Antiedematogenic activity of the indole derivative N-salicyloyltryptamine in animal models.

The N-salicyloyltryptamine (NST) is an indole derivative compound analogue to the alkaloid N-benzoyltryptamine. In the present study, the antiedematogenic activity of NST was investigated in animal models. Firstly, the acute toxicity for NST was assessed according to the OECD Guideline no. 423. The potential NST-induced antiedematogenic activity was evaluated by carrageenan-induced paw edema in rats, as well as by dextran-, compound 48/80-, histamine-, serotonin-, capsaicine-, and prostaglandin E2-induced paw edema in mice. The effect of NST on compound 48/80-induced ex vivo mast cell degranulation on mice mesenteric bed was investigated. No death or alteration of behavioral parameters was observed after administration of NST (2000 mg/kg, i.p.) during the observation time of 14 days. The NST (100 and 200 mg/kg, i.p.) inhibited the carrageenan-induced edema from the 1st to the 5th hour (**p<0.01; ***p<0.001). The edematogenic activity induced by dextran, compound 48/80, histamine, serotonin, capsaicin, and prostaglandin E2 was inhibited by NST (100 mg/kg, i.p.) throughout the observation period (**p<0.01; ***p<0.001). The pretreatment with NST (50, 100 or 200 mg/kg, i.p) attenuates the compound 48/80-induced mast cell degranulation (**p<0.01; ***p<0.001). Thus, the inhibition of both mast cell degranulation and release of endogenous mediators are probably involved in the NST-induced antiedematogenic effect.

Bioassay-guided evaluation of antinociceptive effect of N-salicyloyltryptamine: a behavioral and electrophysiological approach.

We investigated the antinociceptive and nerve excitability effects of the N-salicyloyltryptamine (NST) NST-treated mice exhibited a significant decrease in the number of writhes when 100 and 200 mg/kg (i.p.) were administered (i.p.). This effect was not antagonized by naloxone (1.5 mg/kg, i.p.). NST inhibited the licking response of the injected paw when 100 and 200 mg/kg were administered (i.p.) to mice in the first and second phases of the formalin test. Because the antinociceptive effects could be associated with neuronal excitability inhibition, we performed the single sucrose gap technique and showed that NST (3.57 mM) significantly reduced (29.2%) amplitude of the compound action potential (CAP) suggesting a sodium channel effect induced by NST. Our results demonstrated an antinociceptive activity of the NST that could be, at least in part, associated to the reduction of the action potential amplitude. NST might represent an important tool for pain management.

Predicting college success of the educationally disadvantaged.

Test scores predict the college grades of educationally disadvantaged students at least as well as they do those of the advantaged. High school grades considerably augment the prediction for both groups. Regardless of socioeconomic level, students who are predicted to earn quite low grades within a particular college will tend to have academic difficulties if enrolled in it. There are social and educational justifications for admitting to a particular college some minority-group students who are marginally qualified for it academically, provided that the students are given adequate financial aid and effective remedial courses, tutoring, and coaching. However, if entrants are greatly underqualified academically, new curricula will be required. These may tend to segregate the specially admitted students from the regular student body, thereby diminishing the pacesetter role of the latter. Also, a degree from a special curriculum may not be viewed by employers, graduate schools, and alumni as equivalent to the other degrees awarded by the institution. Thus, admitting students who are seriously underqualified academically for the particular college seems likely to cause frustrations that may be difficult to resolve. Current demands by minority groups for "relevant" courses may reflect the academic difficulties many of their members encounter in present courses more than the educational unsuitability for them of such courses.

Sex differences in mathematical ability: fact or artifact?

A substantial sex difference in mathematical reasoning ability (score on the mathematics test of the Scholastic Aptitude Test) in favor of boys was found in a study of 9927 intellectually gifted junior high school students. Our data contradict the hypothesis that differential course-taking accounts for observed sex differences in mathematical ability, but support the hypothesis that these differences are somewhat increased by environmental influences.

