Blood Sampling Site Research Articles

Big Endothelin-1 and Endothelin-1 Plasma Levels Are Correlated With the Severity of Primary Pulmonary Hypertension

Primary pulmonary hypertension (PPH) is a rare disease of unknown etiology that is characterized by a poor prognosis. This study was undertaken to investigate possible correlations between endothelin (ET)-1 and big ET-1 plasma levels and the severity of PPH. Sixteen consecutive patients with PPH were included. Hemodynamics of patients with PPH were measured by right-heart catheterization, and a 6-min walk test was performed. Plasma levels of the biologically active peptide ET-1 and its precursor big ET-1 were determined in blood samples from the pulmonary artery, peripheral artery, and peripheral vein by radioimmunoassay. A strong correlation was shown between pulmonary vascular resistance, mean pulmonary artery pressure, cardiac output, cardiac index, 6-min walk data, and elevated plasma levels of big ET-1 as well as mature ET-1 plasma levels at all sites of blood sampling (p < 0.01 and p < 0.05, respectively). Levels of circulating ET-1 might become a prognostic marker for patients with PPH and serve as a tool for the selection of patients who may benefit from treatment with ET-receptor antagonists.

Arterial and venous Thrombelastograph variables differ during cardiac surgery.

The Thrombelastograph (TEG; Haemoscope Corp., Skokie, IL) coagulation analyzer is an effective point-of-care monitor for routine clinical practice and clinical research. Prior investigators have used either arterial or venous samples of blood for TEG measurements. We conducted this prospective cohort study to determine potential differences in TEG variables between arterial and venous blood samples. Arterial and venous samples were drawn from 40 cardiac surgical patients, yielding 134 pairs for comparison. Twenty-nine comparisons (control) were between arterial and arterial samples and were not significantly different. For the arterial and venous comparisons (n = 105), mean (+/-sd) arterial and venous values were the following: reaction time, 10 +/- 2 mm vs 13 +/- 4 mm, P = 0.004; maximum amplitude, 59 +/- 9 mm vs 49 +/- 12 mm, P < 0.001; alpha angle, 61 +/- 10 degrees vs 51 +/- 14 degrees, P < 0.001; K, 5 +/- 2 mm vs 8 +/- 4 mm, P = 0.007; and lysis, 2.5 +/- 1.7 vs 2.5 +/- 2.0 (not significant), arterial versus venous, respectively. Arterial blood samples demonstrated TEG values reflecting stronger (larger maximum amplitude) and faster (shorter reaction time and K value, wider alpha angle) clot formation. The results suggest that users of TEG coagulation analyzers should be consistent with the site of blood sampling given the potential differences obtained. Thrombelastograph (TEG) values obtained from venous blood samples differ from values obtained from arterial blood samples. When the TEG coagulation analyzer is used for clinical purposes, it is important to be consistent in the blood collection site.

Surgical Maneuvers Enhance Molecular Detection of Circulating Tumor Cells During Gastric Cancer Surgery

To evaluate the relation between the presence of cancer cells in blood according to the time course during a surgical procedure and liver metastases in patients with gastric cancer. Several studies have reported on the detection of circulating cancer cells in blood by reverse transcriptase-polymerase chain reaction (RT-PCR). However, few reports have examined the relation between molecular detection of circulating cancer cells according to the time course during a surgical procedure and blood-borne metastases. Blood samples from 57 patients with gastric cancer were obtained from the portal vein, peripheral artery, and superior vena cava before and after tumor dissection. After total RNA was extracted from each blood sample, carcinoembryonic antigen (CEA)-specific RT-PCR was performed. CEA-mRNA was detected in the blood of 21 (36.8%) of the 57 patients. CEA-mRNA was not detected in the blood obtained from 15 healthy volunteers and 15 patients with benign disease. The positive rate increased in proportion to the depth of tumor. The incidence of positive CEA-mRNA did not differ among the various sites of blood sampling. The appearance of circulating cancer cells was related to the surgical maneuver. A significant relation was found between the detection of CEA-mRNA and blood-borne metastases. A high incidence of positive CEA-mRNA was found in the blood during gastric cancer surgery. Surgical maneuvers are a possible cause of hematogenous metastasis. The authors found that patients with positive CEA-mRNA had a high risk of blood-borne metastasis even after curative resection.

