Simultaneous Blood Samples Research Articles

Prostacyclin Is Released Mainly from the Splanchnic Region during the Early Phase of Acute Experimental Hemorrhagic Pancreatitis in Dogs

The release of 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TXB2, the stable metabolites of prostacyclin (PGI2) and thromboxane A2 (TXA2) during canine acute hemorrhagic pancreatitis (AHP) was studied using four different catheters in order to obtain simultaneous blood samples from (1) the abdominal aorta (2) the inferior vena cava (3) the right atrium of the heart and (4) the portal vein. Splenectomy was performed prior to the induction of AHP, which was performed with a mixture of trypsin and sodium taurocholate infused into the pancreatic duct. Sampling was performed before the induction of AHP (zero value) and thereafter up to 90 min. Plasma 6-keto-PGF1α increased most in the samples collected from the portal vein, and was significantly higher already after 1 min of induction of AHP when compared to the zero value. Plasma TXB2 increased significantly in all sites except in the inferior vena cava. Plasma TXB2 levels decreased rapidly in the portal vein and the right atrium after the induction of AHP, whereas in the abdominal aorta TXB2 levels remained high up to 90 min after induction compared to the zero value. In conclusion, the splanchnic area seems to be the main origin of the released PGI2 during canine AHP and may also have a role in hemodynamic changes observed in AHP due to its vasoactive properties. TXA2 is released from various sources – possibly mainly from the lungs and kidneys during experimental AHP.

Intravenous 133Xe clearance in preterm neonates with respiratory distress. Internal validation of CBF infinity as a measure of global cerebral blood flow.

An intravenous 133Xe clearance technique is described, giving very low values of global cerebral blood flow (CBF infinity) in mechanically ventilated, preterm infants. External monitoring of the chest is used to estimate the arterial input function to the brain, with a modified correction to allow for increased recirculation due to right-to-left shunting. The results compared well in 10 studies in seven infants, where CBF infinity could also be calculated from direct simultaneous blood sampling from the right radial artery (7.9 ml/100 g/min +/- 2.5 SD vs. 8.4 +/- 3.6, p less than 0.05). In 25 studies in 12 infants the results compared well with those calculated from simultaneous 133Xe concentrations in expired air. Fifteen-minute clearance data gave better precision than 8-min data. The modified chest curve correction was partly effective in a case of extreme right-to-left shunting.

Fetal disposition of Δ 9-tetrahydrocannabinol (THC) during late pregnancy in the rhesus monkey

Three late-term (Gestational Days 146–151) rhesus monkeys were given 0.3 mg/kg Δ 9-tetrahydrocannabinol (THC) intravenously via the maternal radial vein to quantify the placental transfer and fetal disposition of THC, the major psychoactive component of marijuana. Simultaneous blood samples were obtained from a maternal uterine vein and an intraplacental artery at 0, 3, 15, 30, 45, 60, 90, 120, and 180 min after dosing using an intraplacental cannulation technique. Samples of fetal plasma, spleen, testis, lung, brain, liver, bile, kidney, adrenals, thymus, and placenta were obtained at 180 min postdose. Samples were analyzed for THC and a major metabolite, 11-nor-9-carboxy-THC (11-nor), by radioimmunoassay (RIA). Peak plasma THC values were obtained 3 and 15 min after dosing in the mother (1419 ng/ml) and fetus (83 ng/ml), respectively. By 3 hr, maternal and fetal plasma THC levels were equal (37 ng/ml). Maternal plasma was sampled beyond 180 min at 24, 48, 72, and 96 hr postdose, times at which THC and 11-nor concentrations were either near or at the lower limit of sensitivity for the RIA (2 ng/ml). While maternal plasma 11-nor levels peaked at 1 hr (44 ng/ml), almost no 11-nor was detected in fetal plasma (<5 ng/ml). Fetal tissue concentrations of THC were 53 ± 6 ng/g (SE) for brain and 114 ± 10 ng/g for liver, while 11-nor was undetectable in placenta, fetal liver, and fetal brain. These data demonstrate that THC rapidly crosses the placenta and enters the fetus. The lack of 11-nor in fetal plasma and tissues suggests that this metabolite does not readily cross the placenta and that the fetus does not readily metabolize THC to 11-nor at this stage of development. A portion of this data was presented at the 1985 meeting of The American Society of Primatologists and at the 1986 meeting of The Teratology Society. This work was supported in part by NIDA IAG 224-83-0005.

