ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients

The aim of this study was to compare the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin II antagonist losartan on insulin sensitivity and plasma fibrinogen in overweight hypertensive patients. Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and <110 mm Hg] hypertensives aged 43-64 years, after a 4-week placebo period, were randomized to perindopril, 4 mg o.d., or losartan, 50 mg o.d., for 6 weeks. Then, after a new placebo period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the treatment periods, blood pressure was measured, plasma fibrinogen was evaluated, and insulin sensitivity was assessed by the euglycemic, hyperinsulinemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated. Both perindopril and losartan reduced SBP (by a mean of 20.2 mm Hg, p < 0.001 vs. placebo; and 15.8 mm Hg, p = 0.002 vs. placebo, respectively) and DBP (by a mean of 15.2 mm Hg, p = 0.001 vs. placebo, and 11.8 mm Hg, p = 0.01 vs. placebo respectively), with no difference between the two treatments. GIR was significantly increased by perindopril (+2.91 mg/min/kg, p = 0.042 vs. placebo), but not by losartan (+0.28 mg/min/kg, NS). TGR was not modified by losartan but was increased by perindopril (+9.3 g, p = 0.042 vs. placebo). Plasma fibrinogen levels were reduced by perindopril (-53.4 mg/dl, p = 0.022 vs. placebo) but not by losartan (-16.8 mg/dl, NS). The perindopril-induced decrease in fibrinogen was correlated with the increase in GIR (r = 0.39; p < 0.01). These findings suggest that fibrinogen decrease produced by the ACE inhibitor is related to its action on insulin sensitivity, which seems to be dependent not on angiotensin II blockade but rather on other mechanisms.     

Norepinephrine or dopamine for the treatment of hyperdynamic septic shock?

STUDY OBJECTIVE: To compare the ability of dopamine and norepinephrine to reverse hemodynamic and metabolic abnormalities of human hyperdynamic septic shock. DESIGN: Prospective, double-blind, randomized trial. SETTING: An ICU in a university hospital. PATIENTS: Adult patients with hyperdynamic septic shock after fluid resuscitation. INTERVENTIONS: Patients were assigned to receive either dopamine (2.5 to 25 micrograms/kg/min) or norepinephrine (0.5 to 5.0 micrograms/kg/min). If hemodynamic and metabolic abnormalities were not corrected with the maximum dose of one drug, the other was added. MEASUREMENTS AND RESULTS: The aim of therapy was to achieve and maintain for at least 6 h all of the following: (1) systemic vascular resistance index > 1,100 dynes.s/cm5.m2 and/or mean systemic blood pressure > or = 80 mm Hg; (2) cardiac index > or = 4.0 L/min/m2; (3) oxygen delivery > 550 ml/min/m2; and (4) oxygen uptake > 150 ml/min/m2. With the use of dopamine 10 to 25 micrograms/kg/min, 5 of 16 patients (31 percent) were successfully treated, as compared with 15 of 16 patients (93 percent) by norepinephrine at a dose of 1.5 +/- 1.2 micrograms/kg/min (p < 0.001). Ten of 11 patients who did not respond to dopamine and remained hypotensive and oliguric were successfully treated with the addition of norepinephrine. CONCLUSIONS: At the doses tested, norepinephrine was found, in the present study, to be more effective and reliable than dopamine to reverse the abnormalities of hyperdynamic septic shock. In the great majority of the study patients, norepinephrine was able to increase mean perfusing pressure without apparent adverse effect on peripheral blood flow or on renal blood flow (since urine flow was reestablished). At the same time, oxygen uptake was increased.     

