On hot mice, cold facts, and would-be replication.
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Biomedical subjects
Publications and source records attributed to J Hartung.
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An infusion of 0.1% trimetaphan was administered to eight cats with artificially increased intracranial pressure (ICP) in order to decrease their mean arterial pressure (MAP) from 121 +/- 9.5 (SEM) to 58 +/- 4.6 mm Hg in less than 1 min. All cats developed an increase in intracranial pressure (ICP) (from 16 +/- 1.4 to 23 +/- 3.2 mm Hg) accompanied by a partial rebound in MAP. Eight additional cats received 0.1% trimetaphan to decrease their MAP from 128 +/- 13.4 to 52 +/- 8.1 mm Hg over more than 2 min. Four of these cats followed the same pattern, with ICP increases from 19 +/- 1.1 to 31 +/- 3.9 mm Hg, while in the other four ICP did not change. In nine of the 12 cats with an ICP increase, that increase was initiated before the partial MAP rebound. We conclude that trimetaphan causes clinically significant ICP increases in cats with increased ICP, that partial rebound in MAP frequently exacerbates these increases in ICP, and that rapid induction of hypotension tends to increase the frequency with which trimetaphan increases ICP.
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Arnfred's mouse model was used to test the effect of thiopental during hypoxia (5% O2) and anoxia, with and without simultaneous administration of nitrous oxide. As found by Arnfred and others, thiopental without N2O more than doubled survival time during hypoxia (from 5.2 +/- 0.6 to 13.9 +/- 2.6 min). This effect was completely offset by simultaneous use of N2O (from 13.9 +/- 2.6 to 4.8 +/- 0.7 min). Thiopental without N2O also increased survival time during complete anoxia (from 26 +/- 1 to 59 +/- 1 sec). This effect was diminished by 58% when N2O was added (from 59 +/- 1 to 40 +/- 1 sec). We conclude that nitrous oxide diminishes the effect of barbiturates upon survival time in hypoxic and anoxic mice.
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The effect of vecuronium on intracranial pressure (ICP) was investigated in six cats with normal and increased ICP. Cats were anaesthetized with pentobarbitone 33 mg kg-1 i.p. and acepromazine 0.6 mg kg-1 i.p., the trachea was intubated, and the lungs ventilated with nitrous oxide in oxygen. Mean arterial pressure (MAP), heart rate (HR), twitch response and ICP were recorded continuously. After the effect of vecuronium had been ascertained under the condition of normal ICP, and after full recovery of twitch response, pH-adjusted Ringer's lactate solution was infused to the cisterna magna until an ICP baseline of 26 +/- 2 mm Hg was established, and had stabilized. Vecuronium was administered again to determine its effect under the condition of increased ICP. Complete ablation of twitch response was obtained in 68 +/- 15 s with vecuronium 80 micrograms kg-1, and there was no significant change in ICP, MAP, HR or cerebral perfusion pressure (CPP) under either ICP condition.
Anesthesia was induced in 42 adults with thiopentone 3-7 mg/kg i.v. and maintained with isoflurane at a constant inspired concentration of 1-2%. After 30 min of hemodynamic stabilization with continuous muscle relaxation and an absence of surgical stimulation, each patient was randomly assigned to one of four metocurine dosage groups: I - control (n = 11); II - 0.2 mg/kg (n = 10); III - 0.3 mg/kg (n = 10); and IV - 0.4 mg/kg (n = 11). There were no significant hemodynamic changes in Groups I or II. In Groups III and IV mean arterial pressure (MAP) decreased 32% and 26% respectively, and systemic vascular resistance (SVR) decreased 42% and 36%, respectively (P less than 0.01). In Group IV, an increase of 24% in cardiac output was also significant (P less than 0.05). These results, especially in Group IV patients, stand in marked contrast to the lack of hemodynamic effects produced by metocurine during balanced anesthesia.
The influence of three antibiotics (Penicillin G, Oxtetracycline, Polymyxin B), which show different modes of action against gram-negative bacteria, is tested on the growth of liquid E. coli cultures in a flow microcalorimeter. The antibiotics were added during the logarithmic growth phase of the culture when a heat flux of 40 mu W/ml was approached. A supply vessel and a reaction vessel were used for establishing of the baseline and for performing the test, respectively. When testing Oxytetracycline and Polymyxin B the germ content in the nutrient broth was determined, additionally. Some measurements of the optical density of the nutrient broth were carried out parallel to the microcalorimetric investigation on the effect of Polymyxin B. As was to be expected, Penicillin G shows an influence on E. coli at concentrations of about 50 microgram/ml medium, only. An influence of Oxytetracycline on the heat production can be observed at concentrations between 0.3 and 0.6 microgram/ml. Polymyxin B acts on the power-time-curve at 0.025 microgram/ml. The minimum doses of Oxytetracycline and Polymyxin B found by the microcalorimetric technique are distinctly lower than those found by bacterial count and by measuring the optical density. Microcalorimetric results are achieved within 2 hours after adding the test substance to the bacterial culture. Flow microcalorimetry seems to be a promising tool for testing antibacterial drugs.
