Improvement in circulation and in cardiovascular risk factors with a proprietary isotonic bioflavonoid formula OPC-3.

This study investigated the efficacy of isotonic bioflavonoid supplementation, OPC-3 on 61 individuals presenting with risk factors meeting the criteria for metabolic syndrome. Subjects were supplemented with a proprietary isotonic bioflavonoid OPC-3 or placebo over 2 months. Plasma oxidative stress status was significantly lowered by 10.1% with OPC-3. All major cardiovascular risk factors were improved with blood pressure, total cholesterol, and fasting blood glucose lowered. OPC-3 significantly improved endothelial function as evaluated by increased vasorelaxation in reactive hyperemia and enhanced diastolic carotid artery flow. Cardiac ultrasound scanning revealed a significant increase of left ventricular ejection fraction. Skin microcirculation was enhanced, and better tissue perfusion led to significantly increased transcutaneous oxygen partial pressure and decreased pCO(2). With OPC-3 a dramatic and significant plasma C-reactive protein decrease by 52.1% occurred. Individuals may improve key cardiovascular risk factors by daily supplementation with the bioflavonoid OPC-3 as an important part of a healthier lifestyle.

[Defects in spermatogenesis and their correction in patients with chronic abacterial prostatitis].

A total of 28 males aged 20-46 years with chronic abacterial prostatitis (CAP) were divided into two groups. Group 1 patients received standard therapy (prostatotropic, vitamin, antioxidant); group 2 received the same standard treatment plus peloid therapy including silver-containing clay "Bekhtemirskaya". Eleven males with documented fertility (sperm donors) comprised a control group. The participants of the trial were examined for ejaculate indices, activity of the antioxidant system, ion composition of ejaculate, prostatic microcirculation before the treatment, on treatment day 14 and 90. The examination revealed the following disorders in CAP patients: low activity of anti-oxidant enzymes, abnormal static microcirculation, low content of normal spermatozoa in ejaculate. Complex rehabilitation of the patients of both groups improved prostatic microcirculation, raised activity of the antioxidant system resulting in better mobility and viability of spermatozoa. In group 2 the results were better showing the efficacy of local peloid therapy.

The influence of selenium substitution on microcirculation and glutathione metabolism after warm liver ischemia/reperfusion in a rat model.

Ischemia/reperfusion (I/R) injury is a variable yet unavoidable complication in liver surgery and transplantation. Selenium-dependent glutathione-peroxidases (GPx) and selenoproteins function as antioxidant defense systems. One target in preventing I/R injury is enhancing the capacity of endogenous redox defense. It was the aim of this study to analyze the effects of selenium substitution on liver microcirculation, hepatocellular injury and glutathione status in a model of partial warm liver ischemia in the rat. Sodium selenite was administered in three different dosages i.v.: 0.125 microg/g, 0.25 microg/g and 0.375 microg/g body weight and compared to an untreated control group (each n=10). Intravital microscopy was performed after 70 min of partial warm liver ischemia and 90 min of reperfusion. Liver tissue and plasma samples were taken at the end of the experiment for laboratory analysis. Microcirculation improved significantly in all therapy groups in contrast to control animals. ALT levels decreased significantly whereas malondialdehyde levels remained unchanged. In liver tissue, selenium supplementation caused an increase in the amount of total and reduced glutathione without changes in oxidized glutathione. This effect is likely mediated by selenite itself and selenoprotein P rather than by modulating GPx activity. We were able to show that selenite substitution has an immediate protective effect on I/R injury after warm hepatic ischemia by acting as a radical scavenger and preserving the antioxidative capacity of the liver.

Use of microcirculatory parameters to evaluate clinical treatments of chronic venous disorder (CVD).

