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.     

Transdiaphragmatic pressure gradients and the lower esophageal sphincter after tight abdominal wall plication in the rat

BACKGROUND: Gastroesophageal reflux (GER) is increasingly recognized as a complication of surgical closure of gastroschisis and omphalocele. AIM: This study tests the hypothesis that forceful abdominal wall closure reinforces the transdiaphragmatic pressure gradients that constitute the main GER-driving force and challenges the antireflux barrier. MATERIALS AND METHODS: Abdominal and esophageal pressures as well as lower esophageal sphincter pressures (LESP) and length (LESL) were measured in 17 adult rats before tight abdominal wall plication, after it, and 1 week later. RESULTS: This maneuver increased the transdiaphragmatic expiratory gradient from 0.67 +/- 1.31 to 6.97 +/- 2.68 mm Hg (P < .01) and the inspiratory gradient from 4.36 +/- 1.13 to 10.79 +/- 2.31 mm Hg (P < .01) by markedly increasing both the expiratory (from 1.47 +/- 0.74 to 9.44 +/- 1.85 mm Hg; P < .01) and inspiratory (from 0.98 +/- 0.69 to 6.83 +/- 1.55 mm Hg; P < .01) intraabdominal pressures. These changes were transient, and all pressures became normal after 1 week. The antireflux barrier functioned properly under these new conditions because both LESP and the diaphragmatic pinch-cock pressure (DPP) increased, from 20.3 +/- 3.63 to 26.5 +/- 4.31 mm Hg (P < .01) and from 16.4 +/- 7.25 to 22.5 +/- 4.36 mm Hg (P < .01), respectively, while LESL remained unchanged. CONCLUSION: Tight abdominal wall plication in the rat generates high intraabdominal pressures and thus reinforces the transdiaphragmatic pressure gradients, but these conditions elicit a healthy barrier response with sphincteric reinforcement. In addition, these changes are transient and fade out some time after operation. These facts should be taken into account for understanding the pathogenesis of GER after repair of abdominal wall defects in human babies.     

Porous-coated total hip arthroplasty in the young

OBJECTIVE: To evaluate whether thromboxane A2 participates in the ischemia-reperfusion injury associated with acute compartmental syndrome (ACS) and if by using a cyclooxygenase inhibitor this can be either reduced or abolished. DESIGN: To assess the role of thromboxane A2 in ACS, a tourniquet was applied for 2 hours to the hind limb of 12 dogs. Group 1 (n = 6) served as controls while group 2 (n = 6) was pretreated with lysine-acetyl-salicylate (Lysoprim). Blood thromboxane B2 levels and intracompartmental pressures were assayed prior to inflation of the tourniquet and at 5 minutes, 90 minutes, and 24, 72, and 144 hours after deflation. RESULTS: Five minutes after deflation, the compartmental pressure increased from 11.2 +/- 2.2 mm Hg to 16.1 +/- 3.3 mm Hg and 17 +/- 2.2 mm Hg (mean +/- SD) in groups 2 and 1, respectively. At 90 minutes and 24 hours, pressures were 17.1 +/- 3.3 mm Hg and 23.2 +/- 3.3 mm Hg (P<.01) and 15.3 +/- 2.6 mm Hg and 25.2 +/- 1.8 mm Hg (mean +/- SD) (P<.001), respectively, in groups 2 and 1. A similar effect, although of a lesser magnitude, was observed in the counterlateral limb. Thromboxane B2 levels increased from a mean (+/- SD) of 46 +/- 5.5 pg/0.1 mL to 132 +/- 7.5 pg/0.1 mL at 90 minutes in group 1, while remaining unchanged in group 2. CONCLUSIONS: Thromboxane A2 plays a major role in the ischemia-reperfusion injury of acute compartmental syndrome. By using a cyclooxygenase inhibitor both the levels of thromboxane and the compartmental pressures can be reduced.     

