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Reflexes from isolated carotid sinuses of intact and vagotomized conscious dogs.

Exposure of the vascularly isolated carotid sinuses of 8 conscious dogs to static pressures between 50 and 240 mmHg caused significantly smaller increases [23 +/- 5(SE) mmHg] than decreases (37 +/- 4 mmHg) in arterial pressure frossure and heart rate and shifted the stimulus-response curve upward. Bilateral cervical vagotomy in conscious dogs caused sustained (3 h) increases in arterial pressure (40 +/- 5 mmHg), significantly larger than after atropinization (7 +/- 2 mmHg). In anesthetized, but not in conscious dogs, high sinus pressure reversed the hypertension caused by vagotomy. After vagotomy, low sinus pressure resulted in arterial pressures greater than 200 -mHg. In conscious dogs the carotid baroreflex can widely vary arterial pressure and heart rate despite buffering by extracarotid baroreceptors with vagal afferents, but cannot fully compensate for the acute loss of the latter. Extracarotid baroreceptors actively participate with carotid baroreceptors in the regulation of arterial pressure and better buffer carotid baroreflex-induced increases than decreases in arterial pressure.

Anesthesia↗

N omega-nitro-L-arginine and pulmonary vascular pressure-flow relationship in conscious dogs.

We investigated the effects of an inhibitor of nitric oxide (NO) synthesis, N omega-nitro-L-arginine (L-NNA), on the pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs. The L-arginine analogue L-NNA (20 mg/min for 60 min iv) had no effect on the baseline pressure-flow relationship. This result indicates that tonic release of endothelium-derived relaxing factor (EDRF), which is thought to be NO or a labile NO-generating molecule, is not responsible for low resting pulmonary vasomotor tone in conscious dogs. In contrast, L-NNA caused a leftward shift in the dose-response relationship to the thromboxane mimetic U-46619, indicating that the endogenous release of EDRF modulates the pulmonary vascular response to this vasoconstrictor. Finally, after preconstriction with U-46619, L-NNA abolished the pulmonary vasodilator response to bradykinin (1-10 micrograms.kg-1.min-1) but had no effect on the pulmonary vasodilator response to sodium nitroprusside (1-10 micrograms.kg-1.min-1). Thus EDRF does not appear to tonically regulate the baseline pulmonary vascular pressure-flow relationship in conscious dogs. However, EDRF does act to attenuate the magnitude of U-46619-induced pulmonary vasoconstriction. Moreover, the pulmonary vasodilator response to bradykinin is entirely mediated by EDRF in conscious dogs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Chronic isolation of carotid sinus baroreceptor region in conscious normotensive and hypertensive rats.

We have developed a chronic technique to isolate the carotid sinus baroreceptor region in the conscious rat model. Our technique, when used in conjunction with other methods, allows for the study of the control of arterial pressure, heart rate, and cardiac output by the carotid sinus baroreceptor reflex in conscious, unrestrained rats. The performance of our technique was evaluated in two strains: normotensive Sprague-Dawley (SD) rats and spontaneously hypertensive rats (SHR). Each rat was instrumented with an aortic flow probe and a catheter placed in the right femoral artery to monitor cardiac output and arterial pressure, respectively. The cervical sympathetic trunk and aortic depressor nerve were ligated and cut bilaterally, leaving vagus nerves intact. The right and left carotid sinuses were isolated using our new technique. We tested the open-loop function of the carotid sinus baroreceptor reflex system in the conscious rat after recovery from the isolation surgery. We found that changes in nonpulsatile carotid sinus pressure caused significant changes in arterial pressure, heart rate, and total peripheral resistance in both rat strains. However, the cardiac output responses differed dramatically between strains. Significant changes were seen in the cardiac output response of SHR, whereas no significant changes were observed in normotensive SD rats. We have found this technique to be a highly reliable tool for the study of the carotid sinus baroreceptor reflex system in the conscious rat.

Animals↗

Pancreatic islet blood flow in conscious rats during hyperglycemia and hypoglycemia.