Sex differences in mathematical reasoning ability: more facts.

Almost 40,000 selected seventh-grade students from the Middle Atlantic region of the United States took the College Board Scholastic Aptitude Test as part of the Johns Hopkins regional talent search in 1980, 1981, and 1982. A separate nationwide talent search was conducted in which any student under age 13 who was willing to take the test was eligible. The results obtained by both procedures establish that by age 13 a large sex difference in mathematical reasoning ability exists and that it is especially pronounced at the high end of the distribution: among students who scored greater than or equal to 700, boys outnumbered girls 13 to 1. Some hypothesized explanations of such differences were not supported by the data.

Recombinant gene expression in vivo within endothelial cells of the arterial wall.

A technique for the transfer of endothelial cells and expression of recombinant genes in vivo could allow the introduction of proteins of therapeutic value in the management of cardiovascular diseases. Porcine endothelial cells expressing recombinant beta-galactosidase from a murine amphotropic retroviral vector were introduced with a catheter into denuded iliofemoral arteries of syngeneic animals. Arterial segments explanted 2 to 4 weeks later contained endothelial cells expressing beta-galactosidase, an indication that they were successfully implanted on the vessel wall.

Antiparasitic, structural, pharmacokinetic, and toxicological properties of riparin derivatives.

Schistosomiasis, caused by helminth flatworms of the genus Schistosoma, is one of the most important parasitic diseases in the world, affecting over 200 million people in developing countries. Riparins are natural alkamides found in Aniba riparia (Lauraceae) fruits that possess several pharmacological properties. In this study, we reported the synthesis, characterization and structural analysis of six riparin derivatives (A-F), as well as their schistosomicidal activity against S. mansoni worms together with a biological, pharmacokinetic and toxicological in silico evaluation. Firstly, these compounds were synthesized, purified and characterized by elemental analysis, FT-IR spectroscopy, X-ray diffraction and theoretical calculations to evaluate their stability and conformation. Next, the schistosomicidal activity of the riparins was tested against S. mansoni worms. Bioassays revealed that Riparins E and F were the most active compounds, showing half-maximum inhibitory concentration at low micromolar ranges (IC50 values ~10 µM). Also, confocal laser scanning microscopy studies revealed tegumental damage in parasites after exposition with Riparins B, E and F. Additionally, based on MTT assay, all tested riparins showed no cytotoxic potential toward mammalian cells. Finally, in silico analyses were used to predict the absorption, distribution, metabolism, elimination and toxicity (ADMET) of the compounds. Taken together, the results revealed a promising ADMET profile and suggested that riparins could be starting points for lead optimization programs for natural products with antischistosomal properties.

Structure-related blockage of calcium channels by vasodilator alkamides in mice mesenteric artery.

The development of new calcium channel blockers is still relevant for the understanding of their physiological role and pharmacological and therapeutic purposes. For this task, natural products represent a relevant source of new drugs. The present work investigated the mechanism and the structural relationship of the vasodilator effect of riparins I, II and III in mouse small mesenteric artery. Riparins I, II and III induced an endothelium-independent and concentration-dependent vasodilator effect in mesenteric arteries. Riparins II and III were more potent than riparin I, suggesting a structural relationship of the effect of these drugs. All riparins inhibited the contractile effect of KCl, similarly to nifedipine. However, the inhibitory profile was different for the contractile responses to phenylephrine and caffeine, passing from similar to nifedipine with riparin I, for similar to SKF-96365 with riparin III. A comparable effect was observed for the increase in the intracellular calcium concentration induced by caffeine and phenylephrine. These results suggest that the higher hydroxylation provides the alkamides the ability to inhibit non-selective cation channels in addition to the inhibition of L-type calcium channels in mouse mesenteric arteries. These observations may give support to the development of new selective inhibitors of non-selective cation channels using alkamides as leading compounds.

Phospholipid fatty acid composition and vitamin E levels in the retina of obese (fa/fa) and lean (FA/FA) Zucker rats.