The value of capillary whole blood lactate for blood transfusion requirements in anaemia of prematurity.

To evaluate the usefulness of blood lactate as an indication for blood transfusion in anaemia of prematurity by means of a study protocol which considers the site of blood sampling and the repeatability of lactate measurements. Prospective clinical study. Multidisciplinary, neonatalpaediatric intensive care unit of a non-university, teaching children's hospital. Comparison of pre- and 48-h post-transfusion capillary whole blood lactate in 18 anaemic premature babies. In 30 neonates the agreement between capillary and arterial lactate was analysed by using the Bland Altman plot. In 30 stable premature infants four capillary lactate measurements were carried out within 24 h and analysed with regard to variability (coefficient of variation (CV); association between SD and mean) and to establish normal values. In the transfused infants, haematocrit increased from 23 (SD 3)% to 37 (SD 3)%. Mean lactate decreased from 2.5 (SD 1.0) to 1.7 (SD 0.5) mmol/l (p = 0.003). Pretransfusion lactate did not correlate with pre-transfusion haematocrit, heart rate, respiratory rate, number of apnoeas/bradycardias and weight gain (multiple regression). The mean difference between capillary and arterial lactate was 0.17 (SD 0.24) mmol/l and the 95 % confidence interval (CI) was -0.31 to 0.65 mmol/l. The CV of repetitive measurements was 19.8 (SD 9.8)% and SD correlated positively with mean lactate values (p = 0.001); the 95 % CI (normal range for premature infants) was 1.56-1.90 mmol/l. Capillary whole blood lactate measurements in newborn babies agree excellently with arterial values. Lactate measurements add little information to the decision whether to transfuse or not, considering the variability of this parameter in stable premature infants and the lack of correlation with other possible clinical indicators of compromised oxygen delivery.

Evaluation of a transportable [Ca++] and pH analyser and of the impact of different anticoagulants and sampling sites in cattle.

A mobile, hand-held ionized calcium and pH analyser, the IRMA (Immediate Response Mobile Analyser) SL (Diametrics Medical Inc. St. Paul, MN, USA), was evaluated and results interpreted with help from data derived on biological variation in five dry cows. The maximum allowable analytical imprecision (CMAX) was estimated as 1.33% for [Ca++] and 0.12% for pH; the maximal allowable analytical inaccuracy (BMAX) was estimated to be 1.82% ([Ca++]) and 0.09% (pH), and the maximum allowable difference between two methods (MAXDIFF) was calculated as 0.89% ([Ca++]) and 0.08% (pH). These values were compared with the coefficient of variation obtained by calculation from analysis results in blood samples obtained from 51 cows, heifers and calves. The between-cow coefficient of variation (CV), within-cow CV, critical difference (two-sided) and index of individuality were estimated as 4.77, 2.66 and 14.29%, and 1.08 for [Ca++] analysis. For pH measurements, values of 0.12, 0.24 and 0.96% and 2.95 were estimated. The number of samples required to determine the true value of either [Ca++] or pH in an individual cow was 5 and 1, respectively. Further, it was observed that, in investigations of blood Ca++ and blood pH in cattle, neither the use of electrolyte-balanced syringes interchangeable with sodium-heparin vacutainer nor the use of different blood sampling sites was to be recommended. IRMA SL did not correlate significantly with the chosen reference analyser (Stat Profile 5 Analyser; Nova Biomedical, Waltham, MA) with regard to plasma [Ca++] analyses (correlation coefficient r = -0.24, P = 0.22). However, a significant correlation coefficient (r = 0.63, P < 0.01) was found between analyses of pH performed on IRMA SL and Stat Profile 5 Analyser. Analysis on IRMA SL was very easy to perform. It could be a very useful aid in veterinary clinical practice, when determination of plasma pH in cattle is needed. The analyser should not yet be applied uncritically with respect to [Ca++] analyses in cattle.