Mechanisms of kinin B1-receptor-induced hypotension in the anesthetized dog

Our study was performed to investigate the mechanism underlying the phypotensive effect of kinin B1-receptor activation with des-Arg9-bradykinin (des-Arg9-BK), in comparison with B2-receptor activation with bradykinin (BK), in anesthetized dogs. Bolus intravenous and intraarterial injections of both kinins were compared. BK (0.6 microgram/kg) produced a transient hypotension of the same magnitude, regardless of the route of administration (from 110 +/- 6 mm Hg to 66 +/- 6 mm Hg, or -41 +/- 5%). In contrast, intraarterial injection of des-Arg9-BK (0.6 microgram/kg) induced a weaker hypotension compared with its intravenous injection (-27 +/- 2% vs. -39 +/- 3%, p < 0.05). The hypotension induced by both kinins was accompanied by increases in heart rate, maximum left ventricular dP/dt, and aortic blood flow, suggesting a reduction in peripheral resistance. The positive inotropic and chronotropic effects of BK and des-Arg9-BK were found to be mediated by the sympathetic nervous system, because they were abolished by propranolol. The hypotension induced by intravenous and intraarterial injections of BK and intravenous injections of des-Arg9-BK was only slightly reduced after nitric oxide (NO) synthase inhibition with NG-nitro-L-arginine (L-NNA). In contrast, the hypotensive effect of intraarterial injection of des-Arg9-BK was reduced by half after treatment with L-NNA (p < 0.05). Neither bilateral vagotomy nor ganglionic blockade with pentolinium reduced the hypotension induced by both kinins. In conclusion, the hypotensive effect of des-Arg9-BK and BK results from a peripheral vasodilation. The contribution of NO in this vasodilation is substantial for des-Arg9-BK when administered intraarterial but limited for BK and intravenous des-Arg9-BK.     

Nitric oxide synthase inhibition restores vasopressor effects of norepinephrine in ovine hyperdynamic sepsis

To investigate the hypothesis that nitric oxide synthase (NOS) inhibition restores the vasopressor response to norepinephrine (NE) in ovine hyperdynamic sepsis, eight sheep were chronically instrumented. In the non-septic portion of the study, NE was titrated to achieve an increase in mean arterial pressure (MAP) by 15 mm Hg ("small dose"). Small-dose NE was repeated 1 h after administration of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; bolus 5 mg/kg, followed by 1 mg.kg-1.h-1). After 3 days of recovery, sepsis was induced by a continuous endotoxin infusion (Salmonella typhosa, 10 ng.kg-1.h-1). Three animals died during this period (data excluded). After 24 h, small-dose NE was given. If MAP increased less than 15 mm Hg, the NE dose was increased to achieve the targeted MAP change ("large dose"). Finally, both doses of NE were given after L-NAME administration. To increase MAP by 15 mm Hg in nonseptic animals, the rate of NE infusion was 0.18 +/- 0.03 microgram.kg-1.min-1 (small dose). During L-NAME infusion, this NE dose increased MAP by 32 +/- 8 mm Hg. In septic animals, small-dose NE increased MAP by only 9 +/- 2 mm Hg (P < 0.05 versus nonseptic state). To increase MAP by 15 mm Hg, the NE dose had to be increased to 0.34 +/- 0.06 microgram.kg-1.min-1 (large dose). During L-NAME infusion, NE administration increased MAP by 16 +/- 2 mm Hg and 28 +/- 4 mm Hg (small and large dose, respectively). Thus, L-NAME restored the vasopressor response to NE in sepsis, and increased the vasopressor response to NE in a similar fashion in healthy and septic sheep.     

Modulation of intravariceal pressure with pentoxifylline: a possible new approach in the treatment of portal hypertension

OBJECTIVE: In this study the effect of the hemorheological agent pentoxifylline on the pressure of esophageal varices was investigated in portal hypertensive cirrhotic patients. METHODS: Intravariceal pressure was measured endoscopically using the direct puncture technique in 20 patients. Measurements were obtained under baseline conditions and 30 min after double-blind administration of pentoxifylline (1.4 mg/kg BW, n = 10 patients) or an identical volume of NaCl 0.9% solution (n = 10 patients). RESULTS: Under baseline conditions, intravariceal pressure was similar in pentoxifylline and placebo groups (17.3+/-5.5 mm Hg vs 18.8+/-4.6 mm Hg, respectively; p = N.S.). Placebo administration had no significant effect on intravariceal pressure (18.8+/-4.6 mm Hg vs 18.3+/-4.1 mm Hg; p = N.S.). In contrast, pentoxifylline caused a highly significant reduction of intravariceal pressure, (from 17.3+/-5.5 mm Hg to 11.4+/-5.9 mm Hg; p = 0.0001), the overall mean reduction being 36.1+/-14.1% mm Hg. CONCLUSIONS: We concluded that pentoxifylline, by reducing blood flow viscosity, caused a significant decrease in variceal pressure in patients suffering from portal hypertension.     

