Cardiovascular haemodynamic response to repeated mental stress in normotensive subjects at genetic risk of hypertension: evidence of enhanced reactivity, blunted adaptation, and delayed recovery.

To identify unique cardiovascular responses to stressors in a population at genetic risk of hypertension, we studied haemodynamic responses in initial reactivity to, subsequent adaptation to, and final recovery from repeated active mental stress in young, normotensive individuals stratified by hypertension parental history (PH). Two groups (n=21/group) of normotensive white males underwent stress testing. One group (N+PH) had a hypertensive parent, while the other group (N-PH) did not. Cardiovascular response was measured before, during, and after repeated serial-subtraction math. Initial reactivity was measured as the difference between baseline and initial stress response, subsequent adaptation as the difference in response to repeated trials, and final recovery was assessed by the difference between baseline and postbaseline levels. The influence of PH on reactivity, adaptation, and recovery was assessed by repeated measures ANOVA for stroke volume, cardiac output, pre-ejection period, total peripheral resistance, mean successive heartbeat time difference, blood pressure, and heart rate. Multivariate analysis of variance (MANOVA) determined the effect of PH on overall reactivity, adaptation, and recovery. As compared to the N-PH group, initial reactivity was higher in the N+PH group for cardiac index (P<0.05) and pre-ejection period (P<0.05). Subsequent adaptation in the N+PH group was significantly slower for pre-ejection period (P=0.03). Finally, the N+PH group showed delayed recovery in heart rate (P=0.03), diastolic blood pressure (P<0.05), and pre-ejection period (P=0.007). In conclusion, the heightened reactivity, lack of adaptation, and delayed recovery occur in the sympathetic system of normotensive subjects at genetic risk of hypertension, specifically in beta-adrenergic responses (pre-ejection period). The parasympathetic response (mean successive heartbeat time difference) was not different. Increased cardiac output reactivity in the N+PH group (P<0.05) thus precedes any difference in blood pressure reactivity (P<0.99). Delayed recovery of diastolic blood pressure is also found in the N+PH group (P<0.05), which suggests lower baroreceptor sensitivity. Since delayed recovery in heart rate (P=0.03), and diastolic blood pressure (P<0.05) occur in N+PH subjects even before the corresponding changes in reactivity (P>0.10) or adaptation (P>0.07) are seen, these recovery impairments may be among the earliest precursors to the development of essential hypertension in this population. Finally, PH group haemodynamic differences suggest that these traits (reactivity, adaptation, and recovery) may constitute early 'intermediate' phenotypes in the pathogenesis of hypertension.

Involvement of central mu- but not delta- or kappa-opioid receptors in immunomodulation.

Studies completed in both humans and animals have shown that opioids have significant effects on the immune system via pharmacological interactions with the opioid receptor. However, the type of opioid receptor at which morphine binding produces changes in immune status has not been well characterized. To determine the type of opioid receptor involved in opioid-induced immune alterations, the present study assessed the effects of agonists selective for the mu-, delta-, and kappa-opioid receptors. The site of action (i.e., peripheral vs central) at which opioids produce immune changes was investigated by injecting the agonists directly into the left lateral ventricle of the brain. Specifically, Lewis rats received an intracerebroventricular administration of [d-Ala(2),N-Me-Phe(4), Gly-ol(5)]enkephalin (DAMGO), a mu-receptor selective agonist, [D-Pen(2,5)]enkephalin (DPDPE), a delta-opioid receptor agonist, or U69,593, a kappa-receptor agonist. Immune assessments completed 1 h following drug administration showed that the mu-receptor selective agonist DAMGO produced a dose-dependent decrease in natural killer cell activity and T-lymphocyte proliferation to the mitogen concanavalin A (Con A); no immunological changes were found following DPDPE or U69,593 treatment. Calculation of the number of white blood cells per sample showed no differences between rats treated with saline and rats treated with any of the selective agonists. Administration of the opioid antagonist N-methylnaltrexone prior to DAMGO treatment attenuated the DAMGO-induced changes in immune status. Results from the present study indicate that the immunomodulatory effects of opioids can be attributed to interactions with the mu-opioid receptor.

Injuries and injury risk factors among men and women in U.S. Army Combat Medic Advanced individual training.

