Femoral head blood flow in femoral neck fractures. An analysis using intra-osseous pressure measurement

We studied 50 patients with fractures of the femoral neck, 33 intracapsular and 17 extracapsular. Intraosseous pressure was measured by a transducer within the bone to quantify blood flow, and intracapsular pressure by a needle introduced into the joint space. The mean intracapsular pressure was lower in the extracapsular fractures. In these, the mean intraosseous pressure in the femoral head was unchanged by aspiration of the joint. However in the intracapsular fractures aspiration produced a significant decrease in intra-osseous pressure and an increase in pulse pressure within the femoral head. The results suggest that aspiration of intracapsular haematoma produced an increase in femoral head blood flow by relieving tamponade.     

The effect of core decompression on femoral head blood flow in steroid-induced avascular necrosis of the femoral head

Previous reports from this and other laboratories have shown that the histological changes in the femoral head that are associated with steroid treatment are consistent with avascular necrosis of the femoral head. In this experiment, we studied the effect of core decompression on femoral head blood flow in steroid-treated rabbits using the microsphere technique. The results showed that there was a gradual decline of femoral head blood flow in animals that received weekly injections of methylprednisolone without core decompression. The femoral head blood flow in animals that underwent core decompression after six weeks of steroid treatment showed a gradual normalization within four weeks after core decompression.     

Increased blood cortisol in alcoholic patients with aseptic necrosis of the femoral head

Summary Although aseptic necrosis of the femoral head secondary to alcoholism is a very frequent entity, its etiology remains unknown. The same pathogenic mechanism is thought to be shared both by aseptic necrosis secondary to alcoholism and steroid therapy. Since alcohol stimulates adrenal steroid secretion, we have studied serum cortisol and urinary free-cortisol levels in 8 patients with aseptic necrosis of the femoral head due to alcoholism and compared them with those found in 8 age-matched patients with aseptic necrosis of idiopathic origin. Serum cortisol levels and urinary free-cortisol levels were significantly higher in the alcoholic than in the idiopathic group: serum 227±21.7 vs 154±22.1 ng/ml,P<0.001; urine 0.20±0.002 vs 0.13±0.04 μg/mg cr/day,P<0.001. The data indicate that alcohol-induced aseptic necrosis of the femoral head results, at least in part, from increased circulating cortisol.     

Laser Doppler flowmetry for bone blood flow measurement: correlation with microsphere estimates and evaluation of the effect of intracapsular pressure on femoral head blood flow

Laser Doppler flowmetry (LDF) was used to measure bone blood flow in the rabbit femoral head and femoral condyles. To correlate the LDF output signal blood cell flux to in vivo blood flow, simultaneous measurements using LDF and 85Sr-labeled microspheres were made in an adult rabbit model. There was no correlation between the two methods for blood flow in the femoral condyles and the correlation between the two methods for blood flow in the femoral head does not achieve statistical significance. An LDF signal of 0.4 V was approximately equal to a microsphere measured flow rate of 0.4 ml blood/g bone/min. The strength of the correlation in the latter case may have been affected by (a) large arteriovenous shunts, (b) inadequate mixing of the microspheres with a left ventricular injection, and (c) insufficient numbers of microspheres present in the bone samples with which to satisfy the mathematical requirements of the microsphere method. When LDF was used to evaluate the effect of elevated intracapsular pressure on femoral head blood flow in skeletally mature rabbits, femoral head subchondral bone blood flow declined with increasing intracapsular pressure from a baseline value of 0.343 +/- 0.036 to a value of 0.127 +/- 0.27 at 120 cm of water pressure. The decline in femoral head blood flow was statistically significant at pressures of 40 cm of water or higher (p less than 0.001), and evaluation of sections of the proximal femora made from preterminal disulphine blue injections confirmed these findings. Intracapsular tamponade has an adverse effect on femoral head blood flow beginning well below central venous pressure and should be considered in the pathophysiology of posttraumatic and nontraumatic necrosis of the femoral head. Laser Doppler flowmetry was easy to use and appears to be a reproducible technique for evaluating femoral head blood flow, offering distinct advantages over the microsphere technique for measuring bone blood flow. Further studies of the in vivo calibration of the LDF method for bone blood flow are necessary for the method to have potential for clinical application.     