Flow microcalorimetry has found increasing use in many rather different sections of biological science in order to investigate metabolic reactions accompanied by heat production during the last few years. The microcalorimetric technique seems to be adequate for investigating liquid microbial cultures, particularly. Flow microcalorimetry is preferentially used for testing the effect of antibiotics and to a smaller extend the effect of other chemical compounds on bacteria and yeasts. The test substances are usually added during the logarithmic growth phase of the microbial culture or to cultures of nongrowing cells in glucose buffer solution. There are less reports on the addition of the test substances during the steady heat plateau of a respiring or grown through culture. The received power-time-curves are compared to "control curves" recorded under identical conditions without test substances. Difficulties and errors can be caused by external influences (e.g. changes in room temperature) or by latent processes within the detector and tubes of the calorimeter (e.g. mixing reactions, ad- and desorption, adhesion to and growth on the walls of the tubes, obstruction by clots of cells). A substantial advantage of the microcalorimetric technique as compared to traditional bioassays is the continuous monitoring of the effect, an additional advantage is its quick and simple performance. The sensitivity is comparable to other bioassays of antibiotics.
Investigations are carried out to characterize the influence of the phenolic compound m-cresol on the heat production of glucose-respiring E. coli cells suspended in glucose phosphate buffer in a flow microcalorimeter according to the method of Perry et al. (5) The results are usually obtained within one hour. When testing m-cresol by this method thermic irritations occurred. A modified test procedure which largely avoids these troubles is described. The height (Q = heat flow) of the power-time-curves is evaluated 30 min and 60 min after the addition of the test substance. These values are compared to the values obtained from control-curves without any test substance. The 60 min-values seem less variable than the 30 min-values. The minimum effective m-cresol concentrations come to 7.50 mmol/l after 30 min and to 9.37 mmol/l after 60 min. The coefficients of variation are distinctly lower than +/- 10% at concentrations of less than 11.25 mmol/l. The coefficients of variation from 3 to 5 tests can extend +/- 20% both for the 30 min-values and the 60 min-values at higher concentrations (e.g. 15 mmol/l). Under the influence of increasing m-cresol concentrations the germ content in the solution and the heat flow decrease in a similar way. The results indicate that the used flow microcalorimetric technique is suitable to check the effect of a test substance on a test culture within only one hour's time. Possibly, the method can be helpful for pretesting disinfectants. The gathering of further experience with this system seems advisable.
Nitrous oxide is often used as anesthesia during ophthalmic surgery that requires intraocular injection of sulfur hexafluoride gas or air. Ventilation with N2O is known to increase intraocular pressure in the presence of intraocular bubbles, but little is known about the effect of N2O on intraocular bubble volume. Accordingly, we have compared the effect of N2O:O2 ventilation (66% N2O, balance O2) with that of air ventilation and oxygen ventilation on intraocular bubbles of SF6 or air. Aspiration of anterior chamber gas after 180 minutes of N2O:O2 ventilation in cats showed an increase in bubble volume of more than threefold when the original intraocular bubble was SF6 and an increase of more than twofold when the original intraocular bubble was air. In contrast, during air ventilation, intraocular SF6 bubble volume increased by 50%, and intraocular air bubble volume increased by only 7.5%. During O2 ventilation, intraocular SF6 bubble volume increased by 35%, and intraocular air bubble volume decreased by 13%. Our results indicate that N2O is contraindicated when gas is injected into the closed eye.
The effect of atracurium on intracranial pressure (ICP) was investigated in six cats with normal and increased ICP. The cats were anaesthetized with intraperitoneal pentobarbitone (33 mg . kg-1), acepromazine (0.6 mg . kg-1) and incremental fentanyl (p.r.n. approximately equal to 20 micrograms . kg-1), intubated, and ventilated with nitrous oxide in oxygen. Mean arterial pressure (MAP), heart rate (HR), twitch response and ICP were continuously recorded. After the effect of atracurium had been ascertained under the condition of normal ICP, and after full recovery of twitch response, pH-adjusted Ringer's lactate solution was infused into the cisterna magna until an ICP baseline of 26 +/- 2 mmHg was established and stabilized. Atracurium was then administered again to determine its effect under the condition of elevated ICP. Complete ablation of twitch response was obtained in 68 +/- 15 sec with 0.4 mg . kg-1 atracurium, and there was no significant change in ICP, MAP, HR or cerebral perfusion pressure (CPP) whether initial ICP was normal or elevated.
