Biomedical subjects

R L Woods

Publications and source records attributed to R L Woods.

At least 19 recordsLinked to original sources

PubMed1998

ANP and bradycardic reflexes in hypertensive rats: influence of cardiac hypertrophy.

In previous studies we demonstrated that in normotensive rats, but not in spontaneously hypertensive rats (SHR), atrial natriuretic peptide (ANP) enhances bradycardic reflexes through an action on cardiac vagal afferent pathways. The present study aimed to determine whether cardiac hypertrophy, hypertension, or a nonreversible genetic factor accounted for the insensitivity of SHR to ANP action on cardiac reflex pathways. SHR were treated with the angiotensin-converting enzyme (ACE) inhibitor perindopril (3 mg/kg per day) for 6 weeks from 4 to 9 weeks of age (SHR-S, n=10) or for 9 weeks from 4 to 12 weeks of age (SHR-L, n=10) or were untreated (SHR, n=10) to produce differential effects on blood pressure and left ventricle/body weight ratio (LV/BW). Untreated normotensive Wistar-Kyoto rats (WKY, n=10) were also studied. At 13 weeks of age, all rats were instrumented with aortic and jugular catheters, and at 14 weeks we measured heart rate reflexes to rapid intravenous infusions of methoxamine (100 microg/kg, cardiac baroreflex) and serotonin (5 to 60 microg/kg, von Bezold-Jarisch cardiac chemosensitive reflex), with either alpha-rat ANP (150 ng/kg per minute IV) or saline vehicle (270 microL/h IV) infusion. Perindopril treatment for 6-week (SHR-S) and 9-week (SHR-L) durations maintained blood pressure at normotensive levels in both groups. SHR-S exhibited a small degree of cardiac hypertrophy (LV/BW was 8% higher than in WKY but 11% less than in untreated SHR), but LV/BW was normalized in SHR-L (to within 1% of WKY LV/BW). In WKY, ANP significantly (P<0.05) enhanced bradycardic responses to both the cardiac baroreflex (by 42+/-10%) and von Bezold-Jarisch chemosensitive reflex (by 17+/-5%) activation but had no effect in SHR. The cardiac reflex action of ANP was restored in SHR-L (ANP enhanced reflex bradycardia by 28+/-12% and 36+/-8%, baroreflex and von Bezold-Jarisch reflex, respectively; P<0.05), but SHR-S, which developed some cardiac hypertrophy, remained unresponsive to ANP. Our results suggest that the inability of ANP to sensitize cardiac vagal (nonarterial) afferents in SHR was not due to an inherited irreversible component, or the hypertension per se, but was associated with the presence of cardiac hypertrophy. A functional consequence of hypertension-induced cardiac hypertrophy may be the inhibition of the cardioprotective action of ANP through cardiac vagal reflexes.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1998

Predicting the effects of optical defocus on human contrast sensitivity.

We used diffraction modulation transfer functions and model eyes to predict the effect of defocus on the contrast sensitivity function (CSF) and compared these predictions with previously published experimental data. Using the principle that optically induced changes in the modulation transfer function should be paralleled by identical changes in the CSF, we used the modulation transfer function calculations with the best-focus CSF measurements to predict the defocused CSF. An aberration-free model predicted the effects of defocus well when the CSF was measured with small pupils (e.g., 2 mm) but not with larger pupils (6-8 mm). When the model included average aberrations, prediction of the defocused CSF with large pupils was better but remained inaccurate, failing, in particular, to reflect differences between individual subjects. Inclusion of measured aberrations for individual subjects provided accurate predictions in the shape of the monochromatic CSF of two of three subjects with hyperopic defocus and good predictions of the polychromatic CSF of two subjects with hyperopic defocus. Prediction of the effects of myopic defocus by use of measured individual aberrations of one subject were less successful. Hence a diffraction optics model can provide good predictions of the effects of defocus on the human CSF, given that one has knowledge of the individual ocular aberrations. These predictions are dependent on the quality of the aberration measurements.

Contrast Sensitivity↗

PubMed1997

Subjective depth-of-focus of the eye.