激光多普勒血流仪测量股骨头坏死的血流改变

目的 应用激光多普勒血流仪(laser doppler flowmetry,LDF)检测临床确诊为股骨头坏死患者的坏死区和头颈交界正常区的血液灌注量.方法 2007年至2008年对50例股骨头坏死患者82侧行股骨头钻孔减压自体干细胞植入,按照ARCO分期Ⅱ期为A组,46髋(ⅡA 6髋、ⅡB 22髋、ⅡC 18髋);Ⅲ期为B组,36髋(ⅢA 20髋、ⅢB 10髋、ⅢC 6髋),术中用激光多普勒血流仪检测股骨头坏死区及头颈交接区的血流灌注情况,对数据进行统计学处理.结果 A组坏死区灌注量为(30.2±3.0)PU,头颈交界区灌注量为(103.4±4.4)PU,B组坏死区灌注量为(30.6±2.8)PU,头颈交界区灌注量为(103.4±3.9)PU,A组和B组坏死区灌注量均低于正常区,二者比较差异具有统计学意义(P<0.01).而A组和B组之间坏死区和头颈交界区的灌注量差别无统计学意义(P>0.01).结论 LDF可以有效地检测股骨头坏死区血流灌注量减少,为进一步研究股骨头坏死的发病机制提供了理论依据,在股骨头坏死的研究中有应用价值.     

Pravastatin reduces steroid-induced osteonecrosis of the femoral head in SHRSP rats

Background and purpose

Although the definite cause of steroid-induced osteonecrosis of the femoral head (ONFH) is unknown, peripheral circulatory failure, lipid metabolism disturbance, and increased oxidative stress are considered to be possible causes. We investigated whether pravastatin as a statin treatment reduces (1) the incidence of ONFH, (2) the adipocyte area, and (3) bone marrow changes in the femoral head.

Methods

We divided up 81 thirteen-week-old spontaneously hypertensive stroke-prone (SHRSP)/Izm male rats into 4 groups: a control group (group C), a group given pravastatin (group P), a group given steroid (group S), and a group given both pravastatin and steroid (Group PS). The steroid was administered at 15 weeks of age. Pravastatin, as a statin, was administered in the drinking water for 4 weeks. The rats were killed when 17 weeks old. Osteonecrosis was diagnosed based on histopathological examination. Oxidative stress was assessed from immunostaining.

Results

The incidence of histological osteonecrosis was lower in the groups given pravastatin. The percentage of adipocyte area in the bone marrow was lower in the PS group than in the S group. Immunohistochemical staining for oxidative stress showed that staining was less in the PS group than in the S group. Pravastatin had no effect on the blood-derived biochemical findings on lipid metabolism. However, it reduced the incidence of steroid-induced ONFH in these SHRSP rats. We presume that this occurred by reducing oxidative stress and by reducing the percentage of adipocyte area in the femoral heads.

Interpretation

Our data suggest that pravastatin may be effective in reducing steroid-induced ONFH.Every year, 3,000 of the 128 million inhabitants in Japan develop osteonecrosis of the femoral head (ONFH), and the number of patients—particularly those treated with steroid therapy—has been increasing over the years (Hirota et al. 1997). The proposed pathogenesis of steroid-induced ONFH includes increased oxidative stress, lipid metabolism disturbance, and disturbances of the coagulation-fibrinolysis system due to steroid hormones (Fisher 1978, Cheras 1997, Ichiseki et al. 2004, 2006). Statins are lipid-lowering, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (Endo 1992). Some statins have been reported to enhance the antioxidant activity and local lipid kinetics by directly acting on adipocytes and blood vessels, thus reducing the severity and frequency of ONFH (Cui et al. 1997, Pritchett 2001, Ichiseki et al. 2004, 2006, Nishida et al. 2008, Yagi et al. 2008 , Kuribayashi et al. 2010).ONFH observed in spontaneously hypertensive stroke-prone (SHRSP) rats closely resembles human ONFH, not only histologically but also physiologically (Hirano et al. 1989, Wada et al. 2004, Murata et al. 2007, Suzuki et al. 2008). We have reported a 50% incidence of spontaneous osteonecrosis of the femoral head in SHRSP rats at the age of 16–18 weeks, and they develop ONFH more frequently (up to 90%) with steroid administration (Murata et al. 2007, Suzuki et al. 2008). Unlike rabbits, chickens, and other rats, SHRSP rats are an inbred, established model of ONFH.In this work, we studied the ability of pravastatin to reduce the incidence of steroid -induced osteonecrosis in SHRSP rats. We also examined whether pravastatin could reduce the number of sites of osteonecrosis development in individual rats that developed osteonecrosis. Finally, we determined whether pravastatin has any effects on disorders of lipid metabolism and lipid peroxidation after corticosteroid administration.     

