Preferential acetazolamide-induced vasodilation based on vessel size and organ: confirmation of peripheral vasodilation with use of colored microspheres.

When carbonic anhydrase activity decreases, the regional blood flow (rBF) in organs increases as hypercapnia develops. However, the effects of acetazolamide (AZ)-induced vasodilation have not been estimated with respect to vessel size and organs. The aim of this study was to determine the diameter of the capillaries in various organs that respond to inhibition of carbonic anhydrase activity by AZ. White rabbits were anesthetized with urethane and ketamine and infused with AZ. While the systolic blood pressure (SBP), pH, hemoglobin concentration, and base excess did not change, the partial pressure of arterial oxygen (PaO2) increased significantly and the partial pressure of arterial carbon dioxide (PaCO2) decreased significantly with AZ. The rBF was calculated by using 3 different sizes (15, 25, and 50 microm) of colored microspheres (CM). The rBF measured with 15 microm CM in the brain, kidneys, and liver increased in response to AZ, and the rBF in these organs was different with the different sizes of CM. However, the rBF calculated by using the different sizes of CM in the stomach and abdominal muscle did not change after the administration of AZ. The AZ-induced vasodilation occurred in all sizes of vessels in the liver, in the small and medium-sized vessels in kidneys, and in the larger capillaries in the brain.

Gastrotonometry represents dramatic increase in PcO2 after acetazolamide administration.

BACKGROUND: We sought to evaluate the parameters of CO2 transport during the administration of acetazolamide in order to assess the role of carbonic anhydrase in CO2 transport. MATERIALS AND METHODS: The partial pressure of carbon dioxide in tissue (PtCO2), arterial blood (PaCO2) and end-tidal gas (PETCO2) were monitored to study the correlation between PaCO2, PtCO2 and PETCO2 in spontaneously breathing healthy volunteers after the intravenous administration of acetazolamide 6 mg kg-1. RESULTS: At 60 min after the administration of acetazolamide, the PtCO2 peaked at more than 60 mmHg, and although it decreased by 90 min, it then remained stable above the baseline value. The PaCO2 did not change and the PETCO2 decreased significantly. The changes in PtCO2 were greater than those of either PaCO2 or PETCO2. The minute ventilation increased progressively throughout the study. CONCLUSIONS: We concluded that gastrotonometry represents a new method for monitoring the dramatic increase in PtCO2 induced by drugs such as acetazolamide clinically, and that it could be a warning against acetazolamide administration in severe patients without keeping a ventilation and circulation reserve.

Suppressive effect of simvastatin on intramural small coronary arterial lesions in cholesterol-fed rabbits.

The aim of this study was to examine the suppressive effect of simvastatin on intramural coronary arterial lesions in cholesterol-fed rabbits. In one experiment, six groups of rabbits were fed laboratory chow alone or with added 0.1%, 0.2%, 0.3%, 0.5% or 1.0% cholesterol for 16 weeks. In another experiment, four groups of rabbits were fed a 0.5% cholesterol diet and treated with simvastatin at 1, 3, or 5 mg/kg/day or placebo. In each rabbit, the levels of serum total cholesterol (TC) were determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis to the total number of arteries of the same diameter. In the two experiments, there were positive correlations between the lesion induction ratio and integrated TC (r=0.785, P<0.0001 and r=0.763, P<0.0001, respectively). The slopes of the regression lines for integrated TC obtained in the two experiments were similar, but the lesion induction ratio in the simvastatin-treated group was always lower, by about 14%, in comparison with that in the non-simvastatin-treated group. These findings suggest that simvastatin induces lesion reduction not only by reducing the levels of circulating cholesterol but also by directly suppressing the development of lipoidosis.

The antiatherogenic effect of nifedipine on intramural small coronary arterial lesions in cholesterol-fed rabbits.

The objective of this study was to examine the suppressive effect of nifedipine on intramural coronary arterial lesions in cholesterol-fed rabbits. Each rabbit in Groups A (n=6) and B (n=5) was fed a 0.3% cholesterol diet and was orally administered nifedipine (40 mg/day) or placebo. Each rabbit in Groups C (n=5) and D (n=6) was fed a 0.5% cholesterol diet and was orally administered nifedipine (40 mg/day) or placebo. The serum concentrations of total cholesterol (TC) were determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis to the total number of arteries of the same diameter. There were no significant differences between the nifedipine-treated and placebo groups in either the integrated TC or lesion induction ratio in either the 0.3% and 0.5% cholesterol-fed rabbits. This study demonstrates that nifedipine does not suppress atherogenesis in the intramural small coronary arteries of cholesterol-fed rabbits.

Treatment of branch retinal arterial occlusion with sodium ozagrel, a thromboxane A2 synthetase inhibitor.

