Plasma volume expansion with Haemaccel does not impair haemostasis during reduction mammaplasty

OBJECTIVES: An in vivo study under well-controlled conditions was undertaken to determine the effect of Haemaccel, a colloidal plasma volume expander, on normal haemostasis. METHODOLOGY: Twenty patients, who were admitted for reduction mammaplasty, were included in this study. A standardised anaesthesia protocol was followed with all patients. Ten patients received 500 ml Haemaccel and 10 controls received 1,500 ml Ringer's lactate, a crystalloid solution. The solutions were administered intravenously during surgery over a period of 30-40 minutes. Standardised clinical observations and haematological tests were done at the following time intervals: after anaesthesia but before infusion of the plasma substitute, immediately after infusion was completed, and 20, 40 and 60 minutes after infusion. RESULTS: The blood pressure, pulse rate and O2 saturation levels were not influenced by the treatment given. Haemodilution was similar for the two patient groups. The platelet count and plasma levels of fibrinogen decreased in parallel with haemodilution. Thereafter the platelet count gradually increased to pre-infusion counts at 60 minutes. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT) and platelet aggregation in response to adenosine diphosphate (ADP) and collagen were not affected by the plasma volume expander given. Arachidonic acid-induced aggregation decreased significantly after Ringer's lactate was given but did not change when Haemaccel was given. The bleeding time was prolonged slightly, but not significantly, from 7.4 +/- 1.6 minutes to 8.8 +/- 1.6 minutes with Ringer's lactate and from 6.9 +/- 2.0 to 9.7 +/- 3.7 minutes with Haemaccel. CONCLUSIONS: We could not find any scientific evidence that Haemaccel affects haemostasis; neither does it increase bleeding relative to Ringer's lactate.     

Influence of heat shock protein 70 and metallothionein induction by zinc-bis-(DL-hydrogenaspartate) on the release of inflammatory mediators in a porcine model of recurrent endotoxemia

The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. Recent in vitro studies with alveolar macrophages or monocytes show that induction of the stress response in these cells is followed by a decreased liberation of major cytokines [tumor necrosis factor-alpha (TNF alpha) and interleukin-1 (IL-1)] after endotoxin challenge. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an altered pattern of inflammatory mediator release. Therefore, we measured the time course of thromboxane-B2 (TxB2), 6-keto-PGF1 alpha, platelet activating factor (PAF), TNF alpha, interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Klosterhalfen et al., Biochem Pharmacol 43: 2103-2109, 1992). Induction of the stress response was done by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenasparate = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 and metallothionein expression in the lungs, liver, and kidneys and increased plasma levels of TNF alpha, IL-1 beta, IL-6, and TxB2 as opposed to untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators as opposed to the untreated group. The time course of mediator release was identical with the decreasing and increasing three peak profiles described previously. Hemodynamic data presented significantly decreased peak pulmonary artery pressures and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of stress proteins by Zn2+ could be a practicable strategy to prevent sepsis.     

Effects of low density and high density lipoproteins isolated from non-insulin dependent diabetic patients on prostaglandin secretion by mouse macrophage cell line P388D1

We have previously shown that low-density (LDL) and high-density (HDL) lipoprotein from healthy subjects can promote in vitro prostaglandin (PG) release by murine macrophages. In this pilot study, we have measured PG production induced by lipoproteins of six diabetic patients with poor metabolic control, compared to five healthy controls. Plasma lipoprotein levels were similar in both groups. Lipoprotein fractions were purified by sequential ultracentrifugation. After lipoprotein incubation with cells, supernatants were extracted and PG quantified by HPLC. In presence of LDL, in control subjects, there was an increase in total PG production, mainly due to thromboxane B2 (TxB2). In diabetic patients, the secretion pattern was similar. In presence of HDL, in control subjects, total PG secretion was also increased, but it was balanced between TxB2 and prostacyclin. In diabetic patients, at low HDL concentration (10 mg/l) the secretion was mainly due to TxB2, while at higher HDL concentrations (100 mg/l). the secretion was balanced between TxB2 and prostacyclin. Comparison of means of areas under curve for the two groups studied showed that LDL increased all PG secretion in diabetic patients compared to controls (P < 0.05 for PGF2alpha), while HDL increased all PG secretion in controls compared to diabetic patients, except PGF2alpha. Our work suggests a key role of LDL in TxB2 secretion in diabetic patients, which is a major proaggregant and vasoconstrictive agent. There was also an increased secretion of all PG in diabetic patients.     

