Regional Blood Circulation Research Articles

Massage in the treatment of pain syndromes with cervicobrachialgia

The article highlights the basic principles of massage usage in patients with cervicobrachialgia with for pain syndrome relief and movement restoration. We found differences in regional blood circulation reaction and the neuromuscular system response in the affected limb responding to main massage techniques (rubbing and kneading), that makes possible differentiated methodological approach to massage procedures. In patients with muscle-tonic and neurodystrophic clinical manifestations, it is preferable to use a kneading technique in massage procedure. In the presence of vascular manifestations or moderate pain syndrome, the massage procedure can involve both rubbing and kneading. Revealed therapeutic effects, good tolerance for massage is an important evidence for its use as treatment method in patients with cervicobrachialgia, improving patient’s quality of life.

Modern treatment approaches in patients with false joints and lower extremities long bones defects: analytical review

Research of effective treatment methods in patients with pseudoarthrosis and lower extremities long bones defects remains today very relevant. In the structure of traumatological patients general disability it takes up to 33.1% of cases. Surgical techniques are used, such as: intramedullary osteosynthesis, method of open reposition and bone fragments fixation by metal structures, method of transcutaneous osteosynthesis. They are recognized as effective treatment methods in patients with pseudoarthrosis and lower extremities long bones defects, that greatly improves treatment outcomes. Unfortunately, when they are used as single intervention, unsatisfactory therapy results occur in up to half of the cases. Concomitant structural and functional changes of the limb - such as regional blood circulation insufficiency, presence of extensive cicatrical soft tissues defects, changes in bone segment length, joints contractures, etc. - interferes bone consolidation and requires an application of additional treatment methods. Thus, the generally accepted treatment approach in patients with pseudoarthrosis and lower extremities long bones defects is a combination of surgery, pharmacotherapy, methods of physical therapy and physiotherapy in order to optimize the processes of osteoregeneration in non-union area.

Traditional Mongolian medicine Eerdun Wurile improves stroke recovery through regulation of gene expression in rat brain

Ethnopharmacological relevanceEerdun Wurile (EW) is one of the key Mongolian medicines for treatment of neurological and cardiological disorders. EW is ranked most regularly used Mongolian medicine in clinic. Components of EW which mainly originate from natural products are well defined and are unique to Mongolian medicine. Aim of the studyAlthough the recipe of EW contains known neuroactive chemicals originated from plants, its mechanism of action has never been elucidated at molecular level. The objective of the present study is to explore the mechanism of neuroregenerative activity of EW by focusing on the regulation of gene expression in the brain of rat model of stroke. Materials and methodsRat middle cerebral artery occlusion (MCAO) models were treated with EW for 15 days. Then, total RNAs from the cerebral cortex of rat MCAO models treated with either EW or control (saline) were extracted and analyzed by transcriptome sequencing. Differentially expressed genes were analyzed for their functions during the recovery of ischemic stroke. The expression level of significantly differentially expressed genes such as growth factors, microglia markers and secretive enzymes in the lesion was further validated by RT-qPCR and immunohistochemistry. ResultsPreviously identified neuroactive compounds, such as geniposide (Yu et al., 2009), myristicin (Shin et al., 1988), costunolide (Okugawa et al., 1996), toosendanin (Shi and Chen, 1999) were detected in EW formulation. Bederson scale indicated that the treatment of rat MCAO models with EW showed significantly lowered neurological deficits (p < 0.01). The regional cerebral blood circulation was also remarkably higher in rat MCAO models treated with EW compared to the control group. A total of 186 genes were upregulated in the lesion of rat MCAO models treated with EW compared to control group. Among them, growth factors such as Igf1 (p < 0.05), Igf2 (p < 0.01), Grn (p < 0.01) were significantly upregulated in brain after treatment of rat MCAO models with EW. Meanwhile, greatly enhanced expression of microglia markers, as well as complementary components and secretive proteases were also detected. ConclusionOur data collectively indicated that EW enhances expression of growth factors including Igf1 and Igf2 in neurons and microglia, and may stimulate microglia polarization in the brain. The consequences of such activity include stimulation of neuron growth, hydrolysis and clearance of cell debris at the lesion, as well as the angiogenesis.

