Angiotensin II-stimulated secretion of arginine vasopressin is inhibited by atrial natriuretic peptide in humans

We investigated the effect of the intravenous infusion of atrial natriuretic peptide (ANP) on the response of plasma arginine vasopressin (AVP) levels to intravenous infusion of angiotensin II (ANG II) in healthy individuals. Intravenous infusion of ANP (10 ng·kg(-1)·min(-1)) slightly but significantly decreased plasma AVP levels, while intravenous infusion of ANG II (10 ng·kg(-1)·min(-1)) resulted in slightly increased plasma AVP levels. ANG II infused significant elevations in arterial blood pressure and central venous pressure (CVP). Because the elevation in blood pressure could have potentially inhibited AVP secretion via baroreceptor reflexes, the effect of ANG II on blood pressure was attenuated by the simultaneous infusion of nitroprusside. ANG II alone produced a remarkable increase in plasma AVP levels when infused with nitroprusside, whereas the simultaneous ANP intravenous infusion (10 ng·kg(-1)·min(-1)) abolished the increase in plasma AVP levels induced by ANG II when blood pressure elevation was attenuated by nitroprusside. Thus, ANG II increased AVP secretion and ANP inhibited not only basal AVP secretion but also ANG II-stimulated AVP secretion in humans. These findings support the hypothesis that circulating ANP modulates AVP secretion, in part, by antagonizing the action of circulating ANG II.     

Clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning

ObjectiveTo observe the clinical efficacy of intravenous infusion of atropine with micropump in combination with hemoperfusion on organophosphorus poisoning patients, and investigate the potential mechanism.MethodsIn this study, we enrolled 136 organophosphorus poisoning patients who received treatment in this hospital between January 2009 and December 2017, and they were divided into three groups according to the clinical treatment methods, i.e. Group A (comprehensive treatment with HP, n = 47), Group B (continuous intravenous infusion of atropine with micropump, n = 43) and Group C (regular intravenous infusion of atropine, n = 46). In addition to the close monitoring of vital signs, we recorded the atropinization time (min), cholinesterase reactivation time (h), total dose of atropine, recurrence, incidence rate of atropine poisoning (%), hospitalization time (d) and cure rate (%).ResultsIn comparison with Group C, patients in Group A and B manifested more stable vital signs with lower total dose of atropine and incidence rate of atropine poisoning and shorter cholinesterase reactivation time, while the cure rate was remarkably increased (p < 0.05), and no significant differences were observed in atropinization time among three groups (p > 0.05). Compared to Group B and C, total dose of atropine in Group A was significantly decreased with obvious excellence in hospitalization time, reduction of complications and increases in cure rates (p < 0.05). Moreover, patients in Group A had the lowest mortality rate among three groups.ConclusionIn treatment of organophosphorus poisoning patients, HP and continuous intravenous infusion of atropine using micropump can elevate the survival rate, reduce the incidence of adverse reaction, shorten the reactivation time of cholinesterase and decrease the incidence rate of complications, which are superior to the traditional treatment method.     

Insulin affects glucose uptake by muscle and mammary tissues of lactating ewes

Effects of insulin on exchanges of glucose across skeletal muscle and mammary tissue were measured in short-term studies in lactating ewes. Insulin secretion was suppressed by a primed/continuous infusion of somatostatin, then insulin was administered by continuous intravenous infusion of doses that were increased, in a step-wise manner, from 0 to 2 U h-1. Plasma glucose was maintained essentially constant by frequent monitoring and intravenous administration of exogenous glucose. Somatostatin suppressed but did not completely inhibit insulin secretion as shown by maintenance of plasma concentration of C-peptide. As plasma insulin was increased, while arterial glucose was maintained stable, uptake of glucose by skeletal muscle increased and glucose uptake by the mammary gland decreased. These observations confirm the role of insulin in regulating glucose uptake by skeletal muscle and raise the possibility that insulin also regulates glucose uptake by the mammary gland.     

