Transient response of glomerular filtration rate and renal blood flow to step changes in arterial pressure

Measurement of rapid renal hemodynamic changes were made for 90 s in pentobarbital-anesthetized dogs following step increases and decreases in renal arterial pressure between 80 and 120 mm Hg. Transient analysis was used to observe time characteristics of the autoregulatory relationships which are obscured in steadystate measurements. Temporal decoupling of blood flow and glomerular filtration rate (GFR) occurred with both step increases and decreases of arterial pressure. Steady-state autoregulation of blood flow was attained in about 30 s, whereas steady-state autoregulation of GFR was not demonstrably attained even 90 s after the arterial pressure maneuver. The temporal decoupling of renal blood flow and GRR supports the concept of transient involvement of proximal tubular dynamics and efferent resistance changes during acute autoregulation of GFR following step changes in arterial pressure.     

Use of a neonatal blood pressure cuff to monitor blood pressure in the adult finger--comparison with a standard adult arm cuff

This study examined the comorbidity of substance use disorders and other psychiatric disorders in adolescent populations. The study population was comprised of 100 consecutive admissions, ages 13 to 17, to an acute care adolescent psychiatric inpatient unit for substance use disorders. Patients were assessed using the Personal Experience Screening Questionnaire (PESQ) and the substance-use disorder portion of the Structured Clinical Interview for DSM III-R (SCID-R). Thirty-three (33%) patients were identified as having a substance abuse or dependence diagnosis. There was no significant difference in the age between substance users and nonsubstance users. There were significantly more whites in the substance-using group. Sixty percent of all adolescents interviewed had histories of sexual or physical trauma, with trauma being significantly more common in the substance-using group. There were no significant differences in the number or type of other Axis I or Axis II diagnoses between the two groups. While substance users and nonsubstance users had no significant difference in the number of past psychiatric hospitalizations, nonsubstance users had significantly more past medical hospitalizations. These results indicate that high rates of comorbid substance abuse and psychiatric disorders exist in adolescents, and more in-depth study of comorbidity among adolescents is warranted.     

Caffeine abstinence augments the systolic blood pressure response to adenosine in humans

Blood pressure and heart rate responses to adenosine infusion (35, 70, and 140 microg/kg/min, intravenously) were studied in 7 healthy men after 6, 30, 78, 150, and 318 hours of abstinence from regular caffeine use. The finding that caffeine abstinence augmented the systolic pressor response (from -1 +/- 2 mm Hg at 6 hours to +9 +/- 2 mm Hg at 318 hours; p = 0.01) but not the tachycardic response to adenosine has implications for current clinical and research applications of this purine.     

Chronic sodium balance and blood pressure response to captopril in conscious mice

The influence of chronic administration of the converting enzyme inhibitor captopril on blood pressure and sodium balance was evaluated in conscious Swiss Webster mice. Arterial pressure was measured with chronic indwelling catheters, and sodium balance was determined by infusing sodium intravenously in isotonic saline and collecting urine 24 h/d. Experiments to validate sodium balance measurements in mice demonstrated recovery of 100+/-3% of sodium intake under steady-state conditions (n=20 mice on 70 individual days, sodium intake range 160 to 1000 micromol/d). It was further demonstrated that mean arterial pressure, heart rate, and body weight were unaltered from 115+/-7 mm Hg, 646+/-12 bpm, and 34+/-0.6 g, respectively, as sodium intake was increased stepwise from 150 to 900 micromol NaCl per day. An additional validation group (n=7) demonstrated that daily and cumulative sodium balance can be accurately determined during and after the intravenous administration of an agent known to alter renal sodium handling (furosemide 50 mg. kg-1. d-1). Experiments were then performed to examine the influence of intravenous captopril infusion (40 mg. kg-1. d-1, n=7) in mice in which the daily sodium intake was fixed at approximately 200 micromol/d. This dose of captopril was determined to significantly decrease the pressor response to a 10-ng bolus of angiotensin I (Ang I) from 24+/-5 in the control state to 6+/-2 mm Hg (n=5). After 5 days of infusion of the converting enzyme inhibitor, mean arterial pressure significantly fell from 114+/-3 to 58+/-2 mm Hg, body weight significantly decreased from 36+/-1 to 33+/-1 g, and cumulative sodium balance significantly decreased to -270+/-55 micromol. These parameters returned toward control during 5 postcontrol days. Results of this study demonstrate that accurate sodium balance measurements can be obtained from individual conscious mice over a 5-fold range of sodium intake. The experiments also indicate that converting enzyme inhibition has a potent influence to lower blood pressure in normal mice; the hypotensive response appears to be due in part to increased urinary sodium excretion.     

