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Biomedical subjects

G A Gronert

Publications and source records attributed to G A Gronert.

At least 73 records · Page 4Linked to original sources
PubMed1988

Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high-dose atracurium for rapid sequence endotracheal intubation.

Large doses of atracurium (1.5 mg/kg) (six times the ED95) can result in significant histamine release, resulting in systemic hypotension. The efficacy of histamine receptor blockade in attenuating atracurium induced hypotension was therefore studied. Four groups of seven patients each were studied: group I, control; group II, H1 blockade (1 mg/kg diphenhydramine); group III, H2 blockade (cimetidine 4 mg/kg); and group IV, H1 and H2 blockade (diphenhydramine 1 mg/kg and cimetidine 4 mg/kg). All patients were anesthetized with an intravenous narcotic-nitrous oxide technique and then given 1.5 mg/kg atracurium. In group I, mean arterial pressure (MAP) decreased 30 mm Hg after 2 minutes and remained 25 mm Hg below baseline at 3 minutes, a change significantly greater than that in group IV, in which MAP decreased 8 and 7 mm Hg, respectively. H1 receptor blockade was associated with no significant attenuation of changes in MAP. H2 receptor blockade alone was associated with significant decreases in MAP, possibly secondary to enhanced release of histamine via an antagonist effect on recently described H3 receptors. Plasma histamine levels increased significantly 2 minutes after atracurium administration and correlated with hemodynamic changes. It is concluded that combined H1 and H2 receptor blockade attenuates cardiovascular effects associated with large doses of atracurium in humans. Histamine-releasing agents may be contraindicated in patients subject to chronic H2 receptor blockade.

Atracurium↗
PubMed1986

Treatment of porcine malignant hyperthermia: lactate gradient from muscle to blood.

Treatment of MH was studied in 21 pigs, using an isolated perfused caudal body preparation (L1 transection). Halothane one per cent triggered MH; data included oxygen consumption, blood/muscle lactate levels, plasma potassium, acid-base balance. Three treatment protocols had two phases each: A-1, discontinue halothane, inject dantrolene 7.5 mg X kg-1; A-2, inject HCO3- (113 +/- 6 mEq). B-1, Discontinue halothane, inject HCO3- (118 +/- 13 mEq); B-2, inject dantrolene 7.5 mg X kg-1; X C-1, Continue halothane, inject dantrolene 7.5 mg X kg-1; C-2, discontinue halothane, inject HCO3- (101 +/- 8 mEq). Dantrolene and HCO3- acted separately and differently: dantrolene reversed the hypermetabolism, both aerobic and anerobic, and HCO3- reversed the extracellular metabolic acidosis. Semitendinosus muscle biopsies demonstrated that both red and white muscle are involved in MH, that muscle lactate (to 35 mumol X g-1) consistently exceeded blood lactate (to 22 mumol X ml-1), and that blood lactate levels were slow to diminish following treatment. One could expect continued release of muscle lactate into blood, despite adequate therapy of MH; this might suggest a recurrence even when such is not the case.

Animals↗
PubMed1986

Effect of CO2, calcium, digoxin, and potassium on cardiac and skeletal muscle metabolism in malignant hyperthermia susceptible swine.

