Influence of sevoflurane on renal medullary blood flow in humans

Proper anesthetic management is necessary to preserve renal function during anesthesia and surgery. Using ultra-sound color Doppler, we examined the influence of sevoflurane on renal medullary blood flow in 20 adult patients without renal dysfunction. After identifying an interlobar artery in the outer medulla, we measured the velocity of the arterial blood flow before induction of anesthesia, and during sevoflurane anesthesia (1 MAC, 1.5 MAC). The minimum velocity of the interlobar arterial blood flow (Vmin) during wakefulness correlated significantly with creatinine clearance measured preoperatively. We did not find any significant change in Vmin after induction of sevoflurane anesthesia, despite significant decreases in mean arterial blood pressure.     

Pharmacological modulation of spontaneous renal blood flow dynamics

Two mechanisms contribute to renal autoregulation. The faster system, which is thought to be myogenic, operates at 0.1-0.2 Hz (i.e., 5-10 s/cycle), while the slower one, tubuloglomerular feedback, operates at 0.03-0.05 Hz (i.e., 20-30 s/cycle). Both attenuate spontaneous or induced fluctuations of blood pressure, but it has proven difficult to separate their individual contributions because there is potential for interaction between the two. The present study was designed to examine the dynamics of the faster system during pharmacological blockade of tubuloglomerular feedback. Normotensive and hypertensive rats were studied under isoflurane or halothane anesthesia. Administration of the loop diuretic furosemide plus the angiotensin II (ANGII) AT1 receptor antagonist losartan caused a 10-fold or greater natriuresis, indicating profound inhibition of ascending limb salt transport, and also produced characteristic changes in the transfer function relating blood pressure (input) to renal blood flow (output). Operation of the 0.1-0.2 Hz mechanism was essentially unaltered, as shown by the presence of a peak in phase angle at 0.1-0.2 Hz and reduction of gain at frequencies slower than 0.15 Hz. The 0.03-0.05 Hz mechanism was markedly inhibited, as shown by loss of the second phase angle peak at 0.03-0.05 Hz, loss of the local maximum in gain at 0.05 Hz, and loss of the second gain reduction below 0.05 Hz. Both during control and after inhibition of tubuloglomerular feedback, the 0.1-0.2 Hz system attenuated = 50% of the effects of spontaneous blood pressure fluctuations, suggesting that this mechanism, operating alone, can significantly stabilize renal blood flow in the face of spontaneous fluctuations of blood pressure.     

Antidiuretic hormone and the distribution of renal cortical blood flow

The radioactive microsphere method was used to study the distribution of cortical blood flow in anesthetized dogs during water diuresis and during antidiuresis. Infusion of antidiuretic hormone (ADH) at rates ranging from 0.33 to 0.5 mU/kg-min into dogs previously volume expanded with 3% dextrose resulted in an increase in urinary osmolality and a significant increase in fractional flow in the inner cortex. Mean arterial pressure, glomerular filtration rate, and renal plasma flow were unaltered by the infusion of ADH at these doses, suggesting that absolute, as well as fractional, blood flow to the inner cortex increased in response to ADH. In three additional experiments, termination of an infusion of ADH in hydropenic dogs and subsequent induction of water diuresis was accompanied by a shift in fractional cortical blood flow away from the inner cortex. The redistribution of cortical blood flow in response to ADH at a time when the kidney is producing a more concentrated urine supports the hypothesis that this vascular effect of ADH may have functional significance in the urinary concentration ability of the kidney.     

Drinking and blood pressure responses to central injection of L-NAME in conscious rats

The drinking behavior and blood pressure responses to i.c.v. administration of artificial cerebrospinal fluid (aCSF) or NG-nitro-L-arginine methyl ester (L-NAME, 10, 250, or 500 micrograms), an inhibitor of nitric oxide synthase, were examined in conscious rats following either osmotic stimulation (1.0 M NaCl, 15 ml/kg, s.c.) or induction of hemorrhage (0.7 ml/min to a 20% blood volume loss). Water intake increased in all animals. L-NAME at doses of 250 and 500 micrograms, but not 10 micrograms, significantly attenuated water consumption induced by both stimuli. The mean arterial blood pressure (MABP), which increased after osmotic stimulation, was maintained at pressor levels by 250 and 500 micrograms of L-NAME, but decreased progressively and reached basal levels after treatment with aCSF and the lowest dose of L-NAME (i.e., 10 micrograms). Hemorrhage significantly decreased MABP in all rats. The fall in blood pressure associated with hemorrhage returned to control levels in animals treated with 250 and 500 micrograms of L-NAME but not in those treated with aCSF or 10 micrograms of L-NAME. These results indicate that nitric oxide is involved in the regulation of drinking behavior and may play an important role in the central control of blood pressure during osmotic stimulation and hypotensive hemorrhage.     

