Autoregulation of human inner ear blood flow during middle ear surgery with propofol or isoflurane anesthesia during controlled hypotension

We used controlled hypotension to obtain a bloodless cavity during middle ear surgery under an optical microscope. No previous study has assessed the effect of controlled hypotension on inner ear blood flow (IEF) autoregulation in humans receiving propofol or isoflurane anesthesia. In the present study, the IEF autoregulation was determined using laser Doppler flowmetry in combination with transient evoked otoacoustic emissions (TEOAEs) during controlled hypotension with sodium nitroprusside in 20 patients randomly anesthetized with propofol or isoflurane. A coefficient of IEF autoregulation (Ga) was determined during controlled hypotension, with a Ga value ranging between 0 (no autoregulation) and 1 (perfect autoregulation). During controlled hypotension with propofol, IEF remained stable (1%+/-6%; P > 0.05) but decreased by 25%+/-8% with isoflurane (P < 0.05). The Ga was higher during propofol anesthesia (0.62+/-0.03) than during isoflurane anesthesia (0.22+/-0.03; P < 0.0001). Under propofol anesthesia, there were individual relationships between TEOAE amplitude and change in IEF in four patients. Such a correlation was not observed under isoflurane anesthesia. These results suggest that human IEF is autoregulated in response to decreased systemic pressure. Furthermore, isoflurane has a greater propensity to decrease cochlear autoregulation and function than propofol. IMPLICATIONS: The present study shows that inner ear blood flow is autoregulated under propofol, but not isoflurane, anesthesia during controlled hypotension in humans during middle ear surgery. Further studies are needed to explore the postoperative auditory functional consequences of the choice of the anesthetic drug used in middle ear surgery.     

Influence of the renal endothelin A system on the autoregulation of renal hemodynamics in SHRs and WKY rats

In this study, we investigated the influence of a short-term blockade of the renal endothelin A system on the autoregulation of total renal blood flow, cortical renal blood flow, and pressure-dependent plasma renin activity in spontaneously hypertensive rats (SHRs) and normotensive controls [Wistar-Kyoto (WKY) rats]. In anesthetized rats, renal blood flow was measured by a transit-time flow probe and cortical blood flow by a laser flow probe. Blood samples were taken for measurement of plasma renin activity. Renal perfusion pressure was reduced in 5-mm Hg steps by means of a servocontrolled electropneumatic device by an inflatable suprarenal cuff. During the experiments, the rats (n = 6, each group) received an intrarenal infusion of either the selective endothelin A-receptor antagonist BQ123 (3 mg/kg/h) or vehicle. We observed an improvement of total and cortical blood flow autoregulation as indicated by a shift of lower limits of autoregulation to lower threshold pressures [103 +/- 2 vs. 132 +/- 4 mm Hg compared with 98 +/- 3 vs. 120 +/- 4 mm Hg (mean +/- SEM); p < 0.01 resp. p < 0.05] in BQ123-treated SHRs, whereas BQ123 had no influence on breakpoints of autoregulation in WKY rats (p > 0.05). Pressure-dependent plasma renin activity in SHRs was not influenced by BQ123. Renal blood flow autoregulation is improved in SHRs after short-term blockade of the renal endothelin A system. This effect is independent of the renin-angiotensin system. The endothelin A system does not seem to play an important role in the autoregulation of renal blood flow in normotensive WKY rats.     

