Nitric oxide as mediator of bradykinin-induced pancreatic circulatory and metabolic responses

Bradykinin (BK) is an endogenous nonapeptide with potent vasodilator properties of the visceral circulation. BK alters vascular tone via two BK receptor subtypes, B1 and B2. Current experimental evidence suggests that the dilator action of BK in some vessels is mediated primarily by B2 receptor activation. In addition, there are reports that BK increases endothelial generation of vasodilator factors, such as nitric oxide (NO). The present study had two aims. First, to explore the role of BK-receptors in the pancreatic vasodilatatory and metabolic responses to BK. Second aim was to examine whether endogenous NO play a role in the mediation of BK-receptors induced pancreatic circulatory and metabolic activity. In anesthetized dogs, the superior pancreatico-duodenal artery blood flow (SPBF) was measured by ultrasonic blood flowmeter (Transonic System T-206), pancreatic microcirculatory blood flow (PBF) was determined by laser Doppler flowmetry (Periflux 4001 Master). Pancreatic oxygen consumption (PVO2) was calculated as the product of the arteriovenous oxygen difference (AVO2) across the pancreatic circulation and SPBF. Drugs were infused into the superior pancreatico-duodenal artery. BK (0.01-1.0 mg/kg/min) increased maximally SPBF by 180 +/- 15%, PBF by 208 +/- 22% and PVO2 by 145 +/- 11%, respectively. Pretreatment with B2-subtype receptor antagonist, D-Arg, [Hyp3, Thi5,8, D-Phe7] BK inhibited significantly BK-induced increase in SPBF, PBF and PVO2 by 86 +/- 8%, 73 +/- 7% and 85 +/- 6%, respectively. A nitric oxide synthesis inhibitor (L-NNA) administered i.v. at dose of 25 mg/kg 20 min before BK, inhibited significantly the pancreatic hyperemic and metabolic responses. The results presented emphasize an important role of B2 receptors in the mediation of pancreatic circulatory and metabolic responses to bradykinin. Endogenous NO plays a mediatory role in the pancreatic vascular and metabolic responses due to stimulation of B2-receptors.     

Accuracy of portal and forearm blood flow measurements in the assessment of the portal pressure response to propranolol

BACKGROUND/AIMS: The portal pressure response to propranolol varies significantly in individual patients with cirrhosis. At present, propranolol responders can be identified only by measuring the hepatic venous pressure gradient. The aims of this study were: 1) to investigate whether the noninvasive monitoring of portal blood flow by pulsed Doppler ultrasound and forearm blood flow by strain-gauge plethysmography can predict the hepatic venous pressure gradient response to propranolol in patients with cirrhosis, and 2) to analyze the factors that may influence this response. METHODS: Hemodynamic measurements were undertaken in 80 patients with cirrhosis before and after receiving propranolol (0.15 mg/kg i.v., n = 60) or placebo (n = 20). RESULTS: No changes were observed in the placebo group. Propranolol lowered (p < 0.01) hepatic venous pressure gradient from 17.6 +/- 3.8 to 14.7 +/- 3.8 mmHg, portal blood flow from 1122 +/- 363 to 897 +/- 332 ml/min and forearm blood flow from 7.52 +/- 3.1 to 6.12 +/- 2.3 ml/min%. Changes in hepatic venous pressure gradient were correlated (p < 0.01) with those of portal blood flow (r = 0.82) and forearm blood flow (r = 0.54). The reduction in hepatic venous pressure gradient was > 20% in 23 patients ("responders"). The accuracy of portal Doppler flowmetry in identifying responders was higher than that of forearm plethysmography (88.3 vs. 68.3%, p < 0.05). Multivariate analysis proved that previous variceal bleeding was the only factor independently associated with a lack of response to propranolol (relative risk 3.42, 95% CI 1.5-7.4, p < 0.01). Hepatic venous pressure gradient reduction by propranolol was higher in non-bleeders than in bleeders (-19.9 +/- 9.4 vs. -11.3 +/- 8.6%, p < 0.01). CONCLUSIONS: Portal Doppler ultrasound can be used as a reliable surrogate indicator of the hepatic venous pressure gradient response to acute propranolol administration. In addition, our study indicates that this response is mainly influenced by previous variceal hemorrhage.     

