ABSTRACT
BACKGROUND: The Clamshell Septal Occluder has been used to close various congenital heart defects. The purpose of this study was to evaluate the long-term biological response to this device after placement in the canine heart. Previous in vivo studies with device placement were limited to 60 days. METHODS AND RESULTS: An atrial septal defect was created in dogs by blade septostomy followed by balloon dilation. Both old and new (redesigned) devices were placed. Angiographic follow-up was performed at 1, 3, and 6 months and 1 and 2 years after device placement with groups of dogs euthanitized at the same intervals. Gross and microscopic assessment was done on the explanted devices. The implants were covered at least 50% by neointima at 1 month and covered completely by 3 months. There was no thrombus formation. Areas of focal hemorrhage were evident at 1 month and were not present at 3 months. The fibrous capsule that covered the device became more densely organized and neovascularized by 2 years. A focal foreign body reaction at the device-tissue interface persisted for 2 years. There were no arm fractures with either the old or new devices in these dogs. CONCLUSIONS: The Bard Clamshell Septal Occluder is well tolerated in the canine heart for at least 2 years and elicits a normal healing process.
Subject(s)
Foreign-Body Reaction/pathology , Heart Septal Defects, Atrial/surgery , Prostheses and Implants , Wound Healing , Animals , Dogs , Fibrosis , Hemorrhage/pathology , Prosthesis Design , Prosthesis FailureABSTRACT
The percutaneous absorption and disposition of iodochlorhydroxyquin (5-chloro-7-iodo-8-quinolinol; I) from a 3% cream were studied in five dogs over a 28-d topical treatment period. Plasma levels, determined by HPLC, were 0.275-0.525 microgram/mL. The steady-state elimination rate of total I in urine was 2.4-3.0 mg/d. The apparent elimination rate constant and half-life were 0.25 +/- 0.05 d-1 and 3.1 +/- 0.5 d, respectively. Greater than 50% of topically applied I was absorbed over 16 h. Occlusion of the skin without the drug indicated that the skin acted as a reservoir for the drug. Feces analysis for iodochlorhydroxyquin from one dog showed that 27.1 +/- 8.5 mg/d was eliminated via this route. Tissue levels of I 15 d after the 28-d topical treatment were 0.7 microgram/g of liver, 0.2 microgram/g of kidney, and 0.8 microgram/g of mesenteric fat. The apparent rate constants of plasma level decline after a 100-mg iv bolus dose of I were alpha = 3.9 h-1 and beta = 0.6 h-1. The urinary elimination after intravenous administration was biphasic. The rate constant for the slow elimination phase was 0.4 +/- 0.1 d-1, and the half-life was 2.0 +/- 0.5 d. The primary neurological symptoms observed during topical treatment were ataxia and hind limb paralysis. Microscopic examination revealed liver necrosis. A weight loss of 15.3 +/- 2.7% was also observed over the 28-d topical treatment period. The results indicate that significant percutaneous absorption of I occurs, and that chronic high-dose topical treatment may lead to toxicity.
Subject(s)
Clioquinol/metabolism , Hydroxyquinolines/metabolism , Skin Absorption , Adipose Tissue/metabolism , Animals , Body Weight/drug effects , Clioquinol/blood , Clioquinol/toxicity , Dogs , Half-Life , Kidney/metabolism , Kinetics , Liver/metabolism , Male , Time Factors , Tissue DistributionABSTRACT
Changes in total and regional left coronary blood flow in response to ventriculography were studied using electromagnetic and microsphere techniques. Correlation of coronary flows by these methods showed excellent agreement (r = 0.947). Ventriculography produced a characteristic triphasic response in total flow and in endocardial/epicardial perfusion ratios. Changes in coronary flow can be explained as a result of hypotension and vasodilatation.
