Home and neighbourhood built environment features in family-based treatment for childhood obesity.

BACKGROUND: Family-based behavioural weight loss treatment (FBT) for childhood obesity helps families develop strategies to facilitate healthy choices in their home and other environments (e.g. home neighbourhood). The current study examines how the home food environment, both pre-FBT and post-FBT, and the neighbourhoods in which families live are associated with child weight and weight-related outcomes in FBT. METHODS: Parent-child dyads (n = 181) completed a 16-session FBT programme and completed home environment, anthropometric and child dietary/activity assessments at pre-FBT and post-FBT. Parents reported on availability of food, electronics and physical activity equipment in the home. The neighbourhood food and recreation environments around each dyad's residence was characterized using existing data within a geographic information system. RESULTS: Families successfully made healthy home environment modifications during FBT. Regression models showed reducing RED (e.g. high-energy-dense and low-nutrient-dense) foods and electronics in the home during FBT had positive effects on child weight and weight-related outcomes. No neighbourhood food or recreation environment variables were significantly related to outcomes, although having a larger density of public recreation spaces was associated with increases in physical activity at the trend-level. CONCLUSIONS: Modifying the home environment, specifically reducing RED foods and electronics, may be particularly important for FBT success.

Contributions of total and regional fat mass to risk for cardiovascular disease in older women.

The aim of this study was to determine whether trunk fat mass, measured by dual-energy X-ray absorptiometry (DEXA), is predictive of insulin resistance and dyslipidemia, independently of arm and leg fat mass, in postmenopausal women. Total and regional body composition was measured by DEXA in 166 healthy, postmenopausal women (66 +/- 4 yr). Four primary markers of insulin resistance and dyslipidemia were assessed: 1) area under the curve for the insulin (INS(AUC)) response to an oral glucose tolerance test (OGTT), 2) product of the OGTT glucose and insulin areas (INS(AUC)xGLU(AUC)), 3) serum triglycerides (TG), and 4) high-density lipoprotein (HDL)-cholesterol. Trunk fat mass was the strongest independent predictor of each of the primary dependent variables. In multivariate regression models, trunk fat mass was associated with unfavorable levels of INS(AUC), INS(AUC)xGLU(AUC), TG, and HDL-C, whereas leg fat mass was favorably associated with each of these variables. Thus trunk fat is a strong independent predictor of insulin resistance and dyslipidemia in postmenopausal women, whereas leg fat appears to confer protective effects against metabolic dysfunction.

Short-term oral estrogen replacement therapy does not augment endothelium-independent myocardial perfusion in postmenopausal women.

OBJECTIVES: The purpose of this study was to determine the effect of usual-dose estrogen replacement therapy (ERT) on myocardial perfusion and myocardial perfusion reserve (MPR) (evoked by an endothelium-independent vasodilator) in healthy postmenopausal women. Postmenopausal women have a decreased myocardial perfusion reserve compared with younger women. Estrogen infusions are known to enhance endothelium-dependent vasodilation of the epicardial coronary arteries in postmenopausal women, but whether ERT also enhances endothelium-independent myocardial perfusion and perfusion reserve is unclear. METHODS: In 24 healthy postmenopausal women who were not taking ERT, myocardial perfusion at rest, perfusion during the infusion of adenosine (a primarily endothelium-independent vasodilator), and MPR were determined by positron-emission tomography (PET) and oxygen 15-labeled water. The women were then randomly assigned in a double-blind fashion to receive either 0.625 mg of oral conjugated estrogens (Premarin) or placebo per day for 4 to 6 weeks, after which they underwent a repeat cardiac PET study. RESULTS: There was no statistical difference between those assigned to ERT and those assigned to placebo in the measurement of myocardial perfusion at rest (1.21 +/- 0.31 vs 1.16 +/- 0.18 mL/g/min, respectively) in response to adenosine (2.66 +/- 0.96 vs 3.3 +/- 0.45 mL/g/min) or MPR (2.24 +/- 0.83 vs 2.88 +/- 0.64 mL/g/min) after 4 to 6 weeks of oral ERT. There was also no difference between the groups in any of the myocardial perfusion measurements after correction for the rate-pressure product. CONCLUSIONS: Short-term oral ERT does not affect myocardial perfusion at rest in response to adenosine or MPR in healthy postmenopausal women. Thus potential beneficial effects of ERT on vasomotor function may be limited to enhancement of endothelium-dependent vasodilative mechanisms affecting conduit vessels.

