Heightened responses to stressors in patients with inflammatory bowel disease

OBJECTIVES: Several studies suggest that stressful situations (stressors) worsen the course of inflammatory bowel disease (IBD), but the mechanism is not known. Based on several lines of evidence, we hypothesized that psychosocial stress activates the brain-gut axis (BGA) and mucosal mast cells (MC), and activated MC produce proinflammatory cytokines. To test this hypothesis, we determined whether stressor-induced activation of BGA is exaggerated in IBD patients. METHODS: Stress was induced in 15 IBD patients who were in remission (inactive IBD) and in seven controls by a widely used stressor, the cold pressor test (CPT), daily for five consecutive days. Induction of stress was confirmed objectively by measurement of stress hormones (serum cortisol and ACTH), and hemodynamic parameters and subjectively by questionnaire. Activation of the BGA by this stressor was assessed by evaluating colonic mucosal MC histology and degranulation, using electron microscopy (EM). The effects of the stressor on the intestinal mucosa were assessed by changes in inflammatory cell histology, epithelial mitochondria (EM), and oxidative tissue injury (assays for protein oxidation). RESULTS: In both study groups, the stressor resulted in (1) increased levels of stress hormones, (2) the expected changes in hemodynamic parameters, (3) activation and degranulation of MC, (4) mitochondrial damage to epithelial cells, and (5) mucosal protein oxidation. These changes were more marked in IBD patients. CONCLUSIONS: The heightened response to the stressors and the greater epithelial damage in IBD patients suggests that stress-induced activation of the BGA and of mucosal MC is important in the initiation and/or flare up of IBD.     

Atherosclerosis-related responses to cigarette smoking in the baboon

Thirty-six young adult male baboons (Papio cynocephalus) were fed an atherogenic diet (40% calories from lard, 1.5 mg cholesterol/kcal) and taught to puff by operant conditioning with water rewards. Eighteen baboons (smokers) were assigned randomly to smoke 43 cigarettes a day, and 18 baboons (shams) were assigned randomly to puff air under conditions equivalent to those of the experimental group. During months 14-19 of smoking, cigarette-smoking baboons had significantly higher carbon monoxide and thiocyanate concentrations in blood and cotinine concentrations in urine. There were no significant differences in serum total cholesterol, VLDL + LDL cholesterol, HDL cholesterol or triglyceride concentrations of smokers and shams. Smoking baboons had significantly higher fasting blood glucose concentrations and lymphocyte counts. Platelet count, platelet aggregation, food and water intake, and body weight were not significantly different in the two groups.     

Regional circulatory responses to 96 hours of hypoxia in conscious sheep

Exposure of adult ewes to normobaric hypoxia (PaO2 40 mm Hg) for 96 h led to increases of VE (+ 54%), while VO2 decreased by 48%. PaCO2 declined progressively to stabilize at 24 (+/- 1.5 SE) mm Hg by 24-48 h. Cardiac output (thermodilution) was elevated temporarily for 24 h (23-34%) but then returned to normoxic levels, while heart rate (28-42%) and pulmonary artery pressure (38-56%) were increased for the duration of hypoxia. Cerebral blood flow (radiolabelled microspheres) increased transiently for 48 h from 65.9 (+/- 4.4) to 100.4 (+/- 9.9) ml X min-1 X 100 g-1 with no change in its regional distribution. Coronary flow was elevated for the duration of hypoxia from 181 (+/- 15) to between 280 (+/- 33) and 350 (+/- 37) ml X min-1 X 100 g-1 with a more pronounced increment in right heart flow, and a decline in the endocardial/epicardial flow ratio. These regional flow increases resulted from a sustained decrease in pancreatic flow from 234 (+/- 11) to 125 (+/- 13) ml X min-1 X 100 g-1 for 96 h, with persisting decreases in splenic flow from 249 (+/- 30) to 100 (+/- 18), and in renal cortical flow from 787 (+/- 70) to 540 (+/- 31) ml X min-1 X 100 g-1, occurring at 48 and 72 h, respectively. Therefore, there is a redistribution of cardiac output during 96 hours of hypoxia with increased flows to heart and brain, and decreased flows to abdominal viscera.     

