David Miller | University of Glasgow (original) (raw)
Papers by David Miller
British Journal of Pharmacology, 1998
Journal of Muscle Research and Cell Motility, 2012
African Journal of …, 2000
METHODS Preparation of the tissue for recording perfusion pressure. 1-2cm lengths of the proximal... more METHODS Preparation of the tissue for recording perfusion pressure. 1-2cm lengths of the proximal or distal segment of the rat tail artery were prepared for recording the perfusion pressure in vitro. Male Wistar rats (300 to 350gm) were killed by a blow on the head and ...
Cardiovascular Research, 2004
Objectives: Understanding the changed ability of cardiac myofilaments to produce pump work requir... more Objectives: Understanding the changed ability of cardiac myofilaments to produce pump work requires knowledge of kinetics of crossbridge function as well as more widely studied parameters such as Ca-sensitivity and isometric force development. We tested the hypothesis that altered crossbridge kinetics contribute to reduced myofilament work in early-stage heart failure (left ventricular dysfunction, LVD). Methods: The sinusoidal oscillation technique can yield insights into crossbridge function. Dynamic stiffness, oscillatory work and power were assessed in chemically skinned, Ca-activated trabeculae from rabbit ventricles in early-stage failure, 8 weeks after infarction induced by coronary artery ligation (LIG). Results were compared with sham-operated controls (SH). LVD was assessed by echocardiography. Results: Ca-activated force and myofilament Ca-sensitivity were not significantly altered at this early stage of LVD. In maximally Ca-activated preparations, the frequency of minimal dynamic stiffness (f min) was 23% lower in LIG. f min increases by > 80% between pCa 5.8 and 4 in SH but not in LIG. Maximal phase lead and lag angles (between length and tension) were lower in LIG at frequencies near f min , lowering oscillatory work and power. The Lissajous figures (oscillatory work loops) of imposed length vs. tension are often asymmetric near f min. The degree of asymmetry was greater in LIG. Conclusions: Reduced capacity for mechanical power, consistent with depressed haemodynamic performance in LVD hearts, is only partially attributable to crossbridge slowing; changes in the phase relationship will also contribute. These changes are not readily attributable to known alterations in contractile protein isoforms. Some deductions are drawn about which steps in the crossbridge cycle are modified in this model of LVD. Altered cardiac myocyte Ca-transients, reported to be associated with LVD, will be translated into pump work by a contractile machinery that is functionally altered, even though isometric force and myofilament Ca-sensitivity might remain near-normal at this stage.
Journal of muscle research and cell motility, Jan 15, 2018
Journal of Muscle Research and Cell Motility, 1985
Tension responses of rat ventricular trabeculae subjected to successive 'treatment... more Tension responses of rat ventricular trabeculae subjected to successive 'treatment' with EGTA and Triton X-100 are described in order to investigate the effects of chemical 'skinning' techniques. In some preparations the alkaloid saponin was also used before Triton. Ultrastructural evidence is cited that the 'EGTA-treatment' fails to render cells 'hyperpermeable', i.e. freely permeable to small ions, whereas both saponin and Triton do so. In this paper we show that contractile responses like those described previously for the 'EGTA-treated' tissue can be obtained. However, more detailed examination shows that such behaviour is quantitatively distinct from that of conventionally skinned fibres in a way that is incompatible with the notion of 'hyperpermeability'. The Ca-sensitivity after treatment with either EGTA, saponin or Triton is identical in our hands. However, this is not explained by free access of Ca (and EGTA) to the intracellular space in the EGTA-treated preparation: contractures develop with very different time courses, being fastest after Triton and only marginally slower when first exposed to saponin but a factor of five times slower after 'EGTA-treatment' alone. This applies to contractures evoked direct from Ca2+ concentration congruent to 10(-9) M to the test Ca2+ concentration at constant total buffer concentration. 'EGTA-treated' fibres develop tension when ATP or creatine phosphate (CrP) are removed from the bath. However, responses to ADP and to CrP changes persist with millimolar levels of ATP present, quite unlike the Triton-skinned muscle. Exposure to each of a variety of solutions for 24 h produce preparations showing similar behaviour: whatever the explanation for the EGTA-'skinning' phenomenon it is not dependent upon low bathing Ca2+ concentration. On the basis of the functional characteristics described here, and the structural results cited, we conclude that the cell membrane continues to function as a selective permeability barrier after 'EGTA-treatment': this treatment does not produce a model of a selectively 'skinned' cardiac cell.