Repeatability of subjective refraction in myopic and keratoconic subjects: results of vector analysis.

This paper evaluates the repeatability of refraction in keratoconus patients and normal myopes, using representations of spherocylindrical power that are theoretically valid. Data consist of test-retest refraction data from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study and similar data from normal myopes. Dioptric powers are transformed to an orthogonal vector representation of dioptric power. The metric of change is the dioptric difference between test and retest. The median difference between test and retest in keratoconus patients is four to six times larger than in normal myopes. Refraction over a rigid contact lens on a keratoconic cornea improves repeatability but remains approximately twice as large as in normal myopes. The methods demonstrated here possess advantages over previous methods and provide a more valid comparison between test and retest and between different subject groups. The repeatability of refraction in keratoconus patients is substantially worse than in normal myopes.

A comparison of two methods of evaluating cornea-to-contact lens base curve fluorescein patterns in keratoconus.

PURPOSE: The purposes of the study were as follows: (1) to compare the apical fitting relationship of habitual contact lens fluorescein patterns in keratoconus as determined by clinician assessment of on-eye patterns to those determined by photograph readers looking at slides of fluorescein patterns and (2) to determine the validity of the techniques used in assessing the apical fitting relationships of rigid corneal contact lenses on keratoconic corneas. METHODS: Central fluorescein patterns of rigid contact lens-wearing keratoconus patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study were graded as "definite touch," "touch," "clearance," or "definite clearance" by certified clinicians. Photographs of these patterns were evaluated independently by certified, masked photograph readers using the same grading scale. RESULTS: Agreement between "re-reads" of the same fluorescein pattern slides by the photograph readers was substantial (weighted kappa = 0.751). Agreement between assessments of habitual fit fluorescein patterns at the baseline vs. the repeat visits was poor for the photograph readers (weighted kappa = 0.254) and moderate for the clinicians (kappa = 0.480). Agreement between clinicians' and photograph readers' assessment of the habitual contact lens fluorescein pattern at the baseline visit was fair (weighted kappa = 0.382). CONCLUSIONS: Repeatability and validity of this technique were fair to excellent. Many factors influence fluorescein pattern interpretation, and improvement of the objective method of fluorescein pattern assessment by photograph readers will require improved methodology that takes these factors into consideration.

The effects of exercise on the quality of life of frail older adults: a preplanned meta-analysis of the FICSIT trials.

The Frailty and Injuries: Cooperative Studies of Intervention Techniques (FICSIT) was a linked series of randomized clinical trials focused on the benefits of exercise in the frail elderly. This article uses covariate-adjusted preplanned meta-analyses of FICSIT data to evaluate the effect of exercise on quality of life (QOL) outcomes (N = 1,733; age = 73.4 +/- 6.1 years). Results indicate that (a) exercise produced a small but significant improvement in the emotional health component of QOL, trended toward an improved social component, and did not effect perceptions of general health; (b) exercise-related joint and muscle stresses did not increase bodily pain; and (c) QOL improvements were independent of changes in physical functioning. We conclude that exercise can improve QOL in the frail elderly but that the magnitude of the improvement is modest in size. The benefits of a meta-analytical approach for documenting efficacy outcomes across different types of interventions are discussed.

Bone mineral density response to estrogen replacement in frail elderly women: a randomized controlled trial.

CONTEXT: Although hormone replacement therapy (HRT) is an established approach for osteoporosis prevention, little is known about the osteoprotective effects of HRT in frail elderly women. OBJECTIVE: To determine whether HRT increases bone mineral density (BMD) in frail elderly women. DESIGN AND SETTING: Randomized, double-blind, placebo-controlled trial conducted in a US university-based research center from September 1995 to August 2000. PARTICIPANTS: Sixty-seven women aged 75 years or older with mild-to-moderate physical frailty. INTERVENTION: Participants were randomly assigned to receive conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days (n = 45), or matching placebo (n = 22), for 9 months. MAIN OUTCOME MEASURES: The primary outcome measure was 9-month change in BMD of the lumbar spine and hip, measured by dual-energy x-ray absorptiometry. Secondary outcomes were changes in markers of bone turnover. RESULTS: Based on intention-to-treat analyses, HRT resulted in significantly larger increases in BMD of the lumbar spine than placebo (mean change, 4.3% vs 0.4%; between-group difference, 3.9%; 95% confidence interval [CI], 3.5%-4.3%) and total hip (mean change, 1.7% vs -0.1%; between-group difference, 1.8%; 95% CI, 1.5%-2.1%). Compared with placebo, HRT resulted in significant decreases in serum bone-specific alkaline phosphatase levels (mean change, -24% vs 6%; between-group difference, -30%; 95% CI, -26% to -33%) and urine N-telopeptide levels (mean change, -48% vs 4%; between-group difference, -52%; 95% CI, -47% to -55%). CONCLUSIONS: In physically frail elderly women, 9 months of HRT significantly increased BMD compared with placebo in clinically important skeletal regions. Further studies are needed to determine whether these osteogenic effects of HRT in elderly women are associated with a reduction in osteoporotic fractures.