No previous reports have evaluated injuries or injury risk factors during the advanced individual training (AIT) that follows the Army's initial or basic combat training (BCT). This study examined injuries and injury risk factors among 439 men and 287 women participating in combat medic AIT. A questionnaire addressing demographic and lifestyle characteristics (age, race, tobacco and alcohol use, physical activity, etc.) was administered to all subjects. Stature and body mass were obtained from battalion records. Injuries occurring during both BCT and AIT were transcribed from subject medical records. Results indicated that cumulative injury incidence (subjects with one or more injuries) in BCT was 26% for men and 52% for women (p < 0.01), in consonance with previous investigations. In AIT, injury incidence was 24% for men and 30% for women (p = 0.08). In both BCT and AIT, overuse injuries and lower body injuries accounted for the largest proportions of injuries by diagnosis and anatomical location. Logistic regression revealed that older age (> 25 years), split option (a break in service between BCT and AIT), and higher body mass were independent risk factors for AIT injuries among women. None of the examined variables were independent risk factors for AIT injuries among men.

Forced-air warming decreases vasodilator requirement after coronary artery bypass surgery.

Postoperative hypothermia is common and associated with adverse hemodynamic consequences, including adrenergically mediated systemic vasoconstriction and hypertension. Hypothermia is also a known predictor of dysrhythmias and myocardial ischemia in high-risk patients. We describe a prospective, randomized trial designed to test the hypothesis that forced-air warming (FAW) provides improved hemodynamic variables after coronary artery bypass graft. After institutional review board approval and written informed consent, 149 patients undergoing coronary artery bypass graft were randomized to receive postoperative warming with either FAW (n = 81) or a circulating water mattress (n = 68). Core temperature was measured at the tympanic membrane. A weighted mean skin temperature was calculated. Heart rate, mean arterial blood pressure, central venous pressure, cardiac output, and systemic vascular resistance were monitored for 22 h postoperatively. Mean arterial blood pressure was maintained by protocol between 70 and 80 mm Hg by titration of nitroglycerin and sodium nitroprusside. The two groups had similar demographic characteristics. Tympanic and mean skin temperatures were similar between groups on intensive care unit admission. During postoperative rewarming, tympanic temperature was similar between groups, but mean skin temperature was significantly greater in the FAW group (P < 0.05). Heart rate, mean arterial pressure, central venous pressure, cardiac output, and systemic vascular resistance were similar for the two groups. The percent of patients requiring nitroprusside to achieve the hemodynamic goals was less (P < 0.05) in the FAW group. In conclusion, aggressive cutaneous warming with FAW results in a higher mean skin temperature and a decreased requirement for vasodilator therapy in hypothermic patients after cardiac surgery. This most likely reflects attenuation of the adrenergic response or opening of cutaneous vascular beds as a result of surface warming. IMPLICATIONS Forced-air warming after cardiac surgery decreases the requirement for vasodilator drugs and may be beneficial in maintaining hemodynamic variables within predefined limits.

Role of central mu-opioid receptors in the modulation of nitric oxide production by splenocytes.

Previous studies have shown that administration of morphine results in alterations of splenic macrophage nitric oxide production. The present studies were conducted to determine the subtype of opioid receptor involved in the modulation of macrophage nitric oxide production. Moreover, the present work was directed at determining whether nitric oxide production is regulated through opioid receptors in the central nervous system (CNS) or via opioid receptors found directly on splenocytes. The study shows that intracerebroventricular (i.c.v.) administration of the mu-selective opioid agonist, DAMGO, to rats dose-dependently increases the production of nitric oxide by splenocytes stimulated with toxic shock syndrome toxin (TSST-1). The effect of DAMGO is blocked by prior i.c.v. administration of N-methylnaltrexone. In contrast, i.c.v. administration of the kappa-selective agonist, U69,593, and the delta-selective agonist, DPDPE, have no significant effect on the production of nitric oxide. Furthermore, the in vitro administration of DAMGO, DPDPE, or U69,593 to splenocytes cultures does not significantly alter the production of nitric oxide by splenocytes. In addition, the present work shows that elevation of nitric oxide production by i.c.v. administration of DAMGO produces functional changes in splenic lymphocytes. Collectively, these results indicate that mu-opioid receptors within the CNS are involved in the regulation of splenic nitric oxide production.

Effectiveness of methods used to teach breast self-examination.

The efficacy of breast self-examination (BSE) is limited by the extent to which women can be taught to perform a frequent and proficient examination. We randomized 783 women from a health maintenance organization into group instruction, individual instruction, individual instruction with a reminder system, or minimal intervention designed to simulate an office encounter where BSE was encouraged but not taught. The percentage of lumps 1 cm and smaller detected in silicone breast models, the number of false-positive detections, the search technique, and the self-reported BSE frequency were measured before and four months after intervention. Multiple tests for comparisons of interventions showed that the interventions containing BSE instruction were comparable in increasing true- and false-positive detection of lumps and in improving search technique, but the minimal intervention resulted in lower scores for all three outcomes (P less than .0001). Women in all four intervention groups increased their BSE frequency over the four-month follow-up period, but the greatest improvement in frequency was reported among women receiving reminders.