Impaired dynamic cerebral autoregulation in carotid artery stenosis

BACKGROUND AND PURPOSE: If it could be determined whether cerebral blood flow can be maintained (autoregulated) during transient falls in arterial blood pressure, we might be able to identify patients with carotid stenosis who are at risk of stroke. However, conventional methods of determining autoregulation in such patients are invasive and/or expensive. METHODS: We used a new noninvasive method to estimate dynamic cerebral autoregulation in 27 patients with carotid stenosis and 21 age-matched normal controls. After a stepwise fall in arterial blood pressure, we determined the rate of rise of middle cerebral artery blood flow velocity compared with that of arterial blood pressure. We compared the method with a conventional method of determining cerebral hemodynamics, CO2 reactivity. RESULTS: Autoregulatory index (ARI) was significantly reduced in middle cerebral arteries ipsilateral to a stenosed/ occluded carotid artery: mean +/- SD 3.3 +/- 2.2 compared with normal controls (6.3 +/- 1.1; P < .0001) and nonstenosed carotid arteries in patients (5.9 +/- 2.1; P < .002). A subgroup of patients with severe impairment was identified. ARI returned to normal after carotid endarterectomy was performed. In a number of cases, ARI was impaired in the presence of CO2 reactivity. CONCLUSIONS: This simple technique allows identification of impaired autoregulation in patients with carotid artery disease. It may allow identification of patients at risk from transient falls of blood pressure as may occur at the onset of antihypertensive therapy and during surgery. It may allow a subgroup of patients with asymptomatic carotid stenosis who are at risk of hemodynamic stroke to be identified.     

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.     

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.     

Dental chapters of Serefeddin Sabuncuoglu''s (1385-1468?) illustrated surgical book Cerrahiyyetu''l Haniyye

The goal of this study was to determine whether exogenous application of L-arginine could restore impaired agonist-induced increases in arteriolar diameter during diabetes mellitus. We used intravital microscopy to examine reactivity of cheek pouch arterioles (50 microns in diameter) in nondiabetic and diabetic (2 weeks after injection of streptozotocin) hamsters in response to histamine and substance P. In nondiabetic hamsters histamine (1.0 and 5.0 microM) dilated cheek pouch arterioles by 15 +/- 1 and 22 +/- 1%, respectively, and substance P (50 and 100 nM) dilated arterioles by 14 +/- 3 and 21 +/- 4%, respectively. In addition, dilatation of arterioles in response to histamine and substance P in nondiabetic hamsters was abolished by application of an enzymatic inhibitor of nitric oxide synthase (L-NMMA). In contrast, histamine- and substance P-induced increases in arteriolar diameter were markedly reduced in diabetic hamsters. Histamine (1.0 and 5.0 microM) dilated arterioles by only 5 +/- 1 and 4 +/- 2%, respectively, and substance P (50 and 100 nM) dilated arterioles by only 6 +/- 2 and 5 +/- 3%, respectively (p < 0.05 vs. nondiabetic hamsters). Nitroglycerin produced similar vasodilatation in nondiabetic and diabetic hamsters. Next, we examined whether exogenous application of L-arginine (100 microM) could restore impaired histamine- and substance P-induced increases in arteriolar diameter in diabetic hamsters. We found that L-arginine did not restore altered nitric oxide synthase-dependent vasodilatation in diabetic hamsters. These findings suggest that short-term diabetes mellitus alters agonist-induced increases in arteriolar diameter. In addition, the mechanism of altered arteriolar reactivity during diabetes mellitus does not appear to be related to an impaired availability of L-arginine.     

Head-down-tilt bed rest alters forearm vasodilator and vasoconstrictor responses

To test the hypothesis that head-down-tilt bed rest (HDBR) for 14 days alters vascular reactivity to vasodilatory and vasoconstrictor stimuli, the reactive hyperemic forearm blood flow (RHBF, measured by venous occlusion plethysmography) and mean arterial pressure (MAP, measured by Finapres) responses after 10 min of circulatory arrest were measured in a control trial (n = 20) and when sympathetic discharge was increased by a cold pressor test (RHBF + cold pressor test; n = 10). Vascular conductance (VC) was calculated (VC = RHBF/MAP). In the control trial, peak RHBF at 5 s after circulatory arrest (34.1 +/- 2.5 vs. 48.9 +/- 4.3 ml . 100 ml-1 . min-1) and VC (0.34 +/- 0.02 vs. 0.53 +/- 0.05 ml . 100 ml-1 . min-1 . mmHg-1) were reduced in the post- compared with the pre-HDBR tests (P < 0. 05). Total excess RHBF over 3 min was diminished in the post- compared with the pre-HDBR trial (84.8 vs. 117 ml/100 ml, P < 0.002). The ability of the cold pressor test to lower forearm blood flow was less in the post- than in the pre-HDBR test (P < 0.05), despite similar increases in MAP. These data suggest that regulation of vascular dilation and the interaction between dilatory and constrictor influences were altered with bed rest.     

