Immuno-allergic hemolytic anemia connected with streptomycin

The distribution volume of 125l-diatrizoate in rat tissues was studied 5 seconds to 5 minutes after intravenous injection and 5 seconds to 2 minutes after intra-arterial injection. Immediately after injection, diatrizoate was distributed into a larger volume than plasma. Marked temporal changes in the distribution volume of individual tissues occurred during the first 2 minutes. At 5 minutes, the diatrizoate space approached the total extracellular fluid volume, with more than 80% of the contrast agent remaining outside the blood vessels. Thus the relative magnitude of contrast enhancement of a tissue appears to be related to the volume of the rapidly equilibrating extracellular space. Intra-arterial administration can significantly overload muscle with contrast material for about 2 minutes. This and other temporal changes in contrast distribution may prove useful in contrast-enhanced computed tomography using short scanning times.     

Contrast media-induced renal morphologic lesions in diabetic rats

Diabetes mellitus was induced in rats with streptozotocin and after 3 months the animals (n = 48) received an i.v. injection of 1 or 3 g I/kg in the form of high-osmolar diatrizoate, low-osmolar iopromide or iohexol, or of 0.6 g I/kg of high-osmolar Gd-DTPA. The controls were given an i.v. injection of physiologic saline. After 2 hours the kidneys were fixed by perfusion and the renal morphologic changes were semiquantitatively analyzed by two independent observers unaware of the agent administered. The contrast media (CM) induced pronounced cytoplasmic vacuolization in the proximal convoluted tubular cells. Such a lysosomal alteration may indicate CM uptake into the cell, and the ultrastructural evaluation revealed intracellular injuries related to the process. The alterations were most marked following administration of iohexol, but diatrizoate also induced a statistically highly significant vacuolization (p < 0.001). The lysosomal alterations following iopromide administration were not as striking, and Gd-DTPA induced only minor changes.     

Dynamics of myocardial contrast enhancement: an in vivo computed-tomographic study

Enhancement of normal functioning myocardium was quantitated in 15 dogs by serial computed transmission tomographic (CT) images during the bolus (10 ml/sec.) or slow (1 ml/sec.) intravenous injection of diatrizoate contrast media (1 ml/kg body weight) in concentrations of 37, 18.5, or 9.25 g iodine (I)/dl. Homogenous images of myocardial enhancement were obtained. However, major streak artifacts were observed frequently when contrast material was injected as a bolus, and myocardial edges were not defined clearly when contrast material with a concentration of 9.25 g I/dl was injected slowly. Time-attenuation curves of normal myocardial enhancement constructed from serial CT images demonstrated a peak in contrast enhancement (delta Hounsfield units, 22-45) followed by a period of deterioration that lasted two to three minutes. These results can be applied to make optimal use of both single (static) and serial (dynamic) myocardial CT images.     

Sepsis increases endocytosis of endotoxin into hepatocytes

BACKGROUND: Chylomicrons bind endotoxins and accelerate their clearance from plasma to the liver. This results in reduced mortality from septic shock in a rodent model. We hypothesized that the clearance of the LPS-chylomicron (LPS-CM) complex by hepatocytes is due to receptor-mediated endocytosis and that sepsis up-regulates this process. METHODS: Three groups of Sprague-Dawley rats; (1) control; (2) pretreated with 10 micrograms/kg LPS 24 hours before treatment; and (3) pretreated with 17-alpha-ethinyl estradiol (EE, 5 mg/kg subcutaneously for 3 days), were infused with labeled I125-LPS alone or with I125-LPS bound to chylomicron. Livers were removed 2.5, 15, and 30 minutes after LPS injection, and hepatic endosomes were isolated from the liver homogenates by serial ultracentrifugation in sucrose gradients. RESULTS: The injection of I125-LPS-CM complexes resulted in higher levels of endosomal I125-LPS in all groups, as compared with I125-LPS alone. In addition, the endosomal uptake of I125-LPS was markedly increased by both LPS and EE pretreatments. CONCLUSIONS: These data strongly suggest a primary role for receptor-mediated endocytosis in the increased clearance of LPS when bound to chylomicron. In addition, exposure to LPS appears to increase the accumulation of LPS in endosomes by a mechanism similar to that of EE, which is known to up-regulate receptor-mediated lipoprotein uptake. This endogenous pathway for the catabolism of endotoxins may provide a teleological explanation for the hypertriglyceridemia observed during sepsis.     

