Diagnosing pulmonary embolism.
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Heparin↗
Biomedical subjects
W A Seed
Publications and source records attributed to W A Seed.
Effect of adrenaline on cardiac force-interval relationship.
OBJECTIVE: The aim was to test the hypothesis that adrenaline affects the force-interval processes. METHODS: The force-interval processes were studied in eight guinea pig papillary muscles (isometric force) and five anaesthetised dogs with atrioventricular block (maximum rate of rise of left ventricular pressure, LVdP/dtmax). The contractility indices were measured during pacing sequences in which a steady state was interrupted after a variable interval by a premature beat followed by an immediate return to the steady state. RESULTS: The relationship between contractility of the premature beat and the preceding interstimulus interval displays an approximately monoexponential initial rising phase, ie, mechanical restitution. With increasing adrenaline dosage in the isolated preparation there was always a significant increase in the force, and in its rate of rise with interval in some cases. Adrenaline had a variable accelerating effect on the time course of this mechanical restitution in isolated papillary muscles, but no effect in the dog preparation. In the isolated preparation adrenaline also slowed the decay in potentiation of the two beats immediately following the premature contraction. A slope of the relationship between the contractility of the second potentiated beat and that of the first was thus increased. This difference was not apparent in the intact preparation. CONCLUSIONS: The speeding up of mechanical restitution by adrenaline may be interpreted as reflecting the time course of reavailability of contractile activator. The slope of the relationship of contractility to that of the previous beat during the decay of postextrasystolic potentiation may be interpreted as the recirculation fraction of contractile activator; this is increased by adrenaline. However, in addition, adrenaline exerts an inotropic effect by another mechanism.
Animals↗
Mechanical restitution during alternans in guinea pig papillary muscles.
OBJECTIVE: The aim was to investigate alternate acceleration and retardation of mechanical restitution as a possible mechanism for mechanical alternans in isolated myocardium. METHODS: Mechanical alternans was induced in papillary muscles from the right ventricles of 11 guinea pigs (200-300 g) by rapid pacing under hypothermic conditions (T = 27 degrees C). Mechanical restitution curves were constructed by measuring the force responses to stimuli applied following variable test intervals during steady state pacing. Curves were obtained under control conditions (steady state stimulation interval 3 s), and for the beats following the large and small contractions during mechanical alternans. Monoexponentials were fitted to the restitution curves. RESULTS: The mean rate constant for restitution following the large beat in alternans was found to be slightly but significantly smaller than that following the small. Both rate constants obtained during alternans were significantly larger than the control rate constant (restitution was faster in alternans). In addition, as the alternation widened, the restitution curve of the beat following the small contraction developed a higher plateau than that following the large. CONCLUSIONS: The results confirm that the small beat in alternans is followed by faster restitution than the large. This alone is insufficient to explain the observed extent of alternans. The restitution curve for the beat following the small contraction must also rise to a higher plateau. Both the amount of calcium available for intracellular release and the rate at which it is made available vary from beat to beat.
Animals↗
Postextrasystolic potentiation and its contribution to the beat-to-beat variation of the pulse during atrial fibrillation.
BACKGROUND: Beat-to-beat variations in the pulse during atrial fibrillation (AF) have conventionally been attributed to time-dependent changes in filling. We have explored the possibility that they are dependent on the intrinsic myocardial interval force relation. METHODS AND RESULTS: Left ventricular (LV) contractility (maximum rate of rise of pressure, LV dP/dtmax) and ascending aortic blood velocity were measured during cardiac catheterization in 15 patients with AF. Beats preceded by an interval of less than 500 msec were excluded from analysis to reduce the confounding influence of incomplete mechanical restitution. The LV dP/dtmax was then related to the prepreceding interval. An inverse relation consistent with postextrasystolic potentiation was obtained in all 15 patients (Spearman's rank correlations, -0.56 to -0.86; p less than or equal to 0.0001). This relation was confirmed in three patients during pacing that overrode the AF and introduced single-interval variations into steady-state pacing. The ECG sequences from six of the AF patients were used to drive isometrically contracting guinea pig papillary muscle and human right ventricular tissue (n = 7); the same inverse relation was demonstrated. On a beat-by-beat basis, the maximum rate of rise of force in the isolated muscle correlated well with LV dP/dtmax in the patients (r = 0.50-0.86, p less than or equal to 0.0001). The relation of the integral of aortic velocity (AVI, proportional to stroke volume) to prepreceding interval was also inverse, whereas important correlations were demonstrated between LV dP/dtmax and AVI (Spearman's rank correlations, 0.27-0.95; p less than or equal to 0.0001). CONCLUSIONS: This study demonstrates that postextrasystolic potentiation contributes to the characteristic beat-to-beat variation of the pulse in AF.