Tasks and means of therapeutic exercises in patients with breast cancer in pre- and postoperative periods

The mainstay of radical treatment for patients with breast cancer (BC) is a surgical intervention: radical mastectomy (RME) of different modifications or organ-sparing operations. In the preoperative period, the tasks of therapeutic exercises (TEs) are psychological preparation of a patient for active participation in his / her treatment, as well as complete breath training. Classes are done in a group of convalescents, by applying dynamic and static breathing exercises. In the early postoperative period, the tasks of TEs are to prevent hypostatic pneumonia, surgical-site shoulder joint stiffness and to improve systemic and regional blood and lymph circulation. Analysis of 1235 patients who had undergone RME and 212 patients who had radical resection showed that restricted shoulder joint motion due to hand immobilization in an adducted position and late initiation of TEs occurred in 44.6 and 33.5 % of the patients, respectively. Individual TEs classes include breathing exercises, position treatment, and special exercises to restore shoulder joint function and to control posture. Lymphadenectomy and failure to ligate intersected lymphatic vessels lead to inevitable lymphorrhea and seroma. Analysis of 1447 patents indicated that early initiation of TEs failed to affect seroma duration and extent and wound dehiscence. In the latter (that, according to the author»s data, occurs in 3.7 % of cases after RME and in 9.2 % after preoperative radiotherapy), TEs are limited by position treatment until the wound heals or secondary sutures are applied. The tasks of the late postoperative period are recovery of the full range of shoulder joint motion, normal posture, cardiovascular and respiratory adjustments to increased physical exercises, and general tonic exposure. The paper gives TEs sets developed for each period.

Вплив умов професійної діяльності лікарів- мікрохірургів на ризик розвитку судинної патології органа зору

This work was devoted to study of the peculiarities of morphology of the retina with ganglion cells complex and the peculiarities of regional and systemic blood circulation in surgeons and therapists. It was revealed that longtime work under operative microscope results in a decrease of all parameters of blood circulation, that with the data of optical coherent tomography of the retina and optic nerve in surgeons demonstrate the signs of the existence of more high risk of vascular eye pathology then that observed in therapists.

Haemostatic effects induced by microbubble enhanced pulsed therapeutic ultrasound on splenic trauma

Objective To investigate the haemostatic effect of combining pulsed therapeutic ultrasound (TUS) and microbubble (MB) on splenic trauma.Methods Forteen healthy dogs were divided into 3 groups.Six animals were treated by microbubble-enhanced therapeutic ultrasound (MEUS),the other eight animals were treated with TUS only ( n =4) and the MB only ( n =4) served aS the controls.The spleens of all animals were surgically exposed and a 20 mm long,5 mm deep incision was created on the spleens using scalpel.Human prothrombin complex (HPC) was slowly injected prior to the treatment.During the procedure,the initial bleeding rate and the bleeding rate after the treatment were calculated using gauze weighing.Contrast enhanced ultrasound (CEUS) was performed to assess the blocking effects of splenic circulation.The targeted spleens were harvested for pathological examination.Results There were no differences in initial bleeding rate before treatment.After treatment,in the MEUS group oozed blood was found and the bleeding rate were lower than that of the TUS and the MB groups ( P ＜0.05).A nonenhanced or perfusion defect region was formed within the treated area.The histological results showed splenic sinus hyperemia,platelet aggregation and intravascular thrombosis.Conclusions Microbubbles enhanced pulsed therapeutic ultrasound can arrest the regional blood circulation of spleen by disrupting the microvasculature and this can be used in splenic heamostasis for treating spleen trauma. Key words: Ultrasonic therapy; Microbubbles; Splenic rupture; Hemostasis

