Michael L. Nahrwold

Halothane Requirement during Pregnancy and Lactation in Rats

Near-term pregnancy is associated with a decrease in the minimum alveolar concentration (MAC) for halothane in ewes. Although increased progesterone levels might account for this change, a correlation between MAC and the known variations of progesterone levels which occur throughout gestation and the postpartum period has not been performed. Therefore, MAC for halothane was determined in nonpregnant, 10 days pregnant, term, and postpartum lactating rats. MAC values were significantly decreased by 19 per cent on the tenth day of pregnancy, and by 16 per cent at term, but they returned to control values 5 days postpartum. These changes did not correlate with the known changes in progesterone levels during pregnancy and lactation, and the authors conclude that progesterone is not responsible for the reduction in halothane MAC.

Halothane-induced Alterations of Cyclic Nucleotide Concentrations in Three Regions of the Mouse Nervous System

In an effort to determine whether halothane alters cyclic nucleotide levels in the nervous system, mice were exposed to air (control) or halothane 0.7, 1.4, 2.4, 3.0, or 4.4 per cent in air, for 15 minutes. After quick-freezing in liquid nitrogen, levels of 3,5‘-cyclic guanosine monophosphate (cGMP) and 3’,5‘-cyclic adenosine monophosphate (cAMP) in the cerebral cortex, cerebellum, and spinal cord were determined. Lactate and pyruvate were measured in the cerebral cortex and cerebellum as an index of brain oxygenation, and blood-gas and pH values were measured in replicate experiments. Three groups of studies were made: 1) control, 2) low halothane concentrations (0.7–2.4 per cent) without hypoxia and acidosis, and 3) high halothane concentrations (3.0 and 4.4 per cent) accompanied by hypoxia and acidosis. Low halothane concentrations increased cGMP in the cerebral cortex, depressed it in the cerebellum, and had no effect on levels in the spinal cord. Similar alterations were seen after exposure to high halothane concentrations that included a hypoxic component, except that cGMP in the spinal cord was depressed. Since anoxia decreases cGMP in the cerebral cortex and cerebellum, the increase in cGMP in the cortex suggests that the effect of halothane cannot be attributed to hypoxia. The only effect of halothane on cAMP was to depress the levels of the nucleotide in the cortex at halothane concentrations of 2.4 per cent or more. The authors conclude that halothane has a greater effect on cGMP than on cAMP, and that the biochemical responses to the anesthetic vary among regions of the nervous system.

Plasma levels and cardiovascular effects of nitroglycerin in pregnant sheep

The cardiovascular effects and blood levels of intravenous nitroglycerin in mother and foetus were studied in normotensive and hypertensive ewes. Although nitroglycerin produced a reduction in uterine blood flow following a decrease in blood pressure, there was little if any incidence of adverse effects in the foetus. Nitroglycerin was detected in all but two samples of foetal arterial blood but the foetal/maternal artery ratio was only 0.04. Nitroglycerin merits further evaluation for the treatment of acute hypertensive episodes in the preeclamptic patient.RésuméLes effets cardiovasculaires et le niveau sanguin maternel et foetal de la nitroglycérine ont été étudiés chez la brebis normotensive et hypertensive. Bien que la nitroglycérine ait causé une diminution du débit sanguin utérin à la suite de la baisse de la tension artérielle, on n’a pu constater que peu ou pas d’effets nocifs sur le foetus. La nitroglycérine a été détectée dans tous les échantillons de sang artériel foetal à l’exception de deux et le rapport entre le sang foetal et maternel n’a été que de 0.04. La nitroglycérine mérite une évaluation plus approfondie pour le traitement de la crise hypertensive de la parturiente pré-éclamptique.

A Comparison of Methods of Blood Withdrawal and Sample Preparation for Potassium Measurements

The effect on measured potassium values of a number of factors involved in sample acquisition and preparation were investigated. Measured potassium values in either plasma or serum were not influenced by the site of sample withdrawal, the presence of a tourniquet, or the time elapsed between blood sampling and analysis. However, increasing heparin concentrations and/or volumes decreased potassium values. The highest values were obtained in samples obtained in a syringe that had been washed with minimum volumes of heparin. It is concluded that this common clinical practice is based on a sound scientific rationale.

Effect of protamine on plasma ionized calcium in the dog.

Ten anaesthetized, heparinized healthy adult dogs were infused with protamine sulphate 3 mg.kg-1 and plasma ionized calcium was measured. A significant (p < 0.01) decrease in ionized calcium occurred which preceded the maximal reduction in cardiac output and systemic arterial pressure. The clinical implications of these results are discussed.RéSUMéOn a mesuré le calcium plasmatique ionisé après l’administration de sulfate de protamine à la dose de 3 mg.kg-1 chez dix chiens normaux, héparinisés, sous anesthésie générale. On a observé une diminution significative (p < 0.01) du calcium ionisé. Cette diminution précédait la diminution maximale du débit cardiaque et de la pression artérielle que l’on a observée. Les implications cliniques de ces résultats sont discutées.

Cardiac failure associated with hypocalcemia.

Rapid transfusion of citrated whole blood was associated with acute hypotension and a rising central venous pressure in a patient undergoing pelvic exenteration and hemipelvectomy. Evidence of cardiac failure was accompanied by a precipitous decrease in serum ionized calcium (Ca++) concentration. When the rate of blood transfusion was slowed, arterial blood pressure returned to the control level and serum Ca++ increased.