Effects of capsaicin on KCl-induced blood flow and sensory nerve activity changes in the tooth pulp

Potassium ion-containing solutions have been shown to initially excite then depress intradental nerve activity (INA) when applied into deep dentinal cavities. The INA reflects activity originating in intradental A fibers. Application of KCl to deep dentinal cavities also induces an increase in pulpal blood flow (PBF). Capsaicin is known to exert a highly selective desensitizing effect on polymodal C-fiber nerve endings. These C fibers are generally believed to release vasoactive substances in response to stimulation. In order to determine if KCl exerts its vascular effect via activation of capsaicin-sensitive nerve fibers, we examined blood flow and sensory nerve responses to KCl obtained before and after capsaicin desensitization. The A-fiber nerve activity was determined by using INA recording technique. Blood flow was measured simultaneously from the same tooth using laser Doppler flowmetry. Local application of 0.25 M KCl to a deep dentinal cavity induced a brief spike burst and an increase in PBF of 76.0 +/- 14.6% (n = 8). Repeated applications of 0.25 M KCl caused a consistent increase in the peak PBF amplitude (n = 8). Local application of 100 microM capsaicin to a deep dentinal cavity caused an increase in PBF of 116.8 +/- 26.3% (n = 8) lasting 12-18 min, but capsaicin application did not appear to evoke any INA response. The amplitude of PBF in response to capsaicin application declined during repeated applications. Following repeated applications of capsaicin the PBF response to KCl was significantly reduced (9.9 +/- 4.3%, n = 8).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intermittent sequential compression of the lower limbs prevents venous stasis in laparoscopic and conventional colorectal surgery

PURPOSE: This study was designed to evaluate the influence of intraoperative intermittent sequential compression (ISC) on venous blood return from the lower limbs during laparoscopic and conventional colorectal colectomy. METHODS: Fifty patients undergoing laparoscopic (n = 25) or conventional (n = 25) colorectal surgery were included in a prospective study. Peak venous flow (PFV) and the cross-sectional area (CSA) of the femoral vein were assessed by Doppler ultrasound examination intraoperatively. RESULTS: Age, gender, and body mass index were comparable between both groups. Baseline PFV was 21 +/- 6.6 cm/s in the conventional and 18.4 +/- 6.4 cm/s in the laparoscopic group (P = 0.2). ISC increased PFV to 156 +/- 29 percent of the baseline value in the conventional group and to 161 +/- 29 percent in the laparoscopic group. PFV decreased after abdominal insufflation to 127 +/- 19 percent of the baseline value in the laparoscopic group and after laparotomy to 134 +/- 27 percent in the conventional group (P = 0.3). PFV decreased slightly in both groups during surgery but remained well above the baseline value. Baseline CSA was 1.02 +/- 0.17 cm2 in the conventional group and 1 +/- 0.23 cm2 in the laparoscopic group. ISC decreased CSA to 0.91 +/- 0.18 cm2 (conventional) and 0.85 +/- 0.18 cm2 (laparoscopic) after initiation of ISC. CSA was 0.92 +/- 0.18 cm2 after abdominal insufflation in the laparoscopic group, and it was 0.93 +/- 0.18 cm2 after laparotomy in the conventional group (P = 0.4). During surgery, there were no differences in absolute CSA or CSA changes compared with the baseline value in both groups. Postoperative circumference of the calf and thigh were not different between both groups. Postoperative thromboembolic complications did not occur. CONCLUSION: ISC effectively increases venous blood flow from the lower limbs during conventional and laparoscopic colorectal resections and may decrease the risk of postoperative deep vein thrombosis. Therefore, ISC is strongly recommended in every prolonged laparoscopic procedure.     

Lower extremity blood flow and responses to occlusion ischemia differ in exercise-trained and sedentary tetraplegic persons

OBJECTIVE: To test whether lower extremity blood flow and hyperemic responses to vascular occlusion differ among electrically stimulated exercise trained and sedentary tetraplegic persons and subjects without tetraplegia (control). DESIGN: Blinded cross-sectional comparison, control group. SETTING: Academic medical center. PARTICIPANTS: Ten sedentary tetraplegic men, 10 tetraplegic persons previously habituated to electrically stimulated cycling exercise for 0.4 to 7 years, and 10 nondisabled controls. OUTCOME MEASURES: Subjects underwent quantitative Doppler ultrasound examination of the common femoral artery (CFA). End-diastolic arterial images and arterial flow-velocity profiles obtained at rest and following five minutes of suprasystolic thigh occlusion were computer digitized for analysis of heart rate (HR), CFA peak systolic velocity (PSV), CFA cross-sectional area (CSA), flow velocity integral (FVI), and computed CFA inflow volume (IV). RESULTS: No group main effects were observed for resting HR or FVI. At rest, trained tetraplegic men had 14.9% greater PSV, 29.8% larger CSA, and 51.3% greater IV (p values < .05) than sedentary tetraplegic subjects. Resting PSV and IV of the trained subjects did not differ from controls, although CSA was smaller than controls (p < .05). Following occlusion, PSV, CSA, and IV averaged 16.5%, 33.4%, and 65.1% greater for trained tetraplegics persons, respectively, than sedentary tetraplegic subjects (p values < .05). Only CSA differed between the control and the trained groups (p < .05). CONCLUSION: Tetraplegic persons conditioned by electrically stimulated cycling have greater lower extremity blood flow and hyperemic responses to occlusion than do their sedentary counterparts.     