An experiment is described in which the subjective depth-of-focus (DOF) of the eye, defined as the range of focusing errors for which the image of the target appears to have the same clarity, contrast, and form as the optimal in-focus image, was measured as a function of the size of high contrast (99%) Snellen Es for 5 trained subjects under cycloplegia. Mean DOF increased by approximately 60% as the size of the letter detail increased from -0.2 to 0.87 log min arc (Snellen equivalent: 6/3.8 to 6/45), although there were considerable intersubject variations. DOF declined with increasing pupil diameter, the mean total DOFs being 0.86, 0.59, and 0.55 D for 2-, 4-, and 6-mm pupils, respectively. In a second experiment, use of low (21%) contrast letters with a 4-mm pupil and 4 subjects marginally increased the DOF (by 0.08 +/- 0.05 D); refraction also shifted in a myopic direction by a mean of 0.15 +/- 0.06 D compared with the high contrast letters. A third experiment with four less-experienced subjects demonstrated the importance of instruction and training in any measurement involving judgment of just-perceptible defocus blur. The clinical implications of the results for measurements of refraction and amplitude of accommodation are discussed.

Accommodation, Ocular↗

PubMed1997

ANP enhances bradycardic reflexes in normotensive but not spontaneously hypertensive rats.

Baroreflex control of heart rate in spontaneously hypertensive rats (SHR) is defective, largely because of a poor vagal contribution to the reflex. We have demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia in normotensive rats through an action on nonarterial vagal afferent pathways. In the present study, we investigated whether ANP could reverse the baroreflex abnormality in SHR. Heart rate reflexes were activated by three different methods in conscious, instrumented SHR and Wistar-Kyoto rats (WKY) in the presence of intravenous infusions of vehicle (saline) or rat ANP (150 ng/kg per minute). Heart rate responses were measured by (1) the steady-state changes in blood pressure after alternating slow infusions (over approximately 15 to 30 seconds) of a pressor (methoxamine) and depressor (nitroprusside) drug (stimulating predominantly arterial baroreceptors), (2) the ramp method of rapid infusion of methoxamine (over < 10 seconds; stimulating arterial and cardiopulmonary baroreceptors), and (3) the von Bezold-Jarisch method of activating chemically sensitive cardiac receptors through serotonin injections. ANP enhanced the heart rate range of the arterial baroreflex (steady-state method) by 13 +/- 3% in WKY but had no significant effect on the sensitivity or any other parameter of the steady-state baroreflex. When a very rapid rise in blood pressure was elicited by the ramp method in WKY, ANP significantly enhanced baroreflex bradycardia (sensitivity increased by 29 +/- 9%, P < .05). ANP also enhanced the bradycardia of the von Bezold-Jarisch reflex (by 33 +/- 16%, P < .05) in WKY. By contrast, ANP did not influence baroreceptor or chemoreceptor heart rate reflex responses in SHR. We conclude that in normotensive rats, ANP facilitates cardiopulmonary bradycardic reflexes. The lack of effect of ANP in SHR may be related to an underlying structural or genetic alteration in their cardiac sensors, perhaps associated with cardiac hypertrophy, that prevents the ANP-induced activation of cardiac sensory afferents, resulting in cardioinhibition.

Animals↗

PubMed1996

Consequences of monocular diplopia for the contrast sensitivity function.

Though the human eye generally creates a single image on the retina, the literature contains many examples showing perceptual monocular diplopia. Previously, monocular diplopia resulting from astigmatic defocus has been demonstrated to cause a notch (local minimum) in the contrast sensitivity function (CSF). We examine Verhoeff's (1900) model which explains how monocular diplopia can occur through an interaction between defocus and common ocular aberrations. From the measured ocular transverse aberration function and from the measured monocular diplopia of three cyclopleged subjects we predicted multiple notches in the CSF with hyperopic spherical defocus. Monochromatic and polychromatic CSF were measured for vertical gratings with best refraction and with simulated myopia and hyperopia. Multiple notches in CSF were observed experimentally. Notches in the polychromatic CSF were smaller and broader than those found in the monochromatic CSF. Our aberration model was successful in predicting notches in the CSF with hyperopic spherical defocus. The implications for clinical measurement of CSF are discussed.

