Mapping regional cerebral vascular transit time by simultaneous determination of local cerebral blood flow and local cerebral blood volume

We developed a method for autoradiographic mapping of regional cerebral transit time (CTT) by simultaneously measuring local cerebral blood flow (LCBF) and local cerebral blood volume (LCBV). Previously described single-tracer techniques for determination of LCBF and LCBV were modified for dual-tracer,^99mTc and¹⁴C, autoradiography and used to create digital images of LCBF and LCBV from the same brain sections in a series of normal rats. The images were aligned and ratio images (LCBV/LCBF) were then generated which reflected CTT. Regional cerebral transit time was found to vary significantly throughout the brain in a pattern only partially related to that of blood flow. Such CTT heterogeneity could cause errors in implementation of kinetic models which assume uniform or monovariant distributions of vascular transit time.     

The diagnostic value of Doppler echocardiographic indexes of diastolic filling for detecting demand ischemia in anesthetized patients

In awake patients, Doppler indexes of transmitral flow velocities have been shown to be more sensitive for detection of myocardial ischemia than echocardiographic evaluation of systolic wall-motion. The diagnostic value of these indexes in anesthetized patients is unknown. It might differ from that in awake patients because anesthetics and sympathomimetic drugs, which are commonly used in surgical patients with coronary artery disease (CAD), independently affect transmitral flow velocities. Methods: Several previously published transmitral Doppler echocardiographic indicators of ischemia (marked decreases in the ratio of peak early [E] to peak atrial [A] filling velocity [E/A], in the ratio of early to atrial time–velocity integral [E_I/A_I], in E, in E acceleration, and in total diastolic time–velocity integral) were compared with standard wall-motion analysis and ST-segment analysis during dobutamine stress echocardiography (DSE) in 17 anesthetized patients with CAD and 7 age-matched control patients at low risk of CAD. Results: All patients with CAD but no control patients showed new systolic wall-motion abnormalities and/or ST-segment changes. Decreases of >10% in E/A and E_I/A_I were found in 88% and 71% of the patients with CAD and in 71% and 100% of the control patients, respectively. These decreases were found during dobutamine infusion at as low as 10 mcg/kg/min in several control patients. None of the other studied Doppler indexes were found useful to detect ischemia. Conclusions: Doppler echocardiography of diastolic transmitral flow velocities is of no appreciable diagnostic value for detecting ischemia in anesthetized patients who receive dobutamine at 10–40 mcg/kg/min.     

Intratumor distribution of blood flow and of vascular volume in a transplantable rat sarcoma

Summary The intratumor distribution of plasma volume and of blood flow was studied simultaneously by radioisotope techniques in a transplantable, slightly differentiated 20-methylcholanthrene-induced rat sarcoma. A significant change toward lower tumor blood flow was found in the sarcoma with increasing tumor growth, accompanied by a reduced plasma volume. The distributions of plasma volume and blood flow were similar in peripheral and central parts of tumors. However, no significant correlation between plasma volume and blood flow was found in separate tumor specimens.     

Dihydroergotamine decreases the blood content in the skeletal musculature but etilefrine hydrochloride in the splanchnic region in man

Summary Dihydroergotamine (DHE, Dihydergot^®) constricts the capacitance vessels of the striated musculature about twice as strong as etilefrine hydrochloride (E, Effortil^®) for the same increment in central venous pressure. This and the additive effects of both agents on central venous pressure suggested that E may constrict primarily splanchnic capacitance vessels, a hypothesis, that was tested here by looking at the regional distribution of⁹⁹Tc-marked erythrocytes in healthy volunteers.With the subjects supine under a gamma camera the radioactivity was recorded along with central venous pressure, heart rate, and arterial pressure and evaluated for various regions. E was infused twice at a rate of 5 g/kg per minute before and after the injection of DHE (7.5 g/kg).E reduced strongly and selectively the radioactivity in the splanchnic area, not however in skeletal muscle. The reverse held for DHE. Both agents increased the counting rates in the thorax and also central venous pressure, effects which were additive when the two drugs acted together.E preferentially expels blood from the splanchnic vasculature, but DHE from skeletal muscle. The effects add and redistribute blood in favour of the intrathoracic circulation so that the combination of the two agents could be used to advantage for the treatment of cardiac filling disturbances.The support of the Deutsche Forschungsgemeinschaft through the Sonderforschungsbereich 30 Kardiologie Düsseldorf is gratefully acknowledged.     

