Whether nitric oxide is implicated in the contractile function of isolated cardiac ventricular myocytes forms the major part of the work of this thesis. Contracting guinea-pig cardiac myocytes were studied in isolation <I>in vitro</I> using a videomicroscopy length detection system. Studies are presented which establish that nitric oxide attenuates contractility of cardiac ventricular myocytes, both when it is derived from exogenous sources, and when nitric oxide is released from adjacent endothelium in coculture with cardiac myocytes. The coronary microcirculation is in close proximity to cardiac myocytes within the myocardium, thus endothelium-derived nitric oxide may have an important tonic effect on myocardial contractility. This may be particularly important when the diffusing distance from endothelial cell to myocyte is altered in disease states. Myocardial contractility is impaired in endotoxic shock. The hypothesis that this is caused by production of nitric oxide within cardiac myocytes is examined. A model of endotoxic shock was developed. Contractility of cardiac myocytes was substantially impaired. Much of this impairment was caused by nitric oxide production within the cardiac myocytes themselves. Inhibition of nitric oxide synthesis in these cells restored contractility towards normal. Healthy myocytes did not produce effective amounts of nitric oxide. Induction of nitric oxide synthase activity within cardiac myocytes may account for much of the depressed contractility of endotoxic heart failure. Myocardial contractility is impaired following ischaemia-reperfusion. Experiments examining myocyte behaviour in this situation are discussed, but whether activation of nitric oxide synthase contributes to the impaired contractility of myocytes following ischaemia is not established.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:641881 |
| Date | January 1994 |
| Creators | Brady, Adrian J. B. |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/20215 |
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