Lupus erythematosus-like features in patients with cutaneous T-cell lymphoma

The purpose of this clinical study was to review experience in the management, and outcome of eclamptic patients at Rajavithi Hospital. Standardized treatment for all cases of eclampsia has consisted of magnesium sulfate intravenously and intramuscularly to control convulsions by means of Chesley and Tepper's regimen, intravenous hydralazine intermittently to lower diastolic blood pressure when it exceeds 110 mmHg, and initiation of delivery as soon as the patient has regained consciousness and is stable. During a ten-year period there were 167,200 deliveries and 90 eclamptic patients, yielding an incidence of eclampsia of 1 in 1,857 deliveries. There were three maternal deaths (3.3%) due to intracerebral hemorrhage. Serious adverse maternal outcomes were more frequent in women whose convulsions occurred before delivery. Excluding postpartum cases, perinatal mortality of fetuses weighing 1,000 g or more was 11.7 per cent. Magnesium sulfate is the drug of choice for treatment of eclamptic convulsions. In most situations, clinical assessment of deep tendon reflexes, respirations, and urine output is adequate to monitor maternal magnesium toxicity without the need to determine actual maternal serum magnesium levels.     

Reduction of renal functional reserve in kidney transplant recipients: a possible role of arachidonic acid metabolism alterations

AIM: Renal functional reserve (RFR), resulting from an increase in glomerular filtration (GFR) after protein load, is a matter of debate. In kidney transplant recipients most studies have failed to show conclusive results, reporting either the absence, the reduction or the presence of renal reserve in normo-functioning kidneys. The aim of this study was to investigate RFR in kidney transplant patients as well as the possible hormonal vasoactive alterations underlying the reduction of renal reserve reported in some patients. PATIENTS AND METHODS: We studied 8 controls and 25 patients, the latter with no history of acute rejection for at least 12 months and GFR >50 ml/min. The 25 patients were divided into 2 groups based on the presence (10) or the absence (15) of RFR. RESULTS: Both the RFR group and the controls experienced a similar increase of GFR after oral protein load: 24.3 +/- 15.57% vs 24.4 +/- 10.8%. The group without RFR showed a paradoxical reduction of GFR after oral protein load: 13.3 +/- 13.2% (p <0.001). We analyzed the filtration fraction (FF) and observed that the group without RFR had higher values than the group with RFR and the controls: 0.35 +/- 0.11 vs 0.29 +/- 0.07 (p = 0.01) and vs 0.26 +/- 0.02 (p = 0.04). The hyperfiltration state observed in the group without RFR was sustained by a high level of thromboxane. The urine ratio TxB2/6ketoPgF1alpha was higher in the group without RFR than in the RFR group 0.78 +/- 0.2 vs 0.64 +/- 0.1 (p = 0.01). This ratio decreased only in the RFR group after a meat meal. In all the patients, changes of TxB2/6ketoPGF1alpha were inversely correlated to changes of GFR after a meat meal (r = -0.6, p = 0.01). CONCLUSIONS: In conclusion, these data demonstrate that kidney transplant recipients with good organ function can be grouped according to the presence of RFR. RFR appears to be inversely correlated with the TxB2/6ketoPGF1alpha ratio, and its decrease seems to be linked to the failure of thromboxane to decrease and prostacycline to increase after a meat meal.     

Effects of 4 hours magnesium sulfate infusion on fetal heart rate variability and reactivity in a goat model

Effects of magnesium sulfate were investigated on fetal heart rate (FHR) baseline, variability, and reactivity in goats. Six chronically catheterized fetuses of Japanese Saanen goat at 125 to 130 days' gestation (term = 147 days) were used. Magnesium sulfate was directly infused to the fetuses. Short-term variability and long-term variability were obtained according to Huey et al. The baseline, reactivity, short-term variability and long-term variability of the FHR were compared between those receiving magnesium sulfate infusions and those receiving vehicle infusions without magnesium sulfate for 4 hr. Two-way analysis of variance (ANOVA) and Duncan's multiple range test was applied for statistical significance. Four hours magnesium sulfate infusion significantly increased fetal plasma concentration of magnesium from 2.4-6.6 mg/dL, without significant changes in fetal respiratory gases and pH values. The baseline FHR was significantly decreased by magnesium infusion compared with that receiving vehicle infusion. The incidence of acceleration, short-term variability, and long-term variability during the fourth hour of magnesium infusion was also significantly decreased compared to a controlled infusion. The time spent by high amplitude phase of short-term variability and that of long-term variability were also significantly reduced. Significant correlation was obtained between the magnesium concentration and incidence of acceleration at fourth hour of magnesium infusion. Four hours infusion of magnesium sulfate significantly decreases baseline FHR, short-term variability, long-term variability, and reactivity in fetal goats at 0.85 gestation.     

