Continuous monitoring of brain tissue PO2: a new tool to minimize the risk of ischemia caused by hyperventilation therapy

Secondary ischemic events worsen the outcome of patients with severe head injury. Such a secondary ischemic event may be caused by a forced hyperventilation. A consequence of the induced vasoconstriction is the risk of ischemia with an adverse effect on outcome. As a reliable and on-line technique, brain tissue pO2 (p(ti)O2) is used for monitoring regional microcirculation, to detect critical hypoperfusion. On 22 patients with a severe head injury 70 hyperventilation tests were performed from day 0-9 after trauma, calculating TCD-CO2-reactivity (% change of mean flow velocity per mm Hg paCO2 change). Additionally brain p(ti)O2-CO2-reactivity (% change of brain p(ti)O2 per mm Hg paCO2 change) was calculated and introduced. Group A +2 (p(ti)O2 < or = 15 mm Hg, TCD-CO2-reactivity > or = 2.5%, p(ti)O2-CO2-reactivity > 0%) and group B +2 (p(ti)O2 > 15 mm Hg, TCD-CO2-reactivity > or = 2.5%. p(ti)O2-CO2-reactivity > 0%) was formed. P(ti)O2 values in group A+2 decreased to an ischemic level or ischemia aggravated during hyperventilation. In group B+2 no ischemic events occurred. TCD-CO2-reactivity, p(ti)O2-CO2-reactivity and decrease of paCO2 were not significantly different in both groups. 6 out of 22 patients showed, from day 0-9, at least once a risk of (aggravating) ischemia by hyperventilation therapy.     

A model for the extended studies of hepatic hemodynamics and metabolism in swine

To our knowledge postoperative hepatic hemodynamics and hepatic metabolism have not been fully studied on a long-term basis. Our goal was to develop a large animal model that would permit the measurement of hepatic blood flow (BF), perihepatic pressures (P), and hepatic metabolism in a long-term setting. Catheters were inserted into the jugular vein, carotid artery, pulmonary artery, hepatic vein, and portal vein (PV) of 27 commercially bred pigs; ultrasonic transit time flowmeter probes were placed around the hepatic artery and PV. Daily postoperative measurements of jugular vein P, carotid artery P, pulmonary artery P, hepatic vein P, and PVP, as well as hepatic artery BF and PVBF, were recorded for 20 days. Hepatic carbohydrate metabolism was assessed by arteriovenous difference techniques. Jugular vein P, pulmonary artery P, hepatic vein P, PVP, and heart rate reached steady-state values during the first week, with a mean +/- SEM of 1.0 +/- 0.3 mm Hg for jugular vein P, 21.4 +/- 2.1 mm Hg for pulmonary artery P, 4.3 +/- 0.4 mm Hg for HVP, 7.8 +/- 0.5 mm Hg for PVP, and 116 +/- 4 beats per minute for heart rate. Mean carotid artery P increased from 65 +/- 3 mm Hg during surgery to 94 +/- 2 mm Hg on postoperative day 1 (P < 0.001) and to a mean 101 +/- 2 mm Hg thereafter. Total hepatic BF reached a steady-state value of 1,132 +/- 187 ml/min by postoperative day 7 (P = 0.19). Over week 1 hepatic artery BF measured as a percentage of total hepatic BF decreased from 35.0 +/- 3.0% to 15.5 +/- 2.7%, and PVBF increased from 65.0 +/- 3.0% to 84.5 +/- 2.7% (P < 0.005); both variables were steady thereafter. In the hemodynamic steady state the net hepatic balances of glucose, lactate, glycerol, and alanine in 5 pigs were 9.9 +/- 4.0, -4.2 +/- 0.4, -2.3 +/- 1.1, and -0.68 +/- 0.22 micromol/kg per min respectively. The net gut (portal-drained viscera) balances of glucose, lactate, alanine, and glycerol were -2.0 +/- 2.5, 1.1 +/- 0.5, 0.73 +/- 0.18, and -0.69 +/- 0.19 micromol/kg per min respectively. Thus, a reliable large animal model was developed to study acute and chronic hepatic hemodynamics and metabolism.     