Adult↗

PubMed1996

Monocular diplopia caused by ocular aberrations and hyperopic defocus.

As a single aperture, approximately monofocal optical system, the human eye generally creates a single image on the retina. However, the literature contains many reports of perceptual monocular diplopia. While it is easy to understand how distortion may produce monocular diplopia, its reported high incidence in normal eyes is less easily understood. We examine a model which ascribes monocular diplopia to an interaction between defocus and ocular spherical aberration. Using a psychophysical hyperacuity-based alignment procedure we measured the transverse aberration function in 0.5 mm steps horizontally across the pupil in the eyes of three cyclopleged subjects. Ocular transverse aberration functions were derived with best refraction and with simulated myopia and hyperopia. Monocular diplopia was also measured under the same conditions. All three subjects showed significant, but different, degrees of positive spherical aberration. The measured ocular transverse aberration functions were predictably modified by the hyperopic and myopic defocus. Hyperopic defocus combined with positive (myopic) spherical aberration changes a monotonic transverse aberration function with a single inflection point into a biphasic function with two inflection points. The locations of the inflections predict the presence and magnitude of the perceived diplopia. These experimental results confirm Verhoeff's (1900) hypothesis for the ocular cause of monocular diplopia.

Adult↗

PubMed1996

Long-term follow-up of a randomised trial of combined chemoradiotherapy induction treatment, with and without maintenance chemotherapy in patients with small cell carcinoma of the lung.

The toxicity and efficacy of concomitant chemotherapy and radiotherapy as induction therapy was evaluated in patients with previously untreated small cell carcinoma of the lung (SCLC), and in responding patients the value of maintenance chemotherapy was examined. 202 patients received induction chemotherapy with cisplatin and etoposide (EP), in combination with cranial and local radiotherapy. 85 patients (42%) developed grades III and IV myelosuppression, the main toxicity of induction treatment. Of the 154 responding patients, 129 were randomised to maintenance chemotherapy with vincristine, doxorubicin and cyclophosphamide (VAC) or no further treatment. The response rate for the limited disease patients (LD) was 87%, 62% achieving a complete response (CR) and the response rate for extensive disease patients (ED) was 68%, with 26% achieving a CR. 17 patients (11%) completed 10 courses of maintenance chemotherapy. 32 patients (57%) developed grade III and IV neutropenia. Median survival for all patients was 53 weeks (LD, 70 weeks; ED, 42.5 weeks). There was no significant difference in overall survival (OS) or disease-free survival (DFS) in the two randomisation arms. This study shows that EP combined with radiotherapy is an effective induction regimen in SCLC. Maintenance chemotherapy with VAC is not associated with increased survival but has significant toxicity after such induction treatment.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

Evidence for a renomedullary vasodepressor hormone.

1. Recent physiological experiments have established that increasing the perfusion pressure of the kidney causes the release of vasodepressor substance from the renal medulla. 2. The substance is not a platelet activating factor, a prostaglandin or nitric oxide and the vasodepressor response to increased renal perfusion is not due simply to inhibition of renin release. 3. The mechanisms by which the renomedullary vasodepressor substance lowers arterial pressure remain to be determined. Sympathoinhibition may account for part of the response, but the hypotension still occurs in autonomic ganglion blocked animals. 4. The source of substance appears to be the renomedullary interstitial cells, though the control of the production and release of the substance remain to be determined. 5. The substance may be a lipid but it is yet to be fully isolated and identified. 6. The threshold for release of the substance appears to be close to normal resting arterial blood pressure. 7. Despite strong evidence that the renal medulla releases a vasodepressor hormone in response to increased renal perfusion pressure, much is still to be determined regarding the physiology of this hormone and its involvement in the aetiology of hypertension.

Kidney Medulla↗

PubMed1996

Increasing resting vascular tone in conscious dogs does not alter the mesenteric vasoconstrictor responses to ANP.