Adjustment of magnesium sulfate infusion rate in patients with preterm labor

OBJECTIVE: Our purpose was to investigate factors that might influence serum magnesium levels during intravenous magnesium sulfate tocolytic therapy. STUDY DESIGN: Thirty-three women receiving magnesium sulfate for preterm labor participated in this prospective, observational study. Gestational ages were 24 to 34 weeks. Four groups of women were identified according to the maintenance magnesium infusion rate required for arresting preterm labor after 5 g of therapy induction: 1.5, 2, 2.5, and 3 g/h. Serum magnesium samples were drawn after a predefined period of at least 18 hours of arrested preterm labor, at a minimum of every 6 hours. Variables examined included serum albumin; serum protein; serum ionized calcium; serum creatinine; creatinine clearance; 24-hour urine output; maternal height, weight, body surface area; and body mass index. RESULTS: By use of a multivariate stepwise regression model we identified four variables that independently and significantly contributed to the model: magnesium infusion rate (P < .001); total serum protein level (P < .001); serum creatinine level (P = .009); and maternal weight squared (P = .026). Seventy-two percent of the variance was accounted for by use of these parameters. A predictive linear model, developed to relate these factors, produced the following formula: Suggested magnesium infusion rate = 0.89 x Serum magnesium concentration (mg/dL) - 3.16 x Serum creatinine (mg/dL) - 0.66 x Serum total proteins (g/dL) + 0.0001 x (maternal weight)2 (kg) + 2.30. CONCLUSIONS: Serum creatinine, serum protein, and maternal weight can be used to adjust the dose of magnesium sulfate in patients with premature labor to achieve therapeutic serum levels of magnesium more rapidly and safely.     

Effects of tromethamine buffer on coagulation variables and ionized calcium concentration in dogs

OBJECTIVE: To evaluate coagulation variables in 2 groups of dogs after tromethamine administration. ANIMALS: 13 Beagles. PROCEDURES: Both groups of dogs received a 30-minute IV infusion of 10 ml of 0.3M tromethamine/kg of body weight. In unsedated dogs (group 1, n = 8), prothrombin time, activated partial thromboplastin time, normalized ionized calcium concentration, platelet numbers, and platelet function were measured prior to treatment, at the end of the infusion, and 1 hour after the infusion. In xylazine-sedated dogs (group 2, n = 5), buccal mucosal bleeding time and plasma percentage of von Willebrand factor antigen were measured before and 1 hour after infusion, and fibrin degradation products concentration was measured 1 hour after infusion. Platelet function was assessed by determining platelet aggregation and by measuring ATP release from the aggregating platelets over 6 minutes, using a whole blood aggregometer, with 20, 10, and 5 microM ADP and 5 and 10 micrograms of collagen/ml as platelet activation agonists. RESULTS: There was no significant change in any of the variables measured in either group of dogs, compared with baseline values. CONCLUSIONS AND CLINICAL RELEVANCE: When administered to healthy dogs, tromethamine does not change the coagulation indices measured.     

Contribution of the CXC chemokines IP-10 and Mig to the antitumor effects of IL-12

DMP 728 showed a dose-dependent inhibition of platelet aggregation at doses of 0.05 to 0.9 mg per subject, with a maximal inhibition (> 90%) of platelet aggregation at doses of 0.9 mg per subject and higher. Minimal changes in bleeding time from baseline were observed at doses up to 0.6 mg per subject. At the 0.9 mg/subject dose level, bleeding time was prolonged by approximately twofold to threefold above the baseline. At higher doses (1.5 mg/subject to 3.9 mg/subject), bleeding time prolongation was > 30 minutes during the infusion. In all dose groups, bleeding times returned to the control value within 8 hours after cessation of the infusion. Maximum plasma concentration and area under the curve of DMP 728 increased linearly and proportionally to the dose. No clinical changes in vital signs, 12-lead electrocardiograms, physical examinations, coagulation tests, or stool hemoccult tests were observed at any of the doses. In conclusion, DMP 728 is a potent antiplatelet agent and well tolerated at doses ranging from 0.05 to 3.0 mg/subject.     

