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W A Seed

Publications and source records attributed to W A Seed.

At least 55 records · Page 3Linked to original sources

Cardiac action potential duration and contractility in the intact dog heart.

The maximum rate of rise of left ventricular pressure (DP) and action potential duration (a.p.d.) were measured in closed-chest anaesthetized dogs with atrioventricular dissociation and beta-adrenergic blockade. Right ventricular stimulation was carried out with protocols consisting of a conditioning 'priming' period and a test period. When a single test stimulus was introduced at varying intervals after the priming period, DP was found to be maximal at 800-1000 ms. With this single test stimulus fixed at the optimum, DP was found to be a variable inverse function of the a.p.d. of the same beat; no positive correlation could be found between DP and a.p.d. When a second test stimulus at the optimum interval was introduced after the first, the DP (DP2) was found to be strongly dependent on that elicited by the first test stimulus (DP1); the relationship was positive, linear, independent of the method used to vary DP, and independent of whether DP1 was depressed or potentiated. The slope of the relationship was less than 1.0 and the line passed through the point where DP2 = DP1; this is the point of continuous stimulation at the optimum interval in a steady state. This result is consistent with the hypothesis that the coefficient relating DP1 to DP2, at constant a.p.d. of the first test pulse (AP1), is an index of the proportion of the activator of contraction stored during relaxation of test beat 1 which is released again on beat 2. In order to test the hypothesis that the remaining contractility depended on the action potential of test beat 1, AP1 was varied by changing the intervals between the priming stimuli. In order to determine the relationship between DP2 and AP1 it was necessary to carry out multiple regression analysis because DP2 was already known to be strongly dependent on DP1 (point 3 above), i.e. DP2 = BDP(DP1) + BAP(AP1 - D). This analysis yielded highly significant positive values for the coefficients BDP and BAP. This result is compatible with the postulate that a.p.d. influences the amount of the activator of contraction entering the intracellular store, but that this activator is not available for release to the contractile proteins until the next depolarization.

Action Potentials↗

Electrical and mechanical restitution of the human heart at different rates of stimulation.

Action potential duration and contractility are reduced following premature excitations, and gradually increase as the stimulus interval is lengthened. To examine these phenomena of electrical and mechanical restitution in the human heart, we simultaneously measured action potential duration and the maximum rate of left ventricular pressure in five patients undergoing electrophysiological study. Test beats were introduced at varying intervals after the last of a series of steady state intervals. By plotting action potential duration and maximum rate of left ventricular pressure as a function of the test interval, we formed electrical and mechanical restitution curves. When the rate of steady state pacing was increased, there was a decrease in action potential duration and an increase in the maximum rate of left ventricular pressure for all test intervals; i.e., a change in pacing rate affected action potential duration and maximum rate of left ventricular pressure of test responses in a reciprocal fashion. In addition, a higher steady state pacing rate allowed action potentials and contractile responses to be elicited at shorter test intervals, thereby displacing the electrical and mechanical restitution curves to the left. The magnitude of the leftward shift of both curves corresponded closely to the shortening of the steady state action potential duration induced by the increase in pacing rate. These findings confirm for the human heart that both electrical and mechanical restitution occur after membrane repolarization, i.e., as a function of the electrical diastolic interval preceding a beat, and not the stimulus interval.

Action Potentials↗

The relationship between the strength of the human heart beat and the interval between beats.

In 15 patients undergoing cardiac catheterization and pacing tests, the left ventricular (LV) pressure and its maximum rate of rise (LV dP/dt max) were measured with catheter-tip manometers. Atrial or ventricular pacing at a single steady frequency (the priming frequency) was followed by a test pulse at a varying interval (test pulse interval). In 14 subjects in whom it was examined, the contractile response after the test pulse increased with test pulse interval to reach a maximum plateau value--the optimum contractile response (OCR). In five cases, further prolongation of the test pulse interval decreased the contractile response. The optimum test pulse interval occurred at 800-900 msec. An increase in the priming frequency before the introduction of the test pulse caused a progressive increase in OCR, in contrast to the minor effects on LV dP/dt max of the control beats. Similar results were recorded in four other patients in whom contractile response was assessed from the rate of rise of right ventricular pressure. These results indicate that with tachycardia, the interval between beats is insufficient to allow maximum contractile performance (presumed to be activated by calcium ions) to develop. The true effect of increasing heart rate is only revealed by the relationship between OCR and the preceding frequency of contraction.

Adult↗

Location of early atheroma in the human coronary arteries.

We have correlated the location of early atheroma with vessel geometry in the major coronary arteries of subjects dying of noncardiovascular causes under 40 yr of age. We analyzed only those vessels affected minimally by very early (fatty) disease. In each of the three major branches, disease was concentrated close to the entrance and diminished with distance downstream. Circumferential distribution of disease was also not random. In the right coronary artery, lesions were concentrated on the inner wall of the major curvature. Immediately downstream of the entrances of both branches of the left coronary artery, the flow-dividing walls were spared. Further downstream in the left anterior, descending branch plaques followed a spiral distribution. We believe these patterns may be determined by local mechanical factors.

Adult↗

Simultaneous recording of monophasic action potentials and contractile force from the human heart.

Cardiac monophasic action potentials (MAPs) and contractility have been simultaneously measured in man while the heart rate was being changed by right atrial pacing. A new non-suction electrode was used for safe and long-term recording of MAPs from the endomyocardium. Abrupt changes in cycle-length were followed first by a fast, then a slow response in the adaptation of MAP-duration and of contractility (LV dp/dt max) to the new steady state. After increasing the heart rate then slow phase of MAP shortening appears to be related to the slow staircase of contractility, whereas after the step decrease of frequency no such a relation could be observed. The consistency of these results with those obtained in corresponding in-vitro experiments indicates that this methodical approach may be suitable for assessing the process of E-C coupling in the human heart.

Action Potentials↗

Chronic eosinophilic pneumonia.

We described three cases of eosinophilic pneumonia of unknown aetiology investigated clinically and by lung biopsy. The illnesses lasted between six and 20 weeks and consisted of cough, dyspnoea, malaise, and in two cases prolonged pyrexia. All had blood eosinophilia and chest radiographs showing widespread bilateral shadowing; in two cases this had a characteristic peripheral distribution. One patient recovered spontaneously and the other two responded to steroids, with disappearance of pyrexia within 12 hours and radiological clearing within 14 days. Lung function tests during the acute illness showed volume restriction or gas transfer defects or both in two cases. After remission all three showed abnormalities if small airways function. Lung biopsies performed during the acute illness were examined histologically and by transmission electron microscopy, and in two cases by immunofluorescence. There was both intra-alveolar and interstitial eosinophilic pneumonia with bronchiolitis obliterans, microgranulomata, and a vasculitis. Electron microscopy showed numerous eosinophils, many degranulated, and macrophages with phagocytosed eosinophilic granules and intracytoplasmic inclusions. In one case IgM, IgG, and IgA were demonstrated in the bronchial walls and interstitium. No IgE or complement was present. We believe that eosinophil granules are responsible for the tissue damage and fever and suggest mechanisms for this and for the response to steroid therapy.

Aged↗