Hemodynamic responses to atrial natriuretic factor in nephrectomized rabbits: attenuation of the circulatory consequences of acute volume expansion

We investigated the hemodynamic responses to three doses of atrial natriuretic factor [human atrial natriuretic factor-(99-126)] (ANF) in nephrectomized rabbits anesthetized with ketamine and acepromazine. The influence of the different doses of the peptide on the hemodynamic consequences produced by acute volume expansion (0.9% NaCl, 1.4 ml/kg/min for 60 minutes) was also studied. All three dosages of ANF (0.001, 0.01, and 0.2 micrograms/kg/min for 20 minutes) significantly reduced blood pressure. With the lowest dose, the hypotensive effect was associated with reduction in systemic vascular resistance and no significant change in heart rate, stroke volume, central venous pressure, and hematocrit. In contrast, the intermediate and high doses, which resulted in markedly higher plasma levels, caused a significant decrease in heart rate, central venous pressure, and stroke volume; a slight rise in hematocrit; and no change in systemic vascular resistance. Volume expansion produced by saline infusion in an additional group of nephrectomized rabbits increased central venous pressure and decreased hematocrit. When ANF infusion was associated to volume expansion, each dosage of ANF was able to reduce the rise in central venous pressure, while only the higher dosage attenuated the progressive fall in hematocrit caused by volume expansion. Plasma volume, measured at the end of volume expansion was lower in the group treated with the highest dose of ANF than in the control animals (28.2 +/- 9 vs. 35.1 +/- 3 ml/kg, p less than 0.05). We conclude that 1) ANF induces significant hemodynamic effects independently from its renal action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Analysis of circulatory responses to orthostatic stress in the elderly]

An active orthostatic stress test was conducted on 32 elderly patients over 65 years (elderly group) and 17 normal adults, for a comparative evaluation of their blood pressure, heart rates, and plasma catecholamine responses. In addition, 8 patients in the elderly group underwent a study of orthostatic responses with or without sublingual administration of isosorbide dinitrate (ISDN). The results of the orthostatic responses were evaluated by Schellong's method. The elderly group produced a positive reaction in one (3.1%), and a weakly positive reaction in two (6.3%), while the remaining 29 (90.6%) and all of the normal adults showed negative responses. The systolic blood pressure pattern that developed in response to rising among the elderly group was significantly different (p less than 0.001) from that of the normal adult group, but the response pattern seen in the heart rates of the former approximated that of the latter. The plasma norepinephrine concentration 10 minutes after rising increased significantly (p less than 0.001) in both the elderly and normal adult groups. This increase amounted to 1.5-fold in the elderly group and 2-fold in normal subjects, with a less prominent increase shown by the elderly. The norepinephrine levels of the elderly group were significantly higher than those of the normal adults both before and 10 minutes after rising (p less than 0.001 and p less than 0.01, respectively). In the elderly, ISDN caused a significant drop in the systolic blood pressure immediately after rising and a significant increase in the heart rate. Sublingual ISDN administration resulted in a significant increase in the norepinephrine level (p less than 0.05) in association with rising. These findings indicated that the circulatory responses to orthostatic stimuli are inappropriate as clinical data among the elderly and the administration of ISDN exaggerates this shortcoming further.     

Organ-specific responses to circulatory disturbances in heart failure: new insights

Recent studies have provided new insights into the pathophysiology of congestive heart failure. Organ-specific responses to circulatory disturbances may differ via a hypoperfusion state and a venous congestion state. The liver and the kidneys serve as a good example of a differential injury pattern based on the predominant circulatory insult. Cardiorenal syndrome appears to be a kidney-specific response to predominantly right-sided backward heart failure ("congestive state"), rather than forward heart failure. Despite significant progress in our understanding of cardiorenal interactions, there is no specific therapy for the cardiorenal syndrome, which is a marker of the severity of the heart failure state.     