Reduction by indobufen of neutrophil activation in peripheral arterial occlusive disease

We evaluated the effectiveness of indobufen administration in reducing neutrophil activation in a clinical model of ischemia-reperfusion. Thirty stable patients with intermittent claudication due to occlusive peripheral arterial disease of the leg were randomly assigned to two groups. Patients in group I were treated with indobufen [200 mg orally twice daily (p.o. b.i.d.) for a week]; patients in group II received a placebo. Both groups of patients were submitted to standardized treadmill exercise until onset of claudication. Plasma levels of thromboxane B2 (TxB2) and 6-keto-prostaglandin F1alpha(6-k-PGF1alpha) neutrophil filterability, and neutrophil activation (by nitro-blue tetrazolium test) were assessed in blood samples from the femoral vein draining the ischemic leg. The values were obtained at rest and 5, 30, and 60 min after onset of claudication. Urinary albumin excretion was measured at rest and 1 h after onset of claudication. Plasma levels of TxB2 and 6-k-PGF1alpha increased significantly in the placebo group 5 min after onset of claudication, whereas only a slight nonsignificant increase was observed in the indobufen-treated group at the same timepoint.     

Cardiopulmonary and anesthetic effects of propofol in wild turkeys

OBJECTIVE: To determine safety, anesthetic variables, and cardiopulmonary effects of i.v. infusion of propofol for induction and maintenance of anesthesia in wild turkeys. ANIMALS: 10 healthy, adult wild turkeys. PROCEDURE: Anesthesia was induced by i.v. administration of propofol (5 mg/kg of body weight) over 20 seconds and was maintained for 30 minutes by constant i.v. infusion of propofol at a rate of 0.5 mg/kg/min. Heart and respiratory rates, arterial blood pressures, and arterial blood gas tensions were obtained prior to propofol administration (baseline values) and again at 1, 2, 3, 4, 5, 10, 15, 20, 25, and 30 minutes after induction of anesthesia. All birds were intubated immediately after induction of anesthesia, and end-tidal CO2 concentration was determined at the same time intervals. Supplemental oxygen was not provided. RESULTS: Apnea was observed for 10 to 30 seconds after propofol administration, which induced a decrease in heart rate; however, the changes were not significant. Compared with baseline values, respiratory rate was significantly decreased at 4 minutes after administration of propofol and thereafter. Systolic, mean, and diastolic pressures decreased over the infusion period, but the changes were not significant. Mean arterial blood pressure decreased by 30% after 15 minutes of anesthesia; end-tidal CO2 concentration increased from baseline values after 30 minutes; PO2 was significantly decreased at 5 minutes after induction and thereafter; PCO2 was significantly (P < 0.05) increased after 15 minutes of anesthesia; and arterial oxygen saturation was significantly (P < 0.05) decreased at the end of anesthesia. Two male turkeys developed severe transient hypoxemia, 1 at 5 and the other at 15 minutes after induction. Time to standing after discontinuation of propofol infusion was 11 +/- 6 minutes. Recovery was smooth and unremarkable. CONCLUSION: Propofol is an effective agent for i.v. induction and maintenance of anesthesia in wild turkeys, and is useful for short procedures or where the use of inhalational agents is contraindicated.     

Prevention of bleeding after cardiopulmonary bypass with high-dose tranexamic acid. Double-blind, randomized clinical trial

This prospective, double-blind, randomized trial assessed the effectiveness of high-dose tranexamic acid given in the preoperative period on blood loss in patients undergoing cardiopulmonary bypass. One hundred fifty patients scheduled to undergo cardiac operations with cardiopulmonary bypass were randomized into three groups of equal size. The first group received 10 gm of tranexamic acid intravenously over 20 minutes before sternotomy and a placebo infusion over 5 hours. The second group received 10 gm of tranexamic acid over 20 minutes and then another 10 gm infused intravenously over 5 hours. The control group received a placebo bolus and a placebo infusion over 5 hours (0.9% normal saline solution). The blood loss after the operation was measured at 6 hours and 24 hours. The homologous blood and blood products given during and up to 48 hours after operation were recorded. Eighteen percent of the control group patients shed more than 750 ml blood in 6 hours compared with only 2% in both tranexamic acid groups. Patients who shed more than 750 ml blood required 93% more red blood cell transfusions than patients without excessive bleeding. Tranexamic acid (10 gm) given intravenously in the period before cardiopulmonary bypass reduced blood loss over 6 hours by 50% and over 24 hours by 35%. Continued tranexamic acid infusion (10 gm over 5 hours) did not reduce bleeding further. There was no difference in the coagulation profile before operation between patients with and without excessive bleeding. However, coagulation tests done in the postoperative period indicated ongoing fibrinolysis and platelet dysfunction in patients with excessive bleeding.     

