FLOW LOADED CANINE CAROTID ARTERY II. Ultrastructural Changes in the Subendothelial Layer

To study the subendothelial layer of the flow loaded arteries, blood flow changes were produced by constructing an arterio-venous shunt between the common carotid artery and the external jugular vein using eleven adult beagle dogs. One week after operation, the subendothelial layer of the flow loaded canine carotid arteries was observed with a transmission electron microscope. In the arteries loaded by highly elevated blood flow, the subendothelial layer showed thick subendothelial space (300 to 500 nm) with multilayered basement membrane. The microfilaments and microfibrils increased significantly. There were no collagen fibers. Spindle to cylindrical elastic fibers appeared in the lumlnal margin of the internal elastic lamina. On the other hand, in the control arteries, the subendothelial layer was thin (about 50 nm) with scanty basememt-membrane-like material. There were a few microfilaments and microfibrils, but no collagen fibers. The luminal margin of the internal elastic lamina was smooth. It is suggested that these are the wall shear stress dependent subendothelial changes, which would be partly due to the increased protein synthesis by the endothelial cells stimulated by the wall shear stress and be partly due to the wall shear dependent mechanical stress transmitted from the endothelial surface.     

Flow loaded canine carotid artery. II. Ultrastructural changes in the subendothelial layer

To study the subendothelial layer of the flow loaded arteries, blood flow changes were produced by constructing an arterio-venous shunt between the common carotid artery and the external jugular vein using eleven adult beagle dogs. One week after operation, the subendothelial layer of the flow loaded canine carotid arteries was observed with a transmission electron microscope. In the arteries loaded by highly elevated blood flow, the subendothelial layer showed thick subendothelial space (300 to 500 nm) with multilayered basement membrane. The microfilaments and microfibrils increased significantly. There were no collagen fibers. Spindle to cylindrical elastic fibers appeared in the luminal margin of the internal elastic lamina. On the other hand, in the control arteries, the subendothelial layer was thin (about 50 nm) with scanty basement-membrane-like material. There were a few microfilaments and microfibrils, but no collagen fibers. The luminal margin of the internal elastic lamina was smooth. It is suggested that these are the wall shear stress dependent subendothelial changes, which would be partly due to the increased protein synthesis by the endothelial cells stimulated by the wall shear stress and be partly due to the wall shear dependent mechanical stress transmitted from the endothelial surface.     

Stability of hepatitis C virus, HIV, and hepatitis B virus nucleic acids in plasma samples after long-term storage at -20°C and -70°C

The storage of biological samples may affect detection of viral nucleic acid, yet the stability of viral nucleic acid at standard laboratory storage temperatures (-70°C and -20°C) has not been comprehensively assessed. Deterioration of viral RNA and DNA during storage may affect the detection of viruses, thus leading to an increased likelihood of false-negative results on diagnostic testing. The viral loads of 99 hepatitis C virus (HCV), 41 HIV, and 101 hepatitis B virus (HBV) patient samples were measured before and after storage at -20°C and -70°C for up to 9.1 years using Versant branched DNA assays, Cobas Monitor assays, and/or AmpliPrep/AmpliScreen assays. Clinical samples stored at -20°C for up to 1.2 years and at -70°C for up to 9 years showed a statistically significant difference from baseline with respect to HCV RNA titer, although this difference was not greater than 0.5 log(10) unit. The concentration of HIV RNA in clinical samples stored at -20°C for 2.3 years and at -70°C for up to 9.1 years did not differ significantly from the baseline viral load. HBV DNA-positive clinical samples stored at -20°C for up to 5 years and at -70°C for up to 4 years differed significantly in viral load. In all studies, however, the loss of viral load of HCV, HIV, or HBV in clinical samples tested after storage at -20°C and -70°C for up to 9 years ranged from 0.01 to 0.35 log(10) IU/ml and did not exceed 0.5 log(10), which is the estimated intra-assay variation for molecular tests. Hence, the loss was considered of minimal clinical impact and adequate for the detection of HCV, HIV-1, and HBV nucleic acids using nucleic acid assays for the assessment of the infectious risk of cell, blood, and tissue donors.     