Pathophysiology, Diagnosis, and Prevention of Neonatal Anemia

After completing this article, readers should be able to: 1. Describe the best methods of evaluating neonatal anemia. 2. Delineate the most important mechanism of anemia among critically ill term and preterm infants. 3. List the mechanisms of anemia of prematurity. 4. Describe how safe and efficacious criteria for blood transfusion are established. 5. Describe the role of clinical and laboratory postdischarge evaluation with regard to neonatal anemia. Evaluating the etiology of neonatal anemia can be a daunting task. The numerous and diverse causes of this condition can be grouped into three broad pathogenetic categories: 1) decreased erythrocyte production, 2) increased erythrocyte destruction, and 3) blood loss (Table 1⇓ ). View this table: Table 1. Pathophysiologic Classification of Neonatal Anemia The importance of obtaining a complete and accurate history and performing a physical examination for diagnosing anemia cannot be overemphasized. In particular, the infant’s family history and the mother’s obstetric history often are of critical importance in narrowing down the etiologic possibilities. The decision of whether a particular hemoglobin (Hb) value is sufficiently low to meet the criteria for neonatal anemia must be based on the infant’s birthweight, postnatal age, and the site of blood sampling. Failure to consider these factors adequately can lead to errors in diagnosis and unnecessary laboratory tests. At birth and for the first 2 to 3 months of life, healthy preterm infants have lower Hb levels than term infants. Normative data for postnatal Hb levels are readily available in standard neonatology and pediatric textbooks. Values below two standard deviations of the mean are diagnostic of anemia. It is also important to appreciate that Hb determinations performed on capillary blood samples, especially in the first days of life, are higher than those obtained from venous or arterial samples because of red blood cell (RBC) sludging in low-flow capillaries with resultant transudation of plasma. At any …

Estimating antemortem drug concentrations from postmortem blood samples: the influence of postmortem redistribution

Aims—To compare blood drug concentrations during life with postmortem drug concentrations measured from a peripheral site and a central site. Methods—Coroner's cases from October 1990 to July 1997 were reviewed....

Cerebral monitoring: jugular venous oximetry.

The internal jugular vein exits the skull and continues its course, within the carotid sheath, beneath the sternocleidomastoid muscle in a posterolateral approximation to the carotid artery. The jugular bulb is the dilated portion of the jugular vein just below the base of the skull and is the preferred site for blood sampling (see Figure 1). Although blood in the jugular bulb is derived from both cerebral hemispheres (approximately 70% ipsilateral and 30% contralateral) (6–8), it is generally accepted that most patients have a dominant side of venous drainage, usually the right (9,10). The two lateral sinuses that drain to the jugular bulbs differ in size in 88% of patients (11), and mixing of cerebral venous blood within the sinuses is incomplete (1,12)

Physiologically assessed coronary collateral flow and intracoronary growth factor concentrations in patients with 1- to 3-vessel coronary artery disease.

The purpose of this study was to test the hypothesis that there is a relation between collateral flow and intracoronary concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) and that the combined concentrations of both growth factors and the extent of coronary artery disease (CAD) play a role as covariables in such an association. In 76 patients undergoing balloon angioplasty, a collateral flow index (CFI, no units) was determined with sensor-tipped guidewires. Simultaneously, serum concentrations of bFGF and VEGF, obtained at the aortic root from the ostium of the collateralized coronary artery (n = 76) and from the distal position of the occluded coronary artery (n = 34), were determined. There was a direct correlation between CFI and distal VEGF (r = 0.33, P = 0.05) but not bFGF concentrations. Focusing on the proximal sampling site, there was a direct correlation between CFI and both bFGF (r = 0.29, P = 0.01) and VEGF concentrations (r = 0.44, P < 0.0001). The sum of the concentrations of both growth factors was directly associated with CFI irrespective of the proximal (r = 0.51, P < 0.0001) or distal sampling site (r = 0.34, P = 0.048). There was a trend toward higher proximal VEGF concentrations in patients with higher numbers of coronary stenotic lesions (r = 0.25, P = 0.03). In patients with CAD, there is an association between a directly measured index of collateral flow and intracoronary concentrations of bFGF and VEGF. This direct relation is dependent on the site of blood sampling within the coronary artery tree. The association is closest when the combined bFGF and VEGF concentrations are taken into account. In the case of VEGF, it is influenced by the degree of coronary atherosclerosis.