Renal cortical blood flow distribution in obstructive nephropathy in rats

To examine the role of intrarenal hemodynamics in in obstructive nephropathy, we determined cortical blood flow distribution (CBFD) in rats with bilateral ureteral occlusion (BUO) and unilateral ureteral occlusion (UUO) during and after release of obstruction. Prior to release of obstruction of 24 hours' duration, we found that outer cortical perfusion decreased by 20+/-5% in both BUO and UUO rats. Furthermore, one hour after release of BUO, there was rapid normalization of CBFD associated with a modest return of glomerular filtration rate (GFR), an almost complete return of renal blood flow (RBF), and a marked postobstructive diuresis. In contrast, after release of UUO, we observed that outer cortical perfusion remained decreased by 21+/-31%, both GFR and RBF remained markedly depressed, and no diuresis occurred. These data demonstrate (1) marked ischemia of the outer cortex in both BUO and UUO during obstruction, (2) a rapid return of CBFD to a normal pattern after release of BUO, but (3) persistent outer cortical ischemia following release of UUO.     

Effects of sensory restriction upon responses to cortical stimulation in rats.

Assigned 43 Long-Evans hooded rats to 7 groups receiving normal, visually restricted, or auditory restricted rearing experience. Ss were then implanted with bipolar pairs of electrodes in the auditory and visual projection areas. Electrical stimulation of the cortex was used as a discriminative stimulus for a lever-pressing response. The ease of using electrical stimulation of visual or auditory cortex as a discriminative stimulus was related to Ss' paranatal sensory experience. Deleterious effects were limited to the restricted cortical projection area, and there were suggestions of facilitated performance in response to stimulation of the nonrestricted cortical areas. These effects were absent when restriction was induced in adulthood. (28 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cardiovascular responses of conscious rats to carotid body chemoreceptor stimulation by intravenous KCN

This multicentre, double-blind, randomised, crossover study compared the efficacy, safety and tolerability of subcutaneous sumatriptan (6 mg and 12 mg) with placebo in 134 in-patients with cluster headache. Headache improvement to mild or no pain at 5, 10 and 15 min after treatment was recorded. At 10 min, headache relief was reported by 25% (placebo), 49% (6 mg) and 63% (12 mg) of patients and at 15 min the results were 35% (placebo), 75% (6 mg) and 80% (12 mg) (p < 0.001 for all comparisons with placebo). The 12 mg dose was not significantly better than the 6 mg dose and was associated with more adverse events. The 6 mg dose is therefore recommended for the acute treatment of cluster headache.     

Ovarian blood flow in conscious and anaesthetized pregnant rabbits near term and the influence of arterial blood gas tensions

Total ovarian, luteal and stromal blood flows were measured with radioactive microspheres (25 mum diameter) in 7 rabbits anaesthetized with sodium pentobarbitone and 23 conscious rabbits at Day 28 of gestation. Despite major differences in cardiac output, arterial PO2, PCO2, pH and base status, ovarian tissue blood flows were similar in both groups. In the conscious rabbits total ovarian blood flow was negatively related to arterial pressure, and luteal blood flow was negatively related to pressure and arterial pH. In the anaesthetized rabbits ovarian stromal blood flow was positively related to arterial PO2.     

Cardiorespiratory and renal responses to arterial chemoreceptor stimulation by hypoxia or almitrine in men

1. The cardiorespiratory and renal responses to 3 h of normobaric whole-body hypoxic hypoxia (FiO2 = 0.12) as well as to arterial chemoreceptor stimulation by the oral administration of 100 mg almitrine bismesylate during normoxia were measured in 12 normotensive young men undergoing water diuresis. A third series of responses obtained under comparable conditions in the same subjects served as time controls. 2. No significant changes could be detected over time in the parameters measured in control experiments. The subjects reacted to both whole-body hypoxic hypoxia and to pharmacological chemoreceptor stimulation with significant increases in heart rate, tidal volume, minute ventilation and filtration-fraction. Overall renal vascular resistance rose significantly in hypoxia; increases in renal vascular resistance in almitrine experiments were not significant. 3. Renal fractional lithium excretion decreased significantly in response to whole-body hypoxic hypoxia and increased slightly in response to almitrine. Fractional urine and sodium excretion showed negligible changes. 4. The data indicate that, in humans, both almitrine and whole-body hypoxic hypoxia affect not only alveolar ventilation but also renal haemodynamics. 5. The renal electrolyte excretion pattern suggests that under certain circumstances (e.g. dilated renal vascular bed) acute, but well-tolerated, whole-body hypoxic hypoxia can simultaneously stimulate renal proximal tubular sodium reabsorption and inhibit distal tubular sodium reabsorption. The renal tubular responses also indicate that almitrine may influence renal tubular lithium reabsorption by, thus far, unknown mechanisms.     

