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PubMed1987

Developmental toxicity of alprostadil in rats after subcutaneous administration or intravenous infusion.

Timed-pregnant Upj:TUC(SD)spf (Sprague-Dawley) rats were dosed with alprostadil (prostaglandin E1), either subcutaneously on Days 6-15 of gestation at 0.0, 0.5, 1.0, or 2.0 mg/kg/day or by iv infusion into the jugular vein (24 hr/day) on Days 7-15 at 0.0, 0.5, 1.0, 2.0, 4.0, or 6.0 mg/kg/day. Maternal toxicity was observed in all dams receiving alprostadil subcutaneously, the severity of which increased in a dose-related manner. Toxicity also was evident in the offspring in the 2.0 mg/kg/day group as evidenced by a significant increase in the percentage of resorptions and a significant decrease in the percentage of live fetuses. Mean fetal weight was significantly depressed in all three alprostadil-treated groups and several skeletal and visceral variations were significantly higher in the 1.0 and 2.0 mg/kg/day groups than in the vehicle control group; in addition, there were two instances of significantly increased frequencies of skeletal variations in the 0.5 mg/kg/day group. Gross, visceral, and skeletal malformations were significantly increased in the high-dose group. During iv infusion of alprostadil more than 50% of the dams in the 6.0 mg/kg/day group died and there was one death in the 4.0 mg/kg/day group. Significant decreases in maternal weight gain between Days 7 and 11 of gestation were observed at doses of 1.0 mg/kg/day and above. However, continuous iv infusion of this prostaglandin, at dosages which were not severely toxic to the dams, was judged not to be teratogenic or otherwise embryotoxic in rats. The increase in uterine contractions, observed at 1.0 and 2.0 mg/kg after sc administration to rats implanted with chronic uterine microballoons, was consistent with the hypothesis that the developmental toxicity observed after bolus sc administration was the consequence of decreased blood flow in the uterus and/or placenta and/or embryos.

Abnormalities, Drug-Induced↗
PubMed1991

A slow intravenous infusion of N-methyl-DL-aspartate as a seizure model in the mouse.

A seizure model involving slow i.v. infusion of the excitatory amino acid N-methyl-DL-aspartate (NMDLA) in the mouse is described. It allows determination of the threshold doses of NMDLA required to elicit clonic and tonic seizures in individual mice. The NMDA receptor antagonists MK-801, CPP, ifenprodil and 7-chlorokynurenic acid (7-CLK), and diazepam dose-dependently increased the dose of NMDLA required to elicit a tonic seizure. CPP, 7-CLK and diazepam also increased the dose of NMDLA inducing clonic seizures. In contrast, ifenprodil at doses which antagonised tonic seizures had no effect on clonic seizures. The glycine and polyamine modulatory site agonists, D-serine and spermidine respectively, dose-dependently reduced the dose of NMDLA required to induce clonic and tonic seizures. The NMDLA infusion model appears to be more sensitive than the classical bolus injection test and can detect both anticonvulsant and proconvulsant actions mediated by the NMDA receptor complex.

Animals↗
PubMed1990

Pharmacodynamics of enoximone during intravenous infusion.

Twenty-one patients with heart failure (NYHA class II-IV) received a 24-hour infusion of enoximone, followed by a 12-hour washout period. Patients were randomly assigned to one of four treatment groups. Groups I-III received a 0.5 mg/kg bolus, followed by a maintenance infusion of 2.5, 5.0 or 10.0 micrograms/kg/minute. Group IV patients received a maintenance infusion of 5.0 micrograms/kg/minute without the bolus. Serial assessments of haemodynamics, plasma levels of enoximone and enoximone sulphoxide, and ventricular ectopy were performed. Enoximone produced a significant increase in cardiac index (28.1-46.7%) and a decrease in mean pulmonary artery wedge pressure (6.4-35.7%) and systemic vascular resistance (34.7-78.9%). Enoximone had minimal effect on heart rate and blood pressure. In patients who did not receive an initial bolus of 0.5 mg/kg, haemodynamic changes were delayed by approximately 1 hour. Significant haemodynamic improvement was noted at even the lowest infusion rate and did not increase in linear fashion at higher infusion rates. During infusion of enoximone at 10.0 micrograms/kg/minute, both enoximone and its sulphoxide accumulated non-linearly and did not achieve a steady state. No significant adverse effects were noted in these patients. Enoximone infusion at rates greater than 5.0 micrograms/kg/minute may confer minimal additional haemodynamic benefit, while resulting in significant accumulation of enoximone and enoximone sulphoxide. Ventricular ectopy did not increase significantly in most patients.

Cardiotonic Agents↗
PubMed1995

Changes in amino acid levels in rat plasma, cisternal cerebrospinal fluid, and brain tissue induced by intravenously infused arginine-vasopressin.