Effectiveness of heparin in preventing thrombin generation and thrombin activity in patients undergoing coronary intervention

Background Thrombus is important in the pathophysiology of several complications of angioplasty, including abrupt closure and restenosis. Levels of prothrombin fragment F1.2 and fibrinopeptide A reflect thrombin generation and activity. The effect of angioplasty on levels of these markers is unclear. Methods Patients undergoing either balloon angioplasty (n = 30) or directional atherectomy (n = 9) were treated with heparin to maintain an activated clotting time of >300 seconds. Levels of F1.2, fibrinopeptide A, and thrombin-antithrombin complex were measured in the coronary sinus and coronary artery before and after intervention. Angiograms were reviewed for lesion morphologic characteristics and dissection. Results There was no evidence for thrombin generation or increased thrombin activity after angioplasty regardless of lesion morphologic characteristics, dissection, type of intervention, or blood sampling site. In fact, coronary sinus concentrations of F1.2 decreased after intervention (median 0.31 nmol/L; 25th percentile 0.26 nmol/L, 75th percentile 0.37 nmol/L) before intervention to 0.23 nmol/L (25th percentile 0.19 nmol/L, 75th percentile 0.34 nmol/L) after intervention (P =.002). Conclusions Angioplasty performed in the presence of adequate heparin inhibited thrombin even when there was complex lesion morphology or dissection. These data suggest that heparin provides satisfactory thrombin inhibition during routine angioplasty. (Am Heart J 1999;137:250-7.)

PLASMA GLUTAMATE LEVELS DURING CARDIOPULMONARY BYPASS

Glutamate and other excitatory amino acids have been shown to play an important role in the pathogenesis of neuronal damage in acute cerebral ischemia. [1] Using microdialysis, the amount of glutamate released has been found to correlate with infarct size. [2] A recent report [3] showed that progression of ischemic strokes are associated with high concentrations of glutamate in plasma & CSF. In this pilot study, we measured plasma levels of glutamate during cardiac surgery. Methods. After IRB approval and informed consent, 10 patients were studied using standardized techniques (nonpulsatile 32[degree sign]C CPB, [varies as]-stat pH management, membrane oxygenator, arterial-line filter and continuous midazolam/fentanyl infusions). Concurrent blood samples from the jugular bulb and pulmonary artery were drawn at the following times: 1) awake, 2) during anesthesia/surgery, 3) after 1 hour of CPB, 4) end of CPB, and 5) 1 hour post removal of aortic X-clamp. After centrifugation, samples were frozen for later bulk analysis for serum glutamate. Following protein precipitation with perchloric acid, glutamate concentrations were quantitated by a HPLC method using pre-column derivatization of glutamate with o-phthaldehyde followed by fluorescence detection of the substitution isoindole derivative. Glutamate concentrations are expressed in nmol/ml +/- SD. Results. (Table 1) shows the average plasma glutamate levels measured at different times throughout surgery. Glutamate appeared to peak after 1 hour of CPB, showing a 67% increase over the concurrent PA sample. At conclusion of CPB, brain glutamate was increased 22% compared to PA values.Table 1Discussion. We used concurrent jugular bulb and pulmonary artery blood sampling sites to separate brain sources of glutamate from other sources. Our goal is to determine if plasma levels of glutamate can be used as a biochemical marker for the detection and possible quantification of cerebral injury. Correlations of plasma glutamate with postoperative neurocognitive testing will be necessary. Higher levels of glutamate may be detected during normothermic cardiopulmonary bypass, as part of the protective effect of mild hypothermia is related to inhibition of release of excitatory amino acids. [4]

Preferential sites for arterial blood sampling in cattle

The aim of this study was to compare the feasibility and reliability of different methods for obtaining samples of arterial blood from calves and adult dairy cows.

Measuring glycerol turnover, gluconeogenesis from glycerol, and total gluconeogenesis with [2- 13C]glycerol: Role of the infusion-sampling mode

