The effects of halothane or isoflurane, alone and in combination with propofol or thiopental were investigated for their effects on intracranial pressure (ICP) in the rabbit, with inducing artificially-increased ICP with an intracranial balloon. The higher the end-tidal concentrations of either halothane or isoflurane, the lower the mean arterial pressures (MAP) and cerebral perfusion pressures (CPP). However, the ICP was not influenced by the depth of anesthesia for either inhalation anesthetics. The mean ICPs at 1.5 MAC of halothane and isoflurane were 14 +/- 2 and 20 +/- 2 mmHg, respectively. With the increase of intracranial volume using a 0.7 ml-saline balloon, the ICPs were increased to 193 and 205% in halothane and isoflurane anesthesia, respectively. The ICPs were returned to the levels prior to balloon inflation by the injection of thiopental or propofol. The authors conclude that propofol could be used to reduce ICP under halothane or isoflurane anesthesia if it is ascertained to have the characteristics of a balanced coupling between cerebral metabolism and blood flow like barbiturates do and that either halothane or isoflurane with increased concentrations may decrease MAP without significant change of ICP.
*Anesthesia ; Animal ; Female ; *Halothane ; Intracranial Pressure/*drug effects ; *Isoflurane ; Male ; Propofol/*pharmacology ; Rabbits ; Thiopental/*pharmacology

The formalin test is a model of injury-produced inflammatory pain. Anesthetics, in clinically relevant concentrations, affect neutrophils and immune suppression. This study was to determine whether halothane reliably inhibits inflammatory reaction and formalin induced pain behavior or does not. Rats were exposed to 100% oxygen (control) or halothane, respectively for 30 min and then 24 hr later five percent formalin test was assessed. The base values of the paw's diameter were obtained earlier, and then formalin induced edema was assessed by measuring diameters of the injected paws at 5 min, 1 hr, 4 hr and 24 hr after the injection. Nociceptive behavior was quantified by counting the number of times with the paw flinched at 5 min intervals for 60 min. The diameters of edema in the halothane group lessened more than those in the oxygen group at 1 and 24 hr in each following of the injection (p<0.05). The rats pre-administered with oxygen or halothane were similar appearances in nociceptive behaviors. It suggests that halothane anesthesia might inhibit slightly the inflammatory reaction with the formalin-induced edema but might not inhibit the formalin-induced pain behavior in the event of pre-administration halothane 24 hr earlier before the formalin test of rat.
Anesthetics, Inhalation/pharmacology ; Anesthetics, Inhalation/immunology* ; Animal ; Edema/immunology* ; Edema/chemically induced ; Formaldehyde/pharmacology ; Formaldehyde/immunology ; Halothane/pharmacology ; Halothane/immunology* ; Hindlimb/immunology ; Hindlimb/drug effects ; Male ; Rats ; Rats, Sprague-Dawley

BACKGROUNDThe mechanisms of action for volatile anesthetics remain unknown for centuries partly owing to the insufficient or ineffective research models. We designed this study to develop three strains derived from a wild-type Drosophila melanogaster with different sensitivities to volatile anesthetics, which may ultimately facilitate molecular and genetic studies of the mechanism involved.

METHODSMedian effective doses (ED(50)) of sevoflurane in seven-day-old virgin female and male wild-type Drosophila melanogaster were determined. The sensitive males and females of percentile 6 - 10 were cultured for breeding sensitive offspring (S(1)). So did median ones of percentile 48 - 52 for breeding median offspring (M(1)), resistant ones of percentile 91 - 95 for breeding resistant offspring (R(1)). Process was repeated through 31 generations, in the 37th generation, S(37), M(37) and R(37) were used to determine ED(50) for enflurane, isoflurane, sevoflurane, desflurane, halothane, methoxyflurane, chloroform and trichloroethylene, then ED(50) values were correlated with minimum alveolar concentration (MAC) values in human.

RESULTSFrom a wild-type Drosophila melanogaster we were able to breed three strains with high, median and low sevoflurane requirements. The ratio of sevoflurane requirements of three strains were 1.20:1.00:0.53 for females and 1.22:1.00:0.72 for males. Strains sensitive, median and resistant to sevoflurane were also sensitive, median and resistant to other volatile anesthetics. For eight anesthetics, ED(50) values in three strains correlated directly with MAC values in human.

