Application of USAF G-suit technology for clinical orthostatic hypotension: a case study

INTRODUCTION: The purpose of this study was to determine the effectiveness of a USAF anti-gravity suit (G-suit) on the stability of a patient with chronic orthostatic hypotension. METHODS: A 37-yr-old female with a history of insulin-dependent diabetes mellitus (IDDM) and symptomatic orthostasis was evaluated and the results were compared with those of non-diabetic controls, matched for age, height, and weight. Cardiac vagal tone was assessed by determination of standard deviation of 100 R-R intervals (R-R SD). We assessed the carotid-cardiac baroreflex response by plotting R-R intervals (ms) at each of eight neck pressure steps with their respective carotid distending pressures (mm Hg). Heart rate and blood pressure were recorded in response to the Valsalva maneuver (VM) performed at an expiratory pressure of 30 mmHg to assess integrated baroreflex responses. Blood pressures and heart rate were measured during three 5-min stand tests to assess orthostatic responses: a) without G-suit; b) with noninflated G-suit; and c) with inflated G-suit (50 mm Hg). RESULTS: The IDDM patient had minimal baseline cardiac vagal tone (R-R SD = 8.5 ms) compared with the average response of a control group of 24 subjects with orthostatic stability (R-R SD = 67.2 +/- 7.1 ms). Carotid-cardiac baroreflex response was virtually non-existent in the IDDM patient (Gain = 0.06 ms.mm Hg-1) compared to the control subjects (4.4 +/- 0.8 ms.mm Hg-1). VM responses corroborated the lack of cardiac baroreflex response in the IDDM patient, while blood pressure changes during the VM were similar to those of the controls. Upon standing, the IDDM patient demonstrated severe orthostatic hypotension (90 mm Hg SBP) and tachycardia without the G-suit. The G-suit, with and without pressure, reduced hypotension and tachycardia during standing. CONCLUSION: These results demonstrate successful application of Air Force technology as a useful alternative to pharmacologic intervention in the treatment of a patient with autonomic dysfunction leading to supine hypertension and orthostatic hypotension.     

The hypertension of autonomic failure and its treatment

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.     

Heart rate and blood pressure variability in obese normotensive subjects

OBJECTIVE: To assess autonomic modulation of cardiovascular activity in massively obese subjects. DESIGN: Cross-sectional clinical study. SUBJECTS: 43 age-matched normotensive subjects: 15 moderately obese (body mass index (BMI) < 40); 14 massively obese (BMI > 40) and 14 nonobese controls (BMI < 26). MEASUREMENTS: Using power spectral analysis, heart rate and arterial pressure variability were determined at rest and after sympathetic stress (tilt). Two spectral components were analysed: a low-frequency (LF) component at around 0.1 Hz, predominantly reflecting sympathetic modulation and a high-frequency (HF) component at around 0.26 Hz, reflecting parasympathetic modulation. RESULTS: Spectral data for heart rate showed that the massively obese subjects had lower LF [mean +/- s.e.m.] normalized units (NUs) at rest (35.1 +/- 0.9) and after tilt (56.1 +/- 2.1), than the moderately obese subjects (LF NUs at rest 53.9 +/- 4.2, P < 0.001; LF NUs tilt: 66.8 +/- 5.6, P < 0.001) and nonobese control subjects (LF NUs at rest, 56.6 +/- 3.0, P < 0.001); (LF NUs tilt: 81.7 +/- 1.7, P < 0.001). Data for systolic arterial pressure variability measured at rest exhibited the inverse pattern, the massively obese group having higher mean LF values (LF mm Hg2 rest: 15.0 +/- 1.4; LF mm Hg2 tilt: 15.7 +/- 1.5) than the moderately obese group (LF mm Hg2 rest 3.2 +/- 0.7, P < 0.001; LF mm Hg2 tilt: 7.2 +/- 2.0, P < 0.001) and than the nonobese control subjects (LF mm Hg2 rest 3.5 +/- 0.5, LF mm Hg2 tilt 8.5 +/- 0.8, P < 0.001). Regression detected a significant association between BMI and LF of systolic pressure (beta = 0.364; P = 0.0007), In LF of heart rate (beta = -5.555; P = 0.00001) and very low frequency (VLF) of diastolic pressure (beta = -3.305; P = 0.0020). CONCLUSION: Obesity seems to increase sympathetic modulation of arterial pressure, but diminishes modulation of heart rate. Because our obese subjects had high plasma noradrenaline levels, their low LF power of heart rate could reflect diminished adrenoceptor responsiveness.     