Anesthesia affects general hemodynamics and regulation of organ perfusion. We used colored microspheres to measure pancreatic islet blood flow in conscious rats at two time points, during either hyperglycemia or hypoglycemia. This method, using black and green microspheres, was validated by comparison with previous microsphere experiments and by lack of effect of a nonmetabolizable glucose analog, 3-O-methylglucose, on islet perfusion. Basal and glucose-stimulated islet blood flow levels were similar in pentobarbital sodium-anesthetized and conscious rats. However, the basal distribution of pancreatic blood flow was altered by anesthesia (fractional islet blood flow 5.8 +/- 0.4% in conscious rats, 7.9 +/- 0.8% in pentobarbital-anesthetized rats, P < 0.05). Insulin-induced hypoglycemia significantly increased whole pancreatic blood flow in conscious rats, whereas islet blood flow remained unchanged and fractional islet blood flow was decreased (5.8 +/- 0.5% in the basal state, 4.2 +/- 0.4% during hypoglycemia, P < 0.001). Methylatropine pretreatment significantly increased islet blood flow during hypoglycemia by 181%. This result suggests that prevention of hypoglycemia-induced increase in islet perfusion may be mediated, at least in part, by a cholinergic, vagal muscarinic mechanism.

3-O-Methylglucose↗

Pulmonary vascular alpha 1-adrenoreceptor activity in conscious dogs after left lung autotransplantation.

We investigated the extent to which sympathetic alpha 1-adrenoreceptor activation is involved in chronic pulmonary vascular regulation in conscious dogs after left lung autotransplantation (LLA). Continuous left pulmonary vascular pressure-flow plots were generated in conscious dogs 3-4 wk post-LLA and in identically instrumented conscious dogs not subjected to LLA (sham-operated controls). LLA resulted in a marked upward shift in the baseline left pulmonary vascular pressure-flow relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The sympathetic alpha 1-adrenoreceptor antagonist prazosin partially reversed (P < 0.01) the LLA-induced increase in pulmonary vascular resistance. Circulating concentrations of norepinephrine and epinephrine at 2 and 4 wk post-LLA were not significantly different from values measured in control dogs. However, the dose-response relationship to the exogenous administration of the sympathetic alpha 1-adrenoreceptor agonist phenylephrine was shifted (P < 0.05) to the left post-LLA compared with control, which indicates an increase in pulmonary vascular reactivity to alpha 1-adrenoreceptor activation. This effect was not due to a generalized increase in pulmonary vascular reactivity to vasoconstrictor stimuli because the dose-response relationship to the thromboxane analogue U-46619 was not significantly altered post-LLA compared with control. Thus LLA results in a chronic increase in pulmonary vascular resistance in conscious dogs. A component of the increase in pulmonary vascular resistance resulting from LLA is mediated by an enhanced reactivity to sympathetic alpha 1-adrenoreceptor activation.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Discharge pattern of renal sympathetic nerve activity in the conscious rat: spectral analysis of integrated activity.

We investigated the periodic characteristics of bursting discharge in renal sympathetic nerve activity (RSNA) in conscious rats. Employing a discrete fast Fourier transform algorithm, a power spectrum analysis was used to quantify periodicities present in rectified and integrated RSNA whose signal-to-noise ratio in the recordings was greater than six. In conscious rats with intact baroreceptors, RSNA was characterized by four frequency components occurring at about 0.5, 1.5, 6, and 12 Hz, which corresponded to the low-frequency fluctuation of heart rate, respiration, and frequency of heart beat, and its harmonics, respectively. After intravenous infusion of sodium nitroprusside (SNP) to elicit reflex increases in RSNA and heart rate, the power for the component at 6 Hz followed the changes in heart beat frequency and was significantly increased, while those for the three other components were attenuated or experienced no change. In sino-aortic denervated (SAD) conscious rats, all four components were abolished, and the power spectrum was well fitted by a flat or Lorentzian curve, suggesting an almost random pattern. Only a respiratory-related component, which suggested common central modulation, appeared sporadically for short periods but was absent for the most part. Therefore most of this component together with the low-frequency component was also likely due to the baroreceptor-dependent peripheral modulation. The activity was sorted in 15 subgroups on the basis of spike amplitudes in the RSNA. Each subgroup showed frequency characteristics similar to the whole nerve activity. These results suggest that all periodicity in the RSNA of conscious rats with intact baroreceptors is caused by the baroreceptor input.

