PubMed Health⌕ Search

Biomedical subjects

D D Savage

Publications and source records attributed to D D Savage.

At least 55 records · Page 3Linked to original sources

The effects of prenatal alcohol exposure on radial arm maze performance in adult rats.

The hippocampal formation is sensitive to the in utero exposure to ethanol. It is one brain area thought to play an important role in spatial memory. We examined radial arm maze performance in rats exposed to ethanol prenatally. Pregnant rats were placed into the following treatment groups: LC, 17% EDC (ethanol-derived calories), 35% EDC, PF 35% or PF 17%. The LC group was fed lab chow and water ad lib, the 17% EDC and 35% EDC groups were fed a liquid diet containing either 3.3% or 6.7% v/v ethanol, respectively. Pair-fed controls were fed the same volume of an isocaloric diet as was consumed by their respective ethanol-treated groups. At birth, litters were culled to six and cross fostered to untreated surrogate mothers. Testing was initiated at 60 days of age and continued until the test criterion was satisfied. One-half of the rats in the 35% EDC group did not reach criterion. The remainder of the 35% EDC group and the 17% EDC rats attained criterion but required twice as many trials as their respective pair-fed controls. These results suggest that in utero administration of ethanol affects spatial memory capacity in rat, an observation consistent with other deficits seen in hippocampus of rats prenatally exposed to ethanol.

Animals↗

Rose Questionnaire angina among United States black, white, and Mexican-American women and men. Prevalence and correlates from The Second National and Hispanic Health and Nutrition Examination Surveys.

The prevalence of Rose Questionnaire angina and its association with coronary heart disease risk factors and manifestations were investigated in representative samples of the US population. The study populations included 1,135 black and 8,323 white subjects aged 25-74 years examined in the Second National Health and Nutrition Examination Survey, 1976-1980, and 2,775 Mexican-American subjects aged 25-74 years examined in the Hispanic Health and Nutrition Examination Survey, Mexican-American portion, 1982-1983. Age-adjusted prevalence rates of Rose angina were similar among black, white, and Mexican-American women (6.8%, 6.3%, and 5.4%, respectively). An excess in the prevalence of Rose angina was observed in women compared with men for white and Mexican-American persons under age 55 years, but not for those over age 55. Electrocardiographic evidence of myocardial infarction and self-reported heart attack were strongly associated with prevalent Rose angina among white men and women aged 55 years and over, but not among those below age 55. Serum cholesterol, body mass index (weight (kg)/height (m)2), current cigarette smoking, and dyspnea were independently associated with an increased risk of prevalent angina in multivariate logistic models for white women, excluding those with a prior heart attack. Because many younger women with chest pain who may consult physicians are likely to have elevations in cardiovascular risk factors, their self-reported chest pain can be used as an opportunity to intervene and reduce their future risk of cardiovascular disease.

Adult↗

Echocardiographic functions and blood pressure levels in children and young adults from a biracial population: the Bogalusa Heart Study.

M-mode echocardiograms were obtained on 651 healthy subjects, 7-22 years of age, whose diastolic blood pressure levels remained in the same height-, race-, and sex-specific decile during two biannual examinations. Echocardiographic measures of heart size and dynamics were compared across the total blood pressure distribution. Left ventricular stroke volume, cardiac output and ejection fraction, minor axis shortening, velocity of circumferential fiber shortening, and peripheral vascular resistance were correlated with blood pressure levels. There were positive correlations (p less than .001) of cardiac output and stroke volume with both systolic and diastolic blood pressure levels. Left ventricular output and stroke volume were associated with measures of body size, especially height, weight, ponderal index, and body surface area (p less than .001). The left ventricular output and stroke volume increased with age and with systolic blood pressure quintiles in the four race-sex groups. With adjustment for systolic blood pressure and measures of body size, white males had greater cardiac output (1.25 l/minute for ages 18-22 years, p = .01) and stroke volume than black males. Black males had higher peripheral resistance (4.5 mm Hg/(l/minute), p = .01) than whites. These results suggest that different hemodynamic mechanisms operate in the early phase of hypertension in blacks vs. whites in this population.

Adolescent↗

Prenatal ethanol exposure decreases hippocampal mossy fiber zinc in 45-day-old rats.