OBJECTIVES: To evaluate changes on cutaneous microangiopathy in chronic venous disorder (CVD) after use of Cirkan [venotonic drug containing Ruscus aculeatus (plant extract), hesperidine methylchalcone (flavonoid) and vitamin C], elastic compression stockings (ECS) or no treatment for four weeks. PATIENTS AND METHODS: Fifty-five female patients (85 legs), 25 to 57 years, with at least one limb classified as C2,s or C2,3,s (CEAP classification), were allocated consecutively, according to entrance order, in these three groups. Ten healthy women age-matched were also investigated. Using orthogonal polarization spectral technique (noninvasive method), measurements of functional capillary density (FCD, number of capillaries with flowing red blood cells/mm(2)), capillary morphology (CM, % of abnormal capillaries/mm(2)) and diameters (mum) of dermal papilla (DDP), capillary bulk (DCB) and capillary limb (CD) were obtained on the medial perimalleolar region and later analyzed using CapImage software. RESULTS AND CONCLUSIONS: CVD patients showed significant changes on CD and CM compared to healthy subjects in agreement with our previous findings (J Vasc Surg 43:1037-1044, 2006). On Cirkan-treated patients, after 4 weeks, CD decreased on both limbs and CM improved on the left one, suggesting an amelioration of the chronic venous hypertension. No significant changes could be detected on other patient groups. These results confirm the existence of microcirculatory dysfunction in early stages of CVD, probably due to post-capillary hypertension, and further support the venotonic action of Cirkan.

Clinical features, topographic patterns on DWI and etiology of thalamic infarcts.

Thalamic infarcts may lead to diverse neurological disturbances, which easily results in misdiagnosis. Diffusion-weighed magnetic resonance imaging (DWI) is sensitive for the early diagnosis of the infarct and identification of the territory involved. The aim of this study was to analyze the clinical features, topographic appearance on DWI and etiology of thalamic infarcts. We reviewed clinical data, vascular risk factors, topographic patterns and etiology of thalamic infarcts. The patients were divided into 2 groups according to DWI patterns: isolated thalamic infarcts (ISO-TH) and combined thalamic infarcts (COM-TH). The former were further subdivided into 2 subgroups: inferolateral isolated thalamic infarcts (INF-TH) and non-inferolateral isolated thalamic infarcts (NON-INF) according to the vascular territories. The Patients were also divided according to etiology based on TOAST classification. The association of clinical features, DWI patterns and etiology was analyzed. Twenty nine patients were included, among which, 23 (79.3%) were ISO-TH and 6 (20.7%) were COM-TH. The most common territory involved in the ISO-TH was inferolateral territory [n=17 (73.9%)], followed by tuberothalamic artery territory [n=3 (13.0%)], and posterior choroidal artery territory [n=2 (8.7%)]. In COM-TH, the most common territory also was the inferolateral territory (n=3), followed by posterior choroidal artery territory (n=1). In 2 patients, the lesions involved more than one vascular thalamic territory. Significant association between small-vessel occlusion (SVO) and ISO-TH (INF-TH+NON-IFN) infarcts were found. Our study suggested that SVO was more prevalent in ISO-TH, and COM-TH needed more etiological examination. DWI might provide meaningful clues about etiology of thalamic infarcts.

Intraoperative brainstem auditory evoked potential pattern and perioperative vasoactive treatment for hearing preservation in vestibular schwannoma surgery.

OBJECTIVE: In vestibular schwannoma surgery, four different intraoperative brainstem auditory evoked potential (BAEP) patterns (stable BAEP, abrupt loss, irreversible progressive loss, reversible loss) can be identified and correlated with postoperative hearing outcome. Patients with reversible loss significantly benefit from postoperative vasoactive treatment consisting of hydroxyethyl starch and nimodipine. The present study investigates the treatment effect in the remaining three BAEP patterns. METHODS: A retrospective analysis was performed in 92 patients operated on for vestibular schwannoma between 1997 and 2005. Between 1997 and 2001, only patients with reversible loss of BAEP received vasoactive medication. Subsequently, all patients operated on between 2001 and 2005 received a 10 day course of therapy, regardless of the BAEP pattern. Serial audiological examinations before, after surgery and after 1 year were performed in all patients. RESULTS: All 30 patients with reversible loss of BAEP received medication, and postoperative hearing preservation was documented in 21 patients. All 13 patients with stable waves showed hearing preservation, regardless of treatment. In all 24 patients with abrupt loss and in all 25 patients with irreversible progressive loss, postoperative anacusis was documented, regardless of treatment. CONCLUSION: In patients with reversible loss of BAEP, a disturbed microcirculation of the cochlear nerve seems to be the underlying pathophysiological factor. In patients with abrupt or irreversible progressive loss, additional mechanical injury of nerve fibres determines hearing outcome. The study provides evidence that for the purpose of hearing preservation, only patients with reversible loss of BAEP benefit from vasoactive treatment.