Laboratory evaluation of the ESwab transport system for the recovery of carbapenem-resistant Acinetobacter baumannii

Microbiological surveillance for detection of carbapenem-resistant A. baumannii is important, but recovery of A. baumannii is inadequate. We studied A. baumannii recovery by a particular transport system that is possibly superior over standard swabs, using reference and clinical strains. First, the recovery rates relating to the various swabs were compared with regard to various combinations of transport times (0 h, 1 h, 24 h, 48 h), storage times (0 weeks, 1 week, 2 weeks, 4 weeks) and storage temperatures (4°c,-80°c) using live counts. Second, the recovery of different inocula of strains mixed with fecal microbiota was evaluated by plating on selective medium. The new transport system exhibited a decline of <3log10 under almost all conditions studied and performed better than standard swabs under several conditions. If plated on selective media, the new transport system performed well, even after prolonged transport or with a low inoculum, and its processing could be delayed by up to 2 weeks, especially if refrigerated. The new transport system may thus enhance A. baumannii surveillance.     

Effect of vitamin E administration on response to ischaemia-reperfusion of hearts from cold-exposed rats

In both 3,5,3-triiodothyronine (T(3))-induced hyperthyroidism and cold-induced functional hyperthyroidism, the heart displays an increased susceptibility to oxidative challenge in vitro. Hearts from T(3)-treated rats also exhibit an increased susceptibility to ischaemia-reperfusion, a condition that raises free radical production. The present study was designed to establish whether cold-exposed rats exhibit an increased cardiac susceptibility to ischaemia-reperfusion which can be attenuated by vitamin E. The following four groups of animals were used: C, control rats (n = 8, temperature 24°C); C+VE, vitamin E-treated rats (n = 8, temperature 24°C); CE, cold-exposed rats (n = 8, temperature 4°C); and CE+VE, cold-exposed vitamin E-treated rats (n = 8, temperature 4°C). Langendorff preparations from these animals were submitted to 20 min ischaemia followed by 25 min reperfusion. At the end of the ischaemia-reperfusion protocol, homogenates and mitochondria were prepared and used for analytical procedures. With respect to control hearts, cold hearts showed a lower inotropic recovery and a higher oxidative stress, as inferred by higher levels of oxidized proteins and lipids and lower reduced glutathione levels. These changes were prevented when cold rats were treated with vitamin E. Evidence was also obtained that mitochondria are involved in the tissue derangement of cold hearts. Indeed, they display a faster production of reactive oxygen species, which causes mitochondrial oxidative damage and functional decline that parallel the tissue dysfunction. Moreover, vitamin E-linked improvement of tissue function was associated with a lower oxidative damage and a restored function of mitochondria. Finally, the mitochondrial population composition and Ca(2+)-induced swelling data indicate that the decline in mitochondrial function is in part due to a decrease in the amount of the highly functional heavy mitochondria linked to their higher susceptibility to oxidative damage and swelling. In conclusion, our work shows that vitamin E treatment attenuates harmful side-effects of the cardiac response to cold, such as oxidative damage and susceptibility to oxidants, thus preserving mitochondrial function and tissue recovery from ischaemia-reperfusion.     

Pre-eclampsia associated alterations of the elastic fibre system in umbilical cord vessels

