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Biomedical subjects

M B Weinger

Publications and source records attributed to M B Weinger.

At least 55 records · Page 3Linked to original sources
PubMed1991

Prevention of the cardiovascular and neuroendocrine response to electroconvulsive therapy: II. Effects of pretreatment regimens on catecholamines, ACTH, vasopressin, and cortisol.

The neuroendocrine response to electroconvulsive therapy (ECT) was assessed in four patients after pretreatment with esmolol (1.0 mg/kg), fentanyl (1.5 micrograms/kg), labetalol (0.3 mg/kg), and saline solution (control). Each patient received each drug pretreatment using a double-blind, randomized study block-design. During each of the five studies, blood samples were obtained from each patient before anesthetic induction, before ECT shock, and at 1, 5, 10, and 30 min after seizure. Samples were subsequently analyzed for epinephrine, norepinephrine, adrenocorticotrophic hormone (ACTH), arginine vasopressin (AVP), and cortisol. Electroconvulsive therapy after saline pretreatment resulted in a 3-fold and 15-fold increase in norepinephrine and epinephrine levels, respectively (P less than 0.05). The ACTH and cortisol levels gradually increased over 30 min, peaking at values that were two to three times the control values (P less than 0.05). The AVP levels increased significantly after induction of ECT (P less than 0.005) and remained higher than control levels at 5, 10, and 30 min. The effect of pretreatments varied. Pretreatment with esmolol and fentanyl resulted in significant attenuation of the norepinephrine peak after seizure (P less than 0.05). Only esmolol significantly attenuated ECT-induced epinephrine secretion, whereas fentanyl pretreatment significantly reduced release of ACTH after ECT. No pretreatment significantly affected the elevated AVP or cortisol levels seen on emergence or up to 30 min after treatment. The ability of esmolol pretreatment to attenuate serum catecholamine release after ECT is consistent with its ability to block the cardiovascular responses to ECT.

Adrenocorticotropic Hormone↗
PubMed1991

Prevention of the cardiovascular and neuroendocrine response to electroconvulsive therapy: I. Effectiveness of pretreatment regimens on hemodynamics.

Electroconvulsive therapy (ECT) under anesthesia is associated with hypertension and tachycardia. The cardiovascular effects of ECT were studied after pre-treatment of 10 patients with esmolol (1.0 mg/kg), fentanyl (1.5 micrograms/kg), labetalol (0.3 mg/kg), lidocaine (1.0 mg/kg), and saline solution (control), using a double-blind, randomized block-design. Each patient received all five pretreatment regimens over the course of five ECT sessions. During control studies, arterial blood pressure and heart rate increased significantly in all patients after ECT (P less than 0.05 and P less than 0.01, respectively). The rate-pressure product increased by an average of 336% +/- 14% (P less than 0.01). There were appreciable individual differences in the cardiovascular response to ECT, independent of pretreatment (P less than 0.01). Pretreatment with esmolol and labetalol significantly reduced the hemodynamic response to ECT, compared with fentanyl, lidocaine, or saline solution (P less than 0.05). Esmolol attenuated arterial blood pressure to a larger extent than did labetalol (P less than 0.05). Compared with saline solution (control), pretreatment with labetalol, fentanyl, or lidocaine significantly reduced seizure duration (P less than 0.05) and increased the frequency with which a second electrical stimulus was required. In contrast, esmolol pretreatment did not significantly affect seizure duration. Esmolol (1 mg/kg), administered 1 min before induction of anesthesia, produced significant amelioration of the cardiovascular response to ECT with minimal effect on seizure duration.

Adult↗
PubMed1990

Effects of two benzodiazepine inverse agonists, RO 15-4513 and FG 7142, on recovery from pentobarbital and halothane anesthesia in the rat.

A new class of drugs, the benzodiazepine inverse agonists, have recently been shown to antagonize some of the behavioral and sedative effects of benzodiazepines, barbiturates, and alcohol. Preliminary studies suggested that at least one of these drugs, RO 15-4513, may also be able to reverse the general anesthetic properties of volatile halogenated agents. Another inverse agonist, FG 7142, exhibits a similar ability to antagonize alcohol or benzodiazepines. However, FG 7142 is less potent than RO 15-4513 and has less affinity for the benzodiazepine receptor (BZR). The present studies were therefore undertaken to compare the analeptic effects and relative potencies of RO 15-4513 and FG 7142 on the anesthetic properties of pentobarbital compared with the general anesthetic agent halothane as measured by the time for recovery of the righting reflex in the rat. Three basic experimental paradigms were employed. Drug (FG or RO) or carrier was administered 5 minutes prior to the induction of pentobarbital anesthesia. Drug or carrier was administered to anesthetized animals 60 minutes after pentobarbital injection. Lastly, drug or carrier was administered 5 minutes prior to 15 minutes of halothane anesthesia. In addition, the selective benzodiazepine antagonist, flumazenil (RO 15-1788), was used to determine if the effects of the benzodiazepine inverse agonists on recovery from barbiturate or halothane anesthesia were due to activity at the BZR. The results revealed that RO was both more potent and more effective than FG at speeding recovery from barbiturate anesthesia in the rat. RO's effects appeared to be primarily due to BZR inverse agonist activity since it could be reversed by the BZR antagonist, flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗
PubMed1990