Vasomotion and blood flow regulation in hamster skeletal muscle microcirculation: A theoretical and experimental study

A mathematical model of a microvasculature was used to study the effects of myogenic and flow-dependent stimuli on the characteristics of vasomotion and microvascular perfusion regulation. The model includes three branching orders of arterioles derived from in vivo observations and incorporates a mechanism for terminal arteriolar closure during vasomotion. Simulations were performed to evaluate the effect of vasodilation and vasoconstriction on vasomotion pattern, and the changes in arteriolar effective diameter and flow in response to arterial blood pressure variations triggering the regulatory mechanisms. Vasomotion patterns were studied in the hamster cutaneous muscle, visualized by fluorescent microscopy, in control conditions and after injection of acetylcholine (Ach) or NG-monomethyl-L-arginine (L-NMMA). We have found that vasomotion may be caused by different combinations of feedback mechanisms, including a strong rate-dependent myogenic response or a strong flow-dependent mechanism with no rate-dependent response. Decreasing the rate-dependent component of the myogenic mechanism and increasing the time constant of the flow-dependent mechanism causes vessel stabilization and disappearance of vasomotion. In hamster microcirculation, Ach decreased vasomotion frequency and increased vasomotion amplitude and arteriolar effective diameter, whereas L-NMMA caused a slight increase in vasomotion frequency and decrease in effective diameter. Model simulations, under dilatory and constrictory stimuli, confirmed these results. Moreover, the model predicted that mean blood flow is maintained closer to normal despite arterial pressure changes (+/-15% flow changes versus +/-50% pressure variations) when the vessels were in nonoscillatory than when they are in oscillatory state. In conclusion, a large variety of vasomotion patterns affect arteriolar resistance and microvessel perfusion in skeletal muscle. Furthermore, in the presence of vasomotion the network exhibits a poorer aptitude for regulating blood flow during arterial pressure changes (i.e., worse autoregulation) than the nonoscillatory network.     

Relationship between haemodynamics and morphology in pulmonary hypertension. A quantitative intravascular ultrasound study

BACKGROUND: Intravascular ultrasound imaging of the pulmonary arteries has been demonstrated to be a reliable method of quantifying vessel diameter, luminal area and pulsatility. Simultaneous measurement of flow velocity and its response to vasodilators allows the relationship between morphology and functional compromise to be studied, especially endothelial dysfunction. METHODS: In 51 patients (mean age = 49.8 +/- 12.6 years, 17 female) we performed right heart catheterization and simultaneous intravascular ultrasound of pulmonary artery branches. The patients were divided in two groups: group 1 with normal pulmonary artery pressure and pulmonary vascular resistance, and group 2 with pulmonary hypertension (peak pulmonary artery pressure > 30 mmHg and/or mean pulmonary artery pressure > 20 mmHg). Vessel wall and lumen were studied using a 2.9 F intravascular ultrasound catheter with a 30 MHz phased array transducer. Measurement of blood flow velocity was accomplished by a Doppler flow wire (0.018 inch). The maximal flow change during acetylcholine infusion (adjusted to 10(-6); 10(-5), and 10(-4) M concentration in the blood vessel) was measured. RESULTS: There were no significant differences between groups 1 and 2 with respect to age (48.5 +/- 14.3 years vs 50.3 +/- 12.3 years; P = ns), gender (4 female/8 male vs 13 female/26 male; P = ns), luminal area of the vessel segment in which the intravascular ultrasound measurements were obtained (11.8 +/- 6.1 mm2 vs 16.7 +/- 14.3 mm2; P = ns), internal diameter (3.9 +/- 1.2 mm vs 4.2 +/- 1.7 mm; P = ns), and external diameter (6.1 +/- 1.3 mm vs 6.9 +/- 2.1 mm; P = ns). Cross-sectional images of the pulmonary artery wall demonstrated a single ring with high echodensity with a thin inner layer regarded as intima in group 1. In contrast, the majority of patients (n = 35/39) in group 2 demonstrated a thickening of the intimal layer and/or a disturbance of layering of the echogenic arterial wall. The relative wall thickness was higher in group 2 than in group 1 (22.5 +/- 10.4% vs 15.3 +/- 6.5%; P < 0.05). There were no significant correlations between pulmonary artery pressure and wall thickness pulmonary artery pressure and area change in the cardiac cycle, acetylcholine-dependent increase in pulmonary flow and morphological changes in the vessel wall. CONCLUSION: We conclude that intravascular ultrasound is capable of detecting morphological changes in the pulmonary vessel wall in pulmonary hypertension and that vessel wall hypertrophy of small pulmonary segment arteries, as detected by intravascular ultrasound, is not predictive of functional vasodilatory response of resistance vessels of the same vessel area.     