The long-term consequences of prenatal ethanol exposure on histochemically detectable hippocampal mossy fiber zinc was examined using a recently developed quantitative histofluorescence procedure. Pregnant Sprague-Dawley rats were maintained throughout gestation on one of three dietary regimens: (a) a liquid diet containing either 3.35% ethanol, (b) an isocalorically matched liquid diet pair-fed to the 3.35% ethanol group, or (c) lab chow ad libitum. At 45 days of age, offspring from each of the three diet groups were sacrificed for determination of hippocampal mossy fiber zinc and zinc analysis of selected tissues by atomic absorption spectroscopy. Hippocampal mossy fiber zinc was reduced by 36% in dorsal and 20% in ventral hippocampal formation stratum lucidum of rats exposed to the 3.35% ethanol diet compared to the offspring of the pair-fed control and ad libitum control dams. No significant differences in zinc:TS-Q histofluorescence were observed between the ad libitum and pair-fed control groups. No significant differences were observed among groups in tissue wet weight or tissue zinc concentration in any of the brain or other body regions analyzed. These results indicate a long lasting prenatal ethanol exposure-induced reduction in hippocampal mossy fiber zinc in the absence of changes in any indices of total body zinc nutriture. These results suggest that prenatal exposure to relatively low blood ethanol levels (30-40 mg/dl) has subtle, yet long-lasting effects in the hippocampal formation, a brain region important in the process of memory consolidation.

Animals↗

Effect of calcium channel antagonists on calcium uptake and release by isolated rat cardiac mitochondria.

The effects of calcium channel antagonists on Ca2+ uptake and Na+-induced Ca2+ release were studied in isolated rat cardiac mitochondria. Diltiazem, nitrendipine and nimodipine were more effective inhibitors of Na+-induced Ca2+ release (IC50 = 19-100 microM) than of Ca2+ uptake (IC50 = 0.2-1 mM). Nitrendipine and nimodipine had virtually identical IC50 values for inhibiting Ca2+ uptake, but nitrendipine was 3-4 times more potent than nimodipine at inhibiting Na+-induced Ca2+ release. If these calcium channel antagonists achieve intracellular concentrations in the range of 10(-5)-10(-4) M, our results suggest that calcium channel antagonists would preferentially inhibit mitochondrial calcium release more than mitochondrial calcium uptake.

Animals↗

Electrocardiographic estimate of left ventricular mass versus radiographic cardiac size and the risk of cardiovascular disease mortality in the epidemiologic follow-up study of the First National Health and Nutrition Examination Survey.

The prognostic value of a left ventricular (LV) mass index (g/m2) estimated from an electrocardiographic model and radiographic estimates of the relative heart volume (ml/m2) and cardiothoracic ratio for predicting the risk of cardiovascular disease mortality were investigated using Cox regression analysis to adjust for age, systolic blood pressure and history of heart attack in 1,807 men (1,609 white, 198 black) and 2,143 women (1,884 white, 259 black). The study population (ages 35 to 74 years at baseline) was followed from 5 to 12 years (average 9.5 years) for cardiovascular disease mortality. LV mass index and relative heart volume were independent predictors of cardiovascular disease mortality among white men. All 3 cardiac size estimates were independent predictors for cardiovascular disease mortality among white and black women. When LV mass index was used as a dichotomized variable to indicate the presence or absence of LV hypertrophy, the age-adjusted relative risk of cardiovascular disease mortality was 2.48 (95% confidence interval 1.77 to 3.46) for white men, 3.03 (1.49 to 6.16) for black men, 1.86 (1.21 to 2.87) for white women and 2.05 (0.83 to 5.05) for black women. The corresponding prevalence of LV hypertrophy was 15.4% for white men, 36.6% for black men, 20.1% for white women and 17.4% for black women. It is concluded that the electrocardiographic estimate of LV mass index can identify a substantially larger fraction of persons at increased risk for cardiovascular mortality than conventional electrocardiographic criteria for LV hypertrophy and that LV mass index estimated by electrocardiogram is a valuable supplement to radiographic cardiac size estimates in epidemiologic applications.

Adult↗

Elevation of naloxone-sensitive 3H-dihydromorphine binding in hippocampal formation of genetically epilepsy-prone rats.

3H-Dihydromorphine (DHM) binding sites were measured in the brain of non-epileptic control and GEPR rats using in vitro autoradiographic techniques. The number of naloxone-sensitive 3H-DHM binding sites was increased 38-57% in the pyramidal cell layer of ventral hippocampal CA3 and Ca1 of GEPR-3 and GEPR-9 rats compared to non-epileptic controls. No significant differences in 3H-DHM binding were observed in dorsal hippocampal formation, lateral entorhinal cortex, lateral geniculate or cerebellum. The results suggest that an increase in the number of opioid receptors in ventral hippocampus of GEPR rats may be one factor contributing to the enhanced sensitivity of GEPR-9 rats to the proconvulsant effects of morphine.

Acoustic Stimulation↗

Autoradiographic evidence of muscarinic cholinergic receptors in the corpora cavernosa penis of the rat.

