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[Drug therapy of chronic tissue ischemia with improvement of microcirculation].

In this study the experience in treating 213 patients suffering from chronic ischemia with improvement of the microcirculation has been discussed. Medicamental treatment of chronic ischemia in patients with various pathologiic alterations of the circulation is indicated in cases which do not indicate reconstructive surgery. In the abundance of measures adopted in the treatment of these pathologic conditions the authors summarize their experience with the use of Pentoxyphyllin (Trental). During 1976 theyy treated 213 patients with this drug: 142 patients with pathologically altereed arterial circulation 51 patients with pathologically altered venous circulation 20 patienst on whom transplantations using various tissue transplants were used. The plan of administration of the drug, its undesireable side effects and the manifesting vasoactive effects of trental at the microcirculatory level especially on the microcirculation in tissue with pathologicaly altered perfusions has been discussed. Based on the shortlasting and limeted experiences the authors conclude that this drug can be recommended in therapy for various conditions of pathologicaly altered tissues circulation.

Adult↗

Coronary microcirculation during left heart bypass with a centrifugal pump.

To estimate coronary microcirculation during left heart bypass (LHB), we performed an experimental comparison study of LHB and intraaortic balloon pumping (IABP). LHB was performed with a BioMedicus BP-80 pump supporting half of the flow of cardiac output whereas the IABP was pumped in a 1:1 mode for cardiogenic shock in a swine model. Coronary circulations were analyzed by electromagnetic flowmeter, pulsed Doppler velocimeter, and laser Doppler flowmeter. Left ventricular end-diastolic pressure (LVEDP) was reduced significantly by LHB. Although there was no significant difference in epicardial flow between the LHB and IABP groups, endo cardial flow was increased significantly by LHB. In the LHB group, the systolic reverse wave of the coronary velocity called a myocardial invalid circulation was reduced remarkably. There was a significant inverse correlation between endocardial flow and LVEDP. These results suggested that LHB was more effective for myocardial microcirculation than was IABP.

Animals↗

Effect of pulsatile and nonpulsatile assist on heart and kidney microcirculation with cardiogenic shock.

To estimate microcirculation of the heart and kidney in pulsatile and nonpulsatile-assisted circulation, a comparison study was done using a swine model. Acute myocardial infarction was made by ligation of the left coronary artery branches. After cardiogenic shock, animals were divided into 3 groups as follows: Group C (n = 6), no assist provided; Group NP (n = 6), assisted by a nonpulsatile pump (Bio-Medicus BP-80); Group P (n = 6), supported by a pulsatile pump (Nippon Zeon). left coronary artery flow, endocardial and epicardial regional flows, and renal cortex and medulla tissue blood flows were measured. Left coronary artery flow and endocardial and epicardial tissue blood flows decreased in cardiogenic shock, and they recovered to the control level soon after support in both Group N and Group P. Renal medulla and cortex tissue blood flows decreased in cardiogenic shock, and these flows did not recover in either Group N or P. However, cortex blood flow in Group P did improve, but it did not improve in Group N. These results suggested that pulsatile assist was more effective than nonpulsatile assist for microcirculation after cardiogenic shock to avoid deterioration of major organ functions.

Animals↗

Alterations of retinal microcirculation in response to scatter photocoagulation.

PURPOSE: To perform acridine orange digital fluorography on rats after scatter photocoagulation to investigate alterations of retinal microcirculation at the capillary level, the authors used leukocyte dynamics as a parameter. METHODS: Twenty-five pigmented rats (Long-Evans) were studied. Argon laser photocoagulation, extending 6 disc diameters from the optic disc, was delivered to one half of the retina, and the other half was untreated. The total number of burns was 200 +/- 10. Leukocyte hemodynamics in retinal microcirculation were evaluated 4, 7, 14, and 28 days after photocoagulation by acridine orange digital fluorography. The fundus image was obtained by using an argon laser in a scanning laser ophthalmoscope and was recorded on magnetic tapes at a video rate. The images were analyzed by a personal computer-based image analysis system. RESULTS: Leukocyte velocities in the retinal capillaries were significantly decreased immediately after photocoagulation. In the laser-treated area, mean capillary leukocyte velocities were 0.73, 0.92, 1, and 1.3 mm/second on days 4, 7, 14, and 28, respectively (velocity in normal control animals 1.4 mm/second). In addition, leukocyte hemodynamics were compromised in the untreated retina: Mean capillary leukocyte velocities were 0.88, 1.1, 1.2, and 1.3 mm/second on days 4, 7, 14, and 28, respectively. Twenty-eight days after photocoagulation, the velocities recovered to normal values in the treated and the untreated areas of the retina. CONCLUSIONS: Retinal capillary hemodynamics were impaired after scatter photocoagulation, and the hemodynamics in the untreated retina were also affected. Photocoagulation to the retina may influence capillary hemodynamics by diffusible chemical substances and by direct tissue injury.

