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.     

Compartment syndrome in experimental chronic obstructive pancreatitis: effect of decompressing the main pancreatic duct

Chronic pancreatitis is characterized by persistent and severe pain, which can be relieved by decompression of the main pancreatic duct (MPD). Both ductal and interstitial pressures have been shown to be increased in chronic pancreatitis in patients. A study was carried out of pancreatic interstitial pressure and pancreatic blood flow in normal cats and those in which chronic obstructive pancreatitis had been induced 5 weeks earlier to determine the effect of decompression of the MPD. In the normal pancreas, median(interquartile range (i.q.r.)) basal interstitial pressure was 0.05(1.2) mmHg and median(i.q.r.) basal pancreatic blood flow 58.3(24.3) ml per min per 100 g. Secretory stimulation did not change the interstitial pressure significantly, but was associated with a 40 per cent increase in median(i.q.r.) blood flow to 81.8(45.8) ml per min per 100 g. In contrast, in chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.5) mmHg, which was significantly higher than in the normal gland, and median(i.q.r.) pancreatic blood flow was 38.3(9.8) ml per min per 100 g, significantly lower than in the normal pancreas. Furthermore, secretory stimulation was associated with a significant increase in median(i.q.r.) interstitial pressure to 3.3(1.6) mmHg and a simultaneous decrease in median(i.q.r.) blood flow to 31.5(13.7) ml per min per 100 g. After decompression of the MPD in cats with chronic obstructive pancreatitis, the median(i.q.r.) basal interstitial pressure was 2.0(1.4) mmHg and on secretory stimulation 1.8(1.5) mmHg. Decompression thus prevented the increase in interstitial pressure seen in the animals with obstruction. In contrast, ductal decompression improved the median(i.q.r.) basal pancreatic blood flow to 45.9(38.4) ml per min per 100 g and, furthermore, this increased significantly on secretory stimulation to a median(i.q.r.) of 81.4(47.8) ml per min per 100 g. Decompression thus restored the normal pattern of secretory hyperaemia. Within the confines of this model, these observations demonstrate that chronic obstructive pancreatitis exhibits a compartment syndrome that is relieved by duct drainage.     

The effect of chronic hypertension on skin blood flow

OBJECTIVE: To determine whether the cutaneous microvasculature of the spontaneously hypertensive rat (SHR) is affected by chronic hypertension. DESIGN: We used laser Doppler techniques to measure skin blood flow in 22 SHR and in 22 non-hypertensive Wistar-Kyoto (WKY) rats over a 1-year time span, beginning at age 3 months. Sites of measurement included the back, leg, and root of the tail, areas with a predominantly nutritive perfusion, and the plantar surface of the paw, which has a large contribution from large arterioles and venules. Flow was measured at basal skin temperature and at the maximally heat-stimulated condition of 44 degrees C. Systolic tail arterial blood pressures were measured concurrently. RESULTS: At baseline, systolic blood pressures were considerably higher in the SHR (190 +/- 4 mmHg) than they were in the WKY rats (138 +/- 2 mmHg). Skin blood flow values at the three nutritive sites were similar in the two species. However, at 44 degrees C, flow was significantly higher at the paw in the SHR (46.8 +/- 3.5 versus 34.3 +/- 2.2 ml/min per 100 g). We attribute this difference to the effect of high perfusion pressure on large arterioles. During the 1-year measurement period, there was no appreciable change in blood flow in the WKY rats. In contrast, the SHR showed a steady progressive decline in skin blood flow at all sites. The largest decline was at the paw with a rate of fall of about 2.4%/month. After 1 year, there was no difference between paw blood flow in the SHR (27.5 +/- 1.8 ml/min per 100 g) and in the WKY rats (27.6 +/- 1.9 ml/min per 100 g). CONCLUSIONS: Skin blood flow reserve falls in response to chronic hypertension. The rate of fall is greater at sites with significant arteriovenous perfusion that at nutritive sites.     