Although pre-eclampsia (PE) is often associated with fetal hypoxia, hypertension and/or disturbed function of the fetal circulation, the effect of these altered hemodynamic parameters on the structure and composition of umbilical vessels has not been systematically investigated before. Therefore, this study focuses on PE-associated changes of the elastic fibre system in umbilical cord vessels investigated by light and electron microscopy, immunocytochemistry and biochemistry. In umbilical cord veins, no changes in thickness of the vessel wall or of any sublayer were observed. However, the internal elastic lamina of the veins was split in 80% of the PE-group in contrast to 20% in uncomplicated pregnancies. This effect was significant (α <0.01) from 36 weeks of gestation onwards. In umbilical cord arteries, the entire arterial vessel wall was found to be 15% thicker in PE than in uncomplicated pregnancies. The enlargement was caused by an increase of both the tunica intima and tunica media. The thickening of the tunica intima was attributed to a migration of smooth muscle cells towards the endothelium, accompanied by a splitting of the internal elastic lamina. Compared to uncomplicated pregnancies, smooth muscle cells of arteries and veins in PE showed a metabolic activation demonstrated by highly dilated endoplasmic reticulum. A semiquantitative score method as well as a quantitative dot blot assay indicated a PE-associated reduction of elastin expression in the arterial vessel walls. In summary, PE obviously induces a decrease of the elastin content accompanied by a thickening of the vessel wall in umbilical cord arteries. This remodeling of the elastic fibre system, together with an increased migration of smooth muscle cells, might represent part of the functional adaptation system of the umbilical cord arteries on the altered hemodynamic conditions in PE. Accepted: 29 November 1999     

Human skeletal muscle feed arteries studied in vitro: the effect of temperature on α(1)-adrenergic responsiveness

Heat and cold exposure can decrease and increase total peripheral resistance, respectively, in humans. With unique access to human skeletal muscle feed arteries, we sought both to characterize these vessels and to determine the interaction between temperature and α(1)-adrenergic receptor responsiveness. We hypothesized that α(1)-mediated vasocontraction of human feed arteries would be attenuated in response to 39 or 35°C. Skeletal muscle feed arteries were harvested from thirty-two human volunteers and studied using isometric techniques. Vessel function was assessed using KCl, sodium nitroprusside (SNP), phenylephrine (PE) and ACh dose-response curves to characterize non-receptor- and receptor-mediated vasocontraction and vasorelaxation. Single doses of PE (1 mm) and KCl (100 mm) were administered at 37°C and then, in a balanced design, repeated at both 35 and 39°C. The KCl and PE dose-response curves elicited significant vasocontraction (2009 ± 407 and 1974 ± 508 mg developed tension, respectively), whereas SNP and ACh induced the expected vasorelaxation (102 ± 6 and 73 ± 10% relaxation, respectively). Altering the temperature had no effect on inherent smooth muscle function (KCl response), but both a reduction (35°C) and an increase in temperature (39°C) decreased the vasocontractile response to 1 mm PE (37°C, 1478 ± 338 mg; 35°C, 546 ± 104 mg; and 39°C, 896 ± 202 mg; P < 0.05) or across PE dose (P < 0.05, 35 and 39 versus 37°C). Despite clear heterogeneity between both the human volunteers and the feed arteries themselves, this novel approach to the procurement of human vessels revealed a robust 'inverted U' response to altered temperature, such that α(1)-mediated vasocontraction was attenuated with either warming or cooling.     

Cutaneous vascular and core temperature responses to sustained cold exposure in hypoxia

We tested the effect of hypoxia on cutaneous vascular regulation and defense of core temperature during cold exposure. Twelve subjects had two microdialysis fibres placed in the ventral forearm and were immersed to the sternum in a bathtub on parallel study days (normoxia and poikilocapnic hypoxia with an arterial O(2) saturation of 80%). One fibre served as the control (1 mM propranolol) and the other received 5 mM yohimbine (plus 1 mM propranolol) to block adrenergic receptors. Skin blood flow was assessed at each site (laser Doppler flowmetry), divided by mean arterial pressure to calculate cutaneous vascular conductance (CVC), and scaled to baseline. Cold exposure was first induced by a progressive reduction in water temperature from 36 to 23°C over 30 min to assess cutaneous vascular regulation, then by clamping the water temperature at 10°C for 45 min to test defense of core temperature. During normoxia, cold stress reduced CVC in control (-44 ± 4%) and yohimbine sites (-13 ± 7%; both P < 0.05 versus precooling). Hypoxia caused vasodilatation prior to cooling but resulted in greater reductions in CVC in control (-67 ± 7%) and yohimbine sites (-35 ± 11%) during cooling (both P < 0.05 versus precooling; both P < 0.05 versus normoxia). Core cooling rate during the second phase of cold exposure was unaffected by hypoxia (-1.81 ± 0.23°C h(-1) in normoxia versus -1.97 ± 0.33°C h(-1) in hypoxia; P > 0.05). We conclude that hypoxia increases cutaneous (non-noradrenergic) vasoconstriction during prolonged cold exposure, while core cooling rate is not consistently affected.     

