Oxygen delivery and consumption in the perioperative period of coronary artery bypass grafting without blood transfusion

The perioperative changes in relationship between oxygen delivery (D¨_{O 2}) and oxygen consumption (V¨_{O 2}) were examined in forty patients who underwent coronary artery bypass grafting (CABG) without blood transfusion. Hemodilution was performed to maintain hematocrit of 19.2 ± 1.8% during cardiopulmonary bypass (CPB). Hemodynamic and metabolic parameters were measured in four stages; before CPB (stage I), after CPB (stage II), after ICU arrival (stage III), and the following day (stage IV). In each stage, there was a strong positive correlation between V¨_{O 2} and D¨_{O 2}. In stage I, a decrease in D¨_{O 2} was met with low V¨_{O 2}, and there was no imbalance between them (r = 0.67, P 0.01). V¨_{O 2} increased significantly in stage II, and this increased V¨_{O 2} was compensated by an increase in D¨_{O 2} sufficiently to meet tissue oxygen demand (r = 0.59, P 0.01). In stage III and IV, the increases in tissue oxygen requirements were met by increases in oxygen extraction ratio (r = 0.81, P 0.01, r = 0.60, P 0.01, respectively) reflected in lowered mixed venous oxygen tension and saturation. From these results, it is assumed that the adequate relationship between V¨_{O 2} and D¨_{O 2} can be maintained in the perioperative period of CABG without blood transfusion.(Mizushima A, Niimi Y: Oxygen Delivery and consumption in the perioperative period of coronary artery bypass grafting without blood Transfusion. J Anesth 4: 313–318, 1990)     

Deposition of extracellular matrix on silicone intraocular lens implants in rabbits

Purpose: To examine the deposition of extracellullar matrix on silicone intraocular lenses (IOLs) implanted experimentally into rabbit eyes by electron microscopy and to determine the immunolocalization of extracellular matrix components, including collagen types and cellular fibronectin, on these IOLs. Methods: We performed phacoemulsification and aspiration of the crystalline lens and implanted a foldable silicone IOL in the capsular bag of one eye of each of 26 adult albino rabbits under general anesthesia. After 8 weeks the animals were killed and the eyes were enucleated. The silicone IOLs were processed for electron microscopy and for immunohistochemical detection of collagen types I, III, and IV and cellular fibronectin. Results: Electron microscopy revealed deposition of a presumed cell matrix complex on the optic portion of all silicone IOLs, as well as the adhesion of presumed macrophages and foreign-body giant cells. Cellular deposits showed immunoreactivity for cellular fibronectin. Fibrous or membranous deposits exhibited immunoreactivity for cellular fibronectin and collagen types I and III. A few type IV collagen-immunoreactive deposits were also seen. Conclusion: Deposits of extracellular matrix components were observed on silicone IOLs. These deposits may form the scaffolding for the adhesion and proliferation of cells. These matrix components appeared to be the products of cells adhering to the surfaces of IOLs, including lens epithelial cells, macrophages and foreign-body giant cells, indicating that the process of granulation was incomplete.     

Influence of ETR-p1/f1 antisense peptide on endothelin-induced constriction in rat renal arcuate arteries

1. This study set out to examine the endothelin receptor subtypes mediating vasoconstriction in the rat renal arcuate artery. This was done in isolated vessels 120–200 μm in diameter, incubated with a selective agonist and the novel ‘antisense'' peptide to part of the human endothelin_A receptor.
2. Groups of vessels (n=6) were incubated with increasing concentrations of endothelin-1 (ET-1), from 1 to 100 nM, which caused a 65% maximal contraction at the highest dose with an pEC₅₀ of 8.16±0.11 M. By contrast, in six other vessels sarafotoxin 6c over the same dose range gave a minimal contraction (around 5% of maximum).
3. Preincubation of six vessels with the antisense peptide ETR p₁/f1 at 1 μM had no effect on the ET-1 induced vasoconstriction, in terms of displacement of the concentration-response curve or the maximal tension achieved by the agonist. In the six vessels exposed to 4 μM ETR p₁/f1, there was a significant shift of the concentration-response curve and a lower pEC₅₀ at 7.78±0.09 M (P<0.05). At the highest concentrations of ETR p₁/f1, there was a marked suppression of all responses to ET-1, which at the maximal concentrations tested, 0.1 μM, only reached some 10% of the maximal achievable contraction.
4. Increasing ET-1 concentrations up to 2 μM in vessels incubated with 40 μM ETR-p₁/f1 showed that the blockade could be overcome and that the relationship was shifted to the right (P<0.001) by approximately one log unit with a pEC₅₀ of 7.13±0.11 M. A Schild plot of the data indicated the antagonist to be acting competitively at a single population of receptors.
5. At the highest concentrations tested, 40 μM, ETR-p₁/f1 had no effect on noradrenaline-induced contractions, indicating a lack of non-specific actions.
6. Together, these data suggest that at the rat renal arcuate artery the endothelin_A receptor is the predominant functional receptor mediating contraction. Furthermore, this study has shown the potential usefulness of this novel type of ‘antisense'' peptide in blocking receptor activation.