Scintigraphic assessment of regionalized defects in myocardial sympathetic innervation and blood flow regulation in diabetic patients with autonomic neuropathy

OBJECTIVES: This study sought to evaluate whether regional sympathetic myocardial denervation in diabetes is associated with abnormal myocardial blood flow under rest and adenosine-stimulated conditions. BACKGROUND: Diabetic autonomic neuropathy (DAN) has been invoked as a cause of unexplained sudden cardiac death, potentially by altering electrical stability or impairing myocardial blood flow, or both. The effects of denervation on cardiac blood flow in diabetes are unknown. METHODS: We studied 14 diabetic subjects (7 without DAN, 7 with advanced DAN) and 13 nondiabetic control subjects without known coronary artery disease. Positron emission tomography using carbon-11 hydroxyephedrine was used to characterize left ventricular cardiac sympathetic innervation and nitrogen-13 ammonia to measure myocardial blood flow at rest and after intravenous administration of adenosine (140 microg/kg body weight per min). RESULTS: Persistent sympathetic left ventricular proximal wall innervation was observed, even in advanced neuropathy. Rest myocardial blood flow was higher in the neuropathic subjects (109 +/- 29 ml/100 g per min) than in either the nondiabetic (69 +/- 8 ml/100 g per min, p < 0.01) or the nonneuropathic diabetic subjects (79 +/- 23 ml/100 g per min, p < 0.05). During adenosine infusion, global left ventricular myocardial blood flow was significantly less in the neuropathic subjects (204 +/- 73 ml/100 g per min) than in the nonneuropathic diabetic group (324 +/- 135 ml/100 g per min, p < 0.05). Coronary flow reserve was also decreased in the neuropathic subjects, who achieved only 46% (p < 0.01) and 44% (p < 0.01) of the values measured in nondiabetic and nonneuropathic diabetic subjects, respectively. Assessment of the myocardial innervation/blood flow relation during adenosine infusion showed that myocardial blood flow in neuropathic subjects was virtually identical to that in nonneuropathic diabetic subjects in the distal denervated myocardium but was 43% (p < 0.05) lower than that in the nonneuropathic diabetic subjects in the proximal innervated segments. CONCLUSIONS: DAN is associated with altered myocardial blood flow, with regions of persistent sympathetic innervation exhibiting the greatest deficits of vasodilator reserve. Future studies are required to evaluate the etiology of these abnormalities and to evaluate the contribution of the persistent islands of innervation to sudden cardiac death complicating diabetes.     

Acadesine increases blood flow in the collateralized heart during exercise

Acadesine, an adenosine-regulating agent, has been shown to increase coronary flow and exert cardioprotective effects in acutely ischemic myocardium, but a beneficial effect on coronary collateral flow during exercise has not been demonstrated. We examined the effect of acadesine, 100 micromol/min, i.v., on myocardial blood flow during treadmill exercise in six normal dogs and seven dogs with moderately well-developed coronary collateral vessels. Collateral vessel growth was produced with 2-min intermittent occlusions of the left circumflex coronary artery followed by permanent occlusion. During resting conditions, myocardial blood flow in the collateral zone was not significantly less than in the normal zone, but during exercise, blood flow increased by only 79 +/- 21% (from 0.98 +/- 0.29 ml/min/g to 1.64 +/- 0.19 ml/min/g; p < 0.05) in the collateral zone as compared with 118 +/- 32% (from 1.09 +/- 0.28 ml/min/g to 2.14 +/- 0.2 ml/min/g; p < 0.01) in the normal zone. During exercise, acadesine further increased mean blood flow in the collateral-dependent region by 24 +/- 5% (to 2.04 +/- 0.26 ml/min/g; p < 0.05) with no change in the transmural distribution of perfusion. The increase in collateral zone blood flow in response to acadesine resulted from a decrease in both transcollateral resistance from 25.1 +/- 2.7 mm Hg/min/g/ml to 18.8 +/- 8 mm Hg/min/g/ml (p < 0.05) and small-vessel resistance in the collateral-dependent myocardium from 45.3 +/- 6.6 mm Hg/min/g/ml to 36.4 +/- 5.8 mm Hg/min/g/ml (p < 0.05). Acadesine also significantly increased normal-zone flow in the collateralized dogs (to 2.62 +/- 0.33 ml/min/g; p < 0.05). In contrast, acadesine had no effect on coronary blood flow in normal dogs. In dogs with moderately well-developed collateral vessels, acadesine increased blood flow in both the collateral-dependent and normal myocardial zones during exercise. In contrast, acadesine did not increase blood flow in normal dogs. These findings suggest that adenosine metabolism is altered not only in the collateral-dependent region but also in the normal region of hearts with a coronary artery occlusion.     