门静脉高压症猪肝动脉的结构重建

目的 建立猪门静脉高压症模型,探讨门静脉高压症时肝动脉的结构重建.方法猪以四氯化碳、苯巴比妥、乙醇配合高脂、低蛋白、低胆碱饮食进行混合饲养.通过脾静脉插管测压,取肝动脉常规石蜡包埋、切片,用HE 法、Weigert 法、Aniline blue法,Organge G法分别染组织结构、弹性纤维、胶原纤维和平滑肌,用计算机...     

Protocadherin-12 deficiency leads to modifications in the structure and function of arteries in mice

We studied the role of protocadherin-12 on arterial function. This protein belongs to the cadherin superfamily and is located at the intercellular junctions of endothelial cells where it promotes homotypic cellular adhesion. We previously showed that mice deficient for PCDH12 exhibited developmental growth retardation owing to placenta defects without altering neither survival nor fertility. Here, we investigated the effects of PCDH12 deficiency on the structural, mechanical properties and functionality of arteries from adult mice. Histological studies of the PCDH12(-/-) mouse arteries have shown age-independent modifications such as ramifications of medial elastic lamellae, accompanied by the appearance of radial fibers linking together two successive concentric elastic lamellae. Mechanical studies also revealed some age-independent modifications in the PCDH12(-/-) mice arteries such as an increase in inner-diameter and circumferential mid-wall stress. Moreover, the PCDH12(-/-) mice exhibited a mild reduction of blood pressure, thus maintaining the inner-diameter close to its normal value and a normal circumferential wall stress for vascular cells. This is likely a compensation mechanism enabling normal blood flow in the arteries. The vascular phenotypic differences observed between PCDH12(-/-) and wild type mice arteries did not seem to be age-dependent, except for some results regarding the carotid artery: the reactivity to acetylcholine and the circumferential mid-wall stress decreased with ageing in the PCDH12(-/-) mice, as opposed to the increase observed in the wild types. In conclusion, deficiency in one specific interendothelial junction component leads to significant changes in the structure and function of the vascular wall. Possible explanations for the observed modifications are discussed.     

Morphologic changes in the skin and superficial temporal arteries in Sneddon's syndrome

Skin biopsies from livedo's areas of 25 patients and fragments of superficial temporal arteries of 10 patients with Sneddon's syndrome were examined. Pathological changes in the dermis arteries of small and medium calibers were found in the form of the intima hyperplasia, proliferation of vascular wall cell elements (80%), arterial thrombosis (with diameter of 60-200 microns). These changes were found in 68% of observations when clinical and morphological signs of vasculitis were lacking. "Arteriopathy" is the most appropriate term for such lesions. Focal and diffuse fibro-muscular elastic hyperplasia of the intima and muscular layer fibrosis in the wall of superficial temporal arteries may be considered as age-associated lesions. Ultrastructurally, a selective damage of the non-adrenergic part of the nervous apparatus of the dermal arteries and superficial temporal arteries were observed; this suggests the participation of the damaged vascular neurogenic regulation in the formation of organic vascular changes.     