Quantification of infectious duck hepatitis B virus by radioimmunofocus assay

We studied whether a flow-independent increase of luminal wall shear stress (WSS) could dilate hamster arterioles in vivo and which endothelial mediators are potentially involved. To this end the plasma viscosity was elevated by exchanging blood for dextran-erythrocyte solution thereby augmenting WSS. Diameters of small and large arterioles as well as red blood cell velocities were measured before and after exchange of blood for solutions of identical haematocrit containing either high- (HMWD) or low-molecular weight dextran (LMWD). The potential role of endothelial autacoids was investigated by local application of the NO-synthase inhibitor NG-nitro-L-arginine (L-NNA), the inhibitor of cyclooxygenase, indomethacin (3 microM), or the K+-channel blocker, tetrabutylammonium (TBA, 0.1 mM) to assess the potential effects of EDHF. HMWD (n = 11 animals) increased plasma viscosity by 64 +/- 3% and dilated arterioles of all branching orders (A1-A4) significantly [by 24 +/- 3% (A1-A2) and 32 +/- 3% (A3-A4)]. This dilation compensated fully for the calculated initial increase of WSS. LMWD (n = 6) did not affect plasma viscosity or arteriolar diameters. Tissue treatment with L-NNA (30-300 microM, n = 12) substantially diminished the HMWD-induced dilation in small arterioles (A3-A4; to 13 +/- 3%; P<0.05) and virtually abolished it in large ones (A1-A2). Consequently, the calculated WSS increased significantly in these arterioles (by 31 +/- 5%). TBA combined with L-NNA (n = 4) did not reduce further the remaining dilation. Indomethacin (n = 6) had no effect on HMWD-induced dilation. We conclude that an increase of WSS induces a mainly NO-mediated arteriolar dilation. This dilation occurs in all arteriolar branching orders and is of sufficient magnitude to compensate for the initial WSS-increase. Thus, any elevations of WSS fulfil the requirement for a signal to change diameter along the arteriolar tree in a coordinated manner. The fully compensating dilation which we observed indicates that WSS is a controlled variable. It does, however, raise questions as to its role as a continuous endothelial stimulus.     

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.     