解剖M型超声评价室间隔缺损患者肺血管阻力的初步研究

目的：探讨解剖M型超声（AMM）对分析室间隔缺损（VSD）患者肺动脉机械特征及评价肺血管阻力（PVR）的价值。方法：应用AMM观测20例轻症VSD患者、18例重症VSD患者及20例正常人的主肺动脉运动曲线,测量主肺动脉短轴缩短率（PAFS）、主肺动脉外侧壁搏动幅度（PAWPA）、外侧壁快速扩张速率（R—DVR）及外侧壁快速缩短速率（R—CVR）。应用VSD跨隔压差结合肱动脉压计算出肺动脉收缩压,应用肺动脉血流时间间期法计算出PVR值。结果：VSD轻症组及重症组的PAFS、PAWPA、R—DVR及R—CVR均低于对照组,且重症组上述参数的减小幅度更显著（P〈0．05）。结论：AMM可无创评价肺动脉的力学特性,PAFS及PAWPA等参数可作为半定量评价VSD患者PVR的超声指标。     

ITBI和GEDI评估心源性肺水肿患者心脏前负荷变化的局限性

目的研究胸腔内血容积指数（ITBI）和全心舒张末容积指数（GEDI）能否充分评估心源性肺水肿患者心脏前负荷状态。方法对8例心源性肺水肿患者,应用肺动脉导管（SWAN-GANZ）和脉搏指示连续心输出量（PiCCO）监测血流动力学,持续肾脏替代治疗（CRRT）减轻心脏前负荷,分别监测CRRT开始时、8h、16h和24h的中心静脉压（CVP）、肺动脉楔压（PAWP）、ITBI、GEDI等血流动力学指标,分析随着前负荷的减少,这些指标的变化。结果在超滤8h后CVP和PAWP下降即出现显著变化（17．3±2．5掷．16．1±2．2和39．6±4．2％36．0±4．2,P〈0．01）,并随着超滤时间延长,下降更明显,而ITBI和GEDI到超滤24h才出现显著下降（971±133VS．898±51和779±103vs.719±40,P〈0．05）;CVP、PAWP、ITBI和GEDI随着前负荷减少的变异度分别为（16．29±10．37）％、（19．35±9．86）％、（2．95±6．02）％和（3．25±6．03）％。结论IBTI和GEDI在评估心源性肺水肿患者的前负荷状态时敏感性低于CVP和PAWP。     

Prognostic value of blood count parameters in patients with acute coronary syndrome

BackgroundRecent studies have shown that complete blood count (CBC) parameters can effectively predict long-term mortality and re-infarction rates in acute coronary syndrome (ACS). However, the role of these parameters in predicting short term mortality has not been studied extensively. The main objective of this study was to determine whether CBC parameters can predict 30-days mortality and the incidence of major adverse cardiac event (MACE) in ACS patients.MethodologyA total of 297 patients with ACS were recruited in this prospective study. The relationship of baseline white blood cell (WBC) to mean platelet volume ratio (WMR) with MACE and mortality was assessed during a 30-days follow up. The patients were divided into two groups: Group A [WMR < 1000] and Group B [WMR > 1000]. Multivariate COX regression was performed to calculate hazard ratios (HR).ResultsWMR had the highest area under receiver operating characteristics curve and highest discriminative ability amongst all CBC parameters in predicting mortality. Patients in Group B had a higher mortality rate (p < 0.001) than patients in Group A. WBC count (p = 0.02), platelet count (p = 0.04), WMR (p = 0.008), platelet to lymphocyte ratio (p < 0.001) and neutrophil to lymphocyte ratio (p = 0.03) were significantly higher in the MACE-positive group as compared to MACE-negative. In multivariate cox regression analysis, WMR > 1000 (HR = 2.9, 95% confidence interval 1.3–6.5, p = 0.01) was found to be strongest biochemical marker in predicting mortality.ConclusionWMR is an easily accessible and an inexpensive indicator, which may be used as a prognostic marker in patients with ACS.     

