-VES relation) and EDV were quantified. Balloon inflation (BI) in the proximal descending aorta increased LV PES from 100.7 +/- 13.4 to 140.2 +/- 19.3 mmHg (P less than 0.002) and LVEDV from 39.1 +/- 11.3 to 43.3 +/- 12.2 ml (P less than 0.01). The slope of the PES-VES relation was not significantly changed, whereas V100, a volume intercept in the common range of pressures, was reduced from 27.5 +/- 7.3 to 23.7 +/- 6.1 ml (P less than 0.005). PVA-EDV relation was highly linear; its slope was increased after BI. Comparison of beats with matched LVEDV before and after BI showed significant increases in maximum rate of pressure development and PVA; the change in SW after BI was modest and not significant. The efficiency of energy transfer from PVA to SW (TransPVA, SW/PVA X 100) decreased from 52.5 +/- 8.6 to 42.6 +/- 6.3% (P less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Effect of loading conditions, contractile state, and heart rate on early diastolic left ventricular filling in conscious dogs.

We investigated left ventricular (LV) early diastolic filling in 10 normal conscious dogs that had been previously instrumented to measure LV and left atrial (LA) pressures and three orthogonal LV internal dimensions. LV volume was calculated as a general ellipsoid. The pressure within a passive structure increases as it is filled. If myocardial relaxation is rapid enough to substantially aid LV diastolic filling, it may overcome this effect and cause LV pressure to fall despite an increase in volume. Thus, we defined the amount of LV filling that occurred while LV pressure was falling as relaxation filling, which is a measure of the importance of LV relaxation during early diastolic filling. The time constant of relaxation (T) was derived from the exponential fall of LV pressure during isovolumic relaxation. While LV pressure was falling early in diastole (the relaxation filling period), all three LV diameters increased. Autonomic blockade with hexamethonium (5 mg/kg) and atropine (0.1 mg/kg) reduced relaxation filling from 21 +/- 6% (mean +/- SD) to 12 +/- 3% of the stroke volume (p less than 0.01). The mean LA pressure also was significantly decreased (from 12 +/- 2 to 10 +/- 5 mm Hg, p less than 0.05), while the duration of the relaxation filling period and T were unchanged. Positive inotropic stimulation with dobutamine (10 micrograms/kg/min) shortened T without changing LA pressure. The maximum LA-LV pressure gradient, dV/dtmax, and relaxation filling all increased. Augmented preload produced by dextran infusion (500 ml/10 min) caused an increase in LA pressure (from 11 +/- 3 to 21 +/- 8 mm Hg, p less than 0.05) without altering T. This also increased the maximum LA-LV pressure gradient, dV/dtmax, and relaxation filling. Augmented afterload produced by methoxamine (10 mg/3 min i.v.) significantly increased LA pressure (from 9 +/- 4 to 15 +/- 10 mm Hg, p less than 0.05) and lengthened T (from 35 +/- 4 to 50 +/- 7 msec, p less than 0.05) and the duration of relaxation filling (from 36 +/- 5 to 44 +/- 9 msec, p less than 0.01) without altering the maximum LA-LV pressure gradient, dV/dtmax, or LV relaxation filling. Incremental changes in heart rate induced by atrial pacing (from 100-180 beats/min) resulted in progressive decreases in the time constant of LV relaxation and the duration of relaxation filling. The LA pressure was also decreased. There was no corresponding increase in the amount of active LV filling until the heart rate reached 180 beats/min. During all these interventions, T correlated with the duration of LV relaxation filling (r = 0.99. p less than 0.05). The amount of relaxation filling and dV/dtmax both correlated with the maximum LA-LV pressure gradient.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Evaluation of left ventricular mechanical restitution in closed-chest dogs based on single-beat elastance.

The mechanical restitution of the left ventricle of closed-chest dogs was modeled as a monoexponential relation, using peak single-beat elastance as a measure of contractile strength. Data were obtained from nine dogs chronically instrumented with three sets of piezoelectric diameter gauges to assess ventricular volume and high-fidelity manometers to measure pressure. Mechanical restitution curves were obtained during both atrial and ventricular pacing in six dogs. The time constant of mechanical restitution was 64.3 +/- 11.4 msec for atrial and 122.2 +/- 26.3 msec for ventricular paced runs (p less than 0.01). These values are smaller than those previously reported from isolated hearts or isolated muscle segments. Although the time of onset of mechanical restitution was longer for atrial than for ventricular runs (255.1 +/- 14.3 versus 225.1 +/- 9.6 msec, p less than 0.05), the plateau to which mechanical function rose was not different. During ventricular pacing, fusion beats were noted in four dogs. The magnitude of the mechanical contribution of these fusion beats fell to a nadir at approximately 250 msec, suggesting that intracellular calcium available for crossbridge interaction is dropping during this time. In three additional dogs, the time constant of postextrasystolic restitution was found to vary depending on the preceding extrasystolic interval. Thus, mechanical restitution of the ventricle is a dynamic process that can be assessed using an elastance-based approach in the in situ heart.

Animals↗
PubMed1990

Role of ventriculovascular coupling in cardiac response to increased contractility in closed-chest dogs.