A 47-year-old woman with branch retinal arterial occlusion treated with sodium ozagrel is described. The patient presented with acute visual field loss in her right eye. Blood tests demonstrated the elevation of beta-thromboglobulin and platelet factor 4. Sodium ozagrel, a thromboxane A2 synthetase inhibitor, 160 mg daily was administered for 14 days. This treatment prevented exacerbation of retinal arterial thrombosis and produced a marked improvement in the visual field loss. Sodium ozagrel may be a useful drug in the treatment of acute retinal arterial occlusion thought to be caused by thrombosis.

[Strategy for therapy of malignant ascites using MTT assay].

Since the prognosis of patients with malignant ascites is generally poor, the establishment of a therapeutic plan should be done as soon as possible. In order to select the most suitable antitumor agent, a drug-sensitivity test was done by MTT assay using fresh autologous tumor cells as targets. Autologous tumor cells were collected from their ascitic fluids. Results obtained here indicate a possible strategy for the treatment of patients with malignant ascites by MTT assay.

[Preventive effect of simvastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on coronary atherosclerosis in cholesterol-fed rabbits].

A study was made on the effect of simvastatin (the generic name of MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on coronary atherosclerosis in cholesterol-fed rabbits with focus on the serum lipids and morphology. Twenty-seven Japanese white rabbits were divided according to dosage of simvastatin into four groups as follows, group P (placebo, 5 rabbits), group MK 1 (simvastatin 1mg/kg, 5 rabbits), group MK 3 (simvastatin 3mg/kg, 6 rabbits) and group MK 5 (simvastatin 5mg/kg, 5 rabbits). They were placed on a 0.5% cholesterol atherogenic diet for 16 weeks and measurements were made of the concentration of serum lipids weekly. After sacrifice, the degree of surface involvement (SI) of aorta stained with Sudan III and the degree of coronary stenosis (CS) of the left circumflex artery were measured using an image-processing system. Serum total cholesterol (TC) level and beta-lipoprotein level decreased dose-dependently in MK groups compared with group P. High density lipoprotein cholesterol level increased in groups MK 3 and MK 5 slightly. Triglyceride level decreased in groups MK 3 and MK 5. The progressions of SI and CS were suppressed in MK groups dose-dependently. Integrated TC, that is, sum of the serum TC values obtained at each week multiplied by 7 corresponded more closely to CS than SI. Intimal thickening constructed from large foam cells originated from macrophages and proliferating smooth muscle cells included lipid droplets in MK groups was almost similar in group P. But it was likely that lipid droplets in each smooth muscle cell in MK groups were less than in group P. In conclusion, the development of coronary atherosclerosis in cholesterol-fed rabbits was suppressed dose-dependently by simvastatin and it was suggested that this preventive effect was due to reducing the integrated TC and local action to vessel walls by simvastatin. (Fukuoka Acta Med.)

Quantitative analysis of antiatherosclerotic effect of nifedipine in cholesterol-fed rabbits.

Reports concerning the effect of slow calcium-channel blockers on experimental atherosclerosis are controversial. We examined the antiatherosclerotic effect of nifedipine (40 mg/day for 16 weeks) on aorta of rabbits on diets containing 0.3%, 0.5%, and 1.0% cholesterol. There were no significant differences in levels of serum lipids with or without nifedipine in the same cholesterol-fed rabbits. The results obtained show that nifedipine suppressed the extent of lipid deposition and surface involvement (S.I.) in aorta in 0.3% cholesterol-fed rabbits, whereas nifedipine only tended to suppress S.I. in 0.5% cholesterol-fed rabbits and had no effect in 1.0% cholesterol-fed rabbits. The log dose-response relationship of S.I. was obtained by plotting the concentration of cholesterol in the feed or the "integrated value" of the total serum cholesterol (TC), i.e., the cumulative sum of the serum TC values obtained at each week. The log dose-response curve was shifted in parallel with the right in nifedipine groups. The Lineweaver-Burk plot constructed from the dose-response curve had the same points crossing the ordinate with or without nifedipine. These results suggested that nifedipine suppressed S.I. in a competitive manner with cholesterol on the specific binding site of lipid deposition. Electron-microscopic findings also demonstrated that fat droplets in smooth muscle cells, extracellular matrix containing collagen, and elastic fibers decreased in nifedipine-treated rabbits.

The discrepancy between chemotaxis and leukotriene B4 production in a patient with chronic neutrophilic leukemia.

Chronic neutrophilic leukemia (CNL) is a rare type of leukemia. We diagnosed a 81-year-old woman as CNL because she showed that sustained leukocytosis dominated by mature neutrophils, hepatosplenomegaly, high neutrophilic alkaline phosphatase (NAP) score, absence of the Ph1 chromosome and no evidence of leukemoid reaction. During the clinical course, she did not manifest hemorrhagic tendency or infection. We also examined neutrophilic function including chemotaxis, chemiluminescence, nitroblue tetrazolium (NBT) dye reduction, which all indicated normal neutrophil function. Using a reversed phase-high pressure liquid chromatography (HPLC), we detected the production of leukotriene B4 (LTB4) in neutrophils. We found that the LTB4 production was decreased in neutrophils whereas they showed normal chemotaxis. This discrepancy has never, to our knowledge, been reported before in case of CNL.