Assessment of cerebral blood flow and CO2 reactivity after controlled cortical impact by perfusion magnetic resonance imaging using arterial spin-labeling in rats

We measured CBF and CO2 reactivity after traumatic brain injury (TBI) produced by controlled cortical impact (CCI) using magnetic resonance imaging (MRI) and spin-labeled carotid artery water protons as an endogenous tracer. Fourteen Sprague-Dawley rats divided into TBI (CCI; 4.02 +/- 0.14 m/s velocity; 2.5 mm deformation), sham, and control groups were studied 24 hours after TBI or surgery. Perfusion maps were generated during normocarbia (Paco2 30 to 40 mm Hg) and hypocarbia (PaCO2 15 to 25 mm Hg). During normocarbia, CBF was reduced within a cortical region of interest (ROI, injured versus contralateral) after TBI (200 +/- 82 versus 296 +/- 65 mL.100 g-1.min-1, P < 0.05). Within a contusion-enriched ROI, CBF was reduced after TBI (142 +/- 73 versus 280 +/- 64 mL.100 g-1.min-1, P < 0.05). Cerebral blood flow in the sham group was modestly reduced (212 +/- 112 versus 262 +/- 118 mL.100 g-1.min-1, P < 0.05). Also, TBI widened the distribution of CBF in injured and contralateral cortex. Hypocarbia reduced cortical CBF in control (48%), sham (45%), and TBI rats (48%) versus normocarbia, P < 0.05. In the contusion-enriched ROI, only controls showed a significant reduction in CBF, suggesting blunted CO2 reactivity in the sham and TBI group. CO2 reactivity was reduced in the sham (13%) and TBI (30%) groups within the cortical ROI (versus contralateral cortex). These values were increased twofold within the contusion-enriched ROI but were not statistically significant. After TBI, hypocarbia narrowed the CBF distribution in the injured cortex. We conclude that perfusion MRI using arterial spin-labeling is feasible for the serial, noninvasive measurement of CBF and CO2 reactivity in rats.     

Blockade of cerebral blood flow response to insulin-induced hypoglycemia by caffeine and glibenclamide in conscious rats

The possibility that adenosine and ATP-sensitive potassium channels (KATP) might be involved in the mechanisms of the increases in cerebral blood flow (CBF) that occur in insulin-induced hypoglycemia was examined. Cerebral blood flow was measured by the [14C]iodoantipyrine method in conscious rats during insulin-induced, moderate hypoglycemia (2 to 3 mmol/L glucose in arterial plasma) after intravenous injections of 10 to 20 mg/kg of caffeine, an adenosine receptor antagonist, or intracisternal infusion of 1 to 2 mumol/L glibenclamide, a KATP channel inhibitor. Cerebral blood flow was also measured in corresponding normoglycemic and drug-free control groups. Cerebral blood flow was 51% higher in untreated hypoglycemic than in untreated normoglycemic rats (P < 0.01). Caffeine had a small, statistically insignificant effect on CBF in normoglycemic rats, but reduced the CBF response to hypoglycemia in a dose-dependent manner, i.e., 27% increase with 10 mg/kg and complete elimination with 20 mg/kg. Chemical determinations by HPLC in extracts of freeze-blown brains showed significant increases in the levels of adenosine and its degradation products, inosine and hypoxanthine, during hypoglycemia (P < 0.05). Intracisternal glibenclamide had little effect on CBF in normoglycemia, but, like caffeine, produced dose-dependent reductions in the magnitude of the increases in CBF during hypoglycemia, i.e., +66% with glibenclamide-free artificial CSF administration, +25% with 1 mumol/L glibenclamide, and almost complete blockade (+5%) with 2 mumol/L glibenclamide. These results suggest that adenosine and KATP channels may play a role in the increases in CBF during hypoglycemia.     

