Intramuscular Injection of Sevoflurane Detects Malignant Hyperthermia Predisposition in Susceptible Pigs

Background: The authors hypothesized that intramuscular sevoflurane injection allows diagnostic differentiation between malignant hyperthermia-susceptible (MHS) and -nonsusceptible (MHN) pigs by measurement of intramuscular lactate and carbon dioxide partial pressure (Pco2), and that dantrolene reduces the sevoflurane-induced Pco2 increase.

Methods: With approval of the local animal care committee, microdialysis probes with attached microtubing for sevoflurane injection were placed in the adductor muscles of nine MHS and six MHN pigs, and Pco2 probes with microtubing were positioned in the triceps muscle of eight MHS and six MHN pigs. After equilibration, sevoflurane boluses at different concentrations and a sevoflurane-dantrolene bolus were injected synchronously. Lactate, pyruvate, and glucose as well as Pco2 were measured spectrophotometrically, and the rate of Pco2 increase was calculated.

Results: Intramuscular sevoflurane injection increased local lactate and Pco2 dose dependently, and significantly higher in MHS than in MHN pigs. Measurement of the rate of Pco2 increase allowed a distinct differentiation between single MHS and MHN pigs. No significant increase in Pco2 was found with sevoflurane and dantrolene.     

Safety of the use of Tissucol Duo S in cardiovascular surgery: retrospective analysis of 2149 patients after coronary artery bypass grafting.

OBJECTIVE: Fibrin sealant is widely used in almost all fields of surgery and has proved to be an effective therapeutic tool in cardiothoracic surgery. Nevertheless, there have been concerns about early bypass graft occlusion associated with the use of fibrin glue. This analysis has been performed to assess the risks and benefits of Tissucol Duo S in coronary artery bypass grafting (CABG) surgery. METHODS: Two thousand one hundred forty-nine patients were included in this retrospective study, 879 (40.9%) were intra-operatively treated with Tissucol Duo S fibrin glue, 1270 (59.1%) did not receive fibrin glue (control group). Patient characteristics were documented according to the EuroScore. Intra- and postoperative data were collected. Primary endpoint of this study was the 30-day all-cause mortality rate in the Tissucol Duo S treated group compared to the control group. RESULTS: Mean age was 66.6+/-9.4 years, 76.3% of the patients were male. There was an increased 30-day-mortality rate in the Tissucol Duo S group compared to the control group (8.5 vs 3.5%, p<0.001). In order to determine if and to what extent the apparent fibrin effect might be due to confounding effects from covariates, an adjustment for potential confounding was done. However, multivariable adjustment did not reduce the risk of fibrin glue below an odds ratio of 2.2. CONCLUSION: Although the apparent increase in mortality risk associated with the use of fibrin glue could not be eliminated statistically, we consider Tissucol Duo S fibrin glue a safe and effective therapeutic tool in CABG surgery when it is applied correctly. Due to the retrospective character of this study some detailed information about the indication for the use of fibrin glue and its application is missing which may be important cofactors for mortality. For further clarification a prospective randomized study may be useful.     

Distribution and disposition of trospectomycin sulfate in the in vivo rat, perfused rat liver, and cultured rat hepatocytes

Trospectomycin sulfate is an experimental, aminocyclitol antibiotic. It has been shown in preclinical, chronic safety studies in the dog and rat to elicit a reversible, lysosomal phospholipidosis in liver. The present experiments were conducted to characterize the tissue distribution and disposition of 3H]trospectomycin sulfate in the male rat, perfused rat, perfused rat liver, and cultured rat hepatocytes. Following a 5 mg/kg iv dose to four rats, approximately 70% of the dose was recovered within 24 hr primarily in urine as unchanged drug, and the remainder was eliminated with a terminal phase half-life in blood and tissues of 3 days. Fecal excretion was relatively minor (16% of the dose recovered in feces in 7 days) until later timepoints, when it was the principal pathway of terminal phase elimination. The liver sequestered approximately 10% of the dose and had the highest tissue levels of drug at all times measured. Liver perfusion experiments indicated that trospectomycin accumulated in a hepatic depot compartment as parent drug by a first-order process which was nonsaturable up to a 1 mM concentration of drug. Biliary excretion of unchanged trospectomycin by the perfused liver was slow (approximately 3% of the dose in 2 hr) and occurred by both paracellular and transcellular mechanisms. The hepatic depot compartment appeared to be responsible for transcellular biliary excretion, and thus for the sustained fecal excretion observed in vivo. Subcellular distribution experiments indicated that at least 50% of the drug in the hepatic depot was sequestered in organelles having a broad density range. The existence of a trospectomycin depot compartment was also demonstrated in cultured hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Block copolymers with bipyridine containing segments: Synthesis and self-organization by Cu(I) complexation

The synthesis and properties of segmented ABA triblock and (AB)_n multiblock copolymer systems with 6,6′-disubstituted 2,2′-bipyridine (bpy) building blocks B and poly(oxytetramethylene) soft segments A are described. The access to the disubstituted bipyridines in large scale quantities was achieved by modification of conventional synthetic routes. In the presence of copper(I) ions these polymers formed mononuclear [Cu(I)(bpy)₂] complexes in solution through self-assembly. The complexed copolymers were microphase separated systems in bulk with nano to mesoscopic superstructures consisting of copper-bpy complex aggregates in a polyether matrix. The thermal, mechanical and elastomer properties of the block copolymers varied with composition.     

Monitoring left ventricular dilation in mice with PET.

Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.