Action Potentials↗

Lifestyle determinants and mortality in German vegetarians and health-conscious persons: results of a 21-year follow-up.

BACKGROUND: The long-term observation of vegetarians in affluent countries can provide insight into the relative effects of a vegetarian diet and lifestyle factors on mortality. METHODS: A cohort study of vegetarians and health-conscious persons in Germany was followed-up prospectively for 21 years, including 1,225 vegetarians and 679 health-conscious nonvegetarians. Standardized mortality ratios compared with the German general population were calculated for all causes and specific causes. Within the cohort, Poisson regression modeling was used to investigate the joint effects of several risk factors on overall and cause-specific mortality. RESULTS: Standardized mortality ratios for all-cause mortality was significantly below 100: 59 [95% confidence interval (95% CI), 54-64], predominantly due to a deficit of deaths from circulatory diseases. Within the cohort, vegetarian compared with nonvegetarian diet had no effect on overall mortality [rate ratio (RR), 1.10; 95% CI, 0.89-1.36], whereas moderate and high physical activity significantly reduced risk of death (RR, 0.62, 0.64), adjusted for age, sex, smoking, alcohol intake, body mass index, and educational level. Vegetarian diet was however associated with a reduced RR of 0.70 (95% CI, 0.41-1.18) for ischemic heart disease, which could partly be related to avoidance of meat. CONCLUSIONS: Both vegetarians and nonvegetarian health-conscious persons in this study have reduced mortality compared with the general population. Within the study, low prevalence of smoking and moderate or high level of physical activity but not strictly vegetarian diet was associated with reduced overall mortality. The nonsignificant reduction in mortality from ischemic heart diseases in vegetarians compared with health-conscious persons could be explained in part by avoidance of meat intake.

Adult↗

Effects of selective and nonselective alpha-1-adrenoceptor antagonists on intraurethral and arterial pressures in intact conscious dogs.

In this study, we used a novel conscious dog model to evaluate the uroselectivity of selected alpha 1-antagonists either approved for human use or in clinical development for the treatment of symptomatic benign prostatic hyperplasia (BPH) and compared those results to their in vitro binding and functional affinities at alpha 1A, alpha 1B and alpha 1D receptor subtypes. Conscious dogs were instrumented acutely with a balloon catheter for the measurement of changes in prostatic intraurethral pressure (IUP) and chronically with implantable telemetry devices for the measurement of arterial pressure. The pressor effects of the alpha 1-agonist phenylephrine (PE) on IUP and mean arterial pressure (MAP) were compared before and at various time points after oral doses of either terazosin, doxazosin, tamsulosin or Rec 15/2739 (SB 216469). At submaximal doses, terazosin and doxazosin blocked PE-induced increases in MAP to a greater extent than increases in IUP. Tamsulosin blocked both parameters equally at the lowest and highest doses; however, at the intermediate dose, IUP was blocked more than MAP. Rec 15/2739 at each dose always blocked IUP to a greater extent than MAP. While the in vivo uroselectivity of these agents was predicted by radioligand binding and in vitro functional selectivity for the alpha 1A subtype over alpha 1B and alpha 1D subtypes, results from conscious dog experiments indicate that estimates of in vivo uroselectivity also depend upon dose and the time after administration. Our conscious canine model provides the basis for frequent and repeated evaluation of uroselectivity parameters over many hours, thus providing a pharmacological profile of compound effects perhaps more relevant to clinical practice.

Adrenergic alpha-Antagonists↗

Cardiovascular effects of anandamide in anesthetized and conscious normotensive and hypertensive rats.

