Negative inotropic action of propofol is enhanced in the acute ischemic myocardium of dogs

Purpose We investigated the effects of propofol on contractility and oxygen balance in acute ischemic myocardium and compared them with those of normal myocardium using a coronary microembolization model in dogs.Methods In open-chest dogs, the left anterior descending coronary artery (LAD) was perfused through an extracorporeal bypass from the carotid artery. Regional myocardial contractility and myocardial oxygen balance were evaluated along with segment shortening (%SS), regional myocardial oxygen consumption (MVO₂), and lactate extraction ratio (LER) of the area perfused by the LAD. Acute ischemia was produced by repeated injection of microspheres into the LAD-perfused area until %SS decreased by 50% of baseline.Results In normal myocardium, intracoronary infusion of propofol at doses of 1.2 and 2.4mg·kg^–1·h^–1 caused slight decreases in %SS to 83% ± 8% and 80% ± 10%, respectively. In ischemic myocardium, propofol caused greater decreases in %SS (59% ± 18% and 35% ± 20%, respectively). The changes in MVO₂ after propofol infusion generally paralleled the changes in %SS, but LER was not changed in either ischemic or normal myocardium.Conclusion Propofol causes a greater decrease in the contractility of acute ischemic myocardium as compared with normal myocardium in which myocardial oxygen imbalance is not involved as a mechanism.     

Risk factors for cognitive dysfunction after coronary artery bypass graft surgery in patients with type 2 diabetes

OBJECTIVES: The mechanisms of postoperative cognitive dysfunction in patients with diabetes after coronary artery bypass grafting are not fully understood. We sought to determine which type 2 diabetes-related factors contributed to postoperative cognitive dysfunction at 7 days and 6 months after coronary artery bypass grafting. METHODS: One hundred eighty patients with type 2 diabetes who were scheduled for elective coronary artery bypass grafting were studied. As a control group, 100 patients without diabetes mellitus matched for age, sex, and educational level were examined. Hemodynamic parameters (arterial and jugular venous blood gas values) were measured during cardiopulmonary bypass. All patients underwent a battery of neurologic and neuropsychologic tests the day before surgery, 7 days after surgery, and 6 months after surgery. RESULTS: Age (odds ratio 1.5, 95% confidence interval 1.3-1.8, P = .03), presence of hypertension (odds ratio 1.8, 95% confidence interval 1.3-2.0, P = .01), jugular venous oxygen saturation less than 50% time (odds ratio 1.5, 95% confidence interval 1.1-2.0, P = .045), presence of ascending aorta atherosclerosis (odds ratio 1.5, 95% confidence interval 1.1-2.6, P = .01), diabetic retinopathy (odds ratio 2.0, 95% confidence interval 1.3-3.0, P = .01), and insulin therapy (odds ratio 2.0, 95% confidence interval 1.3-3.0, P = .05), were associated with cognitive impairment at 7 days. Insulin therapy (odds ratio 2.0, 95% confidence interval 1.3-3.8, P = .01), diabetic retinopathy (odds ratio 1.3, 95% confidence interval 1.2-2.9, P < .01), and hemoglobin A 1c (odds ratio 1.9, 95% confidence interval 1.3-3.1, P = .047) were associated with cognitive impairment at 6 postoperative months. CONCLUSIONS: Insulin therapy, diabetic retinopathy, and hemoglobin A 1c were factors in cognitive impairment at 7 days and 6 months after coronary artery bypass grafting in patients with type 2 diabetes.     

Mechanism of the immunosuppressive effect in vivo of novel immunosuppressive drug β-SQAG9, which inhibits the response of the CD62L T-cell subset

Introduction

We synthesized sulfo-glycolipid, β-SQAG9 (designate □ β-SQAG9 liposome, because it efficiently forms a liposome structure) that possessed immunosuppressive effects such as inhibition of T-cell responses in human allogeneic MLR and skin allograft survival in rats, and bound to CD62L (L-selectin) in vitro. In this study, we further investigated the immunosuppressive mechanism in vivo by β-SQAG9 liposome in a skin-allografted rat model.

Methods

ACI rats (RT1^a) were grafted skin of LEW rats (RT1¹) treated with PBS or β-SQAG9 liposome IV once a day for 7 days. Subsequently, we investigated the population of T cells and CD62L⁺ T-cell subset in the spleen, axillary lymph nodes (ALNs), and peripheral blood of skin-allografted rats by two-color flow cytometry.

Results

Five of 11 (45.5%) rats that were treated with 50 mg/kg β-SQAG9 liposome showed graft survival and another showed moderate rejection in graft. The CD62L⁺ T-cell subset population in ALNs of β-SQAG9 liposome-treated rats decreased in a dose-dependent manner. No significant difference in the T-cell population was observed between the β-SQAG9 and control groups. These data suggest that β-SQAG9 could bind to the CD62L⁺ T-cell subset in vivo as well as in vitro and affect T-cell migration, which might lead to T-cell tolerance in vivo.     