Diminished venous vascular capacitance in patients with univentricular hearts after the Fontan operation

Patients who have undergone Fontan's operation are known to have impaired cardiac output response to dynamic exercise. This may be due to either poor cardiac function or a limited ability to mobilize blood from capacitance vessels due to increased resting venous tone. We tested the latter hypothesis by determining venous vascular capacitance at rest and during orthostatic stress produced by lower body negative pressure (LBNP) in 6 subjects who had undergone the Fontan operation and 6 healthy age-, sex-, height-, and weight-matched controls. Resting blood volume was similar for Fontan and control subjects (79 +/- 6 vs 70 +/- 3 ml/kg body weight, respectively), while central venous pressure (CVP) was elevated in Fontan subjects (18.4 +/- 1.0 vs 3.5 +/- 0.9 mm Hg, p < 0.05). Forearm venous capacitance at a distending pressure of 40 mm Hg was less in Fontan subjects than in controls (2.6 +/- 0.1 vs 3.9 +/- 0.5 ml/100 ml), while resting plasma norepinephrine level was elevated in Fontan subjects (255 +/- 28 vs 144 +/- 9 pg/ml, p < 0.05). The increase in calf volume (1.6 +/- 0.2 vs 2.3 +/- 0.2 ml) and decrease in CVP (-5.0 +/- 0.5 vs -6.7 +/- 1.1 mm Hg) during -30 mm Hg LBNP were smaller for Fontan than control subjects (p < 0.05). Reduced forearm venous capacitance and diminished pooling of blood into capacitance vessels of the leg during orthostatic stress indicated higher venous tone in Fontan than control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sepsis-induced vasoparalysis does not involve the cerebral vasculature: indirect evidence from autoregulation and carbon dioxide reactivity studies

We have studied cerebral autoregulation and vasoreactivity to carbon dioxide in 10 patients with the sepsis syndrome receiving intensive therapy. All patients were sedated with infusions of midazolam and fentanyl, and their lungs were ventilated mechanically with oxygen-air to maintain normoxia and normocapnia. Inotropic support and antibiotics were administered as necessary. During a period of constant level of sedation and stable haemodynamics, cerebral autoregulation was tested by increasing mean arterial pressure (MAP) by 23 (SD 2) mm Hg from baseline with an infusion of phenylephrine and simultaneously recording middle cerebral artery blood flow velocity (vmca) using transcranial Doppler ultrasonography. Carbon dioxide reactivity was tested by varying PaCO2 between 3.0 and 7.0 kPa and simultaneously recording vmca. There was no significant change in vmca (57 (22) and 59 (23) cm s-1) during the increase in MAP (75 (11) to 98 (10) mm Hg). The mean index of autoregulation (IOR) was 0.92 (SEM 0.03), which was not significantly different from 1, indicating near perfect autoregulation. Although absolute carbon dioxide reactivity was lower than reported previously in awake subjects, relative carbon dioxide reactivity was within normal limits for all patients (11.6 (SEM 0.8) cm s-1 and 20.3 (3) % kPa-1, respectively). We conclude that cerebral carbon dioxide reactivity and pressure autoregulation remained intact in patients with the sepsis syndrome, providing indirect evidence that at least in the early stages of the syndrome, the widespread sepsis-induced vasoparalysis does not involve the cerebral vasculature.     

Code Stroke: rapid transport, triage and treatment using rt-PA therapy. The NINDS rt-PA Stroke Study Group

In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65-79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05) and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. Serum urate was significantly higher during the low compared to high sodium intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons.     

