Chronic double-level cauda equina compression. An experimental study on the dog cauda equina with analyses of nerve conduction velocity

STUDY DESIGN: Nerve conduction velocity was studied in the dog cauda equina subjected to chronic double-level compression. OBJECTIVES: To analyze the effects of chronic double-level cauda equina compression. SUMMARY OF BACKGROUND DATA: Double-level cauda equina compression produces more symptoms in patients and more changes in acute experimental set-ups than does single-level compression. However, there have been no controlled, experimental studies on chronic double-level compression. METHODS: A total of 20 dogs were anesthetized. Two balloons were placed under the lamina of the seventh lumbar vertebra and the first sacral vertebra, respectively. One week (10 mm Hg, n = 5; 0 mm Hg, n = 5) and 1 month (10 mm Hg, n = 5; 0 mm Hg, n = 5) after inflation with a viscous substance, nerve conduction velocity was studied by local electrical stimulation and recording of muscle action potentials in the tail muscles. RESULTS: Nerve conduction velocity was determined over the cranial balloon, the caudal balloon, and both balloons. The data were similar for all three recordings. After 1 week there was a significant reduction in nerve conduction velocity induced by 10 mm Hg, compared with that induced by 0 mm Hg, which showed normal conditions. However, after 1 month this initial reduction in nerve conduction velocity had recovered partially. The reduction was similar to that described for single-level compression in a previous study in which the same compression model was used. CONCLUSIONS: Unlike the acute situation, chronic double-level compression does not induce more changes than single-level compression after 1 week, although the recovery after 1 month of compression is less complete after double-level compression. This less complete recovery may be a result of an adaptation of the nerve tissue and the vascularization of the cauda equina nerve roots to the applied pressure.     

A study of effects of mouthwash on the human oral mucosae: with special references to sites, sex differences and smoking

Nitric oxide has been shown to decrease myocardial contractility and O2 consumption. This study was designed to evaluate the hypothesis that nitric oxide-mediated increases in cyclic GMP require elevated cyclic AMP to produce cardiac depression. Using isolated, Langendorff-perfused rat hearts, we determined the effects of intracoronary nitroprusside (NP, 1 and 10 mM) in the absence and presence of isoproterenol (ISO, 10(-8) M) on cardiac function, O2 consumption, cyclic GMP and cyclic AMP. ISO, with and without NP, increased cyclic AMP (from 287 +/- 21 to 477 +/- 33 pmol/g) without altering cyclic GMP. Left-ventricular pressure increased from 97 +/- 12 to 178 +/- 9 mm Hg and dP/dtmax from 1,786 +/- 275 to 4,049 +/- 354 mm Hg/s. NP increased cyclic GMP (from 4 to 30 pmol/g) in both the absence and presence of ISO, but NP did not alter cyclic AMP. Without ISO, NP insignificantly altered left-ventricular pressure; however, in the presence of ISO, NP significantly decreased left-ventricular pressure by -25 +/- 4 mm Hg and decreased dP/dtmax by -619 +/- 142 mm Hg/s. Isoproterenol increased O2 consumption, but the changes with NP were not significant. When this study was repeated in the presence of LY83583, a guanylate cyclase inhibitor, NP still produced cardiac depression in the presence of ISO. Therefore, cardiodepressant effects of NP were only observed against a background of inotropic stimulation with ISO. However, effects of NP on contractility were unrelated to increases in cyclic GMP or cyclic GMP-induced changes in cyclic AMP.     

The effect of changes in perfusion pressure on uteroplacental blood flow in the pregnant rabbit