We have compared the fatty acid composition of the major classes of phospholipids in the retina of lean (FA/FA) and genetically obese (fa/fa) male Zucker rats. In all phospholipid fractions, there was a higher ratio of n-3 to n-6 fatty acids in obese animals whereas the total content of polyunsaturated fatty acids (PUFA) was unaffected by the genotype. Lower percentages of arachidonic acid (20:4(n-6)) were present in the phosphatidylcholine, phosphatidylinositol and phosphatidylserine fractions in the retina of obese rats. This was associated with a higher level of docosahexaenoic acid (22:6(n-3)) in these fractions. In addition, increased levels of dihomo-gamma-linolenic acid (20:3(n-6)) were present in the retinal phosphatidylcholine and phosphatidylethanolamine of obese animals. These results indicate that modifications of phospholipid fatty acid composition which have previously been reported in peripheral tissues of obese Zucker rats also affect the retina. Furthermore, the retinal levels of vitamin E were higher in obese than in lean rats suggesting differences in the tissue antioxidant status between these two genotypes.

Subchronic administration of riparin III induces antidepressive-like effects and increases BDNF levels in the mouse hippocampus.

Riparin III (Rip III) is an alcamide isolated from Aniba riparia that has presented effects of antidepressant and anxiolytic activities in acute stress behavioral models. The trial's goal was to investigate the activity of Rip III in mice exposed to corticosterone-induced chronic depression model. Swiss female mice, 22-25 g, were distributed in following experimental groups: control group (vehicle1: saline containing 0.1% dimethyl sulfoxide and 0.1% Tween-80, SC+ vehicle 2: distilled water emulsified with 2% Tween-80, PO); stressed group (corticosterone, 20 mg/kg, SC, + vehicle 2, orally); Rip III group (50 mg/kg, orally); and fluvoxamine (Flu) group (50 mg/kg, orally). The mice were exposed to the behavioral tests, and posteriorly, Brain-derived neurotrophic factor protein levels were assessed in hippocampal samples. Statistical analysis of the data was performed by one-way anova, followed by Newman-Keuls test. Both administrations of Rip III and Flu significantly reduced the immobility time in tail suspension and forced swimming tests after 21 days without affecting locomotor function. There was also an increase in BDNF protein levels in the mice hippocampus. These findings further support the hypothesis that Rip III could be a new pharmacological target for the treatment of mood disorders.

Riparin A, a compound from Aniba riparia, attenuate the inflammatory response by modulation of neutrophil migration.

Inflammation is a local tissue response to attacks characterized by vascular and cellular events, including intense oxidative stress. Riparin A, a compound obtained from Aniba riparia, has been shown to have antioxidant activity and cytotoxicity in vitro. This study was aimed at evaluating the anti-inflammatory effect of riparin A against acute inflammation. The results of our evaluations in various experimental models indicated that riparin A reduced paw edema induced by carrageenan, compound 48/80, histamine, and serotonin. Furthermore, it decreased leukocyte and neutrophil counts, myeloperoxidase activity, thiobarbituric acid reactive substance (TBARS) levels, and cytokine (tumor necrosis factor-α and interleukin-1ß) levels increased by carrageenan-induced peritonitis, and reversed glutathione levels. Riparin A also reduced carrageenan-induced adhesion and rolling of leukocytes on epithelial cells and did not produce gastric-damage as compared with indomethacin. In conclusion, the data show that riparin A reduces inflammatory response by inhibiting vascular and cellular events, modulating neutrophil migration, inhibiting proinflammatory cytokine production, and reducing oxidative stress.

Systemic delivery of the interleukin-1 receptor antagonist protein using a new strategy of direct adenoviral-mediated gene transfer to skeletal muscle capillary endothelium in the isolated rat hindlimb.