Mass isotopomer distribution analysis (MIDA) of glucose during infusion of [2- 13C]glycerol is a new method for measuring total gluconeogenesis (GNG). Since this method relies on calculation of the isotopic enrichment (IE) of hepatic triose phosphates (TP), the results should be independent of the sites of tracer infusion and blood sampling. Postabsorptive and starved rats were infused with [2- 13C] glycerol and sampled either in the arterial-venous (A-V) or venous-arterial (V-A) modes. Blood was also sampled from the portal vein. In both postabsorptive and starved rats, glycerol turnover rate (Rt) and the percent contribution of glycerol to total glucose production were higher in the A-V mode than in the V-A mode ( P < .05). Glycerol IE in portal venous blood was intermediate between IE values observed in peripheral arterial and venous blood. Its use for calculating the contribution of glycerol to glucose production reconciled the results obtained with the two infusion-sampling modes in both postabsorptive and starved rats; this contribution was increased by starvation ( P < .01). In postabsorptive rats, total GNG calculated from MIDA of glucose accounted for approximately 50% of glucose production whatever the infusion-sampling mode (A-V, 48.8% ± 4.7%; V-A, 52.2% ± 3.9%). This contribution increased to 90% in starved rats, again, with no difference between A-V (95.2% ± 1.8%) and V-A (89.2% ± 1.3%) modes. In conclusion, during infusion of [2- 13C]glycerol, total GNG measured from MIDA of glucose is independent of the infusion-sampling mode, contrary to calculations of Rt and GNG from glycerol. Measurement of glycerol IE in portal venous blood reconciles the results obtained with the two modes with respect to the contribution of glycerol to GNG.

Preferential sites for arterial blood sampling in cattle

The aim of this study was to compare the feasibility and reliability of different methods for obtaining samples of arterial blood from calves and adult dairy cows. The intermediate branch of the caudal auricular artery was easy to use in animals of all ages. The common carotid artery was also suitable, but only in standing animals. In recumbent animals, the brachial artery and the common palmar digital artery were suitable in calves up to six months old, and the saphenous artery was suitable in both young and adult cattle. The facial, axillary and median caudal arteries were either difficult to use or unreliable.

Pharmacokinetic-pharmacodynamic modelling of zopiclone effects on human central nervous system.

The present data shows the pharmacokinetics and concentration-effect relationship of a single 7.5 mg oral dose of zopiclone in ten healthy volunteers. Plasma concentrations and effects of zopiclone on central nervous system as quantified by changes in saccadic peak velocity and digit symbol substitution test were measured for 17 hr after ingestion of zopiclone. Pharmacokinetics was described with a linear one-compartment open model. Maximum effects preceded peak plasma zopiclone concentrations causing a clockwise hysteresis, i.e. proteresis, in concentration versus effect loops. Therefore, pharmacodynamics was described both with a tolerance model and a model with distributional pseudo-tolerance where the concentration in the blood sampling site is assumed to equilibrate slower with arterial blood than the site of action of zopiclone. Both models related the changes in pharmacodynamics linearly to changes in zopiclone concentrations. The median (range) values for clearance, volume of distribution and elimination half-life were 21 (15-53) L/hr, 132 (58-161) L and 3.4 (1.7-5.7) hr, respectively. Both pharmacodynamic models were able to describe the relationship between zopiclone concentrations and changes in psychomotor performance equally well. However, because the pharmacodynamics of zopiclone were studied in a non-steady-state situation, the mechanism for proteresis, i.e. true tolerance versus distributional pseudotolerance cannot be identified.

Concentrations of prolactin and prostaglandins during and after cardiopulmonary resuscitation: Crit Care Med 1995; 23/8: 1347–1355