The effect of perfusion pressure on uteroplacental blood flow was determined in pregnant rabbits utilizing the radioactive microsphere method. Control mean arterial pressure, 93 mm Hg +/- 2.6 SEM, was raised by carotid ligation to 109 +/- 4.1 mm Hg and then reduced with antihypertensive drugs to 74 +/- 1.3 mm Hg. Over this range of pressure there was no significant change in cardiac output, 605 +/- 36, 523 +/- 37, and 540 +/- 39 ml/min; or uteroplacental blood flow, 30 +/- 3.2, 27 +/- 5.2, and 29 +/- 4.5 ml/min, respectively. When prostaglandin synthesis was inhibited with either indomethacin or meclofenamate (2 mg/kg), uterine vascular resistance was higher but maintenance of uteroplacental flow occurred over a perfusion pressure of 89 +/- 6.7-115 +/- 9.3 mm Hg. With more severe hypotension induced with trimethaphan, control arterial pressure fell from 92 +/- 2.4 to 39 +/- 0.9 mm Hg, cardiac output fell from 514 +/- 17 to 407 +/- 22 ml/min (P less than 0.025) and uteroplacental blood flow fell from 6.1 +/- 0.9 to 2.5 +/- 0.9% of cardiac output (P less than 0.05), which represented an absolute fall from 32.4 +/- 5 to 10.6 +/- 3 ml/min (P less than 0.025). There was no significant change in renal blood flow expressed as percentage of cardiac output, 14.9 +/- 2 and 13 +/- 1.5%, or in absolute flow, 75 +/- 7.7 and 54 +/- 7 ml/min with trimethaphan-induced hypotension. These studies indicate that uteroplacental blood flow is maintained relatively constant over a range of perfusion pressure of 60-140 mm Hg in both normal and prostaglandin-inhibited pregnant rabbits. However, with reduction in pressure to 36-42 mm Hg, uteroplacental blood flow falls, expressed as a percentage of cardiac output and in absolute flow.     

Determination of the facility of aqueous humor outflow in the dog, comparing in vivo and in vitro tonographic and constant pressure perfusion techniques

The gross facility of aqueous humor outflow (C) was estimated in the normal in vivo and in vitro dog eye, using tonography and constant pressure perfusion. Tonographic C value for 36 normal eyes, with the dog anesthetized with ketamine hydrochloride and acetylpromazine maleate, was 0.21 (+/- 0.14, SD); the mean tonographic value in 35 eyes with the patient anesthetized with sodium pentobarbital was 0.15 (+/- 0.09). Constant pressure perfusion of the in vivo normal dog eyes at 20 mm of Hg intraocular pressure yielded a mean C value of 0.13 (+/- 0.07) and at 30 mm of Hg 0.18 (+/- 0.13). As intraocular pressure increased from 10 to 50 mm of Hg, the rate of outflow, as determined by constant pressure perfusion, increased. The C values from in vitro constant pressure perfusion were greater than those in the in vivo eyes and deceased in most eyes as intraocular pressure was increased as compared with the in vivo preparation.     

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.     

A comparison of the effects of doxazosin and terazosin on the spontaneous sympathetic drive to the bladder and related organs in anaesthetized cats

The effects of i.v. infusion of the alpha1-adrenoceptor antagonists doxazosin and terazosin (2 mg kg-1 h-1) on spontaneous hypogastric, renal and inferior cardiac nerve activity, spontaneous bladder contractions, blood pressure, heart rate and femoral arterial flow were investigated separately in alpha-chloralose-anaesthetized cats. Both drugs caused a reduction in hypogastric nerve activity associated with no overt changes in spontaneous bladder contractions. Doxazosin was more potent than terazosin, in that there was a significant reduction in hypogastric nerve activity after 20 min (0.67 mg kg-1) of infusion, while for terazosin this occurred after 40 min (1.33 mg kg-1). Both drugs also caused significant falls in blood pressure of 34 +/- 3 mm Hg and 33 +/- 4 mm Hg after 60 min. This was associated with no change in heart rate for doxazosin while terazosin caused an initial and significant increase in heart rate of 20 +/- 3 beats min-1 by 5 min, declining by 30 min to 1 +/- 5 beats min-1. This terazosin-induced tachycardia was associated with a significant increase in cardiac nerve activity of 128 +/- 22%. Both drugs caused increases in renal nerve activity however only for doxazosin was this increase significant. Femoral arterial conductance was also increased by both drugs, however, for doxazosin this increase was immediate and larger over the infusion period. These results demonstrate that alpha1-adrenoceptor antagonists can reduce sympathetic drive to the bladder and related organs.     