Deliberate hypotensive epidural anesthesia for patients with normal and low cardiac output

The use of hypotensive anesthesia is contraindicated in patients with ventricular dysfunction, even though afterload reduction often improves ventricular performance. The purpose of this study was to prospectively assess systemic hemodynamic responses to deliberate hypotension with epidural anesthesia in patients with chronic left ventricular dysfunction. Hemodynamic measurements were performed in 29 patients undergoing total hip arthroplasty under deliberate hypotensive epidural anesthesia using low-dose intravenous epinephrine infusion to maintain mean arterial pressure (MAP) at 50-60 mm Hg. Intraoperative MAP decreased from 100 +/- 16 to 56 +/- 9 mm Hg by 30 min after epidural injection (P < 0.0005). Concurrently, cardiac index (CI) increased from a preanesthetic baseline value of 2.9 +/- 0.5 to 3.3 +/- 0.9 L.min-1.m-2 at 30 min (P < 0.005) after epidural injection and stroke volume index (SVI) increased from 41 +/- 8 to 50 +/- 14 mL.beat-1.m-2 30 min after epidural injection (P < 0.005). Heart rate and central venous and pulmonary artery diastolic pressures were maintained under hypotension with epidural anesthesia in all patients. During deliberate hypotension with epidural anesthesia, patients with a history of congestive heart failure or low preanesthetic CI (< or = 2.5 L.kg-1.m-2) increased their CI and SVI into the normal range. There were no significant perioperative complications in either of these groups. Hypotensive epidural anesthesia can be used successfully in patients with low cardiac output from ventricular dysfunction undergoing total hip arthroplasty.     

Resection of the metatarsal head for diabetic foot ulcers

Dobutamine-induced hypotension has been disregarded as a marker of more severe functional abnormalities in patients with suspected coronary artery disease. However, its functional significance in patients with myocardial infarction has not been studied. The aim of this study was to define the predictors of systolic blood pressure (SBP) response to dobutamine in patients with previous myocardial infarction. Dobutamine stress (up to 40 microg/kg per minute) echocardiography was performed in 326 patients with prior myocardial infarction referred for evaluation of myocardial ischemia. A 16-segment, four-grade score model was used to assess left ventricular function. Wall motion score index was derived by summation of wall motion score divided by 16. SBP and heart rate increased from rest to peak dobutamine stress (127 +/- 22 vs 134 +/- 27 mm Hg and 72 +/- 14 vs 122 +/- 24 bpm, p < 0.00001 in both). An increase of SBP > or = 30 mm Hg occurred in 50 patients (15%). By multivariate analysis, independent predictors of failure of SBP increase were higher peak wall motion score index (p < 0.001), higher resting SBP (p < 0.01), and medication with calcium channel blockers (p < 0.05). SBP drop > or = 20 mm Hg occurred in 54 patients (17%). Independent predictors of SBP drop were higher resting wall motion score index (p < 0.001), higher resting SBP (p < 0.0001), and older age (p < 0.05). In patients with myocardial infarction, left ventricular function and baseline systolic blood pressure are powerful predictors of SBP response to dobutamine stress testing.     

