The influence of several calcium antagonists and antiarrhythmic drugs on digoxin kinetics and actions were investigated in 36 healthy men during digoxin steady state (0.375 mg/day). The subjects were randomly assigned to three subgroups and each group received placebo (control) and two of the following regimens (doses three times a day) in a randomized sequence for 2 wk each: verapamil (80 mg) and nifedipine (10 mg), verapamil (120 mg) and gallopamil (50 mg), or propafenone (150 mg) and quinidine (250 mg). Plasma digoxin concentration (PDC) rose during the cotreatments in the sequence: gallopamil (+16%) less than propafenone (+37%) less than nifedipine (+45%) less than verapamil (almost independent of dose, +69%) less than quinidine (+118%). These increases in PDC correlated closely to decreases in renal digoxin clearances. Renal creatinine clearance was virtually unaffected. The rise of PDC resulted in increased glycoside effects, as measured by the shortening of systolic time intervals and flattening of T wave. There was a linear correlation between PDC and changes in mean corrected electromechanical systole and T wave flattening. We conclude that, in addition to quinidine, other antiarrhythmic drugs and various calcium antagonists interact kinetically with digoxin and that the increasing PDCs are cardioactive.

OBJECTIVE -The myocardial infarction (MI) registry of the Academic Schwabing Hospital, Munich, investigates the hospital course of diabetic and nondiabetic patients with acute MI. The aim of this study was to improve quality care management and to compare hospital mortality and therapeutic approaches (i.e., PTCA, stenting, GPIIb/IIIa receptor antagonists, glucose-insulin infusion). RESULTS -In 1999, coronary angiography (P Ͻ 0.01), percutaneous transluminal coronary angioplasty (PTCA) (P Ͻ 0.001), and stenting (P Ͻ 0.001) were performed less frequently in diabetic than in nondiabetic patients. During this period, total hospital mortality (29 vs. 16%, P Ͻ 0.01) and mortality within 24 h after admission (14 vs. 5%, P ϭ 0.01) were higher in diabetic than in nondiabetic patients. In 2001, frequencies of coronary angiography, PTCA, and stenting were increased in diabetic patients (P Ͻ 0.001 vs. 1999), and the interventions were comparable with those performed in nondiabetic patients. Furthermore, glucose-insulin infusion was administered in 46% of diabetic subjects. In 2001, total hospital mortality decreased to 17% in diabetic subjects (P ϭ 0.028 vs. 1999) and mortality within 24 h after admission declined to 4% (P ϭ 0.027 vs. 1999). Logistic regression analysis revealed that an increase in the number of therapeutic approaches (also when adjusted for clinical variables) is associated with a reduction in mortality of diabetic patients with acute MI (adjusted odds ratio 0.14, P Ͻ 0.0001). RESEARCH DESIGN AND METHODSCONCLUSIONS -Intensification of multiple advanced therapeutic strategies in diabetic patients with acute MI enables a substantial reduction in hospital mortality. The enforcement leads to rates of hospital mortality that are comparable to those of nondiabetic patients.

In diabetic patients with acute myocardial infarction, early hospital mortality is increased and signs of cardiac autonomic dysfunction and microangiopathy are detected more frequently than in non-diabetic patients. The need for advanced treatment strategies early in the course of diabetic patients with myocardial infarction is emphasized.

Objective-Neurohormonal activation has major impact on the patho-

SUMMARY Plasma hyperviscosity is a striking abnormality in patients suffering from subcortical arteriosclerotic encephalopathy (SAE) and is thought to perpetuate the chronic ischaemic demyelinating process of the periventricular white matter. Ancrod, a defibrinating enzyme, was given to 10 patients with SAE in an attempt to reduce plasma fibrinogen, which would thus normalise hyperviscosity. This was paralleled by a significant improvement of the initially abnormal retinal arteriovenous passage time, as well as a significant augmentation of the C02-induced cerebral vasomotor response. This did not lead, however, to any clinical improvement with respect to performance of neuropsychological tests, recurrence of strokes during a 6 month observation period or improvement of various audiological parameters. The findings indicate that hyperviscosity in patients with SAE is merely an epiphenomenon. A potentially reversible, chronic penumbral state of the brain tissue apparently does not exist in SAE.