Somatosympathetic Reflex and Acupuncture-Related Analgesia

Both acute and chronic pains correspond to nociceptive substances (NSs), which are naturally produced and metabolized by the organism experiencing the pains. The accumulation of NSs in regional tissues triggers a series of pathophysiological reactions and initiates certain threats to the health and the quality of human life. Pharmacological intervention is the most popular treatment for pain relief, which is achieved by either reducing the production of NSs or blocking the transmission of nociceptive signals through the nervous system, but no drug has been developed for the elimination of NSs. Therefore, improving blood circulation to eliminate NSs in painful tissues is an alternative strategy for pain relief. Acupuncture has been proved to be effective for the treatment of certain kinds of pain, but the mechanisms therein remain unclear. The effectiveness of acupuncture analgesia is also variable owing to the uncertainty surrounding the mechanism and the poor standardization of the technique. There is some evidence that acupuncture may induce pain relief by changing the regional blood flow through somatosympathetic reflex (SSR). Therefore, when exploring the mechanisms of SSR in detail, it is helpful to clarify the mechanisms of acupuncture analgesia and to develop a more standardized and effective protocol for acupuncture analgesia. Increasing evidence has suggested that both sympathetic activity and stimulation-induced SSR are differentially controlled in an organ-specific and activity-dependent manner. Vasomotor outflow, which involves the regulation of impaired regional blood circulation, is also differentially controlled in response to specific somatic stimulation. Therefore, we vigorously review the relations between SSR and acupuncture-related analgesia so that we can develop a targeted pain therapy where in certain areas of the body undergo site-specific somatic stimulation, which in turn, can adjust the impaired regional blood circulation.

Serial measurements of quantitative EEG and cerebral blood flow and circulation time after brain infarction.

The quantitative EEG (QEEG), regional cerebral blood flow (rCBF) and circulation time of 17 patients were examined semisimultaneously thrice during the first 3 months after a cerebral supratentorial infarction. The EEG was quantified according to normalized slope descriptor technique in nine patients and by means of a combined period and amplitude analysis in eight patients. Intravenously injected isotopes 133Xenon and 99TcmO4 were used for blood flow and circulation time measurements. The QEEG-values improved during the whole follow-up period. Cerebral blood flow stayed low for all 3 months and did not alter during this period, while initially prolonged circulation time to some extent improved within 2 weeks remaining, however, prolonged even thereafter. A tendency for a positive correlation between QEEG and rCBF values in the infarcted hemisphere could be seen.

Commentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular function

VIEWPOINTCommentary on Viewpoint: The human cutaneous circulation as a model of generalized microvascular functionLacy A. Holowatz, Caitlin S. Thompson-Torgerson, and W. Larry KenneyLacy A. Holowatz, Caitlin S. Thompson-Torgerson, and W. Larry KenneyPublished Online:01 Jul 2008https://doi.org/10.1152/japplphysiol.90436.2008MoreSectionsPDF (28 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor: We thank the commentators for their insightful remarks and for engaging in important dialog on this issue. In our viewpoint article, we asserted that the cutaneous circulation is an accessible microvascular bed that has utility for examining mechanisms underlying microvascular function and dysfunction (3). Microvascular dysfunction a systemic disease process that occurs and progresses in a similar fashion in multiple tissue beds throughout the body (1). Therefore, assessing the mechanisms mediating impaired cutaneous vasoreactivity in clinical populations may provide insights into systemic disease process as well as the underlying mechanisms of lifestyle and pharmacological treatment modalities. Using in vivo skin specific techniques, we and others have demonstrated that cutaneous vascular responsiveness is attenuated in several systemic pathologies, including hypertension, diabetes, heart disease, hypercholesterolemia, aging, renal disease, peripheral vascular disease, and systemic sclerosis. Furthermore, these mechanistic investigations have uncovered similar alterations in specific signaling pathways remarkably similar to those observed in other nutritive vascular beds. The available pharmacological interventions, coupled with skin-specific methodologies to induce vasoconstriction and vasodilation (2), allow for the targeted manipulation of specific vascular signaling pathways in healthy and clinical populations with a degree of insight and rigor not previously available.Each regional circulation possesses autonomic and localized control mechanisms unique to their underlying functions. It is naive to think that one could simply extrapolate specific findings from one regional circulation to another or from the microcirculation to macrocirculation. While the underlying mechanisms mediating vasoreactivity to specific stimuli can be different in different vascular beds (e.g., reactive hyperemia in skin vs. muscle; Refs. 4, 5), we and others have been able to systematically delineate to signaling mechanisms involved in the skin and how they are altered with various pathologies. It is clear that additional rigorous mechanistic research is necessary to more fully understand the impact of the local tissue environment on microvascular control and the generalizability of findings about specific impairments in vascular signaling in the cutaneous circulation to other microcirculations.REFERENCES1 Abularrage CJ, Sidawy AN, Aidinian G, Singh N, Weiswasser JM, Arora S. Evaluation of the microcirculation in vascular disease. J Vasc Surg 42: 574–581, 2005.Crossref | PubMed | ISI | Google Scholar2 Cracowski JL, Minson CT, Salvat-Melis M, Halliwill JR. Methodological issues in the assessment of skin microvascular endothelial function in humans. Trends Pharmacol Sci 27: 503–508, 2006.Crossref | PubMed | ISI | Google Scholar3 Holowatz LA, Thompson-Torgerson CS, Kenney WL. Viewpoint: The human cutaneous circulation as a model of generalized microvascular function. J Appl Physiol; doi:10.1152/japplphysiol.00858.2007.Link | ISI | Google Scholar4 Medow MS, Taneja I, Stewart JM. Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol 293: H425–H432, 2007.Link | ISI | Google Scholar5 Wong BJ, Wilkins BW, Holowatz LA, Minson CT. Nitric oxide synthase inhibition does not alter the reactive hyperemic response in the cutaneous circulation. J Appl Physiol 95: 504–510, 2003.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: L. A. Holowatz, 204 Noll Laboratory, Univ. Park, PA 16802 (e-mail: [email protected]) Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationCited ByIn vivo photoacoustic microscopy of human cuticle microvasculature with single-cell resolutionJournal of Biomedical Optics, Vol. 21, No. 5Opportunities and limitations of laser Doppler flowmetry in the assessment of skin microcirculation in patients with arterial hypertenstion30 March 2015 | Regional blood circulation and microcirculation, Vol. 14, No. 1 More from this issue > Volume 105Issue 1July 2008Pages 389-389 Copyright & PermissionsCopyright © 2008 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.90436.2008History Published online 1 July 2008 Published in print 1 July 2008 Metrics

Kann Ausdauertraining bei der Behandlung schizophrener Erkrankungen hilfreich sein? - Theorie und Perspektiven für die Praxis

Die im Hinblick auf psychopathologische und soziale Heilung immer noch ungünstige Langzeitprognose schizophrener Erkrankungen erfordert, dass konsequent nach weiteren und besseren Behandlungsstrategien gesucht wird. Körperorientierte Therapien, insbesondere körperliches Ausdauertraining, haben sich seit langem bei der Behandlung depressiven Störungen, Angst- und hirnorganischen Störungen als effektiv erwiesen. Für demenzielle Entwicklungen scheint regelmäßige körperliche (sportliche) Aktivität sogar von präventiver Bedeutung zu sein. Entsprechende Untersuchungen an schizophrenen Patienten liegen erstaunlicherweise nicht vor. Die neurowissenschaftliche Grundlagenforschung und vor allem tierexperimentelle Ergebnisse verweisen auf eine Reihe neurophysiologischer Effekte der neuromuskulären Dauerleistung von potenziell therapeutischer Bedeutung. Dies sind Beobachtungen über die adulte hippokampale Neurogenese, Einflüsse auf die Neurotransmission, die globale und regionale Hirndurchblutung und die zerebrale Angiogenese. Vieles spricht also dafür, dass körperliche Dauerleistung unmittelbar zur Gehirngesundheit und damit zur psychischen Gesundheit beiträgt. Die neurobiologischen/neurophysiologischen Grundlagen depressiver Störungen weisen einige Gemeinsamkeiten mit denen der Schizophrenien auf. Auch gibt es phänomenologische Überschneidungen, z.B. depressive Syndrome im Verlauf schizophrener Erkrankungen sowie krankheitsimmanente depressive und dyskognitive Symptome der Schizophrenien. Theoretisch könnten die neurobiologischen Effekte körperlicher Aktivität, die sich u a. positiv bei Depressionen und dyskognitiven Syndromen manifestieren, auch zur Besserung entsprechender Teilsymptome bei Schizophrenien beitragen. Die Durchführung entsprechender Untersuchungen wäre mit keinen besonderen methodischen Schwierigkeiten verbunden. Es wäre an der Zeit, damit zu beginnen.