We previously showed that in anesthetized rats anandamide elicits bradycardia and a triphasic blood pressure response: transient hypotension secondary to a vagally mediated bradycardia, followed by a brief pressor and prolonged depressor response, the latter two effects being similar to those of delta 9-tetrahydrocannabinol (THC). The prolonged depressor but not the pressor response was reduced after alpha-adrenergic receptor blockade or cervical spinal cord transection and was inhibited by the cannabinoid type 1 (CB1) receptor antagonist SR141716A, suggesting CB1 receptor-mediated sympathoinhibition as the underlying mechanism. Here we examined the relationship between sympathetic tone and the cardiovascular effects of anandamide by testing these effects in both conscious and anesthetized, normotensive and spontaneously hypertensive rats. In urethane-anesthetized normotensive rats, SR141716A inhibited the prolonged depressor and bradycardic effects of anandamide and THC with similar potency, whereas it did not affect the pressor response to either agent. Anadamide caused similar hypotension in spontaneously breathing and in paralyzed, mechanically ventilated rats, suggesting that the hypotension is not secondary to respiratory effects. In conscious normotensive rats, anandamide elicited transient vagal activation and a brief pressor response, but the prolonged hypotensive component was absent. SR141716A potentiated and prolonged the brief pressor response to anandamide, suggesting that the depressor response may have been masked by an increased pressor response. All three phases of the anadamide response were present in both anesthetized and conscious spontaneously hypertensive rats, and the hypotensive component, inhibited by SR141716A in both, was more prolonged in the absence (> 50 minutes) than the presence (10 to 15 minutes) of anesthesia. We conclude that anandamide causes a non-CB1 receptor-mediated pressor and a CB1 receptor-mediated prolonged depressor response. The depressor response can be elicited in both conscious and anesthetized animals, but its magnitude depends on preexisting sympathetic tone.

Anesthesia↗

Quantitative assessment of the extent of myocardial infarction in the conscious dog by means of analysis of serial changes in serum creatine phosphokinase activity.

This study was designed to develop a method for quantitative assessment of infarct size in the conscious animal based on serial changes of serum creatine phosphokinase (CPK) activity. From 11 experiments in which myocardial CPK was injected intravenously in conscious dogs, the average CPK distribution space and average CPK fractional disappearance rate from serum were found to be 11.4% of body weight and 0.48% min respectively. In other experiments, myocardial infarction was produced in 22 conscious dogs by constriction of a left coronary artery snare and serum CPK activity was determined at frequent intervals for 24 hr. Since myocardial CPK depletion reflects infarct size, infarct size was determined directly by analysis of myocardial CPK content in the same animals 24 hr after coronary artery occlusion. CPK released from the infarct was determined from observed changes in serum CPK activity analyzed according to a model taking into account the fraction of CPK released from an infarct and the rates of appearance and disappearance of CPK activity from serum. Infarct size was calculated on the basis of observed changes in serum CPK and compared to infarct size determined directly by analysis of myocardial CPK depletion. Agreement was close and results from all experiments fit the equation: [infarct size (g) determined from serum CPK] = 1.13 x [infarct size (g) determined from myocardial CPK] - 1.3, r = 0.96, n = 22. The method described is useful for accurate assessment of infarct size in the conscious animal and for detection of modification of infarct size produced by pharmacologic interventions.

Animals↗

Conscious sedation of pediatric oncology patients for painful procedures: development and implementation of a clinical practice protocol.

Pain during treatment procedures is often identified as the most distressing aspect of the entire cancer experience for a child with cancer. The use of conscious sedation may reduce this procedure-related pain and distress. A clinical practice protocol is necessary to maximize the efficacy and safety of conscious sedation use. In this article, the processes of developing and implementing a conscious sedation protocol for pediatric oncology patients undergoing painful procedures are presented. The protocol itself is included. A review of the literature on conscious sedation is presented, and implications for pediatric oncology nursing practice are discussed.

Adolescent↗

Cost-consciousness among Swiss doctors: a cross-sectional survey.