Therapeutic time window for the 21-aminosteroid, U-74389G, in global cerebral ischemia

A novel 21-aminosteroid (U-74389G), a new potent antioxidant, was evaluated for its protective effect on transient global cerebral ischemia. Ischemia was induced by 20 minutes of four-vessel occlusion in adult male Wistar rats. Injection of 21-aminosteroid (U-74389G, 5 mg/kg intraperitoneally injected) was repeated three times. The second injection was performed 30 minutes after the first injection, and the third injection was performed 210 minutes after that. Experimental animals were divided into five groups according to the time drug administration was initiated. Group I (n = 8) began vehicle administration 30 minutes before occlusion. Group II (n = 9) started 21-aminosteroid administration 30 minutes before occlusion. Drug administration in Group III (n = 9) began at the time of reperfusion, in Group IV (n = 8), 30 minutes after reperfusion, and in Group V (n = 6), 60 minutes after reperfusion. Animals in the control group (n = 5) underwent sham operations. One week after ischemia, the number of viable pyramidal neurons was counted in the hippocampal CA1 subfield. The results were as follows: the number of living neurons in Group I was 18.8 +/- 8.7; in Group II, was 44.7 +/- 9.5; in Group III, was 46.4 +/- 9.4; in Group IV, was 40.3 +/- 6.6; in Group V, was 10.2 +/- 2.5; and in the control group was 131 +/- 3.3. Groups II, III, and IV demonstrated significantly higher numbers of living neurons compared with Group I (P < 0.05). The present study revealed that U-74389G attenuated delayed neuronal death in global cerebral ischemia when it was administered before or soon after the ischemic episode.     

Effect of metoclopramide, ranitidine, and droperidol on the lower sphincter of the esophagus. Experimental study on the opossum (Didelphis albiventris)

Electromanometric measures of the gastroesophageal junction were performed in 20 adult, male and female, anesthetised opossums. The electromanometric examinations were performed according the intermitent pull through technique. The research was divided in four groups, according to the drug to be analysed: group 1 (20 animals) IM injection of physiological solution (control group); group 2 (20 animals) IM injection of metoclopramide; group 3 (20 animals) IM injection of ranitidine; group 4 (20 animals) IM injection of droperidol. Electromanometry was done 15 minutes before the drug injection, just after the injection and 15, 30, 45 and 60 minutes after the injection. In each one of the moments the pressure of the lower esophageal sphincter (LES-mmHg) was analysed. Considering LES pressure the results observed were: in group 1 it was not observed any significative alteration after IM injection of physiologic solution; in group 2 it was observed significative pressure increase, 15 minutes after metoclopramide IM injection; in group 3 it was observed pressure increase, being significative at 15 and 30 minutes after IM injection; in group 4 it was observed significative increase in LES pressure in every moment, 15 minutes after droperidol IM injection.     