Hypertension development in Dahl S and R rats on high salt-low potassium diet: calcium, magnesium and sympathetic nervous system

Dietary combination of high salt with low potassium (HSLK) exacerbates hypertension development in Dahl salt-sensitive (S) rats, and produces a mild degree of hypertension in otherwise salt-resistant (R) rats. Increased blood pressure in both strains is associated with increased urinary excretion of calcium and magnesium. The objective of this study was to determine the effect of blood pressure on body balance of these ions in Dahl rats on HSLK diet. Two groups of S and two groups of R weanlings were all placed on HSLK diet (NaCl=8%, K=0.2%) for eight weeks. One group of each strain was subjected to chemical sympathectomy with 6-hydroxydopamine (6-OHDA) to counteract hypertension development. Urinary norepinephrine was used to determine efficacy of 6-OHDA treatment. Systolic blood pressures of conscious animals were measured daily throughout the study. The last three days on the diet were used to determine total dietary intake and urinary as well as fecal excretion of sodium, calcium and magnesium. At the end of the study, extracellular fluid volume, serum aldosterone and parathyroid hormone were analyzed. Final systolic blood pressures in the 4 groups were as follows: S=235+/-9 mmHg (n=9); R=155+/-3 mmHg (n=8); 6-OHDA S=151+/-6 mm Hg (n=8); 6-OHDA R=117+/-6 mm Hg. Chemical sympathectomy decreased blood pressure in both S and R rats. There was no indication of sodium accumulation in S rats. Associated with reduced parathyroid hormone levels the S strain had significantly less positive balance for calcium than the R strain, primarily due to increased urinary excretion. A less positive balance for magnesium was also observed, due mainly to relatively reduced intestinal absorption of the ion. We conclude that the HSLK diet is associated with inappropriate activation of the sympathetic nervous system and increased arterial pressure in both strains. In addition, since divalent cations may influence blood pressure, we suggest that the observed abnormalities in calcium and magnesium metabolism might independently promote hypertension development in the S strain.     

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 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.     

Comparison between the effects of amlodipine and lisinopril on proteinuria in nondiabetic renal failure: a double-blind, randomized prospective study

Double-blind, randomized controlled studies of longer than 1 week in duration comparing the antiproteinuric potential of long-acting dihydropyridine calcium channel blockers with that of angiotensin converting enzyme (ACE) inhibitors are lacking. Therefore, we performed such a study in patients with nondiabetic renal disease and proteinuria. After a 4-week wash-out period in which patients did not use any medication known to affect proteinuria, 21 patients were randomized in a double-blind fashion to receive either the calcium channel blocker amlodipine (Amlo, 5 to 10 mg) or the ACE-inhibitor lisinopril (Lis, 5 to 10 mg). Throughout the 16-week study period, blood pressure, creatinine clearances, and proteinuria were measured every 2 weeks. In addition, device-measured blood pressure and renal hemodynamic studies were performed at the start and end of the study. Systolic blood pressure fell in the Lis group from 163+/-7 (SEM) to 140+/-8 mm Hg (P < .01) and from 157+/-10 to 147+/-6 mm Hg in the Amlo group; diastolic blood pressure fell from 101+/-3 to 86+/-7 mm Hg in the Lis group and from 98+/-3 to 91+/-2 mm Hg in the Amlo group. Renal hemodynamics were not affected by amlodipine treatment, whereas a fall in glomerular filtration rate (GFR) was seen in lisinopril-treated patients (from 55+/-11 to 50+/-10 mL/min; P < .01). Amlodipine did not significantly affect proteinuria. Lisinopril induced a decline in the protein-creatinine ratio with a maximal effect reached after 12 to 16 weeks of therapy (from 0.39+/-0.17 to 0.26 +/-0.11 g/mmol; P < .009). In conclusion, we could not demonstrate an antiproteinuric effect of the long-acting dihydropyridine calcium channel blocker amlodipine, whereas therapy with the ACE-inhibitor lisinopril resulted in a decrease in proteinuria. Amlodipine did not affect renal hemodynamics, whereas lisinopril induced a fall in GFR.     