Bladder Vasodilatation and Release of Vasoactive Intestinal Polypeptide from the Urinary Bladder of the Cat in Response to Pelvic Nerve Stimulation

In the feline urinary bladder blood flow was determined by means of a direct blood flow measurement technique before and during pelvic nerve stimulation. Simultaneous sampling of venous blood from the bladder was performed, and the output of vasoactive intestinal polypeptide (VIP) was determined by means of radioimmunoassay.Maximal stimulation of the pelvic nerves led to a clearcut increase in intravesical pressure and a small but sustained increase of blood flow in the bladder wall. These changes were associated with a drastic increase in VIP output from the bladder, increasing from a control level of 0.2fmol./min. to 15fmol./min. during stimulation.The results suggest that VIP might be the neurotransmitter responsible for the vasodilatation in the feline urinary bladder in response to pelvic nerve stimulation. The discrepancy between the moderate blood flow increase and the pronounced increase in VIP-release might, however, indicate that VIP exerts its main effects elsewhere in the bladder than in the vascular bed, for instance the detrusor smooth muscle. (J. Urol., 138: 671–673, 1987)

The influence of the sampling point on testicular steroid concentrations in spermatic venous blood: a physiological approach to evaluate testicular secretion.

In the present study, we have evaluated the influence of the location of the blood sampling in the spermatic vein on the steroid concentrations observed. Simultaneous blood sampling at two different points of the spermatic vein (iliac level and pampiniform plexus) was perfomed in the same patients during a surgical protocol for varicocelectomy. In order to further evaluate which of the two sampling points is more useful to investigate testicular secretion, we have performed both forms of sampling in 4 volunteers given an HCG stimulation 24 h before the surgical procedure. It was found that levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP) were higher in the pampiniform plexus (scrotal) than at the iliac sampling point (T scrotal 1,168.343 +/- 142.65 nmol/l, iliac 850.63 +/- 143.411 nmol/l, n = 21, p less than 0.01; 17-OHP scrotal 260.130 +/- 43.14 nmol/l, iliac 164.46 +/- 31.02 nmol/l, n = 17, p less than 0.01). This indicates that spermatic blood collected at the scrotal sampling point has received more blood coming from the testis than the blood collected at the iliac point. We did not observe significant differences in progesterone and delta 4-androstenedione (delta 4) levels between the two samplings. The T/delta 4 ratio was significantly lower in the iliac than in the scrotal sampling (T/delta 4 scrotal 31.420 +/- 6.69; iliac 15.41 +/- 3.84; p less than 0.05). After HCG stimulation, testosterone concentrations were higher in the pampiniform plexus than in the iliac sample. This suggests that the first sampling point is more proper for studying testicular secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

"Levonorgestrel Concentrations in Maternal and Infant Serum During use of Subdermal Levonorgestrel Contraceptive Implants, Norplant, by Nursing Mothers"

Abstract The transfer of levonorgestrel to infants was studied in 42 lactating women in whom the contraceptive subdermal implants, Norplant®, were inserted 30 to 40 days postpartum. The women breastfed their infants for one year. Simultaneous mother and infant blood samples were taken once during the year. The levonorgestrel serum concentrations were measured by radioimmunoassay. During the fi r st postinsertion month, the levonorgestrel concentration in the infants serum amounted, on the average, to 5% of the maternal concentration. Thereafter, the ratio ranged from 8 to 13%. The implications of this finding are discussed.

Chronic push-pull brain perfusion in unrestrained rhesus macaques.

