Design and synthesis of novel substituted quinazoline derivatives as antileishmanial agents.

4-(Substituted-benzylidine)-2-substituted-5,6-dihydrobenzo[h]quinazoline (5a-p) and 4-(substituted-benzylidine)-2-substituted-3, 4, 5, 6-tetrahydrobenzo[h]quinazoline (6a-p) have been synthesized from 2-(substituted-benzylidine)tetralone-1(3a-d) and several substituted guanidine sulfates(4a-d).These compounds were tested for their in vitro antileishmanial activity. The compounds 6i, 6f, 6g show promising antileishmanial activity against Leishmania donovani.

Diagnosis and management options in malignant pleural effusions.

Malignant pleural effusion (MPE) denotes an advanced malignant disease process. Most of the MPE are metastatic involvement of the pleura from primary malignancy at lung, breast, and other body sites apart from lymphomas. The diagnosis of MPE has been traditionally made on cytological examination of pleural fluid and/or histological examination of pleural biopsy tissue that still remains the initial approach in these cases. There has been tremendous advancement in the diagnosis of MPE now a day with techniques i.e. characteristic Ultrasound and computed tomography features, image guided biopsies, fluorodeoxyglucose-positron emission tomography imaging, thoracoscopy with direct biopsy under vision, tumor marker studies and immunocytochemical analysis etc., that have made possible an early diagnosis of MPE. The management of MPE still remains a challenge to pulmonologist and oncologist. Despite having various modalities with better tolerance such as pleurodesis and indwelling pleural catheters etc., for long-term control, all the management approaches remain palliative to improve the quality of life and reduce symptoms. While choosing an appropriate management intervention, one should consider the clinical status of the patient, life expectancy, overall cost, availability and comparative institutional outcomes, etc.

The role of microtubules in platelet secretory release.

The role of microtubules in platelet aggregation and secretion has been analyzed using platelets permeabilized with digitonin and monoclonal antibodies to alpha (DM1A) and beta (DM1B) subunits of tubulin. Permeabilized platelets were able to undergo aggregation and secretory release. However, threshold doses of agonists capable of eliciting a second wave of aggregation and the platelet release reaction were higher than in control platelets exposed to dimethyl sulfoxide, the solvent for digitonin. Both antibodies to alpha and beta tubulin caused a further increase in the threshold concentration of agonists and inhibited the secretory release of permeabilized platelets, but were ineffective using intact platelets. Neither monoclonal antibody inhibited polymerization or depolymerization of platelet tubulin in vitro. Antibodies to platelet actin and myosin also exhibited an inhibitory activity on platelet aggregation albeit less severe than that observed with the antibodies to alpha and beta tubulin. There was evidence of an interaction between DM1A and DM1B and the antibodies to actin and myosin. The interaction of platelet tubulin and myosin was investigated by two different methods. (1) Coprecipitation of the proteins at low ionic strength at which tubulin by itself did not precipitate and (2) affinity chromatography on columns of immobilized myosin. Tubulin freed of its associated proteins (MAPs) by phosphocellulose chromatography bound to myosin in a molar ratio which approached 2. Platelet actin competed with tubulin for 1 binding site on the myosin molecule. MAPs also reduced the binding stoichiometry of tubulin/myosin. Treatment of microtubule protein with p-chloromercuribenzoate or colchicine did not influence its binding to myosin. DM1A and DM1B inhibited the interaction of tubulin and myosin. This effect could also be demonstrated by reaction of electrophoretic transblots of extracted platelet tubulin with the respective proteins. We interpret these results as evidence for an interference of the two monoclonal antibodies to the tubulin subunits (DM1A and DM1B) with the translocation of microtubule protein from its submembranous site to a more central one during the activation process.

Permeabilization of platelets: an investigation of biochemical, ultrastructural and functional aspects.

The biochemical, ultrastructural and functional aspects of digitonin-permeabilized platelets were investigated. Human platelets were permeabilized by exposure to the steroid glycoside digitonin. A 60 microM concentration of this permeabilizer produced a very substantial release of cytosolic enzymes from the platelets. Release from subcellular granules was relatively low and did not inhibit the response of platelets to a series of agonists. Although digitonin-permeabilized platelets required higher threshold concentrations of the usual stimulants, both primary and secondary aggregation as well as the release of nucleotides and enzymes from their respective granules remained intact. Transmission electron micrographs revealed discontinuities in the plasma membrane of digitonin-treated platelets, but scanning electron microscopy showed no difference between control and permeabilized platelets. No substantial loss of structural or membrane proteins could be detected by one- and two-dimensional gel electrophoresis. The pore size produced by digitonin treatment was sufficient to allow entry of 125I-labeled IgG into the platelet cytosolic space.