Role of nitric oxide in maintenance of basal anterior choroidal blood flow in rats

PURPOSE: The aim of this study was to use laser Doppler flowmetry to measure anterior choroidal blood flow in the anesthetized rat and to determine the role of nitric oxide (NO) in the maintenance of basal ocular blood flow in vivo. METHODS: By using laser Doppler flowmetry, blood flow from the anterior choroid in pentobarbital-anesthetized rats was measured continuously. Graded single doses (0.03-300 mg/kg) of the nonselective NO synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) were administered intravenously to establish dose-response relationships. Other groups of animals were tested with L-NAME after the prior administration of L-arginine, with D-NAME, or with the selective neural NO synthase inhibitor 7-nitroindazole. RESULTS: Intravenous administration of L-NAME produced a dose-related depression of anterior choroidal blood flow in the 0.3- to 30-mg/kg range. Maximal depression of approximately 60% occurred at the 30-mg/kg dose, peaked at approximately 30 minutes, and lasted throughout the 60-minute experimental period. At 10 mg/kg, L-NAME reduced ocular blood flow by approximately 50%, an effect that was abolished by pretreatment with intravenous L-arginine (300 mg/kg). Both D-NAME (10 mg/kg, intravenously) and 7-nitroindazole (50 mg/kg, intraperitoneally) were inactive with regard to ocular blood flow depression. CONCLUSIONS: Laser Doppler flowmetry appears to be a useful tool for continuous, online measurement of anterior choroidal blood flow in the rat eye. Results with L-NAME and 7-nitroindazole suggest that local tonic generation of endothelial NO plays an important role in the maintenance of basal anterior choroidal blood flow in this species.     

Effects of sodium nitroprusside and phenylephrine on blood flow in free musculocutaneous flaps during general anesthesia

BACKGROUND: Hypoperfusion and necrosis in free flaps used to correct tissue defects remain important clinical problems. The authors studied the effects of two vasoactive drugs, sodium nitroprusside and phenylephrine, which are used frequently in anesthetic practice, on total blood flow and microcirculatory flow in free musculocutaneous flaps during general anesthesia. METHODS: In a porcine model (n = 9) in which clinical conditions for anesthesia and microvascular surgery were simulated, latissimus dorsi free flaps were transferred to the lower extremity. Total blood flow in the flaps was measured using ultrasound flowmetry and microcirculatory flow was measured using laser Doppler flowmetry. The effects of sodium nitroprusside and phenylephrine were studied during local infusion through the feeding artery of the flap and during systemic administration. RESULTS: Systemic sodium nitroprusside caused a 30% decrease in mean arterial pressure, but cardiac output did not change. The total flow in the flap decreased by 40% (P < 0.01), and microcirculatory flow decreased by 23% in the skin (P < 0.01) and by 30% in the muscle (P < 0.01) of the flap. Sodium nitroprusside infused locally into the flap artery increased the total flap flow by 20% (P < 0.01). Systemic phenylephrine caused a 30% increase in mean arterial pressure, whereas heart rate, cardiac output, and flap blood flow did not change. Local phenylephrine caused a 30% decrease (P < 0.01) in the total flap flow. CONCLUSIONS: Systemic phenylephrine in a dose increasing the systemic vascular resistance and arterial pressure by 30% appears to have no adverse effects on blood flow in free musculocutaneous flaps. Sodium nitroprusside, however, in a dose causing a 30% decrease in systemic vascular resistance and arterial pressure, causes a severe reduction in free flap blood flow despite maintaining cardiac output.     

Histocompatibility antigen studies in women with recurrent miscarriages and Müllerian uterine anomalies

The objective of the present study was to examine the effects of a long-acting angiotensin converting enzyme inhibitor, imidapril ((4S)-1-methyl-3-?(2S)-2-[N-(1S)-1-ethoxycarbonyl-3-phenylpropyl) amino] propionyl?-2-oxoimidazolidine-4-carboxylic acid hydrochloride), for 7 days on the cerebral blood flow autoregulatory response to hypotension in hypertensive rats. We measured the cerebral blood flow at rest and during hemorrhagic hypotension, using laser-Doppler flowmetry. At the same time, the absolute baseline cerebral blood flow values in the parietal cortex were quantified with the hydrogen clearance method. After administration of imidapril at a dose of 5 mg/kg/day for 7 days, the resting value of mean arterial blood pressure was significantly decreased by 25 mm Hg (P < 0.001), cerebral vascular resistance was lowered by 14.4% (P < 0.05) and the lower limit of cerebral blood flow autoregulation was shifted to a lower level, 106+/-11 mm Hg (mean +/- S.D.), from 137+/-8 mm Hg in the control group (P < 0.001), while resting cerebral blood flow remained unchanged. The present results demonstrated that imidapril preserves cerebral blood flow and significantly shifts the lower limit of cerebral autoregulation towards lower blood pressure levels.     