The effects on whole body or cardiac metabolism of carbon dioxide, calcium, potassium, or digoxin were studied in 16 normal swine and 31 swine susceptible to malignant hyperthermia (MHS). Malignant hyperthermia (MH) was defined as an increase in metabolism that occurred in MHS but not in normal pigs. Whole body response: despite a sustained PaCO2 greater than 130 mmHg, MH did not develop in four intact MHS swine during thiopental-N2O anesthesia and controlled ventilation. Drugs given during total cardiopulmonary bypass: MH did not develop in five MHS pigs with blood ionized calcium to 15 mEq/l, in four MHS pigs with digoxin levels to 60 ng/ml, or in four normal pigs with potassium to 10 mEq/l. In six MHS pigs, oxygen consumption increased from 6.5 to 11.6 ml O2 X min-1 X kg-1 when potassium exceeded 6 mEq/l; lactate did not increase. Cardiac response (during extracorporeal right heart bypass): eight pigs (four normal, four MHS) with blood ionized calcium to 5 mEq/l and eight pigs (four normal, four MHS) with digoxin levels above 7.5 ng/ml had increased myocardial oxygen consumption. Cardiac potassium efflux or lactate production did not occur in normal or MHS pigs. Increased arterial potassium (7.4-8.5 mEq/l) did not alter myocardial oxygen consumption or lactate production in four MHS or four normal pigs. MH responses were initiated only by potassium and only in regard to whole body metabolism. Cardiac metabolism increased as a result of specific drugs (calcium, digoxin), unrelated to MH phenomena. Porcine inbreeding resulting in MH susceptibility of skeletal muscle does not imply abnormality in other tissues.

Animals↗
PubMed1986

Use of dantrolene plus multiple pulses to detect stress-susceptible porcine muscle.

Twitch characteristics of tibialis anterior muscles in situ were examined in stress-susceptible and normal swine. Three groups of pigs were studied: (1) purebred Pietrain stress-susceptible, (2) purebred Yorkshire normal, and (3) a crossbred (Pietrain-Yorkshire) litter containing both stress-susceptible and normal animals. Purebred and crossbred stress-susceptible pigs provided qualitatively similar results, as did purebred and crossbred normal pigs. Single stimuli produced greater than normal peak tensions and faster rates of tension development in stress-susceptible animals. Multiple stimuli (2-6 pulses at 5-ms intervals) increased peak tensions and rates of tension development, but did not augment differences between normal and stress-susceptible pigs. Intravenous administration of dantrolene reduced peak tensions and rates of tension development in all groups for single and multiple stimuli. However, the reduction was significantly less (P less than 0.01) for stress-susceptible pigs. Multiple stimuli (4-6 pulses) plus dantrolene amplified differences (P less than 0.01) in contractile properties between normal and stress-susceptible skeletal muscles, with stress-susceptible muscles obtaining larger peak tensions and faster rates of tension development. Normal and stress-susceptible pigs may, therefore, be distinguished by these procedures.

Animals↗
PubMed1985

Verapamil is not a therapeutic adjunct to dantrolene in porcine malignant hyperthermia.

We have investigated the hypothesis that the calcium antagonist verapamil might be useful for prevention or treatment of malignant hyperthermia (MH) in MH-susceptible (MHS) swine. MH episodes were triggered in four groups of four swine with halothane alone or combined with succinylcholine (SCh) and, with and without verapamil. MH episodes were reversed by therapy with dantrolene and NaHCO3 in all groups. Verapamil did not alter MH episodes triggered by halothane alone or combined with SCh. The dantrolene-NaHCO3 requirements for reversal of MH were greater for the groups receiving halothane-SCh, but did not differ in groups pretreated with and without verapamil. In vitro verapamil (25 microM) did not reduce responses of intact muscle fibers to halothane and, in fact, exaggerated some halothane-induced responses. High concentrations of verapamil (0.5 mM) caused contractures in MHS but not in normal muscles. Neither our in vivo nor in vitro results support the use of verapamil in the treatment of MH. Further, doses of dantrolene used to reverse these MH episodes, although admittedly small (1-2 mg/kg), did not produce myocardial depression when used in combination with verapamil.

Anesthesia, Inhalation↗
PubMed1985

Verapamil does not alter succinylcholine-induced increases in serum potassium during halothane anesthesia in normal dogs.