Nonenzymatic glycosylation of erythrocytic proteins in normal and diabetic subjects. Enzymes of nucleoside and nucleotide metabolism.

A modification of the technique of Glyco-Gel affinity column chromatography has been employed to separate glycosylated proteins from nonglycosylated proteins of hemolysates. When glycosylation in hemolysates of 11 type I diabetic subjects was compared with that from 7 normal subjects, significant increases were found in glycosylation of hemoglobin (Hb) (12.1 +/- 6.0% versus 4.7 +/- 0.5%) and purine nucleoside phosphorylase (PNP) (5.3 +/- 3.0% versus 2.1 +/- 0.5%). However, no differences were found for nucleoside diphosphokinase (NDPK) (1.5 +/- 1.1% versus 1.0 +/- 0.4%) and adenylate kinase (AMPK) (0.5 +/- 0.4% versus 0.7 +/- 0.2%). Linear relationships were seen between glycosylated Hb and glycosylated PNP (r = 0.97) or glycosylated NDPK (r = 0.81). On incubation of hemolysates from normal individuals with high glucose (1500 mg/dl or 83 mM) and NaCNBH3 (20 mM), linear increases in the degrees of glycosylation were seen with time. After 18 h, the percentages of glycosylation of Hb, PNP, NDPK, and AMPK were increased from normal values to 31, 24, 11, and 3, respectively. When partially purified human erythrocytic PNP was incubated with various monosaccharides (20 mM) in the presence of NaCNBH3 for 6 h, glycosylation increases of 2-5-fold were seen in the order ribose greater than mannose greater than galactose greater than glucose.

Synthesis and biological evaluation of 6-amino-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (3,7-dideazaguanine).

The synthesis of 6-amino-1H-pyrrolo[3,2-c]pyridin-4(5H)-one (3,7-dideazaguanine, 2) has been accomplished from 3-(ethoxycarbonyl)pyrrole-2-acetonitrile. In contrast to 3-deazaguanine, compound 2 did not show any antitumor, antiviral, or antibacterial properties. Furthermore, it was not a substrate for hypoxanthine-guanine phosphoribosyltransferase or purine nucleoside phosphorylase.

Cardiac perforation from central venous catheters: survival after cardiac tamponade in an infant.

A 2,210-g infant suffered cardiac tamponade, which resulted from atrial perforation by a central venous catheter. The infant survived due to timely diagnostic and therapeutic intervention. Cardiac tamponade should be suspected in any patient with a central venous catheter whose condition deteriorates suddenly. Immediate chest roentgenogram and echocardiogram may be performed to support the diagnosis; but when the patient's condition is deteriorating, a diagnostic (and therapeutic as well!) pericardiocentesis should be performed without waiting for other diagnostic measures. A review of clinical recognition and diagnostic measures for cardiac perforation and tamponade is presented. Preventive measures to avoid this fatal complication of central venous catheters are suggested, and therapeutic interventions are outlined.

Imaging of platelets in right-sided extracardiac conduits in humans.

As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with In-111-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth postoperative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

Significance of plasma adenosine in the antiplatelet activity of forskolin: potentiation by dipyridamole and dilazep.

Forskolin, a plant (Coleus forskohlii) diterpene, inhibits ADP-induced (human: IC50, 2.3 +/- 1.0 microM; rat: IC50, 1.2 +/- 0.5 microM) and collagen-induced (human: IC50, 2.4 +/- 1.2 microM; rat: 0.6 +/- 0.2 microM) platelet aggregation in human and rat platelet-rich plasma (PRP). Human blood levels of adenosine (Ado) are low (100-300 nM) as compared to levels in rat plasma (7.55 +/- 0.51 microM). Ado is a natural antiplatelet and vasodilatory agent produced by vascular endothelium, heart and other body tissues. If the plasma Ado is degraded by pretreatment of PRP with adenosine deaminase (ADA), forskolin inhibition on platelet aggregation is reduced by 2-4 fold both in human and rat blood. On the other hand, if the physiological steady state levels of Ado are maintained by collecting the blood in the presence of the inhibitors of ADA (2'-deoxycoformycin, dCF, 5 microM) and Ado uptake (dipyridamole, 10 microM or dilazep, 2 microM), forskolin inhibition (IC50, 3.2 microM) on platelet aggregation in human PRP is potentiated by 20-40 fold (IC50, 0.075-0.15 microM). Similar potentiated forskolin effect (IC50, 0.53 microM) is seen if the ADA-treated human PRP is replenished with a low level of Ado (50 nM) after ADA inactivation by dCF and Ado-uptake blockade by dilazep. If the plasma is replenished with a higher concentration of Ado (300 nM), greater potentiation is seen (IC50, 0.23 microM). Forskolin is 2-4 fold more inhibitory in rat PRP than in human PRP, partially due to the presence of higher levels of Ado in the rat plasma. These studies demonstrate an important role of plasma Ado in the antiplatelet activity of forskolin and this effect can be greatly potentiated by the clinically used drugs, dipyridamole and dilazep.