Recent studies have questioned the role of acetylcholine in the physiology of penile erectile tissue. The responsiveness of penile erectile tissue to acetylcholine would depend, in part, on the presence of cholinergic receptors on the smooth muscle. The specific binding of [3H]quinuclidinyl benzilate (QNB) to cholinergic receptors in sections of penile crura of the rat was analyzed by in vitro neurotransmitter autoradiography. Silver grain density measurements indicated that muscarinic cholinergic receptor binding sites are located almost entirely over the corpora cavernosa penis. Virtually no specific [3H]QNB binding was present in the tunica albuginea or adjacent skeletal muscle tissue. Within the erectile tissue, specific binding occurred both over the columns of intrinsic smooth muscle which form the walls of the cavernous spaces and around the more distal branches of the penile arteries. The high concentration of muscarinic cholinergic receptors in the corpora cavernosa penis is consistent with the suggestion that acetylcholine has an important, albeit undefined role in the function of penile erectile tissue.

Animals↗

Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. The Framingham Heart Study.

The prevalence of and risk factors associated with echocardiographically determined left ventricular hypertrophy were examined in 4976 participants in the Framingham Heart Study (age, 17 to 90 years). Left ventricular hypertrophy was detected in 356 men (16%) and 513 women (19%). Prevalence increases dramatically with age (P less than 0.001), with 33% of men and 49% of women age 70 or older affected. A significant association between blood pressure and left ventricular hypertrophy is present and occurs at levels of systolic pressure below 140 mm Hg (age adjusted, P less than 0.001). There is a ninefold (women) to tenfold (men) increase from leanest to most obese group (age adjusted, P less than 0.001). In multivariate analysis, age, blood pressure, obesity, valve disease, and myocardial infarction are independently associated in both sexes. We conclude that left ventricular hypertrophy is a common echocardiographic finding for which several risk factors can be identified. These findings support weight reduction and blood pressure control for prevention or regression of this condition.

Adult↗

Overall risk of left ventricular hypertrophy secondary to systemic hypertension.

Stratification of risk for cardiovascular events is a fundamental aspect of the assessment of hypertensive patients. The assessment of left ventricular (LV) hypertrophy is an important component of such stratification. The low prevalence of LV hypertrophy on the electrocardiogram (less than 3%) in patients with borderline or mild hypertension limits the utility of the electrocardiogram for stratification of risk in such patients. The high sensitivity (roughly 10-fold greater) and specificity of echocardiography for detection of LV hypertrophy and assessment of the severity and the various forms of such hypertrophy have prompted critical evaluation of the risk associated with such LV hypertrophy. Initial information suggesting considerable risk associated with echocardiographically detected increases in LV mass suggests significant clinical and public health importance of this tool. Further detailed cost-benefit analyses are needed to aid in assessing the role of echocardiography in the evaluation of patients with borderline and mild hypertension.

Body Weight↗

Risk of ventricular arrhythmias in left ventricular hypertrophy: the Framingham Heart Study.

The association of ventricular arrhythmias with left ventricular (LV) hypertrophy was examined in 6,218 participants in the Framingham Heart Study. Electrocardiographic (ECG) LV hypertrophy was present in 171 subjects and echocardiographic hypertrophy was detected in 869. Echocardiographic LV hypertrophy was associated with increased risk for each of 6 ventricular arrhythmia grades in men (relative risk up to 8.9, p less than 0.01), and 4 of 6 grades in women (p less than 0.05). Similarly, men with ECG LV hypertrophy were at increased risk for 4 of 6 arrhythmia grades (p less than 0.05). However, owing to low prevalence ECG LV hypertrophy was not associated with arrhythmia in women. After adjustment for age, sex, systolic blood pressure, valvular heart disease, angina pectoris and acute myocardial infarction, the association of echocardiographic but not ECG LV hypertrophy with ventricular arrhythmia remained significant (p less than 0.001). Thus, echocardiographic LV hypertrophy is more prevalent and more sensitive for ventricular arrhythmias than ECG LV hypertrophy.

Adult↗

Echocardiographic criteria for left ventricular hypertrophy: the Framingham Heart Study.