CONCLUSIONSThree Drosophila melanogaster strains with high, median and low sensitivity to volatile anesthetics, but with same hereditary background were developed. The ED(50) are directly correlated with MAC in human for eight volatile anesthetics.

Anesthetics, Inhalation ; pharmacology ; Animals ; Chloroform ; pharmacology ; Drosophila melanogaster ; drug effects ; growth & development ; Enflurane ; pharmacology ; Female ; Halothane ; pharmacology ; Isoflurane ; analogs & derivatives ; pharmacology ; Male ; Methoxyflurane ; pharmacology ; Methyl Ethers ; pharmacology ; Trichloroethylene ; pharmacology

BACKGROUND: Since a change in venous capacitance significantly alters venous return and thus affects cardiac output, it is important to know the effects of vasodilators on venous capacitance. The purpose of this study was to examine the effects of sodium nitroprusside and nitroglycerin on venous capacitance during induced hypotension in halothane anesthetized dogs. METHODS: Fourteen mongrel dogs(SNP group: 7, NTG group: 7), weighing 10~15 kg, were anesthetized with N2O 1.5L/min-O2 1.5L/min-halothane 0.5vol%. Each dog received only one drug. In dogs anesthetized with N2O-O2-halothane, mean arterial pressure(MAP) was decreased by 15%(mild hypotension) and 30%(deep hypotension) of control value by sodium nitroprusside(SNP) and nitroglycerin (NTG), respectively. Venous capacitance was assessed before and during induced hypotension by measuring mean circulatory filling pressure(MCFP). MCFP was measured after arresting the circulation by tightening of superior vena cava and inferior vena cava snares simultaneously. RESULTS: As compared with MCFP before induced hypotension, MCFP was significantly decreased by SNP at deep hypotension and NTG at mild hypotension and deep hypotension. As compared with MCFP at mild hypotension, MCFP at deep hypotension was significantly decreased by NTG and SNP, respectively. CONCLUSIONS: These results suggest that NTG has potent venodilating effect at mild and deep induced hypotension, whereas SNP has venodilating effect only at deep induced hypotension.
Animals ; Cardiac Output ; Dogs* ; Halothane* ; Hypotension* ; Nitroglycerin* ; Nitroprusside* ; Pharmacology ; SNARE Proteins ; Sodium* ; Vasodilator Agents ; Vena Cava, Inferior ; Vena Cava, Superior

The purpose of this study was to elucidate the effects of fentanyl and morphine on the ability of epinephrine to induce arrhythmias in halothane-anesthetized dogs. Epinephrine was infused in progressively increasing doses from 0.5 ug/kg/min. Arrhythmogenic dose of epinephrine(ADE), defined as that induces 4 or more premature ventricular contractions within 15 s during 3 min iafusions of epinephrine, was determined before(control) and after pretreatment of either fentanyl(6 ug/kg i.v. plus 6 pg/kg/hr) or morphine(0.2mg/kg i.v. plus 0.2 mg/kg/hr). Blood pressure and heart rate were also measured immediately before(baseline), immediately after infusion of epinephrine. The results were as follows. l) Fentanyl and morphine increased ADE by 37%(2.19+/-0.49 to 3.00+/-0.44 ug/kg/min, p<0.01) and by 43%(2.50+/-0.60 to 3.58+/-0.93 ug/kg/min, p<0.05), respectively. 2) Percent increases in systolic blood pressure at control were similar to those after pretreatment with fentanyl or morphine in both groups, but systolic blood pressures at the time of arrhythmia after pretreatment were lower than those at control in fentanyl(p<0.05) and morphine group(NS). 3) Fentanyl and morphine decreased heart rate by 27%(127+/-8 to 93+/-6 beats/min, p<0.001) and by 13%(118+/-5 to 103+/-5 beats/min, p<0.05), respectively. These results suggest that fentanyl or morphine inhibits epinephrine induced arrhythmias during halothane-oxygen anesthesia. Thus, pretreatment of surgical patients, who were supposed to receive epinephrine during halothane anesthesia, with either fentanyl or morphine might be safe.
Anesthesia ; Anesthetics ; Animals ; Arrhythmias, Cardiac* ; Blood Pressure ; Dogs* ; Epinephrine* ; Fentanyl* ; Halothane* ; Heart ; Heart Rate ; Humans ; Morphine* ; Pharmacology ; Sympathetic Nervous System ; Ventricular Premature Complexes