Evaluation of functional and structural alterations in muscle tissue after short-term cold storage in a new tissue preservation solution

Storage of muscle preparations in vitro is required for the diagnosis of neuromuscular disorders and for electrophysiological tests. The current standard protocols for muscle storage or transport, i.e. placement on 0.9% NaCl-moistened gauze, lead to impaired function and structural alterations. For other tissues, however, improved preservation methods and solutions have recently been described. In this study, functional and structural alterations in the murine diaphragm were compared after storage on 0.9% NaCl-moistened gauze and after storage in different modifications of the new vascular preservation solution TiProtec?. Muscle force generation after nerve stimulation, histological parameters and ATP levels were investigated after 2.5 h of cold storage at 4°C in the different media and 0.5 h of rewarming at 25°C in Tyrode buffer. Murine diaphragms were injured during cold storage and rewarming, with the degree of the alteration being dependent on the type of solution used. There were no histological alterations and no caspase 3 activation in all groups. In contrast, diaphragms stored in the modified TiProtec solution showed markedly better performance concerning force generation after nerve stimulation (7.1 ± 1.1 cN · s) as well as higher ATP content (2.4 ± 0.7 μmol/g) and were superior to storage on 0.9% NaCl-moistened gauze (1.4 ± 0.4 cN · s; 0.3 ± 0.1 μmol/g). In conclusion, the modified TiProtec preservation solution showed promising results for short-term cold storage of murine diaphragms. For further evaluation, the transferability of these positive findings to storage conditions for muscles of other species, especially human muscle tissue, needs to be investigated.     

Mechano-elastic properties of human muscles at different temperatures.

The effect of changes in the muscle temperature on their ability to store elastic energy was studied by having 5 trained subjects perform maximal vertical jumps on a force platform, with and without counter movement, at muscle temperatures between about 32 degrees C and 37 degrees C. The results showed that the heights of vertical jumps were considerably reduced at lowered temperature, but the gain in height after a counter movement in the form of a jump down from a height of 0.4 m over the force platform, was significantly higher in the cold condition. T o test whether this was due to an increased stiffness of the muscles, experiments with imposed sinusoidal length variations at 14 Hz were performed. Delta force XDelta length-1 (i.e.stiffness) increased with isometric tension independent of muscle temperature. Experiments in which the rate of tension development and relaxation in voluntary maximal isometric contractions were measured at different muscle temperatures showed that maximal isometric tension changed by less than 1% per degree but the rate of tension development and relaxation by 3-5% and 5% per degree, respectively, in the temperature range studied (30 degrees to 40 degrees). These data may be explained by the hypothesis that the series elastic components of the active muscle are located in the cross-bridges between myosin and actin filaments. The storage of elastic energy would be enhanced if the rate of breaking of these bridges were decreased at lower temperatures.     

The role of calcium in the mechanism of changes in vascular reactivity due to reserpine

Under the influence of reserpine there is a marked decrease in the calcium concentration in segments of the distal aorta and femoral arteries of rabbits, incubated in salt solution. These changes develop parallel with changes in the character of responses of the vascular segments to direct electrical stimulation (weakening of the effects of contraction, followed by relaxation). A decrease in the calcium concentration in the vascular wall is suggested as one cause of the change in vascular reactivity.All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR E. I. Chazov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 7, pp 45–48, July, 1979.     

高血压项目临床检测样本保存和稳定性标准化研究

目的 探讨不同保存温度和时间条件下高血压五项检测血浆样本的稳定性.方法 收集20例Renin、ALD、ACTH、Cortisol水平不同的受试者样本,分别保存在不同温度(常温、4℃、-20℃、-80℃)和不同时间(24h和48h),另外20例AII水平不同的受试者样本,分别在不同时间(即时、2h、4h、8h、12h、24h)添加酶抑制剂,并在不同温度和时间(常温下2h、4h、6h、8h,4℃下4h、8h、12h、24h,-20℃下12h、24h、48h、72h)下保存,计算偏倚.结果 在室温保存条件下,Renin浓度在24h内降低9%,而4℃条件下保存,24h内升高14%,在-80℃保持稳定.ACTH浓度在室温保存下降低32%,-20℃和-80℃条件下保存比较稳定.ALD和Cortisol浓度受保存温度及时间变化影响较小,48h内变幅在5%以内.AII在采血后的不同时间段添加酶抑制剂,8h后升幅超过10%;样本采集后立即添加酶抑制剂,在常温保存8h条件下及4℃下保存24h后均减少超过50%,而在-20℃条件下48h降幅在10%以内.结论 Renin和ACTH需在-20℃以下的低温保存,ALD和Cortisol对温度没有要求,AII需立即加入酶抑制剂并尽快检测,如果不能尽快检测,需分离血浆后保存在-20℃条件下,并在48h之内完成检测.本研究为临床检验制定完善的高血压五项样本保存条件提供了依据.     