The Chiropractic Outcome Study: pain, functional ability and satisfaction with care

BACKGROUND: Elevation of intraocular pressure in the supine position has been previously described in literature. Aim of this study is to investigate the elevation of intraocular pressure in normal tension glaucoma and its effect on the morphology of the optic disc, visual field function and capillary blood flow of the retina and optic disc. PATIENTS AND METHODS: 56 eyes of 28 preperimetric and advanced normal tension glaucoma patients were prospectively evaluated. Ten eyes of ten normal patients served as a control group for the measurements of the intraocular pressure. In the course of a 24-h pressure profile applanation tonometry was performed in the morning in a supine and three and ten minutes later in a sitting position with Draeger's and Goldmann's tonometers. Arterial blood pressure was measured at the same time. The optic disc's morphology was evaluated by stereo photographs and Laser Scanning Tomography. As a sensory test computer perimetry was used. Capillary blood flow was measured at defined areas of the retina and optic disc. An intraocular pressure above 21 mm Hg in the supine position was used as a criterium to define two groups of normal tension glaucoma patients. RESULTS: In the supine position a statistically significant elevation of intraocular pressure was observed in 24 normal tension glaucoma patients by 6.2 +/- 2.8 mm Hg up to 21.8 +/- 3 mm Hg. Diastolic blood pressure in the supine position (80 +/- 10.5 mm Hg) was significantly lower than in the sitting position (94 +/- 11 mm Hg, p = 0.021). 12 of 28 normal tension glaucoma patients showed an intraocular pressure lower than 22 mm Hg in the supine position. In these patients a tendency towards a higher incidence for the occurrence of optic disc haemorrhages and significantly higher values for blood flow (p < 0.0005) and volume (p < 0.005) in the retina and optic nerve head could be shown. In this group of normal pressure glaucoma patients a higher incidence of migraine and vasospastic complaints was reported in the patients' history. CONCLUSION: In this study some normal tension glaucoma patients showed intraocular pressures in the supine position higher than 21 mm Hg and a lower diastolic arterial pressure. The higher incidence of haemorrhages and higher values for flow and volume parameters of the optic disc in normal tension glaucoma patients with an intraocular pressure lower than 22 mm Hg implicate the existence of two entities: real and pseudo normal tension glaucomas.     

Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation

OBJECTIVES: The purpose of this study was to evaluate the role of autonomic reflexes in the genesis of syncope associated with the onset of paroxysmal atrial fibrillation. BACKGROUND: Syncope associated with paroxysmal atrial fibrillation has been interpreted as an ominous finding predictive of rapid ventricular rates. However, various mechanisms may be involved when heart rate is not particularly high. METHODS: Forty patients (age 60 +/- 14 years, 20 men, 20 women) with syncope and atrial fibrillation were compared with atrial fibrillation without syncope. Carotid sinus massage and head-up tilt testing (at 60 degrees for 60 min at baseline and during isoproterenol infusion) were performed during sinus rhythm. A positive response was defined as the induction of syncope. Atrial fibrillation was also induced on a tilt table at 60 degrees by means of short bursts of atrial pacing. RESULTS: Results of carotid sinus massage were positive in 15 (37%) of 40 patients but in no control subjects (p = 0.002). Head-up tilt test findings were positive in 25 (66%) of 38 patients and in 2 (12%) of 16 control subjects (p = 0.0004). The induction of atrial fibrillation in the upright position elicited syncope in 16 (42%) of 38 patients but in none of 16 control subjects (p = 0.001). At the beginning of atrial fibrillation, systolic blood pressure was lower in patients than in control subjects (88 +/- 32 vs. 127 +/- 32 mm Hg), whereas mean heart rate was similar (142 +/- 35 vs. 134 +/- 25 beats/min). The correlation between heart rate and systolic blood pressure was weak (r = 0.35), and in five patients syncope occurred at a heart rate < or = 130 beats/min. At the time of syncope, heart rate decreased (-12 +/- 21 beats/min) in patients with induced syncope, whereas it remained unchanged in patients without induced syncope (+1 +/- 17 beats/min, p = 0.04) or slightly increased in control subjects (+9 +/- 21 beats/min, p = 0.009). CONCLUSIONS: Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope.     

