Augmented and sustained plasma concentrations after intramuscular injections of molecular variants and deglycosylated forms of tissue-type plasminogen activators.

We have previously explored induction of coronary thrombolysis with tissue-type plasminogen activator (t-PA) administered intramuscularly. Absorption-enhancing agents that rendered the approach feasible were identified, but large amounts of activator were required and initial elevations of concentrations in plasma could not be sustained. The present study was designed to determine whether more therapeutically favorable plasma concentrations could be induced by genetically engineering or chemically modifying t-PA to prolong its half-life based on the hypothesis that the ratio of absorption to clearance would be increased.

Intramuscular administration of human tissue-type plasminogen activator in rabbits and dogs and its implications for coronary thrombolysis.

To determine whether sustained plasma concentration of human tissue-type plasminogen activator (t-PA) can be induced promptly after intramuscular injection with enhancers of absorption devoid of deleterious local and systemic effects, we studied 250 rabbits and 13 dogs. In rabbits with t-PA injected directly into exposed muscle followed by local electrical stimulation at the site, early absorption was increased markedly by addition of 0.63M methylamine plus 0.

Asymptomatic telephone ECG transmissions as an outpatient surveillance system of ventricular arrhythmias: relationship to quantitative ambulatory ECG recordings.

Although ambulatory ECG recordings provide quantitative information in the follow-up of patients with ventricular arrhythmias, they are performed infrequently, potentially missing serious arrhythmias in the unmonitored periods. Telephone ECG systems offer "real-time" ECG information, theoretically functioning as an arrhythmia surveillance system. Thus we incorporated frequent telephone ECG transmissions in two antiarrhythmic drug protocols.

Coronary thrombolysis with facilitated absorption of intramuscularly injected tissue-type plasminogen activator.

Conventional activators of the fibrinolytic system used for coronary thrombolysis entail unavoidable delay, risk of bleeding, or both in contrast to tissue-type plasminogen activator (t-PA). Because the potential benefit of coronary thrombolysis is inversely related to the duration of antecedent ischemia, this study was performed to develop an approach for facilitated absorption of intramuscularly injected t-PA potentially adaptable for prompt, self-medication. In rabbits, absorption was markedly potentiated by hydroxylamine hydrochloride and electrical stimulation at the injection site.