Biomedical subjects

P Westerling

Publications and source records attributed to P Westerling.

6 recordsLinked to original sources

PubMed1997

Feto-maternal distribution of ropivacaine and bupivacaine after epidural administration for cesarean section.

Ropivacaine is a new amino amide local anesthetic less lipophilic and with a lower affinity for plasma proteins than bupivacaine. The purpose of this study was to examine the feto-maternal distribution of ropivacaine and bupivacaine after epidural administration for cesarean section. Healthy parturients were randomly allocated in a double-blinded manner to receive either 0.5% ropivacaine or 0.5% bupivacaine through a lumbar epidural catheter. The total and free concentrations of ropivacaine and bupivacaine were determined in the maternal and umbilical plasma. The total dose (mg/kg) required for adequate surgical anesthesia and the resulting maximum total concentrations did not differ significantly between ropivacaine and bupivacaine. The free plasma clearance of bupivacaine was higher than that of ropivacaine (7382 vs 3344 ml/min, P = 0.0001). The apparent terminal elimination half-life of ropivacaine was shorter than that of bupivacaine (6.0 vs 8.8 h, P = 0.007). At delivery, the maternal free plasma concentration of ropivacaine was more than twice that of the free concentration of bupivacaine (0.072 vs 0.032 microg/ml, P = 0.002). The free concentration of ropivacaine was about twice that of bupivacaine in the umbilical venous (0.06 vs 0.03 microg/ml, P = 0.001) and umbilical arterial (0.05 vs 0.02 microg/ml, P = 0.007) plasma. The more rapid plasma clearance of bupivacaine compared to ropivacaine, leading to lower maternal plasma concentrations and hence to lower umbilical concentrations at delivery, could be explained by the higher lipid solubility, hence greater distribution volume, of bupivacaine.

Clinical Trial↗

PubMed1997

Pharmacokinetic and clinical study of ropivacaine and bupivacaine in women receiving extradural analgesia in labour.

We have compared, in a randomized, double-blind study, the pharmacokinetics of ropivacaine and bupivacaine during labour. Total and free plasma concentrations of ropivacaine and bupivacaine were measured after the first of two extradural doses. The main dose was 20 mg (test dose) and 30 mg, with a top-up dose of 25 mg when requested. After the main dose, Cpmax (total) of ropivacaine (0.50 mg litre-1) was similar to that of bupivacaine (0.48 mg litre-1). At 20 min, Cpmax (free) of ropivacaine (0.04 mg litre-1) was higher than that of bupivacaine (0.02 mg litre-1) (P = 0.0025). The clinical effectiveness of the block was similar in both groups.

Amides↗

PubMed1995

The effects of epidural ropivacaine and bupivacaine for cesarean section on uteroplacental and fetal circulation.

BACKGROUND: Ropivacaine is a new long-acting amide local anesthetic that has been shown in animal studies to have less dysrhythmogenic and cardiotoxic potential than bupivacaine. The intravenous administration of ropivacaine has not been associated with any detrimental effects on uterine blood flow in pregnant ewes. The purpose of this randomized, double-blind study was to examine the effects of epidural ropivacaine for cesarean section on blood flow velocity waveforms in uteroplacental and fetal arteries with color Doppler ultrasound and to assess whether the block modified fetal myocardial function. METHODS: Healthy parturient women with singleton, uncomplicated pregnancies at term received 115-140 mg 0.5% ropivacaine (n = 11) or 0.5% bupivacaine (n = 10) in incremental epidural doses. The first ultrasound measurement was performed before injection of the study drug. Pulsatility indexes (PI) were derived for the blood flow velocity waveforms of the maternal placental and nonplacental uterine arteries; the placental arcuate artery; and the fetal umbilical, middle cerebral, and renal arteries. The fetal heart then was examined by echocardiography. The PI of the maternal uterine arteries and the fetal umbilical artery were measured 5 min after the injection of the local anesthetic. When sensory analgesia had reached the T6-T4 level, the ultrasound measurement was repeated with the same methods and targets as in the baseline measurement. RESULTS: Both drugs provided adequate surgical anesthesia for cesarean section. In the bupivacaine group, the PI values for the maternal placental and nonplacental uterine arteries increased significantly 5 min after the main dose (P = 0.01, P = 0.002) and when sensory analgesia had reached the T6-T4 level (P = 0.004, P = 0.01) as compared with the baseline measurement. Simultaneously, the PI in the fetal middle cerebral artery decreased significantly (P = 0.02). The PI for the maternal uterine artery increased significantly (P = 0.01) after ropivacaine administration but only on the nonplacental side and not until sensory analgesia had reached the T6-T4 level. No effect on the Doppler indexes obtained from the umbilical artery was observed in either group. There were no significant differences relative to baseline values in any fetal myocardial measurement or in any ultrasound measurement between the groups. Neither drug had any detrimental effect on Apgar scores or umbilical cord acid-base status. None of the neonates' conditions was markedly depressed according to neurobehavioral testing. CONCLUSIONS: Within this small study, epidural 0.5% ropivacaine for cesarean section did not compromise the utero-placental circulation in healthy parturient women with uncomplicated pregnancies. It provided surgical anesthesia that was equally effective as that provided by 0.5% bupivacaine.