Cerebrovascular and cardiovascular responses to graded tilt in patients with autonomic failure

BACKGROUND AND PURPOSE: Patients with autonomic nervous system failure often experience symptoms of orthostatic intolerance while standing. It is not known whether these episodes are caused primarily by a reduced ability to regulate arterial blood pressure or whether changes in cerebral autoregulation may also be implicated. METHODS: Eleven patients and eight healthy age- and sex-matched control subjects were studied during a graded-tilt protocol. Changes in their steady state middle cerebral artery mean flow velocities (MFV), measured by transcranial Doppler, brain-level mean arterial blood pressures (MABPbrain), and the relationship between the two were assessed. RESULTS: Significant differences between patients and control subjects (P < .05) were found in both their MFV and MABPbrain responses to tilt. Patients' MFV dropped from 60 +/- 10.2 cm/s in the supine position to 44 +/- 14.0 cm/s at 60 degrees head-up tilt, whereas MABPbrain fell from 109 +/- 11.7 to 42 +/- 16.9 mm Hg. By comparison, controls' MFV dropped from 54 +/- 7.8 cm/s supine to 51 +/- 8.8 cm/s at 60 degrees, whereas MABPbrain went from 90 +/- 11.2 to 67 +/- 8.2 mm Hg. Linear regression showed no significant difference in the MFV-MABPbrain relationship between patients and control subjects, with slopes of 0.228 +/- 0.09 cm.s-1.mm Hg-1 for patients and 0.136 +/- 0.16 cm.s-1.mm Hg-1 for control subjects. CONCLUSIONS: The present study found significant differences between patients and control subjects in their MFV and MABPbrain responses to tilt but no difference in the autoregulatory MFV-MABPbrain relationship. These results suggest that patients' decreased orthostatic tolerance may primarily be the result of impaired blood pressure regulation rather than a deficiency in cerebral autoregulation.     

Value of intracoronary ultrasound and Doppler in the differentiation of angiographically normal coronary arteries: a prospective study in patients with angina pectoris

BACKGROUND: A substantial proportion of patients undergoing heart catheterization for suspected coronary artery disease have normal angiograms. Coronary morphology and blood flow velocity can be assessed very accurately with intracoronary ultrasound and Doppler. The purpose of this study was to use both methods to classify further patients with suspected coronary artery disease but with coronary angiograms adjudged normal at the time. METHODS AND RESULTS: In forty-four patients with suspected coronary artery disease and normal coronary angiograms, intracoronary ultrasound and intracoronary Doppler were performed in the left anterior descending and left main coronary arteries. Coronary flow reserve was obtained by calculating the ratio of the maximal coronary flow mean velocity after the intracoronary administration of 10 mg papaverine to the coronary flow mean velocity at rest. Of 44 patients, 16 (36%) (group I) were found to have normal coronary morphology by intracoronary ultrasound and normal (> 3.0) coronary flow reserve (5.3 +/- 1.8). In seven patients (16%) (group II) there were normal intracoronary ultrasonic findings but a reduced coronary flow reserve (2.1 +/- 0.4). Plaque formation was found in a total of 21 (48%) of the 44 patients; mean plaque sizes were 3.6 +/- 1.6 mm2 for those in group III (normal coronary flow reserve) and 5.0 +/- 2.3 mm2 for those in group IV (reduced coronary flow reserve). Vessel area in both of these groups (16.3 +/- 8.0 mm2 and 19.2 +/- 6.1 mm2) was significantly larger than that of group I (14.6 +/- 5.7 mm2, P < 0.01). Plaque calcification was found in 25% of those in group III and 44% of those in group IV. Thus, only 36% of the patients with normal angiograms were true normal, 48% exhibited early stage of coronary atherosclerosis, and the other 16% might be considered as syndrome X. CONCLUSION: Intracoronary ultrasound and Doppler can be used to differentiate further heart disease in patients with normal coronary angiograms. Only a minority were true normal. Early signs of atherosclerosis cannot be detected by coronary angiography. This may have important therapeutic and prognostic implications.     