Renal hemodynamics during norepinephrine and low-dose dopamine infusions in man

OBJECTIVE: To characterize the effects of pressor doses of norepinephrine and low-dose dopamine (3 micrograms/kg/min) on renal hemodynamics in man, as well as to determine the clinical relevance of combining dopamine with norepinephrine. DESIGN: Prospective, single-blind, randomized study. SETTING: Clinical research unit of a tertiary care hospital. SUBJECTS. Six healthy male volunteers ranging in age between 20 and 28 yrs. INTERVENTIONS: The subjects were assigned randomly to four treatments (1 wk apart) in which renal hemodynamics and electrolyte excretion were assessed. Treatments consisted of 180-min infusions of the following: a) 0.9% sodium chloride (control); b) pressor doses of norepinephrine; c) dopamine at 3 micrograms/kg/min; and d) pressor doses of norepinephrine and dopamine at 3 micrograms/kg/min. Pressor doses of norepinephrine was defined as doses required to increase mean arterial pressure (MAP) by 20 mm Hg. MEASUREMENTS AND MAIN RESULTS: Glomerular filtration rate and renal blood flow were derived from inulin and para-aminohippurate clearances, respectively. Urine output and urine solute excretion were also determined. The mean norepinephrine dose required to increase MAP by 22 +/- 2 mm Hg was 118 +/- 30 ng/kg/min (range 76 to 164). After the addition of dopamine, similar doses of norepinephrine resulted in an MAP increase of 15 +/- 4 mm Hg. Glomerular filtration rate and urine output were comparable under all conditions. The infusion of norepinephrine decreased renal blood flow from 1241 +/- 208 to 922 +/- 143 mL/min/1.73 m2 (p = .03). The addition of dopamine returned renal blood flow to baseline values. The clearance of urine sodium increased significantly with the infusion of dopamine alone (p = .03). All subjects completed the four treatment periods. Adverse events, manifested mostly as palpitations and flushing, were rare and self-limiting. CONCLUSIONS: The addition of dopamine (3 micrograms/kg/min) to pressor doses of norepinephrine normalized renal blood flow in healthy volunteers. These hemodynamic changes were not reflected in urine output and glomerular filtration rate; hence, these monitoring parameters may be unreliable indicators of renal function in the setting of vasopressor therapy. In addition, systemic effects were observed with dopamine (3 micrograms/kg/min), as indicated by a decrease in MAP.     

Nicardipine versus nitroprusside for controlled hypotension during spinal surgery in adolescents

Nicardipine or nitroprusside was used to induce controlled hypotension in healthy adolescents with idiopathic scoliosis undergoing spinal fusion. Twenty patients were randomly assigned to the nitroprusside (N) or nicardipine (C) group. All patients received a standardized anesthetic. A target mean arterial blood pressure (MAP) of 60 mm Hg was achieved by varying the vasoactive infusions only. Moderate hemodilution (PCV = 25) and intraoperative blood salvage were used in all cases. Hemodynamic variables, blood loss, occurrence of reflex tachycardia, and reversibility of the hypotensive state were compared between the two groups. Significant differences were observed between the two groups in the amount of blood loss and reversibility of the hypotensive state. Group C had less blood loss (761 +/- 199 mL) than Group N (1297.5 +/- 264, P < or = .05). Time to restoration of baseline MAP was longer with Group C (26.8 +/- 4.0 min) than Group N (7.3 +/- 1.1 min, P < or = 0.001). Both drugs rapidly achieved a stable, controlled hypotensive state and an acceptable operating field. There was no statistically significant difference between groups with respect to the amount of crystalloid administered or urine output. These results suggest that nicardipine is a safe, effective drug for controlled hypotension in this population and that it may offer the significant advantage of reduced blood loss in these patients.     

Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome. The NO Almitrine Study Group

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.     

Acute hemodynamic changes during carotid artery stenting

To determine the clinical significance of acute hemodynamic disturbances during stenting in the carotid sinus region, we assessed the relation between intraprocedural changes in heart rate (HR) and blood pressure (BP) and adverse neurologic and cardiac outcomes. Eighteen patients underwent carotid stenting with the Wallstent (Schneider Inc). Suitable candidates had at least 60% diameter stenosis of the carotid artery by angiography. Initial and nadir HR and BP were recorded during the predilatation, stent delivery, and postdilatation periods. Bradycardia was defined as HR < or =60 beats/min and hypotension as systolic BP < or =100 mm Hg. Nineteen Wallstents were successfully deployed in all 19 carotid arteries. Some degree of bradycardia or hypotension occurred in 68% of carotid stent procedures, but administration of vasoactive medications was necessary in only 7 patients (37%) with more persistent hemodynamic disturbances. Hypotension or the need for continuous vasopressor therapy was significantly more common during postdilatation (32%) than in the predilatation period (5%) (p = 0.02). Bradycardia was not reduced by prophylactic atropine. In 1 patient the hemodynamic response to stenting may have contributed to an adverse neurologic and cardiac outcome. Thus, despite frequent fluctuations in HR and BP, most carotid stenting procedures were performed with excellent overall results, even in patients at high risk.     