A comparison of manual and controlled-force attachment-level measurements

This study compared the intra-examiner and inter-examiner error of 2 constant force probes to the reading of a conventional manual probe. 3 examiners made repeated examinations of attachment level using a modified Florida probe and a manual North Carolina probe (read to 1 mm or 0.5 mm); relative attachment level measurements were made using a Florida disk probe. One probe was used in each quadrant in 8 subjects with moderate to advanced periodontitis. Error was calculated as the mean of the absolute value of the difference between each examination, and the correlation between values at each examination calculated. Statistically-significant differences between probe type, examiners, and sites were detected using a repeated measures ANOVA accounting for the nesting within subjects. There was a significant difference in error by probe type (modified Florida probe 0.62 +/- 0.03 mm, r = 0.86; Florida stent probe 0.55 +/- 0.05 mm, r = 0.82; manual probe to 1 mm 0.39 +/- 0.02 mm, r = 0.88; manual probe to 0.5 mm 0.40 +/- 0.02 mm, r = 0.89; (p < 0.001). Significant differences were observed by examiners (p < 0.01). These data indicate that both manual and controlled-force probes can provide measurement within less than 1 mm of error; however, individual calibration of examiners remains important in the reduction of error.     

Pulmonary hemodynamics and plasma endothelin-1 during hypoxemia and reoxygenation with room air or 100% oxygen in a piglet model

The immediate effect on the pulmonary circulation of reoxygenation with either room air or 100% O2 was studied in newborn piglets. Hypoxemia was induced by ventilation with 8% O2 until base excess was <-20 mmol/L or mean arterial blood pressure was <20 mm Hg. Reoxygenation was performed with either room air (n = 9) or 100% O2 (n = 9). Mean pulmonary artery pressure increased during hypoxemia (p = 0.012). After 5 min of reoxygenation, pulmonary artery pressure increased further from 24 +/- 2 mm Hg at the end of hypoxemia to 35 +/- 3 mm Hg (p = 0.0077 versus baseline) in the room air group and from 27 +/- 3 mm Hg at the end of hypoxemia to 30 +/- 2 mm Hg (p = 0.011 versus baseline) in the O2 group (NS between groups). Pulmonary vascular resistance index increased (p = 0.0005) during hypoxemia. During early reoxygenation pulmonary vascular resistance index decreased rapidly to values comparable to baseline within 5 min of reoxygenation in both groups (NS between groups). Plasma endothelin-1 (ET-1) decreased during hypoxemia from 1.5 +/- 0.1 ng/L at baseline to 1.2 +/- 0.1 ng/L at the end of hypoxemia (p = 0.003). After 30 min of reoxygenation plasma ET-1 increased to 1.8 +/- 0.3 and 1.5 +/- 0.2 ng/L in the room air and O2 groups, respectively (p = 0.0077 in each group versus end hypoxemia; NS between groups). We conclude that hypoxemic pulmonary hypertension and plasma ET-1 normalizes as quickly when reoxygenation is performed with room air as with 100% O2 in this hypoxia model with newborn piglets.     