The effects of a converting enzyme inhibitor (captopril) and angiotensin II on fetal renal function

1. Renal function was studied in chronically catheterized fetal sheep (119-128 days gestation), before and during treatment of the ewe with the angiotensin converting enzyme (ACE) inhibitor, captopril, which crosses the placenta and blocks the fetal renin angiotensin system. 2. An i.v. dose of 15 mg (about 319 micrograms kg-1) of captopril to salt-replete ewes followed by an infusion to the ewe of 6 mg h-1 (about 128 micrograms kg-1 h-1) caused a fall in fetal arterial pressure (P < 0.01), and a rise in fetal renal blood flow (RBF) from 67.9 +/- 5.6 to 84.9 +/- 8.3 ml min-1 (mean +/- s.e. mean) (P < 0.05). Renal vascular resistance and glomerular filtration rate (GFR) fell (P < 0.01); fetal urine flow (P < 0.01); fetal urine flow (P < 0.01) and sodium excretion declined (P < 0.05). 3. Ewes were treated for the next 2 days with 15 mg captopril twice daily. On the 4th day, 15 mg was given to the ewe and fetal renal function studied for 2 h during the infusion of captopril (6 mg h-1) to the ewe. Of the 9 surviving fetuses, 3 were anuric and 3 had low urine flow rates. When 6 micrograms kg-1 h-1 of angiotensin II was infused directly into the fetus RBF fell from 69 +/- 10.1 ml min-1 to 31 +/- 13.9 ml min-1, GFR rose (P < 0.05) and urine flow (P < 0.01) and sodium excretion increased in all fetuses. 4. It is concluded that the small fall in fetal arterial pressure partly contributed to the fall in fetal GFR but in addition, efferent arteriolar tone fell so that the filtration pressure fell further. Thus maintenance of fetal renal function depends on the integrity of the fetal renin angiotensin system. These findings explain why use of ACE inhibitors in human pregnancy is associated with neonatal anuria.     

Direct measurement of steroid sulfate and glucuronide conjugates with high-performance liquid chromatography-mass spectrometry

Laser Doppler flowmetry (LDF) is a sensitive method for the measurement of microvascular blood flow in tissue. The method has been found useful for estimating skin, liver, or gastrointestinal blood flow. Whether it can be applied laparoscopically and whether it is able to measure the intraparenchymal blood flow of an intraabdominal organ is still unknown. In a pilot study, 6 pigs received a laparotomy for placement of a 19-gauge LDF needle probe into the renal parenchyma. Three different locations of the lower pole kidney were chosen for the blood flow measurement. The reliability of using the instrument to measure the renal tissue blood flow was assessed by comparison of the results of renal arterial blood flow obtained from a well-established methodology--ultrasonic Doppler flowmetry. Recordings were taken following (a) intravenous administration of 0.005 mg/kg norepinephrine, (b) manual compression of the suprarenal aorta, and (c) intravenous injection of a lethal dose of phenobarbital (50 mg/kg). Measurements of LDF were possible in all kidney units. The renal tissue perfusion detected by LDF correlated excellently with the renal arterial blood flow under different renal perfusion pressures. The feasibility of using LDF probe to measure the renal tissue perfusion in a laparoscopic model was then assessed in 15 pigs. Under pneumoperitoneum, the right kidneys were approached transperitoneally with the animal in the decubitus position. A total of three trocars were used. The peritoneum and Gerota's fascia were incised and the LDF needle probe was manipulated and inserted by an endoforceps into the renal tissue via a 5-mm trocar. The insertion of the LDF needle probe was technically feasible in all 15 kidney units, and the depth of insertion could be adjusted under direct vision. Baseline values for the renal cortical and renal medullary blood flow were 50.1 +/- 17.7 and 8.8 +/- 3.3 ml/min/100 g tissue, respectively. Spatial variations of the LDF measurements averaged 6%, and temporal variations over 15 min averaged 5%. Four additional hemodynamic parameters were simultaneously recorded, including left carotid artery blood flow, aortic blood pressure, inferior vena caval pressure, and intraabdominal pressure. It appears that systemic and renal hemodynamic parameters can be monitored reliably and continuously in the porcine model. This method allows further information concerning hemodynamic changes and safety of laparoscopy to be obtained.     

Biplane transoesophageal echocardiography, transthoracic Doppler, and magnetic resonance imaging in the assessment of coarctation of the aorta

