Effect of verapamil on malignant tissue blood flow in SMT-2A tumor-bearing rats.
We investigated the influence of the calcium antagonist verapamil on malignant and normal tissue blood flow using 25-micrometer 113Sn-labeled microspheres. Isogeneic Wistar-Furth rats were inoculated with a metastasizing mammary gland adenocarcinoma (SMT-2A) in the hindlimb musculature and mammary gland. Verapamil was administered as an i.v. bolus via an external jugular vein catheter followed by a supplemental constant infusion with a Harvard infusion pump. Plasma verapamil levels were determined by high performance liquid chromatography, and heart rate and systemic blood pressure were monitored. Verapamil in concentrations of 100 to 200 ng/ml resulted in an approximate 50% increase in tumor blood flow compared to control levels (p less than 0.001) regardless of the site of tumor implantation. These levels were not associated with a significant alteration in arterial blood pressure. These data suggest that verapamil in concentrations currently used in humans may provide a means of improving the delivery of chemotherapeutic agents to solid neoplasms and may also enhance the effectiveness of ionizing radiation treatment by increasing tumor oxygenation.
D000230:Adenocarcinoma / Q000098:blood supply*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000097:blood / Q000494:pharmacology*
D014700:Verapamil