BACKGROUND: Knowing what influences physicians attitudes toward health care costs is an important matter, because most health care expenditures are the results of doctors' decisions. Many decisions regarding medical tests and treatments are influenced by factors other than the expected benefit to the patient, including the doctor's demographic characteristics and concerns about cost and income. METHODS: Doctors (n = 1184) in Geneva, Switzerland, answered questions about their cost-consciousness, practice patterns (medical specialty, public.vs. private sector, number of patients per week, time spent with a new patient), work satisfaction, and stress from uncertainty. General linear models were used to identify independent risk factors of higher cost-consciousness. RESULTS: Most doctors agreed that trying to contain costs was their responsibility ("agree" or "totally agree": 90%) and that they should take a more prominent role in limiting the use of unnecessary tests (92%); most disagreed that doctors are too busy to worry about costs (69%) and that the cost of health care is only important if the patient has to pay for it out-of-pocket (88%). In multivariate analyses, cost-consciousness was higher among doctors in the public sector, those who saw fewer patients per week, who were most tolerant of uncertainty, and who were most satisfied with their work. CONCLUSION: Thus even in a setting with very high health care expenditures, doctors' stated cost-consciousness appeared to be generally high, even though it was not uniformly distributed among them.

Adult↗

Myocardial performance in conscious streptozotocin diabetic rats.

BACKGROUND: In spite of a large amount of studies in anesthetized animals, isolated hearts, and in vitro cardiomyocytes, to our knowledge, myocardial function was never studied in conscious diabetic rats. Myocardial performance and the response to stress caused by dobutamine were examined in conscious rats, fifteen days after the onset of diabetes caused by streptozotocin (STZ). The protective effect of insulin was also investigated in STZ-diabetic rats. METHODS: Cardiac contractility and relaxation were evaluated by means of maximum positive (+dP/dtmax) and negative (-dP/dtmax) values of first derivative of left ventricular pressure over time. In addition, it was examined the myocardial response to stress caused by two dosages (1 and 15 mug/kg) of dobutamine. One-way analysis of variance (ANOVA) was used to compare differences among groups, and two-way ANOVA for repeated measure, followed by Tukey post hoc test, to compare the responses to dobutamine. Differences were considered significant if P < 0.05. RESULTS: Basal mean arterial pressure, heart rate, +dP/dtmax and -dP/dtmax were found decreased in STZ-diabetic rats, but unaltered in control rats treated with vehicle and STZ-diabetic rats treated with insulin. Therefore, insulin prevented the hemodynamic and myocardial function alterations observed in STZ-diabetic rats. Lower dosage of dobutamine increased heart rate, +dP/dtmax and -dP/dtmax only in STZ-diabetic rats, while the higher dosage promoted greater, but similar, responses in the three groups. In conclusion, the results indicate that myocardial function was remarkably attenuated in conscious STZ-diabetic rats. In addition, the lower dosage of dobutamine uncovered a greater responsiveness of the myocardium of STZ-diabetic rats. Insulin preserved myocardial function and the integrity of the response to dobutamine of STZ-diabetic rats. CONCLUSION: The present study provides new data from conscious rats showing that the cardiomyopathy of this pathophysiological condition was expressed by low indices of contractility and relaxation. In addition, it was also demonstrated that these pathophysiological features were prevented by the treatment with insulin.

Animals↗

Delayed transient loss of consciousness in acute carbon monoxide intoxication.

In acute carbon monoxide intoxication the presence of altered consciousness, ranging from transient loss of consciousness to coma, represents a poor prognostic factor and modifies the approach to therapy. Transient loss of consciousness is, as a rule, contemporaneous to the exposure, generally occurring at the scene of the intoxication. We report an unusual case of delayed transient loss of consciousness, occurring in the absence of any other evident aetiology, in one member of an orchestra composed of 110 members after a mass carbon monoxide poisoning.

Acute-Phase Reaction↗

Order effects in the administration of personality measures: the case of the Self-Consciousness Scale.