Reduction of a model for an Onchidium pacemaker neuron

Local brain tissue oxygenation (p(ti)O2) and global cerebrovenous hemoglobin saturation (SjO2) are increasingly used to continuously monitor patients after severe head injury (SHI). In patients, simultaneous local and global oxygen measurements of these types have shown different results regarding the comparability of the findings during changes in CPP and ICP. This is in contrast to theoretical expectations. The aim of this study was to compare p(ti)O2 measurement with cerebrovenous oxygen partial pressure measurement (p(cv)O2) in an animal intracranial pressure model. To this end, a multisensor probe was placed in the left frontoparietal white matter to measure p(ti)O2, pCO2 (p(ti)CO2), pH (pH[ti]), and temperature (t[ti]) while simultaneously measuring these same parameters (p(cv)O2, p(cv)CO2 pH(cv), t[cv]) in the sagittal sinus of 9 pigs under general anesthesia. By stepwise inflating a balloon catheter, placed in supracerebellar infratentorial compartment, ICP was increased and CPP was decreased. The baseline levels of p(ti)O2, p(ti)CO2, and pH(ti) in the noninjured brain tissue showed more heterogeneity compared to the findings in cerebrovenous blood. Both, p(ti)O2 and p(cv)O2 were significantly correlated to the induced CPP decrease. PCO2 was inversely correlated to the course of CPP in both measurement compartments. Temperature measurement showed a positive correlation with CPP in both compartments. These findings demonstrate that brain tissue oximetry and cerebrovenous PO2 measurement are sensitive to CPP changes. The newly available continuous parameters in multisensor probes could be helpful in interpreting findings of cerebral oxygen measurement in man by analyzing the interrelationship of these parameters.     

Pulmonary hypertension after transjugular intrahepatic portosystemic shunt: effects on right ventricular function

The short- and mid-term hemodynamic effects of transjugular intrahepatic portosystemic shunt (TIPS) were studied in 16 sedated cirrhotic patients. Indications included relapsing variceal bleeding (n = 10) and refractory ascites (n = 6). The decrease of porto-atrial pressure gradient (from 20.4 +/- 4.2 mm Hg to 10.1 +/- 2.4 mmHg; P < .05) was associated with an increase of mean pulmonary artery pressure (MPAP) (from 12.3 +/- 3.0 mm Hg to 20.3 +/- 5.3 mm Hg; P < .05) and of right atrial pressure (RAP) from 3.4 +/- 2.6 mm Hg to 8.3 +/- 3.7 mm Hg; P < .05), whereas right ventricular end-diastolic volume (RVEDVI) remained unchanged. The significant increase of cardiac index (CI) (from 4.5 +/- 1.2 L/min/m2 to 5.0 +/- 1.1 L/min/m2; P < .05) was essentially attributable to an increase of heart rate (HR) (from 81 +/- 11 to 88 +/- 10 beats/min; P < .05). Systemic vascular resistance (SVR) decreased (from 812 +/- 281 to 666 +/- 191 dynes/sec/cm5; P < .05), whereas pulmonary vascular resistance (PVR) increased (from 60.6 +/- 29.6 to 82.0 +/- 34.6 dynes/sec/cm5; P < .05). After transient shunt occlusion with a balloon catheter, all of the hemodynamic parameters returned to baseline values, except pulmonary artery pressure, which also decreased but remained significantly increased. One month after TIPS, pulmonary pressure remained elevated, and CI further increased. It is concluded that increased PVR is the major hemodynamic alteration occurring after TIPS placement. It correlates with the decrease of porto-atrial gradient and is probably mediated by both mechanical and neurohumoral factors.     

Intracranial pressure and cerebral perfusion pressure in clinically normal equine neonates

Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were determined in 8 clinically normal neonatal foals. After the foals oriented themselves and nursed the mares, they were sedated as necessary, and local anesthesia was provided for making the skin incisions. Using a technique similar to that used in human beings, an indwelling subdural catheter was placed to measure ICP. Carotid artery catheterization was used to measure arterial blood pressure. Cerebral perfusion pressure was calculated as the difference between mean arterial blood pressure and ICP. Intracranial pressure and CPP readings were taken twice during each 24-hour period, starting at 6 hours of age and continuing through 72 hours of age. Mean (+/- SD) ICP were 5.83 +/- 1.82, 8.81 +/- 2.06, and 9.55 +/- 1.55 mm of Hg (range, 2 to 15 mm of Hg), and mean CPP were 80.19 +/- 10.34, 75.30 +/- 10.86, and 76.80 +/- 12.59 mm of Hg (range, 50 to 109 mm of Hg) for each of the first three 24-hour periods after birth, respectively. All 8 foals had physical and neurologic examinations, CSF analysis, and computerized axial tomography evaluations. The foals manifested normal behavior during the interval of measurements, and adverse effects of the procedure were not detected during the monitoring period. Establishment of normal values for ICP and CPP are important to clinicians who have the opportunity to apply this technique for monitoring and evaluating neonatal foals with signs of CNS dysfunction.     

