Ridley, Paul Damien;
(1991)
Anions and arrhythmias in experimental heart disease.
Doctoral thesis (M.D), UCL (University College London).
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Abstract
Ischaemic heart disease can cause sudden cardiac death from ventricular arrhythmias occuring as a consequence of ischaemia itself, or as a consequence of subsequent reperfusion of ischaemic tissue. Current agents designed to prevent these arrhythmias do not provide adequate protection. Conventionally, antiarrhythmic agents are subdivided into four classes on the basis of actions on 3-adrenoceptors, or on membrane currents carried by cations. We have explored the modulation of anions as a possible new approach to the prevention of sudden cardiac death. Using an isolated rat heart model, we showed that substitution of the chloride anion by nitrate protects against ischaemia- and reperfusion-induced arrhythmias in a concentration-dependent manner without deleterious haemodynamic consequences. Studies of the site of action demonstrated that (i) protection against ischaemia-induced VF resulted largely from an action in the ischaemic zone, and (ii) protection against reperfusion-induced VF resulted principally from an action occurring during reperfusion and within the reperfused tissue. Significant reductions in ventricular arrhythmias were produced by anions with membrane permeabilities greater than chloride and the 'anion, methylsulphate, which is less permeable than chloride was proarrhythmic. These findings strongly support the hypothesis that altered membrane permeability may contribute to the antiarrhythmic activity of some anion surrogates. In conclusion, anions appear to play a hitherto unrecognized role in arrhythmogenesis in ischaemia and reperfusion. Their manipulation represents a novel target for antiarrhythmic agents.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D |
| Title: | Anions and arrhythmias in experimental heart disease |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by ProQuest. |
| Keywords: | Health and environmental sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10120952 |
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