The pitfalls of serial administration of personality measures as a research selection device were explored. Three samples of subjects were administered the Self-Consciousness Scale (Fenigstein, Scheier, & Buss, 1975) either first or last in a series of questionnaires. As predicted, those who responded to the measure last obtained higher private self-consciousness scores. However, the strength of the effect was moderated by the number of other measures included in the testing. Unexpectedly, public self-consciousness scores also were influenced by order of administration of the measure. Subjects who were administered the scale last evidenced lower public self-consciousness scores although this effect reached significance in only one of three samples of subjects. The broader implications of these findings for researchers who employ mass test administration procedures to select subjects for personality research are considered.

Journal Article↗

Testing the dimensionality of the self-consciousness scales.

The self-consciousness scale of Fenigstein, Scheier, and Buss (1975) was subjected to internal and external consistency tests based on the classical test theory model. The scale was found to have five underlying dimensions: two for private self-consciousness (viz., self-reflectiveness and internal state awareness), two for public self-consciousness, and one for social anxiety. The confirmatory factor analysis procedures employed by Burnkrant and Page (1984) are shown to be fallible as indicators of unidimensionality. Theoretical implications of newly identified dimensions in the public self-consciousness subscale are discussed.

Journal Article↗

Validation of the bispectral index monitor during conscious and deep sedation in children.

UNLABELLED: In this study, we tested the validity of the bispectral index (BIS) monitor during conscious and deep sedation of children by comparing it with the University of Michigan Sedation Scale (UMSS), a validated observational pediatric sedation scale. Eighty-six children <12 yr of age were enrolled in this observational study. The subjects underwent conscious or deep sedation administered by non-anesthesiologists for diagnostic or therapeutic procedures in four departments in a children's hospital. Sedation medications varied among departments and were not controlled by the study protocol. An independent observer derived a UMSS score at 10-min intervals for 1 h during sedation; personnel administering sedation medications and performing the procedures were blinded to the BIS and UMSS scores. Significant correlation between BIS scores and UMSS scores was found (r = -0.704, P < 0.0001), including in subjects <6 mo of age (n = 6) (r = -0.761, P < 0.001). Poor correlation was found when ketamine or an oral combination of chloral hydrate, hydroxyzine, and meperidine were used for sedation. We conclude that BIS correlates well with UMSS scores and may be a valid measure of conscious and deep sedation in children. IMPLICATIONS: We compared bispectral index scores with a validated observational scale of conscious and deep sedation in children and found significant correlation. We conclude that the bispectral index may be a valid measurement of depth of sedation in children.

Administration, Oral↗

The association between propofol-induced loss of consciousness and the SNAP index.

The SNAP is a processed electroencephalogram monitor that uses an algorithm based on low- and high-frequency spectral components to derive a SNAP index. In this study we sought to determine the relationship of the SNAP index with loss of consciousness in subjects receiving a bolus of propofol. Unpremedicated subjects were randomized to receive 1 of 11 doses of IV propofol (0, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0, 2.2, or 2.4 mg/kg; n=20 per group). The SNAP index was recorded when the subject became unconscious (end-point) or at 160 s after the injection. Sixty-five percent of subjects achieved the end-point (defined as the time at which the subject dropped a weighted syringe). The 50% effective dose for propofol was 0.97 mg/kg (95% confidence interval [CI], 0.86-1.07 mg/kg). The median awake SNAP index was 92 (range 78-99) and did not differ between subjects who reached the end-point and those who did not. The end-point SNAP index decreased from baseline in the subjects who dropped the syringe to a median of 76 (range, 57-94) at doses > or =1.0 mg/kg but was not different among doses. The index was not different from baseline at 160 s in subjects who did not reach the end-point. Binary logistic regression models predicted a SNAP index 95% effective dose for loss of consciousness of 71 (95% CI, 63-74) and 19 (95% CI, 16-22) for changes in SNAP index from baseline. The areas under the receiver operator characteristic curves for these models were 0.837 and 0.864. The SNAP index correlated with propofol-induced loss of consciousness. It appears to be a useful indicator of loss of consciousness and should be further investigated as a monitor of anesthesia depth.

Adolescent↗