Contrast ultrasound perfusion imaging of lower extremities in peripheral arterial disease: a novel diagnostic method

The purpose of this study was to establish contrast-enhanced ultrasound perfusion imaging (CUPI) of the lower extremities as a novel non-invasive diagnostic tool for patients with peripheral arterial disease (PAD). Ultrasound contrast agent (SonoVue) was injected into a peripheral vein of 16 control subjects and 16 PAD patients and its appearance in the calf muscle was detected by low-energy harmonic ultrasound. Analysis of the wash-in curves revealed that PAD patients had a significantly longer time to peak intensity (TTP), i.e. duration of maximum contrast perfusion [37 s (19-79 s) in control subjects vs. 56 s (32-104 s) in PAD patients at rest, age-adjusted P=0.002]. Exercise stress test of the calf muscle resulted in a decrease of the TTP, maintaining the significant difference in TTP between the groups [19 s (8-37 s) in control subjects vs. 32 s (18-48 s) in PAD patients after exercise, age-adjusted P=0.004]. Neither ankle-brachial index and TTP nor age and TTP showed a significant correlation. CUPI reflects the regional blood circulation of the calf muscle. In this pilot study, PAD patients show a significantly longer TTP than control subjects. The clinical relevance of CUPI is topic of ongoing studies.

《再生医療と歯科補綴学の接点》Ｔｉｓｓｕｅ Ｅｎｇｉｎｅｅｒｉｎｇを応用した下顎骨の再生医療

One goal of jawbone reconstruction is to regenerate bone that is strong enough to support dentures or dental implants. Here we describe mandibular reconstructions using bioabsorbable poly (L-lactic acid) (PLLA) mesh and particulate cancellous bone and marrow (PCBM). PLLA mesh is made of monofilaments spun from molecular weight 20.5 x 10(4) that is elongated and woven into mesh. Mandibles of 62 patients with tumors, cysts, or alveolar atrophy were reconstructed with PLLA mesh trays/sheets and PCBM. The operative procedures were as follows: 1) a heat-softened PLLA mesh sheet or tray was cut and bent to conform to the shape and size of the bone defect; 2) PLLA mesh was fixed to the residual bone with stainless steel wire; and 3) the tray was filled with PCBM harvested from the ilium. Clinical evaluations six months after surgery showed that in 35 cases (56.5%) the results were judged to be excellent (bone formation range: beyond 2/3), in 17 cases (27.4%) they were good (bone formation range under 2/3, but re-operation unnecessary), and in 10 cases (16.1%) they were poor (cases not falling into either category above). Long-term observations showed that in 32 cases (80.0%) bone resorption was less than 10% of the regenerated bone. Among the patients wearing early dentures or dental implants, bone resorption was less. There is a good success rate for jawbone reconstruction surgery using PLLA mesh and PCBM, and patients can expect to have mandibles strong enough to support dentures and dental implants. In addition, there is an advantage of regenerating in the donor site as well. However, we need to develop therapies that combine bioactive factors to promote angiogenesis and osteogenesis or hybrid artificial bone for patients with poor regional blood circulation and for elderly patients who have too few osteoprogenitor cells.