Acute subjective and physiological responses to smoking in adolescents

Aims . To determine the topography of cigarette smoking and the subjective and physiological effects of abstinence and nicotine in adolescents who smoke on a daily versus a non-daily basis.
Design . Repeated measures experiment, non-blinded, involving a single test session.
Setting . Human psychopharmacology laboratory.
Participants . Twenty-one daily and 21 non-daily adolescent cigarette smokers (21 females; 21 males; age 13-18 years) with life-time use greater than 10 cigarettes, responding to radio and print advertisements.
Intervention . Overnight abstinence from cigarettes followed by smoking of a single cigarette furnished by the participant at test.
Measurements . The Fagerstrom Test for Nicotine Dependence, saliva nicotine and cotinine, expired air carbon monoxide (CO), heart rate (HR), self-report scales and smoking topography. Most measurements were performed before and after smoking.
Findings . Saliva nicotine, CO and HR increased, and self-reported intention and desire to smoke decreased, after smoking ( p < 0.001). Fagerstrom scores indicated greater dependence and desire to smoke in daily than in non-daily smokers. HR increased substantially over pre-smoking levels in both groups. Puff topography did not differ between the groups, although collectively these participants appeared to take smaller and more puffs than adult smokers tested under similar conditions.
Conclusion . This study provides initial evidence that adolescent cigarette smokers self-administer physiologically active doses of nicotine very early in their smoking careers. Nicotine dependence in adolescents appears to be a function of the current frequency of cigarette use, and subjective-behavioral consequences of abstinence and smoking are evident even in non-daily smokers.     

Cardiorespiratory responses to sudden release of circulatory occlusion during exercise

Cardiovascular and respiratory parameters were measured during and after release of pressure in thigh cuffs which occluded circulation to the legs of four human subjects exercising on a bicycle ergometer. The subjects exercised at 200 kg/min while thigh cuffs were inflated for 4 min and then released. Responses from 6 to 8 identical experiments were ensemble averaged so the precise timing of delays could be obtained. Five to ten seconds following cuff release, end-tidal CO2 increased, marking arrival of the trapped blood at the lungs. Ten to eighteen seconds after this increase in end-tidal CO2, ventilation, respiratory rate and tidal volume increased. This delay in ventilation must have resulted in an increase in arterial PCO2 and suggests that arterial chemoreceptors mediated the responses, and that no venous chemoreceptors or CO2-flux or disequilibrium receptors in the lung need be postulated.     

Cardiovascular responses to exercise in Nigerian women

Forty-two sedentary Nigerian women participated in the exercise programme aimed at investigating the value of two different training methods in influencing resting systolic and diastolic blood pressures and heart rate. The subjects were randomly divided into three groups. Group I (15 subjects) exercised under Interval Training Protocol (ITP). Group 2 (15 subjects) exercised under Continuous Training Protocol (CTP). The last group (12 subjects) was the control. The training period lasted 12 weeks. Data analysis using analysis of covariance (ANCOVA) revealed significant differences between the pre- and post-training resting systolic and diastolic blood pressure as well as the heart rate measurements. The level of significance for the three cardiovascular variables was 0.001. The interval training group demonstrated superior cardiovascular responses over that of the continuous training group.     

Peripheral circulatory responses to 96 hours of eucapnic hypoxia in conscious sheep