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)     

Prolonged severe hemorrhagic shock and resuscitation in rats does not cause subtle brain damage

OBJECTIVE: Some patients who survived severe hemorrhagic shock (HS) seem to exhibit persistent subtle neurobehavioral deficits. This finding is of concern if limited hypotensive fluid resuscitation is applied in hypotensive victims with penetrating trauma. This study was designed to determine whether subtle brain damage would occur in rats after severe prolonged HS. We hypothesized that rats surviving HS with mean arterial pressure (MAP) controlled at 40 mm Hg for 60 minutes would recover with slight permanent brain damage in terms of cognitive function without morphologic loss of neurons and that rats surviving HS with MAP at 30 mm Hg for 45 minutes (60 minutes were not tolerated) would have grossly abnormal brain function and loss of neurons. METHODS: Under light nitrous oxide-halothane anesthesia, spontaneously breathing rats underwent MAP-controlled HS (HS phase I), volume resuscitation to normotension and invasive monitoring to 60 minutes (resuscitation phase II), and observation to 10 days with detailed assessment of cognitive function (observation phase III). Five conscious rats served as normal controls. Three treatment groups were compared: group 1, shams (11 of 12 rats survived to 10 days); group 2, HS at MAP 40 mm Hg for 60 minutes (10 of 17 rats survived); group 3, HS at 30 mm Hg for 45 minutes (10 of 14 rats survived). RESULTS: On post-HS day 10, all normal controls and all survivors of all three groups were functionally normal with overall performance category = 1 (normal) (overall performance category 1 = normal, 5 = death) and neurologic deficit scores < or = 7% (neurologic deficit scores 0-10% = normal, 100% = brain death). Post-HS beam balance, beam walking, and Morris water maze test results in HS groups 2 and 3 showed latencies not significantly different from those in shams and normal controls. Light microscopic scoring of five selectively vulnerable brain regions and other regions in five coronal sections revealed no ischemic (pyknotic, shrunken, eosinophilic) neurons in any of the survivors to 10 days. There was no statistical difference between normal controls, sham animals, and both HS groups in the number of normal neurons counted in the hippocampal CA-1 region in the 10-day survivors. All nonsurvivors died with intestinal necrosis. CONCLUSION: HS at MAP 40 mm Hg for 60 minutes or MAP 30 mm Hg for 45 minutes does not cause subtle functional or histologic brain damage in surviving rats. Controlling MAP at 30 mm Hg carries a risk of sudden cardiac arrest. These data suggest that limited fluid resuscitation, to maintain MAP at about 40 mm Hg, as recommended for victims of penetrating trauma with uncontrolled HS, is safe for the brain.     

Cytochrome P-450 inhibition blocks bone resorption in vitro and in vivo

BACKGROUND AND METHODS: To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS: In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION: The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.     

Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration

Increased hydrostatic pressure in solid tumor nodules decreases the penetration of chemotherapy into cancerous tissue. This is true for both i.v. and i.p. chemotherapy. The purpose of this study was to determine the influence of increasing intra-abdominal pressures on the pharmacokinetics and tissue distribution of doxorubicin administered i.p. Four groups of 10 Sprague Dawley rats were given i.p. doxorubicin (4 mg/kg) during 60 min combined with no pressure (control), 10, 20 and 30 mm Hg pressures. During the course of i.p. chemotherapy, peritoneal fluid and blood were sampled. Two other groups of 10 rats received the same dose of i.p. doxorubicin during 10 min combined with no pressure and 30 mm Hg pressure. At the end of experiments animals were sacrificed and tissue samples were collected. Doxorubicin concentrations in peritoneal fluid, plasma and tissues were determined by HPLC. Pharmacokinetic studies showed that increased intra-abdominal pressures of 10, 20 and 30 mm Hg did not alter peritoneal fluid AUCs, the plasma AUCs and the peak ratios of i.p. doxorubicin when compared to the control group (no pressure). A subset analysis of high intra-abdominal pressure groups (20 and 30 mm Hg) versus control group showed statistically significant differences in peritoneal fluid AUCs, plasma AUCs and AUC (peritoneal fluid/plasma) ratios. For all groups, the highest tissue concentrations of doxorubicin were found in tissues associated with the parietal peritoneum: the bladder, the abdominal wall and the diaphragm. After 10 min of i.p. chemotherapy, the group treated with 30 mm Hg pressure showed a significant increase of doxorubicin concentrations in these tissues as compared to the control group. This significant increase of tissue doxorubicin concentrations was not found after 60 min of pressure with i.p. chemotherapy; prolonged intra-abdominal pressure was associated with a high incidence of intestinal ischemia. In conclusion, intra-abdominal pressure of 20 and 30 mm Hg significantly decreased the AUC ratios of i.p. doxorubicin but concomitantly increased tissue uptake of doxorubicin in bladder, diaphragm and abdominal wall during the first 10 min of i.p. administration. These findings may have significance in the design of improved strategies to increase tissue concentrations of chemotherapy delivered by an i.p. route.     