Aged↗
The anatomy of radioisotope lung scanning.
An appreciation of the appearances of segmental and lobar defects on a lung scan is important for the diagnosis of pulmonary embolism. The appearances of segmental and lobar ventilation defects of known anatomical location have been examined on 81mKr ventilation scans in normal human subjects, utilizing fibreoptic bronchoscopy to place temporary occlusions under direct vision at the orifices of lobar and segmental bronchi. Scans were obtained in the posterior, posterior-oblique and lateral projections. Anterior views were included if the defects could not be adequately visualized on the other views. The completeness of the occlusion and the site and size of each defect could be confirmed by ventilating the segment itself with 81mKr via the balloon catheter while the occlusion was maintained. Segmental defects located anterior to the hilum of the lung tended to be optimally visualized on the lateral view and defects located posterior to the hilum tended to be optimally visualized on the posterior-oblique view. The size of segmental defects could be underestimated on the lung scan, especially those involving the anterior and lateral basal segments of both lower lobes. Defects involving the medial basal segment of the right lower lobe were undetectable on any view. By implication, the same conclusions apply to 99mTc perfusion scans.
Adult↗
Reference values and prediction equations for normal lung function in a non-smoking white urban population.
Prediction equations for normal lung function have been derived from tests on 179 healthy, non-smoking, white urban dwellers. The subjects, 96 women (height 1.46-1.77 m) and 83 men (height 1.61-1.96 m) aged 18-86 years, underwent measurements of spirometric flow and volume, multi-breath helium dilution lung volumes, and single breath carbon monoxide transfer factor and the single breath nitrogen washout test. Regression analysis using height, age, and weight as independent variables was used to provide predicted values for both sexes. Correlation coefficients were similar to those found in previous studies but normal ranges for spirometic measurements were narrower than in many previous studies, and spirometric flow and volume measurements were higher than those obtained in studies that included cigarette smokers, reflecting our more stringent criteria for selecting subjects and the newer standardised technical methods adopted. Multi-breath helium dilution values for total lung capacity were similar to those found in previous studies but the inspiratory vital capacity was larger and the residual volume reduced. Values for carbon monoxide transfer factor and the single breath nitrogen washout did not differ significantly from existing values. A complete set of lung function reference values and prediction equations for both sexes has been derived from a single population. The exclusion of cigarette smokers and subjects with respiratory symptoms has produced values that should have a greater sensitivity in the detection of mild lung disease.
Adolescent↗
Multi-breath and single breath helium dilution lung volumes as a test of airway obstruction.
Total lung capacity (TLC) and residual volume (RV) measurements derived from multi-breath and single breath helium dilution methods were combined to produce four indices of gas mixing: single breath volume/multi-breath volume ratio (TLCr, RVr) or multi-breath volume minus single breath volume difference (TLCd, RVd). The reproducibility of these indices and their sensitivity and specificity in discriminating between normal subjects and those with mild asthma and severe chronic obstructive pulmonary disease (COPD) was assessed. The total lung capacity ratio (TLCr) was the superior variable overall, providing a single range for both sexes with a specificity and sensitivity similar to that of the forced expiratory volume in one second (FEV1) in the diagnosis of airflow obstruction. Despite the similar sensitivity, correlation between TLCr and FEV1 was only moderate (r = 0.56). This may reflect greater influence of peripheral rather than central airflow obstruction on TLCr. Combining both tests improved sensitivity in the detection of airways obstruction in the asthmatic and COPD groups studied.
Adult↗
Effect of inhaled methacholine on gas mixing efficiency.
1. Pulmonary function tests, including alveolar mixing efficiency by the single-breath and multi-breath methods, and ventilation scans were performed on 16 volunteer subjects. The tests were repeated after the inhalation of a methacholine aerosol in sufficient dosage to increase airways resistance. 2. After inhalation of methacholine there was a significant fall in mean series dead space of 31 ml (P less than 0.05), and mean multi-breath alveolar mixing efficiency fell from 68% to 36% (P less than 0.001), a fall occurring in all subjects. Mean single-breath alveolar mixing efficiency measured on the first breath of the nitrogen washout fell from 76% to 70%, but this change did not reach statistical significance (0.1 greater than P greater than 0.05). 3. In eight of the subjects, technically adequate lung scans and pulmonary function tests were obtained both before and not more than 30 min after methacholine inhalation. In seven there were obvious visible defects on the ventilation scans, and in five of these the computer-calculated underventilation score became abnormal. 4. Thus inhalation of methacholine causes maldistribution of ventilation, a fall in alveolar mixing efficiency and a fall in series dead space, presumably brought about by bronchoconstriction. The parallel component of this maldistribution of ventilation, as judged by 81mKr ventilation scanning, does not of itself seem to be sufficient to explain the fall in alveolar mixing efficiency, and therefore a degree of diffusion limitation is probably involved as well.