Rheovasographic Evaluation of Peripheral Blood Circulation at Lengthe­ning of Lower Extremities in Children

Rheovasography was applied for the evaluation of blood circulation in the femur and crus before and after restoration of lower extremity length. There were 51 children, aged 5—18, with acquired pathology of proximal (39 patients) and distal (12 patients) metaepiphysis of femur. Positive dynamics in regional blood circulation was noted both in proximal and distal extremity segments at 1—5 years follow up after lengthening

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Diagnosis and correction of regional blood circulation disorders in acute adontogenic inflammatory diseases of maxillas

The complex study of vascular tonus and microcirculation state in patients with acute odontogenic inflammatory diseases is performed. The revealed microcirculation disorders correlated with regional hypertension. These changes reflected the regional hemodynamics disorders growing with acute odontogenic periostitis, acute adontogenic osteomyelitis complicated by perimaxilla soft tussue phlegmon. The complex correction method of mentioned hemodynamics disorders is developed.

Resuscitative effects of polynitroxylated αα-cross-linked hemoglobin following severe hemorrhage in the rat

αα-Cross-linked hemoglobin (ααHb) is an example of a hemoglobin-based oxygen carrier (HBOC) with significant cardiovascular activity. This may compromise the safety and efficacy of this HBOC by causing systemic hypertension and reducing blood flow to some organs. The present work is based on the hypothesis that incorporating antioxidant activity into an HBOC in the form of a covalently attached nitroxide may prevent these effects. We have tested this hypothesis by adding antioxidant activity to ααHb with 2,2,6,6-tetramethyl-piperidinyl-1-oxyl (Tempo) to create polynitroxylated ααHb (PN-ααHb). The new compound PN-ααHb acts as an antioxidant in our in vitro and in vivo assays. In this study urethane-anesthetized rats were hemorrhaged to a mean arterial pressure (MAP) of 35–40 mmHg and maintained for 30 min. Animals were resuscitated with solutions of (1) 10% PN-ααHb (43 mmHg), (2) 10% ααHb (43 mmHg), (3) 7.5% albumin (43 mmHg), (4) 300% Ringers lactate (RL), and (5) 0.9% normal saline equal to the shed blood volume (SBV). Hemodynamics and regional blood circulation was measured at baseline, following hemorrhage, and at 30 and 60 min postresuscitation using a radioactive microsphere technique. Base deficit (BD) was measured at baseline, following hemorrhage, and at 60 min following resuscitative fluid infusion. Finally survival was determined as the time following resuscitation until secession of heart rhythm. Saline and 300% RL resuscitation did not improve BD, systemic hemodynamics, or regional blood circulation. PN-ααHb, ααHb, and albumin significantly improved these parameters, however, only PN-ααHb and ααHb improved survival. PN-ααHb was found to be less hypertensive than ααHb due to blunted increases in both cardiac output and systemic vascular resistance. This study demonstrates that, by using ααHb as a scaffold for polynitroxylation, improvement in vasoactivity and resuscitative efficacy may be possible. In conclusion, the addition of antioxidant activity in the form of polynitroxylation of a low molecular weight Hb (ααHb) may create a safe and efficacious resuscitative fluid.

Effects of intravenous administration of prostacyclin on regional blood circulation in awake rats.