Potency of propofol, thiopentone and ketamine at various endpoints in New Zealand White rabbits

Effective plasma concentrations of propofol, thiopentone and ketamine were determined at different endpoints in a study with randomized, crossover design in nine New Zealand White rabbits. A continuous infusion was used (30 ml/h) with concentrations of 10 mg/ml for propofol, 25 mg/ml for thiopentone and 20 mg/ml for ketamine. The endpoints were loss of the righting reflex, loss of purposeful reactions to tail clamping (as an example of a peripheral pain stimulus) or to intranostril insufflation of ammonia vapour (as an example of a central reflex stimulus), and the recovery of these reflexes and reactions. According to the ED50 values the potency ratios of propofol, thiopentone and ketamine were at the loss of righting reflex 1:1.8:1.2, at the loss of reaction to ammonia vapour 1:1.5:1.6, and at the loss of reaction to tail clamping 1:1.5:3.9, respectively. Recovery was significantly faster after propofol than after thiopentone and ketamine. Measuring the effective plasma concentrations of intravenous anaesthetics provides a method of relating dose to effect, but there still remains a variable gap between plasma concentration and effect.     

Investigation of the pharmacokinetics and determination of tramadol in rabbit plasma by a high-performance liquid chromatography-diode array detector method using liquid-liquid extraction

An HPLC system using a new, simple and rapid liquid-liquid extraction and high-performance liquid chromatography-diode array detector method (HPLC-DAD) detection was validated to determine tramadol concentration in rabbit plasma. The method described was applied to a pharmacokinetic study of intravenous tramadol injections in rabbits. The extraction with ethylacetate yielded good response. The recovery of tramadol from plasma averaged 90.40%. Serial plasma samples were obtained prior to, during and after completion of the infusion for determination of tramadol concentrations. Tramadol concentrations were measured using reverse-phase high-performance liquid chromatography and pharmacokinetic application with intravenous tramadol in rabbits revealed that tramadol followed one-compartment open model. Maximum plasma concentration (C(max)) and area under the plasma concentration-time curve (AUC) for tramadol were 14.3 microg mL(-1) and 42.2 microg h mL(-1), respectively. The method developed was successfully applied to a simple, rapid, specific, sensitive and accurate HPLC method for investigation of the pharmacokinetics of tramadol in rabbit plasma.     

Liquid chromatographic determination of the plasma concentrations of cefotaxime and desacetylcefotaxime in plasma of critically ill patients

A method for the simultaneous determination of cefotaxime (CTX) and desacetylcefotaxime (DES) in plasma was developed, using acetonitrile protein precipitation and high-performance liquid chromatography (HPLC) with UV-detection at 285 nm. Desacetylcefotaxime was also analysed after conversion in highly acidic medium to its lactone form (DES-lactone). The chromatographic separation was performed on a C18 Aqua column. The lower limit of quantitation was 1 microg/ml for CTX and 0.5 microg/ml for DES and DES-lactone, using 25 microl of plasma samples. The linearity of the calibration curves was satisfactory as indicated by correlation coefficients of > or =0.990. The within-day and between-day precisions were <12% (n = 18) for the two products and the accuracy was between 88 and 101%. The developed HPLC method was applied for CTX and DES determination in plasma samples of critically ill patients after continuous intravenous infusion of CTX.     