Six dogs were studied to determine whether verapamil pretreatment exacerbates the increase in serum potassium levels associated with succinylcholine. Dogs were anesthetized with halothane, 1.26 +/- 0% (mean +/- SEM; end tidal). Arterial blood-gas tensions, blood pressure, heart rate, temperature, and serum potassium levels were measured. Each dog underwent control and experimental studies separated by seven days. In the experimental study, a 0.15 mg/kg bolus of verapamil was followed by a 4.0 micrograms X kg-1 X min-1 continuous infusion of verapamil. Normal saline was used in the control study. Succinylcholine, 1 mg/kg bolus, was given 10 min after the initial saline or verapamil bolus. Vital signs again were measured 1, 3, 5, 10, and 15 min after succinylcholine, and plasma verapamil levels were measured 8 and 15 min after verapamil administration. Serum potassium concentrations increased from 3.9 +/- 0.2 to 5.0 +/- 0.2 mEq/L in control studies and from 3.7 +/- 0.2 to 4.8 +/- 0.3 mEq/L in animals pretreated with verapamil. Verapamil pretreatment does not alter the increase in serum potassium induced by succinylcholine in normal dogs.

Anesthesia↗
PubMed1985

Electrical stimulation triggers porcine malignant hyperthermia.

Metabolic, haemodynamic and neuroendocrine responses to electrical neuromuscular stimulation were measured in five normal and five malignant hyperthermia-susceptible pigs. Normal animals recovered after stimulation but susceptible pigs showed malignant hyperthermia-like responses. Catecholamine levels were higher in malignant hyperthermia-sensitive than in normal pigs at all sampling times.

Animals↗
PubMed1984

Canine gastrocnemius disuse atrophy: resistance to paralysis by dimethyl tubocurarine.

Ten dogs developed unilateral gastrocnemius disuse atrophy after unilateral hindlimb immobilization in a cast for 25 days. Dose-response curves to dimethyl tubocurarine (MTC) were determined during anesthesia with pentobarbital sodium-N2O. Bolus and continuous infusion increments of MTC every 30 min provided steady-state blood levels at each stage of paralysis. Both gastrocnemius tendons were sectioned and attached to transducers. Both sciatic nerves were stimulated every 30 min: 2 Hz for 2 s, a 15-s pause, 50 Hz for 2 s. Dose-response curves, computer calculated by nonlinear regression using a sigmoid maximal effect model of the Hill equation, were parallel for the data relating blocking of tetanus to dose of MTC. The 50% paralyzing dose (tetanus) for control vs. casted gastrocnemius muscle was 64 vs. 813 mg/kg; corresponding plasma concentrations were 0.12 vs. 2.0 micrograms/ml. Thus in vivo simultaneous tension measurements of both gastrocnemius muscles, one casted and one uncasted, demonstrated resistance to paralysis by MTC in muscle with disuse atrophy.

Animals↗
PubMed1983

Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. The effects of halothane and dantrolene.

Calcium-induced calcium release and halothane-induced calcium release from pig sarcoplasmic reticulum (SR) were studied. The SR prepared from pigs susceptible to malignant hyperthermia (MH) was shown to release calcium at a much lower level of calcium content than in normal pig SR. The concentration above which halothane can release calcium is 40 microM for both MH-SR and normal SR, although the latter required a high calcium content to demonstrate the calcium release. Dantrolene was shown to inhibit the halothane-induced calcium release. Results suggest that SR plays an important role in pathogenesis of MH.

Animals↗
PubMed1983

Failure to induce malignant hyperthermia in myotonic goats.

Six goats with myotonia congenita were exposed for 1 h to 1% halothane and a single injection of suxamethonium i.v. in an attempt to induce malignant hyperthermia. No evidence of malignant hyperthermia occurred. Suxamethonium did produce a myotonic response in each goat, lasting 10-20s, which was accompanied by a transient increase in aerobic metabolism as indicated by a decrease in PvO2 from 6.6 to 5.7 kPa, an increase in PaCO2 from 5.1 to 6.1 kPa and an increase in PVCO2 from 5.5 to 6.3 kPa. There was no evidence of any metabolic acidosis since the transient changes in pH and buffer base were consistent with the increase in carbon dioxide tension. It is concluded that in goats myotonia congenita does not predispose to susceptibility to malignant hyperthermia.

Animals↗