Why the study?
Does myocardial noradrenaline depletion via reserpine or immunosympathectomy alter the positive inotropic effect or toxicity of ouabain in animal models?
Does myocardial noradrenaline depletion via reserpine or immunosympathectomy alter the positive inotropic effect or toxicity of ouabain in animal models?
The positive inotropic effect of ouabain is not mediated by myocardial noradrenaline release, though noradrenaline depletion may reduce ouabain toxicity in heart failure.
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Noradrenaline depletion does not blunt ouabain inotropy in feline HF models; leaves open any clinical relevance for digitalis safety.
A possible relationship between myocardial noradrenaline and the cardiac effects of ouabain has been investigated. Pretreatment with reserpine, with or without acute adrenalectomy, failed to reduce the positive inotropic effect of ouabain in cats. Similarly, reserpine did not reduce the positive inotropic effect of ouabain in cats which had developed congestive heart failure from chronic pulmonary artery stenosis and which had approximately 40% of the normal amount of myocardial noradrenaline. The positive inotropic effect of ouabain on isolated papillary muscles from reserpine-treated rabbits and on the isolated left atria from reserpine-treated rats or rats with immunosympathectomy was also normal. Depletion of myocardial noradrenaline did not influence the toxicity of ouabain except in cats with congestive heart failure. In these cats, pretreatment with reserpine increased the arrhythmic and the lethal dose of ouabain. Reserpine or immunosympathectomy produced a marked depletion of myocardial noradrenaline stores. It is concluded that the positive inotropic effect of ouabain is not due to a release of noradrenaline from the heart. The mechanism by which pretreatment with reserpine reduces the toxicity of ouabain in cats with congestive heart failure is not clear. It may or may not be due to a depletion of myocardial noradrenaline.
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Wendlandt et al. (1967) studied this question.
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