Severe community-acquired pneumonia

Although vasodilation is conventionally held to be the predominant microvascular response to a wound, there has been no previous attempt to actually quantitate skin blood flow within and in the neighborhood of wounds. In particular, there has been no differentiation between sites with primarily nutritive (NUTR) blood flow and those with considerable arteriovenous (AV) perfusion. We used our previously described model of cutaneous blood flow in the rat to study the blood flow response to wounding. We measured skin blood flow at the centers and at the undisturbed perimeters of wounds placed at the back, a NUTR site, and at the paw, an AV site, in 11 Wistar Kyoto rats. Measurements were performed at baseline, and then at 3 hr, 24 hr, 72 hr, and 7 days postwounding. At 3 hr, flow at the center of the back wound had increased to 11.3 +/- 1.4 ml/min/100 g from a baseline of 2.1 +/- 0.1 ml/min/100 g and remained elevated at 7 days (8.3 ml/min/100 g). Flow at the perimeter of the back wound rose as well, but not as high as at wound center, to twice the baseline level (4.1 ml/min/ 100 g at Day 7). Flow values at control sites on the back did not increase from baseline. Flow at the center of the paw wound rose from 7.2 +/- 0.5 ml/min/100 g at baseline to 15.6 +/- 4.3 ml/min/100 g at Day 3 but then fell back to 6.9 +/- 0.9 ml/min/100 g at Day 7. There was only a very small increase in the basal temperature wound response at the paw perimeter. Blood flow at all wound sites showed a response to heat. At the back, heating to 44 degrees stimulated an 80% increase in blood flow at baseline. This degree of increase was maintained at both the center and the perimeter of the back wound. In contrast, although there was also a thermal response at the paw wound center, it was of much lower magnitude than the nonwounded baseline response. As a result, the heat-stimulated flow value actually fell over the 7 days to approximately half of the baseline level. At the paw wound periphery, there was an initial fall in the heat stimulated response, but it then recovered to the baseline level and remained stable over the 7 days. Thus, the skin blood flow response seen at the paw wound challenges the conventional concept of vasodilation as the expected wound blood flow response. The mechanisms of blood flow response in the healing wound may be more complex than the simple inflammatory vasodilation conventionally postulated.     

Medical and social factors affecting early teenage pregnancy. A literature review and summary of the findings of the Louisiana Infant Mortality Study

The acute effects of small doses of intravenous propranolol on renin release and on circulatory dynamics were studied at the time of renal arteriography in 12 persons with essential hypertension. All of the subjects had a normal peripheral renin response to chronic sodium depletion and all had normal renal function. Seven subjects received a 10-mEq sodium diet. At the time of arteriography, arterial blood pressure, pulse rate, cardiac output, renal blood flow, and arterial and renal venous renin activity were measured before and 6-20 minutes after the intravenous administration of propranolol (9-18 mjg/kg). Average renin secretion rate in the salt-depleted subjects fell from 367 +/- 80 (SEM) U/ml per 100 g/min to 122 +/- 51 U/ml per 100 g (P=0.03) and renal plasma flow fell from 189 to 155 ml/min per 100 g (P = 0.018). We also found that in the salt-loaded subjects, renal plasma flow fell from 213 to 184 ml/min per 100 g (P = 0.025), whereas renin secretion did not change significantly in either group. We conclude that propranolol rapidly blocks renin release despite circulatory changes which ordinarily constitute a stimulus for renin secretion, i.e., renal vasoconstriction and reduced renal blood flow.     

What is the blood flow to resting human muscle?

1. An investigation was carried out in five healthy lean adults to assess whether forearm and calf plethysmography largely reflect muscle blood flow as measured by 133Xe and whether there is substantial variability in the blood flow to muscles located at different sites in the body. 2. Blood flow to forearm and calf flexors and extensors, biceps, triceps and quadriceps was assessed using the 133Xe clearance technique. Blood flow to forearm skin and subcutaneous adipose tissue was also measured using the 133Xe clearance technique, whereas blood flow to the forearm and calf was measured using strain gauge plethysmography. 3. The mean blood flow to different muscles ranged from 1.4 +/- 0.6 (gastrocnemius) to 1.8 +/- 0.7 (forearm extensor) ml min-1 100 g-1 muscle (1.4 +/- 0.6 and 1.9 +/- 0.8 ml min-1 100 ml-1 muscle, respectively) but there were no significant differences between them. Forearm and calf blood flows (2.7 +/- 0.3 and 3.0 +/- 0.7 ml min-1 100 ml-1 limb tissue, respectively) were about 50% to more than 100% greater (P < 0.025) than blood flow to the muscles within them (1.7 +/- 0.5 and 1.4 +/- 0.5 ml min-1 100 g-1 muscle, respectively, or 1.8 +/- 0.6 and 1.5 +/- 0.5 ml min-1 100 ml-1 muscle, respectively). In contrast, the blood flows to 100 g of forearm skin (9.1 +/- 2.6 ml min-1 100 g-1) and adipose tissue (3.8 +/- 1.1 ml min-1 100 g-1) were higher than the blood flow to 100 g of forearm (P < 0.01 and not significant, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