Urine profiles and kidney histology after ionic and nonionic radiologic and magnetic resonance contrast media in rats with cisplatin nephropathy

RATIONALE AND OBJECTIVES: The nephrotoxic drug cisplatin has been used successfully in treating some cancers. Patients with suspected carcinoma frequently undergo examinations with contrast media. We examined whether ionic and nonionic radiologic and magnetic resonance contrast media would have any effect on cisplatin nephropathy in rats. METHODS: Urine and serum profiles were monitored for 24 days after intravenous (i.v.) injections of saline, diatrizoate, iohexol, gadopentetate dimeglumine, and gadodiamide in high doses (4.59 mmol/kg body weight) in rats that received a weekly intraperitoneal (i.p.) injection of cisplatin (1 mg/kg) for 10 weeks. There were 10 rats in each group. Another 10 rats injected with both i.p. and i.v. saline served as control subjects. After euthanization, rats' kidneys were removed for examination by light microscopy and electron microscopy. RESULTS: Light and electron microscopy showed severe morphologic changes, including tubular dilatation, atrophy, and necrosis induced by cisplatin; however, the contrast media did not induce any additional morphologic changes. Gadopentetate dimeglumine, diatrizoate, and iohexol significantly increased (3-20 times) albuminuria compared with i.v. saline in cisplatin nephropathy, whereas gadodiamide did not. Albuminuria was highest after diatrizoate injection. All four contrast media caused an immediate and transient significant increase in the excretion of the brush border enzymes alkaline phosphatase and gamma-glutamyltransferase (125-500 times) and the cytoplasmatic enzymes alanine aminopeptidase and lactate dehydrogenase (16-100 times). Compared with saline, the ionic agents significantly increased the excretion of both glucose (two times) and sodium (three to five times), whereas the nonionic agents did not. CONCLUSION: High doses of radiologic and magnetic resonance contrast agents cause temporary dysfunction in rats with cisplatin nephropathy. Gadodiamide caused the least dysfunction and diatrizoate the most.     

Projections from the superior olive and lateral lemniscus to tonotopic regions of the rat's inferior colliculus

The projections to physiologically defined tonotopic regions of the central nucleus of the inferior colliculus (ICC) from the adult rat's superior olivary complex (SOC) and lateral lemniscus were investigated using retrograde tract tracing methods. Iontophoretic injections of the retrograde tracers, Fluoro-Gold (FG) or horseradish peroxidase (HRP), were made into the ICC through a glass micropipette, which also served as a recording electrode to determine the frequency response at the injection site. Injections were made into frequency-specific regions based on the best responses of neurons to contralaterally presented tones between 2 25 kHz. In the dorsal nucleus of the lateral lemniscus (DNLL) neurons were labeled both ipsilaterally and contralaterally to the injection site with a larger proportion projecting to the contralateral side. The distribution of labeled cells was concentric, with high frequencies represented along the outer margin and low frequencies represented centrally within DNLL. The lateral superior olive (LSO) was labeled bilaterally, with high frequencies represented medially and low frequencies laterally along the nuclear axis. The projection from the medial superior olive (MSO) was ipsilateral, with high frequencies represented ventrally and low frequencies dorsally. The projection from the superior paraolivary nucleus (SPN) was also largely ipsilateral, with high frequencies represented medially and low frequencies laterally. The intermediate and ventral nuclei of the lateral lemniscus (INLL and VNLL) were also labeled ipsilaterally and exhibited a distribution of tracer that depended on the frequency of the injection site: the low frequency projection was banded but the high frequency projection was more evenly distributed.     

Obstructive jaundice due to compression of the common hepatic duct by right hepatic artery--a case associated with the absence of the lateral segment of the left hepatic lobe

A functionalized derivative of the mu opioid agonist carfentanil was synthesized (NH2-carfentanil) and showed high specific activity when radiolabeled with iodine. [127I]NH2-carfentanil displayed high affinity and pronounced mu-binding selectivity with a delta/mu selectivity ratio of over 1200. The ability of [125I]NH2-carfentanil to interact in vivo with opioid receptors was determined in mouse brain using ex vivo binding techniques. Twenty minutes after intraperitoneal injection, 0.1% of the [125I]NH2-carfentanil injected into the mouse was present in the brain. [125I]NH2-carfentanil specific binding was inhibited by co-injection of naloxone or morphine while naltrindole, a delta-selective antagonist, was unable to displace the bound radioligand. Autoradiographic experiments revealed a heterogeneous distribution of [125I]NH2-carfentanil specific binding sites, maximal binding occurred in areas with high densities of mu receptors. Peripherally administered iodo-NH2-carfentanil selectively labelled central mu opioid receptors in mouse indicating great potential for single photon emission computed tomography studies.     