Inhibition of human and rat platelet aggregation by extracts of Mo-er (Auricularia auricula).

Hot water extracts of Mo-er (1 gm by 15 ml of water), an oriental food (Auricularia auricula), inhibit strongly both human and rat platelet ADP-induced aggregation. HPLC analysis of two varieties of Mo-er, A. auricula and A. polytricha (a black tree fungus), shows that they contain adenosine (Ado), 133 and 154 micrograms per gram of dry fungus, respectively. The inhibition of ADP-induced platelet aggregation by Mo-er extracts and by Ado was compared. Mo-er extracts caused a more rapid onset and a longer duration of inhibition that produced by equivalent amounts of Ado. Furthermore, Mo-er extract treated with adenosine deaminase to degrade the Ado retained the capacity to inhibit platelet aggregation. The inhibitory effects of Mo-er extracts of ADP-induced human platelet aggregation are greatly potentiated by the inhibitors of cyclic AMP phosphodiesterase such as oxagrelate (phthalazinol) and papaverine. The inhibition of platelet aggregation is only partially blocked by 2',5'-dideoxy-adenosine (DDA), an inhibitor of platelet adenylate cyclase and 5'-deoxy, 5'-methylthioadenosine (MTA), an antagonist of ADO receptors. ADP-induced rat platelet aggregation is strongly inhibited by Mo-er extracts, but not by Ado. This inhibition is not reversed by either DDA or MTA. These findings indicate that Mo-er extracts contain an agent (or agents) in addition to Ado, that blocks platelet aggregation by a mechanism that does not involve the platelet cyclic AMP system.

Pre- and postoperative electrophysiologic assessment of children with secundum atrial septal defect.

Sinus node (SN) and atrioventricular node (AVN) dysfunction after repair of atrial septal defect (ASD) may be caused by inherent nodal abnormalities and not related to altered hemodynamics. To assess the preoperative prevalence and postoperative persistence of nodal dysfunction, 21 consecutive children, mean age 5.4 years, underwent electrophysiologic evaluations before ASD repair. Preoperative SN recovery time was prolonged in 11 patients and was associated with abnormal AVN response to rapid atrial pacing in 5. There were no significant differences in age, hemodynamic values or shunt size between children with normal and those with abnormal nodal function. Atrial and AVN refractory periods were normal. The ASD was repaired in 9 children with SN dysfunction. Electrophysiologic studies performed 4 to 16 months after surgical correction showed improvement in all electrophysiologic values. However, SN function remained abnormal. Significant decreases were observed in atrial (p less than 0.05) and AVN (p less than 0.05) refractory periods, with increased atrial conduction velocity (p less than 0.01) and AVN Wenckebach response to atrial pacing (p less than 0.01). ASD repair improved nodal and atrial muscle electrophysiologic function, theoretically by relieving stress on atrial impulse propagation. SN and AVN dysfunction may persist as an inherent part of the ASD complex.

Effect of dipyridamole therapy on myocardial ischemia in patients with stable angina pectoris receiving concurrent anti-ischemic therapy.