A system was developed to permit perfusion of local brain regions and simultaneous peripheral blood sampling in free-moving caged monkeys. The system comprises a calvarial headpiece that contains multiple push-pull cannulas (PPC), a flexible stainless steel tether, a four-channel fluid swivel, and a surgical procedure for simultaneous multisite brain cannulation. Rhesus macaques were fitted surgically with an indwelling jugular catheter and PPC directed into the third ventricle, median eminence, and preoptic area. These animals were tethered for periods of 14-70 h during which brain perfusates and peripheral blood samples were collected at 10- to 30-min intervals through the tether-swivel assembly. Levels and pulsatile patterns of gonadotropin-releasing hormone in 10-min perfusate samples and luteinizing hormone and cortisol in sequential plasma samples were quantified by specific radioimmunoassays. The normal endocrine profiles in these animals suggest that this system provides a valuable method to study patterns of neurosecretions in an unrestrained simian.

Pharmacokinetic approach to the estimation of hepatic removal of insulin.

We simultaneously measured hepatic insulin removal invasively and estimated hepatic clearance and extraction of insulin pharmacokinetically from cardiac output and peripheral plasma concentrations (relatively) noninvasively. The invasive methods involved continuous electromagnetic measurements of portal venous and hepatic arterial blood flow and simultaneous intermittent sampling of blood from the portal and hepatic veins and femoral artery for assay of insulin concentrations. The noninvasive method assumed that hepatic plasma flow is proportional to cardiac output and that hepatic clearance is a constant fraction of total body clearance of insulin. In anesthetized dogs (n = 6), endogenous insulin was suppressed with somatostatin (800 ng/kg/min) while biosynthetic human insulin (0.25, 0.50, and 1.00 mU/kg/min) was infused to steady state during three consecutive 90-min periods. Insulin concentrations were directly proportional to the infusion rate (p less than 0.01). Hepatic blood flow accounted for 20 +/- 2% of cardiac output. Measured hepatic clearance accounted for 51 +/- 5% of total body clearance of insulin and correlated with the pharmacokinetic estimates (p less than 0.01); the estimates of hepatic clearance ranged from 91 to 114% of the measured values. We conclude that this pharmacokinetic approach, which requires only samples of peripheral blood and estimates of hepatic blood flow, may be used to study the hepatic removal of insulin relatively noninvasively.

83 RELIABLE NON-INVASIVE MONITORING OF THEOPHYLLTNE THERAPY IN INFANTS AND CHILDREN: MEASUREMENT OF SALIVA THEOPHYLLINE CONCENTRATIONS

The use of saliva (Sa) theophylline (Th) for monitoring Th therapy is not routinely used in infants and young children due to the inapplicability of the usual technique (chewing on a piece of paraffin) to obtain stimulated Sa in this age group. Simultaneous blood and Sa samples mere obtained in 57 infants and children (age: 3 mo-14 ys; mean: 3.3ys) under Th therapy. Th was given po (slow release preparations or elixir) or i.v. Mean ± SD dose was 21.3±6.4 mg/kg/day. Sa secretion was stimulated by placing citric acid crystals on the tongue. Plasma (P1) and Sa Th mas analysed by competitive fluorescence polarization immunoassay (TDx). Mean ± SD P1/Sa Th concentration ratio was 1.78±0.25 within a wide PI Th concentration range (3.1-32.1 meg/ml). Good correlation existed between both determinations (r=0,98). Interindividual coefficient of variation (CV) was 14%; mean intraindiuidual CV was 5.2%. Mean estimated/actual Pl Th ratios determined in the following 48 samples studied was 0.98±0.11, CV 11.2%. Th measurements in citric-acid stimulated saliva represent a convenient, non-invasive and reliable method for monitoring theophylline therapy in infants and children.