Inhibition of hypoxic pulmonary hypertension by heparins of differing in vitro antiproliferative potency

Heparin inhibits smooth-muscle cell (SMC) growth in vitro and inhibits the development of hypoxic pulmonary hypertension and vascular remodeling in vivo. We wondered whether preparations of heparin with different antiproliferative potency in vitro would differ in their ability to inhibit the development of hypoxic pulmonary hypertension in vivo. Two such heparins, a weakly antiproliferative lot of Elkins-Sinn (E-S) (% inhibition of SMC growth at 10 micrograms/ml = 13 +/- 9% [mean +/- SEM, n = 24]) and a more active lot from Upjohn (UJ) (% inhibition = 71 +/- 12% [n = 12, p < 0.05 versus E-S]), were infused subcutaneously (300 U.S.P. units/day; E-S 300 versus UJ 300) via an osmotic pump into guinea pigs exposed to hypoxia (10% O2) for 10 d, after which pulmonary artery pressure (PAP; mm Hg) and cardiac index (CI; ml/min/kg) were measured in room air. Hypoxic controls (HC) received saline. PAP increased from 11 +/- 1 mm Hg in normoxic controls (NC) (n = 5) to 24 +/- 1 mm Hg in HC (n = 8, p < 0.05). The PAP was lower in the E-S 300 (21 +/- 1; n = 7, p < 0.05 versus HC and NC) and even lower in the UJ 300-treated group (18 +/- 0.5; n = 7, p < 0.05 versus HC and NC). Total pulmonary vascular resistance (TPR; mm Hg/ml/min/kg) increased significantly from 0.038 +/- 0.002 in NC to 0.076 +/- 0.003 (p < 0.05) in HC. There was no difference in TPR between the HC and the E-S 300-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of right ventricular systolic pressure during incremental exercise by Doppler echocardiography in adults with atrial septal defect

STUDY OBJECTIVES: Pulmonary hypertension is the most important complication in patients with atrial septal defect (ASD), but its role in limiting exercise has not been examined. This study sought to evaluate exercise performance in adults with ASD and determine the contribution of elevated pulmonary artery pressure in limiting exercise capacity. DESIGN: We used Doppler echocardiography during exercise in 10 adults (aged 34 to 70 years) with isolated ASD (New York Heart Association class I, II) and an equal number of matched control subjects. Incremental exercise was performed on an electrically braked upright cycle ergometer. Expired gases and VE were measured breath-by-breath. Two-dimensional and Doppler echocardiographic images were obtained at rest prior to exercise to determine ASD size, stroke volume (SV), shunt ratio (Qp:Qs), right ventricular outflow tract (RVOT) size, and right ventricular systolic pressure at rest (RVSPr). Doppler echocardiography was repeated at peak exercise to measure right ventricular systolic pressure during exercise (RVSPex). RESULTS: Resting echocardiography revealed that RVOT was larger (21+/-4 vs 35+/-8 mm, mean+/-SD; p=0.0009) and RVSPr tended to be higher (17+/-8 vs 31+/-8 mm Hg; p=0.08) in ASD; however, left ventricular SV was not different (64+/-23 vs 58+/-23 mL; p>0.05), compared with control subjects. Despite normal resting left ventricular function, ASD patients had a significant reduction in maximum oxygen uptake (VO2max) (22.9+/-5.4 vs 17.3+/-4.2 mL/kg/min; p=0.005). RVSPex was higher (19+/-8 vs 51+/-10 mm Hg; p=0.001) and the mean RVSP-VO2 slope (1+/-2 vs 18+/-3 mm Hg/L/min; p=0.003) and intercept (17+/-4 vs 27+/-4 mm Hg; p=0.05) were higher in the ASD group. VO2max correlated inversely with both RVSPr (r=-0.69; p=0.007) and RVSPex (r=-0.67; p=0.01). CONCLUSION: These findings suggest that adults with ASD have reduced exercise performance, which may be associated with an abnormal increase in pulmonary artery pressure during exercise.     