The content of electrolytes (Na, K, Ca, Mg) in vertebrate otoliths and otoconia

IVOX (intravenous oxygenator and CO2 removal device) augments venous gas exchange in patients with severe respiratory failure. Controlled hypoventilation with permissive hypercapnia reduces airway pressures during mechanical ventilation and augments CO2 exchange through the IVOX. To quantify the additive effects of gradual permissive hypercapnia and IVOX on gas exchange and reduction of airway pressures, 13 adult sheep underwent tracheostomy and severe smoke inhalation injury. Seven were mechanically ventilated alone (control), and six had mechanical ventilation, systemic anticoagulation, and implantation of IVOX (size 7 with 0.21-m2 surface area) (IVOX group). Both groups were anesthetized and paralyzed for 24 hr. In the IVOX group, minute ventilation was decreased in a stepwise fashion to produce a gradual increase in PaCO2, from 30 to 95 mm Hg, over 12 hr, and then sustained for an additional 12 hr. Sodium bicarbonate was given intravenously as necessary to keep arterial pH above 7.25. There were no significant differences in mean arterial pressure, cardiac output, or pulmonary artery pressure between the two groups. In the IVOX/permissive hypercapnia group, IVOX CO2 removal increased as a linear function of PaCO2 (y = 0.87x + 8.99, R2 = 0.80). IVOX CO2 removal was only 40 ml/min at normocapnia (40 mm Hg) but increased to 91 ml/min when PaCO2 was 95 mm Hg. Both peak inspiratory pressure and minute ventilation of the IVOX/permissive hypercapnia group were significantly lower than the control group, 30 +/- 4 mm Hg vs 51 +/- 3 mm Hg and 3.9 +/- 0.3 liters vs 8.4 +/- 0.5 liters (P < 0.05) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fetoplacental vascular tone during fetal circuit acidosis and acidosis with hypoxia in the ex vivo perfused human placental cotyledon

OBJECTIVES: Our purpose was to determine the effects of acidosis and acidosis-hypoxia on fetoplacental perfusion pressure and its response to angiotensin II. STUDY DESIGN: Perfused cotyledons from 14 placentas were studied with either an acidotic fetal circuit perfusate (n = 7) or an acidotic-hypoxic fetal circuit perfusate (n = 7). Each cotyledon's fetal vasculature was initially perfused under standard conditions and bolus injected with 1 x 10(-10) moles of angiotensin II. Fetoplacental perfusate was then replaced with either an acidotic medium (pH 6.90 to 7.00 and Po2 516 to 613 mm Hg) or an acidotic-hypoxic medium (pH 6.90 to 7.00 and Po2 20 to 25 mm Hg) followed by an angiotensin II injection. The vasculature was subsequently recovered with standard perfusate and again injected with angiotensin II. Perfusion pressures within each group were compared by one-way analysis of variance, and results were expressed as mean pressure +/- SEM. RESULTS: Resting fetoplacental perfusion pressure did not change when the fetal circuit perfusate was made acidotic (28 +/- 1 mm Hg vs 25 +/- 2 mm Hg) or acidotic-hypoxic (26 +/- 2 mm Hg vs 25 +/- 2 mm Hg). The maximal fetoplacental perfusion pressure achieved in response to angiotensin II did not differ with an acidotic perfusate (41 +/- 2 mm Hg vs 38 +/- 1 mm Hg) or with an acidotic-hypoxic perfusate (39 +/- 2 mm Hg vs 36 +/- 2 mm Hg). CONCLUSIONS: In the perfused placental cotyledon fetoplacental perfusion pressure and pressor response to angiotensin II are not affected by fetal circuit acidosis or acidosis-hypoxia. This suggests that neither fetal acidosis nor fetal acidosis combined with hypoxia has a direct effect on fetoplacental vascular tone.     