Effect of dehydroepiandrosterone sulfate on uterine artery flow velocity waveforms in term pregnancy

OBJECTIVE: To investigate the interrelation between estrogen synthesis by the fetoplacental unit and uteroplacental hemodynamics in term pregnancy. METHODS: Transvaginal color Doppler flow imaging and pulsed Doppler ultrasonographic assessments were made on ten normal full-term pregnant women before and 3, 5, 10, 30, and 60 minutes after the administration of a 200-mg intravenous dose of dehydroepiandrosterone sulfate (DHAS) in 20 mL of 5% dextrose. Ten normal full-term pregnant women received 20 mL of 5% dextrose as controls. The pulsatility index (PI) values for the uterine artery, heart rate, and mean arterial pressure were recorded. Plasma estradiol (E2) was measured before and 10 minutes after the infusion. RESULTS: In the DHAS group, uterine artery PI decreased from baseline by 26% (P < .05) after 5 minutes, and the mean reduction was 36% (P < .05) after 10 minutes and 15% (P < .05) after 30 minutes. The PI returned to the baseline value 60 minutes later. In the control group, there was no change in uterine artery PI. No change was found in heart rate or mean arterial blood pressure in the control or DHAS groups. The mean plasma E2 increased from 22.3 +/- 6.6 to 56.2 +/- 24.1 ng/mL (P < .05) 10 minutes after the infusion in DHAS subjects, whereas there was no significant change in plasma E2 in the controls. CONCLUSION: Dehydroepiandrosterone sulfate induces a significant decrease in the uterine artery PI, which suggests a possible decrease in uterine vascular impedance in term pregnancy.     

In vivo and in vitro studies of the inhibitory effect of propofol on human platelet aggregation

BACKGROUND: The inhibitory effects of propofol on platelet aggregation are controversial because the fat emulsion used as the solvent for propofol may affect platelet function. The effects of propofol on platelet intracellular calcium ion concentration and on aggregation were investigated. METHODS: Platelet aggregation was measured in 10 patients who received an intravenous infusion of propofol. Intralipos, the propofol solvent, was infused in 10 healthy volunteers and platelet aggregation were measured. The in vitro effects of propofol and Intralipos on platelets were also investigated. The inhibitory effects of various concentrations of propofol were studied. The effects of propofol on the changes in intracellular calcium level using a fluorescent dye, fura-2, were also observed. Template bleeding time was measured to determine the effect of propofol in clinical use. RESULTS: Platelet aggregation was significantly inhibited by infusion of propofol, although bleeding time was not prolonged. Intralipos did not inhibit platelets either in vivo or in vitro. Propofol significantly inhibited platelet aggregation in vitro and at 5.81 +/- 2.73 microg/ml but not at 2.08 +/- 1.14 microg/ml. The increase of intracellular calcium concentration was inhibited both in influx and discharge of calcium. CONCLUSIONS: Propofol inhibited platelet aggregation both in vivo and in vitro. Inhibition of platelet aggregation appeared to be caused by propofol itself and not by the fat emulsion. This inhibitory effect was also supported by the suppressed influx and discharge of calcium. No change in the bleeding time suggests that this inhibitory effect does not impair hemostasis clinically.     