No evidence for an ischemic penumbra in massive experimental intracerebral hemorrhage

OBJECTIVES: To determine the effect of massive intracerebral hemorrhage (ICH) on regional cerebral blood flow (rCBF) and metabolism, and to test the hypothesis that there is persistent ischemia in the perihematoma region after ICH. BACKGROUND: Cerebral ischemia is postulated to be one of the mechanisms of neural injury after ICH. Presumably the hematoma induces ischemia by mechanical compression of the surrounding microvasculature. METHODS: The authors induced ICH in eight anesthetized mongrel dogs by autologous blood injection (7.5 mL) under arterial pressure in the deep white matter adjacent to the left basal ganglia. They measured serial rCBF using radiolabeled microspheres in regions around and distant to the hematoma, as well as cerebral oxygen extraction, oxygen consumption (CMRO2), glucose utilization, and lactate production by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were monitored continuously. All measurements were recorded at 0.5, 1.0, 2.0, 3.5, and 5.0 hours after induction of ICH and compared with prehematoma values. Evans Blue dye was injected at the end of the experiment, and intensity of staining was compared with three control animals. RESULTS: Compared with prehematoma ICP (12.5+/-2.0 mm Hg, mean+/-standard error), significant elevation in ICP was observed after ICH peaking at 5 hours (34.4+/-5.2 mm Hg). Compared with prehematoma MAP (125.8+/-7.0 mm Hg), significant elevation in MAP was observed at 120 minutes after onset of hematoma (139.1+/-4.6 mm Hg), with return to the prehematoma value by 5 hours. There were no significant changes observed in cerebral oxygen extraction (51.4+/-4.3% versus 44.8+/-4.9%) and CMRO2 (1.8+/-0.3 versus 1.64+/-0.2 mL O2/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. There were no significant differences observed in rCBF in the perihematoma gray (18.2+/-0.9 mL/100 g/min versus 20.1+/-1.5 mL/100 g/min) or white matter (15.6+/-1.4 mL/100 g/min versus 15.3+/-1.1 mL/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. No changes were observed in cerebral glucose utilization, lactate production, and rCBF in other regions after introduction of ICH. Permeability of the blood-brain barrier was more prominent in the ipsilateral hemisphere in animals with ICH compared with control animals. CONCLUSIONS: Despite a prominent increase in ICP and MAP after ICH, the authors found no evidence to support the presence of an ischemic penumbra in the first 5 hours after ICH. Thus, other mechanisms for acute neural injury and late rCBF changes after ICH must be investigated.     

Rat hindlimb muscle blood flow during level and downhill locomotion

During eccentrically biased exercise (e.g., downhill locomotion), whole body oxygen consumption and blood lactate concentrations are lower than during level locomotion. These general systemic measurements indicate that muscle metabolism is lower during downhill exercise. This study was designed to test the hypothesis that hindlimb muscle blood flow is correspondingly lower during downhill vs. level exercise. Muscle blood flow (determined by using radioactive microspheres) was measured in rats after 15 min of treadmill exercise at 15 m/min on the level (L, 0 degrees) or downhill (D, -17 degrees). Blood flow to ankle extensor muscles was either lower (e.g., white gastrocnemius muscle: D, 9 +/- 2; L, 15 +/- 1 ml. min-1. 100 g-1) or not different (e.g., soleus muscle: D, 250 +/- 35; L, 230 +/- 21 ml. min-1. 100 g-1) in downhill vs. level exercise. In contrast, blood flow to ankle flexor muscles was higher (e.g., extensor digitorum longus muscle: D, 53 +/- 5; L, 31 +/- 6 ml. min-1. 100 g-1) during downhill vs. level exercise. When individual extensor and flexor muscle flows were summed, total flow to the leg was lower during downhill exercise (D, 3.24 +/- 0.08; L, 3.47 +/- 0. 05 ml/min). These data indicate that muscle blood flow and metabolism are lower during eccentrically biased exercise but are not uniformly reduced in all active muscles; i.e., flows are equivalent in several ankle extensor muscles and higher in ankle flexor muscles.     