Measurement of intraocular pressure after epikeratophakia

AIMS: To assess the accuracy of three commonly used tonometers in eyes after epikeratophakia. METHODS: Five eye bank eyes with sutured epikeratophakia buttons were connected to a manometer and a pressure transducer. Intraocular pressure was adjusted in 5 mm Hg increments from 0 to 50 mm Hg. The intraocular pressure was measured at each increment using a Goldmann tonometer, a pneumatonometer, and a Tono-pen. RESULTS: The difference between the manometer (actual pressure) and the Goldmann tonometer ranged from -19 to +9 mm Hg (mean (SD) overestimation 2.6 (5.8) mm Hg). The pneumatonometer error ranged from -27.5 to +5.5 mm Hg (mean (SD) overestimation 4.7 (6.1) mm Hg), and for the Tono-pen the range was -18 to +11 mm Hg (mean (SD) overestimation 0.05 (7.9) mm Hg). The correlation coefficients for the three tonometers were 0.94, 0.92, and 0.87 for the Goldmann tonometer, pneumatonometer, and Tono-pen respectively. CONCLUSION: The Goldmann tonometer had the best correlation with the manometer in eye bank eyes with epikeratophakia (correlation coefficient 0.94), but none of the tonometers was accurate over the entire range of pressures tested. Detection of glaucoma in eyes with epikeratophakia cannot rely on tonometry alone, but requires examination of the optic nerve and visual field.     

Viscoelastic relaxation and regional blood flow response to spinal cord compression and decompression

STUDY DESIGN: To better understand the relationships between primary mechanical factors of spinal cord trauma and secondary mechanisms of injury, this study evaluated regional blood flow and somatosensory evoked potential function in an in vivo canine model with controlled velocity spinal cord displacement and real-time piston-spinal cord interface pressure feedback. OBJECTIVES: To determine the effect of regional spinal cord blood flow and viscoelastic cord relaxation on recovery of neural conduction, with and without spinal cord decompression. SUMMARY OF BACKGROUND DATA: The relative contribution of mechanical and vascular factors on spinal cord injury remains undefined. METHODS: Twelve beagles were anesthetized and underwent T13 laminectomy. A constant velocity spinal cord compression was applied using a hydraulic loading piston with a subminiature pressure transducer rigidly attached to the spinal column. Spinal cord displacement was stopped when somatosensory evoked potential amplitudes decreased by 50% (maximum compression). Six animals were decompressed 5 minutes after maximum compression and were compared with six animals who had spinal cord displacement maintained for 3 hours and were not decompressed. Regional spinal cord blood flow was measured with a fluorescent microsphere technique. RESULTS: At maximum compression, regional spinal cord blood flow at the injury site fell from 19.0 +/- 1.3 mL/100 g/min to 12.6 +/- 1.0 mL/100 g/min, whereas piston-spinal cord interface pressure was 30.5 +/- 1.8 kPa, and cord displacement measured 2.1 +/- 0.1 mm (mean +/- SE). Five minutes after the piston translation was stopped, the spinal cord interface pressure had dissipated 51%, whereas the somatosensory evoked potential amplitudes continued to decrease to 16% of baseline. In the sustained compression group, cord interface pressure relaxed to 13% of maximum within 90 minutes; however, no recovery of somatosensory evoked potential function occurred, and regional spinal cord blood flow remained significantly lower than baseline at 30 and 180 minutes after maximum compression. In the six animals that underwent spinal cord decompression, somatosensory evoked potential function and regional spinal cord blood flow recovered to baseline 30 minutes after maximum compression. CONCLUSIONS: Despite rapid cord relaxation of more than 50% within 5 minutes after maximum compression, somatosensory evoked potential conduction recovered only with early decompression. Spinal cord decompression was associated with an early recovery of regional spinal cord blood flow and somatosensory evoked potential recovery. By 3 hours, spinal cord blood flow was similar in both the compressed and decompressed groups, despite that somatosensory evoked potential recovery occurred only in the decompressed group.     