Dexmedetomidine, a selective alpha 2-agonist, does not potentiate the cardiorespiratory depression of alfentanil in the rat.

The authors examined the cardiovascular and respiratory effects of the highly selective alpha 2-adrenergic agonist dexmedetomidine, both alone and in combination with the synthetic opiate alfentanil. Spontaneously ventilating rats (n = 28) were pretreated with dexmedetomidine, 10 or 30 micrograms/kg; dexmedetomidine, 30 micrograms/kg in combination with the central-acting alpha 2-antagonist idazoxan, 10 mg/kg; or vehicle. Fifteen minutes later all rats received alfentanil, 500 micrograms/kg. Pretreatment with dexmedetomidine reduced heart rate in a dose-related fashion. Administration of alfentanil also caused a significant reduction in heart rate. However, following alfentanil, the dexmedetomidine-treated animals did not have significantly greater bradycardia than control animals. An increase in blood pressure was observed in those animals receiving the larger dose of dexmedetomidine, but this difference disappeared following injection of alfentanil. The addition of idazoxan to the pretreatment regimen prevented the changes seen with dexmedetomidine. Pretreatment with dexmedetomidine produced no significant changes in arterial pH or PCO2. In all groups, administration of alfentanil resulted in a decrease in arterial pH that ultimately became a mixed respiratory and metabolic acidosis. The acidosis promptly resolved following injection of naloxone (1 mg/kg). It appears that dexmedetomidine, at the doses given, has little or no effect on respiration. Dexmedetomidine decreases heart rate but does not add to bradycardia following alfentanil. There is a hypertensive effect seen at the higher dose of dexmedetomidine, but this effect disappears when the drug is given in conjunction with alfentanil. These data show that addition of the alpha 2-agonist dexmedetomidine will not worsen the cardiovascular and respiratory depression associated with high-dose opiates in the spontaneously ventilating rat.

Adrenergic alpha-Agonists↗
PubMed1989

Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat.

The highly-selective alpha-2 adrenergic agonist dexmedetomidine (D-MED) is capable of inducing muscle flaccidity and anesthesia in rats and dogs. Intense generalized muscle rigidity is an undesirable side effect of potent opiate agonists. Although the neurochemistry of opiate-induced rigidity has yet to be fully elucidated, recent work suggests a role for a central adrenergic mechanism. In the present study, the authors determined if treatment with D-MED prevents the muscle rigidity caused by high-dose alfentanil anesthesia in the rat. Animals (n = 42) were treated intraperitoneally with one of the following six regimens: 1) L-MED (the inactive L-isomer of medetomidine), 30 micrograms/kg; 2) D-MED, 10 micrograms/kg; 3) D-MED, 30 micrograms/kg; 4) D-MED [30 micrograms/kg] and the central-acting alpha-2 antagonist, idazoxan [10 mg/kg]; 5) D-MED [30 micrograms/kg] and the peripheral-acting alpha-2 antagonist DG-5128 [10 mg/kg], or; 6) saline. Baseline electromyographic activity was recorded from the gastrocnemius muscle before and after drug treatment. Each rat was then injected with alfentanil (ALF, 0.5 mg/kg sc). ALF injection resulted in a marked increase in hindlimb EMG activity in the L-MED treatment group which was indistinguishable from that seen in animals treated with saline. In contrast, D-MED prevented alfentanil-induced muscle rigidity in a dose-dependent fashion. The small EMG values obtained in the high-dose D-MED group were comparable with those recorded in earlier studies from control animals not given any opiate. The high-dose D-MED animals were flaccid, akinetic, and lacked a startle response during the entire experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1988

Localization of brainstem sites which mediate alfentanil-induced muscle rigidity in the rat.