Evidence for endothelin involvement in the pulmonary vasoconstrictor response to systemic hypoxia in the isolated rat lung

We investigated the effect of systemic hypoxia (Krebs-Henseleit solution gassed with 5% CO2/95% N2) on an isolated, perfused rat lung. Hypoxia resulted in a slowly developing sustained increase in pulmonary perfusion pressure (PPP) accompanied by an increase in lung weight (LW). The endothelin (ET) receptor antagonists BQ123 (3 and 10 microM), BQ788 (3 microM) and bosentan (1.5 and 5 microM) all attenuated the hypoxia-induced increases in LW and PPP. In addition, phosphoramidon (1 microM), an ET-converting enzyme inhibitor, also significantly attenuated the hypoxia-induced increases in PPP and LW. The use of two agents that alter peptide secretion, phalloidin (10 and 50 nM) and colchicine (100 nM), and the peptide synthesis inhibitor cycloheximide (5 microM) all significantly attenuated the hypoxia-induced increases in PPP and LW. The increase in PPP and LW after the onset of hypoxia was accompanied by an increase in perfusate levels of ET-1 compared with normoxic time-matched controls. The results show that in this model, systemic hypoxia is capable of causing a sustained vasoconstriction and increased LW. The fact that these increases can be attenuated by an ET-converting enzyme inhibitor, ET receptor antagonists and agents that block peptide synthesis and secretion, together with the increase in perfusate levels of ET-1, suggests that ET production and release contribute to the changes seen.     

An additive effect of cold exposure and hypoxia on pulmonary artery pressure in sheep

When shorn sheep were exposed to cold (3 degrees C) pulmonary artery pressure (PPA) increased by 24 per cent. When they were caused to breathe an air mixture containing only 11 per cent oxygen there was a similar rise in PPA (27 per cent). During simultaneous exposure to 3 degrees C and low oxygen tension, the rise in PPA was greater than the sum of the two separate treatments (61 per cent). These results indicate the possible significance of cold exposure in the occurrence of high mountain sickness.     

Postexercise systolic blood pressure response: clinical application to the assessment of ischemic heart disease

Stress test parameters indicating the presence and extent of coronary artery disease have traditionally included such variables as exercise duration, and the blood pressure and ST-segment responses to exercise. The three-minute systolic blood pressure ratio, another important indicator of significant coronary artery disease, is a useful and readily obtainable measure that can be applied in all patients who are undergoing stress testing for the evaluation of known or suspected ischemic heart disease. The ratio is calculated by dividing the systolic blood pressure three minutes into the recovery phase of a treadmill exercise test by the systolic blood pressure at peak exercise. A three-minute systolic blood pressure ratio greater than 0.90 is considered abnormal and has a diagnostic accuracy of approximately 75 percent for the detection of coronary artery disease (i.e., an accuracy comparable to that of ST-segment depression). Higher values for the ratio are associated with more extensive coronary artery disease, as well as an adverse prognosis after myocardial infarction. Thus, the three-minute systolic blood pressure ratio provides information that is complementary to the traditional exercise test parameters for identifying high-risk ischemic heart disease.     

Relaxation training and opiod inhibition of blood pressure response to stress.

The present study was designed to determine the role of endogenous opioid mechanisms in the circulatory effects of relaxation training. Opioid mechanisms were assessed by examination of the effects of opioid receptor blockade with naltrexone on acute cardiovascular reactivity to laboratory stress before and after relaxation training. 32 young men with mildly elevated casual arterial pressure were recruited for placebo-controlled naltrexone stress tests and relaxation training. The results indicated that relaxation training significantly reduced the diastolic pressure response to mental arithmetic stress. Opioid receptor blockade with naltrexone antagonized the effects of relaxation training. These findings suggest that some of the physiological effects of relaxation training are mediated by augmentation of inhibitory opioid mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sociotropic cognition moderates blood pressure response to interpersonal stress in high-risk adolescent girls