Transport of amino acid aryl amides by the intestinal H+/peptide cotransport system, PEPT1

The oxygen tension (PO2) in the renal cortex and outer renal medulla in 26 rats was studied by use of oxygen microelectrodes before and after injection of x-ray contrast media (CM). The CM, iopromide, ioxaglate and iotrolan were administrated intravenously in iodine equivalent doses (1,600 mg iodine/kg body wt). Ringer's solution was used as the control. In the outer medulla, all three CM induced a decrease in PO2: iopromide (N = 6) from 30 +/- 3 to 18 +/- 4 mm Hg; ioxaglate (N = 7) from 32 +/- 6 to 15 +/- 4 mm Hg; and iotrolan (N = 6) from 36 +/- 3 to 14 +/- 4 mm Hg. All these decreases were significant. After the injection of Ringer's (N = 7) there was an increase from 34 +/- 3 to 35 +/- 3 mm Hg. In the cortex a slight decrease was noted for injection of CM, but this was significant only after injection of iotrolan. All tested contrast media decrease PO2 in the outer renal medulla, which may partly explain contrast medium-induced acute renal failure.     

Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts

OBJECTIVES: The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. BACKGROUND: Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. METHODS: The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. RESULTS: Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p < 0.0001; MCI-154: from 3.36 +/- 1.26 to 5.37 +/- 2.14 mm Hg/ml per m2, p < 0.0001); dobutamine increased total Vo2 (from 0.22 +/- 0.08 to 0.27 +/- 0.09 ml O2, p < 0.05) and PVA-independent Vo2 (from 0.019 +/- 0.019 to 0.091 +/- 0.051 ml O2, p < 0.005); but MCI-154 did not change these variables significantly. Consequently, the oxygen cost of contractility (delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p < 0.05). CONCLUSIONS: These results suggest that the cardiotonic action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.     

Efficacy of dead-space washout in mechanically ventilated premature newborns

The prosthetic dead space makes a significant contribution to the total dead space in low-birth-weight premature newborns receiving artificial ventilation in response to respiratory distress. Use of an endotracheal tube with capillaries molded into the tube wall enables washout of the dead space without insertion of a tracheal catheter. In 10 premature newborns (mean gestational age, 27.5 +/- 2.2 wk; mean weight, 890 +/- 260 g) receiving continuous positive-pressure ventilation (Paw = 12.7 +/- 1.8 cm H2O; FIO2 = 39 +/- 17%), tracheal gas insufflation (TGI) for CO2 washout was conducted using this technique. The flow of tracheal insufflation (0.5 L/min) was derived from the inspiratory line of the ventilator circuit and blown into the trachea. Intratracheal pressures showed little or no TGI-related modification ( < 1 cm H2O). A control system enabled TGI discontinuation in the event of a pressure rise. At constant ventilation pressure, PaCO2 decreased by 12.1 +/- 5.9 mm Hg (delta PaCO2 = -26 +/- 12%) under TGI, whereas PaO2 remained unchanged. While maintaining PaCO2 constant, peak inspiratory pressure (PIP) was decreased by 5.4 +/- 1.7 cm H2O (delta PIP = -22.0 +/- 8.3%). TGI showed immediate efficacy (PCO2 reduction of at least 5 mm Hg) in nine of the 10 newborns who then received chronic TGI (14 to 138 h). TGI appears to be an effective method, suitable for long-term clinical application, enabling a reduction in the aggressive nature of conventional ventilation.     

Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group

BACKGROUND: Improvement of angina pectoris symptoms after cholesterol lowering has raised questions as to the underlying mechanisms. METHODS: Rabbit experiment: We compared arterial blood samples from New Zealand White cholesterol-supplemented rabbits (n = 6) with nonsupplemented rabbit samples (n = 4) in a closed-loop circulation diffusion system. The pH and partial pressures of oxygen (pO2) and carbon dioxide (pCO2) were measured continuously. The samples were first oxygen (O2) saturated (pO2, 160 mm Hg; pCO2, 4 mm Hg) and then desaturated in 100% nitrogen. Cholesterol levels were determined in whole blood, plasma (P Chol), red blood cells (RBCs), and RBC membranes. Human experiment: We exposed quadruple desaturated venous blood samples (n = 4) with P Chol levels of 87 to 400 mg/dL in a gas exchanger to capillary gas conditions (pO2, 23 mm Hg; pCO2, 46 mm Hg). After 15 minutes we performed blood gas analyses and compared our results to baseline values. RESULTS: In the rabbit experiment the cholesterol-supplemented group as compared to the control group showed higher plasma pO2 levels during the saturation phase and lower plasma pO2 levels during the desaturation phase. It also had a markedly increased RBC membrane cholesterol content: 121 +/- 3 (standard error of the mean [SEM]) mg/dL versus 22 +/- 1.7 mg/dL in the control group (P < .05). This barrier to RBC membrane O2 diffusion caused delayed O2 entry into the RBCs during saturation, with a higher plasma pO2, and delayed O2 release from the RBCs during desaturation, with a lower plasma pO2. In the human experiment the P Chol level was inversely correlated with the percentage change of O2 content in milliliters of O2 per deciliter of blood (P < .05). CONCLUSIONS: Increased RBC membrane cholesterol in hypercholesterolemia appears to decrease the transmembrane O2 diffusion rate.     

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.     

Genetic variation at the short tandem repeat loci HumvWA, HumFXIIIB, and HumFES/FPS in the Egyptian and Yemenian populations

Eighteen head-injured patients undergoing hyperventilation were studied for changes in jugular venous oxygen saturation (SjvO2) and arteriovenous oxygen content difference (AVDO2) in response to changes in PaO2 and PaCO2. SjvO2 decreased significantly from 66% +/- 3% to 56% +/- 3% (mean +/- SD) when PaCO2 decreased from 30 to 25 mm Hg at a PaO2 of 100-150 mm Hg. SjvO2 values returned to baseline (66% +/- 2%) when PaCO2 was restored to 30 mm Hg. Repetition of the study at a PaO2 of 200-250 mm Hg produced a similar pattern. However, SjvO2 values were significantly greater with PaO2 within the range of 200-250 mm Hg (77% +/- 4% and 64% +/- 3%) than SjvO2 measured at a PaO2 of 100-150 mm Hg at PaCO2 values of both 30 and 25 mm Hg. AVDO2 also improved with a PaO2 of 200-250 mm Hg at each PaCO2 (P < 0.001). In conclusion, decreases in SjvO2 associated with decreases in PaCO2 may be offset by increasing PaO2. IMPLICATIONS: The adequacy of cerebral oxygenation can be estimated in head-injured patients by monitoring jugular bulb oxygen saturation and the arteriovenous oxygenation content difference. Increasing the partial pressure of arterial oxygen above normal offset deleterious effects of hyperventilation on jugular bulb oxygen saturation and arteriovenous oxygenation content difference in head-injured patients.     