Stimulation of endogenous catecholamine release by theophylline: a proposed additional mechanism of action for theophylline effects

Therapeutic response to theophylline in asthma is generally attributed to its effect in increasing intracellular 3',5' cyclic adenosine monophosphate (cAMP) by competitive inhibition of cAMP phosphodiesterase. However, because of discrepancies between therapeutic serum theophylline concentration achieved clinically and those required for in vitro phosphodiesterase inhibition, we explored the possibility that theophylline may act through adrenomedullary secretion of catecholamines. Five healthy, nonasthmatic male and female adults were studied with a double-blind, randomized, crossover protocol. Theophylline (5 mg/kg) and placebo were administered in a capsule dosage form. Plasma catecholamines epinephrine (E), norepinephrine (NE), and dopamine (DA) were measured by a radioenzymatic assay at baseline and after administration of theophylline at 1, 2, and 3 hr. Significant differences between theophylline- and placebo-treated groups (p less than 0.05) were seen at 3 hr for mean percentage increase over baseline with E (120% +/- 25.3%) and NE (48.02% +/- 17.94%) after theophylline therapy (mean peak level 7.2 +/- 0.48 micrograms/ml). Epinephrine plasma concentration was significantly greater (p less than 0.001) at 3 hr compared with baseline (105 +/- 16 vs 56 +/- 18 pg/ml), while NE (448 +/- 52 vs 320 +/- 36 pg/ml) did not attain significance (p = 0.136). A significant correlation (p less than 0.05) was found between the percentage increase over basal for E (r = 0.58) and NE (r = 0.66) and serum theophylline levels. DA was not significantly increased at any time period. Thus theophylline in clinically relevant concentration appears to stimulate adrenomedullary secretion of catecholamine. Whether this is an important mechanism of action in asthma or explains some side effects of theophylline remains to be determined.     

Evidence for adaptive autoregulatory displacement in hypotensive cortical territories adjacent to arteriovenous malformations. Columbia University AVM Study Project

We hypothesized that chronic hypotension in normal vascular territories fed by arteriovenous malformation pedicles may reset the lower limit of autoregulation and allow flow to remain constant over a lower pressure range. We studied the effect of increasing systemic mean arterial pressure (SMAP) with phenylephrine on cerebral blood flow using a novel technique. Fourteen patients undergoing 15 procedures were studied before endovascular embolization of arteriovenous malformations under neuroleptic conscious sedation. Mean pressures were transduced via a 1.5-F intracranial microcatheter, which was passed under fluoroscopic guidance into the target feeding artery. The microcatheter was positioned (unwedged) at a point that was relatively hypotensive to systemic pressure but that irrigated normal cortex on angiography; feeding mean arterial pressure (FMAP) and SMAP were recorded. A bolus of 133Xe in saline was injected into the microcatheter, and washout was recorded for 3 minutes by a scintillation detector placed over the vascular territory of the injected pedicle. SMAP was then increased approximately 25 mm Hg by phenylephrine infusion, a second bolus was given, and washout was recorded. After exclusion of the shunt spike, initial slope was calculated. The SMAP (mean +/- standard error) increased from 65 +/- 3 to 89 +/- 2 mm Hg (P < 0.0001), and FMAP increased from 46 +/- 3 to 63 +/- 3 mm Hg (P < 0.0001); cerebral blood flow did not change (40 +/- 2 to 40 +/- 2 ml/100 g per min, P = 0.9199). Dividing the cases on the basis of the baseline FMAP into a "severe" hypotensive group (FMAP = 38 +/- 2; n = 7) and a "moderate" hypotensive group (FMAP = 54 +/- 3; n = 8), cerebral blood flow did not change in either group during phenylephrine challenge. Chronic hypotension does not necessarily result in "vasomotor paralysis" with loss of the ability to vasoconstrict to acute increases in perfusion pressure. Instead, it appears to displace adaptively the lower limit of autoregulation in affected vascular territories by a shift of the autoregulatory curve to the left, conceptually analogous to the adaptive displacement seen with chronic hypertension and its treatment.     

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.     