Fastigial stimulation increases ischemic blood flow and reduces brain damage after focal ischemia

Electrical stimulation of the cerebellar fastigial nucleus (FN) increases CBF and reduces brain damage after focal ischemia. We studied whether FN stimulation "protects" the brain from ischemic damage by increasing blood flow to the ischemic territory. Sprague-Dawley rats were anesthetized (halothane 1-3%) and artificially ventilated through a tracheal cannula inserted transorally. CBF was monitored by a laser-Doppler probe placed over the convexity at a site corresponding to the area spared from infarction by FN stimulation. Arterial pressure (AP), blood gases, and body temperature were controlled, and the electroencephalogram (EEG) was monitored. The stem of the middle cerebral artery (MCA) was occluded. After occlusion, the FN was stimulated for 60 min (100 microA; 50 Hz; 1 s on-1 s off) while AP was maintained at 97 +/- 11 mm Hg (mean +/- SD) by controlled hemorrhage. Rats were then allowed to recover, and infarct volume was determined 24 h later in thionin-stained sections. In unstimulated rats (n = 7), proximal MCA occlusion reduced CBF and the amplitude of the EEG. One day later, these rats had infarcts involving neocortex and striatum. FN stimulation after MCA occlusion (n = 12) enhanced CBF and EEG recovery [61 +/- 34 and 73 +/- 43%, respectively at 60 min; p < 0.05 vs. unstimulated group; analysis of variance (ANOVA)] and reduced the volume of the cortical infarct by 48% (p < 0.05). In contrast, hypercapnia (PCO2 = 64 +/- 4; n = 7) did not affect CBF and EEG recovery or infarct volume (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced ultrasonography in the diagnosis of renal tumors

Possible impairment of the L-arginine-nitric oxide (NO) pathway in the rostral ventrolateral medulla of adult spontaneously hypertensive rats (SHR) was investigated by microinjecting N(G)-nitro-L-arginine methyl ester (L-NAME), NOC 18 (an NO donor), or L-arginine. Unilateral injection of L-NAME (10 nmol/50 nL) into the rostral ventrolateral medulla significantly increased mean arterial pressure (MAP) in both SHR and Wistar-Kyoto rats (WKY). The increases in MAP did not differ significantly between the two strains (15+/-3 versus 10+/-2 mm Hg, respectively; n=8). In contrast, microinjection of L-arginine elicited significant (P<.05) dose-dependent decreases in MAP in both strains, and these depressor responses were significantly greater in SHR than in WKY (in 10 nmol of L-arginine: -29+/-2 versus -15+/-2 mm Hg, respectively; n=8, P<.01). Similarly, microinjection of NOC 18 (10 nmol/50 nL) reduced MAP in both strains, and the depressor response was also significantly greater in SHR than in WKY (-38+/-7 versus -22+/-3 mm Hg, respectively; n=8, P<.05). These results suggest that the L-arginine-NO pathway in the rostral ventrolateral medulla is impaired in SHR and that this impairment may contribute to the increase in arterial pressure in this animal model of genetic hypertension.     

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.     

A case report of two siblings with familial leukoencephalopathy in normotensive male adults with alopecia and lumbago

The aim of the study was to examine the hypotensive efficacy and tolerance of bisoprolol in elderly patients. Sixty patients (40 <65 years and 20 >65 years) with mild-to-moderate essential hypertension (diastolic blood pressure (DBP) between 95 and 109 mm Hg) were included in the study. After a 2-week run-in period on placebo, patients began bisoprolol therapy (5 mg/d) for 12 weeks. After 4 weeks the dose was increased to 10 mg/d in those with a DBP > or =95 mm Hg. Additionally, in 10 patients over 65 years old, 24-h ambulatory BP monitoring (ABPM) was performed, after placebo and after bisoprolol (5 mg) administration. The hypotensive efficacy of bisoprolol in the elderly and younger patients was similar. Before and after treatment the mean difference of systolic BP (SBP) was 19.6 +/- 12.5 mm Hg and DBP 9.6 +/- 6.2 mm Hg in the younger patients and 16.1 +/- 13.6 mmHg and 9.5 +/- 6.0 mmHg in the elderly patients. Bisoprolol produced a similar reduction in heart rate (23.1% vs 17.1%) in the estimated groups. The tolerance of bisoprolol was good in both groups. There were no significant differences in adverse drug reactions between the groups.     