Mechano-Elastic Properties of Human Muscles at Different Temperatures

The effect of changes in the muscle temperature on their ability to store elastic energy was studied by having 5 trained subjects perform maximal vertical jumps on a force platform, with and without counter movement, at muscle temperatures between about 32°C and 37°C. The results showed that the heights of vertical jumps were considerably reduced at lowered temperature, but the gain in height after a counter movement in the form of a jump down from a height of 0.4 m over the force platform, was significantly higher in the cold condition. To test whether this was due to an increased stiffness of the muscles, experiments with imposed sinusoidal length variations at 14 Hz were performed. Δforce ×Δlength^-1 (i.e. stiffness) increased with isometric tension independent of muscle temperature. Experiments in which the rate of tension development and relaxation in voluntary maximal isometric contractions were measured at different muscle temperatures showed that maximal isometric tension changed by less than 1 % per degree but the rate of tension development and relaxation by 3–5 % and 5 % per degree, respectively, in the temperature range studied (30° to 40°). These data may be explained by the hypothesis that the series elastic components of the active muscle are located in the cross-bridges between myosin and actin filaments. The storage of elastic energy would be enhanced if the rate of breaking of these bridges were decreased at lower temperatures.     

Effect of simulated dives on diastolic function in healthy men

Scuba diving may elicit acute changes to human cardiovascular function. Environmental stresses such as immersion, cold, and venous gas microbubbles all have been shown to contribute to right ventricular overload and impaired left ventricular filling after single dives. We investigated cardiac function after simulated dry chamber dives. Twenty male divers [mean age 31 years, standard deviation (SD) 8 years, mean body mass index 26 kgm⁻² (SD 3 kgm⁻²)] participated in the study. All subjects had normal ECG, stress-ECG, and transthoracic echocardiography at rest. Echocardiographic assessment of diastolic function [E/A-ratio, deceleration time (DT), isovolumic relaxation time (IVRT), E/e′-ratio] was performed directly prior to and 20 and 80 min after two simulated dry hyperbaric chamber dives (maximal pressure 600 kPa, duration 60 min) that were conducted within 1 week. DT statistically significantly decreased from 163 ms (SD 14 ms) to 125 ms (SD 15 ms) 20 min after the dive (p < 0.0001), whereas 80 min after decompression these changes tended to return to baseline [146 ms (SD 14 ms); p = 0.06]. There was no statistically significant change in heart rate, E/A-ratio or E/e′-ratio after 20 or 80 min compared to baseline. These changes could be reproduced after the second dry chamber dive. No gas microbubbles were detectable during or after decompression from either dive. Simulated hyperbaric dry chamber dives were associated with a transient decrease in deceleration time in healthy men. Factors other than immersion, cold, or nitrogen microbubbles may contribute to acute changes in cardiac function after single scuba dives.     

甲状腺癌术后不同时间拔除引流条的效果分析

目的 探讨甲状腺癌术后不同时间拔除引流条的疗效。方法 收集我院80例甲状腺癌手术患者临床资料,术后24 h内拔除引流条40例设为A组,术后24~48 h拔除引流条40例设为B组。比较两组患者手术资料（术中出血量、手术时间、淋巴结转移数）、换药次数、术后48 h平均体温、敷料渗液浑浊率、切口感染率、皮下积液率及手术至出院时间。结果 两组患者年龄、性别、手术时间、出血量、淋巴结转移情况比较,差异无统计学意义（P＞0.05）;B组换药次数为（3.45±0.64）次,较A组（2.10±0.50）次增加,B组患者术后48 h内平均体温为（37.54±0.73）℃,较A组（37.08±0.46）℃升高;B组敷料渗液浑浊率（30.00%）及切口感染率（12.50%）也较A组的（10.00%）、0增加,差异具有统计学意义（P＜0.05）,而皮下积液率及手术至出院时间比较,差异无统计学意义（P＞0.05）。结论 甲状腺癌术后早期拔除引流条安全、有效。     

