Modulation of Healthy Pig Coronary Arteries by Self-Expanding Stents

Objectives: To evaluate the expansion ratio of a self-expanding stem over time, and the chronic effect of stent pressure on the vessel wall . Methods: Self-expanding stents, developed by Medtronic Inc. (Minneapolis, MN, USA) and the Rouen group (Letac, Cribier, France), were implanted in 21 normal pig coronary arteries. Animals were sacrificed after recatheterization at 1 day (group I, n = 4), I week (group 2, n = 3), 3 weeks (group 3, n = 5), or 8 weeks (group 4, n = 4). Histological morphometry of the vessel medial and neointimal layers was performed. Changes were related to the, stent diameter and. its force on the vessel wall . Results: The stent expansion ratio gradually increased from 73% to 93% after 8 weeks, which implicates that radial force decreased concomitantly from 0.10 N to 0.03 N. Media compression under the rods ranged from 4l%-66% immediately after stent implantation. The mean compression was unrelated to stent expansion and remained nearly the same (40%-50%) during follow-up. Individual media rod compression ranged from 5%-95%. The neointimal layer on top of the rods increased until the third week after stent implant (neointimal thickness 211 ± 108 μm). The layer significantly decreased at 8 weeks (neointimal thickness 65 ± 9 μm). The cross-sectional neointimal area increased gradually only at the end of the stent during the 8-week follow-up . Conclusions: The self-expanding stent implanted in normal pig coronary arteries reached a gradual relaxation state 8 weeks after implantation due to the persistent radial force. This radial force induces medial wall compression, which was only positively related to the thickness of the neointimal layer at 3 weeks after implant . (J Interven Cardiol 1996;9:45–52)     

Renal Excretion and Accumulation Kinetics of 2-Methylbenzoylglycine in the Isolated Perfused Rat Kidney

The effect of protein binding on kidney function has been studied by investigating the renal accumulation and secretion of the hippurate analogue 2-methylbenzoylglycine in the isolated perfused rat kidney in the absence and presence of bovine serum albumin (BSA). Experiments were performed with either 2.5% pluronic or a combination of 2.2% pluronic and 2% BSA as oncotic agents; a wide concentration range (1–190 μg mL^?1) of 2-methylbenzoylglycine was studied. Tubular secretion appeared to be a function of the amount of unbound drug in the perfusate and was best described by a model consisting of a high and low affinity Michaelis-Menten term. Parameters obtained after the analysis of renal excretion data were maximum transport velocity for the high affinity site (T_M,H) = 3.0 ± 2.8 μg min^?1, Michaelis-Menten constant for tubular transport for the high affinity site (K_T,H) = 0.5 ± 0.8 μg mL^?1, maximum transport velocity for the low affinity site (T_M,L) = 250 ± 36 μg min^?1, and Michaelis-Menten constant for tubular transport for the low affinity site (K_T,L) = 62 ± 17 μg mL^?1. The compound accumulated extensively in kidney tissue, ratios up to 175 times the perfusate concentration were reached. Accumulation data were best analysed by a two-site model similar to the model used to describe renal excretion. Calculated parameters were theoretical maximum capacity of the high affinity site (R_M,H) = 26 ± 23 μg g^?1, affinity constant for renal accumulation at the high affinity site (K_A,H) = 0.2 ± 0.4 μg mL^?1, theoretical maximum capacity of the low affinity site (R_M,L)= 1640 ± 1100 μg g^?1 and affinity constant for renal accumulation at the low affinity site (K_A,L) = 60 ± 58 μg mL^?1. The very high accumulation in kidney tissue could be explained by active tubular uptake, mediated by the secretory mechanisms involved, and dependent on the amount of free drug in the perfusate. This study shows that anionic drugs, subject to active secretion, may reach high concentrations in tubular cells even at low plasma concentrations.     

A New Stimulation Protocol for Cardiac Assist Using the Latissimus Dorsi Muscle

When treating severe cardiac failure with dynamic cordiomyoplasty, knowledge about the optimal way of stimulating the latissimus dorsi (LDJ muscie is of obvious importance. We evaluated a new stimulation protocol in/our goats using in situ electrical stimulation of the left LD muscle. Stimulation was started using a burst of two pulses with an interpulse interval of 100 msec for 50 bursts/min. The number of pulses was increased every 2 weeks concomitant with a decrease in interpulse interval. This resulted after 12 weeks in 60 bursts/min using bursts of six pulses with an interpulse interval of 20 msec after 12 weeks. Force measurements, which were done every 2 weeks, shoived an early decrease in contraction and relaxation speed as reflected in the ripple (= interstimulus amplitude/peak force amplitude measured at 10 HzJ. Fatigue resistance increased significantly within 4 weeks of conditioning as indicated by preservation of force, positive dF/dt, and negative dF/dt. Full preservation of these variables was seen even during a 1-hour fatigue test at the end of the conditioning period. Skeletal muscle enzyme activity as an indicator of muscle domage showed a significont rise in creatine kinase enzyme activity only on the first day following the start of LD stimulation. LD muscle biopsies revealed almost complete transformation to type I muscle fibers with a significant increase in capillary/fiber ratio when compared to the nonsfimulated LD muscle. However, some biopsies, in particular near the electrodes, did show some signs of skeletal muscle damage. Contraction characteristics of the fully transformed LD muscles were tested by increasing the number of bursts of six pulses from 50/min to 100/min. Interpulse intervals of 20 and 33 msec were used. These tests revealed thaf maximal force, positive dF/dt, and negative dF/dt was reached with 50 bursts/min using a six pulse burst with interpulse intervals of 20 msec.     

Immunocytochemical detection of basement membrane antigens in the histopathological evaluation of laryngeal dysplasia and neoplasia

Immunocytochemical detection of intrinsic components of the basement membrane (type IV collagen and laminin) was performed in biopsies of carcinoma in situ, dysplasia and hyperplasia of the laryngeal mucosa. We found a distinct and continuous basement membrane, containing both laminin and type IV collagen, at the border between epithelial cells and mesenchymal stroma in normal as well as in hyperplastic and dysplastic mucosa. In contrast, irregular discontinuities were found in some cases of carcinoma in situ and in invasive carcinoma. In addition, immunoreactivity for intracytoplasmic basement membrane components was noticed occasionally in neoplastic epithelial cells. In areas of inflammation, infiltration of leucocytes into the epithelium was occasionally accompanied by sharply defined small interruptions of the basement membrane. Our results indicate that immunohistochemical detection of basement membrane components can be of value for the demonstration of microinvasive growth in laryngeal cancer.