Waist circumference vs body mass index for prediction of disease risk in postmenopausal women.

OBJECTIVE: To test the sensitivity of waist circumference (central adiposity) as an index of disease risk in postmenopausal women. DESIGN: Retrospective analysis of postmenopausal women tested at Washington University School of Medicine. SUBJECTS: A total of 323 healthy postmenopausal (66+/-5 y; mean+/-s.d.) women not using any hormone replacement. MEASUREMENTS: Body composition, hyperinsulinemia (insulin area), triglycerides and HDL-cholesterol. RESULTS: Excess waist size had a stronger association with hyperinsulinemia and hypertriglyceridemia than body mass index (BMI; kg/m(2)) in otherwise healthy, postmenopausal women. After adjusting for BMI, a strong relation existed between waist circumference and insulin area, HDL-cholesterol and triglycerides (P<0.01). Conversely, after adjusting for waist circumference, no relation was apparent between BMI and the dependent variables of interest. The strength of the association between waist circumference and disease risk became most apparent when analyses were restricted to normal-weight women (BMI 24--28 kg/m(2)). When BMI was held constant, hyperinsulinemia and triglyceridemia increased dose-dependently with changes in waist size. CONCLUSION: Waist circumference, an easily obtained index of central adiposity, is a more sensitive measure of relative disease risk than is BMI in middle-aged and older women, particularly in normal-weight individuals.

Heart rate-lowering calcium antagonists in hypertensive post-myocardial infarction patients.

OBJECTIVES: To analyse effects of a heart rate-lowering calcium antagonist in hypertensive post-myocardial infarction patients. DESIGN AND METHODS: From three large, randomized, placebo-controlled, secondary prevention trials investigating verapamil or diltiazem (the first and second Danish Verapamil Infarction Trials and the Multicentre Diltiazem Post-Infarction Trial) data from a total of 1,325 hypertensive post-myocardial infarction patients (drugs = 667, placebo = 658) were pooled to assess effect of blinded therapy on mortality and event rates. RESULTS: Treatment with heart rate-lowering calcium antagonists was associated with significant reduction in event rates [21.4 versus 27.4%; risk ratio (RR) = 0.76, confidence interval (CI) = 0.61 -0.95, P= 0.013]. Mortality rates in the treatment group were 15.1 versus 17.5% in the control group (RR = 0.87, CI = 0.66-1.13, P= 0.296). Among the subset of 964 hypertensive patients without pulmonary congestion, there was some reduction in mortality rate (11.3 versus 15.3% in the control group; RR = 0.72, P= 0.066) and significant reduction in event rates (18 versus 24.4% for control group; RR = 0.70, P= 0.011). In patients with pulmonary congestion and hypertension, however, calcium antagonists were associated with a 25% increase in mortality (RR = 1.25, P= 0.339), while event rate RR was 1.00. After an adjustment for significant covariates, RR for mortality in treatment versus control groups was 0.76 (P= 0.159). For event rates, RR was 0.74 (P= 0.057). CONCLUSIONS: Heart rate-lowering calcium antagonists decrease event rates in hypertensive post-myocardial infarction patients, but only in those without pulmonary congestion.

The relationship between parental modeling, eating patterns, and dietary intake among African-American parents.

OBJECTIVE: This article examines the relationship between the frequency with which African-American parents report modeling healthful dietary behaviors for their children and parental dietary intake. DESIGN: Cross-sectional, baseline data from a community-based dietary change study to reduce fat intake and increase fruit and vegetable consumption among African-American parents was analyzed to identify role-modeling behaviors. SUBJECTS/SETTING: Subjects were 456 African-American parents who participated in a dietary change study as part of a national parent education group. Participants completed the Parental Dietary Modeling Scale, an eating patterns questionnaire and a food frequency questionnaire. STATISTICAL ANALYSES PERFORMED: Descriptive statistics and stepwise multiple linear regression analyses were conducted. RESULTS: Parental modeling of healthful dietary behavior was associated with the performance low-fat eating patterns (r = 0.48; P < .001), lower dietary fat intake (r = -0.30; P < .001), and higher consumption of fruits and vegetables (r = 0.18; P < .001). APPLICATIONS: The frequency with which parents model healthful dietary behaviors may be associated with parental dietary intake and may have long-term implications for the development of childhood eating patterns. Dietetics professionals need to carefully assess parents' current dietary modeling behaviors and inform parents about how performance of these general behaviors may affect their child's ultimate nutrition health.