骨水泥阻塞骨干髓腔后远侧骨干骨内压和骨血流改变的实验研究

[目的]探讨骨水泥阻塞股骨近中段骨干髓腔后对股骨远端骨内压和骨血流的影响.[方法]采取兔左侧股骨髓腔内灌注PMMA骨水泥而右侧不灌注作为正常对照的方法,制作骨水泥阻塞股骨近中段骨干髓腔的兔动物模型.将32只实验兔分成5组,随机取出8只不做模型作为正常对照组,其余24只制作模型后,根据不同的观察时间段随机分成术后当天（T0）、术后4周（T4）、术后8周（T8）、术后16周（Ti6）4个观察组,每组6只.使用生理测压仪,对正常和模型动物双侧股骨远端骨内压进行测量和比较.采用核素骨显像（ECT）方法,对模型动物双侧股骨远端动态和静态显像进行检测和比较.[结果]（1）骨内压：正常兔股骨远端双侧骨内压无差异性（P＞0.05）：T0、T4、T8、T16实验侧骨内压明显增高,双侧有差异性（P＜0.01）.造模后在不同观察时间段对照侧骨内压均无差异性（P＞0.05）,实验侧处于持续骨内高压状态,T0与T4、T0与T8、T0与T16、T4与T8、T8与T16均无差异性（P＞0.05）,T4与T16有差异性（P＜0.05）;（2）核素骨显像：T0、T4实验侧核素计数均比对照侧明显降低,T8、T16实验侧核素计数均超过对照侧,T16最高;各时间段实验侧/对照侧核素计数比值中T0与T8、T0与T16、T4与T16、T8与T16、T4与T8均有差异性（P＜0.05）,而T0与T4无差异性（P＞0.05）.核素骨动态和静态显像的变化趋势完全一致.[结论]骨水泥阻塞股骨近中段骨干髓腔后严重破坏了骨内和髓内的血液循环状态,引起了局部血流动力学的改变.导致股骨远端的骨内压和骨血流发生了一系列的变化,骨内压持续升高并长期存在.     

Blood flow and microdialysis in the human femoral head

Background If it would be possible to detect lack of flow and/or the development of ischemia in bone, we might have a way of predicting whether a broken bone will heal. We established microdialysis (MD) and laser Doppler (LD) flow measurement in the human femoral head in order to be able to detect ischemia and measure changes in blood flow.

Material and methods In 9 patients undergoing total hip arthroplasty for primary osteoarthrosis, two MD catheters were inserted into the femoral head through two drill holes after the blood flow had been visualized by LD. Then primary samples were collected with the femoral head in situ; thereafter, the head was removed and samples were collected over the following 4 hours ex vivo. The variables obtained by MD were concentrations of glucose, lactate, pyruvate, and glycerol in extracellular fluid.

Results The results showed development of ischemia with a statistically significant decrease in glucose concentration and elevation of the lactate/pyruvate ratio over time. The LD showed flow with the femoral head in situ and lack of flow when the femoral head was removed.

Interpretation The use of MD was established in the human femoral head. Ischemic levels were detected within 2 h of cessation of blood flow in most patients.     

幼犬髋关节外周动脉对股骨头前外侧部血流的影响

目的动态评估结扎幼犬不同数量髋外周动脉后,股骨头前外侧部血流量的变化。方法将18只杂种幼犬的36个髋关节进行分组,A组为结扎任意1条动脉,B组为结扎任意2条动脉,C组为结扎任意3条动脉,D组为结扎任意4条动脉,E组为结扎全部5条动脉。应用氢廓清技术测量结扎髋外周动脉前、后的股骨头前外侧部血流量。结果(1)正常情况下,股骨头前外侧部血流量平均为(0.1397±0.0515)ml·min-1·ml-1;(2)5条主要动脉中,结扎1条或2条动脉后血流量轻微降低,但无统计学意义。结扎动脉数超过3条后,平均血流量显著降低。结论(1)氢廓清技术是一种简单、可靠、经济的局部组织血流定量测定方法。(2)通过氢廓清技术可以获得满意的股骨头血流资料,股骨头前外侧部血供主要靠3条髋外周动脉供养。     

The impact of vasoactive substances on intraosseous pressure and blood flow alterations in the femoral head: a study based on magnetic resonance imaging