Sigmoidal curve-fitting of baroreceptor sensitivity in renovascular 2K1C hypertensive rats

The time course of changes in baroreceptor reflex sensitivity in Goldblatt two-kidney one clip (2K1C) hypertension was studied 3, 7 and 30 days after renal artery clipping by means of a sigmoidal curve-fitting analysis. Experiments were performed in 54 adult male Wistar rats (N = 9 per group) weighing 200-300 g. The reflex heart rate responses were elicited by alternate intravenous bolus injections of phenylephrine (delta +5 to +50 mmHg) and sodium nitroprusside (delta -5 to -50 mmHg). A clear upper and lower plateau (reflex tachycardia and bradycardia, respectively) was noted in both sham and hypertensive groups. Although the resting mean arterial pressure was significantly increased in all hypertensive groups (131 +/- 3, 149 +/- 7 and 168 +/- 11 mmHg, respectively, 3, 7 and 30 days after clipping), when compared to the sham group (108 +/- 2 mmHg), significant changes in baroreceptor reflex function were observed only in 7- and 30-day groups. Baroreflex sensitivity was markedly reduced in these hypertensive rats (2.3 +/- 0.3 and 1.9 +/- 0.3 bpm/mmHg, respectively) compared to the sham group (4.2 +/- 0.3 bpm/mmHg). In addition, a reduced baroreflex heart rate range was observed in these groups (117 +/- 12 and 107 +/- 10 bpm, respectively) compared to the sham group (165 +/- 11 bpm). These data indicate an impairment of baroreflex function in conscious 2K1C hypertensive rats which seems to be secondary to arterial hypertension.     

EndothelinA receptor blockade improves nitric oxide-mediated vasodilation in monocrotaline-induced pulmonary hypertension

BACKGROUND: Nitric oxide (NO) and endothelin (ET) have been implicated in the pathogenesis of pulmonary hypertension (PH). Chronic ETA antagonist therapy reduces PH in monocrotaline (MCT)-treated rats. Interactions between the L-arginine-NO pathway and the ET system have been described. We therefore studied the effect of long-term treatment with an oral ETA antagonist (LU 135252) on NO-related vasodilation in isolated lungs from control rats and rats with MCT-induced PH. METHODS AND RESULTS: Three weeks after MCT injection, PH was associated with an increase in right ventricular pressure (from 27.4 +/- 0.9 to 66.6 +/- 4.1 mm Hg) and a decrease in endothelium-independent vasodilation in response to sodium nitroprusside (10(-10) to 10(-5) mol/L; delta Emax, from 11.1 +/- 0.9 to 2.7 +/- 0.3 mm Hg). Endothelium-dependent vasodilation in response to acetylcholine (10(-9) to 10(-4) mol/L) and the calcium ionophore A23187 (10(-9) to 10(-7) mol/L) remained unaffected. Treatment with LU 135252 did not significantly affect the endothelium-dependent and -independent vasodilations in control rats. However, in MCT-treated rats, LU 135252 therapy significantly reduced right ventricular pressure (39.7 +/- 2.1 mm Hg), potentiated acetylcholine-induced vasodilatation (delta Emax, from 1.6 +/- 0.2 to 3.7 +/- 0.4 mm Hg), and improved the responses to sodium nitroprusside (delta Emax, from 2.7 +/- 0.3 to 5.6 +/- 0.6 mm Hg). LU 135252 did not significantly alter the non-receptor-mediated endothelium-dependent vasodilation to A23187 or pulmonary constitutive NO synthase activity. CONCLUSIONS: MCT PH is associated with a reduced smooth muscle responsiveness to NO but a maintained endothelium-dependent vasodilatory potency. Long-term ETA antagonist therapy not only restores smooth muscle responsiveness to NO but also increases endothelium-dependent dilation in response to acetylcholine. This mechanism may contribute to the therapeutic benefit of ETA antagonists in PH.     