1. There is considerable in vitro evidence that, at high concentrations, atrial natriuretic peptide (ANP) acts directly on pre-constricted blood vessels to cause vasorelaxation. Previously, we have seen vasoconstriction rather than vasodilatation in conscious dogs at physiological levels of the peptide. It is possible that the low resting vascular tone in our conscious, unstressed animals prevented the manifestation of the relaxant properties of ANP in vivo. 2. In the present study in conscious, instrumented dogs, we studied the mesenteric vascular responses to 10 min infusions of ANP (10, 25, 50 and 100 ng/kg per min, i.v.) when resting vascular tone was enhanced with a continuous infusion of AVP (75 pg/kg per min, i.v.) and compared these with responses in the normal condition (no added AVP). 3. Mesenteric vascular resistance was increased by ANP (10, 25, 50 and 100 ng/kg per min) by 9 +/- 2, 20 +/- 6, 29 +/- 7 and 32 +/- 9%, respectively. Increased resting vascular tone did not alter the mesenteric vasoconstrictor response to ANP. Thus, the discrepancy between in vitro (vasorelaxation) and in vivo (vasoconstriction) findings may be the result of the widely different concentrations of ANP used, rather than the state of resting vascular tone.

Animals↗

PubMed1996

Alveolar epithelial lining fluid cellularity, protein and endothelin-1 in children with congenital heart disease.

This study applied bronchoalveolar lavage (BAL) to children with congenital heart disease (CHD) prior to elective cardiac catheterization (n = 48), to determine the influence of pulmonary blood flow and viral infection on the alveolar epithelial lining fluid (ELF) concentration of leucocytes, protein and endothelin-1 (ET-1). Lower respiratory tract (LRT) viral infection was defined as either a positive immunofluorescence for virus, or a virus cultured from the bronchoalveolar lavage fluid (BALF). Haemodynamic status was determined at cardiac catheterization. Normative data for BALF, but not ELF parameters, were obtained from 26 asymptomatic, noninfected normal children undergoing elective surgery. In the absence of LRT infection, the BALF macrophage, lymphocyte and neutrophil differential in CHD was not significantly different from the normal controls. In CHD, both increased pulmonary-to-systemic flow ratio (Q'p/Q's) and increased pulmonary artery-to-left ventricular pressure ratio PAP/LVP were associated with a decrease in ELF protein (rs = -0.59; p < 0.0001; and rs = -0.50; p < 0.0001 respectively). A respiratory virus was isolated from the BALF in 8 (17%) of CHD children. Virus isolation was associated with an increased ELF total protein (p < 0.05 vs no infection), a decreased alveolar macrophage differential count (p < 0.01), and an increased neutrophil differential count (p < 0.05). ET-1 was detected in the BALF of 83% of the noninfected CHD children compared to only 23% of the controls (p < 0.001). ELF ET-1 concentrations did not correlate with haemodynamic status in CHD, but were up to 100 times higher than paired plasma levels. We conclude that, in congenital heart disease, both lower respiratory tract viral infection and increased pulmonary blood flow and/or pulmonary vascular pressure influence the alveolar milieu. High alveolar epithelial lining fluid concentrations of endothelin-1 occur in congenital heart disease, but the stimulus for pulmonary endothelin-1 production is unclear.

Bronchoalveolar Lavage Fluid↗

PubMed1996

Spatial frequency dependent observer bias in the measurement of contrast sensitivity.

A previously reported spatial frequency dependent change in contrast sensitivity, apparently produced by the psychometric method used, was investigated in two experiments. A relative reduction in the measured contrast sensitivity function at higher spatial frequencies was found when using a simple single staircase procedure, even when all external characteristics of the presentation procedure were the same as a more sophisticated and more reliable psychometric method (adaptive probit estimation). The estimated false-negative response rate was found to be greater for the single staircase procedure and was greater at a higher spatial frequency, while the false-positive response rate to interleaved blank presentations did not vary between spatial frequencies and between the two psychometric methods. This supports the suggestion that some subjects, given a knowledge of the psychometric method controlling grating contrast, may adopt different decision criteria at different spatial frequencies.

Adult↗

PubMed1995

Intrarenal infusions of endothelin in conscious dogs: interactions with prostanoids and angiotensin II.