Circulating arginine-vasopressin (AVP) is known to reduce the blood-to-brain transfer of large neutral amino acids (AA). As a first step to examine whether the reduced uptake by brain endothelial cells is reflected in changes in large neutral amino acid levels of the extracellular fluid environment of cells within the nervous tissue, we measured the concentrations of amino acids in plasma, cerebrospinal fluid (CSF), and hippocampal tissue of rats before and after infusion of AVP (34 and 68 ng/min/kg, respectively) over the time period of 60 min. AA levels changed in all compartments investigated during both saline and AVP infusions. Whereas in the saline-infused controls changes in CSF AA levels paralleled those in plasma, this correlation was abolished by raising AVP concentrations. The effect of AVP was found to be i) dependent on the AA, ii) different with respect to direction and iii) magnitude of changes in AA levels, and iv) in some cases dose dependent. In summary, AVP infusion increased plasma levels of 10 AA, but decreased all 15 AA measured by some 30% in CSF. In contrast to CSF, levels of AA were slightly enhanced in the hippocampal tissue. The results are not solely explicable by a reduced blood-to-brain transfer of AA. We conclude that further mechanisms by which AVP affects the availability of AA to the brain may exist. The physiological significance of the findings might be related to brain osmoregulation, especially in situations of stress.

Amino Acids↗
PubMed1991

The importance of added albumin during continuous intravenous infusion of interleukin-2 with alpha-interferon.

We treated 14 patients (4 malignant melanoma/10 renal carcinoma) with a combination of continuous infusion interleukin-2 (IL-2) and subcutaneous alpha-interferon. Variable concentrations of albumin were added to the infusion of IL-2. The toxicity of this regimen seems to be related to the percentage of albumin added to the IL-2 infusion. Partial responses were observed in 3 cases. Interestingly, 1 patient's response appeared dependent on the addition of human serum albumin. The mechanism of these effects is unknown, but the use of albumin with IL-2 should be carefully investigated in future studies.

Adolescent↗
PubMed1990

Treatment of cancer pain of the head and neck by continuous intravenous infusion of high-dose morphine: report of two cases.

Two pain-ridden patients in the terminal stage of a malignancy of the head and neck were treated with high-dose morphine which was administered as a continuous IV infusion along with a hyperalimentation solution using a pump. Good pain relief and a lessening of anxiety were achieved after failure to control pain in spite of the use of the analgesic ladder recommended by the WHO.

Female↗
PubMed1996

Full-thickness burn and venous thrombosis following intravenous infusion of microwave-heated crystalloid fluids.

Use of microwave-heated crystalloid fluid has been recommended as one method of correcting hypothermia during resuscitation. We report a case of full-thickness burns and venous thrombosis after microwave-heated crystalloid was infused in the management of a ruptured aortic aneurysm. This case highlights the severity of the burn injury that can occur with infusion of heated fluids. Measuring the temperature of the fluid before the start of the infusion will avoid this complication.

Aged↗
PubMed1986

Effects of intravenously infused Fluosol-DA 20% in rats.

Rats were injected with a fractionated 50 ml/kg dose of Fluosol-DA 20% with and without exposure to 100% oxygen. Animals were killed at 24, 43, 92, and 183 days post-treatment and samples taken for hematological, hepatic enzyme, histological, and perfluorochemical analyses. There were no significant differences in hemograms or hepatic enzyme findings between treatment and control groups. Differences in organ weights and histology were a result of perfluorochemical (PFC) accumulation in the tissues of treated animals. All changes were reversible. There were no effects from breathing high oxygen levels in either treatment or control animals.

Animals↗
PubMed1991

Efficacy and safety of a short-term (6-h) intravenous infusion of dopexamine in patients with severe congestive heart failure: a randomized, double-blind, parallel, placebo-controlled multicenter study.

Dopexamine hydrochloride is a new synthetic catechol that offers a unique profile of adrenergic and dopaminergic activity. In this multicenter, parallel design, placebo-controlled study, 45 patients with functional class III or IV chronic congestive heart failure were randomized to receive a placebo infusion or one of three different doses of dopexamine. After a 2-h dose titration sequence, patients received a 6-h constant dose infusion. During this 6-h period, dopexamine was infused at rates of 1, 2 and 4 micrograms/kg body weight per min in the low, intermediate and high dose groups, respectively. In patients receiving high dose infusion, dopexamine produced a 78% increase in cardiac index associated with a 43% decrease in systemic vascular resistance and 24% increase in heart rate (p less than 0.05 vs. placebo for all three variables). There was a trend (p = NS) toward a moderate increase in cardiac index at low and intermediate doses. In patients randomized to receive dopexamine, right atrial, systemic arterial, pulmonary artery and pulmonary capillary wedge pressures showed minimal change from baseline and did not differ statistically from the placebo response. Very few patients developed adverse reactions related to dopexamine, although five patients randomized to receive high dose and three patients randomized to receive intermediate dose dopexamine required dose reduction because hemodynamic variables exceeded arbitrary safety limits or the patients developed symptoms related to the study medication. dopexamine in higher doses effectively increases cardiac index in association with a reduction in systemic vascular resistance. Additional clinical studies are indicated to evaluate the merits of dopexamine in comparison with other inotropic and vasodilator medications.