The road to danger: the comparative risks of driving while sleepy.

OBJECTIVES/HYPOTHESIS: A large sector of the population of the United States has sleep deprivation directly leading to excessive daytime sleepiness. The prevalence of excessive daytime sleepiness in this population ranges from 0.3% to 13.3%. The consequences of even 1 to 2 hours of sleep loss nightly may result in decrements in daytime functions resulting in human error, accidents, and catastrophic events. The magnitude of risks in the workplace or on the highways resulting from sleepiness is not fully understood or appreciated by the general population. Hence, to more clearly emphasize the magnitude of these risks, we question whether mild sleep deprivation may have the same effect as alcohol on reaction times and driving performance. STUDY DESIGN: Nonrandomized prospective cohort investigation. METHODS: Sixteen healthy matched adult subjects (50% women) were stratified into two groups, sleep deprived and alcohol challenged. The sleep-deprived group was further subdivided into acute (one night without sleep) and chronic (2 h less sleep nightly for 7 d) sleep deprivation. Each group underwent baseline reaction time testing and then drove on a closed course set up to test performance. Seven days later, the group repeated this sequence after either sleep deprivation or alcohol intake. RESULTS: There were no significant between-group differences (sleep deprivation or alcohol challenged) in the changes before and after intervention for all 11 reaction time test metrics. Moreover, with few exceptions, the magnitude of change was nearly identical in the two groups, despite a mean blood alcohol concentration of 0.089 g/dL in the alcohol-challenged group. On-track driving performances were similar (P =.724) when change scores (hits and errors) between groups were compared (baseline minus final driving trial). CONCLUSION: This comparative model suggests that the potential risks of driving while sleepy are at least as dangerous as the risks of driving illegally under the influence of alcohol.

Effects of hormone replacement therapy on serum lipids in elderly women. a randomized, placebo-controlled trial.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death among older women. In observational studies, the incidence of CHD has been reduced in postmenopausal women who take hormone replacement therapy (HRT). A low serum level of high-density lipoprotein (HDL) cholesterol is one of the risk factors predictive of death from CHD. OBJECTIVE: To determine the effects of HRT on serum lipid and lipoprotein levels in elderly women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University research center. PARTICIPANTS: 59 sedentary women 75 years of age or older. INTERVENTION: Participants were assigned to 9 months of oral therapy with placebo or conjugated estrogens, 0.625 mg/d, plus trimonthly medroxyprogesterone acetate, 5 mg/d for 13 days. MEASUREMENTS: Serum lipid and lipoprotein levels. RESULTS: After 9 months of treatment, women in the HRT group compared with women in the placebo group had decreased low-density lipoprotein cholesterol levels (mean change [+/-SD], -0.47 +/- 0.69 mmol/L [-18.2 +/- 26.5 mg/dL] vs. -0.06 +/- 0.32 mmol/L [-2.2 +/- 12.2 mg/dL], respectively; between-group difference, 0.41 mmol/L [95% CI, 0.09 to 0.74 mmol/L], 16 mg/dL [95% CI, 3.5 to 28.5 mg/dL]; P = 0.01) and increased HDL cholesterol levels (mean change, 0.21 +/- 0.27 mmol/L [8.1 +/- 10.5 mg/dL] vs. 0.06 +/- 0.11 mmol/L [2.4 +/- 4.3 mg/dL], respectively; between-group difference, 0.15 mmol/L [CI, 0.008 to 0.29 mmol/L], 5.7 mg/dL [CI, 0.8 to 10.6 mg/dL]; P = 0.02). The observed changes were independent of age at menopause onset, baseline lipid values, body weight, waist circumference, percentage body fat, and peak aerobic power. CONCLUSIONS: In women 75 years of age or older, HRT improved the lipoprotein profile to the extent observed previously in younger postmenopausal women. Further studies are needed to evaluate whether these effects protect against CHD in this population.

Effects of hormone replacement therapy on cognitive performance in elderly women.