Cold stimulus fingertip lacticemy test--an effective method to monitor acute therapeutic intervention on primary Raynaud's phenomenon and systemic sclerosis.

OBJECTIVES: The recently developed cold stimulus fingertip lacticemy test (CS-FTL) provides biochemical assessment of peripheral perfusion in patients with Raynaud's phenomenon (RP). We evaluated how the CS-FTL test can assess the acute effect of nifedipine in microvascular dynamics on primary RP and RP secondary to SSc. METHODS: A double-blinded controlled trial with crossover design was performed in 20 primary RP and 20 SSc patients. Patients received one single sublingual placebo or 10 mg nifedipine capsule, with crossover after a 15-day washout period. FTL was determined in resting conditions (pre-CS-FTL) and 10 min after CS (post-CS-FTL), before and 1 h after drug administration. Percent variation in post- vs pre-CS-FTL was expressed as deltaCS-FTL. RESULTS: Before intervention, CS induced FTL decrease in primary RP (deltaCS-FTL = -21.3 +/- 13.0%) and FTL increase in SSc patients (deltaCS-FTL = +24.5 +/- 21.2%). Placebo had no effect on pre-CS-FTL, post-CS-FTL and deltaCS-FTL in primary RP and SSc. Nifedipine induced a significant decrease in pre-CS-FTL (1.94 +/- 0.45 vs 1.57 +/- 0.41 mg/dl; P = 0.005) and post-CS-FTL (1.53 +/- 0.35 vs 1.32 +/- 0.37 mg/dl; P = 0.004) in primary RP and a significant decrease in post-CS-FTL (3.18 +/- 1.43 vs 2.56 +/- 1.30 mg/dl; P = 0.028) and deltaCS-FTL (+15.9 +/- 24.7% vs -12.9 +/- 16.6%; P = 0.001) in SSc. CONCLUSIONS: The CS-FTL test was able to demonstrate and quantify a dual effect of nifedipine on the biochemical dimension of peripheral perfusion in primary RP and in SSc patients in which there was a significant improvement in tissue perfusion in resting conditions and after exposure to a CS. The CS-FTL test will enrich the armamentarium for investigation and clinical evaluation of conditions associated with RP.

Microvessel damage may play an important role in tumoricidal effect for murine h(22) hepatoma cells with hyperthermia in vivo.

BACKGROUND: In the present study, murine H(22) hepatoma cells were provided hyperthermia with different thermal dose in vitro and in vivo, thereafter we investigated the apoptosis, necrosis rates, and intratumoral microvessel density (MVD) to determine that microvessel damage plays an important role in the tumoricidal effect of hyperthermia. METHODS: H(22) hepatoma cells were inoculated in the right hind legs of mice with immunosuppression. Local hyperthermia was administered to these mice for 15, 30, and 45 min, respectively. After hyperthermia, some mice with heat treatment of 30 min were killed at 3, 6, 12, 24, 48, 72, and 96 h after operation and others were immediately sacrificed. All tumor tissues were removed. They were analyzed for the death rate of tumor cells by flow cytometer (FCM) and observed MVD by immunohistochemistry. H(22) hepatoma cells in vitro were also given hyperthermia for 15, 30, and 45 min, respectively, and analyzed for the death rate by FCM. RESULTS: Most of the dead cells were apoptotic cells in the initiation phase of hyperthermia, then the necrosis rates rose gradually. The difference of death rates between in vivo and in vitro was significant for hyperthermia for 15 min, 30 min, and 45 min (P < 0.05). A strong positive linear correlation (r = -0.879) was observed between the death rate of tumor cells and MVD. CONCLUSION: Our study has shown that microvessel damage may play an important role in tumoricidal effect of hyperthermia.

Omega 3 - Omega 6: What is right for the liver?