Gastro-intestinal tract function in sheep infused with somatostatin

The effect of a 5-day continuous intravenous infusion of somatostatin (4.6 ng min-1 kg-1) was studied, using anoestrous ewes given 791 g dry matter per day of a 60:40 lucerne hay:oat grain pelleted diet from a continuously moving belt. 51Cr-EDTA, 103Ru-phenanthroline and lignin were used as markers to determine digesta mean retention times (MRT) by a continuous infusion-total sampling procedure. The somatostatin infusion increased the concentration of somatostatin in venous plasma within the physiological range from 10 to 76 ng/l, decreased plasma concentrations of prolactin and thyroxine, but had no effect upon plasma concentrations of insulin and glucagon. It had no effect upon digesta-free weight of the rumen and omasum but consistently decreased the weight of all post-ruminal segments of the gastrointestinal (GI) tract. The infusion increased the accumulation of digesta in the abomasum and caecum. Total MRT of all three markers in the entire GI tract was unaffected by somatostatin infusion, but the proportion of total MRT spent in the abomasum + small intestine + caecum increased and the proportion spent in the large intestine and rumen decreased. Somatostatin infusion decreased apparent endogenous abomasal secretion, increased water flow from the rumen and into the abomasum and decreased voluntary water consumption. It is proposed that the prime site of somatostatin action was in the abomasal to caecal region, where somatostatin-secreting D cells are found in greatest concentration, that effects observed in the large intestine and rumen may represent secondary compensatory mechanisms and that the effects observed were due to direct action of somatostatin and were not mediated by other GI hormones.     

Effects of intravascular infusions of plasma on placental and systemic blood flow in fetal sheep

Six singleton fetal sheep of 118-122 days gestational age were instrumented with flow sensors on the brachiocephalic artery, the postductal aorta, and the common umbilical artery and with arterial and venous intravascular catheters. At 125-131 days of gestation, we started week-long continuous recordings of flows and pressures. After control measures had been obtained, the fetuses were given continuous intravenous infusions of adult sheep plasma at an initial rate of 229 ml/day. After 1 wk of infusion, fetal plasma protein concentrations had increased from 34 to 78 g/l, arterial and venous pressures had increased from 42 to 64 and from 2.7 to 3.7 mmHg, and systemic resistance (exclusive of the coronary bed) had increased from 0.047 to 0.075 mmHg.min(-1).ml(-1), whereas placental resistance had increased from 0.065 to 0.111 mmHg.min(-1).ml(-1). Fetal plasma renin activities fell as early as 1 day after the start of infusion and remained below control (all changes P < 0.05). All flows decreased slightly although these decreases were not statistically significant. Thus the increase in arterial pressure was entirely due to an increase in systemic and placental resistances.     

Central mechanisms of acute ANG II modulation of arterial baroreflex control of renal sympathetic nerve activity

Short-term intravenous infusion of angiotensin II (ANG II) into conscious rabbits reduces the range of renal sympathetic nerve activity (RSNA) by attenuating reflex disinhibition of RSNA. This action of ANG II to attenuate the arterial baroreflex range is exaggerated when ANG II is directed into the vertebral circulation, which suggests a mechanism involving the central nervous system. Because an intact area postrema (AP) is required for ANG II to attenuate arterial baroreflex-mediated bradycardia and is also required for maintenance of ANG II-dependent hypertension, we hypothesized that attenuation of maximum RSNA during infusion of ANG II involves the AP. In conscious AP-lesioned (APX) and AP-intact rabbits, we compared the effect of a 5-min intravenous infusion of ANG II (10 and 20 ng x kg(-1) x min(-1)) on the relationship between mean arterial blood pressure (MAP) and RSNA. Intravenous infusion of ANG II into AP-intact rabbits resulted in a dose-related attenuation of maximum RSNA observed at low MAP. In contrast, ANG II had no effect on maximum RSNA in APX rabbits. To further localize the central site of ANG II action, its effect on the arterial baroreflex was assessed after a midcollicular decerebration. Decerebration did not alter arterial baroreflex control of RSNA compared with the control state, but as in APX, ANG II did not attenuate the maximum RSNA observed at low MAP. The results of this study indicate that central actions of peripheral ANG II to attenuate reflex disinhibition of RSNA not only involve the AP, but may also involve a neural interaction rostral to the level of decerebration.     