Endothelin (2, 5, and 10 pmol/kg/min) was infused into the renal artery of conscious dogs, producing graded and progressive reductions in renal blood flow (RBF) without initial vasodilatation, parallel reductions in glomerular filtration rate (GFR), and reduced Na+ excretion, but little change in urine flow. Pretreatment of the dogs with either ibuprofen (20 mg/kg orally) or aspirin (30 mg/kg p.o.) did not significantly alter the effects of endothelin (5 pmol/kg/min) on RBF, GFR, or Na+ excretion. However, endothelin caused antidiuresis in these cyclooxygenase-inhibited dogs, indicating that the effects of endothelin on water reabsorption were prostanoid mediated. Treatment with captopril (1.5 mg/kg + 0.5 mg/kg/h) did not significantly alter any of the responses to endothelin. The local effects of endothelin in the kidneys of conscious dogs were vasoconstriction and reduced Na+ excretion which were not mediated or modified by either angiotensin II or prostanoids.

Analysis of Variance↗

PubMed1995

Nitric oxide inhibition does not prevent the hypotensive response to increased renal perfusion in rabbits.

1. The involvement of nitric oxide (NO) and platelet activating factor (PAF) in the systemic depressor responses to increased renal perfusion pressure (RPP) were investigated. 2. In anaesthetized rabbits, the left kidney was perfused via an extracorporeal circuit which allowed RPP to be increased from 65 mmHg to 125 mmHg. The response of systemic blood pressure (SBP) to increasing RPP was measured in the same rabbits. 3. One group of rabbits (n = 5) was treated with NG-nitro-L-arginine (NOLA) to inhibit NO synthase activity (20 mg/kg i.v. bolus). Another group (n = 5), received 250 mmol/L NaHCO3 (4 mL/kg bolus) as vehicle treatment. 4. Following an increase in RPP to 125 mmHg, SBP fell at a rate of 0.43 +/- 0.06 mmHg/min in the vehicle treated rabbits. After NO synthase inhibition the rate of fall in SBP of 0.34 +/- 0.07 mmHg/min was not significantly different from that in the vehicle group (P = 0.3). 5. Blockade of NO synthesis did not alter the renal blood flow, renal vascular resistance changes and pressure-related natriuresis and diuresis responses to increased RPP to 125 mmHg. 6. PAF receptor blockade, using WEB 2086 (0.5 mg/kg plus 0.5 mg/kg/h), did not alter the systemic, renal haemodynamic or urinary responses to increasing renal perfusion pressure to 125 mmHg. 7. These findings indicate that neither NO nor PAF play an important role in the blood pressure lowering activity, intrarenal haemodynamics and urinary excretory responses observed when RPP was increased to a level within the physiological range.

Animals↗

PubMed1995

Renal medullary antihypertensive mechanisms.

1. Increasing renal perfusion pressure, using an extracorporeal circuit in rabbits and dogs, causes release from the kidney of a vasodepressor substance. 2. The hypotensive response occurs in denervated kidneys, and it is not due to platelet activating factor, nitric oxide, prostanoids or suppression of renin release. 3. In the rabbit, the pressure threshold for release of the hypotensive substance appears to be slightly above normal resting pressures. 4. The source of the hypotensive substance is medullary, since the hypotensive response to increased renal perfusion pressure is abolished in dogs and rabbits whose medullae are damaged by bromoethylamine treatment. 5. The chemical nature of the hypotensive substance remains unknown. 6. Thus the renal medulla appears to possess a hypotensive hormone, released in response to elevation of renal perfusion pressure. Many aspects of the physiology and pathology of the substance and its significance in blood pressure regulation remain to be determined.

Animals↗

PubMed1995

Regional systemic ANP differences in fetal lambs: role of coronary sinus outflow distribution.