Linoleic and alpha-linolenic acids are the fatty acids designated as "essential" since they are not synthesized by mammalian cells and must be provided in the diet. The recent dietary shift towards the consumption of n-6 (omega-6) at the expense of n-3 (omega-3) polyunsaturated fatty acids (PUFAs) is thought to be a primary cause of many diseases related to the Western diet. The body converts linoleic acid to arachidonic acid and derives eicosapentaenoic acid from alpha-linolenic acid. Ideally the effects of these fatty acids and their eicosanoid derivatives are tailored to the specific biological needs of the body. The balance between n-3 and n-6 PUFAs is essential for metabolism and maintenance of the functions of both classes. The availability of n-3 long chain PUFAs plays a major role in regulating both fat accumulation and its elimination by the liver. Derangement of hepatic n-6:n-3 PUFA ratio impacts on the histological pattern of fatty liver through modulation of the amount of intrahepatic lipids. Moreover, the influence of PUFAs and their eicosanoid products on hepatic microcirculation and ischemia/reperfusion injury has been demonstrated in many studies. This concise review article will focus on the role of PUFAs and eicosanoids in hepatic steatosis, microcirculation and ischemia/reperfusion injury.

Compound Danshen injection improves endotoxin-induced microcirculatory disturbance in rat mesentery.

AIM: To investigate the effect of compound Danshen injection on lipopolysaccharide (LPS)-induced rat mesenteric microcirculatory dysfunctions and the underlying possible mechanism by an inverted intravital microscope and high-speed video camera system. METHODS: LPS was continuously infused through the jugular artery of male Wistar rats at the dose of 2 mg/kg per hour. Changes in mesenteric microcirculation, such as diameters of arterioles and venules, velocity of RBCs in venules, leukocyte rolling, adhesion and emigration, free radicals released from post-capillary venules, FITC-albumin leakage and mast cell degranulation, were observed through an inverted intravital microscope assisted with CCD camera and SIT camera. Meanwhile, the expression of adhesion molecules CD11b/CD18 and the production of free radical in neutrophils, and the expression of intercellular adhesion molecule 1 (ICAM-1) in human umbilical vein endothelial cells (HUVECs) were quantified by flow cytometry (FACS) in vitro. RESULTS: The continuous infusion with LPS resulted in a number of responses in microcirculation, including a significant increase in the positive region of venule stained with Monastral blue B, rolling and adhesion of leukocytes, production of oxygen radical in venular wall, albumin efflux and enhanced mast cell degranulation in vivo, all of which, except for the leukocyte rolling, were attenuated by the treatment with compound Danshen injection. Experiments performed in vitro further revealed that the expression of CD11b/CD18 and the production of oxygen free radical in neutrophils, and the expression of ICAM-1 in HUVECs were increased by exposure to LPS, and they were attenuated by compound Danshen injection. CONCLUSION: These results suggest that compound Danshen injection is an efficient drug with multi-targeting potential for improving the microcirculatory disturbance.

The effect of sensory nerve stimulation on sensory nerve function in people with peripheral neuropathy associated with diabetes.

OBJECTIVE: To assess the effect of sensory nerve stimulation in older people with peripheral neuropathy associated with diabetes (DPN). MATERIALS AND METHODS: A randomized, placebo controlled, double blind trial was used to assess the effect of 12 weeks of low frequency sensory nerve stimulation (LF-SNS) in the lower limb [International Patent Application No. PCT/AU2004/001079: 'nerve function and tissue healing' (Z. Khalil)]. Response to capsaicin, basal microvascular blood flow, electric cutaneous threshold and oxygen tension were assessed pre- and post-treatment and between limbs. PARTICIPANTS: People 55 years of age or older diagnosed with DPN: 35 active and 31 placebo participants. RESULTS: Between groups comparisons: no significant differences occurred between stimulation groups. Within subject comparisons: in the active LF-SNS group, comparing stimulated to contralateral legs, there were significant increases in size of capsaicin flare [t(1,33)=3.65, p<0.05] and capillary blood flow [t(1,34)=-0.33, p<0.05]. There was a trend to improvement in time to initial flare response [t(1,34)=-1.86, p=0.07]. No changes were evident in the placebo group. RESPONDER ANALYSES: In a group of 'responders', the time to initial flare response (p<0.05, r=0.64), size of capsaicin flare (p<0.05 r=1.0) and microvascular blood flow (p<0.05, r=0.60) improved significantly after LF-SNS. CONCLUSIONS: The observed data suggest that LF-SNS improves nerve function in a subset of people with DPN. Targeting toward probably 'responders' may deliver the greatest benefit from short-term therapy. Testing optimal application in others seems warranted.

Long-term effects of oral vitamin C supplementation on the endothelial dysfunction in the iris microvessels of diabetic rats.