Chronic silastic central venous catheterization for induction, maintenance and support of persistent granulocytopenia in rabbits

In order to investigate new approaches in diagnosis, prevention and treatment of infectious complicating chemotherapy-induced granulocytopenia, we developed and prospectively evaluated a method of chronic central venous catheterization for the induction, maintenance and support of persistent granulocytopenia in rabbits. The method entails a central venous silastic catheter with a subcutaneous tunnel and a heparin lock device for repeated non-traumatic sampling of blood and administration of medications. During the course of 10 months, 226 rabbits were studied. Mean duration of catheter placement was 27 days, 17 of which were spent in granulocytopenia. Two-way flow was sustained throughout the duration of placement in 205 rabbits (91%) and for 5,845 (95%) of a total 6,163 catheter-days. All but two catheters could be flushed throughout the duration of their placement. Postoperative infectious complications related to catheter insertion developed in less than 1% of the rabbits. This method of chronic catheterization safely provides long-term venous access for studies requiring frequent venous access, including the painless induction, maintenance, and support of chronic granulocytopenia in rabbits.     

Motilin release by intravenous infusion of nutrients and somatostatin in conscious dogs

to investigate the regulatory mechanism of motilin release, plasma motilin was measured by radioimmunoassay in healthy dogs during the fasting state and after intravenous administration of various nutrients and somatostatin. The fasting plasma motilin levels of these dogs were found to fluctuate intermittently. Intravenous glucose loading lowered plasma motilin, but immediately after the end of the glucose infusion as abrupt rise of plasma motilin was observed. Mixed amino acids administered intravenously abruptly inhibited motilin secretion, and plasma motilin levels remained low even 45 min after the end of the infusion. On the other hand, no remarkable change in plasma motilin was noted after the fat infusion. Following somatostatin infusion, plasma motilin was significantly decreased, remaining low even 30 min after the end of the infusion. These observations led us to conclude than motilin secretion is regulated by somatostatin and by nutrients coming through intravenous routes.     

The Lumped Constant in the Deoxyglucose Procedure Declines with Age in Fischer-344 Rats

Concentrations of [14C]2-deoxy-D-glucose ([14C]DG) and of glucose were measured in plasma of arterial and sagittal sinus venous blood from awake Fischer-344 rats at 3, 12, and 24 months of age, during continuous intravenous infusion of [14C]DG and after a steady-state arterial plasma concentration of [14C]DG was reached. Brain extraction, i.e., the difference between arterial and venous plasma concentrations divided by the arterial plasma concentration, was calculated for both [14C]DG and glucose. Because exchange of both substances between rat plasma and erythrocytes is slow, the ratio of the brain extraction of [14C]DG to that of glucose is identical to the lumped constant in the deoxyglucose procedure of Sokoloff et al. [J. Neurochem. 28, 897-916. (1977)]. This ratio equaled 0.502 +/- 0.015 (SEM) at 3 months, 0.456 +/- 0.007 at 12 months, and 0.418 +/- 0.006 at 24 months of age (n = 15); the means differed significantly from each other (p less than 0.05). The results indicate that the lumped constant declines between 3 and 24 months of age in awake rats, and suggest that many reported age reductions in regional cerebral glucose utilization, of 15-25%, are artifactual.     

Prevention of microvascular thrombosis with low-dose tissue plasminogen activator.

In a blind, randomized study, two groups, each of seven rabbits, were treated with either a very low dose of human melanoma cell line-derived tissue-type plasminogen activator (t-PA) or isotonic saline. t-PA (0.067 mg/kg of body weight) was administered intraaortically, 20 percent being given as a 30-second "bolus" infusion just prior to the reperfusion of intimectomized central ear arteries and the rest as a continuous infusion during the next 2 hours. Arteriotomic bleeding times, accumulations of 32P-labeled platelets, patency, and sizes of thrombus deposits 2 hours after reperfusion were recorded. To confirm the presence of tissue plasminogen activator in plasma, fibrin-plate lysis assays of arterial plasma were performed immediately before and 1/2 hour and 2 hours after starting drug infusion. Arteriotomic bleeding times were similar in both groups. Transient "oozing" from wound edges occurred in 40 percent of rabbits treated with tissue plasminogen activator. Patency was significantly increased and thrombus deposits were smaller in the tissue plasminogen activator group. Plasma from animals treated with tissue plasminogen activator caused massive lysis of fibrin plates, whereas plasma from control animals caused little or no lysis. Platelet accumulations were very similar in both groups, indicating that occlusive thrombi mainly consisted of other elements than platelets (e.g., fibrin and red cells). Scanning electron microscopy showed normally adhering and aggregating platelets in both groups. This study shows that mild fibrinolytic stimulation with tissue plasminogen activator significantly improves patency in severely traumatized small-caliber arteries and indicates that such treatment may be one approach to prevent thrombosis at microvascular anastomotic sites.     