Current gene therapy strategies using adenoviral vectors to target the lung or liver have been complicated by an acute inflammatory response that can result in loss of transgene expression as well as tissue injury and necrosis. Skeletal muscle comprises 40% of total body weight; it possesses a high density, accessible capillary network that is resistant to injury and thus may be a logical target for adenoviral vectors. We hypothesized that adenoviral transduction of the rat skeletal muscle capillary bed during vascular isolation would achieve efficient gene transfer sufficient to achieve systemic serum levels of a recombinant protein without significant tissue injury. During vascular isolation of the hindleg, a replication-incompetent adenovirus (Ad) encoding for either the marker gene, human placental alkaline phosphatase (hpAP), or interleukin-1 receptor antagonist (IL-1ra) was infused and subsequently flushed from the circulation after a 30-min dwell period. Gene transfer over a 10(9)-10(12) particle/ml range to the gastrocnemius capillary endothelium and muscle fibers was highly efficient and titer-dependent, reaching maximum transduction rates of 71 +/- 7% and 25 +/- 5%, respectively, 5 days after gene transfer (n = 3-8 rats/group, p < 0.05). hpAP transgene expression was barely detectable at 14 days. No significant tissue injury or necrosis of the skeletal muscle was observed at 5 and 14 days, and distant organ gene transfer was minimal or absent. Gastrocnemius muscle from rats (n = 4) given Ad-IL-1ra had 241 +/- 66 pg IL-1ra/mg protein at 5 days, while those given Ad-hpAP, negative control (n = 3) had 35 +/- 14 pg IL-1ra/mg protein (p < 0.05). Ad-IL-1ra rats (n = 4) had serum levels of 185 +/- 20 pg/ml IL-1ra at 5 days whereas Ad-hpAP control rats (n = 5) had no IL-1ra detectable (p < 0.0001). Athymic rats given Ad-IL-1ra (n = 6) had serum levels of 493 +/- 62 pg/ml IL-1ra 14 days after transduction, and IL-1ra was detected for up to 98 days. Sera from Ad-IL-1ra athymic rats significantly inhibited IL-1 beta-induced (1 ng/ml) prostaglandin E2 (PGE2) production from cultured endothelial cells by 82 +/- 2% (p < 0.001). Thus, this gene transfer strategy is the first to result in substantial transduction of both skeletal muscle capillary endothelium and fibers, sufficient to achieve pharmacologic levels of IL-1ra. Although no acute tissue injury or necrosis was observed, persistence of transgene expression in athymic rats suggests that loss of expression in normal rats was by an immune-mediated mechanism.

Dual cell cycle-specific mechanisms mediate the antimitogenic effects of nitric oxide in vascular smooth muscle cells.

OBJECTIVE: To determine the cell cycle specificity and intracellular mechanisms involved in inhibition by nitric oxide (NO) of vascular smooth muscle cell mitogenesis. METHODS: Cultured rat aortic smooth muscle cells were synchronized by serum withdrawal, treated with the NO donor S-nitroso-N-acetylpenicillamine and the cyclic GMP analog 8-Br-cGMP at various times during cell cycle progression, and DNA synthesis measured during the S phase. Two additional NO donors, 5-nitroso-glutathione and diethylamine NONOate, were used to confirm the inhibition of DNA synthesis by S-nitroso-N-acetylpenicillamine, and the ability of two antagonists of free NO to reverse the effects of NO donors was also evaluated. Bypass of ribonucleotide reductase by use of exogenous deoxynucleosides was attempted to determine whether inhibition of this S-phase enzyme was the mechanism by which NO inhibited DNA synthesis during the S phase. RESULTS: Vascular smooth muscle cell mitogenesis was inhibited by cyclic GMP (cGMP) up to late G1 phase of the cell cycle, which corresponded to the point of greatest sensitivity to exogenous NO. In contrast to cGMP, three different NO donors inhibited DNA synthesis when added to cells synchronized in S phase, beyond the restriction point of cell cycle control in late G1 phase. This S-phase inhibition was reversible by removal of the NO donor or addition of two NO antagonists and was not observed with non-NO analogs of the donors. Inhibition by NO donors in S phase was neither reversed by the guanylate cyclase inhibitor methylene blue nor mimicked by exogenous cGMP. The S-phase inhibition by all three NO donors was reversed partially by bypass of ribonucleotide reductase, establishing this enzyme as an S-phase target of NO. CONCLUSIONS: These findings demonstrate that NO inhibits smooth muscle mitogenesis by cGMP-dependent and -independent mechanisms acting at distinct points in the cell cycle. NO is the first endogenous substance to have been shown to inhibit mitogenesis beyond the restriction point in late G1 phase, suggesting that it plays a role in regulation of cells that have lost normal mechanisms of G1 growth control, such as the hyperproliferative smooth muscle cells noted in hypertension and restenosis.