Regional differences of cerebral blood flow in the preterm infant

The purpose of our study was to evaluate the regional distribution of the resting cerebral blood flow (CBF) pattern in preterm neonates. Sixty-eight preterm babies with a gestational age of less than 34 weeks and a birth weight of less than 1500 g were enrolled into the study. The CBF was measured by the noninvasive intravenous 133Xenon method at three different times. Depending on the age we classified our measurements into three groups. Group 1: measurement between 2-36 h (n = 46). Group 2: measurement between 36-108 h (n = 39). Group 3: measurement between 108-240 h (n = 41). In all three groups CBF was significantly lower in the occipital region than in the frontal and parietal regions (group 1: frontal region 12.8 +/- 3.5 ml/100 g/min, parietal region 12.8 +/- 3.9 ml/100 mg/min, and occipital region 11.6 +/- 3.18 ml/100 g/min; group 2: frontal region 15.4 +/- 4.2 ml/100 g/min, parietal region 15.3 +/- 4.1 ml/100 g/min, and occipital region 13.4 +/- 3.5 ml/100 g/min; group 3: frontal region 14.6 +/- 3.6 ml/100 g/min, parietal region 14.6 +/- 3.2 ml/100 g/min, and occipital region 12.8 +/- 2.7 ml/100 g/min.). CBF did not differ between the left and the right hemispheres in either of the three measured regions. No gradient was found in infants between 108 h and 240 h of age with periventricular leukomalacia and periventricular haemorrhage. CONCLUSION. In preterm neonates the antero-posterior gradient of CBF is already present. Periventricular leukomalacia as well as periventricular haemorrhage may affect the regional regulation of CBF.     

Viscoelastic relaxation and regional blood flow response to spinal cord compression and decompression

STUDY DESIGN: To better understand the relationships between primary mechanical factors of spinal cord trauma and secondary mechanisms of injury, this study evaluated regional blood flow and somatosensory evoked potential function in an in vivo canine model with controlled velocity spinal cord displacement and real-time piston-spinal cord interface pressure feedback. OBJECTIVES: To determine the effect of regional spinal cord blood flow and viscoelastic cord relaxation on recovery of neural conduction, with and without spinal cord decompression. SUMMARY OF BACKGROUND DATA: The relative contribution of mechanical and vascular factors on spinal cord injury remains undefined. METHODS: Twelve beagles were anesthetized and underwent T13 laminectomy. A constant velocity spinal cord compression was applied using a hydraulic loading piston with a subminiature pressure transducer rigidly attached to the spinal column. Spinal cord displacement was stopped when somatosensory evoked potential amplitudes decreased by 50% (maximum compression). Six animals were decompressed 5 minutes after maximum compression and were compared with six animals who had spinal cord displacement maintained for 3 hours and were not decompressed. Regional spinal cord blood flow was measured with a fluorescent microsphere technique. RESULTS: At maximum compression, regional spinal cord blood flow at the injury site fell from 19.0 +/- 1.3 mL/100 g/min to 12.6 +/- 1.0 mL/100 g/min, whereas piston-spinal cord interface pressure was 30.5 +/- 1.8 kPa, and cord displacement measured 2.1 +/- 0.1 mm (mean +/- SE). Five minutes after the piston translation was stopped, the spinal cord interface pressure had dissipated 51%, whereas the somatosensory evoked potential amplitudes continued to decrease to 16% of baseline. In the sustained compression group, cord interface pressure relaxed to 13% of maximum within 90 minutes; however, no recovery of somatosensory evoked potential function occurred, and regional spinal cord blood flow remained significantly lower than baseline at 30 and 180 minutes after maximum compression. In the six animals that underwent spinal cord decompression, somatosensory evoked potential function and regional spinal cord blood flow recovered to baseline 30 minutes after maximum compression. CONCLUSIONS: Despite rapid cord relaxation of more than 50% within 5 minutes after maximum compression, somatosensory evoked potential conduction recovered only with early decompression. Spinal cord decompression was associated with an early recovery of regional spinal cord blood flow and somatosensory evoked potential recovery. By 3 hours, spinal cord blood flow was similar in both the compressed and decompressed groups, despite that somatosensory evoked potential recovery occurred only in the decompressed group.     