Comparative accuracy of three automated techniques in the noninvasive estimation of central blood pressure in men

Automated devices have regularly replaced manual sphygmomanometry for the determination of blood pressure not only in homes and clinics, but also in emergency and critical care settings. Few studies exist that correctly assess the accuracy of these devices, and even fewer that specifically compare commercially available units that rely on different physiologic events for measurement. Six hundred pressure measurements were obtained from 120 subjects using 1 of 3 randomly selected blood pressure monitors. In addition, central arterial pressure measurements were obtained simultaneously and directly from the ascending aorta of each subject. Overall, these devices tended to overestimate diastolic (+2.5 mm Hg, p < 0.0001) and mean (+3.8 mm Hg, p < 0.0001) pressures, but not systolic (+0.7 mm Hg, p = NS) pressure. Compared with the other 2 devices, device I, relying on oscillometric detection, demonstrated a significantly smaller mean absolute error for diastolic pressure (4.9 +/- 3.0 vs 7.0 +/- 4.8 and 6.2 +/- 5.3 mm Hg, p < 0.0001) and mean pressure (4.0 +/- 3.2 vs 7.8 +/- 5.9 and 8.6 +/- 7.5 mm Hg, p < 0.0001), and a trend toward smaller error with systolic pressure (6.8 +/- 6.5 vs 7.3 +/- 6.8 and 8.0 +/-5.6 mm Hg, p = 0.19). Clinically significant (+/-10 mm Hg) errors were common with each device (24.8% overall), but serious (+/-20 mm Hg) errors were unusual (3.2%) and did not occur at all with device I during diastolic and mean pressure measurement. All of the devices tested could be expected to perform satisfactorily in most clinical settings provided that an average error of 4.0 to 8.6 mm Hg is tolerable. This level of accuracy typically extended throughout the range of pressures anticipated in most noncritical clinical situations. As implemented in the devices tested, noninvasive measurement by oscillometry with stepped deflation is more accurate than automated auscultation.     

Evaluation of a pulsatile pediatric ventricular assist device in an acute right heart failure model

BACKGROUND: The development of pulsatile ventricular assist devices for children has been limited mainly by size constraints. The purpose of this study was to evaluate the MEDOS trileaflet-valved, pulsatile, pediatric right ventricular assist device (stroke volume = 9 mL) in a neonatal lamb model of acute right ventricular failure. METHODS: Right ventricular failure was induced in ten 3-week-old lambs (8.6 kg) by right ventriculotomy and disruption of the tricuspid valve. Control group 1 (n = 5) had no mechanical support whereas experimental group 2 (n = 5) had right ventricular assist device support for 6 hours. The following hemodynamic parameters were measured in all animals: heart rate and right atrial, pulmonary arterial, left atrial, and systemic arterial pressures. Cardiac output was measured by an electromagnetic flow probe placed on the pulmonary artery. RESULTS: All results are expressed as mean +/- standard deviation and analyzed by Student's t test. A p value less than 0.05 was considered statistically significant. Base-line measurements were not significantly different between groups and included systemic arterial pressure, 80.6 +/- 12.7 mm Hg; right atrial pressure, 4.6 +/- 1.6 mm Hg; mean pulmonary arterial pressure, 15.6 +/- 4.2 mm Hg; left atrial pressure, 4.8 +/- 0.8 mm Hg; and cardiac output, 1.4 +/- 0.2 L/min. Right ventricular injury produced hemodynamics compatible with right ventricular failure in both groups: mean systemic arterial pressure, 38.8 +/- 10.4 mm Hg; right atrial pressure, 16.8 +/- 2.3 mm Hg; left atrial pressure, 1.4 +/- 0.5 mm Hg; and cardiac output, 0.6 +/- 0.1 L/min. All group 1 animals died at a mean of 71.4 +/- 9.4 minutes after the operation. All group 2 animals survived the duration of study. Hemodynamic parameters were recorded at 2, 4, and 6 hours on and off pump, and were significantly improved at all time points: mean systemic arterial pressure, 68.0 +/- 13.0 mm Hg; right atrial pressure, 8.2 +/- 2.3 mm Hg; left atrial pressure, 6.4 +/- 2.1 mm Hg; and cardiac output, 1.0 +/- 0.2 L/min. CONCLUSIONS: The results demonstrate the successful creation of a right ventricular failure model and its salvage by a miniaturized, pulsatile right ventricular assist device. The small size of this device makes its use possible even in small neonates.     

Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure. A double-blind, placebo-controlled, randomized crossover trial

BACKGROUND: The pharmacological effects of infusion of human brain natriuretic peptide (hBNP) in patients with severe congestive heart failure have not been characterized previously. METHODS AND RESULTS: Twenty patients with severe congestive heart failure were randomized in a double-blind, placebo-controlled, crossover trial to receive incremental 90-minute infusions of hBNP (0.003, 0.01, 0.03, and 0.1 microgram/kg per minute) or placebo on 2 consecutive days. At the highest completed dose of the hBNP, mean pulmonary artery pressure decreased from 38.3 +/- 1.6 to 25.9 +/- 1.7 mm Hg; mean pulmonary capillary wedge pressure decreased from 25.1 +/- 1.1 to 13.2 +/- 1.3 mm Hg; mean right atrial pressure decreased from 10.9 +/- 1 to 4.8 +/- 1.0 mm Hg; mean arterial pressure decreased from 85.2 +/- 2.0 to 74.9 +/- 1.7 mm Hg; and cardiac index increased from 2.0 +/- 0.1 to 2.5 +/- 0.1 L/min per square meter (all P < .01 versus placebo). Urine volume and urine sodium excretion increased significantly during hBNP infusion when compared with placebo infusion (90 +/- 38 versus 67 +/- 27 mL/h and 2.6 +/- 2.4 versus 1.4 +/- 1.2 mEq/h, respectively, both P < .05 versus placebo), whereas creatinine clearance and urinary potassium excretion did not change. CONCLUSIONS: Infusion of incremental doses of hBNP is associated with favorable hemodynamic and natriuretic effects in patients with severe congestive heart failure.     

Mechanisms underlying the antireflux effect of Nissen fundoplication in children

BACKGROUND/PURPOSE: It is reported that the main mechanism responsible for gastroesophageal reflux (GER) is transient lower esophageal sphincter (LES) relaxation in children. However, the effect of Nissen fundoplication on transient LES relaxation has not been investigated in children. This study examined the effect of Nissen fundoplication on motor patterns of the LES in children with pathological GER. METHODS: Esophageal manometry and pH were recorded concurrently for 2 hours after administration of apple juice (10 mL/kg). In seven children documented to have pathological GER by prolonged esophageal pH monitoring (%time pH less than 4.0>5.0), studies were performed preoperatively and 1 to 3 months after surgery. RESULTS: Nissen fundoplication virtually eliminated reflux in all patients. Percentage of time pH was less than 4.0 reduced from 15+/-9 to 0+/-0. Basal LES pressure did not change significantly (pre, 21+/-10 mm Hg v post, 27+/-9 mm Hg). The number of transient LES relaxation reduced significantly from 13+/-4 to 7+/-7, and the mean nadir LES pressures during swallow-induced LES relaxation and transient LES relaxation increased significantly from 1+/-1 mm Hg to 13+/-5 mm Hg and from 0+/-0 mm Hg to 11+/-7 mm Hg, respectively. CONCLUSIONS: Our findings suggest the antireflux effects of Nissen fundoplication may be based on changes of LES motor patterns that result in incomplete LES relaxation and reduction of the number of transient LES relaxation.     