Adult↗

PubMed1993

CCKB receptor activation reduces glutamate-induced depolarization in slices of rat cerebral cortex.

Recent studies on cell cultures have indicated that the neuropeptide cholecystokinin (CCK) can prevent glutamate-induced cytotoxicity. In a preparation of rat cortical tissue placed into a two-compartment bath, the cortical tissue could be depolarized, relative to the corpus callosum, by superfusions of KCl or glutamate (1.25-10 mM). Caerulein (1-100 nM), a CCK receptor agonist, caused a rightward shift of the glutamate dose-response curve. The effect of caerulein was abolished by adding L365,260 (1 microM), a selective CCKB receptor antagonist. These findings suggest that CCK may be a physiological antagonist of glutamate-mediated neurotransmission in the rat brain.

Animals↗

PubMed1991

Functional changes in GABAA receptor stimulation during the oestrous cycle of the rat.

1. Slices of rat cuneate nucleus were used to study whether or not gonadal steroids influence the gamma-aminobutyric acid (GABA) system in vivo. Females in different stages of the oestrous cycle as well as steroid-treated (oestrogen, progesterone or both) ovariectomized animals were used. 2. Functional changes in the GABAA receptors were assayed using the effects of potentiators (benzodiazepine, barbiturate) and antagonists (picrotoxin) on the muscimol control dose-response curves. 3. The potentiating effect of the benzodiazepine, flurazepam was unchanged during the oestrous cycle, and the hormone treatments did not alter this effect. 4. During oestrus, an increase was seen in the potentiating effect of the barbiturate (pentobarbitone). This suggests a synergistic effect between barbiturates and gonadal steroids. Progesterone treatment also increased the effect of pentobarbitone. 5. The antagonistic action of picrotoxin was unaffected during the oestrous cycle. However, progesterone (or progesterone and oestrogen) treatment reduced the potency of picrotoxin. 6. This study supports the idea that endogenous steroids (presumably progesterone) affect the GABAA receptors during the oestrous cycle by a mechanism associated with the barbiturate site of the GABAA receptor complex.

Animals↗

PubMed1988

Dopamine mediated behavior and GABA influence.

The possibility of interactions between GABA and dopaminergic central nervous mechanisms in the expression of spontaneous behavior was investigated using the behavior pattern shown by male rats in an exploratory test situation. The present study corroborates the facilitatory action of low doses of the dopamine agonist apomorphine on the investigative activity element of the male rats exploratory behavior pattern, as shown previously. In addition it was found that the GABA agonist baclofen in different doses (1.2-4.8 mg/kg IP) selectively increased this activity. Pretreatment with a submaximal dose of baclofen (1.2 mg/kg) potentiated the effect of apomorphine (25 micrograms/kg), indicating that baclofen has the same effect on behavior as presynaptically active dopamine agonists. Thus GABA mechanisms might influence dopamine mediated behavior. The investigative activity which previously has been considered to reflect the adaptive state of an animal is suggested to be influenced by a changed activity in GABA neurons, DA neurons or an interaction between these two systems in the various brain structures involved in the expression of this behavior.

Animals↗