Increased effective vascular compliance and venous pooling of intravascular volume during sustained venodilation in conscious dogs

Summary The hemodynamic effects of the long-acting antianginal drug molsidomine were studied in 8 chronically instrumented conscious dogs by measuring the partition of the intravascular volume and the effective compliance of the total vascular bed. The blood volume of the resting dogs was varied by ±4 ml/kg in a cycle of blood infusion, withdrawal and reinfusion within 12 minutes. Relating the observed alterations in mean right atrial pressure to the induced changes in intravascular volume, an effective compliance of 2.9±0.4 ml· mm Hg^–1·kg^–1 (mean±SD) was found. Heart rate, total peripheral vascular resistance and the local capacity of the distal femoral vein did not change significantly during the cycle of volume alterations. Following 0.1 mg/kg molsidomine i.v., mean right atrial pressure was lowered by 1.6 mm Hg and mean left atrial pressure by 3.4 mm Hg; the effective compliance was elevated to 4.7±0.6 ml·mmHg^–1·kg^–1 (p<0.001) and the central blood volume was lowered from 17.8±3.1 to 14.8±3.3 ml/kg (p<0.01) while total blood volume remained constant. The decline in stroke volume and the reflexly induced increase in heart rate correlated with the control heart rate. Mean arterial pressure declined from 101±7 to 91±14 mmHg (p<0.05) and total peripheral vascular resistance remained unaffected. It is concluded that molsidomine exerts its hypotensive effect by dilation within the vascular low-pressure system and that this dilation can be described quantitatitely in conscious animals by the analysis of the total effective vascular compliance.Supported by grant Ba 408/10 from Deutsche Forschungsgemeinschaft. Part of the study was performed at Physiologisches Institut der Universität München.     

Platelet vascular endothelial growth factor is a useful predictor for prognosis in Kawasaki syndrome

Kawasaki syndrome (KS) is an acute febrile vasculitis of childhood. Coronary artery abnormalities (CAA) are a significant problem in KS patients. High dose intravenous immunoglobulin (IVIG) is effective for reducing the occurrence of CAA. Clinical and histopathological findings suggest that vascular endothelial growth factor (VEGF) is involved in CAA. In circulating blood, newly activated platelets are the major source of VEGF, which is released in large amounts in vascular inflammation. The present study analysed 80 KS patients (69 IVIG responders and 11 IVIG non-responders) and evaluated the role of platelet VEGF in KS vasculitis. Serum VEGF and platelet VEGF levels were significantly higher in KS patients than controls ( P  <   0·001). Platelet VEGF reflected the reactivity of IVIG treatment and was decreased in responders ( P  <   0·001), but remained increased in non-responders ( P  =   0·01). Platelet VEGF levels, but not serum VEGF levels, before IVIG were significantly correlated with the maximum CAA z -score ( r  = 0·524, P  =   0·02). Our findings demonstrate that platelet VEGF may reflect the severity of vasculitis related to the pathological development of CAA in KS. Platelet VEGF may be an important feature of KS pathophysiology.     

Serial pulmonary blood volume changes with supine exercise in normal subjects and in coronary artery disease patients

Relative changes in pulmonary blood volume (PBV) were assessedserially at first stage, peak and post-supine exercise in 13young normal volunteers and 33 coronary artery disease (CAD)patients.Gatedblood pool imaging was used with time correced count calculationof a region over the lung and comparison to he rest image. Innormal subjects, the PBV ratio did not change with exercisebut dropped significally immediately post-exercise. In CAD patients,the PBV ratio increased in the first exercise stage, increasedfurther at peak exercise, and fell significantly following exercisecessation. In the three stages studied, significantly higherPBV ratios were demonstrated in the CAD patients compared tonormal subjects, but with significant overlap between he twogroups. No significant relation was found between PBV changesand the number of diseased vessels, severity score (Gensini),left ventricular end-diastolic pressure, exercise-limiting symptoms,andleft and right ventricular ejection fraction at rest and withexercise. Despite the different response of the PBV ratio toexercise between normals and CAD patients, a significant overlaplimits the value of this ratio as a discriminator of the presence,severity or location of CAD.     