Prevalence and characteristics of different types of homeboundness among community-living older adults

BACKGROUND: Little is known about the epidemiologic features of different types of homeboundness among the elderly. PURPOSE: This cross-sectional study examined prevalence and characteristics of "type 1" and "type 2" homeboundness (see definitions below) among community-living older adults. METHODS: The subjects comprised all residents aged 65 years and over living in Yoita, Niigata Prefecture, and Hatoyama, Saitama Prefecture. Subject data on sociodemographics, and physical, mental and social functioning were collected through in-person interview. Persons were defined as being homebound if he/she went outdoors only once a week or less often. Homeboundness was further classified into "type 1" or "type 2", based on the hierarchical mobility level classification (levels 1 or 2 vs. levels 3, 4, or 5). "Type 1" homebound persons included those who could not get out into the neighborhood without assistance (i.e, levels 3, 4, or 5). "Type 2" included those who were homebound, though they could get out at least into the neighborhood unassisted (i.e., levels 1 or 2). We focused on characteristics of "type 1" and "type 2" homeboundness as compared with those of respective controls, ie., non-homebound persons within the same mobility categories. RESULTS: Out of the eligible subjects (1588 in Yoita, and 1135 in Hatoyama), 1544 and 1002 persons participated in the survey (response rates of 97.2% and 88.3%, respectively). Among the participants, "type 1" and "type 2" homeboundness was found for 4.1% and 5.4%, respectively, in Yoita, and 3.3% and 6.8% in Hatoyama. After adjustment for potential confounders such as age, gender and mobility level, we found a significant regional difference in the prevalence of "type 2" but not of "type 1" (OR of "type 2" for Hatoyama/Yoita 1.44; 95% CI 1.02-2.03). Both types of homeboundness increased with advancing age; "type 1" and "type 2" featured in over 10% of persons aged at least 85 years and 80 years, respectively. Even after controlling for potential confounders, "type 2" showed a higher prevalence with walking disability and incontinence, and reported lower self-rated health, more depressed mood, lower functional capacity and lower social functioning. "Type 1" showed a higher prevalence with fear of falls, but a lower prevalence with basic ADL disability and a high score for Intellectual Activity, indicating reduced self-efficacy. CONCLUSIONS: Prevalence of "type 1" and "type 2" homeboundness among community-living older adults differs depending on the residential area and age of the subjects. A substantial proportion of "type 2" homebound persons are at high risk of functional decline, indicating that "type 2" as well as "type 1" homebound persons need care-preventive programs.     

Prognosis of different types of homeboundness among community-living older adults: two-year prospective study

PURPOSE: This 2-year prospective study was conducted to determine prognosis of two different types of homeboundness among community-living older adults and explore whether those types of homeboundness exert independent effects even after controlling for potential confounders. METHODS: Out of all residents aged 65 years and over who lived in Yoita, Niigata, Japan (n = 1,673), 1,544 persons participated in the baseline survey which was conducted in November, 2000 (response rate, 92.2%). They were followed for the subsequent 2 years in terms of mortality, institutionalization and functional status (mobility, IADL, BADL, and cognition). Persons were defined as being homebound if he/she went outdoors only once a week or less often. Homeboundness was further classified into types 1 or 2, based on the hierarchical mobility level classification (levels 1 or 2 vs. levels 3 or over). Type 1 homebound persons included those who could not get out into the neighborhood without assistance (i.e., levels 3 or over). Type 2 included those who were homebound though they could get out at least into the neighborhood unassisted (i.e., levels 1 or 2). We compared two-year prognosis between the type 2 homebound cases and controls (the non-homebound individuals in levels 1 or 2), or the type 1 homebound and controls (the non-homebound in levels 3 or over). Multiple regression analysis or multiple logistic regression models were used to analyze independent effects of the homebound status on the prognosis, controlling for potential confounders such as age, gender, chronic conditions, functional status, and psychosocial variables at baseline. RESULTS: At baseline there were 1,322 non-homebound in levels 1 or 2 (87.0%), 81 type 2 homebound (5.3%), 39 non-homebound in levels 3 or over (2.6%), and 78 type 1 homebound older persons (5.1%) . As compared to controls, type 2 homebound elderly showed increased risks of functional decline even after controlling for potential confounders. Relative risks of type 2 homeboundness for developing mobility loss, IADL and ADL disability, and cognitive impairment (MMSE < 20) were 3.20(95% CI, 1.60-6.38), 2.85(1.20-6.82), 1.52(0.61-3.75), and 3.05(1.06-8.78) in the partially adjusted model, and 2.49(1.20-5.17), 2.25(0.90-5.63), 1.46(0.54-3.94) and 2.41(0.71-8.17) in the fully adjusted model. Type 1 homebound elderly showed an increased risk for mortality (33.3% vs. 5.1%), but a lower risk for institutionalization (9.0% vs. 25.6%). The independent effect of type 1 was not significant when mortality and institutionalization were combined (relative risk, 2.05[0.54-7.75] in the fully adjusted model). CONCLUSIONS: Type 2 homeboundness is an independent risk factor for functional decline among competent older persons, while the prognosis of older persons with a low functional state is poor, regardless of type 1 homeboundness or not.     