The target of these investigations was a study of covalent binding the antipsychotic drug clozapine and the tripeptide glutathione. Other workers, primarily using radioisotopes, have found many adducts of clozapine and glutathione. We wanted to see how well the chlorine atom in clozapine could serve as an alternate to the use of a radiolabel using the Chemical Reaction Interface/Mass Spectrometer technique with HPLC introduction (HPLC/CRIMS). Here, we examine the capabilities of two such schemes that were previously used with GC introduction: Cl detection with SO2 as the reactant gas; and Cl and S detection using NF3 as the reactant gas. Detecting chlorine as HCl with SO2 was accomplished giving linearity over an 80-fold range of sample size. Incubations of the drug and glutathione with a peroxidase/peroxide system system yielded several metabolites characterized as novel conjugates of clozapine by electrospray mass spectrometry. This tentative identification of two conjugates was confirmed by examining the incubation mixture with NF3 as the CRIMS reactant gas. The simultaneous appearance of both Cl and S is consistent with covalent binding of clozapine to glutathione. A nearly doubled ratio of S to Cl in one peak confirmed the presence of a di-glutathione conjugate. These experiments support our proposition that element selective detection of HPLC effluents with CRIMS can supply additional information, not previously available using radioisotopic methods.     

Fast and slow components of cerebral blood flow response to step decreases in end-tidal PCO2 in humans

This study examined the dynamics of the middle cerebral artery (MCA) blood flow response to hypocapnia in humans (n = 6) by using transcranial Doppler ultrasound. In a control protocol, end-tidal PCO2 (PETCO2) was held near eucapnia (1.5 Torr above resting) for 40 min. In a hypocapnic protocol, PETCO2 was held near eucapnia for 10 min, then at 15 Torr below eucapnia for 20 min, and then near eucapnia for 10 min. During both protocols, subjects hyperventilated throughout and PETCO2 and end-tidal PO2 were controlled by using the dynamic end-tidal forcing technique. Beat-by-beat values were calculated for the intensity-weighted mean velocity (VIWM), signal power (P), and their instantaneous product (P.VIWM). A simple model consisting of a delay, gain terms, time constants (tauf,on, tauf, off) and baseline levels of flow for the on- and off-transients, and a gain term (gs) and time constant (taus) for a second slower component was fitted to the hypocapnic protocol. The cerebral blood flow response to hypocapnia was characterized by a significant (P < 0.001) slow progressive adaptation in P.VIWM, with gs = 1.26 %/Torr and taus = 427 s, that persisted throughout the hypocapnic period. Finally, the responses at the onset and relief of hypocapnia were asymmetric (P < 0.001), with tauf,on (6.8 s) faster than tauf,off (14.3 s).     

Effect of episodic eucapnic and hypocapnic hypoxia on systemic blood pressure in hypertension-prone rats

Repetitive episodic (18-24 s twice per minute) hypocapnic hypoxia (HH) administered chronically (7 h/day, 35 days) to Sprague-Dawley or Wistar-Kyoto rats results in a sustained increase in daytime blood pressure (BP). We examined acute and chronic BP response to episodic HH and eucapnic hypoxia (EH) in borderline hypertensive rats [first generation (F1) cross between spontaneously hypertensive and Wistar-Kyoto rats]. We hypothesized that episodic HH and EH would create a greater increase in acute and chronic BP in this breed of rat than in previously studied strains. We also examined neural mechanisms by which BP changes from hypoxia are induced. BP and heart rate were examined acutely in nine F1 rats during baseline, HH, EH, EH with prazosin, and EH with prazosin and atropine. Five groups of male F1 rats were studied after 35-day exposure to the following: Unhandled (n = 8): no treatment; Sham (n = 10): episodic compressed air; HH (n = 14): daily episodic hypoxia (2.7%); EH1 (n = 12); hypoxia 2.9%, CO2 8.4%; and EH2 (n = 11): hypoxia 2.8% and CO2 10.5%. Under acute conditions, HH caused a 34.2-mmHg and EH a 77.9-mmHg increase in mean BP. Prazosin partially blocked the increase in BP. Under chronic conditions, HH caused a 10.3-mmHg increase in daytime mean BP, whereas EH caused a fall in mean BP of 16.6 and 9.3 mmHg in the two separately studied groups. In the F1 rat, acute EH causes an elevation of BP but chronic EH causes a fall in BP. The acute response to EH is not predictive of what occurs after chronic exposure in the hypertension-prone F-1 rat.     