Conscious sheep acclimatizing to hypoxia (PaO2 40 mm Hg, PaCO2 24 mm Hg) respond with increases in cardiac output (Qco) and cerebral blood flow lasting for 24 and 48 h, respectively. Coronary flow increases in a sustained fashion, while there are progressive decreases in renal, splenic and pancreatic flows. In the present study, 5 adult ewes were exposed to similar levels of normobaric hypoxia (PaO2 40 mm Hg) but the PaCO2 was maintained at eucapnic levels (32 mm Hg). VE increased (+210%) while VO2 decreased by 35%. Ventilatory sensitivity to CO2 was unchanged. Qco (thermodilution) was elevated for 96 h (+20%) as stroke volume was maintained at normoxic levels and heart rate increased (+36%). Pulmonary artery pressure increased (+35%) along with plasma catecholamine levels (+116-196%). There were sustained elevations of cerebral flow (radiolabelled microspheres) from 79.1 (+/- 9.2 SEM) to 121.6 ml X min-1 X 100 g-1 (+/- 10.8), coronary flow from 183 (+/- 22.1) to 373 ml X min-1 X 100 g-1 (+/- 46.3), diaphragm flow (+400%) and intercostal muscle flow (+186%) with no apparent redistribution of Qco. Therefore, the cardiac and peripheral circulatory response patterns are altered significantly in eucapnic hypoxia. The rate of O2 delivery to brain and several abdominal viscera is higher.     

Sympathetic neural responses to smoking are age dependent

OBJECTIVE: Smoking is an important risk factor for cardiovascular disease. Sympathetic responses to cigarette smoking may be implicated in the link between smoking and cardiovascular disease. We tested the hypothesis that the sympathetic neural responses to smoking are age dependent. METHODS: We examined the effects of cigarette smoking and sham smoking on muscle sympathetic nerve activity, blood pressure and heart rate in 14 normotensive middle-aged (49 +/- 4 years) and 12 young (29 +/- 4 years) habitual smokers matched for body mass index (25 +/- 2 kg/m2 in both groups). RESULTS: Sham smoking had no significant effect on sympathetic drive, blood pressure or heart rate in either group. Cigarette smoking increased heart rate in both middle-aged subjects and young subjects. In comparison to younger subjects, middle-aged smokers showed similar smoking-related increases in systolic blood pressure (SBP) [10 +/- 3 versus 12 +/- 2 mmHg, respectively, not significant (NS)]. Smoking decreased sympathetic nerve activity by 28 +/- 12% of baseline values (P < 0.01) in young subjects. However, muscle sympathetic nerve activity did not change significantly after smoking in middle-aged subjects (5 +/- 8%, NS), despite the increased blood pressures, which would be expected to inhibit sympathetic activity. By contrast, in young subjects, the heart rate increase (22 +/- 2 bpm) was greater than that seen in middle-aged subjects (13 +/- 2 bpm, P < 0.01). CONCLUSIONS: The autonomic responses to smoking are age dependent. While blood pressure increases are similar in both groups, young subjects respond to smoking by marked increases in heart rate and suppression of central sympathetic outflow. In middle-aged subjects, the heart rate increase is less marked, but sympathetic vasoconstrictor activity is not suppressed.     

Hemodynamic evaluation of a chronically implanted, electrically powered left ventricular assist system: responses to acute circulatory stress

Hemodynamic stress testing was performed in four calves with a chronically implanted left ventricular assist device consisting of a double-valved pump interposed between the left ventricular apex and the descending thoracic aorta. The device was powered either pneumatically (n = 1) or with a transcutaneous energy transmission system (n = 3). Hemodynamic evaluation (cardiac output and right and left ventricular and pulmonary and carotid artery pressures) was carried out at baseline and during all hemodynamically stressed states. Atrial pacing and ventricular pacing to a heart rate of 140 beats/min resulted in no significant change in right or left heart filling pressures or cardiac output. Preload reduction with nitroprusside or transient inferior vena cava balloon occlusion resulted in a marked decrease in left ventricular pressure with preservation of mean arterial pressure. Phenylephrine administration resulted in a marked rise in mean arterial pressure with no change in cardiac output or filling pressure. Induction of ventricular fibrillation resulted in a decrease of mean left ventricular pressure to 11 +/- 8 mm Hg, but mean arterial pressure was maintained at greater than or equal to 50 mm Hg. It is concluded that a multicomponent, implantable, electrically powered assist system is capable of maintaining a normal cardiac output under a wide range of loading conditions and chronotropic states. Although this device is clearly preload dependent, it is capable of maintaining normal systemic pressures during conditions of severe left ventricular dysfunction and circulatory collapse.