Surgical treatment of thoracic aortic aneurysm in patients with concomitant coronary artery disease

Objective: Surgical treatment of thoracic aortic surgery in patients with coronary artery disease was investigated. Methods: Between 1990 and April 2003, 330 patients underwent elective thoracic aortic surgery. Fifty-six patients who underwent aortic root reconstruction were excluded and 274 patients were examined. Fifty-four (20%) patients showed concomitant coronary artery disease. Ten had undergone coronary revascularization previously; and 3 underwent coronary revascularization [2 coronary artery bypass grafting (CABG), 1 percutaneous transluminal coronary angioplasty (PTCA)] before aortic surgery. Twenty-three patients underwent elective CABG simultaneously and 2 patients had additional coronary artery bypass because of cardiac ischemia during operation. The number of patients who underwent thoracic aortic surgery including Asc Ao+AVR was 2, hemi arch 1, total arch 15, distal arch 5, distal arch+LV aneurysmectomy 1, and thoracoabdominal Ao 1. Two patients underwent coronary revascularization with arterial grafts and the others with SVG grafts. Results: There was one hospital death (4%). In patients without coronary bypass, 2 patients suffered cardiac ischemic events. Conclusion: Our thoracic aortic operations with concomitant CABG using SVG were overall successful. Our current strategies for thoracic aortic surgery in patients with concomitant coronary artery disease include conducting a dipyridamole myocardial perfusion-imaging test first in patients not at risk of coronary artery disease, and if the test is positive, coronary angiography is performed and aggressive coronary revascularization is conducted where possible.     

Comparison of colorimetric and HPLC methods for determination of delta-aminolevulinic acid in urine with reference to dose-response relationship in occupational exposure to lead

Both traditional colorimetry and recently developed HPLC-fluorometry have been in use for determination of delta-aminolevulinic acid in urine (ALA-U), an effect marker of occupational exposure to lead (Pb). The present study was initiated to compare the values by the two methods on an epidemiology basis among workers occupationally exposed to lead (Pb), to estimate quantitatively the colorimetry-associated increment over the values by the HPLC method, to evaluate ALA-U determination in occupational health service for Pb-exposed workers, and to identify a critical Pb-B to induce an elevation in ALA-U. For this purpose, blood and urine samples were collected from three groups of Pb-exposed workers (both men and women in combination, including smokers) and analyzed for Pb in blood (Pb-B; measured in all subjects) and ALA-U (by colorimetry or HPLC), i.e., Group 1 (164 subjects with urinalysis by the two methods), Group 2 (2,923 subjects by colorimetry), and Group 3 (2,540 subjects by HPLC). ALA-U when measured by colorimetry was higher than the values by HPLC, and that the mean difference on a group basis was 1.4 mg/l (in a range of 1.1 to 1.8 mg/l), irrespective of Pb-B levels. It was also found that the increase in ALA-U was small when Pb-B was relatively low (e.g., < or = 40 microg/100 ml), and that the increase on a group basis in response to an increase in Pb-B from 5 to 40 microg/100 ml was as small as < or = 0.6 mg/l. Thus, ALA-U appeared to be not a sensitive marker of Pb effects at low Pb-B levels. ALA-U however increased substantially with a point of inflection at the Pb-B level of about 17-34 microg/100 ml. Thus it was concluded that ALA-U as measured by colorimetry is greater than ALA-U by HPLC by 1.4 mg/l on average irrespective of intensity of Pb-exposure, which may induce bias in evaluation of health effect, and that ALA-U levels will increase when Pb-B is in excess of 17-34 microg/100 ml.     

Allergic airway eosinophilia is suppressed in ovalbumin-sensitized Brown Norway rats fed raffinose and alpha-linked galactooligosaccharide

We recently found that dietary raffinose suppressed allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats. Using this model in the present study, we compared the efficacy of other oligosaccharides with that of raffinose. Brown Norway rats were immunized s.c. with ovalbumin on d 0 and exposed to aerosolized ovalbumin on d 20; broncho-alveolar lavage fluid was obtained on d 21. In Expt. 1, rats were fed a control diet or diets supplemented with different oligosaccharides (50 g/kg diet, raffinose, alpha-linked galactooligosaccharide, fructooligosaccharide, and xylooligosaccharide). The number of eosinophils in the fluid was significantly lower in rats fed raffinose and alpha-linked galactooligosaccharide diets than in those fed the control diet. Dietary fructooligosaccharide and xylooligosaccharide did not affect airway eosinophilia. In Expt. 2, i.p. administration of raffinose and alpha-linked galactooligosaccharide, but not fructooligosaccharide and xylooligosaccharide, suppressed airway eosinophilia in rats fed the control diet. In Expt. 3, suppression of airway eosinophilia by dietary alpha-linked galactooligosaccharide occurred in cecectomized rats administered neomycin. Reduced levels of interleukin (IL)-4 and IL-5 mRNA in lung tissue were associated with the suppression of airway eosinophilia. We propose that indigestible oligosaccharides differ in their suppressive effect on allergic airway eosinophilia in ovalbumin-sensitized Brown Norway rats and that the effect appears not to be mediated by intestinal microflora.