Adrenergic Agonists↗
PubMed1994

The treatment of metastatic renal cell carcinoma by continuous intravenous infusion of recombinant interleukin-2.

Between March 1989 and June 1990, 133 patients were treated with interleukin 2 (rIL-2) for metastatic renal cell carcinoma (RCC) in a multicentre open non-randomised study. The results show an objective response rate of 14% (95% confidence interval 8-21) with 4 patients achieving a complete remission. This is in keeping with the data from previous studies using rIL-2 by continuous infusion. It is of interest that 87% of objective responses occurred in hospitals that entered 5 or more patients.

Adult↗
PubMed2004

Effects of intravenous infusion of highly purified vitamin B2 on lipopolysaccharide-induced shock and bacterial infection in mice.

We investigated the effect of an i.v. infusion of highly purified vitamin B(2) (riboflavin 5'-sodium phosphate: purity >97%) on lipopolysaccharide-induced shock and bacterial infection in mice. Six hours after lipopolysaccharide injection or 1 h after bacterial infection, vitamin B(2) or human activated protein C (APC) was administered by 6-h i.v. infusion. Vitamin B(2) at 10 mg/kg/6 h and up to 80 mg/kg/6 h significantly improved lipopolysaccharide-induced endotoxin shock. APC was also effective at low doses, but was deleterious at higher doses. Moreover, vitamin B(2) at 80 mg/kg/6 h significantly reduced the lethality of Escherichia coli and Staphylococcus aureus infection, whereas APC at up to 600 units/kg/6 h was ineffective. The i.v. infusion of vitamin B(2) reduced the elevations of proinflammatory cytokines and nitric oxide induced by lipopolysaccharide. These results suggest that i.v. infusion of vitamin B(2) represents a promising strategy for the treatment of sepsis and septic shock.

Animals↗
PubMed1999

Effect of intravenous infusion of a beta-adrenergic blocking agent on the haemodynamic changes in human masseter muscle induced by cold-pressor stimulation.

Eight healthy non-smoking males (mean age: 24.1 +/- 1.1 years) without any history of chronic muscle pain and migraine participated in this study. Haemoglobin (Hb) and oxygen (O2) saturation in the right masseter muscle were continuously recorded with a non-invasive near-infrared spectroscopic device. Heart rate and blood pressure were also recorded. The experiment had three phases: a placebo drug (physiological saline) with cold-pressor trial, a 30-sec maximal voluntary clenching (MVC) trial, and a propranolol with cold-pressor trial. The saline and drug trials each involved continuous recording for 1 min before, 2 min during and 5 min after the cold-pressor stimulation (4 degrees C). Physiological saline (20 ml) or propranolol hydrochloride (20 ml) were infused at the rate of 2 ml/min. This infusion was begun 20 min before the baseline recording and participants did not know which solution (saline or propranolol) was being infused. For the MVC trial, each participant was asked to perform a 30-sec clench of their jaw-closing muscles. There was a rest period of 15 min between each trial. The individual Hb and O2 data were normalized so that the baseline at the beginning of the experiment was equal to zero, and the Hb and O2 data were normalized as a percentage of the individual's own highest absolute Hb and O2 after and during the MVC, respectively. The results showed that the mean baseline Hb 1 min before cold-pressor stimulation was significantly lower in the beta-blocker trial than in the placebo trial (p = 0.035). The mean change in Hb from baseline during cold-pressor stimulation in the beta-blocker trial was also significantly less than in the placebo trial (p = 0.035). The mean Hb rebound change after the cold-pressor stimulation in the beta-blocker trial was significantly higher than in the placebo trial, and no significant heart-rate differences were observed in the period after cold-pressor stimulation. Overall, the mean heart rate before and during that stimulation was significantly lower in the beta-blocker trial than the placebo trial (p < 0.001). There was no significant mean blood-pressure difference between placebo and beta-blocker trials at any time. These results suggest that beta-adrenoceptor blocking decreases the blood volume in the resting masseter, suppresses the incremental blood-volume change during cold-pressor stimulation, and discloses a hidden vasoconstrictive effect after that stimulation.

Adrenergic beta-Antagonists↗