Although it is known that the atrial natriuretic peptide (ANP) level in right ventricular (RV) blood supplying the caudal part of the fetus is greater than in left ventricular blood perfusing the cephalic part of the fetus, the extent to which any preferential passage of coronary sinus blood into the right ventricle contributes to regional differences between ANP levels in fetal cephalic and caudal arteries is unknown. To address this question, experiments were performed in eight late-gestation fetal lambs, 3-7 days after catheters were inserted into the left atrium, major arteries and veins, and coronary sinus (via the left hemiazygous vein). The plasma ANP level in the abdominal aorta (171 +/- 33 pg/ml) was higher than in the carotid artery (103 +/- 15 pg/ml; P < 0.05), and both were lower than in the coronary sinus (736 +/- 89 pg/ml; P < 0.005). The coronary sinus outflow, measured with radioactive microspheres injected into the hemiazygous vein, was preferentially distributed to the right ventricle (94.7 +/- 1.3%) and thence to the abdominal aorta (89.5 +/- 1.6%). This streaming of the coronary sinus outflow contributed 13.3 +/- 0.9 and 1.4 +/- 0.4 pg/ml to ANP levels in the abdominal aorta and carotid artery, respectively, and thereby accounted for 11.9 +/- 0.9 pg/ml of the abdominal aorta-carotid artery ANP difference of 68 +/- 25 pg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Effects of exercise on aspects of visual function.

Strenuous exercise has been reported to affect various aspects of visual and ocular function. In the first of two experiments, the effects of cycling, jogging and stair running on a range of visual functions were examined. None of these forms of exercise was found to have any significant effect on visual acuity, refractive error, dark focus, amplitude of accommodation or pupil size. Contrast sensitivity (CS), measured by an ascending method of limits (AML), was found to improve significantly after cycling and jogging but not after stair running. To investigate if the apparent improvement in CS was related to a change in 'sensitivity' or a change in decision criteria, CS was re-measured before and after cycling using both the AML and a 'criterion-free' method of constant stimuli (MOCS) procedure. Results obtained using the AML, confirmed the findings of the first experiment. However, results obtained using the MOCS procedure showed no significant change with exercise. This suggests that the improvement in CS found using the AML was due to a shift in subjects' decision criteria rather than a physiological change in 'sensitivity'. It is argued that this change in decision criteria may be related to the positive mood changes which have been found to occur after exercise. This study demonstrates the importance of differentiating between changes in 'sensitivity' and changes in decision criteria especially where mood or motivation (and hence decision criteria) may be confounded with the independent variable. This is particularly important when evaluating the effects of exercise on visual function or evaluating the efficacy of vision training.

Accommodation, Ocular↗

PubMed1994

Exercise does not increase visual field sensitivity.

The effect of exercise on visual field sensitivity was investigated for both static and kinetic visual fields using the Humphrey Field Analyser (HFA). The visual fields of 20 young visually normal subjects were measured before and after a 10-min controlled period of exercise. Ten of these 20 subjects then formed a control group, where the same experimental regime was followed without the exercise period. A significant increase in mean static sensitivity in the superior field was found as a result of exercise; however, this is likely to be a learning effect as a similar increase was also found for the control condition. Exercise had no other effect on either the kinetic or static visual fields.

Adult↗

PubMed1994

Nonuniform enhancement of baroreflex sensitivity by atrial natriuretic peptide in conscious rats and dogs.

The influence of atrial natriuretic peptide (ANP) on the blood pressure (BP)-heart rate (HR) baroreflex was studied in conscious chronically instrumented dogs and rats. In both species, sigmoid steady-state baroreflex curves were constructed from the baroreflex changes in HR to alternating slow injections of vasopressor and vasodepressor drugs. When this method was used in dogs, ANP caused a small but significant (P < 0.05) enhancement of the sensitivity (22 +/- 10%) and curvature (26 +/- 10%) of the baroreflex, which was without a change in HR range. In rats, ANP had no significant effect on any baroreflex parameter derived from steady-state curves. By contrast, in the same rats, fast reflex HR responses to rapid increases in BP (ramp) exposed a substantial (81 +/- 21%) ANP-induced enhancement of baroreflex sensitivity. Contribution from arterial vs. nonarterial afferents to the baroreflex is not uniform between these two techniques (steady state reflects largely arterial baroreceptor input, ramp evokes a greater proportion of cardiopulmonary afferent activation). The present study demonstrated that baroreceptor HR reflex responses to ANP depend on the baroreflex techniques employed and probably exposed a selectivity by ANP for nonarterial baroreflex pathways.

Animals↗