Use of antihypertensive drugs and trends in blood pressure in the elderly

BACKGROUND: During the 1980s data became available from randomized trials concerning the clear benefits of treating hypertension in the elderly. In three large communities, we examined the impact of these findings on rates of treatment, use of specific antihypertensive drugs, and rates of elevated blood pressure as well as distributions of levels. METHODS: In 1981 the National Institute on Aging initiated population-based cohort studies in the residents of three communities who were 65 years and older. East Boston, Mass; Washington and Iowa counties, Iowa; and New Haven, Conn. Participation rates ranged from 80% to 85% across sites with 10,294 community-dwelling participants in the combined cohorts. Baseline evaluation included inhome blood pressure assessment and medication inventory. Repeated in-home evaluations occurred 3 and 6 years after baseline and follow-up rates ranged from 71% to 88%. RESULTS: Use of antihypertensive drugs increased over time in all three communities: the age- and sex-adjusted rates of use were between 14% and 32% higher in 1988 and 1989 relative to 1982 and 1983. Parallel declines in the use of thiazide diuretics occurred in all three populations along with large increases in the use of angiotensin-converting enzyme inhibitors and calcium channel blockers. In East Boston and New Haven mean systolic blood pressure decreased substantially over time and the prevalence of elevated systolic pressure (> or = 160 mmHg) decreased overall as well as by age and sex. In Iowa the mean levels of systolic blood pressure were lowest at baseline and increased slightly. CONCLUSIONS: The reported evidence about the benefits of treatment for hypertension in the elderly was followed by substantial increases in treatment rates. The use of drugs with proven efficacy declined while the use of newer agents with theoretical advantages, not yet tested in clinical trials of mortality, increased. In the United States, the ongoing therapeutic efforts to lower elevated blood pressure in elderly populations may be contributing to the continuing decline in cardiovascular and stroke mortality.     

Use of nonlinear methods to assess effects of clonidine on blood pressure in spontaneously hypertensive rats

In spontaneously hypertensive rats (SHR), chronic infusion of clonidine failed to decrease blood pressure and blood pressure variability. We used nonlinear methods to get a deeper insight on the effects of clonidine on blood pressure dynamics. For 24 h and 4 wk, clonidine (0.1 mg . kg-1 . day-1 sc) was infused by minipumps in the conscious SHRs, and, for comparison, a vehicle was infused in SHRs and in Wistar-Kyoto rats. Blood pressure was recorded for 30 min before and after treatments. We used the Lyapunov exponent, approximated by the inverse of the lmax index derived from the recurrence plot method, to characterize nonlinear dynamics. Before treatment, lmax index of blood pressure was lower (P < 0.01) in the SHRs than in the Wistar-Kyoto rats. Clonidine significantly increased lmax (P < 0.01) to the level observed in normotensive rats, at 24 h and up to 4 wk after infusion. We conclude that clonidine has a significant chronic effect on blood pressure dynamics, as evidenced by nonlinear methods. Our study also suggests that the mechanisms governing blood pressure variations are nonlinear.     

Women''s anger: relationship of suppression to blood pressure

Myeloablative therapy followed by allogeneic bone marrow transplantation (BMT) has proven to be curative therapy in patients with hematologic malignancies. Relapse, however, remains a major cause of treatment failure for patients with advanced disease. During the past 15 years, we have gained considerable experience with the combination of fractionated total-body irradiation (FTBI) and etoposide followed by allogeneic BMT for hematologic malignancies. In an attempt to decrease post-transplant relapse rates, 67 patients under the age of 50 years with high-risk or advanced-stage hematological malignancies received an intensified regimen of FTBI and etoposide plus cyclophosphamide followed by BMT from a genotypically-matched related donor. The regimen consisted of 1320 cGy of FTBI in 11 fractions, 60 mg/kg of etoposide (VP-16), and 60 mg/kg of cyclophosphamide (CY). Fifty-three patients received cyclosporine and prednisone for graft-vs.-host disease (GVHD) prophylaxis and 14 patients received cyclosporine, methotrexate, and prednisone. Diagnosis at BMT included 45 patients with acute leukemia, 7 patients with chronic leukemia, and 15 patients with high-grade non-Hodgkin's lymphoma (NHL). Actuarial disease-free survival (DFS) at 3 years was 42% +/- 12% for the entire group with a median follow-up of 50 months (range 20-74) for 28 patients who remain alive in continued complete remission (CR). Actuarial 3-year-DFS was 38% +/- 14% in 52 patients with acute or chronic leukemia and 60% +/- 25% in 15 patients with NHL with relapse rates of 45% +/- 16% and 21% +/- 11%, respectively. DFS at 3 years was 40% +/- 18% in 32 patients with acute leukemia in 1st relapse or 2nd CR or chronic myelogenous leukemia in accelerated phase, and was 32% +/- 22% in 20 patients with more advanced disease. Regimen related mortality occurred in 9 patients (4, veno-occlusive disease of the liver; 2, multi-organ failure; 1, diffuse alveolar hemorrhage; 1, central nervous system (CNS) hemorrhage; 1, adult respiratory distress syndrome (ARDS). The combination of FTBI, etoposide, and cyclophosphamide followed by allogeneic BMT is an effective and relatively well-tolerated regimen for patients with advanced hematologic malignancies. The role for this regimen should be further defined by prospective clinical trials.     