1. The effects of intravenous infusion of prostacyclin (PGI2, 0.1, 0.2, 0.3 and 1.0 microg kg(-1) min(-1) lasting 5 min) on regional blood flow and regional vascular resistance have been studied in awake rats using the radioactive microsphere method. 2. The control values of blood flow to the heart, kidney, small intestine, hind limb muscle, pericranial skin and brain as well as the corresponding vascular resistance were not modified by an i.v. infusion (0.1 ml min(-1)) of Tris-buffer (the vehicle of PGI2). 3. The i.v. infusion of PGI2 produced graded dose-dependent decreases of MAP (r=0.87, P<0.001; ED20=0.73 [0.13-2.55] microg kg(-1) min(-1)) as well as decreases of vascular resistance in the heart (r=0.83, P<0.001; ED30=0.17 [0.09-0.31] microg kg(-1) min(-1)), pericranial skin (r=0.88, P<0.001; ED30=0.28 [0.18-0.43] microg kg(-1) min(-1)) and small intestine (r=0.74, P<0.001; ED30=0.21 [0.11-0.39] microg kg(-1) min(-1)), which led to dose-related increases of blood flow to these territories. 4. On the contrary, PGI2 increased vascular resistance in skeletal muscle (r=0.73, P<0.001; ED30=0.20 [0.10-0.39] microg kg(-1) min(-1)) with corresponding reductions in blood flow. The low doses reduced renal blood flow but there were no significant changes during the high ones. Cerebral vessels did not dilate during any infusion of PGI2 and cerebral blood flow decreased as MAP fell (r=0.56, P<0.01). 5. We conclude that, in awake rats, the coronary vessels are extremely sensitive to the vasodilating effect of PGI2 and that the mesenteric vessels and those of the pericranial skin are very responsive too. Moreover, autoregulation is inefficient to maintain cerebral blood flow during infusion of PGI2.

Modulation of resuscitative effect of diaspirin cross-linked hemoglobin by L-NAME in rats.

Diaspirin Cross-linked Hemoglobin (DCLHb), a hemoglobin-based oxygen carrier, improves regional blood circulation and systemic hemodynamics in normal and hemorrhaged rats. The action of DCLHb is partly mediated by its scavenging effect on nitric oxide. This study was undertaken to determine the effect of DCLHb on nitric oxide mechanism in hemorrhagic conditions. We studied the modulation of cardiovascular effects of DCLHb by a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) in hemorrhaged rats. The base deficit, survival time, oxygen consumption, and blood circulation to the brain, heart, gastrointestinal tract, and kidneys were determined in 1) DCLHb (100 mg/kg, intravenously (i.v.), 2) L-NAME (2 mg/kg, i.v.), 3) L-NAME (2 mg/kg, i.v.) + DCLHb (100 mg/kg, i.v.), and 4) L-arginine (100 mg/kg/h, i.v.) + DCLHb (100 mg/kg, i.v.) treated rats. Hemorrhage was induced in urethane-anesthetized male rats by bleeding them at a rate of approximately .5 to 1 mL/min, until a mean arterial pressure of 35-40 mmHg was achieved. This blood pressure was maintained for 30 min. Sham-operated nonhemorrhaged rats survived for >300 min, whereas hemorrhaged rats survived for only 85+/-31 min. Hemorrhage significantly increased base deficit and decreased oxygen consumption. A significant decrease in heart rate, mean arterial pressure, cardiac output, stroke volume, and in blood flow to the gastrointestinal tract and kidneys was observed after hemorrhage. Resuscitation with DCLHb produced a significant increase in survival time, oxygen consumption, heart rate, mean arterial pressure, cardiac output, total peripheral resistance, and blood flow to the brain, heart, and kidneys. In contrast, resuscitation with L-NAME did not improve base deficit, survival time, oxygen consumption, systemic hemodynamics, or regional blood flow. L-arginine pretreatment did not affect DCLHb-induced resuscitation of hemorrhaged rats. Furthermore, L-NAME (pretreated or co-administered) attenuated the resuscitative effect of DCLHb. These data suggest that nitric oxide mechanism may not be the only mechanism involved in the resuscitative effect of DCLHb.

Dose-dependent effect of diaspirin cross-linked hemoglobin on regional blood circulation of severely hemorrhaged rats.