Improved orthostatic tolerance in familial amyloidotic polyneuropathy with unnatural noradrenaline precursor L-threo-3,4-dihydroxyphenylserine

Disabling orthostatic hypotension, due to insufficiency of the autonomic nervous system, is a common complication of type I familial amyloidotic polyneuropathy (FAP). We investigated whether oral treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-Dops), a noradrenaline precursor, might be of therapeutical benefit. In twenty untreated FAP patients, aged 33 to 44 years, who, because of severe orthostatic hypotension, were bedridden or constrained to a sitting life, supine and erect blood pressure (BP), plasma noradrenaline and tilting time, defined as the interval (s) between the beginning of a 60 degrees head-up tilt and the occurrence of orthostatic symptoms (dizziness, blurred vision or near syncope) were determined before and at repeated intervals during oral treatment with L-threo-Dops, 100 mg bid, for 6 months. Before treatment supine mean BP was 80 (76-85) mmHg (mean and 95% CI), supine plasma noradrenaline was low, 59 (41-77) pg/ml and tilting time ranged from 38 to 118 s. In response to tilt, mean BP immediately fell by 36 (31-41) mmHg, whereas plasma noradrenaline increased by only 11 (0-21) pg/ml (p = 0.05). After 3 to 5 days of treatment with L-threo-Dops all patients experienced marked improvement of their orthostatic tolerance as reflected by their ability to walk freely around. This effect sustained throughout the six months of treatment. Plasma noradrenaline increased moderately by 37 (11-63) pg/ml (p = 0.02) and supine mean BP increased by 8.6 (5.8-12.4) mmHg (p < 0.001) during chronic treatment. Supine or nocturnal hypertension did not develop, the fall in mean BP in response to tilt diminished by 12.5 (6.5-17.3) mmHg (p < 0.001) and tilting time became longer than 600 s in all patients. Because of its efficacy, its sustained duration of action and the lack of side effects, L-threo-Dops is advocated to improve orthostatic tolerance in patients with autonomic insufficiency due to FAP.     

Hypocapnia and cerebral hypoperfusion in orthostatic intolerance

BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS: Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.     

Clinical cancer research in a managed-care environment

PURPOSE: Autoregulation of optic nerve head blood flow (Fonh) in response to decreases in perfusion pressure has been demonstrated in animals and humans. The aim of this study was to determine change in Fonh when systemic blood pressure is increased. METHODS: Blood flow parameters, i.e. relative mean velocity, number, and flux of red blood cells in the ONH tissue (Velonh, Volonh and Fonh, respectively) were measured by laser Doppler flowmetry in one eye of 13 normal subjects (aged 16 to 58 years), at baseline, during, and after isometric exercises consisting of squatting. Brachial artery blood pressure was measured by sphygmomanometry. IOP was measured at baseline and at the end of squatting. RESULTS: During squatting mean arterial pressure increased from 103 +/- 6 mm Hg to 139 +/- 58 mm Hg (average +/- 95% confidence interval), IOP increased from 13 +/- 0.5 to 17 +/- 1 mm Hg. An average increase in PPm from 56 +/- 4 to 80 +/- 7 mm Hg induced no significant (p > 0.05) change in the blood flow parameters. The sensitivity (detection threshold) of the blood flow changes was 8%. CONCLUSION: This study shows for the first time in human autoregulation of Fonh when PPm is increased by increasing the systemic blood pressure.     

Effect of physical fitness on vanillylmandelic acid excretion during immersion

The effects of 4--6 h head-out immersion on excretion of vanillylmandelic acid (VMA), blood pressure and plasma volume were estimated in 8 endurance-trained (TR) and 8 untrained (UT) subjects. In the trained only a slight increase of VMA excretion occurred (4 h value: +2.7 +/- 10.9 ng/ml GFR), but there was a highly significant increase in the UT (+29.0 +/- 17.2 ng/ml GFR). VMA values during control experiments in supine position tended to decrease in both groups. Systolic and diastolic blood pressure fell by 20 mm Hg after beginning of immersion; in the UT plasma volume was reduced while it remained constant in TR. The results indicate that orthostatic intolerance (o.i.) after immersion is not effected by decreased sympathetic innervation of vessels; in contrast it seems to be partly compensated for by an elevated sympathetic activity at least in the UT. As a main cause for the post-immersion o.i. one might suggest a decrease in renin activity.     