Liver toxicity of diatrizoate and a non-ionic contrast medium (C29). Coeliac angiography in the rabbit

Toxic effect on the liver of diatrizoate and a new non-ionic contrast medium (C29) were investigated using coeliac angiography in rabbits. The contrast media were injected in doses of 5 ml/kg rabbit with a concentration of 370 mg I/ml. Serum levels of ALAT, ASAT, ALP and bilirubin did not change significantly after the injections.     

The changes of blood gas analysis values and platelet aggregability on acute phase in the experimental model of pulmonary embolism prepared by sephadex G-75 (SG-75) injection

To study pathophysiologic phenomena in acute pulmonary embolism, we injected sephadex G-75 (SG-75) into rabbit auricular veins and measured the changes in blood gases and in platelet aggregability. Severe hypoxemia developed within 10 minutes of SG-75 injection. Microscopic examination of samples taken 120 minutes after SG-75 injection pulmonary artery had been embolized by the SG-75 particles, and that thrombin had formed around the particles. The lowest platelet counts were measured 10 minutes after SG-75 injection. The rates of platelet aggregation induced by adenosine diphosphate and by platelet-activating factor were abnormally low until 40 minutes after SG-75 injection. These results suggest that platelets were activated by anoxia and that the activated platelets moved around the emboli after obstruction of the pulmonary artery. We conclude that decreases in PaO2 and changes in platelet aggregability exacerbate the pathophysiologic processes in acute pulmonary embolism.     

Nasal mucosa examination by means of endoscopy

The pharmacokinetics of kanamycin and gentamicin were studied after intramuscular (IM) and intravenous (IV) (constant infusion over 20 minutes) administration in newborn infants. The serum concentrations, half-lives, area-under-the-curve values, and volumes of distribution were similar for each drug after both routes of administration. Based on these pharmacological similarities, it is likely that these aminoglycosides can be given safely and effectively as constant IV infusions to neonates in whom IM injections are not feasible.     

Differential effect of morphine on dopaminergic neurons in frontal cortex and striatum of the rat

Lactate dehydrogenase-5 and creatine kinase from rabbit muscle were labeled by coupling with N-hydroxysuccinimidyl 3-(4'-hydroxy-[3',5'-125I]diiodophenyl)propionate. After purification, the analytical recovery of catalytically-active labeled enzyme averaged 90% for lactate dehydrogenase, 81% for creatine kinase. The labeled enzymes were injected intravenously into rabbits and disappearance from plasma of catalytic activity and radioactivity was measured. The disappearance curves for lactate dehydrogenase-5 differed considerably from those observed with the enzyme labeled by direct iodination. The discrepancy was due to rapid hydrolysis in vivo of the labeled amide-enzyme linkage, because about 50% of the injected radioactivity appeared in the urine as 125I-labeled 3-(4'-hydroxy-3',5'-diiodophenyl)propionic acid within 4-8 h of injection. Similar outputs were observed after administration of this acid to rabbits. The free acid was also detected in the urines of rabbits within 4-8 h of the intravenous injection of creatine kinase labeled similarly. We conclude that this method of labeling is unsuitable for preparing radioactive enzymes for study of their catabolism.     

Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3

Rats were exposed to either NO2 or O3 to determine whether nonciliated cells (Clara cells) could divide and differentiate into ciliated cells in the terminal bronchioles. Dividing cells were labeled with tritiated thymidine, visualized in the light and electron microscopes using autoradiographic techniques, and studied for up to 15 days after labeling. Electron microscopic autoradiography 1 hour after injection of tritiated thymidine showed that all labeled cells in the terminal bronchioles were nonciliated. However, 4 days after injection of tritiated thymidine, 67.8 per cent of the labeled cells were nonciliated and 32.2 per cent were ciliated. Light microscopic autoradiography showed that the new labeled ciliated cell population was stable for up to 15 days. These results indicate that nonciliated cells divide and the sister cells may form new ciliated and nonciliated cells. Thus, nonciliated cells can act as progenitor cells for the terminal bronchiolar epithelium.     

Auditory epithelial migration. III: An immunohistologic study using anti-BrdU antibody on tympanic membrane in mouse

A localization pattern of epidermal cells on the tympanic membrane (TM) and their migratory patterns were studied in mice, by means of immunohistologic technique using an anti-bromodeoxyuridine (BrdU) antibody. The BrdU was instilled intraperitoneally and the animals were painlessly sacrificed between 1 hour and 10 days after the injection. An immunostaining technique using anti-BrdU antibodies was applied on whole mount TM tissues. One hour after injection, BrdU-labeled cells were found in the handle of the malleus (HM) region and in the annular region of the pars tensa of the TM. Some labeled cells were observed in the intermediate region of the upper half of the superior quadrant, but no labeled cells were found in the remaining part of the intermediate region. Labeled cells were also evident in the pars flaccida without any particular pattern of distribution. As time elapsed after the injection, the labeled cells first appearing in the HM region had migrated laterally and inferiorly from the HM toward the annulus, while those in the annular region had considerably decreased in number. Results of the present study are the following: 1) the proliferation center of epidermal cells in the pars tensa is located in two different areas, i.e., the HM region and annular region, 2) newly generated cells in the HM region migrated from the HM region toward the annular region, whereas those in the annular region migrate from the the annular region to the external auditory canal, and 3) no specific generation center is located in the pars flaccida. On the basis of these results, we discuss the relationship between the site of the proliferation center of epidermal cells and their migratory patterns.     

Enzyme-linked immunosorbent assay and flow cytometric methods to screen hybridoma culture supernatants for antibodies to bovine neutrophil surface antigens, and monoclonal antibody production and characterization

Enzyme-linked immunosorbent assay and flow cytometric methods to screen hybridoma culture supernatants for antibodies to bovine neutrophils (surface antigen-specific) were optimized. Sensitivity of the 2 methods was compared. A panel of 14 murine monoclonal antibodies (MAB) to surface antigens of bovine polymorphonuclear neutrophilic leukocytes (neutrophils) was produced by hybridoma technology, and their isotypes were determined by whole-cell ELISA. Monoclonal antibody reactivity with neutrophils, eosinophils, and lymphocytes isolated on phosphate-buffered saline solution and on Ficoll-sodium diatrizoate were compared. Biochemical characterization of antigens recognized by MAB was performed by immunoblot analysis. Neutrophil plasma membranes were isolated on sucrose gradients (20, 32, and 50%) and purified for polypeptide characterization. Neutrophil surface proteins were characterized by external labeling with 125I. The flow cytometric method was proven to be more sensitive and rapid than ELISA to screen hybridoma supernatants. This method allowed light-scatter gating of live neutrophil populations for analysis, which eliminated nonspecific binding of antibodies to contaminating cells and dead neutrophils. The optimal conditions for flow cytometric analyses were 5 x 10(5) neutrophils and 1 micrograms of fluorescein-labeled F(ab')2/assay as the second antibody. The optimal conditions for hybridoma screening by ELISA were neutrophil concentration of 2.5 x 10(5)/well, using a 96-well polystyrene microtitration plate as solid support, and 2,2'-azino-di[3-ethyl-benzthiazoline sulfonate (6)] with H2O2 as the chromatogenic substrate. Tissue culture plates as solid support and 3,3', 5,5'-tetramethyl benzidine, with H2O2 as the chromogenic substrate, were equally as sensitive. Panel MAB reacted differently with neutrophils, eosinophils, and lymphocytes. Isolation of these cells from blood on Ficoll-sodium diatrizoate generally did not alter MAB reactivity. Coomassie blue-stained gels of neutrophil plasma membrane proteins contained about 25 polypeptide bands, 13 of which were major bands. Autoradiography revealed about 11 surface proteins, 5 of which were heavily labeled with 125I. Monoclonal antibody S7G8 identified a 65-kd protein and MAB S8G10 identified 65- and 70-kd proteins. On the basis of molecular weight, MAB S7G8 and S8G10 are comparable to human CD15, CD16, and CD64 molecules. The MAB generated in this study are potential candidates to discern bovine neutrophil function and heterogeneity.     