Assessment & Evaluation in Higher Education, 1999
Test unreliability due to guessing in multiple-choice and true/false tests is analysed from first... more Test unreliability due to guessing in multiple-choice and true/false tests is analysed from first principles, and two new measures are described, with the intention that they should be of a sort that is easily communicated without reference to the underlying statistics. One measure is concerned with the resolution of defined levels of knowledge and the other with the probability of examinees being incorrectly ranked. How the measures decrease with both test length and number of response options per question is quantified. It is concluded that the results of many tests currently conducted are likely to be unacceptably unreliable. Procedures for increasing test reliability are discussed in a logical sequence intended to aid their understanding.
Objectives: Understanding the changed ability of cardiac myofilaments to produce pump work requir... more Objectives: Understanding the changed ability of cardiac myofilaments to produce pump work requires knowledge of kinetics of crossbridge function as well as more widely studied parameters such as Ca-sensitivity and isometric force development. We tested the hypothesis that altered crossbridge kinetics contribute to reduced myofilament work in early-stage heart failure (left ventricular dysfunction, LVD). Methods: The sinusoidal oscillation technique can yield insights into crossbridge function. Dynamic stiffness, oscillatory work and power were assessed in chemically skinned, Ca-activated trabeculae from rabbit ventricles in early-stage failure, 8 weeks after infarction induced by coronary artery ligation (LIG). Results were compared with sham-operated controls (SH). LVD was assessed by echocardiography. Results: Ca-activated force and myofilament Ca-sensitivity were not significantly altered at this early stage of LVD. In maximally Ca-activated preparations, the frequency of minimal dynamic stiffness ( f min ) was 23% lower in LIG. f min increases by > 80% between pCa 5.8 and 4 in SH but not in LIG. Maximal phase lead and lag angles (between length and tension) were lower in LIG at frequencies near f min , lowering oscillatory work and power. The Lissajous figures (oscillatory work loops) of imposed length vs. tension are often asymmetric near f min . The degree of asymmetry was greater in LIG. Conclusions: Reduced capacity for mechanical power, consistent with depressed haemodynamic performance in LVD hearts, is only partially attributable to crossbridge slowing; changes in the phase relationship will also contribute. These changes are not readily attributable to known alterations in contractile protein isoforms. Some deductions are drawn about which steps in the crossbridge cycle are modified in this model of LVD. Altered cardiac myocyte Ca-transients, reported to be associated with LVD, will be translated into pump work by a contractile machinery that is functionally altered, even though isometric force and myofilament Ca-sensitivity might remain near-normal at this stage.
British Journal of Pharmacology, 1998
Journal of Muscle Research and Cell Motility, 2012
African Journal of …, 2000
METHODS Preparation of the tissue for recording perfusion pressure. 1-2cm lengths of the proximal... more METHODS Preparation of the tissue for recording perfusion pressure. 1-2cm lengths of the proximal or distal segment of the rat tail artery were prepared for recording the perfusion pressure in vitro. Male Wistar rats (300 to 350gm) were killed by a blow on the head and ...
Cardiovascular Research, 2004
Objectives: Understanding the changed ability of cardiac myofilaments to produce pump work requir... more Objectives: Understanding the changed ability of cardiac myofilaments to produce pump work requires knowledge of kinetics of crossbridge function as well as more widely studied parameters such as Ca-sensitivity and isometric force development. We tested the hypothesis that altered crossbridge kinetics contribute to reduced myofilament work in early-stage heart failure (left ventricular dysfunction, LVD). Methods: The sinusoidal oscillation technique can yield insights into crossbridge function. Dynamic stiffness, oscillatory work and power were assessed in chemically skinned, Ca-activated trabeculae from rabbit ventricles in early-stage failure, 8 weeks after infarction induced by coronary artery ligation (LIG). Results were compared with sham-operated controls (SH). LVD was assessed by echocardiography. Results: Ca-activated force and myofilament Ca-sensitivity were not significantly altered at this early stage of LVD. In maximally Ca-activated preparations, the frequency of minimal dynamic stiffness (f min) was 23% lower in LIG. f min increases by > 80% between pCa 5.8 and 4 in SH but not in LIG. Maximal phase lead and lag angles (between length and tension) were lower in LIG at frequencies near f min , lowering oscillatory work and power. The Lissajous figures (oscillatory work loops) of imposed length vs. tension are often asymmetric near f min. The degree of asymmetry was greater in LIG. Conclusions: Reduced capacity for mechanical power, consistent with depressed haemodynamic performance in LVD hearts, is only partially attributable to crossbridge slowing; changes in the phase relationship will also contribute. These changes are not readily attributable to known alterations in contractile protein isoforms. Some deductions are drawn about which steps in the crossbridge cycle are modified in this model of LVD. Altered cardiac myocyte Ca-transients, reported to be associated with LVD, will be translated into pump work by a contractile machinery that is functionally altered, even though isometric force and myofilament Ca-sensitivity might remain near-normal at this stage.