Left ventricular contractile performance, ventriculoarterial coupling, and left ventricular efficiency in hypertensive patients with left ventricular hypertrophy

Contractile performance of hypertrophied left ventricle may be depressed in arterial hypertension. Ventriculoarterial coupling is impaired when myocardial contractile performance is reduced and when afterload is increased. The left ventricular contractile performance and the ventriculoarterial coupling were evaluated in 30 hypertensive patients with moderate left ventricular hypertrophy and 20 control subjects. Left ventricular angiography coupled with the simultaneous recording of pressures with a micromanometer were used to determine end-systolic stress/volume index, the slope of end-systolic pressure-volume relationship, ie, end-systolic elastance, effective arterial elastance, external work, and pressure-volume area. In hypertensive patients, left ventricular contractile performance, as assessed by end-systolic elastance/ 100 g myocardial mass, was depressed (4.35 +/- 1.13 v 5.21 +/- 1.89 mm Hg/mL/100 g in control subjects P < .02), when end-systolic stress-to-volume ratio was comparable in the two groups (3.85 +/- 0.99 g/cm2/mL in hypertensive patients versus 3.51 +/- 0.77 g/cm2/mL in control subjects). Ventriculoarterial coupling, evaluated through effective arterial elastance/end-systolic elastance ratio, was slightly higher in hypertensive patients (0.53 +/- 0.08 v 0.48 +/- 0.09 mm Hg/mL in control subjects, P < .05), and work efficiency (external work/pressure-volume area) was similar in the two groups (0.78 +/- 0.04 mm Hg/mL in hypertensive patients versus 0.80 +/- 0.03 mm Hg/mL in control subjects). This study shows that despite a slight depression of left ventricular contractile performance, work efficiency is preserved and ventriculoarterial coupling is almost normal in hypertensive patients with left ventricular hypertrophy. Thus, it appears that left ventricular hypertrophy might be a useful means of preserving the match between left ventricle and arterial receptor with minimal energy cost.     

Role of nitric oxide in regulation of brain stem circulation during hypotension

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-5) mol/L and 10(-4) mol/L N(omega)-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10(-5) mol/L and 60 to 75 mm Hg in the 10(-4) mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 +/- 8% in the 10(-5) mol/L and 12 +/- 5% in the 10(-4) mol/L L-NNA group versus 34 +/- 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10(-5) mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.     

Plasmin, substilisin-like endoproteases, tissue plasminogen activator, and urokinase plasminogen activator are involved in activation of latent TGF-beta 1 in human seminal plasma

OBJECTIVES: To compare the effects of simulated and mild actual hemorrhage on parameters used traditionally to assess hemorrhaging patients: heart rate (HR), blood pressure (BP), and Shock Index (SI = HR/systolic BP), with stroke distance (SD) measured ultrasonically as an index of cardiac stroke volume. MATERIALS and METHODS: Hemorrhage was simulated in 19 healthy volunteers by the application of graded lower-body negative pressure (LBNP) (0, -20, -40, and -60 mm Hg) to pool blood in the lower body and reduce venous return. Measurements were also made before and after a standard blood donation (450 mL) in nine healthy volunteers. MEASUREMENTS and MAIN RESULTS: SD decreased significantly and progressively from the baseline level of 23.8+/-5.7 cm (mean+/-SD) at each level of LBNP: by 3.4+/-1.9, 7.4+/-2.5, and 11.8+/-3.2 cm at LBNP of -20, -40, and -60 mm Hg, respectively. Neither HR nor SI changed significantly at the lowest level of LBNP (-20 mm Hg), but they showed progressive, significant increases thereafter. Mean BP did not change significantly at any level of LBNP. Similarly, after a controlled hemorrhage of 450 mL, SD decreased significantly by 3.3+/-1.6 cm from 22.2+/-2.8 cm, whereas HR and SI remained unchanged and mean BP increased slightly. CONCLUSION: Changes in SD may provide an earlier indication of progressive blood loss than either HR or BP alone or in combination.     

Time and frequency domain analyses of heart rate variability during orthostatic stress in patients with neurally mediated syncope