Mechanics of breathing in patients with atrial septal defect

Mechanics of breathing and pulmonary diffusing properties were investigated in 24 adult patients with atrial septal defect. The patients were divided into 3 groups according to mean pulmonary artery pressure: less than 19 mm Hg (group I), 20 to 24 mm Hg (group II), and greater than 25 mm Hg (group III). The only change observed in group I was a marked increase in diffusing capacity. Patients of group II showed not only an increase in diffusing capacity, but also an overt decrease in maximal expiratory flow at all lung volumes and at any given driving pressure. For these two groups, a highly significant inverse correlation was found between changes in diffusing and elastic lung properties (r = -0.71; P less than 0.001). In patients of group III, the expiratory flow remained clearly decreased; furthermore, lung compliance and lung volumes were sharply reduced, airway resistance was elevated, and diffusing capacity was normal. Finally, from group I to group III, the lung elastic recoil became progressively diminished at small lung volumes. These results suggest that an increased pulmonary blood volume induces an increase in diffusing capacity and a slight decrease in lung compliance. Simultaneous existance of high intravascular pressure strengthens the effects of increased pulmonary blood volume on lung mechanics and results in significant abnormalities in the lung mechanical behavior. It is postulated that these effects are due to a competition for space between vessels and airways within the bronchovascular sheaths, with a subsequent compression of small airways.     

Prognostic factors in restoration of pulmonary flow after submassive pulmonary embolism: a multiple regression analysis

There is now increasing evidence that high pulse pressure, which is an indicator of large artery stiffness, is an independent risk factor for cardiovascular mortality, especially coronary mortality, in different populations. We have recently shown in a large French population that in male subjects aged 40 to 69 years, increased pulse pressure was a strong predictor of cardiovascular mortality, especially coronary mortality. In the present report, we analyzed the effect of pulse pressure in men and women of the same cohort after classifying them as normotensive (systolic blood pressure [SBP] <140 mm Hg and DBP <90 mm Hg) or hypertensive (SBP >/=160 mm Hg or DBP >/=95 mm Hg). After adjustment for age, mean blood pressure, and other risk factors, the relative risk (95% confidence limits) for cardiovascular mortality for an increase of 10 mm Hg of pulse pressure was 1.20 (1.01 to 1.44) in normotensives and 1.09 (1.03 to 1.14) in hypertensives. Cardiovascular and coronary death rates were similar in the group of normotensive men with a pulse pressure >50 mm Hg and in the group of hypertensive men with a pulse pressure <45 mm Hg. No association between cardiovascular mortality and pulse pressure was observed in either normotensive or hypertensive women (0.85 [0.60 to 1.21] and 1.0 [0. 91 to 1.11], respectively). Low mortality rates could explain this observation in normotensive but not in hypertensive women, in whom cardiovascular mortality rates were relatively high. Because a high pulse pressure in men is an independent predictor of cardiovascular mortality in both hypertensives and in those considered as having normal blood pressure, this parameter could aid in evaluating cardiovascular risk.     

Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension

The efficacy and tolerability of extended-release felodipine (felodipine-ER) and nifedipine gastrointestinal therapeutic system (nifedipine GITS) were compared in a multicenter, prospective, open-label clinical trial of 277 patients with mild-to-moderate uncomplicated essential hypertension (sitting diastolic blood pressure [SiDBP] > or = 95 and < or = 115 mm Hg). After a 3-week washout period, patients were randomized to receive felodipine-ER (5 mg once daily) or nifedipine GITS (30 mg once daily); during a subsequent 6-week titration phase, the once-daily felodipine-ER dose could be increased to 10 mg and the nifedipine GITS dose to 60 or 90 mg in an attempt to achieve adequate blood pressure response (SiDBP < or = 90 mm Hg, or < 100 mm Hg with a > 10-mm Hg reduction from baseline, as measured 24 hours after dosing [trough]). At the end of titration, the mean daily doses of felodipine-ER and nifedipine GITS were 8 and 50 mg, respectively. Mean changes in sitting systolic blood pressure (SiSBP)/SiDBP were -14/-12 and -16/-13 mm Hg, respectively. All reductions were significant when compared with baseline (P < 0.01), but there were no significant differences between treatment groups. Adequate blood pressure response occurred in 77% of the felodipine-ER group and 80% of the nifedipine GITS group; this difference was not significant. Blood pressure changes were similar among sex and race subgroups. A higher percentage of older patients (> 55 years of age) than younger patients (< or = 55 years of age) reached goal SiDBP with both drugs. Patients with adequate SiDBP response continued receiving their assigned medication for an additional 6-week maintenance period. Reductions in SiDBP and SiSBP from baseline continued to be significant in both treatment groups. No clinically important changes in heart rate were noted. A total of 28 patients (15 in the felodipine-ER group and 13 in the nifedipine GITS group) withdrew from the study because of inadequate blood pressure response. At least one adverse experience occurred in 55% of the felodipine-ER group and 63% of the nifedipine GITS group, prompting withdrawal of 14 patients (10%) and 16 patients (11%), respectively. Headache and edema were the most common adverse experiences. The incidence and pattern of adverse experiences did not differ significantly between treatments. The results of this study demonstrate that once-daily felodipine-ER and nifedipine GITS are similarly highly effective and generally well tolerated in patients with essential hypertension.     

Activation of amylin gene transcription by LIM domain homeobox gene isl-1

The main objective of the Ambulatory Blood Pressure and Treatment of Hypertension (APTH) trial is to test the hypothesis that antihypertensive treatment based on ambulatory monitoring may be more beneficial than treatment guided by conventional sphygmomanometry. After a 2-month run-in period on single-blind placebo, hypertensive patients were randomized to two groups, one in which the target pressure was a sitting diastolic pressure from 80 through 89 mm Hg on conventional sphygmomanometry (conventional blood pressure [CBP] group), and one in which a daytime (from 10 to 20 h) diastolic pressure from 80 through 89 mm Hg had to be achieved (ambulatory blood pressure [ABP] group). After randomization all patients were started on lisinopril 10 mg/day. One month later lisinopril could be continued at 10 or 20 mg/day or discontinued depending on the attained blood pressure level. This article is an interim report on 207 patients followed for two months into the trial. At one month lisinopril was discontinued more frequently in the ABP than the CBP group (24 vs 9 patients, p = 0.004). Nevertheless at two months, blood pressure control was not significantly different in the two treatment groups. The baseline-adjusted differences in systolic pressure between the two treatment arms of the trial (ABP-CBP group) were +2.7 mm Hg (95% confidence interval [CI]): -2.9, +8.3) for the conventional pressure, +0.4 mm Hg (CI: -4.3, +5.1) for the 24 h pressure, -0.1 mm Hg (CI: -5.1, +4.8) for the daytime pressure and -0.7 mm Hg (CI: -6.7, +5.4) for the night-time pressure. The corresponding differences in diastolic pressure were -1.3 mm Hg (CI: -4, +1.4), +0.1 mm Hg (CI: -3, +3.1), -1.1 mmgH (CI: -4.4, +2.1) and +0.3 mm Hg (CI: -3.7, +4.3), respectively. Thus, the present findings do not refute the APTH research hypothesis. In terms of blood pressure control and the number of patients remaining on antihypertensive drugs, treatment based on ambulatory recordings may be preferable to treatment guided by conventional sphygmomanometry.     