Acridine Orange↗

Initial observations on the ocular microcirculation in man. I. The anterior segment and extraocular muscles.

Gold-coated, plastic corrosion casts of the human ocular microcirculation were studied by scanning electron microscopy to define the angioarchitecture of the anterior segment, ciliary processes, and extraocular muscles. Several arterial branches from the major arterial circle (MAC) supplied each ciliary process. The afferent arterial supply may be regulated by a sphincter mechanism at its branch point from the MAC. The ciliary processes and ciliary muscle seem to be drained by iris veins and prominent venules, one of which is present between each pair of ciliary processes, and directly into pars plana veins. The predominant drainage channel of the ciliary processes is directly into the pars planar veins; the ciliary muscle seems to be drained by the other two routes primarily. The extraocular muscles possess a rich blood supply. No anastomoses of the anterior ciliary arteries with the MAC were noted, although they did contribute to the blood supply of the iris, ciliary muscle, and episcleral vascular complex.

Aqueous Humor↗

The relationship of macular microcirculation to visual acuity in diabetic patients.

OBJECTIVE: To assess the perifoveal microcirculation in diabetic maculopathy without clinically significant macular edema and its relationship to visual acuity. DESIGN: Prospective analysis. SETTING: A teaching hospital. PATIENTS: Fifteen patients with impaired visual acuity of 20/50 or worse, a diabetic control population with unaffected visual acuity (matched age, gender, retinopathy stage), and 52 healthy controls were enrolled. INTERVENTIONS: Study consisted of video-fluorescein angiography with image analyses and hemoglobin A1c measurements. MAIN OUTCOME MEASURES: Macular capillary blood velocity, capillary density (perifoveal intercapillary area), and foveal avascular zone. RESULTS: The capillary blood velocity was significantly reduced in both diabetic groups (P < .001) when compared with healthy controls, but did not differ significantly among the two diabetic groups. The perifoveal intercapillary area and foveal avascular zone were significantly enlarged in both diabetic groups compared with healthy controls (P < .001). The foveal avascular zone (P < .01) and perifoveal intercapillary area (P = .01) were further enlarged in the diabetics with reduced visual acuity. The visual acuity correlated significantly with foveal avascular zone (R2 = .51) and perifoveal intercapillary area (R2 = .24), indicating an association between enlargement and declined visual acuity. CONCLUSIONS: Capillary blood velocity remained unchanged regardless of presence of visual impairment, whereas foveal avascular zone and perifoveal intercapillary area indicated ischemia. This may help in defining a critical hypoxic threshold for visual loss and identifying the presence of an ischemic diabetic maculopathy.

Adult↗

Biphasic effects of static magnetic fields on cutaneous microcirculation in rabbits.

The biphasic effects of locally applied static magnetic fields (SMF) on the cutaneous microcirculation within a rabbit ear chamber (REC) were evaluated under conscious conditions. The microcirculatory vasomotion within a REC was measured continuously and analyzed multilaterally by microphotoelectric plethysmography, a real-time image analyzer and an image shearing monitor. SMF intensities at the REC were controlled at 1 mT and the duration of exposure was 10 min. Seventy-eight experimental trials were carried out on 22 healthy adult rabbits weighing 2.6-3.5 kg. Five experimental groups were chosen at random: 1) no pharmacological treatment or SMF exposure, 2) increased vascular tone induced by noradrenaline infusion without SMF exposure, 3) increased vascular tone induced by noradrenaline infusion with SMF exposure, 4) decreased vascular tone induced by acetylcholine infusion without SMF exposure, 5) decreased vascular tone induced by acetylcholine infusion with SMF exposure. The results demonstrated that SMF significantly enhanced vasodilatation, with increased vasomotion under noradrenaline-induced high vascular tone as well as vasoconstriction with reduced vasomotion under acetylcholine-induced low vascular tone. This suggests, therefore, that SMF can modulate vascular tone due to biphasic modification of vasomotion in the cutaneous tissue.