In beagle dogs, the alterations of intraosseous pressure and blood supply in the femoral head that result from the administration of vasoactive substances were examined, and the changes were documented by magnetic resonance imaging (MRI). Vasoactive substances were infused into the medial and lateral circumflex femoral arteries of 12 beagle dogs. All infusions were done under standardised conditions with simultaneous measurements of venous blood flow and intraosseous pressure distribution in the proximal femur. The drugs were infused in three cycles of 30 min each separated by 30 min recovery periods, followed by MRI examination at the end of each experiment. At an intraosseous pressure of 14.3 (± 4.2) mm Hg in the femoral head epiphysis (I), 11.6 (± 2.7) mm Hg in the greater trochanter (II) and 9.3 (± 3.2) mm Hg in the femoral shaft (III), a baseline flow of 96.2 (± 18.8, n = 12) ml/min was measured in the femoral vein. After infusing bradykinin at a concentration of 10^–6 moles, which is commonly known to lead to cerebral and subcutaneous oedema formation by vessel dilatation, the intraosseous pressure increased to (I): 49.1 (± 6.2) mm Hg, (II): 42.5 (± 5.8) mm Hg and (III): 38.3 (± 7.1) mm Hg in the three measured femoral areas (n = 3). After the bradykinin injection, femoral vein flow increased to a peak value of 238.4 (± 43.4) ml/min and then dropped to 62.3 (± 14.2) ml/min after discontinuation of the bradykinin infusion. In a second and third series of tests, hyperosmolar (20% NaCl) and hypoosmolar (distilled water) solutions were applied, also resulting in increased but lower mean intraosseous pressure values (17.3 ± 4.1 and 25.7 ± 5.1 ml/min, respectively) in all regions. When administering bradykinin, MRI scans taken immediately after completion of the experiment showed substantial oedema in the femoral muscular system, but without any changes of osseous signals in T₁- or short time inversion recovery (STIR)-weighted images, nor did any changes occur when solutions of 20% NaCl or distilled H₂O were injected. The results of our experiments demonstrate that acute increases of intraosseous pressure do not cause MRI signal alterations. We therefore conclude that in addition to the described pressure increase, other intraosseous alterations must occur to lead to the detectable signal changes found among patients with diagnosed femoral head necrosis. Finally, the short time period between the rise in intraosseous pressure and performing a conventional MRI may be one reason for missing the development of an intraosseous oedema. On the other hand, conventional MRI might have additional disadvantages for detecting intraosseous fluid compared with a dynamic imaging modality. Received: 19 December 1997     

Effect of intracapsular hyperpressure on femoral head blood flow. Laser Doppler flowmetry in dogs

Intracapsular hyperpressure in the hip joint of dogs affected femoral head blood flow, especially in the juvenile animals. Graphic recording of the laser Doppler signal curve using rapid sampling time demonstrated venous hip joint tamponade in both juvenile and adult dogs. Laser Doppler flowmetry seems to be a sensitive and reproducible method to demonstrate femoral-head blood-flow changes.     

Effect of intracapsular hyperpressure on femoral head blood flow: Laser Doppler flowmetry in dogs

Intracapsular hyperpressure in the hip joint of dogs affected femoral head blood flow, especially in the juvenile animals. Graphic recording of the laser Doppler signal curve using rapid sampling time demonstrated venous hip joint tamponade in both juvenile and adult dogs. Laser Doppler flowmetry seems to be a sensitive and reproducible method to demonstrate femoral-head blood-flow changes.     

Increased perfusion of the femoral head in transient bone marrow edema syndrome

The pathophysiology of transient bone marrow edema syndrome is not known. Ischemia has been suggested as the pathophysiologic factor, because the histologic findings are similar to those of early stage osteonecrosis. Angiographic studies of osteonecrotic femoral heads have shown arterial interruption and impaired perfusion. The current report describes the angiographic and scintigraphic findings of transient bone marrow edema syndrome of the hip in a 45-year-old man. The nutrient arteries were dilated, and the femoral head perfusion was increased compared with the unaffected contralateral side. These findings suggest that a vasomotor response plays a role in the pathogenesis of transient bone marrow edema syndrome. The disease might be a reversible process after temporary ischemia of the femoral head.     

Avascular necrosis and the blood supply of the femoral head

Postmortem femoral artery perfusion revealed abnormalities in the femoral head pattern of vessels in steroid-treated renal transplant patients as compared with controls. Degenerative changes were found in some of the arteries and arterioles of the hip capsule and femoral head in the renal transplant patients. Two of these patients' femoral heads showed microfocal avascular necrosis. Although high-dose steroids were used in these patients, none had suffered clinically from hip disease while alive. These findings suggest the possibility that local arterial disease may be involved in the pathogenesis of avascular necrosis.     

Radial to femoral arterial blood pressure differences during liver transplantation

This observational study compared femoral and radial arterial blood pressure in 72 patients undergoing liver transplant surgery. Simultaneous femoral and radial arterial blood pressures, cardiac index, core temperature and vasoconstrictor therapy were recorded at seven time points during the operation. No significant differences between radial and femoral pressures were found at the start of surgery. Femoral and radial systolic arterial blood pressures were statistically significantly different during liver reperfusion (mean (SD) arterial pressure = 92 (22) mmHg vs. 76 (22) mmHg, p < 0.01). Mean arterial blood pressures showed no statistically significant differences throughout the study. Vasoconstrictor drug administration was associated with a larger systolic pressure difference between femoral and radial arteries (28 (24) mmHg in patients being given vasoconstrictor drugs vs. 9 (19) mmHg in patients not needing vasoconstrictors during reperfusion, p < 0.001). In conclusion, differences in systolic arterial blood pressure occur between femoral and radial arterial monitoring sites during liver reperfusion, and in particular in patients being given vasoconstrictor therapy. Thus, if femoral arterial monitoring is not available, clinicians should rely on mean rather than systolic arterial pressure measurements from a radial artery catheter during liver transplantation.