Selective blood sampling from the inferior petrosal sinus using digital subtraction angiography

Simultaneous bilateral venous sampling of blood from the inferior petrosal sinuses helps in the differentiation between peripheral and central ACTH hypersecretion. One can also locate the site of a hormonally active hypophyseal micro-adenoma that cannot be demonstrated by other methods. The authors have experience with fifteen patients and discuss the indications, technique and problems as well as the advantages of using digital subtraction angiography.

The measurement of liver blood flow in conscious calves.

Observations were made following single I.V. injections or during continuous I.V. infusions of sulphobromophthalein (BSP) in three Jersey calves (3-5 months of age) which had an indwelling hepatic vein catheter, surgically implanted under general anaesthesia. Simultaneous sampling of blood from a peripheral (jugular) vein and an hepatic vein enabled calculations of hepatic plasma flow (E.H.P.F.) based on the Fick principle. Estimates of E.H.P.F. in nine single injection experiments gave a mean flow of 38.6 ml X min-1 X kg-1 compared to 32.6 ml X min-1 X kg-1 estimated in seven continuous infusion experiments. The over-all mean haematocrit in the three calves was 30.0% and the E.H.P.F. values are equivalent to hepatic blood flows of 55 and 47 ml X min-1 X kg-1 respectively. In thirteen out of fourteen experiments the plasma clearance of BSP in jugular vein blood after a single I.V. injection of 5 mg BSP X kg-1 body weight was best fitted by a double exponential model of distribution of BSP. Parameters from these exponentials were used to calculate E.H.P.F. by the method of Clarkson, Hardy-Smith & Richards (1976) and gave values of 11.3 ml X min-1 X kg-1, clearly indicating that the method cannot be applied in conscious calves.

Changes in central and peripheral renin-angiotensin system after furosemide injection.

To examine the effects of acute stimulation on the peripheral and central renin-angiotensin system, simultaneous sampling of blood and cerebrospinal fluid (CSF) for measurements of plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (PAng I-ir), plasma angiotensin II-immunoreactivity (PAng II-ir), plasma angiotensinogen and cerebrospinal fluid angiotensin II-ir (CSF Ang II-ir) and CSF angiotensinogen was carried out following intravenous injection of furosemide (5 mg/kg) in conscious dogs. Administration of furosemide induced marked increases in PRA, Ang I-ir, PAng II-ir and CSF Ang II-ir, however, neither plasma nor CSF angiotensinogen was changed. Furthermore, a relatively large dose (20 mg/kg/min) of intravenously infused synthetic Ang II for 20 min produced a five-fold increase in PAng II-ir compared with no significant increase in CSF Ang II-ir. In spite of significant suppression of PRA and PAng I-ir, there were no significant changes in either plasma or CSF angiotensinogen. These results primarily suggest that the peripheral and the brain renin-angiotensin systems may be linked and that acute changes in the peripheral renin-angiotensin system do not alter either plasma or CSF angiotensinogen.

A simplified method for chronic portal vein cannulation in the rat

A simple technique is described for chronic cannulation and repeated blood sampling from the portal vein of the conscious undisturbed rat. The method employs a straight cannula and allows precise location of the tip. Blood flow in the portal vein is not obstructed. The present technique was used in combination with chronic cannulation of the superior vena cava. Simultaneous blood sampling from the two cannulas was successfully carried out at fifteen minute intervals over six hour periods. The system and the sampling were well tolerated by the rats.

Nonneoplastic gonadal testosterone secretion as a cause of vaginal cell maturation in streak gonad syndrome.

Endocrine studies were carried out on 3 patients with streak gonad syndrome, 2 of whom had slight proliferative vaginal smear patterns, and the 3rd had slight hirsutism with increased muscle mass but an atrophic type vaginal smear pattern. Simultaneous sampling of peripheral, adrenal and streak gonadal venous blood revealed mildly increased testosterone secretion by the streaks in the 2 patients who had proliferative cytohormonal patterns. Histologic examination of their streak gonads showed hilus cell hyperplasia. It might be suggested that hilus cell hyperplasia was the source of the increased testosterone secretion in these 2 patients and thus resulted in slight maturation of the vaginal epithelium.