Optimising antiemesis in cancer chemotherapy: efficacy of continuous versus intermittent infusion of high dose metoclopramide in emesis induced by cisplatin.

Thirty three untreated patients being given cisplatin received metoclopramide (7 mg/kg) for antiemesis by either continuous or intermittent infusion in a random order. Each patient received intravenous dexamethasone in addition. High pressure liquid chromatography was used to measure plasma concentrations of metoclopramide. The two regimens were evaluated for antiemetic efficacy and the incidence of side effects. The intermittent metoclopramide regimen resulted in peak and trough plasma concentrations of metoclopramide with accumulation at eight hours, while the loading dose and continuous infusion resulted in mean plasma concentrations greater than 0.85 micrograms/ml (2.8 mumol/l) throughout the eight hour period. The continuous infusion was associated with a significant improvement in nausea and vomiting and reduction in diarrhoea. Major control of emesis (two episodes or fewer) was achieved in 27 patients receiving continuous metoclopramide compared with 18 receiving intermittent metoclopramide.     

Brittle diabetes: long-term control with a portable,continuous, intravenous insulin infusion system.

A young woman had severe brittle diabetes mellitus that was critically unmanageable with all conventional insulin treatment. Continuous subcutaneous and intramuscular infusions of insulin also failed to control her metabolic instability. Use of a continuous intravenous infusion, however, whereby a portable, variable-rate, battery-operated syringe pump delivered insulin through a subcutaneously tunnelled central venous catheter, resulted in good control. When she was receiving hourly intramuscular insulin injections (a mean of 778 IU daily) mean blood glucose concentrations had been 22.1 +/- 1.4 mmol/l (398 +/- 25 mg/100 microliters). After she had received the intravenous infusion for one month as an outpatient mean blood glucose concentration was 8.2 +/- 0.46 mmol/l (148 +/- 8 mg/100 microliters) and only 80 IU insulin daily was required. Follow-up after over five months of use showed that few complications had occurred. The system is simple to use and safe, and the diabetes had been stabilised such that she could enjoy a near-normal life style.     

Measurement of Glomerular Filtration Rate by Inulin Clearance without Urine Collection

A continuous infusion method for measuring inulin clearance (and hence glomerular filtration rate) which does not require urine collection has been re-evaluated and found to give satisfactory results. In two non-oedematous and anephric patients the plasma level of inulin became virtually constant four hours after a single intravenous dose, and hence this is the minimum time required for the infusion with this method.     

Effect of total colectomy and PYY infusion on food intake and body weight in rats

PYY (3-36) is postulated to act as a satiety factor in the gut-hypothalamic pathway to inhibit food intake and body weight gain in humans and rodent models. We determined the effect of 14-day continuous intravenous infusion of PYY (3-36) (175 microg/kg/day) on food intake and body weight gain in colectomized male Wistar rats. Colectomy caused an increase in plasma PYY levels at 7 days which was reduced at 14 days but still significantly elevated compared to basal preoperative values. Animals treated with continuous PYY (3-36) infusion had significantly elevated PYY levels compared to the control group throughout the whole experiment, but showed a similar pattern of food intake and body weight gain. In conclusion, although continuous intravenous infusion is the most physiologically relevant method to mimic high postprandial PYY levels, we did not observe any significant effect on food intake and body weight gain in non-food deprived colectomized animals. This suggests that PYY has, if at all, only a minor role in food intake in rats.     