Journal of muscle research and cell motility, Jan 15, 2018
Journal of Muscle Research and Cell Motility, 1985
Tension responses of rat ventricular trabeculae subjected to successive 'treatment... more Tension responses of rat ventricular trabeculae subjected to successive 'treatment' with EGTA and Triton X-100 are described in order to investigate the effects of chemical 'skinning' techniques. In some preparations the alkaloid saponin was also used before Triton. Ultrastructural evidence is cited that the 'EGTA-treatment' fails to render cells 'hyperpermeable', i.e. freely permeable to small ions, whereas both saponin and Triton do so. In this paper we show that contractile responses like those described previously for the 'EGTA-treated' tissue can be obtained. However, more detailed examination shows that such behaviour is quantitatively distinct from that of conventionally skinned fibres in a way that is incompatible with the notion of 'hyperpermeability'. The Ca-sensitivity after treatment with either EGTA, saponin or Triton is identical in our hands. However, this is not explained by free access of Ca (and EGTA) to the intracellular space in the EGTA-treated preparation: contractures develop with very different time courses, being fastest after Triton and only marginally slower when first exposed to saponin but a factor of five times slower after 'EGTA-treatment' alone. This applies to contractures evoked direct from Ca2+ concentration congruent to 10(-9) M to the test Ca2+ concentration at constant total buffer concentration. 'EGTA-treated' fibres develop tension when ATP or creatine phosphate (CrP) are removed from the bath. However, responses to ADP and to CrP changes persist with millimolar levels of ATP present, quite unlike the Triton-skinned muscle. Exposure to each of a variety of solutions for 24 h produce preparations showing similar behaviour: whatever the explanation for the EGTA-'skinning' phenomenon it is not dependent upon low bathing Ca2+ concentration. On the basis of the functional characteristics described here, and the structural results cited, we conclude that the cell membrane continues to function as a selective permeability barrier after 'EGTA-treatment': this treatment does not produce a model of a selectively 'skinned' cardiac cell.
Assessment & Evaluation in Higher Education, 1999
Test unreliability due to guessing in multiple-choice and true/false tests is analysed from first... more Test unreliability due to guessing in multiple-choice and true/false tests is analysed from first principles, and two new measures are described, with the intention that they should be of a sort that is easily communicated without reference to the underlying statistics. One measure is concerned with the resolution of defined levels of knowledge and the other with the probability of examinees being incorrectly ranked. How the measures decrease with both test length and number of response options per question is quantified. It is concluded that the results of many tests currently conducted are likely to be unacceptably unreliable. Procedures for increasing test reliability are discussed in a logical sequence intended to aid their understanding.
Objectives: Understanding the changed ability of cardiac myofilaments to produce pump work requir... more Objectives: Understanding the changed ability of cardiac myofilaments to produce pump work requires knowledge of kinetics of crossbridge function as well as more widely studied parameters such as Ca-sensitivity and isometric force development. We tested the hypothesis that altered crossbridge kinetics contribute to reduced myofilament work in early-stage heart failure (left ventricular dysfunction, LVD). Methods: The sinusoidal oscillation technique can yield insights into crossbridge function. Dynamic stiffness, oscillatory work and power were assessed in chemically skinned, Ca-activated trabeculae from rabbit ventricles in early-stage failure, 8 weeks after infarction induced by coronary artery ligation (LIG). Results were compared with sham-operated controls (SH). LVD was assessed by echocardiography. Results: Ca-activated force and myofilament Ca-sensitivity were not significantly altered at this early stage of LVD. In maximally Ca-activated preparations, the frequency of minimal dynamic stiffness ( f min ) was 23% lower in LIG. f min increases by > 80% between pCa 5.8 and 4 in SH but not in LIG. Maximal phase lead and lag angles (between length and tension) were lower in LIG at frequencies near f min , lowering oscillatory work and power. The Lissajous figures (oscillatory work loops) of imposed length vs. tension are often asymmetric near f min . The degree of asymmetry was greater in LIG. Conclusions: Reduced capacity for mechanical power, consistent with depressed haemodynamic performance in LVD hearts, is only partially attributable to crossbridge slowing; changes in the phase relationship will also contribute. These changes are not readily attributable to known alterations in contractile protein isoforms. Some deductions are drawn about which steps in the crossbridge cycle are modified in this model of LVD. Altered cardiac myocyte Ca-transients, reported to be associated with LVD, will be translated into pump work by a contractile machinery that is functionally altered, even though isometric force and myofilament Ca-sensitivity might remain near-normal at this stage.