OBJECTIVES To assess differences in plasma prolactin and prostaglandin concentrations in resuscitated and nonresuscitated patients during cardiopulmonary resuscitation (CPR), and to compare changes of prostaglandin and prolactin concentrations with hemodynamic variables in the immediate postresuscitation phase. DESIGN Prospective, descriptive study. SETTING Emergency medical service at a university hospital. PATIENTS Twenty-nine patients ranging in age from 39 to 87 yrs with out-of-hospital cardiac arrest. INTERVENTIONS Venous blood samples were taken during CPR and at 5, 15, 30, and 60 mins after restoration of spontaneous circulation in order to measure plasma concentrations of prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 by immunoassay. Heart rate and blood pressure were measured at 5, 15, 30, and 60 mins after restoration of spontaneous circulation. MEASUREMENTS AND MAIN RESULTS In 15 patients, restoration of spontaneous circulation was achieved; in the remaining 14 patients, successful resuscitation was not possible. During CPR, the mean plasma prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 concentrations were 95.9 +/- 13.6 micrograms/L, 357 +/- 61 ng/L, 228 +/- 28 ng/L, 277 +/- 66 ng/L, and 375 +/- 78 ng/L, respectively, in resuscitated patients, and 23.9 +/- 5.6 micrograms/L (p = .0001), 192 +/- 22 ng/L (p = .005), 202 +/- 31 ng/L (p = .528), 221 +/- 40 ng/L (p = .713), and 344 +/- 77 ng/L (p = .780), respectively, in nonresuscitated patients. At 60 mins after restoration of spontaneous circulation, the mean plasma prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 concentrations were 50.1 +/- 9.5 micrograms/L, 306 +/- 42 ng/L, 503 +/- 87 ng/L, 278 +/- 55 ng/L, and 355 +/- 30 ng/L, respectively. Mean values of systolic arterial blood pressure were 114 +/- 12 mm Hg at 30 mins and 123 +/- 18 mm Hg at 60 mins. No significant correlations were found between hemodynamic values and plasma concentrations of prolactin or prostaglandins. CONCLUSIONS Prolactin and prostaglandin concentrations were increased during cardiac arrest and CPR. Successful initial resuscitation was associated with increased prolactin and prostaglandin F2 alpha concentrations during CPR. Decreased concentrations in non-resuscitated patients may have been a result of exhaustion of the neuroendocrine and eicosanoid systems, or may be due to differences in bioavailability at the site of blood sampling based upon differences in hemodynamics.

Dosimetry of [15O]water: A physiologic approach

Earlier dosimetry estimates for [15O]water assumed its instantaneous equilibrium with total body water. This assumption leads to an underestimation of the absorbed doses to organs with high blood flows, since the biodistribution of this short-lived radiopharmaceutical is dependent upon blood flow to organs. We have developed a physiologically based whole body blood flow model (WBBFM) using a commercially available icon-driven mathematical simulation software package and applied it to the reevaluation of [15O]water dosimetry in humans. The WBBFM uses multiple parallel compartments to represent organs, heart chambers, the injection site for [15O]water, and blood sampling sites (arterial and venous). Input values to the WBBFM include organ blood flows, organ masses, organ water volumes, organ:blood partition coefficients, injected activity and S-values of [15O]. The WBBFM is based on the same assumptions that are used in calculating regional blood flow using [15O]water and simulates the human body closely in its physiologic response. The activity in each organ is derived from the simulation and is used to calculate absorbed doses. The WBBFM calculated absorbed doses in microGy/MBq (mrad/mCi) to various organs are as follows: heart--2.66 (9.84), kidneys--2.20 (8.15), thyroid--1.83 (6.78), brain--1.66 (6.13), ovaries--1.25 (4.61), breast--1.24 (4.59), and small intestine--1.03 (3.83). These values are approximately two- to threefold higher than the earlier estimates of Kearfott [J. Nucl. Med. 23, 1031-1037 (1982)] and similar to the recent findings of Herscovitch et al. [J. Nucl. Med. 34, 155P (1983)]. We believe this approach yields more realistic dosimetry estimates for [15O]water. Accordingly, we have revised the amount of [15O]water administered during regional blood flow studies at our institution. The relative ease and accuracy of this approach suggests its usefulness in dosimetry estimation for other freely diffusible radiopharmaceuticals.

Concentrations of prolactin and prostaglandins during and after cardiopulmonary resuscitation