Prostanoid release from ex vivo perfused canine arteries and veins: effects of prolonged perfusion, intermittent perfusion, as well as exposure to exogenous arachidonic acid, thrombin and bradykinin.

Regulation of prostanoid release from ex vivo perfused vessel segments is not fully understood. A series of perfusion experiments were performed with canine arteries and veins to define certain regulatory phenomena. Arteries were perfused with pulsatile flow of 90 ml/min at a pressure of 100 mmHg, and veins with nonpulsatile flow of 90 ml/min at a pressure of 7 mmHg. Segments were perfused with Hanks' balanced salt solution for five 15-min periods with the perfusate exchanged after each study period. With onset of perfusion, there was an initial burst of prostacyclin release to 127 +/- 40 pg/mm2, declining to 32 +/- 10 pg/mm2 after 60 minutes (p less than 0.005). If perfusion continued for 5.5 hours, there was a stable release period between 1 and 3 hours, followed by a very slow decline. At that time addition of arachidonic acid (AA) increased prostacyclin release six-fold (p less than 0.01). Vessels perfused for 1 hour and then rested for another hour, responded to reperfusion at the second onset of flow with a two-fold increase in prostacyclin release (p less than 0.01). Vessels perfused with thrombin, bradykinin or AA (either added to each perfusate or only to the last perfusate) exhibited greater prostacyclin release than did control segments. Release of thromboxane steadily declined with time in all parts of the study, and only increased with the addition of AA to the perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal anatomic changes on magnetic resonance imaging and gadolinium-enhanced magnetic resonance angiography after renal revascularization. Original investigation.

RATIONALE AND OBJECTIVES: The anatomic and hemodynamic renal changes after renal arterial revascularization (RAR) were investigated. METHODS: Thirty-seven kidneys and 40 renal arteries were evaluated in 20 patients by using magnetic resonance imaging/magnetic resonance angiography (MRI/MRA) to assess pre- and post-RAR renal length and mass, parenchymal thickness, renal enhancement, renal artery caliber, poststenotic dilation, and signal dephasing on 3D phase contrast (PC). The kidneys and renal arteries were segregated into three groups. Group 1 included 16 patients who benefited from RAR (defined as clinical improvement based on decreased serum creatinine or fewer number of antihypertensive medications) in whom 26 renal arteries in 25 kidneys were studied. Intervention included renal artery endarterectomy (n = 20); aortorenal bypass (n = 3); renal artery reimplantation (n = 3); and percutaneous transluminal angioplasty (PTA; n = 1). A total of 27 interventions was performed, as PTA failed for one patient who subsequently underwent aortorenal bypass before reimaging. Group 2 included four patients who did not clinically benefit. A total of eight revascularized arteries were studied in seven kidneys. In group 3, six renal arteries in five kidneys from groups 1 and 2 without RAS/RAR were analyzed as an internal control. RESULTS: Technical success (defined as increased vessel caliber after intervention) was achieved in 33 of the 34 revascularized arteries. A statistically significant increase in renal length occurred regardless of clinical outcome (pre-RAR, 9.5 cm; post-RAR, 10.5 cm; P < 0.0001). Parenchymal thickness and renal mass, however, improved only in patients who benefited clinically from RAR. Parenchymal enhancement was unchanged in any of the groups studied. No significant morphologic changes were detected in the control group. CONCLUSIONS: Magnetic resonance imaging and Gd-MRA detect anatomic and hemodynamic changes that occur with renal revascularization.