Administration, Inhalation↗
Review: Relation between beat interval and force of the heartbeat and its clinical implications.
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Animals↗
Blood flow patterns in the human aorta studied by magnetic resonance.
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Aorta↗
Clinical features and therapy of acute thallium poisoning.
Severe acute thallium poisoning in a young man is described. He presented with transient loss of consciousness and paraesthesiae of finger tips and lips, with a blood thallium concentration of 5750 micrograms/l (levels above 200 micrograms/l are toxic). He rapidly lost limb sensation and power and later required temporary mechanical ventilation and nasogastric feeding. The neurological sequelae one year afterwards are a flaccid paraparesis, cerebellar ataxia and mental impairment. Immediate cardiovascular complications included hypertension, sinus tachycardia, ECG abnormalities and an episode of ventricular fibrillation. We were able to assess the relative merits of different methods advocated for enhancing thallium excretion. Oral Prussian blue, forced diuresis and haemodialysis were found to be the most effective: 2000 mg of thallium were eliminated over 20 days, 820 mg over 46 days and 225 mg over 25 days respectively by these methods. Haemofiltration was ineffective. Diethyldithiocarbamate, a chelating agent, brought about a rise in serum thallium concentration accompanied by clinical deterioration and its use should be abandoned.
Acute Disease↗
Relation of human cardiac action potential duration to the interval between beats: implications for the validity of rate corrected QT interval (QTc).
Fourteen patients undergoing routine cardiac catheterisation were paced at a steady frequency; after this test, stimuli were introduced with a variable preceding interval (test pulse interval). The QT interval of the electrocardiogram and the duration of the monophasic action potential of the right ventricle were measured. QT interval is a function of action potential duration; the two variables were very closely correlated in this study. Both these variables increased in duration with increasing test pulse interval. A biphasic response, as previously reported, was not seen. An increase in steady state pacing frequency caused QT interval and action potential duration to decrease for any given R-R interval. When frequency of stimulation was suddenly increased and then maintained, there was an immediate action potential shortening followed by a further more gradual shortening occurring over several minutes. These results imply that a simple correction of QT interval for heart rate (QTc) is inadequate. It is concluded that the relation between action potential duration (or QT interval) and heart rate depends on both the instantaneous interval between beats and the duration of the prevailing heart rate.
Action Potentials↗
Lung scan abnormalities in asthma and their correlation with lung function.
We have used asthma as a model of airways disease to test how well an automated, quantitative method of analysis of lung scans correlates with physiological measurements of disturbed lung function and gas exchange. We studies 25 asthmatics (age 16-73) of widely differing severity (forced expiratory volume in 1-s (FEV1) 22%-123% of predicted value), who had airways tests, arterial blood gas analysis, and krypton-technetium lung scans within a short time of each other. In all patients with airways obstruction and in some with normal function during remission, scans showed the typical appearances of multiple defects of ventilation and perfusion. The severity of ventilation defects was computed from the posterior view of the krypton scan compared to an age- and sex-matched normal range to yield an underventilation score. This correlated closely with the severity of airways obstruction as measured by forced expiratory manoeuvres. Ventilation and perfusion defects were usually imperfectly matched; the severity of this was computed using a subtraction method applied to the counts on the posterior krypton and technetium scans. The degree of mismatch was inversely related to the arterial partial pressure of oxygen (r = -0.86). The results suggest that computer scan analysis can provide useful functional information about the lung in airways disease.
Adolescent↗
Interpretation of negative results in fine needle aspiration of discrete pulmonary lesions.
A retrospective analysis was carried out on a consecutive series of 181 percutaneous fine needle aspiration biopsies of discrete pulmonary lesions, in which the outcome was established in 95%. In primary bronchial carcinoma the technique had a sensitivity of 86%. There was no relationship between the size, location, or radiological appearance of the lesion and the incidence of false negative results. The principal reason for failure to diagnose malignancy was inadequacy of the material provided for cytological examination. For metastatic neoplasms of non-bronchial origin the procedure had a sensitivity of 42% and a significantly greater false negative rate than for primary bronchial malignancy. For the entire series 72 (40%) of the procedures failed to produce a definite diagnosis, 29 (40%) of these cases subsequently proving to be malignant. A positive diagnosis was established in only 16% of patients with benign conditions. Review of published reports and consideration of the role of this and other biopsy techniques in the investigation of discrete pulmonary lesions lead to the conclusion that needle aspiration biopsy seems particularly appropriate in the investigation of inoperable patients with probable bronchial carcinoma in whom sputum cytology and bronchoscopy do not yield a diagnosis.