While both dobutamine and pacing tachycardia augment left ventricular (LV) contractility, whether overall cardiovascular response to these stimuli is comparable is not known. To address this question we studied seven dogs previously instrumented with three LV diameter gauges and LV pressure manometers. After ganglionic blockade and sedation, caval occlusions were performed at heart rates of 120, 160, and 200 bpm before (C), and 160 and 200 bpm after administration of 10 micrograms/kg per min dobutamine, i.v. (D). The effective arterial elastance (Ea) went up from 14.2 +/- 4.5 mmHg/ml at C120 to 19.6 +/- 8.8 (P less than 0.025 vs C120) and 24.2 +/- 10.4 (P less than 0.001 vs C120) mmHg/ml at C160 and C200. Ees, the slope of the end-systolic pressure-volume relation, increased with pacing from 9.7 +/- 4.6 to 11.7 +/- 4.3 (P less than 0.02), and 13.2 +/- 5.7 (P less than 0.02) mmHg/ml at 160 and 200 bpm. With dobutamine infusion Ea went down, and Ees was further increased to 37.0 +/- 20.9 mmHg/ml at 160 bpm (P less than 0.002 vs C160), and 53.0 +/- 22.6 mmHg/ml at 200 bpm (P less than 0.002 vs C200). Comparison of stroke work and pressure-volume area from single beats with matched LV end-diastolic volumes showed that these were both increased by dobutamine, but not by pacing tachycardia. While increased heart rate after dobutamine markedly increased contractility, Ea was not changed, and neither stroke work nor pressure-volume was further increased. Thus, how well an increase in contractility is transmitted to the periphery is determined in part by arterial behavior. Assessment of both the arterial system and cardiac contractility is necessary to fully evaluate the overall impact of an inotropic stimulus.

Animals↗
PubMed1990

Reduced reproductive efficiency in mice with schistosomiasis mansoni and in uninfected pregnant mice injected with antibodies against Schistosoma mansoni soluble egg antigens.

Female CBA/J mice were infected with approximately 15 cercariae of Schistosoma mansoni and mated with normal syngeneic males 7 weeks later. Uninfected mice were bred in parallel, and both groups were subsequently bred several more times. Pregnancies were documented by formation of vaginal plugs, and daily records were kept concerning the status of the pregnancies, delivery, and offspring. One hundred thirty-two pregnancies in uninfected mice resulted in 101 (77%) viable litters. In contrast, 133 pregnancies in mice infected with S. mansoni lead to 45 (34%) viable litters. The decreased number of viable litters born or raised by infected mothers resulted from maternal death during pregnancy (5%), spontaneous abortion (20%), and infanticide (42%). Observations of multiparous infected mice indicated that this reduced rate of production of viable, surviving offspring was not different in subsequent pregnancies nor influenced by the duration of the infection. At 2 weeks of age, offspring of infected mice weighed significantly less than offspring of equal-sized litters from uninfected mice, but this weight differential was not sustained beyond 2 weeks of age. Subsequent studies compared the effects on uninfected pregnant mice of injections of antibodies against S. mansoni soluble egg antigens (immunoaffinity-purified from sera of mice with 16 week S. mansoni infections) vs. normal mouse immunoglobulin. After repeated injections of these antibodies during multiple pregnancies, lowered reproductive efficiencies (37%) were observed as compared to parallel studies of pregnant mice injected with normal mouse immunoglobulin (67%).

Animals↗
PubMed1990

The effects of the pericardium on function of normal and enlarged hearts.

In summary, the pericardium is a membranous structure that surrounds the heart. Its physical properties are such that it is distensible when the total intrapericardial volume is small and inextensible when total intrapericardial volume is large. The pericardium serves to limit acute cardiac distention and to modulate the phenomenon of ventricular interdependence. It is a dynamic structure that, when subjected to chronic stretching--either due to the gradual accumulation of intrapericardial fluid or to cardiac enlargement--will grow to accommodate its contents, such that the working range of pressures between it and the surface of the heart is low. The precise level of cardiac distention that is necessary to engage the pericardium is unknown, but studies in normal and dilated hearts suggest that, at the upper end of the normal volume range of the heart, the intrapericardial volume is just sufficient to reach the noncompliant portion of the tissue's length-tension relation. Further studies are needed to determine whether this behavior represents a hemodynamic protective mechanism in normal animals.

Cardiomegaly↗
PubMed1989

A-to-D conversion from paper records with a desktop scanner and a microcomputer.

A novel method for digitizing signals contained in paper records is presented. This method is based on the use of an inexpensive optical scanner to translate the image on paper into a binary, bit map data structure. Several algorithms which recognize the signal line in the bit map and translate it into a series of numbers which are equivalent to the output of electronic analog-to-digital converters are described. The method was validated by comparison both with idealized test patterns of varying frequency content and with electronically digitized pressure and pressure time derivative tracings from chronically instrumented dogs. The root mean square error for the physiological signals was 3.5-3.9% of peak-to-peak full scale, corresponding to roughly 50% more than the thickness of the signal line on the paper.

Algorithms↗