SBIR-STTR Award

The feasibility of retrovenous myocardial drug delivery (Xylocaine C14) to treat and control arrhythmias will be tested in the sheep after coronary artery occlusion and compared to the standard intravenous route. End points of number and type of arrhythmias, Xylocaine dose, plasma, and myocardial Xylocaine C14 concentrations will be determined. The demonstration of our hypothesis "that retrovenous myocardial drug delivery is superior to intravenous therapy after coronary artery occlusion" could provide an effective method for the treatment of ventricular arrhythmias.

Thesaurus Terms:
Drugs, Drug Delivery Systems, Heart Disorders, Arrhythmia, Heart, Myocardium, Pharmacology Study Section, Phenylamides, Lidocaine Dosage And Route, Injections, Dosage And Route, Route Of Administration, Drugs, Pharmacology, Bioavailability, Heart Disorders Chemotherapy, Heart Disorders, Coronary Occlusions And Thrombosis, Heart, Ventricles, Therapy Evaluation Mammals, Artiodactyla, Sheep, Radioisotopes, Carbon, Radiotracers

A novel retrovenous myocardial drug delivery system has been developed and Phase I feasibility demonstrated in sheep with acute LAD coronary artery occlusion. Control sheep with intravenous lidocaine therapy developed ventricular fibrillation in a mean time of 12.5 minutes after PTCA-LAD occlusion. In contrast, retrovenously treated sheep with an identical lidocaine dose and venous blood survived prolonged study periods to 3 hours despite infarction in the area-at-risk, severe ECG changes, and myocardial depression. Phase II work will determine the efficacy of combined retrovenous arterialized blood and lidocaine for prevention of arrhythmias and salvage of ischemic myocardium. A dose-response of retrovenous lidocaine after coronary artery occlusion will be obtained. Four-lumen retrovenous catheters will be fabricated and tested to evaluate our hypothesis that recirculation of therapeutic agents via the coronary sinus reduces the effective dose and thus the proarrhythmic or toxic effects of the therapeutic agents. A second hypothesis will be tested in a model of acute coronary thrombosis that retrovenous t-PA thrombolytic therapy by itself or in combination with selective arterial or intravenous therapy accelerates clot lysis and time of myocardial reperfusion. The retrovenous drive system developed during Phase I will be modified for controlled drug delivery with safeguards and alarms for Phase III clinical application.

Thesaurus Terms:
Biomedical Engineering, Instrumentation Clinically Oriented, Dosage And Route, Perfusion, Dosage And Route, Route Of Administration, Drugs, Drug Delivery Systems, Heart Disorders Chemotherapy, Heart Disorders, Coronary, Myocardial Ischemia And Hypoxia, Heart Vessels, Coronary Veins, Coronary Sinus, Therapy Evaluation, Non-Human Biomaterials, Development And Preparation Of Biomaterials, Biomedical Engineering, Medical Equipment Safety, Blood Coagulation, Plasminogen Activators, Cardiovascular Agents, Cardiotonic And Cardioprotective Drugs, Dosage And Route, Dosage, Drugs Adverse Effects, Drugs, Pharmacology, Bioavailability, Heart Disorders Chemotherapy, Fibrinolytic Therapy, Heart Disorders, Arrhythmia, Ventricular Fibrillation, Heart Disorders, Coronary Occlusions And Thrombosis, Heart Disorders, Coronary, Myocardial Infarct, Heart Prosthesis, Auxiliary, Aortic Balloon Pumping, Phenylamides, Lidocaine, Catheterization, Heart Circulation, Heart Pharmacology Animals, Chordates, Mammals, Carnivores, Dogs, Animals, Chordates, Mammals, Ungulates, Sheep, Heart Disorders Diagnosis (Incl Exams), Models, Disease Models, Heart Surgery, histopathology