Nitric oxide inhibition of endothelial cell mitogenesis and proliferation.

BACKGROUND: Endothelial cell (EC) proliferation is essential in vascular repair after injury to the vessel wall. Impaired EC proliferation may be an important factor contributing to vessel wall disease. Nitric oxide (NO) inhibits proliferation of many cells, including smooth muscle cells (SMC). We tested the hypothesis that NO inhibits EC proliferation and DNA synthesis. METHODS: Cultured canine venous ECs were treated with NO donors: S-nitroso-N-acetylpenicillamine (SNAP), S-nitroso-glutathione (GSNO), or spermine NONOate (SP NO). Proliferation was determined by cell counts after 48 hours. Parallel proliferation studies were done with rat aortic SMC. ECs synchronized in S phase were treated with the NO donor diethylamine NONOate (DEA NO), and DNA synthesis was measured as the incorporation of tritiated thymidine. A NO antagonist, cPTIO, was used to reverse the effects of DEA NO: RESULTS: Concentration-dependent (1 to 100 mmol/L) inhibition of EC proliferation (11% to 71% inhibition; p < 0.05) was seen with SNAP. Similar inhibition of proliferation was noted with the NO donors GSNO and SP NO and in SMC treated with SNAP. DEA NO caused concentration-dependent (0.1 to 1 mmol/L) inhibition of EC DNA synthesis (39% to 85% inhibition; p < 0.05), which was reversed by cPTIO. CONCLUSIONS: NO inhibits proliferation and mitogenesis of cultured ECs. This may occur in certain pathologic states, where production of NO in plaques and diseased vessels impedes reendothelialization, thus contributing to adverse thrombotic and vasospastic events.

Ultrastructure of human and transplanted canine veins: effects of different preparation media.

Human saphenous veins were studied to determine alterations resulting from preparation by moist gauze wrapping, balanced salt solution immersion, and heparinized whole blood storage at 4 degrees C. Morphologic derangements of endothelial cells, smooth muscle cells, and adventitial tissues were pronounced in the nonblood preparations. In a second study, 20 canine jugular vein segments were interposed into the iliofemoral arterial circulation, with half the grafts prepared in balanced salt solution and half in whole blood. Veins were harvested monthly for 10 months, being subjected to light and electron microscopic examinations. No thromboses or stenoses occurred. Diffuse graft dilatation affected veins three times more often when stored in lactated Ringer's solution than when stored in heparinized blood. Medial thinning, ranging from 20% to 54%, occurred in veins stored in the balanced salt solution. Endothelial regeneration was complete in all grafts within 30 days after implantation. However, medial and adventitial injury to veins prepared in balanced salt solution appeared progressive, with fibrodysplastic tissue replacing smooth muscle cells. Plasmacytosis and neutrophil infiltrates, consistent with chronic active inflammation, often accompanied fibroproliferative changes. Alterations in medial structures, rather than endothelial injury, may have an important influence on the long-term durability of transplanted vein grafts.

Effects of differing rates of protamine reversal of heparin anticoagulation.