This study compared flow-sensitive magnetic resonance imaging with biplane transoesophageal echocardiography in combination with continuous wave Doppler from the suprasternal notch in patients with native coarctation or after surgical repair. Twenty patients (mean age 33 years, range 17-60) were investigated, of whom 15 had undergone surgery at mean age 13 years, range 5-43. Peak and mean flow in the ascending and descending aorta as well as coarctation peak velocity were determined with the magnetic resonance imaging phase contrast technique. Coarctation peak velocity was also measured by Doppler from the jugulum. Magnetic resonance imaging axial sections as well as biplane transoesophageal echocardiography were used to measure the smallest diameter of the constricted segment. Sixteen healthy volunteers, mean age 36 years, range 22-63, provided reference values for magnetic resonance imaging determined volume of flow in the aorta. Peak flow in the descending aorta was 9.2 +/- 3.7 l. min-1 (reference 13.0 +/- 2.5, P < 0.01) and mean flow 3.1 +/- 0.9 l. min-1 (reference 3.4 +/- 0.8, P > 0.05). The ratio of descending-to-ascending peak flow was 0.54 +/- 0.17 (reference 0.69 +/- 0.10, P < 0.01) and mean flow 0.68 +/- 0.15 (reference 0.69 +/- 0.08, P > 0.05). The coarctation velocity was slightly higher with Doppler than with magnetic resonance imaging (+0.24 +/- 0.44 m. s-1, 95% confidence interval +0.45 to +0.02 m. s-1, P = 0.05). The coarctation diameter was slightly larger with magnetic resonance imaging than with transoesophageal echocardiography (1.4 +/- 3.5 mm, 95% confidence interval +3.1 to -0.3 mm, P = 0.11). Both methods are suitable for the assessment and follow-up of coarctation of the aorta. Flow assessment with magnetic resonance imaging provides a hitherto unavailable measure with which to assess the severity of obstruction.     

Differing effects of anesthetics on splanchnic arterial blood flow during hemorrhagic shock

The effect of anesthesia on splanchnic blood flow was examined during hemorrhagic shock and resuscitation. Sprague-Dawley rats were anesthetized with the inhalation anesthetic, methoxyflurane, or pentobarbital (65 mg/kg). Transonic Doppler flow probes were placed around the superior mesenteric artery (SMA) and the abdominal aorta, and the animals were subjected to acute hemorrhage (or sham) to 30 mmHg for 90 min followed by 30 min of resuscitation with shed blood (n = 6/group). At 90, 105, and 120 min, sham animals in both anesthetic groups showed comparable blood pressures with a 50% decrease in SMA and aortic blood flow. Acute hemorrhage decreased SMA blood flow by 94.5 +/- 0.01 and 86.0 +/- 2.8%, respectively, in the pentobarbital and methoxyflurane groups, with similar changes occurring in aortic blood flow. During resuscitation, arterial pressure remained significantly depressed and SMA blood flow decreased by 65% in the pentobarbital group, whereas blood pressure returned to control levels and SMA blood flow increased to 56% of control values (P < 0.001) in the methoxyflurane group. The findings indicate that the choice of anesthetic agent may significantly impact splanchnic blood flow and needs to be taken into account when designing experiments examining effects of hemorrhagic shock.     

Molecular basis of type III hyperlipoproteinemia in Germany

1. The aim of the present investigation was to evaluate the effect of cloricromene on myocardial infarct size, regional myocardial blood flow and neutrophil accumulation in a canine model of ischaemia-reperfusion. 2. Dogs were instrumented to measure blood pressure, left anterior descending (LAD) coronary flow (flow probe) and regional myocardial blood flow (coloured microspheres). Two groups were studied: (i) CLO (n = 8) received an infusion of cloricromene (15 micrograms/kg per min); and (ii) VEH (n = 8) received saline. Infusions began at the onset of ischaemia (60 min) and continued through reperfusion (180 min). 3. Haemodynamic responses were not different between groups. Cloricromene reduced the area of necrosis expressed as a percentage of the area at risk from 35 +/- 3% in the VEH group to 23 +/- 4% in the CLO group (P < 0.05). Regional myocardial blood flow in the ischaemic region was different between groups; VEH dogs showed an early reperfusion hyperaemia followed by a progressive reduction in flow, while CLO dogs exhibited a gradual increase in reflow in the absence of an early hyperaemic response (P < 0.05). Left anterior descending flow was enhanced during the reperfusion period in the CLO group compared with VEH (P < 0.05). Cloricromene reduced polymorphonuclear neutrophil (PMN) infiltration (myeloperuxidase activity) in all myocardial regions when compared with VEH (non-ischaemic zone, 0.34 +/- 0.54 vs 0.05 +/- 0.01 IU/100 mg; ischaemic zone, 2.03 +/- 0.80 vs 0.24 +/- 0.08 IU/100 mg; and necrotic zone, 0.56 +/- 0.04 vs 3.59 +/- 1.09 IU/100 mg for VEH vs CLO groups, respectively; P < 0.01). In a separate in vitro preparation, cloricromene reduced adherence of platelet-activating factor (PAF)-stimulated PMN to canine coronary endothelium. Stimulation of PMN by 100 nmol/L PAF resulted in adherence of 176 +/- 36 compared with 48 +/- 12 cells/mm2 in PAF-stimulated PMN treated with 100 mumol cloricromene (P < 0.001). 4. These data indicate that cloricromene reduces myocardial infarct size in a canine model of ischaemia-reperfusion injury. Postischaemic blood flow patterns are significantly different in cloricromene-treated dogs. Cloricromene-mediated reductions in infarct size, neutrophil accumulation and adherence may play a role in this effect.     