The current study was aimed to investigate effects of long-term supplementation of vitamin C on the iris microcirculation in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in male Wistar-Furth rats by intravenous injection of STZ (55 mg/kg b.w.). The rats were divided into three groups: control rats (CON), STZ-induced diabetic rats (STZ), and STZ rats supplemented with vitamin C (STZ-vitC). For supplementation of vitamin C, ascorbic acid (1 g/l) was added into the drinking water. The experiments were performed at different periods (8, 12, 24 and 36 weeks) after injection of STZ. Blood glucose, tissue lipid peroxidation and plasma vitamin C were measured. To examine the endothelial function, leukocyte adhesion to the venular endothelium was evaluated in the iris post-capillaries by means of counting the number of leukocytes labeled with rhodamine 6G. Blood flow perfusion in the iris was monitored using a laser Doppler flow meter. In the STZ rats, hyperglycemia was induced with an increase in HbA(1c) and lipid peroxidation but with a decrease in the plasma vitamin C level which improved by vitamin C supplementation. The number of adherent leukocytes increased significantly, associated with reduction in the iris blood flow perfusion, at 8, 12, 24 and 36 weeks after injection of STZ. In the STZ-vitC rats, the iris blood flow perfusion was significantly increased in comparison with the STZ rats, while the leukocyte adhesion was decreased at 24 and 36 weeks. The statistical analysis shows that the leukocyte adhesion decreased with increase in the iris blood flow perfusion in STZ and STZ-vitC rats. In conclusion, vitamin supplementation suppressed leukocyte adhesion and thus endothelial dysfunction, associated with increase in iris blood flow perfusion in diabetes. The antioxidant vitamin C may be a therapeutic agent for preventing diabetic retinopathy.

Endothelial-neutrophil interactions during ischemia and reperfusion injury: basic mechanisms of hyperbaric oxygen.

Ischemia/reperfusion injury plays a central role in the development of tissue injury during multiple central nervous system diseases including acute stroke. Neutrophil adhesion to the endothelium indicates a major component of ischemia/reperfusion pathophysiology, and may be a target for therapeutic intervention. Hyperbaric oxygen has been documented to reduce ischemia/reperfusion injury in a number of different experimental models and in a single human randomized clinical trial. One mechanism responsible for the beneficial effect of hyperbaric oxygen in treatment of ischemia/reperfusion injury involves suppression of neutrophil-endothelial adhesion. This review intends to describe the current basic mechanisms responsible for hyperbaric oxygen-mediated inhibition of neutrophil-endothelial interactions following ischemia/reperfusion injury.

Hyperbaric oxygenation in fluid microembolism.

Because clinicians require objectively demonstrable neurological deficits to confirm a diagnosis, the recognition of embolic events in the nervous system is generally restricted to the effects of ischemic necrosis produced by arterial occlusion. However, magnetic resonance imaging (MRI) has shown that lesser degrees of damage associated with small emboli are common, especially in the mid brain, and are usually clinically silent. They are frequently associated with atheromatous embolism in the elderly, but microembolic debris, such as fat, is common in the systemic venous return of healthy people and generally trapped in the microcirculation of the lung being removed by phagocytosis. However, pulmonary filtration may fail and microemboli may also pass through an atrial septal defect in so-called 'paradoxical' embolism. Studies of bubbles formed on decompression in diving have demonstrated the importance of pulmonary filtration in the protection of the nervous system and that filtration is size dependant, as small bubbles may escape entrapment. Fluid and even small solid emboli, arresting in or passing through the cerebral circulation, do not cause infarction, but disturb the blood-brain barrier inducing what has been termed the 'perivenous syndrome'. The nutrition of areas of the white matter of both the cerebral medulla and the spinal cord depends on long draining veins which have been shown to have surrounding capillary free zones. Because of the high oxygen extraction in the microcirculation of the gray matter of the central nervous system, the venous blood has low oxygen content. When this is reduced further by embolic events, tissue oxygenation may fall to critically low levels, leading to blood-brain barrier dysfunction, inflammation, demyelination and eventually, axonal damage. These are the hallmarks of the early lesions of multiple sclerosis where MR spectroscopy has also shown the presence of lactic acid. Significant elevation of the venous oxygen tension requires oxygen to be provided under hyperbaric conditions. Arterial tension is typically increased ten-fold breathing oxygen at 2 atmospheres absolute (ATA), but this results in only a 1.5-fold increase in the cerebral venous oxygen tension. The treatment of decompression sickness, and both animal and clinical studies, have confirmed the value of oxygen provided under hyperbaric conditions in the restoration and preservation of neurological function in the 'perivenous' syndrome.