Maintenance of baseline angiotensin II potentiates insulin hypertension in rats

Chronic insulin infusion in rats increases mean arterial pressure (MAP) by a mechanism dependent on angiotensin II (Ang II). However, the fact that plasma renin activity (PRA) decreases with insulin infusion suggests that Ang II sensitivity is increased and that the parallel reduction in Ang II may partly counteract any hypertensive action of insulin. This study tested that hypothesis by clamping Ang II at baseline levels during chronic insulin infusion. Sprague-Dawley rats were instrumented with artery and vein catheters, and MAP was measured 24 hours per day. In seven angiotensin clamped rats (AC rats), renin-angiotensin II system activity was clamped at normal levels throughout the study by continuous intravenous infusion of the angiotensin-converting enzyme inhibitor benazepril at 5 mg/kg per day (which decreased MAP by 18+/-2 mm Hg) together with intravenous Ang II at 5 ng/kg per minute. Control MAP in AC rats after clamping averaged 99+/-1 mm Hg, which was not different from the 101+/-2 mm Hg measured before clamping Ang II levels. Control MAP in the 8 vehicle-infused rats averaged 105+/-2 mm Hg. A 7-day infusion of insulin (1.5 mU/kg per minute IV) plus glucose (20 mg/kg per minute IV) increased MAP in both groups of rats; however, the increase in MAP was significantly greater in AC rats (12+/-1 versus 5+/-1 mm Hg). This enhanced hypertensive response to insulin in AC rats was associated with a greater increase in renal vascular resistance (153+/-10% versus 119+/-6% of control) and a significant increase in renal formation of thromboxane (149+/-11% of control). Thus, decreased Ang II during insulin infusion limits the renal vasoconstrictor and hypertensive actions of insulin, and this may be caused, at least in part, by attenuation of renal thromboxane production.     

N-acetylcysteine attenuates endotoxin-induced leukocyte-endothelial cell adhesion and macromolecular leakage in vivo

OBJECTIVE: To determine the influence of N-acetylcysteine on endotoxin-induced leukocyte-endothelial cell adhesion, vascular leakage, and venular microhemodynamics. DESIGN: Randomized, blinded, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Thirty male Wistar rats. INTERVENTIONS: After pretreatment with N-acetylcysteine (150 mg/kg; n = 40; group A) or 0.9% saline solution (n = 10; group B) animals were given an intravenous infusion of endotoxin (Escherichia coli lipopolysaccharide 026:B6; 2 mg/kg/hr) over 120 mins. Animals in the control group (n = 10; group C) received a volume-equivalent infusion of 0.9% saline solution. MEASUREMENTS AND MAIN RESULTS: Leukocyte adherence, red cell velocity (VRBC), vessel diameters, venular wall shear rate, and macromolecular leakage were determined in mesenteric postcapillary venules using in vivo videomicroscopy at baseline and at 30, 50, 90, and 120 mins after the start of the endotoxin challenge. Endotoxin exposure induced a marked increase in adherent leukocytes (group B: baseline, 391 +/- 24 cells/mm2; 120 mins, 1268 +/- 131 cells/mm2; p < .01). N-acetylcysteine pretreatment attenuated the adherence of leukocytes during endotoxemia (baseline, 366 +/- 28 cells/mm2; 120 mins, 636 +/- 49 cells/mm2; p < .01 vs. baseline; p < .01 vs. group B). Leukocyte adherence in control animals (group C) did not increase significantly. Administration of N-acetylcysteine did not influence the decrease in VRBC observed during endotoxemia. In group B1 VRBC decreased during the infusion of endotoxin from 2.0 +/- 0.2 mm/sec at baseline to 1.1 +/- 0.2 mm/ sec after 120 mins (p < .01 vs. baseline; p < .05 vs. group C), and in group A from 2.2 +/- 0.2 mm/sec to 1.1 +/- 0.1 mm/sec after 120 mins (p < .01 vs. baseline; p < .05 vs. group C). In group C, VRBC remained unchanged (baseline, 1.7 +/- 0.2 mm/sec; at 120 mins, 1.5 +/- 0.2 mm/sec). The venular diameters remained unchanged in all groups during the entire study period. After 120 mins, the venular wall shear rate decreased from 502 +/- 62 secs-1 at baseline to 272 +/- 46 sec-1 in group B (p < .01), and from 563 +/- 45 secs-1 at baseline to 283 +/- 31 secs-1 in group A (p < .01). No differences in venular wall shear rate were observed between these groups. In group C, the venular wall shear rate remained unchanged (baseline, 457 +/- 54 secs-1; at 120 mins, 409 +/- 51 secs-1). Macromolecular leakage, expressed as perivenular/intravenular fluorescence intensity after injection of fluorescence-labeled albumin, increased from 0.29 +/- 0.03 to 0.58 +/- 0.03 (p < .01) during the infusion of endotoxin in group B. In contrast, pretreatment with N-acetylcysteine diminished the extravasation of albumin (baseline, 0.27 +/- 0.01; at 120 mins, 0.37 +/- 0.02; p < .01 vs. baseline; p < .01 vs. group B). CONCLUSION: These results demonstrate that N-acetylcysteine attenuates endotoxin-induced alterations in leukocyte-endothelial cell adhesion and macromolecular leakage, suggesting N-acetylcysteine might be therapeutic in the prevention of endothelial damage in sepsis.     