Metabolic fate of extracted glucose in normal human myocardium.

Glucose is an important substrate for myocardial metabolism. This study was designed to determine the effect of circulating metabolic substrates on myocardial glucose extraction and to determine the metabolic fate of glucose in normal human myocardium. Coronary sinus and arterial catheters were placed in 23 healthy male volunteers. [6-14C]Glucose was infused as a tracer in 10 subjects. [6-14C]Glucose and [U-13C]lactate were simultaneously infused in the other 13 subjects. Simultaneous blood samples were obtained for chemical analyses of glucose, lactate, and free fatty acids and for the the isotopic analyses of glucose and lactate. Glucose oxidation was assessed by measuring myocardial 14CO2 production. The amount of glucose extracted and oxidized by the myocardium was inversely correlated with the arterial level of free fatty acids (r = -0.71; P less than 0.0001). 20% (range, 0-63%) of the glucose extraction underwent immediate oxidation. Chemical lactate analysis showed a net extraction of 26.0 +/- 16.4%. However, isotopic analysis demonstrated that lactate was being released by the myocardium. In the 13 subjects receiving the dual-carbon-labeled isotopes, the lactate released was 0.09 +/- 0.04 mumol/ml and 49.5 +/- 29.5% of this lactate was from exogenous glucose. This study demonstrates that the circulating level of free fatty acids plays a major role in determining the amount of glucose extracted and oxidized by the normal human myocardium. Only 20.1 +/- 19.4% of the glucose extracted underwent oxidation, and 13.0 +/- 9.0% of the glucose extracted was metabolized to lactate and released by the myocardium. Thus, 60-70% of the glucose extracted by the normal myocardium is probably stored as glycogen in the fasting, resting state.

Extraction Ratio of Cyclosporine in a Liver Transplant Patient with Organ Rejection

Cyclosporine, a cyclic polypeptide with potent immunosuppressive properties, 1 has been successfully used to prevent the rejection of transplanted organs such as kidneys, livers, hearts, and bone marrow. 2–5 It is highly lipophilic and is eliminated primarily by metabolism in the liver. 6 Recent studies in transplant patients indicate cyclosporine to be a low-to-intermediate clearance drug. We had a unique opportunity to directly determine the hepatic extraction ratio of this drug in a pediatric liver transplant recipient. The patient was a 4-year-old male who underwent liver transplantation for α1-antitrypsin deficiency. Subsequent to his first transplantation, he progressed well until 1 month following surgery when he developed hepatic artery thrombosis. He received a second liver 53 d after the first transplant. On the day prior to the second transplant, the liver function tests were as follows: alkaline phosphatase, 63 IU/L; serum glutamic oxaloacetic transaminase (SGOT), 654 IU/L; serum glutamic pyruvic transamine (SGPT), 273 IU/L; bilirubin (total), 1.0 mg/dL; bilirubin (direct), 0.2 mg/dL. This indicated that the patient did not have a normally functioning liver. The patient did not receive any drugs known to induce or inhibit the drug-metabolizing enzyme systems of the liver at any time prior to the second transplant. At the time of the study, the patient received cyclosporine and a low dose of prednisolone as immunosuppressants, captopril for the treatment of hypertension, and systemic antibiotics. Prior to the operation, 30 mg im of secobarbital was administered. Just prior to the removal of the first transplanted liver, simultaneous blood samples were obtained from the hepatic and portal veins. Blood samples were kept frozen until analyzed for whole blood cyclosporine concentration by HPLC. The blood was extracted using the procedure of Sawchuck and Cartier. 7 Samples were analyzed using a 5-μm C18 , column (Supelco, Bellefonte, PA) heated to 70°C and UV detection (model 441; Waters Associates, Milford, MA) at 214 nm. Standards were prepared in blank blood, and the internal standard was cyclosporine D (Sandoz Pharmaceuticals, Basel, Switzerland). The mobile phase was 68% acetonitrile, delivered at 1.8 mL/min. Under these conditions, the retention time for cyc1osporine was 9.8 min and that for cyclosporine D was 12.8 min. The CV of the analytical method was 3.95% at 600 ng/mL (n = 10). The concentration of cyc1osporine in the portal vein (PV) was 596 ng/mL, whereas the hepatic vein (HV) concentration was 500 ng/mL. The hepatic extraction ratio was: In this patient, the first transplanted liver was 740 g in weight. The hepatic blood flow in humans is 100 mL/100 g of liver weight. 8 Therefore, based on an estimated blood flow of