Previous work has demonstrated that direct injections of methylnaloxonium (MN), a relatively lipophobic quaternary opiate antagonist, in the area of the nucleus raphe pontis (RPn) significantly attenuated alfentanil-induced rigidity. It was hypothesized that other hindbrain sites, particularly the other raphe nuclei, might play a role in this rigidity. Therefore, a study was performed in which 57 rats, divided into four groups, were implanted with chronic guide cannulae directed at brain sites anterior, lateral, or posterior to the RPn. After each animal was pretreated with intracerebral injections of MN, alfentanil (0.5 mg/kg) was administered subcutaneously. Electromyographic activity was recorded from the gastrocnemius muscle as a measure of hindlimb rigidity. Each animal was subsequently injected at 4 to 5 day intervals with MN two additional times at sites 1 and 2 mm deeper, respectively, than the initial injection. Data were thus obtained on animals treated with either MN or saline at 3 successive histologically identified sites which were either anterior, lateral or posterior to the RPn. The administration of MN into two specific sites in the region just lateral to the nucleus raphe pontis significantly [F(1,38) = 18.68 and 5.02 respectively, p less than 0.05] reversed the rigidity produced by systemic alfentanil administration. There was a weak effect of MN injections anterior to the RPn but this could not be localized to any one site. These results suggest that discrete brainstem regions involved in opiate action can be sensitively and selectively identified by direct intracranial injections of a lipophobic opiate antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗
PubMed1987

Intrathecal dynorphins suppress hindlimb electromyographic activity in rats.

Intrathecal administration of dynorphin A-(1-17) produced suppression of hindlimb electromyographic activity in rats. This effect was seen also with the [D-Ala2]dynorphin (A-(1-17) analog. Intrathecal saline or the prototypical kappa opiate agonist, U50488, did not produce any change in electromyographic activity. These results, along with others, suggest that dynorphin or degradation fragment(s) of dynorphin, induces inhibition of ventral horn output and may possibly have toxic effects on ventral horn cells of the spinal cord.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1987

End-tidal carbon dioxide as a measure of arterial carbon dioxide during intermittent mandatory ventilation.

To determine if end-tidal carbon dioxide tension (PETCO2) is a clinically reliable indicator of arterial carbon dioxide tension (PaCO2) under conditions of heterogeneous tidal volumes and ventilation-perfusion inequality, we examined the expiratory gases of 25 postcardiotomy patients being weaned from ventilator support with intermittent mandatory ventilation. Using a computerized system that automatically sampled airway flow, pressure, and expired carbon dioxide tension, we were able to distinguish spontaneous ventilatory efforts from mechanical ventilatory efforts. The PETCO2 values varied widely from breath to breath, and the arterial to end-tidal carbon dioxide tension gradient was appreciably altered during the course of several hours. About two-thirds of the time, the PETCO2 of spontaneous breaths was greater than that of ventilator breaths during the same 70-second sample period. The most accurate indicator of PaCO2 was the maximal PETCO2 value in each sample period, the correlation coefficient being 0.768 (P less than 0.001) and the arterial to end-tidal gradient being 4.24 +/- 4.42 mm Hg (P less than 0.01 compared with all other measures). When all values from an 8-minute period were averaged, stability was significantly improved without sacrificing accuracy. We conclude that monitoring the maximal PETCO2, independent of breathing pattern, provides a clinically useful indicator of PaCO2 in postcardiotomy patients receiving intermittent mandatory ventilation.

Carbon Dioxide↗
PubMed1987

Ketanserin pretreatment reverses alfentanil-induced muscle rigidity.

Systemic pretreatment with ketanserin, a relatively specific type-2 serotonin receptor antagonist, significantly attenuated the muscle rigidity produced in rats by the potent short-acting opiate agonist alfentanil. Following placement of subcutaneous electrodes in each animal's left gastrocnemius muscle, rigidity was assessed by analyzing root-mean-square electromyographic activity. Intraperitoneal ketanserin administration at doses of 0.63 and 2.5 mg/kg prevented the alfentanil-induced increase in electromyographic activity compared with animals pretreated with saline. Chlordiazepoxide at doses up to 10 mg/kg failed to significantly influence the rigidity produced by alfentanil. Despite the absence of rigidity, animals that received ketanserin (greater than 0.31 mg/kg i.p.) followed by alfentanil were motionless, flaccid, and less responsive to external stimuli than were animals receiving alfentanil alone. Rats that received ketanserin and alfentanil exhibited less rearing and exploratory behavior at the end of the 60-min recording period than did animals that received ketanserin alone. These results, in combination with previous work, suggest that muscle rigidity, a clinically relevant side-effect of parenteral narcotic administration, may be partly mediated via serotonergic pathways. Pretreatment with type-2 serotonin antagonists may be clinically useful in attenuating opiate-induced rigidity, although further studies will be necessary to assess the interaction of possibly enhanced CNS, cardiovascular, and respiratory depression.

Adjuvants, Anesthesia↗