L-Arginine normalizes coronary vasomotion in long-term smokers

BACKGROUND: Noninvasive measurements of myocardial blood flow (MBF) with PET revealed an abnormal coronary vasomotor response to cold pressor test in healthy long-term smokers. If coronary endothelial dysfunction accounted for this abnormality, we hypothesized that it could be reversed by L-arginine as the substrate for NO synthase. METHODS AND RESULTS: MBF was quantified with 13N-labeled ammonia and PET in 11 healthy smokers (age, 45+/-10 years; 27+/-10 years of smoking) and in 12 age-matched nonsmokers on 2 separate days. On day 1, MBF was measured at rest and, after intravenous L-arginine, during cold pressor test. On day 2, MBF was measured during cold pressor test and then at rest during L-arginine. Baseline rate-pressure product (RPP) (6559+/-1590 versus 7144+/-1157 bpmxmm Hg) and MBF (0.65+/-0.14 versus 0.73+/-0.13 mL x g-1 x min-1) were similar in nonsmokers and smokers. Cold pressor test increased RPP similarly in both groups (53+/-26% versus 46+/-26%), whereas MBF increased in nonsmokers (to 0.93+/-0.25 mL x g-1 x min-1; P<0.05) but not in smokers (0.80+/-0.16 mL x g-1 x min-1). The percent MBF increase differed between nonsmokers and smokers (44+/-25% versus 11+/-14%; P=0.0017). However, after L-arginine, the magnitude of MBF response to cold pressor test no longer differed between groups (48+/-36% versus 48+/-28%), whereas RPP again increased similarly in the 2 groups (59+/-30% versus 44+/-16%). L-Arginine had no effect on resting MBF in smokers or nonsmokers. CONCLUSIONS: Our findings implicate the coronary endothelium as the major site of the abnormal vasomotor response in long-term smokers. Cold pressor test combined with PET imaging may allow the noninvasive identification of coronary endothelial dysfunction in humans.     

Effects of changes in intraocular pressure on human ocular haemodynamics

PURPOSE: Myogenic autoregulation is the ability of a vascular bed to maintain blood flow despite changes in perfusion pressure. Ocular perfusion pressure is defined as the difference between ocular arterial pressure and ocular venous pressure, the latter dependent on intraocular pressure (IOP). The aim of the present study was to investigate the effect of moderate increases in IOP on ocular haemodynamics. METHODS: Changes in IOP (+ 10 mmHg, +20 mmHg) were induced by a suction cup in 10 healthy subjects. Ocular fundus pulsations in the macula and the optic disc were measured by laser interferometry; blood flow velocities in the central retinal artery (CRA) and in the ophthalmic artery (OA) were measured by Doppler sonography. RESULTS: Changes in IOP caused a significant reduction in fundus pulsations, which was more pronounced in the macula (at +10 mmHg: -9 +/- 2%, p < 0.01; at +20 mmHg: -19 +/- 3%, p < 0.001) than in the optic disc (at +10 mmHg: -5 +/- 2% (ns); at +20 mmHg: -9 +/- 3%, p < 0.01). Mean flow velocity in the CRA was reduced by -5 +/- 3% at +10 mmHg (ns) and by -14 +/- 5% at +20 mmHg (p < 0.005), resistive index was increased by +4 +/- 1% at +10 mmHg (p < 0.05) and by +6 +/- 2% at +20 mmHg (p < 0.01). In contrast, a rise in IOP did not affect blood flow parameters in the OA. CONCLUSIONS: Our results from fundus pulsation measurements indicate that choroidal blood flow decreases when IOP is increased. The Doppler sonographic findings in the CRA indicate reduced blood flow velocity in this artery during raised IOP.     

The effect of clonidine on cerebral blood flow velocity, carbon dioxide cerebral vasoreactivity, and response to increased arterial pressure in human volunteers

BACKGROUND: Because patients may be taking clonidine chronically or may be receiving it as a premedication before surgery, the authors investigated its effect on cerebral hemodynamics. METHODS: In nine volunteers, middle cerebral artery mean blood flow velocity (Vm) was measured using transcranial Doppler ultrasonography (TCD). CO2 vasoreactivity was measured before clonidine administration (preclonidine), 90 min after clonidine, 5 microg/kg orally, then following restoration of mean arterial pressure (MAP) to the preclonidine level. In addition, Vm was measured after a phenylephrine-induced 30-mmHg increase in MAP. RESULTS: After clonidine administration, Vm decreased from 62 +/- 9 to 48 +/- 8 cm/s (P < 0.01), and MAP decreased from 86 +/- 10 to 63 +/- 5 mmHg (P < 0.01; mean +/- SD). Clonidine decreased the CO2 vasoreactivity slope from 2.2 +/- 0.4 to 1.2 +/- 0.5 cm x s(-1) x mmHg(-1) (P < 0.05); restoring MAP to the preclonidine level increased the slope to 1.60 +/- 0.5 cm x s(-1) x mmHg(-1), still less than the preclonidine slope (P < 0.05). CO2 vasoreactivity expressed as a percentage change in Vm, decreased after clonidine, 3.5 +/- 0.8 versus 2.4 +/- 0.8 %/mmHg (P < 0.05); this difference disappeared after restoration of MAP, 3.1 +/- 1.2 %/mmHg. With a 30-mmHg increase in MAP, Vm increased by 13% before and after clonidine (P < 0.05). CONCLUSIONS: Clonidine, 5 microg/kg orally, decreases Vm and slightly attenuates cerebral CO2 vasoreactivity, therefore decreased cerebral blood flow and mildly attenuated CO2 vasoreactivity should be anticipated.     