Eosinophil surface antigen expression and cytokine production vary in different ocular allergic diseases

OBJECTIVES: Improving methods of donor heart preservation may permit prolonged storage and remote procurement of cardiac allografts. We hypothesized that continuous, sanguineous perfusion of the donor heart in the beating, working state may prolong myocardial preservation. METHODS: We developed a portable perfusion apparatus for use in donor heart preservation. Contractile, metabolic, and vasomotor functions were monitored simultaneously in an isolated swine heart. The metabolic state was monitored by myocardial tissue pH. Vasomotor function was assessed in isolated coronary ring chambers. Hearts were randomized into 3 groups: group I (n = 5), cardioplegic arrest, 12-hour storage at 4 degrees C with modified Belzer solution, and 2-hour sanguineous reperfusion in the working state; group II (n = 6), 12-hour continuous perfusion in the beating working state, 30 minutes of arrest (to simulate re-implantation time), and 2 hours of reperfusion, as above; group III (n = 7), coronary ring control hearts. RESULTS: At 2 hours of reperfusion, left ventricular developed pressure in group II was higher than in group I (mean +/- standard deviation: 90 +/- 6 mm Hg, 53 +/- 15 mm Hg, P = .005). Significantly less myocardial edema was observed in group II than in group I (73% +/- 4%, 80% +/- 1% water content, P = .01). Significantly less myocardial acidosis was noted in group II than in group I during preservation (pH 7.3 +/- 0.01, 6.1 +/- 0.03, P < .001) and reperfusion (pH 7.3 +/- 0.008, 6.8 +/- 0.05, P < .001). Coronary endothelial vasomotor function was better preserved in group II than in group I as evidenced by dose-response relaxation of coronary rings to 10(-8) mol/L bradykinin (37%, 55% delta baseline, P = .01). CONCLUSION: This new method extends the current preservation limit and avoids time-dependent ischemic injury, thereby allowing for distant procurement of donor organs.     

Role of nitrates in pharmacologic modulation of reflected waves and their significance in the treatment of arterial hypertension in the elderly

OBJECTIVE: To analyse the efficacy of a sustained release form of isosorbide mononitrate in the treatment of isolated systolic hypertension in the elderly. PATIENTS: 24 patients suffering from essential hypertension and with an average age of 68.5 +/- 1.1 years were studied: 20 male and four female patients, all with isolated systolic hypertension (systolic blood pressure (SBP) > 160 mmHg and diastolic blood pressure (DBP) < 90 mmHg). None of the patients had received pharmacological treatment for their hypertension. None were receiving other medication or displayed concomitant pathologies. METHODS: Assessment of all the patients was made with the measurement of their occasional blood pressure, ambulatory measurement of blood pressure and the measurement of pulse wave velocity in two arterial zones (carotid-femural) by mecanography before and after thirty days of monotherapy with a single 50 mg dose of a sustained release form of isosorbide mononitrate. Four patients were withdrawn from tests due to signs of intolerance to the drug. RESULTS: A fall in occasional blood pressure was recorded, with statistical significance in relation to SBP only: SBP-192 +/- 15.5-->164 +/- 10.2 mm Hg (p < 0.001); DBP-85 +/- 4.2-->83 +/- 5.4 mm Hg. Ambulatory blood pressure readings also showed a significant drop in average SBP readings over the 24 hours: SAP 152.6 +/- 13.6-->140.5 +/- 15.4 mm Hg (p < 0.03); DBP 77.2 +/- 8.7-->72.3 +/- 5.47 mm Hg. No significant changes in pulse wave velocity were recorded for the zones studied: carotid-femural -20.8 +/- 6.0-->21.7 +/- 5.1 m/sec; femural-foot -4.5 +/ -1.4-->4.4 +/- 2.6 m/sec; a marked alteration in the morphology of arterial pulse in the aortic zone was observed, however, with a clear levelling off and reduction of the systolic peak. CONCLUSION: Treatment with nitrates may be a new and effective alternative for the treatment of the age group in question. It acts specifically on the pathophysiological mechanisms of isolated systolic arterial hypertension in the elderly. Changes in reflected wave velocity (retrogrades) seem to cause the significant reduction in SBP, observed in this group of patients.     