Of 6,148 original cohort and offspring subjects of the Framingham Heart Study who underwent routine evaluation, a healthy group of 347 men (aged 42 +/- 12 years) and 517 women (aged 43 +/- 12 years) was identified to develop echocardiographic criteria for left ventricular (LV) hypertrophy. Healthy subjects were defined as normotensive, receiving no cardiac or antihypertensive medications, nonobese and free of cardiopulmonary disease. Echocardiographic criteria (in accordance with the American Society of Echocardiography convention) for LV hypertrophy, based on mean plus 2 standard deviations for LV mass, LV mass corrected for body surface area and LV mass corrected for height in this healthy sample are, respectively: 294 g, 150 g/m2 and 163 g/m in men and 198 g, 120 g/m2 and 121 g/m in women. Criteria based on LV mass/height result in higher prevalence rates of LV hypertrophy than LV mass/body surface area while still correcting for body size. The prevalence of LV hypertrophy in the entire study population (using LV mass/height criteria) is 16% in men and 19% in women. Until outcome guided criteria for LV hypertrophy are developed, application of sex-specific criteria based on a healthy population distribution of LV mass offer the best approach to echocardiographic diagnosis of LV hypertrophy.

Adult↗

Echocardiographically determined left ventricular structural and functional correlates of complex or frequent ventricular arrhythmias on one-hour ambulatory electrocardiographic monitoring.

The associations between 6 echocardiographic measurements and ventricular arrhythmias on 1-hour ambulatory electrocardiograms were evaluated in 3,348 subjects of the Framingham Heart Study who were free of symptomatic coronary artery disease, congestive heart failure and valvular heart disease and were not receiving diuretic drugs or other blood pressure or cardiac medications. Age-adjusted estimates of association between echocardiographic measurements of left ventricular (LV) structure and function and complex or frequent (Lown grade 2 or greater) ventricular arrhythmia were computed using logistic regression. In this bivariate model only LV internal diameter (systolic and diastolic) and fractional shortening were associated with arrhythmia in both sexes (p less than 0.01). When all variables were entered into a multivariate model, only age and systolic LV internal diameter remained independently associated with arrhythmia (p less than 0.001). Thus, LV chamber size and function are important predictors of risk for ventricular arrhythmia. Systolic LV internal diameter, which reflects both functional and structural information, is the only measurement independently predictive of arrhythmia risk in persons free of apparent heart disease.

Adult↗

Effect of age, sex, and body surface area on echocardiographic left ventricular wall mass in normal subjects.

M-mode echocardiography was used to estimate left ventricular wall mass in 136 older normal subjects (Group I: 78 men and 58 women, ages 20 to 97 years) and 105 younger normal subjects (Group II: 52 male and 53 female subjects, ages 1 day to 23 years). Echocardiographic left ventricular mass (in grams) was estimated from the following formula: left ventricular mass = 1.05 ([ left ventricular internal diastolic dimension + ventricular septal thickness (diastole) + posterior wall thickness (diastole)] - [left ventricular internal diastolic dimension]). In both groups, female subjects had a slightly smaller left ventricular mass than male subjects (mean difference 7.2% in Group I, p less than 0.05, and 3.6% in Group II, p = 0.05) for any given age and body surface area. Left ventricular mass varied linearly with body surface area and increased as a function of age. In group I subjects, echocardiographic left ventricular mass (in grams) could be estimated by the general formula: left ventricular mass = 124 (body surface area) + A +/- C, where A is the age-dependent intercept; +/- C encompasses a 95% prediction interval for normal values, which is assumed to be nearly constant (+/- 58 g); and body surface area is expressed in square meters. In the Group II (younger) subjects, with age not considered, left ventricular mass (in grams) could be estimated from the following formula: left ventricular mass = 115 (body surface area) -11 +/- C, where +/- C = +/- 32% and this 95% prediction interval varies as a percentage of the mean.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Considerations in the use of echocardiography in epidemiology. The Framingham Study.

To quantify potential biases in the use of echocardiography in epidemiologic studies, we assessed the relationship of sex, age, vital capacity, body fatness, and overt cardiovascular disease to prevalence of acceptable echocardiograms in 6148 Framingham men and women aged 17 to 90 years. Echocardiograms adequate to assess left ventricular chamber dimensions and wall thickness, aortic root, and left atrial dimensions as well as mitral and aortic valves were obtained in 4947 (80%) of the 6148 subjects. The prevalence of acceptable echocardiograms ranged from less than 50% for those more than 80 years of age to more than 96% for subjects under 30 years of age. A significant learning curve was apparent, particularly in the older subjects (more than 60 years of age) for whom prevalence of acceptable echocardiograms rose from a minimum of 28% during the first 5 months of studies to a maximum of 74 to 81% during studies 2 years later. The likelihood of unacceptable echocardiograms was slightly greater in men. Obesity (in subjects younger than 60 years of age), lower vital capacity, and overt cardiovascular disease were associated with unacceptable echocardiograms, independent of age. Consideration of these biases should aid in the interpretation and planning of epidemiologic and other studies using echocardiography.

Adult↗