Endothelial nitric oxide synthase is a molecular vascular target for the Chinese herb Danshen in hypertension.

Danshen, a Chinese herb, reduces hypertension in Oriental medicine. We hypothesized that Danshen acts partially through endothelial nitric oxide synthase (eNOS) signaling mechanisms. We tested the hypothesis using tanshinone II(A), an active ingredient of Danshen, and the two-kidney, one-clip renovascular hypertension model in hamsters. Oral tanshinone (50 microg/100 g body wt) reduced mean arterial pressure (MAP) from 161.2 +/- 6.9 to 130.0 +/- 7.8 mmHg (mean +/- SE; P < 0.05) in hypertensive hamsters. MAP in sham-operated hamsters was 114.3 +/- 9.2 mmHg. Topical tanshinone at 1 microg/ml and 5 microg/ml increased normalized arteriolar diameter from 1.00 to 1.25 +/- 0.08 and 1.57 +/- 0.11, respectively, and increased periarteriolar nitric oxide concentration from 87.1 +/- 11.3 to 146.9 +/- 23.1 nM (P < 0.05) at 5 microg/ml in hamster cheek pouch. N(G)-monomethyl-L-arginine inhibited tanshinone-induced vasodilation. Hypertension reduced eNOS protein relative to sham-operated control. Tanshinone prevented the hypertension-induced reduction of eNOS and increased eNOS expression to levels higher than sham-operated control in hamster cheek pouch. Topical tanshinone increased normalized arteriolar diameter from 1.0 to 1.47 +/- 0.08 in the cremaster muscle of control mice and to 1.12 +/- 0.13 in cremasters of eNOS knockout mice. In ECV-304 cells transfected with eNOS-green fluorescent protein, tanshinone increased eNOS protein expression 1.35 +/- 0.05- and 1.85 +/- 0.07-fold above control after 5-min and 1-h application, respectively. Tanshinone also increased eNOS phosphorylation 1.19 +/- 0.07- and 1.72 +/- 0.20-fold relative to control after 5-min and 1-h application. Our data provide a basis to understand the action of a Chinese herb used in alternative medicine. We conclude that eNOS stimulation is one mechanism by which tanshinone induces vasodilation and reduces blood pressure.

Effect of shenfu injection on gastrointestinal microcirculation in rabbits after myocardial ischemia-reperfusion injury.

AIM: To investigate the effect of shenfu injection on gastrointestinal microcirculation after myocardial ischemic-reperfusion (IR) injury in rabbits and probe into the mechanism. METHODS: Forty healthy flap-eared white rabbits were randomly divided into 4 groups: IR injury control group (group I), shenfu injection 5 mL/kg per h group (group II), shenfu injection 10 mL/kg per h group (group III) and shenfu injection 20 mL/kg per h group (group IV). The four groups were treated with Lactated Ringer's solution, shenfu injection 5, 10, and 20 mL/ kg per h were infused intravenously 30 min before experiment respectively. The values of hemodynamics [mean arterial pressure (MAP), heart rate (HR), gastric intramucosal partial pressure of carbon dioxide (PCO2), blood gas analysis and pH] were measured and compared with those before myocardial ischemia, 60 min after myocardial ischemia and 60, 90, and 180 min after reperfusion. RESULTS: The MAP, HR and gastric intramucosal pH were (70.50 +/- 4.50) kPa, (165 +/- 14) beats per min, 7.032 +/- 0.024 in group I 60 min after myocardial ischemia, which were significantly decreased compared with those before myocardial ischemia (88.50 +/- 9.75 kPa, 217 +/- 18 beats per min, 7.112 +/- 0.035, P < 0.05). The MAP, HR and gastric intramucosal pH were significantly decreased in group I 60, 90, and 180 min after reperfusion (61.50 +/- 5.25 kPa, 133 +/- 31 beats per min, 6.997 +/- 0.025) compared with those before reperfusion respectively (P < 0.05), whereas the values were insignificantly different in groups II, III or IV after reperfusion, compared with those before reperfusion, and there were no significant differences between groups II, III, and IV after reperfusion. CONCLUSION: Pre-infusion of shenfu injection has a protective effect on gastrointestinal microcirculation after myocardial IR injury in rabbits, in a dose independent manner.