Ventilatory response to hypoxia in humans. Influences of subanesthetic desflurane

The tegument of herpes simplex virus type 1 (HSV-1) virus particles is a complex assemblage of virus proteins whose relative proportions within virions are essentially constant for a particular strain of virus. To examine the processes controlling incorporation into the tegument, we constructed a HSV-1 recombinant that expresses two copies of gene UL49, which encodes the major tegument protein VP22. One copy specifies the unmodified form of VP22 under the control of the native promoter while the second expresses an epitope-tagged version of the protein via the human cytomegalovirus immediate early promoter. In cells infected with the recombinant virus, the overall levels of VP22 synthesized were about fivefold higher than those for wild-type virus, due to the high levels of expression of tagged protein. Analysis of virus particles revealed that the amount of VP22 in the tegument was approximately two- to threefold higher in recombinant virions and L-particles than in particles produced by wild-type virus. These results provide the first evidence that, for certain proteins, the level of polypeptide synthesis can act as a controlling factor for the amount of protein incorporated into tegument.     

Use of non-invasive positive pressure ventilation for cardiogenic pulmonary edema in emergency care units

The work reported by L'Her et al. in this issue of La Presse Médicale demonstrates the feasibility of applying simple intensive care techniques in situations frequently encountered in emergency care units. These authors used a face mask for continuous positive pressure ventilation in patients over 70 years of age admitted for respiratory distress related to cardiogenic pulmonary edema. In these elderly patients, the authors noted an improvement in blood gases, respiratory rate and heart rate and did not observe any secondary effect. Acute respiratory failure was cured in 90% of the cases without referral to the intensive care unit. The mechanism of action of continuous positive airway pressure, or spontaneous ventilation with positive expiratory pressure, is different from simple oxygen therapy. Two mechanisms are intimately related. The main effect is ventilatory assistance resulting from a "re-aeration" of the pulmonary parenchyma which increases compliance and reduces work required to overcome elastic retraction forces. Likewise the increased pulmonary volume reduces pulmonary resistance. Positive airway pressure also has an effect on left ventricular function. Indeed, after-load is reduced by the reduction in the large negative intrathoracic pressure swing. Lower energy expenditure required for respiration also greatly reduces total oxygen consumption and improved blood gases favor oxygen supply to the myocardium. The contraindications of continuous positive airway pressure are related to abnormal control of the upper airways and major hemodynamic disorders. Prudence is also required in case of shock due to the risk of major respiratory muscle fatigue. The question could also be raised as to the risk in elderly patients where cardiogenic pulmonary edema is often associated with a certain degree of chronic bronchitis. It is now known that these patients have an intrinsic positive expiratory pressure which considerably increases respiratory work. Symptomatic treatment in this type of disorder is mechanical and continuous positive airway pressure diminishes this work. Cardiogenic pulmonary edema in the elderly is thus an excellent indication for spontaneous ventilation with positive expiratory pressure. Improvement in these simple techniques, their widespread use and a better understanding of their limitations remain important challenges for the future.     

Arterial blood pressure response to transient arousals from NREM sleep in nonapneic snorers with sleep fragmentation

STUDY OBJECTIVES: To assess the hemodynamic effects of graded arousals during nonrapid eye movement (NREM) sleep in patients with partial upper airway obstruction during sleep without obstructive sleep apnea/hypopnea, overnight beat-to-beat BP was recorded in six patients. SETTING: At the end of each nonapneic obstructive event, EEG responses were graded as follows: grade 2, grade 1, and grade 0 were defined as increased high-frequency EEG lasting >15 s, 3 to 15 s, and no EEG arousals according to the American Sleep Disorders Association, respectively. MEASUREMENTS AND RESULTS: The following were observed during grade 0, 1, and 2 EEG patterns (mean+/-SD): systolic pressure increased by 7.1+/-1.5, 11.7+/-1.9, and 14.2+/-3.4 (p<0.005), respectively; diastolic pressure increased by 4.6+/-0.6, 6.7+/-1.7, and 9.4+/-3.0 (p<0.005), respectively; heart rate increased by 2.9+/-0.4, 3.9+/-2.2, and 8.6+/-4.6 (p<0.005), respectively. CONCLUSIONS: We conclude that nonapneic-nonhypopneic obstructive events are followed by arterial systemic pressure increases whose magnitude varies with the grade of the arousal.