The effects of oral dipyridamole on exercise performance and anginal symptoms were evaluated in 15 men with stable angina pectoris. In a double-blind, randomized, crossover design, patients received 75 mg of dipyridamole or placebo every 8 hours for 2 weeks in addition to their previously prescribed cardiac medications. Graded exercise tolerance testing was performed twice before randomization, at the end of each treatment period, and after single-blind placebo washout. When compared with baseline tests, the time to onset of 0.1 mV ST-segment depression was similar between dipyridamole and placebo treatments (316 +/- 89 vs 345 +/- 102 seconds, respectively, p = not significant). No significant differences existed between treatments in the peak systolic blood pressure-heart rate product or in the duration of exercise. Angina pectoris occurred during all 3 baseline exercise tests in 7 of the 15 subjects; the time to onset of angina was unchanged by either treatment. Analysis of symptom diaries conducted in 13 patients revealed no significant alteration in reported anginal symptoms during dipyridamole treatment compared with placebo treatment (0.6 +/- 0.9 vs 0.3 +/- 0.4 episodes per week). Ambulatory electrocardiographic monitoring in 12 patients revealed few episodes of ischemia during daily activities with no alteration in frequency of episodes during treatment periods. Plasma concentrations of dipyridamole did not correspond with the outcomes of exercise testing. It is concluded that chronic oral dipyridamole therapy given in its usual clinical dose does not adversely affect exercise performance, daily anginal episodes or ambulatory ischemia in patients receiving concurrent anti-ischemic medication.

A simple assay for ecto-5'-nucleotidase using intact pulmonary artery endothelial cells. Effect of endotoxin-induced cell injury.

Adenosine may be protective in acute vascular injury by inhibiting platelet aggregation and neutrophil oxidant release. In contrast, adenine nucleotides, which may be released with acute vascular injury, stimulate platelet aggregation and neutrophil oxidant release. Ectonucleotidases, membrane enzymes that catabolize extracellular nucleotides, are the primary mechanism for degrading circulating nucleotides to adenosine. Ecto-5'-nucleotidase converts extracellular AMP to adenosine. We hypothesized that endothelial cell injury alters ecto-5'-nucleotidase activity. Using a novel assay first reported by Jamal et al. (Biochem J 250: 369-373, 1988) with rat adipocytes, we studied the properties of ecto-5'-nucleotidase in intact monolayers of cultured bovine pulmonary artery endothelial cells (BPAEC) and examined the effect of endotoxin on enzyme activity. The assay uses a fluorescent analog of AMP, 1,N6-etheno-AMP (E-AMP), as the substrate for ecto-5'-nucleotidase, and measures ethenoadenosine (E-Ado) formation. Etheno-AMP in Hepes buffer, pH 7.4, at 22 degrees, was added to confluent monolayers of BPAEC; samples of supernatant were collected after various intervals, and E-AMP and E-Ado were quantitated by HPLC. Using these methods we found a Km of 15 +/- 6 microM, a pH optimum of 7.48, minimal effect of MgCl2 or CaCl2 at physiologic pH, and inhibition by alpha,beta-methylene ADP, a known 5'-nucleotidase inhibitor. We established that the monolayer assay was indeed measuring cell surface associated 5'-nucleotidase. To determine the effect of endotoxin, we incubated confluent monolayers with endotoxin in Minimal Essential Medium plus 10% fetal bovine serum for 24 hr, washed them, and assessed the conversion of E-AMP to E-Ado by the endotoxin-injured cells. Endotoxin stimulated endothelial ecto-5'-nucleotidase activity. This increase in 5'-nucleotidase activity in response to endotoxin injury may represent an important clearance mechanism for circulating adenine nucleotides and may be protective in acute vascular injury by increasing adenosine production.

Platelet-activating factor (PAF)-induced platelet aggregation. Modulation by plasma adenosine and methylxanthines.

This study examined the role of plasma adenosine in the modulation of platelet-activating factor (PAF) activity on platelet aggregation and serotonin (5-HT) release in human platelet-rich plasma (PRP). In addition, the effects of methylxanthines (e.g. theophylline and caffeine) were studied on PAF-induced platelet aggregation in PRP isolated from blood samples from healthy subjects. Also, PAF-induced platelet aggregation was examined in PRP samples of patients receiving theophylline treatment. These studies demonstrate that plasma adenosine levels (0.1 to 0.3 microM) play a key role in negative modulation of PAF activity on platelet aggregation and 5-HT release. After depletion of plasma adenosine, the platelet-aggregating activity of PAF was increased greatly (> 10-fold). PAF at concentrations of 0.1 to 12 microM caused no 5-HT release in PRP containing normal amounts of adenosine (blood collected in the presence of 2'-deoxycoformycin and dilazep), whereas PAF at 0.1 microM caused 5-HT release (45%) in adenosine-depleted PRP, demonstrating that plasma adenosine is much more inhibitory of 5-HT release than platelet aggregation. The adenosine antagonists theophylline (50 microM), caffeine (50 microM) and a xanthine derivative, 3,7-dimethyl-l-propargylxanthine (DMPX, 10 microM) (a more specific adenosine A2 receptor antagonist), potentiated PAF activity on platelet aggregation in PRP samples containing adenosine. Also, patients receiving theophylline treatments showed significantly greater platelet aggregation induced by PAF in their PRP samples. PAF induced a rapid increase (80% in 15 sec) in intracellular Ca2+ mobilization, which was strongly inhibited by adenosine (IC50, 0.3 microM). Our studies suggest that agents that can increase plasma adenosine levels (e.g. inhibitors of adenosine uptake and adenosine metabolism) or methylxanthines may be useful in altering (inhibiting or enhancing, respectively) PAF actions on platelets and other tissues.