Measurement of renal vein blood flow in rats by high-field magnetic resonance

The aim of the present study was to examine whether magnetic resonance imaging (MRI) based method for non-invasive in vivo measurement of vein blood flow in rats could be used to estimate renal blood flow (RBF). Measurements were performed using a high-field (7 Tesla) MRI scanner with a short echo time phase contrast velocity measurement pulse sequence. The method was evaluated in vitro by flow measurements in an acrylic pipe and in vivo by recording left renal vein blood flow in normal and unilaterally nephrectomized rats. In a subset of animals RBF was measured by a direct method using 14C-tetraethylammoniumbromide. In vitro a high accuracy was found between applied and MRI measured flow rates in the range from 0.5 to 33 ml/min (r = 0.997; P < 0.001). In vivo the MRI measured left renal vein blood flow was 70% higher in unilaterally nephrectomized animals compared to control animals (3.4 +/- 0.4 ml/min/ 100 g body wt vs. 2.0 +/- 0.1 ml/min/100 g body wt, P < 0.001). Direct measurements of RBF revealed comparable values (3.4 +/- 0.3 ml/min/100 g body wt vs. 2.3 +/- 0.4 ml/min/100 g body wt, P = 0.05). In addition, the left kidney volume was recorded by MRI with an increase amounting to 40% (1.18 +/- 0.05 ml vs. 0.84 +/- 0.02 ml; P < 0.001) in the nephrectomized group compared to controls. Finally, a positive correlation was seen between left renal vein blood flow and MRI measured renal volume (r = 0.91; P < 0.001). In summary, MRI is a non-invasive tool by which measurement of renal vein blood flow can be performed, and it is concluded that MRI-based renal vein flow measurements can be used to estimate RBF in small rodents.     

Cardiovascular and renal effects of hypoxia in conscious carotid body-denervated rats

The contribution of peripheral arterial chemoreceptors to cardiovascular and renal responses to acute hypocapnic hypoxia is currently not well understood. We compared the effects of normobaric hypoxia on mean arterial blood pressure (MABP), heart rate, glomerular filtration rate (GFR), renal blood flow (RBF), and renal volume and electrolyte excretion in conscious unilaterally nephrectomized carotid body-denervated (n = 10) and sham-operated (n = 10) control rats. Thirty minutes of normobaric hypoxia (12.5% O2) resulted in significant reductions in arterial PO2 and PCO2 as well as decreases in MABP, GFR, RBF, and renal sodium, potassium, and water excretion. These effects occurred more rapidly and/or were significantly more pronounced in carotid body-denervated than in sham-operated rats. These data indicate that moderate acute hypocapnic hypoxia has profound effects on systemic and renal hemodynamics as well as on renal excretory function in conscious rats. We conclude that stimulation of the peripheral arterial chemoreceptors can partially offset the hypoxia-induced decreases in MABP, RBF, GFR, urine flow, and urinary sodium and potassium excretion, thereby helping to maintain cardiovascular as well as fluid and electrolyte homeostasis.     

Transient response of glomerular filtration rate and renal blood flow to step changes in arterial pressure

Measurement of rapid renal hemodynamic changes were made for 90 s in pentobarbital-anesthetized dogs following step increases and decreases in renal arterial pressure between 80 and 120 mm Hg. Transient analysis was used to observe time characteristics of the autoregulatory relationships which are obscured in steadystate measurements. Temporal decoupling of blood flow and glomerular filtration rate (GFR) occurred with both step increases and decreases of arterial pressure. Steady-state autoregulation of blood flow was attained in about 30 s, whereas steady-state autoregulation of GFR was not demonstrably attained even 90 s after the arterial pressure maneuver. The temporal decoupling of renal blood flow and GRR supports the concept of transient involvement of proximal tubular dynamics and efferent resistance changes during acute autoregulation of GFR following step changes in arterial pressure.     

Continuous measurement of changes in internal carotid and vertebral arterial blood flow with chronically implanted ultrasonic Doppler probes in anesthetized and conscious rabbits

Chronically implanted ultrasonic Doppler flowmeters were used to obtain simultaneously recorded flow velocity signals from internal carotid and vertebral arteries, and the sagittal sinus, in rabbits. All three signals increased to 144 +/- 7-215 +/- 35% of baseline during hypercapnia (arterial Pco2 55 mmHg) in both anesthetized and conscious animals. During the period of change in inspired CO2, the relationship between simultaneously recorded mean internal carotid and mean sagittal sinus signals was linear, with the correlation ranging from 0.83 to 0.96. Since forebrain arterial inflow must approximate forebrain venous outflow, the high correlation between internal carotid and sagittal sinus signals indicates that these measures provide reliable and valid indices of cerebral blood flow (CBF). Vertebral and internal carotid angiography confirmed the location of Doppler probe. Chronically implanted ultrasonic Doppler flowmeters can, thus, provide continuous noninvasive measurements of cerebral arterial flow in both anesthetized and conscious rabbits.     