Autonomic regulation of nasal vessels during changes in body position

The effects of postural changes on nasal airflow and nasal capillary blood flow were investigated in 15 healthy volunteers. Measurements were performed following nasal application of saline solution (control), the alpha-1 receptor antagonist prazosin, the alpha-2 receptor antagonist yohimbine, and after application of both prazosin and yohimbine. Nasal airflow in the control experiments did not significantly differ in the upright (362 +/- 166 ml/s), dorsally recumbent (350 +/- 167 ml/s) and 70 degrees head down position (311 +/- 167 ml/s). Following application of prazosin, nasal airflow was reduced to 223 +/- 121 ml/s in the upright position. Prazosin treatment significantly reduced nasal airflow to 177 +/- 111 ml/s when subjects were placed in dorsally recumbent positions and to 117 +/- 104 ml/s in 70 degrees head down positions (P < 0.001). Following application of yohimbine, nasal airflow remained stable when subjects were turned from upright (348 +/- 165 ml/s) to supine position (352 +/- 186 ml/s), whereas it was reduced to 199 +/- 137 ml/s in the head-down position. Application of both prazosin and yohimbine significantly increased nasal capillary blood flow in laser Doppler flowmetry measurements (P < 0.05). Changes in body position with or without application of the active drugs did not alter nasal capillary blood flow. These findings suggest that nasal congestion due to increased filling pressure in nasal capacitance vessels following postural changes is mainly prevented by alpha-1 adrenergic mechanisms.     

Increasing survival in AIDS patients with cytomegalovirus retinitis treated with combination antiretroviral therapy including HIV protease inhibitors

Intravascular Doppler is widely used for experimental studies in the coronary circulation. We designed this study to assess baseline bloodflow and arteriolar resistance in the porcine renal circulation and to study the vasomotor responses of vasoactive drugs. In anesthesized piglets (n = 15), renal arterial diameter was measured with quantitative angiography and blood flow velocity with a Doppler wire (Cardiometrics). Bloodflow and resistances were calculated at baseline and after injection of vasoactive drugs (isosorbide dinitrate, papaverine). This allowed us to determine the renal bloodflow reserve (the capacity of the kidney to augment basal bloodflow). Injection of isosorbide dinitrate was associated with an increase in average peak velocity of 64% (P < 0.01) and a small (from 4.5 to 4.74, P < 0.01) but significant increase in renal artery diameter, resulting in an increase in bloodflow of 82% (P < 0.01) and a decrease in arteriolar resistance of 46% (P < 0.01). Bloodflow returned to baseline (4.76 +/- 1.48 mL/s) approximately 5 min after isosorbide injection. Average Peak Velocity increased almost twofold after papaverine injection (60 +/- 10 to 108 +/- 24 cm/sec, P < 0.01). There was a significant (P < 0.01) increase in arterial bloodflow of 96% in the right and 79% in the left renal artery after injection of papaverine with a corresponding significant (P < 0.01) decrease in arteriolar resistance of 49% in the right and 44% in the left renal artery. Using a combination of quantitative angiography and intravascular Doppler allows easy measurement of baseline renal blood flow and of the effects of vasodilator drugs on bloodflow and resistance. The results show that a vasodilatator reserve exists in the renal circulation but is less marked than that reported in the coronary circulation.     

Signal improvement of pulmonary venous Doppler flow prifile after intravenous injection of levovist]

The analysis of the pulmonary venous flow Doppler pattern can assist in the determination of the severity of mitral regurgitation and, in conjunction with transmitral flow pattern, the assessment of left ventricular diastolic dysfunction. In about one third of the cases, however, transthoracic ultrasonography is not able to record an adequately analyzable pulmonary venous flow pattern. The aim of the study was to examine and compare the effect of the echo-enhancing agent Levovist on the pulsed-wave Doppler flow quality of the transthoracically (TTE) and transesophageally (TEE) recorded pulmonary venous flow. In 26 consecutive patients, a qualitative (score system) and quantitative analysis of the pulmonary venous flow pattern was obtained before and after peripheral venous injection of Levovist at concentrations of 200 mg/ml (low dose) and 400 mg/ml (high dose). The number of measurable studies for the antegrade pulmonary venous flow increased after Levovist from 85% to 96% for TTE and from 96% to 100% for TEE. The retrograde flow as seen by TTE was adequately analyzable in only 45% before and in 73% after injection of Levovist (p < 0.02). Before any contrast enhancement, the retrograde pulmonary venous flow recorded by TEE could be analyzed in 77% of the patients with the percentage increasing to 88% and 92% after administration of a low and high dose of Levovist, respectively (p < 0.05). In particular, the quality score of the retrograde flow was significantly altered by the administration of Levovist (increase from 1.8 +/- 1.0 to 2.6 +/- 1.1 (low dose Levovist), p < 0.05 and to 2.7 +/- 1.3 (high dose Levovist). p < 0.05). The pulsed-wave Doppler evaluation by TTE without Levovist underestimated the velocities of the antegrade and retrograde pulmonary venous flow After administration of Levovist, the recorded values are comparable to those obtained by TEE. An analogous pattern is encountered when quantifying the duration of the retrograde flow component. Thus, the peripheral venous injection of Levovist leads to an improved quality of the pulmonary venous flow Doppler signal recorded by TTE. Qualitatively and quantitatively the values recorded by TTE after administration of Levovist are comparable to those of the TEE technique without an echo-enhancing agent.     