Role of adenosine uptake and metabolism by blood cells in the antiplatelet actions of dipyridamole, dilazep and nitrobenzylthioinosine.

Adenosine (Ado, 10 microM) did not inhibit ADP-induced human platelet aggregation in whole blood. However, if the blood was preincubated with dipyridamole (10 microM), a potent inhibitor of the erythrocytic nucleoside transport system (NTS), Ado acted as a strong inhibitor of platelet aggregation. Similarly, Ado inhibited platelet aggregation in whole blood in the presence of other potent NTS inhibitors, dilazep (1 microM) and p-nitrobenzylthioinosine (NBMPR, 1 microM). RA 233 (10 microM), an analog of dipyridamole which is a potent inhibitor of platelet cAMP phosphodiesterase (PDE), did not evoke the Ado effect in whole blood. However, in platelet-rich plasma (PRP), RA 233 potentiated strongly Ado-mediated inhibition, whereas dipyridamole, dilazep and NBMPR were without activity. 5'-Methylthioadenosine (MTA), an Ado receptor antagonist, reversed the inhibition produced by a nucleoside transport system inhibitor plus Ado in whole blood. Dipyridamole (10 microM), dilazep (1 microM) or NBMPR (1 microM) blocked [14C]Ado (10 microM) uptake by blood cells in whole blood, whereas RA 233 (10 microM) was not effective. The combination of 2'-deoxycoformycin (dCF, 5 microM), a tight-binding inhibitor of adenosine deaminase (ADA), plus 5-iodotubercidin (ITu, 10 microM), a potent inhibitor of adenosine kinase (Ado kinase), gave comparable Ado-mediated inhibition of platelet aggregation in whole blood as was obtained when the blood was pretreated with dilazep. These studies suggest that the in vivo antiplatelet actions of drugs such as dipyridamole and dilazep result from their abilities to block erythrocytic Ado uptake and subsequent metabolism, thus elevating the extracellular steady-state concentration of the physiologically occurring, antiplatelet agent, Ado.

Adenosine metabolism in human whole blood. Effects of nucleoside transport inhibitors and phosphate concentration.

Adenosine (Ado, 10 microM) was metabolized in whole blood within 1 min, primarily to hypoxanthine and ATP. The concentration of Ado, the activities of adenosine deaminase (ADA) and Ado kinase, the Km values for Ado with ADA and Ado kinase, and the substrate inhibition of Ado kinase are factors that govern the Ado metabolism between deamination and phosphorylation. If ADA activity was blocked by 2'-deoxycoformycin (dCF, 5 microM), a tight-binding inhibitor of ADA, most of the Ado (96%) was incorporated into adenine nucleotides, whereas if Ado kinase activity was blocked with 5-iodotubercidin (10 microM), Ado was mainly (95%) metabolized into hypoxanthine. A high phosphate concentration (25 mM) caused marked increases in the formation of IMP. The nucleoside transport inhibitors dilazep (1 microM), dipyridamole (10 microM) and nitrobenzylthioinosine (NBMPR, 1 microM) strongly blocked cellular Ado metabolism. In the presence of nucleoside transport inhibitors, Ado which slowly enters the cell was metabolized principally by Ado kinase rather than ADA. Dilazep, NBMPR and dipyridamole were more effective in blocking Ado uptake and metabolism by erythrocytes suspended in a protein-free medium than by cells suspended in plasma.

Acute postoperative obstruction of extracardiac conduit due to separation of thin fibrous peel.