Clinical cancer research in a managed-care environment

PURPOSE: Autoregulation of optic nerve head blood flow (Fonh) in response to decreases in perfusion pressure has been demonstrated in animals and humans. The aim of this study was to determine change in Fonh when systemic blood pressure is increased. METHODS: Blood flow parameters, i.e. relative mean velocity, number, and flux of red blood cells in the ONH tissue (Velonh, Volonh and Fonh, respectively) were measured by laser Doppler flowmetry in one eye of 13 normal subjects (aged 16 to 58 years), at baseline, during, and after isometric exercises consisting of squatting. Brachial artery blood pressure was measured by sphygmomanometry. IOP was measured at baseline and at the end of squatting. RESULTS: During squatting mean arterial pressure increased from 103 +/- 6 mm Hg to 139 +/- 58 mm Hg (average +/- 95% confidence interval), IOP increased from 13 +/- 0.5 to 17 +/- 1 mm Hg. An average increase in PPm from 56 +/- 4 to 80 +/- 7 mm Hg induced no significant (p > 0.05) change in the blood flow parameters. The sensitivity (detection threshold) of the blood flow changes was 8%. CONCLUSION: This study shows for the first time in human autoregulation of Fonh when PPm is increased by increasing the systemic blood pressure.     

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.     

Prolonged systemic and regional haemodynamic effects of intracerebroventricular angiotensin II in conscious sheep

1. The haemodynamic mechanisms by which infusion of angiotensin II (AngII), either into the lateral cerebral ventricles (i.c.v.) or intravenously (i.v.), increased arterial pressure were studied in conscious sheep. 2. Sheep were previously fitted with flow probes for measurement of cardiac output and coronary, mesenteric, renal and iliac blood flows. 3. Intracerebroventricular AngII (10 nmol/h for 1 h) increased arterial pressure by 11 +/- 4 mmHg (P < 0.001) due to vasoconstriction, predominantly in the mesentric vasculature. These effects developed over 30 min and took 2 h to return to control. Following the infusion renal conductance increased continuously for 3 h, resulting in a parallel increase in renal blood flow (to 75 +/- 18 mL/min above control, P < 0.001). 4. Intracerebroventricular AngII increased plasma vasopressin from 0.8 +/- 0.3 to 7.2 +/- 1.8 pg/mL (P, 0.01), and reduced plasma renin concentration from 0.9 +/- 0.3 to < 0.4 nmol/L/h. 5. The pressor effect of i.v. AngII (5, 10, 25, 50 nmol/h) also depended on peripheral vasoconstriction, but the pattern of responses was different. The greatest degree of vasoconstriction occurred in the renal, followed by the mesentric and iliac vascular beds; these effects were rapid in onset and offset. 6. In conclusion, the pressor responses to both i.c.v. and i.v. angiotensin depended on peripheral vasoconstriction, but there were contrasting regional haemodynamic changes. ICV AngII caused a prolonged pressor response, mainly due to mesentric vasoconstriction possibly partly due to vasopressin release, and following the infusion there was a pronounced, long-lasting renal vasodilatation. In contrast, i.v. AngII caused vasoconstriction preferentially in the renal vascular bed and its effects were short lasting.     