Epidemiology of extrapulmonary tuberculosis among persons with AIDS in the United States

We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32 patients with mild to moderate essential hypertension (EH). After a 2-week single-blind, placebo run-in period, patients were randomized in a double-blind, parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week period. At the end of the placebo period and during the last week of treatment, patients underwent 24-h ABPM. Initial office BP mean values were similar in both groups (169.8 +/- 14/102.5 +/- 6 vs. 167.1 +/- 14/98.7 +/- 5 mm Hg, respectively, p = NS). A comparable decrease in office mean values of systolic BP (SBP, -22.3 +/- 13 vs. -19.1 +/- 16 mm Hg) and diastolic BP (DBP, -12.0 +/- 5 vs. -8.1 +/- 8 mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly between patients treated with AM or NTR with regard to 24-h SBP (120.0 +/- 10 vs. 132.5 +/- 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3 +/- 6 vs. -5.2 +/- 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 +/- 4 vs. -3.7 +/- 6 mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate (HR). At equivalent once-daily dosage, AM was more effective than NTR in decreasing BP assessed by 24-h ABPM.     

CDTect-RIA and CDTect-EIA for determination of serum carbohydrate-deficient transferrin compared

Little is known of the factors that regulate CBF in sleep. We therefore studied 10 lambs to assess the vasodilatory processes that underlie cerebral autoregulation during sleep. Lambs, instrumented to measure CBF (flow probe on the superior sagittal sinus), sleep state, and cerebral perfusion pressure (CPP), were rapidly made hypotensive by inflating a cuff around the brachiocephalic artery to reduce CPP to 30 mm Hg in each state. During control periods, cerebral vascular resistance (CVR in mm Hg/mL/min) was lower in active sleep (2.8 +/- 0.3, mean +/- SD, P < or = 0.001) than in wakefulness (3.9 +/- 0.6) and quiet sleep (4.3 +/- 0.6). The CVR decreased promptly in each state as CPP was lowered. The time (seconds) required for maximal cerebral vasodilation to occur was longer in active sleep (35 +/- 11) than in quiet sleep (20 +/- 6, P < or = 0.001) and wakefulness (27 +/- 11, P < or = 0.05). The CVR decreased less in active sleep (0.6 +/- 0.3, P < or = 0.001) than in quiet sleep (1.5 +/- 0.3), although the changes in CPP induced with brachiocephalic occlusion were equal in each state. In conclusion, our studies provide the first evidence that the vasoactive mechanisms that underlie autoregulation of the cerebral circulation function during sleep. Moreover, our data reveal that the speed and the magnitude of the vasodilatory reserves available for autoregulation are significantly less in active sleep than in quiet sleep.     

Effects of alpha1-blockade on the forearm vascular resistance responses to lower body negative pressure in young borderline hypertensives

To determine whether alpha1-blockade affects the forearm vascular resistance responses to lower body negative pressure (LBNP) in borderline hypertensives, six hypertensives (HTN; mean arterial pressure [MAP] = 109.9 +/- 1.7 mm Hg, mean +/- SE) and seven normotensives (NTN; MAP = 81.5 +/- 1.4 mm Hg) underwent exposures of LBNP at pressures of -10, -20, and -40 mm Hg during systemic alpha1-receptor blockade (BLK) and during placebo (PLA). Resting forearm vascular resistance (FVR) was greater in HTN than in NTN during PLA (34.8 +/- 5.4 v 17.5 +/- 3.1 units; P < .05), but not during BLK (28.1 +/- 5.2 v 25.3 +/- 9.9 units). When expressed as a percentage of resting FVR, LBNP evoked an increased FVR (P < .001) that did not differ significantly between BLK and PLA in either group. FVR was higher (P < .001) in HTN than in NTN throughout both trials; at -40 mm Hg of LBNP during BLK, the increase in FVR was greater (P < .05) in HTN than in NTN (131 +/- 42 v 48 +/- 15%). MAP (relative to resting) was maintained throughout LBNP during PLA but, at -40 mm Hg, was lower (P < .01) during BLK for both groups. HR was elevated in BLK and was increased at -40 mm Hg (P < .01) for each group in each trial. This increase was greater during BLK (P < .05). These data suggest that borderline hypertensives have a greater vasoconstrictor response to LBNP than do normotensives and alpha1-blockade does not appear to attenuate this response.