Differentiation of the effect of diuretic urine extracts on the renal medullary blood flow (author''s transl)]

1. The isolation of transferrin from rat serum by means of affinity chromatography on CNBr-activated Sepharose 4 B is described. -2. Subfractionation by isoelectric focusing yielded two transferrin fractions with identical biological behaviour but with small differences in isoelectric point (6.0 and 5.8) and sialic acid contents.     

Method for the determination of cerebral blood flow in conscious rabbits

A procedure for the determination of cerebral blood flow by the local clearance method after intracarotid injection of 133Xe in the conscious rabbit is described. The inert radioactive indicator is injected into a permanent nylon catheter equipped with a two-way Gordth's needle inserted into the common carotid artery and filled with heparin, emerging behind the shoulders of the animals. All branches of the homolateral common carotid artery except the internal carotid artery were ligated. Studies of the distribution of colored tracers (dark blue ink) and radioactive tracers (99mTc albumin microspheres) show that the main localization of the injected indicator is within the homolateral hemisphere. Brain to blood partition coefficients of 133Xe are worked out for rabbit's gray matter (0.576 +/- 0.048) and white matter (0.808 +/- 0.023). The slope method for first and second component of the wash-out Xenon curve is used for CBF calculations. CBF determinations in 9 normal rabbits result in 84.27 +/- 5.59 and 16.69 +/- 2.44 ml/min x 100 g tissue, respectively, for the fast and slow component. Significant changes do not occur in serial determinations within 2 hr.     

Renal vascular responses to angiotensin II in conscious spontaneously hypertensive and normotensive rats

It has been postulated that exaggerated renal sensitivity to angiotensin II may be involved in the development and maintenance of hypertension in the spontaneously hypertensive rat (SHR). The purpose of this study was to compare the renal vascular responses to short-term angiotensin II infusions (50 ng/kg/min, i.v.) in conscious SHRs and Wistar-Kyoto (WKY) rats. Renal cortical blood flow was measured in conscious rats by using quantitative renal perfusion imaging by magnetic resonance, and blood pressure was measured by an indwelling carotid catheter attached to a digital blood pressure analyzer. Renal vascular responses to angiotensin II were similar in control SHRs and WKY rats. Pretreatment with captopril to block endogenous production of angiotensin II significantly augmented the renal vascular response to exogenous angiotensin II in the SHRs but not in the WKY rats. The renal vascular responses to angiotensin II were significantly greater in captopril-pretreated SHRs than in WKY rats (cortical blood flow decreased by 1.66 +/- 0.13 ml/min/g cortex in WKY rats compared with 2.15 +/- 0.14 ml/min/g cortex in SHR; cortical vascular resistance increased by 10.5 +/- 1.4 mm Hg/ml/min/g cortex in WKY rats compared with 15.6 +/- 1.7 mm Hg/ml/min/g cortex in SHRs). Responses to angiotensin II were completely blocked in both strains by pretreatment with the angiotensin II AT1-receptor antagonist losartan. Results from this study in conscious rats confirm previous findings in anesthetized rats that (a) the short-term pressor and renal vascular responses to angiotensin II are mediated by the AT1 receptor in both SHRs and WKY rats, and (b) the renal vascular responses to angiotensin II are enhanced in SHRs compared with WKY rats when endogenous production of angiotensin II is inhibited by captopril pretreatment.     

Echo-Doppler evaluation of the renal arterial flow in hepatic cirrhosis

In liver cirrhosis the sodium retention depends on a decreased renal perfusion by arteriolar vasoconstriction. To evaluate the usefulness of echo-Doppler in detecting such hemodynamic impairment, we studied 16 cirrhotic patients and 16 healthy subjects as control group. We measured Pulsatility Index (P.I.) and Resistivity Index (R.I.). Both parameters resulted to be statistically higher in cirrhotic patients than in controls; moreover they resulted to be higher in cirrhotics with ascites than in those without. Therefore echo-Doppler can detect intraparenchymal renal vasoconstriction in cirrhosis, this impaired perfusion is already evident before ascites formation.