Late postoperative obstruction of extracardiac conduits may occur in some patients and may result from one of several mechanisms. Severe intraoperative or early postoperative obstruction of such conduits is very rare. Herein we describe a case of acute, severe, early postoperative obstruction of an extracardiac conduit; this followed partial excision and replacement of a Hancock conduit in which late postoperative calcific valvular stenosis had occurred. Unexpectedly elevated right ventricular pressure should suggest the possibility of acute conduit obstruction. In cases with partial conduit replacement, the remaining segment should be carefully inspected for the presence of a peel; if a peel is present, it should be removed from the conduit even if it is considered thin and nonobstructive.

Clinicopathological correlates of obstructed right-sided porcine-valved extracardiac conduits.

Thirteen of 308 patients (4.2%), who had received right-sided valved extracardiac conduits at the Mayo Clinic from November, 1972, to April, 1977, have required conduit replacement because of obstruction. Patients were 5 to 16 years old at initial operation and 8 to 20 years old at reoperation; the duration of conduit implantation was 27 to 79 months (mean 50). Four patients (31%) were asymptomatic; exertional dyspnea was present in eight (62%) and dizziness was reported in one (8%). Signs of conduit obstruction included increasing intensity of murmurs in 11 (85%), cyanosis in two (15%), and heart failure in one (8%). Peak pressure gradients from the right ventricle to the pulmonary arteries ranged from 50 to 140 mm Hg (mean 87) and correlated well with the degree of conduit obstruction. Catheter pullback allowed accurate localization of stenosis within the conduit, whereas angiography alone did not. The site of major obstruction was in the proximal conduit in five (38%), at the valve in nine (69%), and in the distal conduit or side branches in six (46%); stated differently, major stenosis affected the valve alone in five (38%), the graft alone in four (31%), and both the valve and the graft in four (31%). Valvular changes leading to stenosis included thrombosis, commissural fusion, and calcification, and changes consistent with insufficiency included tears, fusion of cusps to the conduit wall, and, in one case, infective endocarditis. Within the conduit, nonvalvular obstruction was due to formation of a thick fibrous peel (or neointima). Progressive thickening of the peel appeared to be due to organization of thrombus between the peel and conduit and not due to luminal mural thrombus. In one case, the peel formed a flap-valve, causing even further obstruction. Since many patients are asymptomatic, and since late conduit stenosis may develop unpredictably by several mechanisms, long-term follow-up is necessary.

Pathogenesis of nonobstructive fibrous peels in right-sided porcine-valved extracardiac conduits.

An autopsy study was conducted of 14 cardiopulmonary specimens in which porcine-valved extracardiac conduits had been placed from the right ventricle to the pulmonary artery. The gross and light microscopic appearance of the tissue lining in such conduits was evaluated. In no instance was the lining considered obstructive. The conduits had been in place for varying lengths of time ranging from 1 day to 5 years. The neointima appeared to begin developing as early as the first postoperative day as a thin layer of platelet-fibrin thrombus, followed by incorporation of red blood cells and a few leukocytes. Between 2 to 3 weeks postoperatively, such shallow thrombotic linings had become organized by fibroblastic migration and proliferation from both the proximal and distal anastomosis sites. However, incomplete development of the neointima frequently led to fenestrations. Peels, or neointimae, older than 1 month did not change, having densely fibrous luminal surfaces and having thrombus or necrotic thrombotic debris along the interface between the conduit and peel. These findings support the concept that progressive thickening of the lining peel takes place primarily along the interface between the peel and the conduit rather than the interface between the peel and the lumen.

Modified Blalock-Taussig shunt in infants and young children. Clinical and catheterization assessment.

The effectiveness of 19 modified Blalock-Taussig shunts performed with expanded polytetrafluoroethylene was evaluated clinically and by cardiac catheterization with angiography 4 to 24 months after operation. Fifteen patients underwent operation in infancy. Conduit diameters included 4 mm (nine cases), 5 mm (eight cases), and 6 mm (two cases) sizes. Two of the 4 mm conduits failed after 1 year following implantation. The remaining 17 shunts (89%) remained widely patent. In patients with patent shunts, the oxygen saturation values were significantly improved from the preoperative values. Two children demonstrated associated subclavian artery occlusion distal to the graft anastomosis. There were no deaths. Thirteen children underwent more complete elective cardiac repair 5 to 24 months later. Although the modified Blalock-Taussig procedure is an effective short-term alternative to the classic Blalock-Taussig shunt, the effectiveness of the 4 mm diameter conduit may be limited without postoperative anticoagulant therapy.