Development of photosynthetic electron transport in greening barley

Oxygen tension and potential difference were measured in the gastric mucosa of anesthetized dogs with an ultramicroelectrode technqiue while total blood flow and arteriovenous oxygen content difference were measured. In the control period, measurements were: gastric blood flow, 102.4 +/- 3.0 ml per min per 100 g of tissue; calculated oxygen consumption, 2.4 +/- 0.1 ml per min per 100 g of tissue; intracellular oxygen tension, 15.0 +/- 0.6 mm Hg; and intracellular potential difference, -50.8 +/- 1.5 mv. When gastric blood flow was reduced 50% by tourniquet ischemia, oxygen tension decreased 20% (P less than 0.05) but electrical potential and oxygen consumption did not change. When blood flow was reduced 75%, oxygen tension and potential difference decreased significantly, 60% and 35%, respectively, but oxygen consumption was unchanged. Zero blood flow reduced oxygen tension, electrical potential, and total oxygen consumption to zero; release of the arterial tourniquet allowed them to return to control levels. The critical oxygen tension at which the electromotive force generated by the gastric mucosal cells was reduced averaged 9 mm Hg. This suggests that safety factors exist in the gastric circulation which permit a 60% reduction in total gastric blood flow to occur before an insufficiency of intracellular oxygen begins to limit cellular metabolism within the mucosa.     

Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1

The mechanisms regulating coronary collateral circulation are largely unknown owing to both the complex and variable nature of clinical models and the difficulty to obtain quantitative and differentiated flow measurements within the various coronary tree portions. With the aim of assessing collateral flow reserve, we studied 19 patients with effort angina, without myocardial infarction and with isolated occlusion of either the left anterior descending coronary artery (n = 14) or the circumflex coronary artery (n = 5). Flow values were measured basally, during atrial pacing induced tachycardia and following ev dipyridamole infusion (0.56 mg/kg of body weight in 4 min), by means of positron emission tomography and nitrogen-13 ammonia as flow tracer, within both regions depending on collateral circulation and the remote ones. Results have been compared with those obtained in 13 normal subjects. Basal flow values in regions depending on collateral circulation and in the remote regions (0.61 +/- 0.11 vs 0.63 +/- 0.17 ml/min/g) were found to be similar, but lower than in normal subjects (1.00 +/- 0.20 ml/min/g, p < 0.01). During atrial pacing, flow increased to 0.83 +/- 0.25 and to 1.11 +/- 0.39 ml/min/g, in the regions depending on collateral circulation and in the remote regions, respectively (p < 0.05 as compared to baseline); again, values were lower than in normal subjects (1.86 +/- 0.61 ml/min/g, p < 0.01). Dipyridamole infusion further increased flow in the remote regions (1.36 +/- 0.57 ml/min/g, p < 0.01 as compared to atrial pacing) but it did not in the regions depending on collateral circulation (0.94 +/- 0.37 ml/min/g, NS as compared to atrial pacing); both values were lower than in normal subjects (3.46 +/- 0.78 ml/min/g, p < 0.01). Flow reserve in the regions depending on collateral circulation was found to have a direct linear correlation with the one in the remote regions (r = 0.83; p < 0.01). In conclusion, in spite of basal hypoperfusion, collateral circulation maintains a flow reserve which, even if reduced, is able to cope with moderate increments in oxygen consumption. An analogous flow reduction can be observed in the remote regions, suggesting that the entire coronary tree is involved, beyond the obstructive lesions of the main arterial branches.     

Role of luminal volume changes in the increase in pulmonary blood flow at birth in sheep

The mechanism by which pulmonary blood flow increases and pulmonary vascular resistance decreases after birth is not fully understood. The aim of this study was to simulate the decrease in lung volume caused by the onset of air-breathing at birth and determine whether it can duplicate the changes in pulmonary blood flow and vascular resistance that occur at this time. In chronically catheterized fetal sheep near term (145 days of gestation), fetal pulmonary arterial blood flow was measured, using coloured microspheres, before and after fetal lung liquid volumes were reduced from 52.2 +/- 2.7 to 21.2 +/- 1.6 ml kg-1. During the 30 min period following the reduction in lung liquid volume, the pulmonary-to-systemic arterial pressure difference decreased from 6.8 +/- 1.2 mmHg (pulmonary > systemic) to 1.6 +/- 0.5 mmHg. Reducing the volume of fetal lung liquid increased pulmonary blood flow from 59.1 +/- 10.5 to 204.2 +/- 40.4 ml min-1 (100 g tissue)-1 and reduced pulmonary vascular resistance from 0.53 +/- 0.20 to 0.14 +/- 0.04 mmHg min ml-1 (100 g tissue)-1. We conclude that a reduction in fetal lung liquid volume, which simulates the reduction in lung volume that occurs at birth, causes a 3- to 4-fold increase in pulmonary blood flow and a reduction in pulmonary vascular resistance of a similar magnitude. Thus, the reduction in lung volume associated with the lung changing from a liquid- to an air-filled organ, may partly account for the increase in pulmonary blood flow and decrease in pulmonary vascular resistance at birth.     