The role of autonomic balance during upright tilt in patients with neurally mediated syncope is unclear. To assess the characteristics of autonomic tone during orthostatic stress, 15 patients (mean age 32 years) with recurrent episodes of syncope (> or = 2) and a positive response to a 30-minute 60 degrees upright tilt were compared with the following control groups: (1) 15 patients (mean age 33.5 years) with > or = 2 episodes of recurrent syncope and a negative tilt response, and (2) 15 age- and sex-matched healthy volunteers (mean age 34 years) with no previous history of presyncope or syncope. Time domain measurements assessed were mean RR interval, standard deviation of normal RR intervals, and percentage of normal consecutive RR intervals differing by > 50 ms. Frequency domain measurements of the low-frequency (LF) and high-frequency (HF) bands were obtained, and the LF/HF ratio was also calculated. All variables were calculated in the supine position and during the first 5 minutes of upright tilt. No significant difference was observed in the time and frequency domain variables in the supine position between control groups with a negative head-up tilt response and the group with a positive response. The percentage of normal consecutive RR intervals differing by > 50 ms during the first 5 minutes of head-up tilt was significantly higher in the group with positive tilt tests than in the controls (25 +/- 12% vs 7 +/- 4%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Power spectral analysis of heart rate variability during graded head-up tilting in patients with vasodepressor syncope

1. Two groups of age- and sex-matched subjects, eight healthy controls and 10 patients, suffering from recurrent vasodepressor syncope, participated in a study to examine autonomic function and sequential changes in power distribution of heart rate (HR) variability during graded head-up tilt. 2. The following autonomic function tests were performed: valsalva ratio, HR responses to deep breathing and posture, BP responses to sustained handgrip and postural change. Each subject was tilted at 15 degrees, 30 degrees, 45 degrees, 60 degrees and 80 degrees head-up, each for 15 min, or until symptoms occurred. The eight control subjects completed the tilt study without any symptoms, while all 10 patients developed presyncope and/or syncope at various tilt angles. 3. Resting blood pressure (BP) was lower in the patient group, while resting HR, autonomic function tests and resting HR variability components were similar in the two groups. 4. The control group showed a progressive increase in low frequency power component (LF) from supine to end tilt (delta LF 20.06 +/- 14.50%) and a progressive fall in high frequency (HF) component (delta HF - 24.62 +/- 10.64%). In contrast, in the patient group, LF fell during tilt in the presyncope period (delta LF - 10.57 +/- 12.93%, P < 0.01 vs control group). HF and HF:LF ratio responses did not differ significantly in the two groups. 5. At end tilt, the increase in plasma noradrenaline was significantly greater in the control group than in the patient group (delta NA 0.83 +/- 0.27 vs 0.28 +/- 0.14 pmol/mL, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of the vessel wall properties in hemodialysis patients

Compliance is an important property of the arterial system and abnormalities in compliance can greatly affect cardiovascular function. The elastic properties of the common carotid artery were therefore studied in 24 normotensive hemodialysis patients and 24 healthy normotensives using a noninvasive technique. The hemodialysis patients and the control subjects were matched for blood pressure. Arterial distension was measured by Doppler analysis of the vessel wall movements and blood pressure was recorded by finger-phlethysmography (Finapres). The vessel wall distensibility (DC: 2.49 +/- 0.23 10(-3)/mm Hg; mean +/- SEM) was significantly reduced and the end diastolic diameter (d: 7.3 +/- 0.3 mm) was significantly increased in younger hemodialysis patients (36.3 +/- 2.0 years) when compared with age-related controls (DC: 3.44 +/- 0.24 10(-3)/mm Hg; d: 6.3 +/- 0.3 mm; mean +/- SEM). In older hemodialysis patients (60.2 +/- 2.3 years), there was no significant difference in vessel wall distensibility (DC: 1.55 +/- 0.15 10(-3)/mm Hg) and vessel diameter (d: 7.8 +/- 0.3 mm) as compared with age-matched controls (DC: 1.77 +/- 0.14 10(-3)/mm Hg; d: 7.2 +/- 0.3 mm). The results show that vessel wall distensibility of the common carotid artery is decreased in younger hemodialysis patients as compared with age-matched healthy subjects. The volume expanded state in hemodialysis patients cannot account for the decreased arterial distensibility, since volume depletion by hemodialysis was not associated with a significant change of arterial distensibility (DC 2.14 +/- 0.44 10(-3)/mm Hg before, DC 2.26 +/- 0.45 10(-3)/mm Hg after ultrafiltration, NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

Stress-induced left ventricular outflow tract obstruction: a potential cause of dyspnea in the elderly