The effect of diltiazem-induced hypotension on intracranial pressure (ICP) was studied in dogs with normal and elevated ICP. Eight dogs were anesthetized with intravenous pentobarbital, intubated, and ventilated with N2O:O2. Mean arterial pressure (MAP), heart rate (HR), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), and cardiac out-put (CO) were recorded. A ventriculostomy was performed for measurement of ICP. Baselines were established, and diltiazem was infused to reduce MAP 40 +/- 1% for 10 min. After recording the effects of diltiazem-induced hypotension during normal ICP, ICP was elevated by infusion through a ventriculostomy cannula of pH-adjusted Ringer's lactate, baselines were reestablished, and MAP was again reduced by 40 +/- 1% with diltiazem. When baseline ICP was normal, diltiazem-induced hypotension produced a statistically significant increase in ICP (4.8 +/- 0.6 mm Hg) and a decrease in cerebral perfusion pressure (CPP). When baseline ICP was elevated, a smaller increase in ICP occurred (1.3 +/- 0.5 mm Hg). Although these increases in ICP were not clinically significant, the dose of diltiazem required to lower MAP 40% caused significant alterations in HR, systemic vascular resistance, CO, and PCWP. Serious cardiac rhythm disturbances occurred in five of eight dogs when baseline ICP was normal and in six of eight dogs when baseline ICP was elevated. The relatively long duration of diltiazem's hemodynamic effect and the high incidence of cardiac rhythm disturbances make it an unsuitable drug for inducing deliberate hypotension.
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Fifty-one patients were divided randomly into four groups: halothane in oxygen; fentanyl plus nitrous oxide in oxygen; enflurane in oxygen; or isoflurane in oxygen. Standardized bleeding time was measured using a Simplate II bleeding device before and at least 40 min after the induction of anaesthesia. Arterial pressure was maintained at +/- 20% of control values and temperature was kept at 35-37 degrees C. The bleeding time was prolonged by 33% in the halothane group (P less than 0.01) and by 20% in the nitrous oxide-fentanyl group (n.s.). There was essentially no change in bleeding time in the groups receiving enflurane or isoflurane, although there was considerable variability within each group, which did not seem to be related to differences in sex, age, type of surgery, concentration of agent used or surgical procedure.
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Investigations on the infestation with endoparasites in stomach and gut of feral rabbits from the region of Leipzig. During the hunting periods in the years 1976 till 1979 the viscera of 122 wild rabbits shot in two different biotopes in the area of Leipzig were examined for endoparasites. 63.11% harboured Ctenotaenia ctenoides and Cittotaenia denticulata and 8.19% Cysticercus pisiformis. Graphidium strigosum was demonstrated in 36.88%, Trichostrongylus retortaeformis in 82.78%, Passalurus ambiguus in 13.11% and Trichuris leporis in 7.13% of the rabbits. 71.13% of the rabbits shed oocysts of six different species of intestinal coccidia in their faeces and Eimeria stiedai--infections were diagnosed in the livers of 1.63% of the rabbits. Regional differences were demonstrated in the frequency of Graphidium strigosum-, Passalurus ambiguus- and tapeworm infestations of the wild rabbits examined.
The effect of tetrodotoxin-induced hypotension on intracranial pressure (ICP) was investigated in cats with normal and artificially increased ICP. Cats were anesthetized with intraperitoneal pentobarbital (25-30 mg/kg), intubated, and ventilated with nitrous oxide in oxygen. Mean arterial pressure (MAP), heart rate (HR), and pulmonary arterial pressure (PAP) were continuously recorded. A double 18-gauge needle was inserted into the cisterna magna; ICP was continuously monitored from one needle and the other was used to increase and maintain ICP at 27 +/- 4 mm Hg by infusion of pH-adjusted Ringer's lactate solution. After control measurements were taken, tetrodotoxin (TTX) was given intravenously in each cat when ICP was normal and increased. Injection of 8-16 micrograms TTX (approximately equal to 2-4 micrograms/kg) decreased MAP 40-50% for 8-12 min under both initial ICP conditions. Whether initial ICP was normal or elevated, no significant increase occurred in ICP (0.6 to 1 mm Hg), and cerebral perfusion pressure (CPP) was not jeopardized. When initial ICP was normal, TTX caused a decrease in HR that was statistically but not clinically significant. The change in HR when initial ICP was increased was not statistically or clinically significant. No significant change in PAP was apparent during TTX-hypotension under either initial ICP condition.