BACKGROUND: Protamine sulfate reversal of heparin anticoagulation may be associated with adverse cardiovascular side effects. The purpose of this study was to determine whether diminished systemic oxygen consumption and hemodynamic changes were more likely to accompany rapid versus slow protamine administration. METHODS: Fifteen patients undergoing abdominal aortic aneurysm resection in a prospective randomized double-blinded study received intravenous protamine (1.5 mg/kg) rapidly during a 3-minute period (group I, n = 7) or slowly during a 15-minute period (group II, n = 8). Systemic oxygen consumption (VO2) and hemodynamic parameters were assessed for up to 20 minutes after protamine administration began. RESULTS: Blood pressure declines (millimeters of mercury) were greatest in group I with rapid protamine administration (-19 systolic and -9 diastolic) compared with group II with slow protamine administration (-12 systolic and -1 diastolic). Heart rate fell markedly in both groups I and II. Cardiac output (CO) declined in group I at virtually all time periods. Similar CO declines in group II occurred 10 minutes after protamine infusion had begun and persisted for 3 minutes after protamine administration was complete. Maximum VO2 decreases were -16% (60 seconds into protamine infusion) and -13% (1.5 minutes after protamine infusion) in groups I and II, respectively, with statistically significant declines (p < 0.05) occurring only in group I compared with baseline values. Statistically significant differences (p < 0.01), however, were found when mean declines during and after protamine infusion were compared with controls for both CO and VO2 in both groups. CONCLUSIONS: Significant declines in systemic VO2 and hemodynamic perturbations accompany protamine reversal of heparin anticoagulation during aortic surgery. Rapid protamine administration increases the magnitude of these adverse responses.

Hypotension and hypertension as consequences of baroreceptor dysfunction following carotid endarterectomy.

Arterial pressure regulation is often labile following carotid endarterectomy. Hemodynamic data from 100 consecutive endarterectomies allowed definition of three distinct postoperative blood pressure responses. A hypotensive response (group I) affected 28 patients in whom mean arterial pressure decreased from 168 +/- 29/90 +/- 15 mm Hg before operation to 110 +/- 21/68 +/- 16 mm Hg after operation (P less than 0.001). Maximum hypotension occurred 5.3 hours after endarterectomy. The preoperative pulse, 80 +/- 9 beats/min, fell to a low of 64 +/- 12 beats/min after operation (P less than 0.001). A significant hypertensive response (group II) affected 19 patients in whom mean blood pressure rose from 160 +/- 29/87 +/- 15 to 223 +/- 32/110 +/- 22 mm Hg (P less than 0.001). Maximum hypertension was noted 2.3 hours after endarterectomy. This was unaccompanied by significant pulse changes. Fifty-three patients remained normotensive (group III). Their preoperative blood pressure (150 +/- 14 mmHg). Fluctuations in pressure did not correlate with age, indication for operation, or degree of ipsilateral and contralateral carotid arterial stenosis. Postendarterectomy hypotension and hypertension appear to represent transient baroreceptor dysfunctions.

Attenuation of hemodynamic and hematologic effects of heparin-protamine sulfate interaction after aortic reconstruction in a canine model.

This investigation documented the effect of protamine sulfate pretreatment on the adverse hemodynamic and hematologic sequela of rapid intravenous protamine administration in heparinized dogs having undergone prior implantation of aortic prostheses. Fourteen dogs underwent infrarenal aortic replacement with 6 mm inner diameter by 7 cm knitted Dacron double-velour grafts. Carotid arterial, central venous, and pulmonary arterial catheters were placed for continuous hemodynamic monitoring. All dogs were adequately anticoagulated with heparin (150 IU/kg) and reversed with protamine (1.5 mg/kg/10 sec) after graft insertion. Pretreatment regimens studied included normal saline (n4), protamine 0.75 mg/kg (n5), and protamine 2.25 mg/kg in three divided doses of 0.75 mg/kg each (n5). All pretreatment agents were administered 3 minutes before heparinization. Blood pressure (BP), heart rate (HR), pulmonary artery pressure (PAP) and cardiac output (CO) were measured. Hematologic assessments included platelet count (PC), leukocyte count, thrombin clotting time, and total hemolytic complement. Significant salutory effects were associated with protamine pretreatment regarding BP, HR, PAP, CO, and PC. It is concluded that adverse hemodynamic effects of protamine reversal are blocked and certain hematologic effects are reduced with protamine pretreatment before heparinization and its reversal in this canine experimental model.