Anatomical and morphological factors correlating with rupture of intracranial aneurysms in patients referred for endovascular treatment

Ambulatory blood pressure (ABP) measurements were performed in a Danish population of 295 males and 275 females aged 19-21 years. Individualised day and night periods were defined from the subjects own recording of bedtime and rising on the day of their ABP measurements. During these individualised periods the ABP values for daytime, night-time and for the whole 24-h period were measured. The mean +/- s.d. values for systolic/diastolic ABP for the whole population were (124+/-11)/(70+/-7) mm Hg in the daytime, (106+/-12)/(60+/-9) mm Hg in the night-time, and (120+/-11)/(68+/-7) mm Hg in the whole 24-h period. Males had a mean systolic ABP of 9 mm Hg and mean diastolic ABP of 5 mm Hg higher than females. In males mean +/- s.d. systolic/diastolic ABP values in the daytime were (129+/-10)/(73+/-7) mm Hg, in the night-time (111+/-12)/(63+/-8) mm Hg, and in the whole 24-h period (125+/-10)/(71+/-7) mm Hg. The corresponding values in females were (119+/-10)/(68+/-6) mm Hg, (103+/-11)/(57+/-8) mmHg, and (115+/-10)/(66+/-6) mm Hg, respectively. In conclusion this study provides sex-specific normal values for ABP in a 19 to 21-year-old age group based on individualised daytime and night-time periods.     

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.     

Oxygen-haemoglobin dissociation curve in hypoxic rats of first or second generation

1. Albino Wistar rats were raised in a normobaric hypoxic environment (10% O2 in N2). Two generations of hypoxic rats were observed for changes in their haemoglobin-oxygen (Hb-O2) dissociation curves (ODC), 2,3-diphosphoglycerate (2,3-DPG), haemoglobin (Hb), and Hill co-efficients at P50 (n50). The first generation were called (H1) and the second generation (H2). The control group (N) had a normoxic environment. 2. Thirty-five rats (13 N rats, 12 H1 rats and 10 H2 rats) were used. The 2,3-DPG was significantly higher in both hypoxic groups when compared with N rats (2.02 +/- 0.51 mmol/L) but 2,3-DPG of H2 rats was significantly lower than that of H1 rats (H1 = 3.48 +/- 0.58 mmol/L and H2 = 2.76 +/- 0.54 mmol/L). The haemoglobin values were N = 2.00 +/- 0.26, H1 = 2.65 +/- 0.32 and H2 = 2.36 +/- 0.30 mmol/L, respectively. 3. We observed considerable differences in Hb-O2 affinity between the three groups of rats. In standard conditions (pH = 7.400; pCO2 = 40 mmHg at 37 degrees C) the H1 rats showed a significantly decreased Hb-O2 affinity (P50,st = 37.0 +/- 1.3 mmHg) when compared with both H2 and N rats; the H2 rats showed a significantly increased Hb-O2 affinity (P50,st = 31.1 +/- 1.5 mmHg) when compared with controls N (P50,st = 34.7 +/- 2.1 mmHg). There were no significant differences in n50 values: N = 2.88 +/- 0.44; H1 = 2.88 +/- 0.77; and H2 = 2.94 +/- 0.67.(ABSTRACT TRUNCATED AT 400 WORDS)