Volume control during periodic changes of blood volume in the alert rat

Summary Blood (3.4–13.5% of blood volume) was pumped in and out of the circulation of rats at different rates and period lengths during continuous measurements of blood conductivity (reciprocally related to hematocrit) and arterial pressure. Hct followed the same zig-zag course as the induced changes of blood volume in every case, indicating that fluid shifts (v) between interstitium and intravascular space closely follow blood volume changes. As the het increase during reinfusion was not as great as the preceding decrease, hct dropped continuously during the 20–90 minutes of experimentation, so that a final volume increase (v) by about 4% was calculated, which was confirmed by a corresponding decrease of plasma protein concentration. Both final v and v during periodic volume change (% B.V.) were greater when arterial pressure dropped. v was directly related to % B.V. but not to its rate of change. Heart rate dropped slightly at the end of the reinfusion periods, whereas it rose to control at the end of the withdrawal periods. The results were regarded as evidence of blood volume regulation proportional to the absolute volume of blood lost in non-hypotensive hemorrhage.Supported by DFG-grant AZ 3/3     

The effect of controlled changes in volume on the active state of the rabbit isolated left ventricle

Summary The contractile properties of isovolumically contracting isolated rabbit left ventricles are studied under the influence of controlled rapid volume changes during systole and diastole. The time integral of the pressure curve (TTI), representing the active state, is used to quantify the energy consumption of the ventricle. Steady state conditions resulting from an introduced volume change show a TTI/EDV relation which represents the Starling curve. However, immediately after a quick volume increase (decrease) introduced in diastole, the TTI/EDV ratio has a higher (lower) value than indicated by the Starling relation. This shows a volume dependent activation (deactivation), related to changes in the inotropic state of the heart muscle cells within the ventricular wall.A volume increase at a later moment (in systole) always produces a lower rate of activation. Indeed, if the rapid volume change, is introduced at moments later than 70% of time to peak pressure, TTI is less than observed from the Starling mechanism, indicating a deactivation When comparing the decreasing effect on the active state introduced by volume decrease during systole, it is shown that this effect is not only a function of the amplitude of the decrease itself but is highly dependent upon the way EDV is reached.     

Islet transplants in diabetic Lewis rats prevent and reverse diabetes-induced increases in vascular permeability and prevent but do not reverse collagen solubility changes

Summary The effects of islet transplantation on diabetes-induced increases in vascular permeability and collagen solubility were examined in new granulation tissue vessels and collagen formed after induction of streptozotocin diabetes in male Lewis rats. Albumin permeation was increased by 50% (p<0.001) and collagen solubility was decreased by 50% (p<0.001) in granulation tissue from untreated diabetic animals as compared with controls. The islet transplants reversed diabetes-induced vascular permeability increases in tissues formed prior to islet transplantation (tissue to blood isotope ratio =2.1±0.1 - SD for controls, 3.2±0.2 for diabetic rats and 2.0±0.2 for diabetic rats given islets) and prevented permeability increases in new tissues formed following transplantation (tissue to blood isotope ratio =2.1±0.1 for controls, 3.3±0.8 for diabetic rats and 1.9±0.2 for diabetic rats given islets). In contrast, while islet transplants prevented diabetes-induced decreased collagen solubility in tissues formed after transplantation (controls = 24%, diabetic rats =12%, and diabetic rats given islets =24%), collagen solubility in tissues formed prior to islet transplantation was virtually unaffected. These findings indicate that collagen changes induced by the diabetic milieu are not nearly as readily reversed by normalization of the diabetic milieu as (diabetes-induced) alterations in vascular functional integrity.     

Nitric oxide and vascular endothelial growth factor concentrations are increased but not related in vitreous fluid of patients with proliferative diabetic retinopathy.