Disinhibition of AVP release during noradrenaline and angiotensin II infusions in dogs by maintaining normotension with sodium nitroprusside

Noradrenaline (NA) and angiotensin II (A II) were infused intravenously in conscious dogs without (series I) and with (series II) additional infusions of sodium nitroprusside at doses re-establishing normal levels of mean arterial pressure (MAP). In series I, NA infusion (1.6 micrograms/min per kg for 30 min) initially elevated MAP by some 25 mm Hg and lowered heart rate by some 30 beats/min. Plasma concentrations of arginine vasopressin (AVP) remained constant, while those of A II and atrial natriuretic factor were slightly, but significantly, increased. Infusion of A II (10 or 20 ng/min per kg for 30 min) induced similar rises in MAP and slight reductions of heart rate and increased plasma AVP by 70% and atrial natriuretic factor by 60%. In series II, sodium nitroprusside (1-4 micrograms/min per kg) was added for 30 min to infusions of NE (1.6 micrograms/min per kg) and A II (20 ng/min per kg) in order to maintain MAP at its control level. This resulted in an 11-fold increase in plasma AVP during NA infusion and a 19-fold increase during A II infusion. Infusing sodium nitroprusside (4 micrograms/min per kg) alone lowered MAP to clearly hypotensive levels, but the resulting rises in plasma AVP were less than, rather than equal to, those seen at normotensive MAP levels during the combined infusions of sodium nitroprusside with A II or NA, respectively. It is concluded that both NA and A II exert strong stimulatory actions on AVP release which are, however, counteracted by inhibitory influences arising from the hypertensive effects of NA and A II.     

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.     

Exercise hemodynamics in small (< or = 21 mm) aortic valve prostheses assessed by Doppler echocardiography

Exercise Doppler echocardiography was used to assess hemodynamics in 25 patients with a < or = 21 mm aortic valve prosthesis (14 with a Medtronic-Hall 21 mm valve, three with a Medtronic-Hall 20 mm valve, three with a Sorin 21 mm valve, one with a Duromedics 21 mm valve, and four with a Carpentier-Edwards 21 mm valve). A symptom-limited upright bicycle exercise test was performed, and Doppler gradients were recorded during exercise. Gradients increased with exercise from 30 +/- 8/16 +/- 4 mm Hg (peak/mean) at rest to 46 +/- 12/24 +/- 7 mm Hg during exercise; both p < 0.001. Mean exercise gradient exceeded 30 mm Hg in five patients, and the highest mean gradient recorded was 37 mm Hg. Within the group of mechanical valves, gradients at exercise were similar for different types of valves. A linear relationship was found between gradients at rest and during exercise (peak r = 0.75, mean r = 0.77; both p < 0.001). Additional findings were midventricular velocities exceeding 1.5 m/sec in late systole in 10 patients (40%) and intraventricular flow (> or = 0.2 m/sec) toward the apex during isovolumic relaxation in 11 patients (44%). The patients with these velocity patterns had significantly smaller left ventricular cavities (end-diastolic diameter 39.8 +/- 4.8 vs 46.5 +/- 4.2 mm, p < 0.01; end-systolic diameter 24.2 +/- 3.0 vs 28.5 +/- 4.5 mm, p = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS)     

The minimal sequence needed to define a functional DNA terminator in Bacillus subtilis

BACKGROUND: We wished to determine whether transcutaneous oximetry or laser Doppler flowmetry (LDF) could identify patients at risk for wound failure after conservative, limb-sparing surgery for extremity sarcomas. METHODS: Studies were performed on postoperative days (PODs) 1, 4/5, 7, and 9. Measurements of transcutaneous oxygen pressure (tcPO2) were taken at breathing room air (BL) and 100% oxygen (rate tcPO2). LDF measurements were taken at multiple sites along the wound, and a perfusion index was calculated. RESULTS: Twenty-four patients were studied. Four (17%) had nonhealing wounds. There was no difference in tcPO2 (BL) values between healed and nonhealing wounds. Measurement of rate tcPO2 on POD 1 was significantly lower in the nonhealing wounds than in those with normal healing (28.5 +/- 12.1 mm Hg vs 14.3 +/- 16.2 mm Hg, mean +/- SD, p = 0.03). Rate tcPO2 values increased significantly in healing wounds from POD 1 to PODs 7 and 9 (p = 0.006, p = 0.009). This increase was absent in nonhealing wounds. A clear separation was noted in rate tcPO2 values between groups, with a minimum rate tcPO2 value recorded in a healed wound of 9 mm Hg/min, compared with the maximum value in a nonhealing wound of 7 mm Hg/min. The LDF perfusion index failed to predict wound healing at any of the measured time points. CONCLUSIONS: This study showed that measurement of tcPO2 during oxygen inhalation can accurately predict wound healing in patients after excision of an extremity sarcoma.