High-performance liquid chromatographic analysis of chlorhexidine in saliva after mouthrinsing

BACKGROUND: Neutrophils contribute to the host defense mechanism, but they can cause remote organ injury in peritonitis. The purpose of this study was to examine neutrophil adhesion to the peritoneum and remote organs simultaneously in peritonitis using a fluorescence microscopic method. STUDY DESIGN: Experiment 1: Sprague-Dawley rats (n = 16) were injected intraperitoneally (ip) with saline solution or 10(5), 10(7), or 10(9) Escherichia coli. Five hours after challenge, 1 x 10(6) fluorescein-labeled neutrophils were infused. Two minutes after neutrophil injection, five peritoneal samples (the greater omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Lung myeloperoxidase (MPO) activity was also determined. Experiment 2: Rats (n = 23) were given 10(9) E. coli ip. Before challenge (0 h) or at 1, 5, or 10 h after challenge, labeled neutrophils were infused. Then, the labeled neutrophil numbers in organs and lung MPO activities were assessed as described for Experiment 1. Hemodynamic and arterial blood gas data were also obtained in another set of rats before and at 1, 5, 8 and 10 h after 10(9) E. coli ip challenge. RESULTS: Experiment 1: The labeled neutrophil numbers in the peritoneum, lungs, and kidney showed significant positive correlations with the injected bacterial numbers. Lung MPO also positively correlated with E. coli number and labeled neutrophil number in the lungs. Experiment 2: Labeled neutrophil numbers in the peritoneum and kidney peaked at 5 h. The pulmonary labeled neutrophil number rose, reaching a plateau at 5 h. No remarkable change was observed in the hepatic labeled neutrophil number. There was a positive correlation between lung MPO activity and pulmonary labeled neutrophil number. Hemodynamic and blood gas data reflected a hyperdynamic state. CONCLUSIONS: Concomitant dose-dependent increases in neutrophil adhesion in the peritoneum, lungs, and kidney were observed in this peritonitis model. Increased neutrophil adhesion was transient in the peritoneum and kidney but persistent in the lungs. Strategies modulating neutrophil adhesion in organs are anticipated to be useful for the treatment of peritonitis.     

The distribution of Nematospiroides dubius within the small intestine of laboratory mice