Comparison of Cardiovascular Responses to Anesthesia and Operation When Intravenous Lidocaine or Morphine Sulfate Is Used as Adjunct to Diazepam-nitrous Oxide Anesthesia for Cardiac Surgery

Intravenous lidocaine was evaluated as an anesthetic adjunct and its hemodynamic effects compared to those of morphine sulfate. Forty patients undergoing surgery for coronary artery bypass or aortic valve replacement for moderate aortic stenosis were randomly assigned to one of two groups. Patients in group 1 received a total dose of 2 mg/kg of morphine sulfate while those in group 2 received 21 mg/kg of lidocaine. In addition, patients in both groups were given 0.6 mg/kg of diazepam and 50% N2O in oxygen.Peak plasma lidocaine levels in group 2 occurred following sternotomy. Electroencephalo-graphic evidence of seizure activity was absent at this time. Indices of myocardial performance (cardiac index, stroke work index) were depressed following induction of anesthesia and remained depressed up to institution of cardiopulmonary bypass in patients given lidocaine. Arterial blood pressure changed minimally. In contrast, patients given morphine demonstrated an increase in cardiac index and left ventricular stroke work index following tracheal intubation. Arterial blood pressure and systemic vascular resistance initially decreased following induction of anesthesia and increased with tracheal intubation in patients receiving morphine sulfate. Arterial blood pressure, stroke work index, and systemic vascular resistance increased further in these patients while cardiac index returned to control values during the period of surgical stimulation.Electrocardiographic changes indicative of myocardial ischemia did not differ in the two groups. The relationship between myocardial oxygen supply and demand, as reflected by the rate pressure product and endocardial viability ratio indices, was, however, adversely affected during surgical stimulation in the patients given morphine.Lidocaine produced stable clinical anesthesia without large fluctuations in hemodynamic function. In contrast to morphine, lidocaine depressed the hypertensive and tachycardic responses to surgery, thus favorably influencing the balance between myocardial oxygen supply and demand.

Alterations in Influenza Virus Pulmonary Pathology Induced by Diethyl Ether, Halothane, Enflurane, and Pentobarbital Anesthesia in Mice

Three-week-old CD-1 mice infected with the PR-8 (mouse-adapted) strain of influenza virus while exposed to enflurane demonstrated a decrease in virus titers from the lungs of infected animals, less abnormality of lung histology, and an increase in survival in animals as compared with those receiving the other anesthetics tested. Greater than 90% mortality occurred in groups of mice which inhaled aerosolized virus and received no anesthesia, pentobarbital, diethyl ether, or halothane anesthesia 96 h following infection. Infected mice anesthetized with enflurane 96 h post-infection had significantly lower mortality rate (68%) when compared with the other groups.Halothane-anesthetized mice receiving intranasal influenza virus during anesthesia demonstrated increased survival and a delay in the mean day of death when compared with animals receiving either diethyl ether or pentobarbital anesthesia. Animals receiving enflurane during virus inoculation had an even lower mortality rate and a later mean day of death when compared with infected animals receiving any of the other three anesthetics.Examination of lungs from animals infected during anesthesia demonstrated influenza virus titers significantly less in the animals that received enflurane anesthesia when compared with the other groups. Histologic sections of lungs revealed extensive spread of the disease process into the alveoli and interstitium of the lungs of animals infected while receiving pentobarbital or diethyl ether anesthesia. Animals infected during halothane demonstrated pathologic characteristics similar to pentobarbital- and diethyl-ether-treated groups; however, the changes were not as extensive. Mice infected during exposure to enflurane revealed only a mild bronchopneumonia.

Is Depression of Mitochondrial Respiration a Predictor of In-vivo Anesthetic Activity?

Previous data suggest that depression of mitochondrial respiration might be used as a predictor of in-vivo anesthetic activity. This hypothesis was tested by comparing the effects in vivo and in vitro of four volatile compounds with widely varying actions on the central nervous system. Caroxin-D and Caroxin-F, fluorocarbons devoid of anesthetic activity, were without effect on mitochondrial respiration. Hexafluoroisopropyl methyl ether (ISO), an inhalation anesthetic, depressed mitochondrial respiration in a fashion similar to that demonstrated for halothane, diethyl ether, methoxyflurane, enflurane, isoflurane, and fluroxene. These data support the above-mentioned hypothesis. However, flurothyl, an inhalation convulsant, also inhibited mitochondrial respiration. Moreover, while the effects of ISO and flurothyl are antagonistic in vivo, they were additive in vitro. It is concluded that the hypothesis that depression of mitochondrial respiration might be used as a predictor of in-vivo anesthetic activity is not valid.

Anesthetic action and virus replication: inhibition of measles virus replication in cells exposed to halothane.

Replication of measles virus in BSC cells was studied in the presence of halothane, a commonly used volatile anesthetic. At clinical concentrations of the anesthetic, appearance of progeny virus was decreased in a dose-related manner. This inhibition was reversible as the removal of halothane allowed virus replication to be resumed. Studies attempting to elucidate the mechanism of action of the anesthetic inhibition of virus replication revealed that halothane did not directly inactivate the virus particle or prevent viral adsorption to the cell. Infectious virus and nucleocapsid production were decreased or stopped, depending on the anesthetic dosage used. Direct immunofluorescent staining for measles virus antigen was negative in cells treated at the higher concentrations of halothane. Recovery of nucleocapsid production started within a few hours after removal of halothane. Furthermore, the combined inhibitory effects on viral ribonucleic acid synthesis of 5-azacytidine and halothane were additive. This evidence suggests that inhibition of measles virus replication occurs at or before ribonucleic acid synthesis. Images