A thin cardiac muscle preparation of rat (ventricular trabeculae) was used in the two studies described in this Thesis. First, I investigated the mechanisms by which volatile anaesthetics decrease cardiac contractility using trabeculae loaded with a fluorescent Ca2+ indicator. Second, I employed confocal laser scanning microscopy to determine the three-dimensional microstructure of perimysial collagen fibres over the range of sarcomere lengths (1.9 - 2.3 µm) in which passive force increases steeply. The volatile anaesthetics halothane (0.23 – 3 %) and isoflurane (0.48 - 4%) produced dose-dependent decreases in the amplitudes of the intracellular Ca2+ transients and twitch force. They also produced changes in cellular autofluorescence, consistent with an increase in the concentration of the reduced forms of nicotinamide adenine nucleotides and flavoproteins. When the fluorescent Ca2+ indicator signals were corrected for changes in cellular autofluorescence, the volatile anaesthetics did not significantly change diastolic [Ca2+]. In the presence of halothane or isoflurane, restoration of Ca2+ transients to control levels, achieved by elevation of external [Ca2+], did not restore peak force. Moreover, maximal Ca2+-activated force, elicited using ryanodine tetani, was reduced by halothane and isoflurane. Thus, the negative inotropic actions of halothane and isoflurane in cardiac muscle reflect both reduced availability of Ca2+ and decreased responsiveness of the contractile system to Ca2+. Reconstructed three-dimensional images showed that perimysial collagen fibres are wavy (as distinct from coiled) cords which straighten considerably as sarcomere length is increased from ~1.85 µm (near-resting length) to ~2.3 µm. These observations are consistent with the notion that the straightening of these fibres is responsible for limiting cardiac sarcomere length to ~2.3 µm.
| Identifer | oai:union.ndltd.org:ADTP/275469 |
| Date | January 1999 |
| Creators | Hanley, Peter John |
| Publisher | ResearchSpace@Auckland |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated., http://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm, Copyright: The author |
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