OBJECTIVE: To determine the effects of 9 months of hormone replacement therapy (HRT) on cognitive performance in women aged 75 years and older. METHODS: A 9-month randomized, double-blinded, placebo-controlled parallel trial. Fifty-two elderly postmenopausal women (age range 75-91 years) without known contraindications to HRT or evidence of dementia or depression were enrolled. Participants were randomly assigned in a 1:2 ratio to placebo or conjugated estrogens at 0.625 mg/d plus trimonthly medroxyprogesterone acetate at 5 mg/d for 13 days (HRT). Main outcome measures were change from baseline and rate of change from baseline for the following psychometric tests: Verbal Fluency Test, Weschler Paired Associate Learning and 20 min Delayed Recall, Trailmaking A and B Tests, Cancellation Random Letter and Random Form Tests. RESULTS: At baseline, women in the HRT group reported a younger age of onset of menopause and a higher prevalence of hysterectomy, but otherwise did not differ from women in the placebo group. After 9 months of treatment, there were no significant group differences for any of the cognitive performance measures. The lack of an observed group-by-time difference for all cognitive tests remained after controlling for age of onset of menopause, education, and previous hysterectomy. CONCLUSIONS: Although conclusions are limited by small sample size and the relatively short duration of treatment, results suggest that 9 months of estrogen replacement in combination with trimonthly progestin does not improve cognitive performance in women over 75 years who do not have dementia or depression.

Risk factors for asthma morbidity and mortality in a large metropolitan city.

Morbidity and mortality due to asthma continues to increase despite advances in understanding the pathophysiology and treatment of the disease. We evaluated the potential risk factors for asthma morbidity and mortality in a large metropolitan city (St. Louis, MO) using small area geographic analysis. We found that the risk of hospitalization for children with asthma was 8.4 times greater (95% confidence interval [CI] 7.0-9.9) in lower socioeconomic zip code areas and 5.3 times greater (95% CI 4.7-5.9) in those zip codes with a higher percentage of African Americans. Similarly, the risk of death due to asthma was 6.4 times greater in the lower socioeconomic zip code areas (95% CI3.4-12.1). Lower socioeconomic status and African American race are strong risk factors for hospitalization and mortality from asthma. Public policy and healthcare resources need to be organized and directed more efficiently to this population.

Defining left ventricular segmental and global function by echocardiographic intraventricular contrast flow patterns.

Contrast echocardiography improves left ventricular (LV) endocardial border delineation by enhancement of the blood-tissue interface. In particular, the contrast appearing within the LV chamber exhibits characteristic flow patterns over the cardiac cycle, which may be related to the surrounding myocardial wall motion. To determine the relation between the LV intracavitary contrast flow pattern and surrounding wall motion, we reviewed the contrast-enhanced images of 348 consecutive patients studied at rest. We defined 2 different patterns of intracavitary contrast flow as visualized from apical views: a swift, vertical, and homogeneous flow towards the apex (pattern A), and a distinctly protracted, swirling, and heterogeneous flow (pattern B). Images recorded on videotapes were reviewed and the type of pattern (A or B) was determined within the initial 30 to 45 seconds of contrast appearance in the left ventricle. Contrast flow patterns interpreted by independent reviewer were then compared with the interpretation of the LV segmental and global function in each patient. Results demonstrate that 224 of 245 (91%) patients exhibiting pattern A had normal LV segmental function. Furthermore, all but 1 patient (102 of 103) with pattern B had > or =1 wall motion abnormality (p <0.0001). Contrast flow pattern B was observed irrespective of the location of LV wall motion abnormality. Global LV function was normal in 93% of patients exhibiting pattern A, whereas varying degrees of LV dysfunction were noted in 83% of patients with pattern B (p <0.0001). The presence of mitral regurgitation (p = 0.46), aortic insufficiency (p = 0.066), or mitral inflow Doppler abnormality (p = 0.102) was not significantly associated with either pattern. Thus, during contrast echocardiography, the LV intracavitary contrast flow pattern complements the assessment of global and segmental LV function.

Long-term effects of diltiazem and verapamil on mortality and cardiac events in non-Q-wave acute myocardial infarction without pulmonary congestion: post hoc subset analysis of the multicenter diltiazem postinfarction trial and the second danish verapamil infarction trial studies.