Study on the variation and mechanism of diameter of nailfold capillary and its blood flow speed in patient with chronic pain syndrome]

Diameter of nailfold capillaries and their blood flow speed in 90 patients with pain syndrome were measured accurately by using YJD clinical microcirculatory image analyser, and the data obtained were compared with that of 31 normal subjects. The results showed (1) Shortening of capillary loop and slow down of blood flow were revealed in patients no matter where the location of pain was; (2) The disturbance of microcirculation was more prominent in case of chronic pain patient, manifested chiefly as slow down of blood flow speed (0.19 +/- 0.09 mm/s in afferent branch) and increase of loop diameter (15.86 +/- 6.50 microns), as compared with those in normal subjects (0.35 +/- 0.13 mm/s and 14.01 +/- 3.31 microns respectively), the difference were significant, P < 0.01; (3) Typing according to Syndrome Differentiation of TCM, the afferent loop diameter of the Blood Stasis type were 9.23 +/- 1.65 microns, it was significantly different from that of other types; and the blood flow speed of this group was markedly slowing down (0.18 +/- 0.08 mm/s in afferent branch), the change was of significant difference in comparing with normal group, P < 0.01. Authors considered that the mechanism of changes in microcirculation was related to increase of blood viscosity and spasm or diastole of capillaries induced by neurohumoral regulation, and many humoral factors, as histamine, may take part in this procedure.     

Managing complex orthodontic problems: the use of implants for anchorage

In congestive heart failure captopril modifies the left ventricular filling pattern mainly by unloading the heart. We investigated whether the structural characteristics of the left ventricle may influence the acute effects of captopril on this pattern in patients with untreated hypertensive (H group, 6 patients) or idiopathic (I group, 14 patients) cardiomyopathy. We evaluated changes of pulsed Doppler mitral flow, of systemic arterial and wedge pulmonary pressures 40 min after 25 mg captopril administered sublingually, and correlated these changes with the M-mode echocardiographic relative wall thickness index (h/r). Baseline mean arterial pressure (H = 137 +/- 20 mm Hg, mean +/- SD, I = 95 +/- 19 mm Hg; p < 0.001), and h/r (H = 0.38 +/- 0.03, I = 0.28 +/- 0.09; p < 0.05) were greater in the high blood pressure group; wedge pressure, echocardiographic biplane ejection fraction, and Doppler indexes of the left ventricular filling were similar in the two populations. After captopril, ejection fraction did not change significantly, mean arterial pressure decreased significantly in hypertensive patients (H group, baseline = 137 +/- 20, captopril = 119 +/- 10, p = 0.02; I group, baseline = 95 +/- 19, captopril = 90 +/- 24, p = nonsignificant), and the wedge pressure was reduced by the same extent in both groups (H group, baseline = 27.7 +/- 3, captopril = 21 +/- 7, p < 0.05; I group, baseline = 20 +/- 12, captopril = 15 +/- 8, p < 0.05). In the H group early mitral flow increased [(E wave integral) x (mitral annulus area)] by 38 +/- 15%, and was almost steady in the I group (-1.3 +/- 30%; group H vs. I = p < 0.01); late mitral flow [(A wave integral) x (mitral annulus area)] showed a pattern exactly opposite to this (H = +0.4 +/- 40%, I = +38 +/- 19; p < 0.01). In the whole population there was a significant correlation between the early/late flow ratio variations and baseline h/r (r = 0.6, p < 0.05). In chronic congestive heart failure, changes in left ventricular filling with captopril are related to h/r: a higher index, as recorded in the H group, is associated with "true normalization' of the filling pattern after captopril; a lower index, as recorded in the I group, is associated with "pseudonormalization' despite a similar decrease of left ventricular filling pressure.