Differential regional hemodynamic effects of corticotropin in conscious sheep

The regional hemodynamic effects of 5 days of intravenous infusion of corticotropin (ACTH) (5 micrograms/kg per day) were examined in conscious sheep (n = 8). Mean arterial pressure increased from 81 +/- 2 to 93 +/- 3 mm Hg (P < .001) on day 2 of ACTH and remained at this level during the infusion. Cardiac output increased from 5.13 +/- 0.19 to 6.06 +/- 0.33 L/min (P < .01) because of an increase in stroke volume from 65 +/- 4 to 79 +/- 8 mL per beat (P < .01); heart rate remained unchanged. ACTH did not alter total peripheral conductance but had differential effects on regional conductances. Mesenteric conductance fell from 5.8 +/- 0.2 to a minimum of 4.9 +/- 0.3 (mL/min)/mm Hg (P < .05), and renal conductance increased from 3.5 +/- 0.3 to 4.6 +/- 0.3 (mL/min)/mm Hg (P < .001). There was a small increase in iliac conductance (P < .05) and no change in coronary conductance. Mesenteric and iliac conductances fell progressively over 24 to 48 hours, whereas renal conductance increased rapidly after 3 hours of ACTH, reaching a maximum after 6 hours. Renal blood flow was increased during ACTH infusion from 278 +/- 18 to 403 +/- 23 mL/min (P < .001); mesenteric blood flow was unchanged; there was a small increase in iliac blood flow (P < .01); and coronary blood flow increased (P < .05), paralleling the change in cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravascular ultrasound in endovascular stent-grafts for peripheral aneurysm: a clinical study

The present series of experiments was performed to investigate the influence of acute intracranial hypertension on the upper limit (UL) of cerebral blood flow (CBF) autoregulation. Three groups of eight rats each--one with normal intracranial pressure (ICP) (2 mmHg), one with ICP = 30 mmHg, and one with ICP = 50 mmHg--were investigated. Intracranial hypertension was maintained by continuous infusion of lactated Ringer's solution into the cisterna magna, where the pressure was used as ICP. Cerebral perfusion pressure (CPP), calculated as mean arterial blood pressure (MABP)-ICP, was increased stepwise by continuous intravenous infusion of norepinephrine. CBF was calculated by the intracarotid 133Xe method. In all three groups the corresponding CBF/CPP curve included a plateau where CBF was independent of changes in CPP, showing intact autoregulation. At normal ICP the UL was found at a CPP of 141 +/-2 mmHg, at ICP = 30 mmHg the UL was 103+/-5 mmHg, and at ICP = 50 mmHg the UL was found at 88+/-7 mmHg. This shift of the UL was more pronounced than the shift of the lower limit (LL) of the CBF autoregulation found previously. We conclude that intracranial hypertension is followed by both a shift toward lower CPP values and a narrowing of the autoregulated interval between the LL and the UL.     

Renal hemodynamics in the rat before and during inhibition of angiotensin II

Renal blood flow (RBF) was measured with a noncannulating electromagnetic flow transducer in anesthetized rats which had been maintained for 3-5 wk on low, normal, or high salt plus deoxycorticosterone diets. After base-line observations, one of two dissimilar inhibitors of the renin-angiotensin system, angiotensin I converting enzyme inhibitor SQ 20881 or the structural analogue [Sar1,Ala8]angiotensin II was administered intravenously. The employed doses of SQ 20881 and [Sar1,Ala8]angiotensin II effectively inhibited the pressor and renal vasoconstrictor responses induced by exogenous angiotensin I and II, respectively, in each dietary group. Both inhibitors vasodilated kidneys in salt-restricted rats; however, neither affected base-line renal hemodynamics in salt-loaded rats. Pressure-flow relationships were evaluated by clamping the aorta to reduce renal perfusion pressure. Renal blood flow was autoregulated between 100 and 140 mmHg with the same efficiency before and during inhibition of angiotensin II in each dietary group. These data indicate that angiotensin II modifies base-line RBF and renal vascular resistance and are consistent with the view that the renin-angiotensin system is not an essential mechanism responsible for autoregulation of RBF in the rat.