AIMS: Several reports have implicated nitric oxide (NO) in the angiogenic process. The assessment of NO stable end products, nitrite and nitrate (NOx), is commonly used as a measure of NO production in biological fluids. The aims of the study were to investigate NOx concentrations in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to evaluate the relationship between NOx and vascular endothelial growth factor (VEGF). PATIENTS AND METHODS: Serum and vitreous fluid samples were obtained simultaneously at the time of vitreoretinal surgery from 23 patients with PDR, and 17 control non-diabetic patients with non-proliferative ocular disease. NOx was determined by using the Griess reaction and VEGF levels were assessed by ELISA. RESULTS: The intravitreous concentration of NOx was significantly elevated in patients with PDR in comparison with the control group (31.6 +/- 2.96 micromol/l vs. 18 +/- 2.46 micromol/l; P = 0.01). However, we did not detect any differences between NOx serum concentrations. We observed a correlation between serum and vitreous levels of NOx in diabetic patients (r = 0.79; P < 0.001), but not in the control group. Intravitreous levels of VEGF in patients with PDR were higher than those obtained in serum (1.42 ng/ml (0.12-7.62) vs. 0.12 ng/ml (0.03-0.42); P < 0.01). Vitreal levels of VEGF were strikingly higher in patients with PDR than in the control subjects (1.42 ng/ml (0.12-7.62) vs. 0.009 ng/ml (0.009-0.04); P < 0.001). No correlation between vitreal concentrations of NOx and VEGF was observed, either in diabetic patients or in the control group. CONCLUSIONS: NOx and VEGF are increased but not related in the vitreous fluid of diabetic patients with PDR. Our results suggest that serum diffusion could play a significant role in explaining the increase of NOx. By contrast, intraocular production seems to be the main factor responsible for the intravitreous enhancement of VEGF.     

Risk scores for risk stratification in acute coronary syndromes: useful but simpler is not necessarily better.

AIMS: Our objectives were (i) to compare the discriminatory performance of the Thrombolysis in Myocardial Infarction risk score (TIMI RS), Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy risk score (PURSUIT RS), and Global Registry of Acute Cardiac Events risk score (GRACE RS) for in-hospital and 1 year mortality across the broad spectrum of non-ST-elevation acute coronary syndromes (ACS) and (ii) to determine their incremental prognostic utility beyond overall risk assessment by physicians. METHODS AND RESULTS: We calculated the TIMI RS, PURSUIT RS, and GRACE RS for 1,728 patients with non-ST-elevation ACS in the prospective, multicentre, Canadian ACS II Registry. Discriminatory performance was measured by the c-statistic (area under receiver-operating characteristic curve) and compared by the method described by DeLong. TIMI RS, PURSUIT RS, and GRACE RS all demonstrated good discrimination for in-hospital death (c-statistics = 0.68, 0.80, 0.81, respectively, all P < 0.001) and 1 year mortality (c-statistics = 0.69, 0.77, 0.79, respectively, all P < 0.0001). However, PURSUIT RS and GRACE RS performed significantly better than the TIMI RS in predicting in-hospital (P = 0.036 and 0.02, respectively) and 1 year (P = 0.006 and 0.001, respectively) outcomes. In multivariable analysis adjusting for the use of in-hospital revascularization, stratification by tertiles of risk scores (into low, intermediate, and high-risk groups) furnished independent and greater prognostic information compared with risk assessment by treating physicians for 1 year outcome. CONCLUSION: Compared with TIMI RS, both PURSUIT RS and GRACE RS allow better discrimination for in-hospital and 1 year mortality in patients presenting with a wide range of ACS. All three risk scores confer additional important prognostic value beyond global risk assessment by physicians. These validated risk scores may refine risk stratification, thereby improving patient care in routine clinical practice.     

The spun micro-haematocrit and mean red cell volume are affected by changes in the oxygenation state of red blood cells

In this study we examined the effects of in vitro oxygenation and deoxygenation on the spun micro-haematocrit (packed cell volume or PCV) and the electronically measured mean cell volume (MCV) and haematocrit (Hct) of red blood cells. Because PCV and/or MCV and Hct are being used for calibration of haematology analysers, it is important that their potential variability caused by outside factors is known. We found that these parameters did vary with the oxygenation state of the erythrocyte and conclude that the effect is most likely caused by a combination of water shifts due to intracellular carbamate and bicarbonate formation, and conformational changes in haemoglobin. The results of the study have implications for whole blood calibration and for short term imprecision assessments of automated haematology analysers. To ensure consistent results, we recommend that blood specimens be fully oxygenated before reference work or reproducibility studies of MCV, Hct and/or PCV are attempted.     