CSF acid-base regulation and ventilation in iso- and hypocapnic Hacetate acidosis

Intravenous infusion in conscious rabbits of Hacetate decreases both arterial CO2 partial pressure PaCO2 and cerebrospinal fluid (CSF) HCO3- more than observed with HCl or HNO3 infusion. These acids did not affect CSF HCO3- in isocapnic conditions, and this study asks whether Hacetate infusion will do so. Arterial, central venous, and cisterna magna catheters were implanted in pentobarbital-anesthetized rabbits and all subsequent measurements were performed in the conscious state. Hacetate was infused intravenously over 6 h to decrease plasma HCO3- the same amount in a group allowed to decrease its PaCO2 in response to the acid (hypocapnic) and one in which PaCO2 was maintained at control levels (isocapnic). CSF HCO3- decreased significantly in isocapnia, although the change was less than in hypocapnia. Stoichiometrically by 6 h the measured CSF HCO3- change was balanced by an increase in acetate in hypocapnia and the sum of an increase in acetate and a decrease in chloride in isocapnia. Mechanistically, net acetate entry into CSF appears to involve an exchange for chloride as proposed for NO3-/Cl- and a process that lowers CSF HCO3-. This process could be competitive replacement of HCO3- by acetate in the CSF production mechanism or nonionic diffusive entry of Hacetate into CSF with subsequent titration of HCO3-. The decreases in CSF HCO3- result from the acetate mechanism and the hypocapnic effect on Cl- and HCO3-. The greater ventilatory response results from the greater CSF acidification or a specific effect of acetate per se.     

Clonidine and morphine increase atrial natriuretic peptide secretion in anesthetized rats

In order to determine whether the activity of central alpha 2-adrenergic and opioid receptors influence plasma atrial natriuretic peptide (ANP) levels, clonidine and morphine were infused into the lateral cerebral ventricle for 45 min in anesthetized Sprague-Dawley rats. The central administration of a low dose of clonidine (10 ng/min) caused a significant increase in plasma ANP without changing arterial blood pressure or central venous pressure. Pretreatment with yohimbine (5 micrograms/min) completely blocked the effect of clonidine. Central infusion of morphine (100 ng/min) also elevated plasma ANP levels and naloxone (5 micrograms/min) blunted this effect. Intravenous infusion of the same dose of clonidine or morphine did not affect plasma ANP levels. Moreover, the effect of clonidine on plasma ANP was partially blocked by pretreatment with naloxone (5 micrograms/min). These results suggest that central alpha 2-adrenergic and opioid receptors may be involved in ANP secretion.     

Protection of ischemic myocardium by exogenous phosphocreatine (neoton): pharmacokinetics of phosphocreatine, reduction of infarct size, stabilization of sarcolemma of ischemic cardiomyocytes, and antithrombotic action

The effect of exogenous phosphocreatine on ischemic myocardium was studied in experimental infarction in rabbits and in total ischemia of pig heart tissue (in vitro). It is shown that single dose administration of phosphocreatine is followed by its rapid clearance from blood plasma (with a half lifetime of 4-6 min), but constantly high plasma concentration of phosphocreatine can be maintained by its intravenous infusion. When administered by this method into rabbits during experimental myocardial infarction, phosphocreatine reduces by 40% the size of the necrotic zone. Morphological electron microscopic studies using a lanthanum tracer method showed significant protection of the sarcolemma of cardiomyocytes in the perinecrotic zone by phosphocreatine. In vitro studies on the model of total ischemia also showed significant protection of cardiac sarcolemma from irreversible ischemic injury and reduction in the rate of high-energy phosphate depletion in the presence of phosphocreatine in the extracellular space. Additionally, it is demonstrated that creatine kinase released during myocardial infarction into the blood flow and exogenous phosphocreatine administered intravenously may significantly inhibit platelet aggregation by rapid removal of ADP, and thus potentially improve microcirculation during myocardial infarction.