Diaspirin cross-linked hemoglobin (DCLHb), a hemoglobin-based blood substitute, has been found to improve systemic hemodynamics, cutaneous oxygen tension, and normalization of blood lactate levels and acid-base equilibrium after hemorrhage in animals. The present study was conducted to determine the dose-dependent effect of a 10% solution of DCLHb (20, 50, and 100% of shed blood volume; SBV) on regional blood circulation in hemorrhaged rats. Hemorrhage was induced in urethane-anesthetized rats by bleeding them at a rate of approximately .5 to 1 mL/min until a mean arterial pressure of 35-40 mmHg was achieved. This was maintained for up to 90 min to reach a base deficit of more than -12 mmol/L. Hemorrhage significantly decreased oxygen consumption, mean arterial pressure, cardiac output, stroke volume, and regional blood circulation, but increased total peripheral resistance. The vehicle Ringer's lactate (RL at 20% of SBV, intravenously) did not produce any improvements in oxygen consumption, base deficit, systemic hemodynamics, and regional blood circulation. DCLHb increased oxygen consumption, decreased base deficit, and produced significant improvements in systemic hemodynamics and regional blood flow in a dose-dependent manner. The increase in blood flow was highly significant until 60 min, but was less marked at 120 min, after resuscitation with DCLHb. Resuscitation with RL (300% of SBV) significantly improved systemic and regional blood circulation. However, the improvement was greater after resuscitation with DCLHb (50 or 100% of SBV) as compared with RL at 300% SBV. DCLHb in the dose of 50% of SBV produced maximal resuscitative effects, which were comparable to a DCLHb dose of 100% of SBV. The effect of DCLHb at 50% of SBV on renal cortical blood perfusion, concentration of moving red blood cells (CMBC), and blood velocity was also studied using laser Doppler flowmetry. Hemorrhage produced a decrease in renal cortical blood perfusion (85.3%), which was due to a decrease in the CMBC (61.0%) and their velocity (64.2%). Resuscitation with the RL did not produce any improvement in renal cortical perfusion. However, resuscitation with DCLHb significantly increased renal cortical perfusion (364.7%) due to an increase in both CMBC (123.4%) and their velocity (109.9%). It is concluded that DCLHb in a dose of 50% of SBV produces maximal improvement in regional blood circulation of hemorrhaged rats.

Role of sympathetic nervous system in cardiovascular effects of centrally administered endothelin-1 in rats.

Centrally administered endothelin-1 (ET-1) produces a biphasic response, an initial increase followed by a decrease in blood pressure (BP). The pressor effect is due to stimulation of the sympathetic nervous system and/or release of vasopressin. The mechanism responsible for the depressor effect after central administration of ET-1 is still not known. Systemic and regional circulatory effects of intracerebroventricular (i.c.v.) administration of ET-1 (100 ng) were determined in anesthetized rats, using a radioactive microsphere technique. BP, cardiac output, and stroke volume were significantly decreased 30, 60, and 120 min after central administration of ET-1. Heart rate and total peripheral resistance were not altered. ET-1 produced a reduction in blood flow to the brain (83%), heart (62%), kidneys (53%), gastrointestinal tract (43%), portal system (46%), and musculoskeletal system (55%). To determine the role of the central nervous system in cardiovascular effects of centrally administered ET-1, experiments were performed in cervical-sectioned rats. The changes in systemic and regional blood circulation induced by centrally administered ET-1 in normal rats were not observed in cervical-sectioned rats. Pretreatment with a specific antagonist of ETA receptors, BQ-123 (10 micrograms i.c.v.), antagonized systemic and regional circulatory effects of ET-1. Centrally administered clonidine (1 microgram i.c.v.) produced hypotension and bradycardia, known to be mediated through the sympathetic nervous system. Pretreatment with an ETA receptor antagonist, BMS-182874 (50 micrograms/kg iv), blocked clonidine-induced hypotension and bradycardia. We conclude that centrally administered ET-1 stimulates ETA receptors to produce systemic and regional circulatory changes mediated by the sympathetic nervous system.