Influence of storage temperature on the responsiveness of human platelets to agonists

To investigate the effects of storage temperature on the responsiveness to agonists of human platelets prepared from stored blood, we measured the aggregability and acid-base status of platelets from 96 healthy subjects before and after storage of whole blood at 4 degrees C and room temperature (RT) up to 48 hr. After 24 hr storage at 4 degrees C, there were no significant differences in agonist-induced platelet aggregability, compared to fresh specimens. When blood was kept at RT for 24 hr, all of the platelet samples showed non-responsiveness (< 20% aggregability) to epinephrine and 70% (67/96) revealed impaired responsiveness (20 to 60% aggregability) to adenosine diphosphate (ADP); there were no samples that showed impaired- or non-responsiveness to collagen or ristocetin. Among the 67 samples that showed impaired responsiveness to ADP after RT storage, 62 (93%) exhibited the loss of a secondary wave of aggregation in response to ADP. After storage of blood at RT for 48 hr (pH 6.81 +/- 0.06), mean values of maximal platelet aggregability to epinephrine, ADP, collagen, and ristocetin were 8%, 16%, 19%, and 70%, which were significantly lower than the corresponding mean values after storage of blood at 4 degrees C for 48 hr (pH 7.04 +/- 0.04) (ie, 66%, 69%, 102%, and 91%, p < 0.01). In summary, refrigerated storage of human blood improves the stability of platelet responsiveness to agonists. Storage at RT causes platelet non-responsiveness to epinephrine and disturbs the release reaction of endogenous ADP.     

Estrogen-induced augmentation of endothelium-dependent nitric oxide-mediated vasodilation in isolated rat cerebral small arteries

We examined chronic effects of 17beta-estradiol (E(2)beta) on the responses of isolated rat anterior cerebral small arteries to vasoactive substances with special reference to endothelial function. Female Sprague-Dawley rats were separated into four groups: (1) sham-operated group (Sham), (2) sham-operated plus E(2)beta treated group (Sham+E), (3) ovariectomized group (OVX), (4) ovariectomized plus E(2)beta treated group (OVX+E). 5-Hydroxytryptamine (5-HT) (10(-10)-10(-3) M) and U46619 (10(-15)-10(-8) M) induced concentration-dependent contractions in the cerebral small arteries. The 5-HT- and U46619-induced contractions were not affected by pretreatment with 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME). No significant difference in high potassium (80 mM)- and the agonists-mediated contractions was observed among the four groups. Administration of acetylcholine (ACh) (10(-9)-10(-3) M) and sodium nitroprusside (SNP) (10(-8)-10(-3) M) caused dose-related relaxations in the cerebral small arteries precontracted by 10(-8) M U46619. Chronic treatment with E(2)beta caused a significant potentiation of the ACh-induced relaxations in the Sham+E and OVX+E groups. The dose-response curve for ACh in the OVX group was quite similar to that obtained with the Sham group. The ACh-induced relaxation was reduced significantly by pretreatment with 3 x 10(-5) M L-NAME, and an additional treatment with 10(-3) M L-arginine reversed significantly the L-NAME-induced inhibition. The removal of endothelial cells produced a significant reduction of the ACh-induced relaxation. Indomethacin (10(-5) M) did not alter the ACh-induced relaxation. The findings suggest that E(2)beta potentiates ACh-induced endothelium-dependent relaxation in rat anterior cerebral arteries and that the potentiation may be, in part, mediated by increasing production and release of endogenous NO from the endothelial cells.