Relationship between myocardial uptake and actions in heart failure of methyldigoxin.

Abstract

1 Problems have been encountered in recent years in confirming useful benefit to patients with heart failure and sinus rhythm from acute exposure to digitalis glycosides, though effectiveness of these preparations upon cardiac contractile performance is indisputable. Undesired effects such as those upon systemic vascular resistance have been invoked to explain this. 2 Detailed haemodynamic responses have been studied by cardiac catheterisation in nine such patients for 30 min after intravenous methyldigoxin infusion. Myocardial glycoside uptake was simultaneously assessed. 3 Methyldigoxin uptake by the heart was rapid, passing its peak within 20 min, and was followed by substantial elution. 4 A small progressive and significant increase in cardiac output was observed, though left ventricular filling pressures were not significantly reduced after methyldigoxin. Cardiac contractile function as assessed by left ventricular maximum dP/dt, measured in six patients, showed consistent improvement.

Myocardial Uptake of Drugs and Clinical Effects

“…Initial attempts to utilise this technique (in all cases to study various digitalis glycosides) met with only limited success, largely for technical reasons such as inadequate frequency of sampling, lack of determination of whole blood drug concentrations and drug administration via infusion rather than bolus injection (Hayward et al 1983;Marks et al 1964;Selden & Neill 1975).…”

“…Uptake of Methyldigoxin An attempt to correlate myocardial uptake of methyldigoxin and its positive inotropic actions in patients with heart failure (Hayward et al 1983) was limited by the use of a 5-minute period of drug infusion followed by drawing of arterial and coronary sinus samples 10, 20 and 30 minutes after cessation of infusion. This permitted only the detection of a phase of net drug efflux from the myocardium, suggesting that the initial net uptake phase had been of less than 15 minutes duration.…”