To assess differences in plasma prolactin and prostaglandin concentrations in resuscitated and nonresuscitated patients during cardiopulmonary resuscitation (CPR), and to compare changes of prostaglandin and prolactin concentrations with hemodynamic variables in the immediate postresuscitation phase. Prospective, descriptive study. Emergency medical service at a university hospital. Twenty-nine patients ranging in age from 39 to 87 yrs with out-of-hospital cardiac arrest. Venous blood samples were taken during CPR and at 5, 15, 30, and 60 mins after restoration of spontaneous circulation in order to measure plasma concentrations of prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 by immunoassay. Heart rate and blood pressure were measured at 5, 15, 30, and 60 mins after restoration of spontaneous circulation. In 15 patients, restoration of spontaneous circulation was achieved; in the remaining 14 patients, successful resuscitation was not possible. During CPR, the mean plasma prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 concentrations were 95.9 +/- 13.6 micrograms/L, 357 +/- 61 ng/L, 228 +/- 28 ng/L, 277 +/- 66 ng/L, and 375 +/- 78 ng/L, respectively, in resuscitated patients, and 23.9 +/- 5.6 micrograms/L (p = .0001), 192 +/- 22 ng/L (p = .005), 202 +/- 31 ng/L (p = .528), 221 +/- 40 ng/L (p = .713), and 344 +/- 77 ng/L (p = .780), respectively, in nonresuscitated patients. At 60 mins after restoration of spontaneous circulation, the mean plasma prolactin, prostaglandin F2 alpha, 15-keto-13,14-dihydro-prostaglandin F2 alpha, 6-keto-prostaglandin F1 alpha, and thromboxane B2 concentrations were 50.1 +/- 9.5 micrograms/L, 306 +/- 42 ng/L, 503 +/- 87 ng/L, 278 +/- 55 ng/L, and 355 +/- 30 ng/L, respectively. Mean values of systolic arterial blood pressure were 114 +/- 12 mm Hg at 30 mins and 123 +/- 18 mm Hg at 60 mins. No significant correlations were found between hemodynamic values and plasma concentrations of prolactin or prostaglandins. Prolactin and prostaglandin concentrations were increased during cardiac arrest and CPR. Successful initial resuscitation was associated with increased prolactin and prostaglandin F2 alpha concentrations during CPR. Decreased concentrations in non-resuscitated patients may have been a result of exhaustion of the neuroendocrine and eicosanoid systems, or may be due to differences in bioavailability at the site of blood sampling based upon differences in hemodynamics.

Postmortem investigation of serum myoglobin levels with special reference to electrical fatalities

The serum myoglobin levels of 58 fatalities were investigated with special reference to correlations of the myoglobin-concentrations with the postmortem interval, the site of blood sampling and the cause of death (especially concerning death caused by electric current). An increase of the myoglobin values with the passage of postmortem time is obvious. The topographical sampling site plays an important role; the highest concentrations are found adjacent to striated muscles (i.e. in blood from the heart or the femoral vein). There was no significant correlation of myoglobin values and death by electric current.

931-115 Phase I Studies on Inogatran, a New Selective Thrombin Inhibitor

Inogatran is a new, synthetic, active site inhibitor of thrombin with a molecular weight of 439 dalton. Inogatran (pINN) selectively, rapidly and competitively binds thrombin with a Ki value of 15 nmol/l. In vitro it doubles the plasma thrombin time at a concentration of 23 nmol/1 and the activated partial thromboplastin time (APTT) at 1.1 μmol/1. Thrombin induced platelet aggregation is inhibited at an IC50 of 17 nmol/1 Inogatran was studied in healthy male human volunteers with regard to tolerability, pharmacokinetics and effects on haemostasis. It was given intravenously as a bolus in doses from 0.002 to 1.1 μmol/kg (n = 2-4 at each dose). The highest peak plasma concentration observed was 7 μmol/1 corresponding to an APTT prolongation of 3 times. The drug was also given as a constant infusion over 4 h at a dose of 0.73 μmol/kg per h (n = 16) which resulted in a mean plasma concentration at steady state of 1.9 μmol/l and an APTT prolongation of 2.3 times. Finally, it was given as a bolus with radiolabeled compound in a total dose of 25 μmol (n = 16). The drug was well tolerated and without side effects with the exception of slightly increased bleeding tendency at the blood sampling site. Inogatran had a volume of distribution of 0.26 ml/kg and a total plasma clearance of 6.1 ml/min per kg, resulting in a half life of about one hour. The drug was not metabolised and it was excreted unchanged with the elimination evenly distributed between urine and faeces. Ex vivo the thrombin time was linearly correlated to the plasma concentration while the APTT-concentration curve was non-linear. At the highest plasma concentrations a slight prolongation of the capillary bleeding time was seen in some subjects. Markers of thrombin activity (thrombin-antithrombin complex and prothrombin fragments 1–2) decreased during the constant infusion of the drug. There was no effect on fibrinolysis (PAI-l and t-PA activities) or protein C. It is concluded that inogatran is a safe and effective anticoagulant with favourable pharmacokinetics for i.v. use