Recent reports have suggested the use of intravenous 201T1 (thallium-201) for myocardial imaging with the gamma scintillation camera. In order to better appreciate the possible utility of this agent in humans we examined its distribution and kinetics in 13 patients and in six mongrel dogs, three with experimental coronary artery occlusion. In addition, 201T1 was compared to 86Rb (rubidium-86) in 84 rats. In the rat heart, the concentration of 201T1 was 30% higher than that of 86Rb ten minutes after injection. Moreover, myocardium-to-blood ratios for 201T1 averaged 51:1, but only 32:1 for 86Rb ten minutes after administration. In the dog heart, the distribution of 201T1 paralleled that of radioiodinated (131I) albumin particles injected into the left atrium and, thus, appears to be related to regional blood flow. Its concentration in ischemic regions decreased to 32.3% of the normally perfused myocardium. In the patients with a recent or old myocardial infarction, areas of decreased 201T1 uptake were easily identified and corresponded in location to that by ECG. Repeat scans 24 hours after the initial injection showed a significant retention of 201T1 by the myocardium. 201T1 blood levels in humans 15 minutes after injection were low (averaging 1.06% +/- 0.41% SD of the total dose per liter) and these levels decreased with a biological half-life of 3.1 +/- 0.7 days. Twenty-four hour urinary excretion rates ranged from 0.6 to 6.5% of the total dose and appeared related to urinary flow and the concentation of 201T1 in blood. Because of the higher target to background ratios, 201T1 compares favorably with radioactive rubidium. 201T1 in diagnostic doses remained without detectable adverse effects and appears promising as an agent for visualizing abnormal regional myocardial perfusion in patients with coronary artery disease.     

Passive care and active rehabilitation in a patient with failed back surgery syndrome

Blood-borne cytokines enter the brain by transport across the blood-brain barrier (BBB) or by leakage through extracellular pathways at sites, such as circumventricular organs (CVOs), without a BBB. We used radioactively labeled albumin (T-Alb) to differentiate the relative contribution of transport and extracellular pathways to the passage of interleukin-1 alpha ([125I]IL-1 alpha) across the BBB. The major mechanism of entry for [125I]IL-1 alpha after intravenous (i.v.) injection was a saturable transport system with extracellular pathways accounting for only a small fraction of entry into brain. CVOs concentrated blood-borne [125I]IL-1 alpha in a saturable manner to a much greater extent than did the cerebral cortex and cerebellum, but accounted for less that 5% of total brain uptake. After intracerebroventricular (i.c.v.) injection, [125I]IL-1 alpha and T-Alb were concentrated in the CVOs, especially the median eminence, although CVOs contained less that 1% of the substances injected. Distribution after i.c.v. injection was largely due to diffusion and leakage through extracellular pathways. We conclude that after i.c.v. injection, leakage across extracellular pathways accounts for the small but concentrated amount of [125I]IL-1 alpha found in CVOs. After i.v. injection, transport across the BBB accounts for the majority of [125I]IL-1 alpha in brain.     

Local drug delivery with porous balloons in the rabbit: assessment of vascular injury for an improvement of application parameters

OBJECTIVES: Sufficient intramural drug concentrations with the use of porous balloon catheters can be achieved with additional vascular trauma only. However, effective delivery of a potent drug even in deeper layers of the vessel wall might outweigh these traumatic side effects. Given the porous balloon catheter, the parameters of injection pressure and applied fluid volume will influence the interventional result. METHODS: We tested a 2.5-mm porous balloon (35 75-micron pores) in the right carotid artery of New Zealand rabbits and used injection pressures of 1, 2, and 5 atm and fluid volumes of 2 and 4 ml of low-molecular-weight heparin solution in combination with the different parameters (n = 5 animals/group). In 50 rabbits, an intimal fibromuscular plaque was induced by using the electrostimulation model. Balloon dilatation and then application of the porous balloon was performed in 30 animals, 10 animals were only electrostimulated, and 10 animals served as a control group with balloon dilatation only. The vessels were excised 7 d after intervention, stained, and analyzed histomorpologically. Anti-Xa assays revealed the extent of systemically escaped drug, and serial cuts allowed for exact determination of vessel wall injuries. RESULTS: Effective local drug delivery could not be achieved with an injection pressure of less than 2 atm. Specific pressure-driven effects such as jet injuries could be identified. When the pressure was high enough for disruptive drug delivery (> or = 2 atm), fluid volumes of 4 ml led to loose elastic membranes and local thickening within the media. CONCLUSIONS: Sufficient intramural drug distribution using porous balloon catheters can be achieved with low injection pressures. Different fluid volumes strongly determine the extent of additional vascular injury.