Comparative effects of synthetic pentasaccharide, low-molecular-weight heparin, unfractionated heparin and recombinant hirudin on the generation of factor VIIa and prothrombin activation after coagulation of human plasma

OBJECT OF THE STUDY: The aim of the study was to assess, whether the pneumatic pressure of an antishock-trouser (AST) of 20-40 mm Hg induces a decreased oxygenation of the anterior tibial muscle and attenuates muscular response potential (MRP) of n. peronaeus profundus? METHODS: Among 22 normotensive, healthy volunteers the AST were tested by applying pressure values between 0 and 100 mm Hg and measuring the intracompartmental pressure, the muscular oxygen pressure as well as the MRP by electroneurographic means within a period of 6 hours. RESULTS: The median initial intracompartmental pressure value of the m. tibialis anterior was 12.0 mm Hg (Q25%/Q75%: 8.9/17.3), the muscular oxygen pressure 14.8 mm Hg (Q25%/Q75%: 11.5/22.0). Transmission of the pneumatic AST-leg segment pressure to the muscle: 97.7% (Q25%/Q75%: 89.2/99.8). Already in the low AST pressure field (20-40 mm Hg) a severe hypoxia occurred in one case. A reduction of MRP was noticed at an AST pressure rate of 10 mm Hg. In 5 of 6 cases AST pressure values of 60 mm Hg led to pathological pO2-values within 5-20 minutes. Almost without exception AST-pressure rates < 60 mm Hg resulted in an anoxia of the muscle and loss of the MRP. CONCLUSIONS: We should demand that the AST are only applied with models where the pressure generated within the single segments can be controlled by pressure gauge. The application of the AST seems to be justified for polytraumatised in severe haemorrhagic shock where the risk of a local tissue ischemia with systemical consequences must deliberately be accepted.     

Depression of cardiac function after deep hypothermic circulatory arrest in deeply anesthetized neonatal lambs

Cardiac dysfunction is common after neonatal cardiac operations. Previous in vivo studies in neonatal animal models however, have failed to demonstrate decreased left ventricular function after ischemia and reperfusion. Cardiac dysfunction may have been masked in these studies by increased endogenous catecholamine levels associated with the use of light halothane anesthesia. Currently, neonatal cardiac operations are often performed with deep opiate anesthesia, which suppresses catecholamine surges and may affect functional recovery. We therefore examined the recovery of left ventricular function after ischemia and reperfusion in neonatal lambs anesthetized with high-dose fentanyl citrate (450 micrograms/kg administered intravenously). Seven intact neonatal lambs with open-chest preparation were instrumented with left atrial and left ventricular pressure transducers, left ventricular dimension crystals, and a flow transducer. The lambs were cooled (< 18 degrees C) on cardiopulmonary bypass (22 +/- 6 minutes), exposed to deep hypothermic circulatory arrest (46 +/- 1 minutes), and rewarmed on cardiopulmonary bypass (30 +/- 10 minutes). Catecholamine levels and indexes of left ventricular function were determined before (baseline) and 30, 60, 120, 180, and 240 minutes after termination of cardiopulmonary bypass. Levels of epinephrine, norepinephrine, and dopamine were unchanged from baseline values. Left ventricular contractility (slope of end-systolic pressure-volume relationship) was depressed from baseline value (31.7 +/- 9.3 mm Hg/ml) at 30 minutes (15.7 +/- 6.4 mm Hg/ml) and 240 minutes (22.7 +/- 6.4 mm Hg/ml) but unchanged between 60 and 180 minutes. Left ventricular relaxation (time constant of isovolumic relaxation) was prolonged from baseline value (19.0 +/- 3.0 msec) at 30 minutes (31.4 +/- 10.0 msec) and 240 minutes (22.1 +/- 2.8 msec) but unchanged between 60 and 180 minutes. Afterload (left ventricular end-systolic meridional wall stress) was decreased at 30, 60, and 240 minutes. Indexes of global cardiac function (cardiac output, stroke volume), preload (end-diastolic volume), and left ventricular compliance (elastic constant of end-diastolic pressure-volume relationship) were unchanged from baseline values. In deeply anesthetized neonatal lambs exposed to ischemia and reperfusion, left ventricular contractility, relaxation, and afterload are markedly but transiently depressed early after reperfusion and mildly depressed late after reperfusion.