     

Intracellular activation and cytotoxic action of RS-1541 against cultured human tumor cells

RS-1541, an acyl-derivative of rhizoxin (Fig. 1), is a potent antitumor compound. This agent showed cytotoxicity in vitro on some cultured human tumor cells, although it was less potent than rhizoxin. Rhizoxin exhibited antitumor effects by inhibiting the polymerization of tubulin, whereas RS-1541 did not inhibit tubulin polymerization in vitro. However, cell cycle analysis in vivo showed that the two agents had the same mode of action. The cytotoxicity of RS-1541 was enhanced when the initial cell density of the cells was increased. The cytotoxicity was also enhanced when the membrane fraction of St-4 cells, which were the most sensitive to RS-1541 among the cell lines tested, was added to the target cells. When St-4 cells were incubated with [¹⁴C]-RS-1541, significant amounts of [¹⁴C]-rhizoxin were produced within the cells. Further fractionation of the crude membrane showed that the activity that enhanced the cytotoxicity of RS-1541 (RS-1541-enhancing activity) belonged to the mitochondrial-lysosomal fraction, not to the microsomal fraction. Both the enhancing activity and the activity that converting [¹⁴C]-RS-1541 to [¹⁴C]-rhizoxin (RS-1541-converting activity) were inhibited by treatment with chloroquine, an inhibitor of lysosomal function. Cholesterol esterase derived fromCandida cylindracea had RS-1541-enhancingand-converting activities. These data suggest that RS-1541 exerts its cytotoxic action after being converted to rhizoxin within the cells by a lysosomal enzyme such as cholesterol esterase.Abbreviations DMSO Dimethylsulfoxide - PBS(-) Ca²⁺ Mg²⁺-free phosphate-buffered saline - HCO60 hydrogenated castor oil polyethylene glycor ether - DMA dimethylacetamide - RSB reticulocyte standard buffer, consisting of 10mM NaCl, 1.5 mM MgCl₂, and 10 mM TRIS-HCl, (pH 7.4) - TLC thin-layer chromatography - ara-C 1--D-arabinofuranosylcytosine - LDL low-density lipoprotein     

Evaluation of a compressive-type skeletal muscle pump for cardiac assistance

BACKGROUND: Recent investigations have focused on using the latissimus dorsi muscle for cardiac assistance. Although cardiomyoplasty has been applied clinically, other procedures remain experimental, but promising, modes of cardiac assistance. We assessed the latissimus dorsi muscle as an in situ energy source for circulatory assist devices. METHODS: We developed a pneumatic chamber as a compressive-type muscle actuator. The chamber was implanted under the latissimus dorsi muscle and converted contractile power into pneumatic pressure. The effect of chamber position and size and the influence on muscle blood flow were examined. After muscle conditioning, the pump performance of a circulatory assist device driven by the chamber was evaluated. RESULTS: The chamber functioned better when placed in the proximal position of the latissimus dorsi muscle. The size affected the generated pneumatic pressure, and the higher resting pressure of the chamber reduced the muscle blood flow. The maximum stroke work of the circulatory assist device was greater than that of the right ventricle but less than that of the left ventricle. The chamber could drive the circulatory assist device against the systemic range of afterload in which a high preload was available. Long-term adhesion surrounding the chamber reduced the pressure generation capability. CONCLUSIONS: The compressive-type muscle actuator using the latissimus dorsi muscle generated acceptable hemodynamic work for right ventricular bypass or aortic counterpulsation.     

The investigation of age-specific PSA reference range as the cut-off values in the mass screening for prostatic cancer

BACKGROUND: The objective of this study is to determine age-specific PSA reference ranges in Japanese healthy men and investigate the effectiveness of these ranges as the cut-off values in the mas screening for prostatic cancer. METHODS: The study included a total of 5,206 male aged from 55 to 89 years old who wished to submit the mass screening for prostatic cancer in an urban area of Kyoto in 1995-1997, but had no evident prostatic cancer. We measured serum PSA levels by the filter paper method (Delfia PSA kit). RESULTS: We found the increase in serum PSA levels with the advancing age. With the 95th percentile for serum PSA as the upper limit, the age-specific PSA reference ranges were determined to be 2.1 ng/ml for patients aged 55 to 59 years old, 3.2 ng/ml for 60 to 69 years old, 4.4 ng/ml for 70 to 79 years old, 6.5 ng/ml for 80 to 89 years old. If we used these ranges as the cut-off values in the mass screening this time, five cases from 76 to 89 years old of prostatic cancer were overlooked. CONCLUSIONS: We found the increase in serum PSA levels with advancing age. But the positive proof of using this range to a mass screening for prostatic cancer was not certified, because time incidence of prostatic cancer in the examinees was uncertain and there is a possibility of overlooking some cases.     

Roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection

An essential role of murine CD4+ T cells in immune reactivity and skin graft rejection in discordant xenogeneic combinations have been reported. Our study was conducted to further clarify the roles of CD4+ and CD8+ T cells in discordant skin xenograft rejection, by using CD4 and CD8 knockout [C57BL/6 Cr Slc (B6; H-2b) background] mice. When human skins were grafted on CD8 knockout mice or B6 mice, both hosts rejected human skin grafts within 12 days after grafting. By contrast, survival of human skin grafts was significantly prolonged in CD4 knockout mice (mean survival times=19.3+/-(SD) 1.6 days; median 19 days). Fully allogeneic C3H/He Slc (H-2k) skin grafts were rejected within 14 days in CD4 knockout mice, suggesting that non-CD4+ T cells in CD4 knockout mice were immunocompetent for allograft rejection. In spleens of these recipient mice, CD8+ T cells seemed to be activated 10 days after human skin grafting. Immunohistological analysis revealed the infiltration of CD8+ T cells at the site of transplanted human skin on CD4 knockout mice. To further examine the role of CD8+ T cells in CD4 knockout mice, human skin grafting was performed on day 0 followed by administration of anti-CD8 monoclonal antibody on days 0, 5, and 14. The administration of anti-CD8 monoclonal antibodies caused the significant prolongation of human skin graft survival. These results indicate the following two conclusions: (1) CD4+ T cells have an essential role in rejecting discordant human skin xenografts rapidly and (2) however, CD8+ T cells also are capable of rejecting discordant human skin xenografts.     

Use of ultrasound-guided percutaneous needle biopsy in the diagnosis of mediastinal tumors

We herein report the usefulness of ultrasoundguided percutaneous needle biopsy for histological diagnosis in 18 patients with mediastinal tumors. Computed tomography revealed these tumors to be in contact with the chest wall. The preoperative diagnosis was thymoma in 7 patients, germinoma in 5, neurogenic tumor in 3, and other in 3. The most commonly encountered indication for an ultrasound-guided percutaneous needle biopsy was an anterior mediastinal lesion (78%; 14 of 18 patients). In 16 (89%) of the 18 patients, the biopsy diagnosis corresponded to the post-operative diagnosis. No complications were encountered in any of the patients. This new technique of ultrasound-guided percutaneous needle biopsy is both relatively simple and highly accurate and may thus be useful for outpatients. Preoperative ultrasound-guided percutaneous needle biopsy is thus considered to be a safe and reliable method for the histological diagnosis of mediastinal tumors, and a good alternative to traditional biopsy techniques such as mediastinoscopy or thoracotomy.Presented at the 11th Biennial Asian Congress on Thoracic and Cardiovascular Surgery, Kuala Lumpur, Malaysia, November, 21–25, 1993.     

Acute toxicity,percutaneous absorption and effects on hepatic mixed function oxidase activities of 2,4,4′-trichloro-2′-hydroxydiphenyl ether (Irgasan® DP300) and its chlorinated derivatives

Acute toxicity of 2,4,4-trichloro-2-hydroxydiphenyl ether (Irgasan^® DP300) (I) and its three chlorinated derivatives, 2,3,4,4-tetrachloro-2-hydroxydiphenyl ether (II), 2,4,4,5-tetrachloro-2-hydroxydiphenyl ether (III) and 2,3,4,4,5-pentachloro-2-hydroxydiphenyl ether (IV), in mice were examined by intraperitoneal injection. The LD₅₀ values of Irgasan DP300, II, III and IV were 1,090, 710, 650 and 430 mg/kg, respectively.The percutaneous absorptions of these tritiated compounds were also examined by the application on the backs of mice. The radioactivities in most tissues reached to the maximal levels at 12 h or 18 h after dosing, which corresponded to 11–76% of the maximal levels given by the oral administration (Kanetoshi et al. 1988a). These results show the high percutaneous absorbability of Irgasan DP300 and its chlorinated derivatives.The intraperitoneal administrations of III and IV to rats induced hepatic microsomal aminopyrine N-demethylase and aniline 4-hydroxylase activities similarly to phenobarbital. These chlorinated derivatives also increased cytochrome P-450 content, and the activities of aminopyrine N-demethylase and N-methylaniline N-demethylase in hepatic microsomes from mice. The extents of the increases were similar to those by phenobarbital and 3-methylcholanthrene.