Tissue physiology and the response to heat.

The most important physiological parameter influencing tissue response to heat is blood flow. At mild hyperthermia temperatures blood perfusion increases in many tumours and this effect is heating time-, temperature- and tumour-dependent. These flow increases can improve tumour oxygenation. When heating is terminated, perfusion and oxygenation commonly recover, although how quickly this occurs appears to be tumour-specific. While these effects are unlikely to have any anti-tumour activity they can be exploited to improve the combination of heat with other therapies. However, since similar physiological effects should occur in normal tissues, such combination therapies must be carefully applied. Heating tumours to higher temperatures typically causes a transient increase in perfusion during heating, followed by vascular collapse which if sufficient will increase tumour necrosis. The speed and degree of vascular collapse is dependent on heating time, temperature and tumour model used. Such vascular collapse generally occurs at temperatures that cause a substantial blood flow increase in certain normal tissues, thus preferential anti-tumour effects can be achieved. The tumour vascular supply can also be exploited to improve the response to heat. Decreasing blood flow, using transient physiological modifiers or longer acting vascular disrupting agents prior to the initiation of heating, can both increase the accumulation of physical heat in the tumour, as well as increase heat sensitivity by changing the tumour micro-environmental parameters, primarily an increase in tumour acidity. Such changes are generally not seen in normal tissues, thus resulting in a therapeutic benefit.

Systemic function, oxygenation and microvascular correlation during treatment of hemorrhagic shock with blood substitutes.

Systemic function and oxygenation changes during hemorrhagic shock treatment were continuously monitored and correlated with real-time microvascular changes. After splenectomy, each dog (n = 12) was hemorrhaged (MAP = approximately 50 mmHg; approximately 40% blood loss = 32-36 ml/kg) and randomly assigned to 4 resuscitation groups: autologous/shed blood, hemoglobin-based oxygen-carrier/Oxyglobin, crystalloid/saline, and colloid/Hespan. Systemic function and oxygenation changes were continuously monitored and measured using standard operating room protocols. Computer-assisted intravital microscopy was used to non-invasively videotape and objectively analyze and quantify real-time microvascular changes in the conjunctival microcirculation. All measurements were made during pre-hemorrhagic (baseline), post-hemorrhagic and post-resuscitation phases of the study. Pre-hemorrhagic microvascular changes were similar in all 12 dogs (venular diameter = 43 +/- 12 microm; red-cell velocity = 0.6 +/- 0.2 mm/s). All dogs showed similar significant (P<0.01) post-hemorrhagic microvascular changes: approximately 20% decrease in venular diameter; approximately 80% increase in red-cell velocity. These microvascular changes correlated with post-hemorrhagic systemic function and oxygenation changes. The resuscitations restored microvascular changes to pre-hemorrhagic values; the microvascular reversals also correlated with post-resuscitation systemic function changes in all groups. However, only shed blood resuscitation restored oxygenation level close to pre-hemorrhagic values. All 12 dogs survived resuscitation treatments despite differences in oxygen-carrying capability between groups.

Venous ulcers: microcirculatory improvement and faster healing with local use of Pycnogenol.

Chronic venous insufficiency (CVI) causes a well-defined microangiopathy described as venous hypertensive microangiopathy (VHM) leading to venous ulcerations. VHM is mainly observed in the distal part of the leg, in the perimalleolar region. In VHM edema is the consequence of increased capillary pressure and reduced local clearance, and this affects local perfusion. The healing of venous ulcers is usually very slow. Many treatments are available, but there is still no standard. Oral Pycnogenol is effective in venous disease and particularly in controlling edema. The aim of this study was the evaluation of the local effects of Pycnogenol on ulcers healing associated with venous hypertension. The study lasted 6 weeks including 18 patients (16 completed the study) with venous ulcerations. The oral treatment with Pycnogenol was compared with a combination treatment including oral and local treatment. In subjects treated with the combination treatment (oral and local), venous ulcers healed better (there was a faster reduction in ulcerated area) in comparison with oral treatment only. According to this pilot study Pycnogenol appears to have an important role in local treatment of venous ulcers improving healing and signs/symptoms.