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Biomedical subjects

J W Dean

Publications and source records attributed to J W Dean.

29 records · Page 2Linked to original sources

Arrhythmia in heart failure: role of mechanically induced changes in electrophysiology.

Various mechanisms have been suggested to explain the high prevalence of ventricular arrhythmia in patients with heart failure, but as yet there is no unifying theory. There is growing evidence that changes in myocardial mechanical properties may directly alter cardiac electrophysiology by a process of mechanoelectric feedback. Moreover, when changes in cardiac loading similar to those seen in heart failure are produced experimentally in normal heart, there is a greater tendency to arrhythmogenesis. The intimate relation between changes in mechanical function and arrhythmia in heart failure could account for the lack of effect of most conventional antiarrhythmic drugs on arrhythmogenesis, and the beneficial effect of peripheral vasodilators. This paper argues that mechanically induced changes in electrophysiology are very important in the development of arrhythmia in cardiac failure; there may be no need to implicate other mechanisms, such as relative ischaemia, metabolic changes, or changes in sympathetic tone.

Action Potentials↗

Effect of changes in load on monophasic action potential and segment length of pig heart in situ.

There is increasing evidence that mechano-electric feedback, defined as a change in mechanical state that precedes and alters transmembrane potential, operates in a wide variety of preparations and species including man. Load reduction is becoming a common therapeutic tool in a variety of clinical settings but the electrophysiological effects of these manoeuvres is not known. In this study the effect of changes in loading conditions on the time course of ventricular repolarisation were examined in the in situ heart in 13 pigs anaesthetised with halothane. Monophasic action potentials, electrocardiograms and segment length changes were recorded from the left ventricular epicardium using suction operated devices. Afterload was decreased by intravenous infusion of sodium nitroprusside, and increased by aortic cross clamping. Infusion of sodium nitroprusside resulted in a rise in action potential duration (measured at 70% repolarisation) in all 21 infusions (mean 3.4 ms), which was linearly related to the fall in systolic left ventricular pressure (r = 0.72, p less than 0.001) and the change in minimum systolic segment length (r = 0.46, p less than 0.05), but not to the change in maximum diastolic length (r = 0.33, NS). Aortic constriction, sufficient to elevate peak systolic left ventricular pressure back to the control level, restored the changes in action potential duration to normal. In addition, there were concomitant changes in the QT interval and T wave of the epicardial ECG. These findings show that mechano-electric feedback operates in the in situ heart and has potential importance in the clinical setting where changes in systemic blood pressure may directly alter cardiac electrophysiology.

Action Potentials↗

Lectins inhibit cell binding and spreading on a laminin substrate.

This study examined the effects on cell binding and spreading of the exposure of laminin substrates to the lectins Wheat Germ Agglutinin or Concanavalin A. Exposure of laminin to Wheat Germ Agglutinin inhibited binding of mouse B16 F1 melanoma cells in a dose dependent manner. Exposure to Concanavalin A had no deleterious effects on binding but did inhibit cell spreading. Both effects were completely prevented by the specific sugars for each lectin. These effects may be due to the proximity of N-linked oligosaccharides to the known cell binding sites of laminin.

Animals↗

Secretion of atrial natriuretic peptide from the heart in man.

Plasma concentrations of atrial natriuretic peptide were measured in eight patients undergoing elective cardiac catheterisation and angiography. All patients had normal resting pressures in the cardiac chambers and no clinical evidence of heart failure. Plasma atrial natriuretic peptide rose significantly from the superior vena cava into the right atrium and right ventricle. The increase into the right atrium was variable, with no increase in three subjects, but there was a consistent increase in all subjects from the superior vena cava to to the right ventricle. These findings in the right atrium are probably caused by inadequate mixing and streaming of blood from the coronary sinus containing high concentrations of atrial natriuretic peptide. There was no increase in the concentration of natriuretic peptide from the pulmonary artery to the left ventricle, but the concentrations in the left ventricle were significantly higher than in the superior vena cava. These findings demonstrate that the heart secretes atrial natriuretic peptides in the absence of cardiac failure. Studies based on sampling of the right atrium will not accurately measure cardiac secretion of atrial natriuretic peptide and will therefore be likely to obscure the mechanisms responsible for regulating its secretion. The right ventricle and pulmonary artery are the best sampling sites to measure atrial natriuretic peptide release from the right atrium.

Aged↗

Exaggerated responsiveness to thyrotrophin releasing hormone: a risk factor in women with coronary artery disease.

Thyroid function tests were performed and thyroid antibodies and serum cholesterol concentrations measured in 12 women aged 60 years or under with severe coronary artery disease proved by coronary angiography. This group was compared with 11 women with normal coronary angiography. Ten out of the 12 women with coronary artery disease had an exaggerated response of thyroid stimulating hormone to thyrotrophin releasing hormone compared with two out of 11 controls (p less than 0.008). The mean serum cholesterol concentration was significantly higher in those with coronary artery disease than in the controls. Thyroid antibodies were present in four of those with coronary artery disease and one of the controls. There was no difference in the risk factors for coronary artery disease between the two groups except for cigarette smoking. Eleven out of 12 in the coronary artery disease group smoked cigarettes compared with four out of 11 in the control group (p less than 0.01). Minimal impairment of thyroid function is an important risk factor for coronary artery disease in women.

Coronary Disease↗

Beyond quality circles: self-managing teams.

A more extreme form of change than QCs, self-managing teams are informally estimated to have evolved in more than 200 U.S. plants. Indications are, however, that this is but the beginning--despite middle managers' fears that such teams will erode their power.

Group Processes↗

Fibronectin and laminin enhance gingival cell attachment to dental implant surfaces in vitro.

The objective of this study was to determine if the biologically active molecules laminin and fibronectin could influence gingival cell attachment to implant surfaces in vitro. Flat squares of the following implant materials were tested: smooth, plasma-sprayed, and hydroxyapatite-coated titanium. The surfaces were coated with equimolar quantities of either laminin, fibronectin, or bovine serum albumin. Fibronectin coating of implant surfaces resulted in two to three times the enhancement of gingival fibroblast binding on all implant surfaces tested (P < .01), with a lesser effect on epithelial cells. Laminin coating resulted in three to four times the enhancement of gingival epithelial cell binding on all implant surfaces tested (P < .01), with a lesser effect on fibroblasts. The two cell types exhibited distinct preferences for the different molecules tested with the surface roughness having some influence.

Analysis of Variance↗