Calculation of absolute cerebral blood volume and cerebral blood flow by means of electron-beam computed tomography (EBT) in acute ischemia

The utility of electron beam computed tomography (EBT) to estimate cerebral blood volume (CBV) and cerebral blood flow (CBF) was evaluated. Eleven patients with suspected acute cerebral ischemia were investigated. The EBT was performed with an acquisition time of 50 ms per slice at eight parallel levels. To compare signal/noise and contrast/noise ratios the data from the EBT investigation were compared to a similar examination on a spiral CT. The signal/noise ratio with EBT was about 30%, the contrast/noise ratio 25% of that with spiral CT. The absolute values of CBV were 4.9 +/- 1.2 ml/100 g (EBT); CBF was 50.5 +/- 7.0 ml/100 g/min in normal contralateral brain tissue. In four patients with proven infarcts on follow-up, the ischemic areas had a CBV ranging from 1.7 to 3.8 ml/100 g, while CBF ranged from 9.4 to 24.5 ml/100 g/min. Using a bolus injection of contrast material, calculation of absolute CBV and CBF is feasible using EBT. Advantages of EBT are the absolute measurements possible and it's multislice capability. Disadvantages, however, are caused by the high image noise, limiting the demarcation of ischemic tissue.     

Confocal tomographic angiography of the optic nerve head in patients with glaucoma

BACKGROUND: Essential hypertension is characterized by an impairment of endothelium-dependent vasodilatation. OBJECTIVE: To test whether antihypertensive treatment with the angiotensin converting enzyme inhibitor lisinopril can improve vasodilatation in response to endothelium-dependent agonists in essential hypertensive patients. DESIGN AND METHODS: We studied the effect of acute (6-8 h after dosing), prolonged (1 month) and chronic (12 months) lisinopril treatment on forearm blood flow response (strain-gauge plethysmography) induced in 10 hypertensive patients (aged 43.6 +/- 8.1 years, blood pressure 151.4 +/- 6.8/99.8 +/- 3.3 mmHg) by intrabrachial infusions of 0.15, 0.45, 1.5, 4.5, and 15 microg/100 ml per min acetylcholine and 5, 15, and 50 ng/100 ml per min bradykinin, two endothelium-dependent vasodilators, and 1, 2, and 4 microg/100 ml per min sodium nitroprusside, an endothelium-independent vasodilator. At baseline, vascular response was compared with that of 10 normotensive subjects (aged 42.4 +/- 6.6 years, blood pressure 118.4 +/- 6.1/77.8 +/- 3.4 mmHg). RESULTS: Hypertensive patients had blunted (P < 0.01 or less) vasodilatations in response to infusions of acetylcholine (from 3.7 +/- 0.3 to 18.3 +/- 4.9 ml/100 ml per min) and bradykinin (from 3.7 +/- 0.4 to 15.8 +/- 2.6 ml/100 ml per min) compared with those of controls (from 3.6 +/- 0.3 to 25.3 +/- 5.2 ml/100 ml per min for acetylcholine and from 3.7 +/- 0.3 to 26.9 +/- 4.9 ml/100 ml per min for bradykinin) whereas the responses to infusion of sodium nitroprusside were similar (from 3.6 +/- 0.3 to 18.5 +/- 3.9 and from 3.6 +/- 0.3 to 16.4 +/- 1.8 ml/100 ml per min, respectively). Acute and prolonged lisinopril treatments significantly (P < 0.05 or less) improved vasodilatation in response to infusion of bradykinin (from 3.7 +/- 0.4 to 24.5 +/- 4.9 and from 3.7 +/- 0.3 to 22.1 +/- 4.9 ml/100 ml per min, respectively), but not in response to infusions of acetylcholine and of sodium nitroprusside. Chronic lisinopril treatment increased (P < 0.05) the response to infusions of not only bradykinin (from 3.5 +/- 0.5 to 27.6 +/- 5.3 ml/100 ml per min), but also of acetylcholine (from 3.5 +/- 0.5 to 27.8 +/- 8.0 ml/100 ml per min) and sodium nitroprusside (from 3.4 +/- 0.6 to 25.9 +/- 8.5 ml/100 ml per min). However, when the responses to infusions of acetylcholine and bradykinin were normalized with respect to that to infusion of sodium nitroprusside, only the vasodilatation in response to infusion of bradykinin was shown to have been increased by lisinopril treatment. CONCLUSIONS: Administration of lisinopril to patients with essential hypertension can selectively increase vasodilatation in response to infusion of bradykinin.     