The main objective of this retrospective analysis was to evaluate the long-term effect of the heart rate-lowering calcium antagonists verapamil and diltiazem on the incidence of combined cardiac events and all-cause mortality in patients who had experienced a non-Q-wave acute myocardial infarction (AMI), but who did not also have pulmonary congestion. In addition, factors having an independent association with these 2 outcomes were identified. Of 817 non-Q-wave patients, 81 (9.9%) died during 12 to 52 months of follow-up. The unadjusted mortality rate was 42% lower in patients randomized to calcium antagonist therapy than placebo (7.2% vs 12.4%, p = 0.010). Non-Q-wave patients who died during follow-up were older than patients who survived (62 vs 58 years, p = 0.001). Other factors found to have an independent association with all-cause mortality included diuretic use (RR 2.79), diabetes mellitus (RR 2.86), and New York Heart Association class >I (RR 1.73). The covariate adjusted all-cause mortality risk ratio associated with randomization to calcium antagonist therapy was 0.65 (95% confidence interval [0.40 to 1.05, p = 0.079]). Overall, 153 patients (18.7%) died or had nonfatal reinfarction. The unadjusted combined event rate was 31% lower in patients randomized to calcium antagonist therapy than to placebo (15.2% vs 21.9%, p <0.006). Factors found to have an independent association with cardiac events included age, diabetes (RR 2.82), diuretic use (RR 2.04), and previous AMI (RR 1. 71). In addition, randomization to the calcium antagonist group had a significant independent association with reduced cardiac events (p = 0.031). The covariate adjusted event rate RR associated with randomization to the calcium antagonist group was 0.69 (95% confidence interval [0.49 to 0.97]). In conclusion, the heart rate-lowering calcium antagonists diltiazem and verapamil may play an important role in reducing long-term mortality and reinfarction in non-Q-wave AMI without pulmonary congestion.

Role of tissue factor-mediated coagulation in ischemia/ reperfusion-induced injury of Langendorf-perfused rabbit hearts.

BACKGROUND: Production of oxygen free radicals, and activation of neutrophils and plasma complement contribute to myocardial reperfusion injury, but the role of coagulation has not been assessed. OBJECTIVE: To characterize tissue-factor-mediated generation of thrombin and its association with tissue injury during reperfusion from normothermic ischemia of isolated, Langendorf-perfused rabbit hearts. METHODS: Activation of coagulation was assessed by addition of 12% rabbit plasma and human fibrinogen to Krebs-Henseleit-buffer perfusate with measurement of levels of human fibrinopeptide A (hFPA) in the heart effluent as an index of thrombin-mediated formation of fibrin. RESULTS: Concentrations of hFPA in the effluent were minimal during non-ischemic perfusion (5 +/- 5 ng/ml, n=6) and during 50 min of ischemia (13 +/- 3 ng/ml, n=6), but increased markedly during the first 20 min of reperfusion (to 41 +/- 29 ng/ml, P=0.03 versus before reperfusion). Addition to the perfusate of 10 microg/ml recombinant human tissue-factor-pathway inhibitor, the physiologic inhibitor of tissue-factor-mediated coagulation, abolished increases in the level of hFPA after reperfusion. However, indexes of myocardial injury manifested during reperfusion, including decrease in recovery of left ventricular pressure developed, increase in left ventricular end-diastolic pressure, and increase in activity of creatine kinase in the heart effluent, were not improved by anticoagulation with recombinant human tissue-factor-pathway inhibitor. CONCLUSION: Our results do not support the hypothesis that coagulation plays a major role in ischemia/reperfusion injury of Langendorf-perfused rabbit hearts.

Effects of diminished expression of connexin43 on gap junction number and size in ventricular myocardium.

Gap junction number and size vary widely in cardiac tissues with disparate conduction properties. Little is known about how tissue-specific patterns of intercellular junctions are established and regulated. To elucidate the relationship between gap junction channel protein expression and the structure of gap junctions, we analyzed Cx43 +/- mice, which have a genetic deficiency in expression of the major ventricular gap junction protein, connexin43 (Cx43). Quantitative confocal immunofluorescence microscopy revealed that diminished Cx43 signal in Cx43 +/- mice was due almost entirely to a reduction in the number of individual gap junctions (226 +/- 52 vs. 150 +/- 32 individual gap junctions/field in Cx43 +/+ and +/- ventricles, respectively; P < 0.05). The mean size of an individual gap junction was the same in both groups. Immunofluorescence results were confirmed with electron microscopic morphometry. Thus when connexin expression is diminished, ventricular myocytes become interconnected by a reduced number of large, normally sized gap junctions, rather than a normal number of smaller junctions. Maintenance of large gap junctions may be an adaptive response supporting safe ventricular conduction.