DIGITALIS AND THE AILING HEART

Comments on 4 recent examples of digitalis research The development of glycoside radioimmunoassay has provided for the first time an accurate means of measuring digitalis serum levels, which has led to considerable study, and insight, into the pharmacology of digoxin. Four recent studies highlight some of the advances being made.

It has been shown that in patients with sinus node dysfunction, digitalis does not exert negative chronotropic effects, nor does it further prolong sinus node recovery time. This has been confirmed by Reiffel, lA. et al. [American Journal o/Cardiology 43: 983 (May 1979)] who have further shown, however, that in the absence of parasympathetic function (vagal blockade by atropine) digoxin does slow heart rate and prolong sinus node recovery time in these patients. It appears to be a direct effect of the glycoside, rather than an antiadrenergic action. However the effect seems limited to the sick sinus syndrome only and may have limited clinical relevance. An IV trial of digoxin prior to long term therapy, as advocated by the authors, does not seem warranted, and routine digoxin, it would seem, can be used safely in such patients . IV nitroprusside, in congestive heart failure + myocardial infarction, alleviates elevated LV filling pressure and increases cardiac output to normal. Raabe, D.S. [American Journal 0/ Cardiology 43: 990 (May 19 79)J has shown that addition of IV digoxin results in further elevation of cardiac output and further reduction of vascular resistance without affecting LV filling pressure. However the addition of digitalis to these patients was unnecessary and potentially hazardous because the nitroprusside alone had already corrected the abnormal haemodynamics . Where the effect of nitroprusside is unsatisfactory, the infusion rate should be increased, then a cardiotonic agent (dopamine or dobutamine) added if necessary. When LV filling pressure is raised but cardiac output is normal a diuretic or long-acting nitrate is used. Digitalis is no longer an agent of first choice for this condition. In patients with chronic coronary artery disease, some with normal ventricular function and others with ventricular dysfunction, Loeb, H.S. et aJ. [American Journal a/Cardiology 43: 995 (May 1979)] showed that ouabain had a negligible effect on coronary haemodynamics, myocardial metabolism or clinical signs of ischaemia. These. findings are unexpected. In the chronic ischaemic heart group with ventricular dysfunction, digitalis should have exerted an antianginal effect, and the lack of evidence for this might well have been a result of insensitive methodology. In the final paper, Kleiman, J.H. et al. [American Journal a/Cardiology 43: /001 (May 1979)] were unable to demonstrate any major beneficial effect of digoxin on LV function and regional dyssynergy in patients with chronic coronary heart disease, in whom the heart was 'visualised' by radio-opaque markers surgically implanted in the heart wall. However other studies have shown that IV ouabain considerably improves LV function and segmental dyssynergy. Positive responses have also been seen in coronary-occluded dog hearts after IV ouabain, indicating that the acutely ischaemic heart does respond to digitalis, the positive inotropic action decreasing with increasing ischaemia. Clearly the stimulation of ventricular contractile state is dependent upon the interplay of direct and indirect cardiac and vascular effects , resulting in varying - even opposite - changes in cardiac output, peripheral vessel dynamics and myocardial oxygen consumption. Future research should:

• clarify the nature of digitalis receptors, • define the subcell contractile and toxic mechanisms, • elucidate the action of digitalis in different types of cardiac disease, • and formulate alternative therapy for management of heart failure refractory to digitalis and diuretics.

Mason. D:T. and Awan. N.A.: American Journal of Cardiology 43: 1056 (May 1979)

0156-2703/79/0526-0005 $00.50/0 \l:)ADIS Press . INPHARMA 26 May 1979 5