Automated heparin-delivery system to control activated partial thromboplastin time: evaluation in normal volunteers

BACKGROUND: Unfractionated heparin is used widely; however, control of the level of anticoagulation remains its greatest problem, with fewer than 35% of patients having activated partial thromboplastin times (aPTTs) within a range of 55 to 85 seconds in recent trials. METHODS AND RESULTS: We developed and tested a prototype of an automated heparin control system (AutoHep) in which a computer-based titration algorithm adjusted the heparin infusion to reach a target aPTT. In 1 study, 12 healthy male subjects received an intravenous infusion of heparin with the rate determined by AutoHep and were randomized to receive an initial bolus or no bolus of heparin preceding the infusion. A second study evaluated the automated blood sampling system in 12 subjects. Of the 344 end-point aPTT measurements, 78% were within +/-10 seconds of the target (prespecified primary end point), and 89% were within a +/-15-second range. The time to achieve a target aPTT was 93 minutes without and 150 minutes with an initial heparin bolus. The total percentage of time within the target range +/-15 seconds was 46 of 48 hours (96%). The automatic blood sampling system successfully obtained 96% of all scheduled samples. CONCLUSIONS: These results suggest that the AutoHep system has the potential to significantly improve aPTT control of intravenous heparin compared with current clinical practice.     

Tirofiban. A review of its use in acute coronary syndromes

Tirofiban is an intravenously administered nonpeptide glycoprotein IIb/IIIa receptor antagonist which specifically inhibits fibrinogen-dependent platelet aggregation and prolongs bleeding times in patients with acute coronary syndromes. Adenosine diphosphate (ADP)-induced platelet aggregation returns to near-baseline levels within 4 to 8 hours after cessation of a tirofiban infusion, a finding consistent with the drug's elimination half-life of approximately 2 hours. Three large clinical trials have shown that, when administered with a standard heparin and aspirin regimen, tirofiban reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave myocardial infarction (MI) and in patients undergoing percutaneous revascularisation. In PRISM-PLUS, a study involving 1915 patients with unstable angina/non-Q-wave MI, administration of intravenous tirofiban (0.4 microgram/kg/min loading dose for 30 minutes followed by a 0.10 microgram/kg/min infusion) with heparin for at least 48 (mean 71.3) hours reduced the 7-day risk of the composite end-point of MI, death and refractory ischaemia by 32% compared with heparin alone. The between-group risk reduction remained significant at 30 days (22%) and 6 months (19%). Similarly, in high-risk patients undergoing coronary angioplasty in RESTORE, the addition of tirofiban (10 micrograms/kg bolus in the 3 minutes prior to intervention followed by 0.15 microgram/kg/min for 36 hours) to a standard heparin regimen significantly reduced the risk of ischaemic complications by 38% on day 2 and 27% on day 7 compared with heparin alone. Although interim analysis in PRISM-PLUS showed that the use of tirofiban without heparin increased the 7-day risk of death compared with heparin alone, this finding was inconsistent with the effects of tirofiban on the risk of death in PRISM, a study involving 3232 patients with unstable angina/non-Q-wave MI. Tirofiban is generally well tolerated. Bleeding complications were the most commonly reported events associated with tirofiban in clinical trials, but the rate of major bleeding in tirofiban recipients was not significantly different from that reported with heparin. Thrombocytopenia (platelet count < 90,000 cells/microliter) occurred slightly more frequently with tirofiban (with or without heparin) than with heparin alone. CONCLUSIONS: Tirofiban reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave MI and high-risk patients undergoing revascularisation when used against a background of heparin and aspirin. Furthermore, the drug has an acceptable tolerability profile. Therefore, intravenous tirofiban is likely to be used as an adjunct to heparin and aspirin in patients with acute coronary syndromes including high-risk patients undergoing revascularisation.     

Inhaled nitric oxide inhibits human platelet aggregation, P-selectin expression, and fibrinogen binding in vitro and in vivo

BACKGROUND: Recent data suggest that inhaled NO can inhibit platelet aggregation. This study investigates whether inhaled NO affects the expression level and avidity of platelet membrane receptors that mediate platelet adhesion and aggregation. METHODS AND RESULTS: In 30 healthy volunteers, platelet-rich plasma was incubated with an air/5% CO2 mixture containing 0, 100, 450, and 884 ppm inhaled NO. ADP- and collagen-induced platelet aggregation, the membrane expression of P-selectin, and the binding of fibrinogen to the platelet glycoprotein (GP) IIb/IIIa receptor were determined before (t0) and during the 240 minutes of incubation. In addition, eight patients suffering from severe adult respiratory distress syndrome (ARDS) were investigated before and 120 minutes after the beginning of administration of 10 ppm inhaled NO. In vitro, NO led to a dose-dependent inhibition of both ADP-induced (3+/-3% at 884 ppm versus 70+/-6% at 0 ppm after 240 minutes; P<.001) and collagen-induced (13+/-5% versus 62+/-5%; P<.01) platelet aggregation. Furthermore, P-selectin expression (36+/-7% of t0 value; P<.01) and fibrinogen binding (33+/-11%; P<.01) were inhibited. In patients with ARDS, after two who did not respond to NO inhalation with an improvement in oxygenation had been excluded, an increase in plasma cGMP, prolongation of in vitro bleeding time, and inhibition of platelet aggregation and P-selectin expression were observed, and fibrinogen binding was also inhibited (19+/-7% versus 30+/-8%; P<.05). CONCLUSIONS: NO-dependent inhibition of platelet aggregation may be caused by a decrease in fibrinogen binding to the platelet GP IIb/IIIa receptor.     