OBJECTIVES: We sought to identify the pattern of disturbed left ventricular physiology associated with symptom development in elderly patients with effort-induced breathlessness. BACKGROUND: Limitation of exercise tolerance by dyspnea is common in the elderly and has been ascribed to diastolic dysfunction when left ventricular cavity size and systolic function appear normal. METHODS: Dobutamine stress echocardiography was used in 30 patients (mean [+/-SD] age 70 +/- 12 years; 21 women, 9 men) with exertional dyspnea and negative exercise test results, and the values were compared with those in 15 control subjects. RESULTS: Before stress, left ventricular end-diastolic and end-systolic dimensions were reduced, fractional shortening was increased, and the basal septum was thickened (2.3 +/- 0.5 vs. 1.4 +/- 0.2 cm, p < 0.001, vs. control subjects) in the patients, but posterior wall thickness did not differ from that in control subjects. Left ventricular outflow tract diameter, measured as systolic mitral leaflet septal distance, was significantly reduced (13 +/- 4.5 vs. 18 +/- 2 mm, p < 0.001). Isovolumetric relaxation time was prolonged, and peak left ventricular minor axis lengthening rate was reduced (8.1 +/- 3.5 vs. 10.4 +/- 2.6 cm/s, p < 0.05), suggesting diastolic dysfunction. Transmitral velocities and the E/A ratio did not differ significantly. At peak stress, heart rate increased from 66 +/- 8 to 115 +/- 20 beats/min in the control subjects, but blood pressure did not change. Transmitral A wave velocity increased, but the E/A ratio did not change. Left ventricular outflow tract velocity increased from 0.8 +/- 0.1 to 2.0 +/- 0.2 m/s, and mitral leaflet septal distance decreased from 18 +/- 2 to 14 +/- 3 mm, p < 0.001. In the patients, heart rate rose from 80 +/- 12 to 132 +/- 26 beats/min and systolic blood pressure from 143 +/- 22 to 170 +/- 14 mm Hg (p < 0.001 for each), but left ventricular dimensions did not change. Peak left ventricular outflow tract velocity increased from 1.5 +/- 0.5 m/s (at rest) to 4.2 +/- 1.2 m/s; mitral leaflet septal distance fell from 13 +/- 4.5 to 2.2 +/- 1.9 mm (p < 0.001); and systolic anterior motion of mitral valve appeared in 24 patients (80%) but in none of the control subjects (p < 0.001). Measurements of diastolic function did not change. All patients developed dyspnea at peak stress, but none developed a new wall motion abnormality or mitral regurgitation. CONCLUSIONS: Although our patients fulfilled the criteria for "diastolic heart failure," diastolic dysfunction was not aggravated by pharmacologic stress. Instead, high velocities appeared in the left ventricular outflow tract and were associated with basal septal hypertrophy and systolic anterior motion of the mitral valve. Their appearance correlated closely with the development of symptoms, suggesting a potential causative link.     

Significance of the rate of systemic change in blood pressure on the short-term autoregulatory response in normotensive and spontaneously hypertensive rats

Cerebral autoregulation, the physiological regulatory mechanism that maintains a constant cerebral blood flow (CBF) over wide ranges of arterial blood pressure, was investigated in normotensive and spontaneously hypertensive rats by means of laser-Doppler flowmetry. Systemic arterial hypertension was produced at rates ranging from 0.02 mm Hg/second to 11 mm Hg/second by constant infusion of epinephrine and norepinephrine. Systemic arterial hypotension was produced at rates ranging from -0.03 mm Hg/second to -12 mm Hg/second, either by bleeding the animals into a reservoir or by compressing the abdomen. In those cases with a low rate of change in systemic arterial blood pressure (SABP), the measurements lasted for 5 +/- 2 minutes, and in those with a high rate of change in SABP, measurements lasted for 40 +/- 30 seconds. The purpose was to record the time of onset and course of autoregulation in the basal ganglia in response to slow or rapid changes in SABP. CBF in the basal gray matter remained at baseline values (i.e., autoregulation was functioning) if the rate of increase of SABP did not exceed a critical value (0.10 mm Hg/second in the normotensive rats; 0.35 mm Hg/second in the spontaneously hypertensive rats). When hypertension was produced at faster rates, CBF followed arterial blood pressure passively, and no autoregulatory response was observed for 2 +/- 1 minutes. Hypotension did not change the baseline CBF when it was not produced at a rate faster than -0.4 mm Hg/second in normotensive rats and -0.15 mm Hg/second in spontaneously hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)