胸腔血容量指数与外肺水指数对烧伤患者肺水肿的早期预测价值

目的研究胸腔血容量指数与外肺水指数对烧伤患者肺水肿的早期预测价值。方法选取2013年1月到2014年12月在我院烧伤科接受治疗及Pi CCO检测且伤后10天内发生肺水肿的严重烧伤患者42例,根据患者肺水肿类型分为肺损伤型组与静水压型组,对比两组Pi CCO监测指标及肺损伤评分,探索EVLWI与ITBVI、氧合指数的相关性。结果两组患者EVLWI水平相差不大,但静水压型组ITBVI及氧合指数均明显大于非损伤组,Murray评分明显低于肺损伤组;EVLWI与ITBVI呈显著正相关性,r=0.921,P0.05;EVLWI与氧合指数呈明显的负相关性,r=-0.718,P0.05。结论烧伤早期实行监测胸腔血容量指数与外肺水指数对患者发生肺水肿预测和鉴别具有重要参考意义。     

Complete blood count using VCS (volume, conductivity, light scatter) technology is affected by hyperlipidemia in a child with acute leukemia

Asparaginase, an effective drug in the treatment of childhood acute lymphoblastic leukemia (ALL), has become an important component of most childhood ALL regimens during the remission induction or intensification phases of treatment. The incidence range of asparaginase‐associated lipid abnormalities that are seen in children is 67–72%. Lipemia causes erroneous results, which uses photometric methods to analyze blood samples. We describe a case of l ‐asparaginase‐associated severe hyperlipidemia with complete blood count abnormalities. Complete blood count analysis was performed with Beckman COULTER^® GEN·S? system, which uses the Coulter Volume, Conductivity, Scatter technology to probe hydrodynamically focused cells. Although an expected significant inaccuracy in hemoglobin determination occurred starting from a lipid value of 3450 mg/dl, we observed that triglyceride level was 1466 mg/dl. Complete blood count analysis revealed that exceptionally high hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration levels vs. discordant with red blood cell count, mean corpuscular volume, and hematocrit levels. Total leukocyte count altered spontaneously in a wide range, and was checked with blood smear. Platelet count was in expected range ( Table 1 ). Thus, we thought it was a laboratory error, and the patient’s follow‐up especially for red cell parameters was made by red blood cell and hematocrit values.

Table 1. Patient’s complete blood count analysis according to the days of induction

High‐phosphorus diet controlled for sodium elevates blood pressure in healthy adults via volume expansion

Whether increasing exposure to dietary phosphorus can lead to adverse clinical outcomes in healthy people is not clear. In this open‐label prospective cross‐over study, we are to explore the impact of various dietary phosphorus intake on mineral, sodium metabolisms and blood pressure in young healthy adults. There were 3 separate study periods of 5 days, each with a 5 days washout period between different diets interventions. Six young healthy male volunteers with normal nutrition status were recruited in Phase I Clinical Research Center and sequentially exposed to the following diets: (a) normal‐phosphorus diet (NPD): 1500 mg/d, (b) low‐phosphorus diet (LPD): 500 mg/d, (c) high‐phosphorus diet (HPD): 2300 mg/d. HPD induced a significant rise in daily average serum phosphate (1.47 ± 0.02 mmol/L [4.56 ± 0.06 mg/dl]) compared to NPD (1.34 ± 0.02 mmol/L [4.15 ± 0.06 mg/dL]) and LPD (1.17 ± 0.02 mmol/L [3.63 ± 0.06 mg/dL]) (p < .05). Daily average levels of serum parathyroid hormone and fibroblast growth factor 23 in HPD were significantly higher, and serum 1,25(OH)₂D₃ was remarkably lower than those in LPD. HPD induced a significant decrease in daily average serum aldosterone and an increase in daily average atrial natriuretic peptide level compared to LPD. The 24‐hour urine volume in HPD subjects was less than that in LPD subjects. HPD significantly increased daily average systolic blood pressure by 6.02 ± 1.24 mm Hg compared to NPD and by 8.58 ± 1.24mm Hg compared to LPD (p < .05). Our study provides the first evidence that 5‐day high‐phosphorus diet can induce elevation in SBP in young healthy adults, which may due to volume expansion.