Protective effect of the sodium/hydrogen exchange inhibitors during global low-flow ischemia

A technique for noninvasive quantitative magnetic resonance imaging of perfusion is presented. It relies on using endogenous water as a freely diffusible tracer. Tissue water proton spins are magnetically labeled by slice-selective inversion, and longitudinal relaxation within the slice is detected using a fast gradient echo magnetic resonance imaging technique. Due to blood flow, nonexcited spins are washed into the slice resulting in an acceleration of the longitudinal relaxation process. Incorporating this phenomenon into the Bloch equation yields an expression that allows quantification of perfusion on the basis of a slice-selective and a nonselective inversion recovery experiment. Based on this technique, quantitative parameter maps of the regional cerebral blood flow (rCBF) were obtained from eight rats. Evaluation of regions of interest within the cerebral hemispheres yielded an average rCBF value of 104 +/- 21 ml/min/100 g, which increased to 219 +/- 30 ml/min/100 g during hypercapnia. The measured rCBF values are in good agreement with previously reported literature values.     

Regional cerebral blood volume after severe head injury in patients with regional cerebral ischemia

OBJECTIVE: Recent early cerebral blood flow (CBF) studies in cases of severe head injury have revealed ischemia in a substantial number of patients with a variety of computed tomographically demonstrated diagnoses. The underlying derangements causing this early ischemia are unknown, but cerebral blood volume (CBV) measurements might offer some insight into this pathological abnormality. METHODS: For this purpose, stable xenon-enhanced computed tomography was used for assessment of CBF, and a dynamic computed tomographic imaging technique was used for determining CBV. Based on the occurrence of regional ischemia (CBF < 20 ml/100 g/min), seven patients with varying anatomic lesions revealed by computed tomography were identified for comparison between CBF and CBV in ischemic and nonischemic areas. RESULTS: Both CBF (15+/-4.3 versus 34+/-11 g/min, P < 0.002) and CBV (2.5+/-1.0 versus 4.9+/-1.9 ml/100 g) exhibited significantly lower values in the ischemic zones than in the nonischemic zones (means+/-standard deviations). Among 26 patients with or without ischemia observed during their initial follow-up studies, which were conducted between Days 2 and 8, all patients showed CBF and CBV values within the low-normal range. CONCLUSION: These data evidently support the suggestion that compromise of the microvasculature is the cause of early ischemia, rather than vasospasm of the larger conductance vessels.     

Pentoxifylline reduces nephrotoxicity associated with cyclosporine in the rat by its rheological properties

BACKGROUND: The goals of this study were to evaluate whether administration of pentoxifylline (POF) reduces the nephrotoxicity associated with cyclosporine (CsA) in the rat, and whether the effect of POF is related to its rheological properties. METHODS: Mean arterial pressure was measured by an intraarterial catheter. Glomerular filtration rate and renal plasma flow were determined by measuring inulin and para-aminohippurate clearances, after double-blind coadministration for 10 days of CsA (25 mg/kg/day) with either vehicle or POF (45 mg/kg every 12 hr). These results were compared with those obtained in control rats. Blood viscosity and erythrocyte deformability were also evaluated after treatment using a cone plate viscometer and a filtration method, respectively. RESULTS: No changes were observed in mean arterial pressure in both groups compared with controls. Glomerular filtration rate was significantly lower in CsA-treated rats (0.3+/-0.1 ml/min/100 g) than in control animals (0.6+/-0.1 ml/min/100 g, P<0.02). The coadministration of CsA with POF normalized the glomerular filtration rate (0.6+/-0.1 ml/min/100 g). A parallel decrease in renal plasma flow was observed in CsA-treated rats compared with controls (CsA+vehicle: 1.5+/-0.2 vs. control: 2.2+/-0.1 ml/min/100 g, P<0.02), this effect completely reversed by cotreatment with POF (3.1+/-0.2 ml/min/100 g). Blood viscosity was significantly higher in CsA-treated rats than in the control group (CsA+vehicle: 5.6+/-0.7 vs. control: 5.0+/-0.4 m x Pa x s, P<0.05). This effect was associated with a lower erythrocyte deformability (CsA+vehicle: 1.2+/-0.2 vs. control: 1.5+/-0.3 ml/min, P<0.05). These rheological abnormalities were normalized by coadministration with POF (blood viscosity: 4.9+/-0.7 m x Pa x s and erythrocyte deformability: 1.9+/-0.4 ml/min, P<0.05). CONCLUSIONS: Our results show that administration of POF prevents the nephrotoxicity associated with CsA. This beneficial effect could be related to its rheological properties.