The late luteal phase in infertile women: comparison of simultaneous endometrial biopsy and progesterone levels

Endometrial biopsy specimens were obtained from 107 normally menstruating infertile women 2 to 3 days before the anticipated onset of menses and were day-dated according to histologic criteria. A simultaneous blood sample was obtained for measurement of progesterone (P) and beta-subunit of human chorionic gonadotropin. Of 98 biopsies which could be accurately dated, 56 were in-phase (IP) and 42 were out-of-phase (OOP). Mean serum P levels were significantly lower in women with OOP biopsies undertaken more than 4 days before the onset of menses. A sharp decline in serum P levels was observed in women with IP but not OOP biopsies, so that on the final premenstrual day serum P levels were significantly higher than normal in women with OOP biopsies. Pregnancy continued without interruption in two of six patients who underwent biopsy in the cycle of conception. One patient had an ectopic pregnancy; and the three remaining pregnant patients, all with subnormal P values, aborted. The study suggests that there is a high frequency of minor abnormalities in luteal function in normally menstruating, infertile women for whom tubal and male factors were normal. The frequency of subclinical pregnancy (2 of 107) was lower than anticipated from earlier studies.

Performance of a quality-assessment scheme for blood glucose meters in general practice.

We describe our experience with a quality-assessment scheme for Glucometer users in General Practice based on simultaneous blood samples taken on filter paper strips and posted to the laboratory. The accuracy of results from these blood glucose meters outside the laboratory was below generally accepted laboratory standards; 30% of results fell outside +/- 20% of the laboratory value. Only 58% of the filter paper strips sent out were returned for analysis, suggesting a lack of awareness of the benefits and importance of such a scheme by the G.P. Glucometer users.

Effect of heparin on arterial blood gases

To evaluate changes in arterial blood gas samples caused by the addition of liquid heparin, 50 patients had three simultaneous blood samples drawn, each with one of three amounts of heparin. The liquid heparin decreased statistically the PCO2, PO2, HCO3, and base excess, while the pH remained unchanged. By using a 2-cc blood sample with a 5-cc glass syringe and a 11/2-inch, 18-gauge needle to draw the heparin solution up to the 2-cc mark, and then completely evacuating it, we found that 0.025 cc of solution remained to coat the syringe. Although this remaining solution would cause a 1.25% error in the blood gas results, the error would be acceptable because it is generally less than the standard deviation of the laboratory results. Excess liquid heparin statistically exaggerated or produced false results consistent with a metabolic acidosis with respiratory compensation. We recommend that the complete evacuation of liquid heparin from the sampling syringe be included when performing an arterial blood gas analysis.

Preoperative lateralization of ACTH-secreting pituitary microadenomas by bilateral and simultaneous inferior petrosal venous sinus sampling.

PREVIOUS reports have established the utility of selective catheterization of the inferior petrosal sinus for determination of plasma ACTH concentrations in the diagnosis of pituitary-dependent hypercortisolism.1 2 3 4 5 Preliminary studies suggest that hormonal secretion from a laterally located microadenoma drains preferentially into the ipsilateral inferior petrosal sinus.6 7 8 If this occurs consistently, simultaneous sampling of bilateral venous blood should provide a means of localizing the microadenoma in one side of the pituitary gland, aiding the surgeon's search for small lesions or, if the microadenoma cannot be found, allowing excision of the half of the gland containing the tumor. In this study we correlated . . .