Biopsy, Needle↗
Computer analysis of ventilation-perfusion scans for detection and assessment of lung disease.
A previously reported computer analysis has been used to provide numerical ventilation-perfusion lung scan data, for comparison with tests of airways function and results of arterial blood gas analysis in 11 patients with pulmonary embolism, 18 with asthma, and 37 with chronic obstructive lung disease. In pulmonary embolism an index of underperfusion showed high sensitivity, and an index of ventilation-perfusion mismatching correlated well with severity (hypoxaemia). In asthma an index of underventilation was sensitive and correlated well with severity of airways obstruction. In chronic obstructive lung disease the same index was sensitive but correlated poorly with severity. This was attributed to heterogeneity of the lung disease (airways obstruction plus emphysema) in chronic obstructive lung disease. Ventilation-perfusion mismatching was frequently present in airways disease, and was often of great severity in chronic obstructive lung disease. Discrimination between pulmonary embolism and either type of airways disease was possible by using a combination of underfusion and underventilation indices. The technique offers the prospect of increasing the information derived from lung scans and of automating the reporting of scans.
Adult↗
Observations on the mechanism of hypoxaemia in acute minor pulmonary embolism.
An automated computer analysis of ventilation-perfusion lung scans was used to derive graphical data from lung scans of 11 patients with acute minor pulmonary embolism, free of pre-existing cardiorespiratory disease, and with no evidence of intrapulmonary complication or pleural effusion. In each case the analysis showed the presence of areas of lung, remote from those affected by the pulmonary embolism, that had a pathological disturbance of ventilation-perfusion matching with relative overperfusion. Such a disturbance would cause hypoxaemia. When the extent of the mismatching was calculated in terms of relative blood flow and alveolar ventilation it correlated well with the degree of arterial hypoxaemia. It is proposed that in acute minor pulmonary embolism the development of ventilation-perfusion mismatching in areas of lung unaffected by the embolic event may be an important mechanism of hypoxaemia.
Acute Disease↗
Relationships between beat-to-beat interval and the strength of contraction in the healthy and diseased human heart.
Twenty-six adult patients, classified by clinical and catheter criteria into groups of those with normal and abnormal left ventricular function, were studied during cardiac catheterization. Right heart pacing was established, and left ventricular dP/dt was measured with end-catheter manometers. By varying the interval preceding a test beat after periods of steady pacing it was confirmed that recovery of left ventricular mechanical function (maximum dP/dt) occurs approximately 800 msec (optimum interval) after a beat. The augmentation of maximum dP/dt of the first 2 beats after an extrasystole, each spaced at the optimum interval, was also studied; the amount of potentiation was varied by alterations in extrasystolic interval. Potentiation decayed from the first to the second postextrasystolic beat with a ratio that was fixed in each individual patient. The ratio (recirculation fraction) was higher in patients with normal than in those with abnormal left ventricular function (mean +/- SD 0.52 +/- 0.10 vs 0.37 +/- 0.11, p less than .005). There was an inverse relationship between this ratio and the degree of potentiation of the first postextrasystolic beat (r = .80, p less than .001). We postulate a disturbance of excitation-contraction coupling mechanisms to explain these effects.
Adult↗
An automated quantitative analysis of ventilation-perfusion lung scintigrams.
We have devised an automated computer analysis of ventilation (Kr-8 1m) and perfusion (Tc-99m) lung images that produces a graphical image of the distribution of ventilation and perfusion, and of ventilation-perfusion ratios. The analysis has overcome the following problems: the identification of the midline between two lungs and the lung boundaries, the exclusion of extrapulmonary radioactivity, the superimposition of lung images of different sizes, and the format for presentation of the data. Therefore, lung images of different sizes and shapes may be compared with each other. The analysis has been used to develop normal ranges from 55 volunteers. Comparison of younger and older age groups of men and women show small but significant differences in the distribution of ventilation and perfusion, but no differences in ventilation-perfusion ratios. Examples are presented to demonstrate that the technique can discriminate between normal and abnormal scintigrams. The analysis of serial images from one individual shows high reproducibility.
Adult↗