Isolated magnesium malabsorption in a 10-year-old boy

Isolated magnesium malabsorption (congenital hypomagnesemia) has been reported in approximately 30 patients worldwide. Patients typically present by 6 months of age with convulsions and diarrhea. We report an unusual case of isolated magnesium malabsorption in an older boy with no diarrhea.     

Thromboxane A2 receptor-specific antagonism in hypothermic cardiopulmonary bypass

Using a thromboxane A2 receptor-specific antagonist, SQ 30,741, this study was undertaken to define the role of thromboxane A2 in postischemic myocardial reperfusion injury and in the heparin-protamine reaction. Eighteen heparinized (300 units/kg) sheep were placed on cardiopulmonary bypass (CPB) after complete instrumentation, cooled to 28 degrees C, and had their aortas crossclamped for 1 hour. They were then rewarmed to 36 degrees C and weaned from CPB without inotropic support. Control sheep (n = 6) received a saline infusion throughout the procedure. Bolus animals (n = 6) received 5 mg/kg of SQ 30,741 at 5 minutes after discontinuation of CPB and before protamine sulfate administration. Infusion animals (n = 6) received an SQ 30,741 bolus of 5 mg/kg followed by a continuous infusion of 5 mg.kg-1 hr-1 of SQ 30,741 initiated before CPB. All animals received 5 mg/kg of protamine sulfate over a 15-second period 15 minutes after being weaned from CPB. Control animals exhibited significantly decreased global myocardial function after the 1-hour ischemic interval. Further significant functional decline and increase in pulmonary pressure occurred after protamine sulfate administration. Bolus animals experienced a similar postischemic injury, but had no further decrease in function following protamine infusion. Infusion animals had significantly improved global myocardial function after bypass compared with both other groups and were also protected from the deleterious effects of protamine sulfate administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of magnesium sulfate and lidocaine in the treatment of ventricular arrhythmias in experimental amitriptyline poisoning in the rat

OBJECTIVES: Amitriptyline poisoning is associated with ventricular arrhythmias. Standard treatment is sodium bicarbonate but further intervention may be necessary. The present study compared the actions of lidocaine and magnesium sulfate on ventricular tachycardia induced by amitriptyline. DESIGN: Nonrandomized, controlled, intervention trial. SETTING: University laboratory. SUBJECTS: Thirty male Wistar rats anesthetized with pentobarbital and mechanically ventilated. INTERVENTIONS: After pretreatment with norepinephrine, the animals were subjected to a continuous infusion of amitriptyline. After the appearance of ventricular tachycardia, they were treated with magnesium sulfate (45 mg/kg + 15 mg/kg/min) or lidocaine (1 mg/kg + 0.5 mg/kg/min) or glucose infusion as a control. MEASUREMENTS AND MAIN RESULTS: In the group treated with magnesium sulfate, electrocardiogram tracings demonstrated that nine of ten animals converted from ventricular tachycardia to sinus rhythm compared with one of ten in both the lidocaine- and glucose-treated groups (p < .001). The animals treated with magnesium sulfate also had a significantly longer total time in sinus rhythm (10.0 +/- 1.6 mins) than those rats treated with lidocaine (1.7 +/- 1.5 mins) or glucose (1.5 +/- 1.5 mins). Magnesium sulfate significantly decreased blood pressure and heart rate, but no severe hemodynamic side effects were observed. CONCLUSIONS: Magnesium sulfate is effective in converting ventricular tachycardia in hyperadrenergic amitriptyline poisoning. In contrast, lidocaine had no effect on arrhythmias.