Acetylcholine↗

Dynamic MR imaging (DEMRI) of microcirculation in bone sarcoma.

If chemotherapy is to be effective against bone sarcoma, the cytotoxic agents must reach all tumor cells in effective quantities. Although many clinical trials include studies of the pharmacokinetics of these agents in blood or cerebrospinal fluid, there have been no accurate or widely applicable methods of determining whether chemotherapeutic agents reach all regions of a solid tumor. This review discusses the use of dynamic contrast-enhanced magnetic resonance imaging (DEMRI) to assess the microcirculation and interstitium of bone sarcoma. DEMRI studies provide a means of exploring leakage of contrast agent into tumor interstitium (extracellular extravascular spaces [EES]). In clinical observations of numerous series of patients with bone sarcoma, measures of contrast uptake (access) have convincingly demonstrated a relationship with measures and predictions of the tumor's response to preoperative chemotherapy. The results of these studies have indicated that greater access at the time of presentation, greater decrease in access during therapy, and low access at the completion of preoperative therapy correspond to better response and longer disease-free survival. Although questions remain about how these novel dynamic imaging methods can best be used to measure drug access noninvasively, we are optimistic that such measures can be developed to reflect the range of biological variation within and between naturally occurring solid tumors.

Antineoplastic Agents↗

Impact of a nickel-reduced stainless steel implant on striated muscle microcirculation: a comparative in vivo study.

The impairment of skeletal muscle microcirculation by a biomaterial may have profound consequences. With moderately good physical and corrosion characteristics, implant-quality stainless steel is particularly popular in orthopedic surgery. However, due to the presence of a considerable amount of nickel in the alloy, concern has been voiced in respect to local tissue responses. More recently a stainless steel alloy with a significant reduction of nickel has become commercially available. We, therefore, studied in vivo nutritive perfusion and leukocytic response of striated muscle to this nickel-reduced alloy, and compared these results with those of the materials conventional stainless steel and titanium. Using the hamster dorsal skinfold chamber preparation and intravital microscopy, we could demonstrate that reduction of the nickel quantity in a stainless steel implant has a positive effect on local microvascular parameters. Although the implantation of a conventional stainless steel sample led to a distinct and persistent activation of leukocytes combined with disruption of the microvascular endothelial integrity, marked leukocyte extravasation, and considerable venular dilation, animals with a nickel-reduced stainless steel implant showed only a moderate increase of these parameters, with a clear tendency of recuperation. Titanium implants merely caused a transient increase of leukocyte-endothelial cell interaction within the first 120 min, and no significant change in macromolecular leakage, leukocyte extravasation, or venular diameter. Pending biomechanical and corrosion testing, nickel-reduced stainless steel may be a viable alternative to conventional implant-quality stainless steel for biomedical applications. Concerning tolerance by the local vascular system, titanium currently remains unsurpassed.

Animals↗

Gill microcirculation of the air-breathing climbing perch, Anabas testudineus (Bloch):relationships with the accessory respiratory organs and systemic circulation.

The general macrocirculation and branchial microcirculation of the air-breathing climbing perch, Anabas testudineus, was examined by light and scanning electron microscopy of vascular corrosion replicas. The ventral aorta arises from the heart as a short vessel that immediately bifurcates into a dorsal and a ventral branch. The ventral branch distributes blood to gill arches 1 and 2, the dorsal branch to arches 3 and 4. The vascular organization of arches 1 and 2 is similar to that described for aquatic breathing teleosts. The respiratory lamellae are well developed but lack a continuous inner marginal channel. The filaments contain an extensive nutritive and interlamellar network; the latter traverses the filament between, but in register with, the inner lamellar margins. Numerous small, tortuous vessels arise from the efferent filamental and branchial arteries and anastomose with each other to form the nutrient supply for the filament, adductor muscles, and arch supportive tissues. The efferent branchial arteries of arches 1 and 2 supply the accessory air-breathing organs. Arches 3 and 4 are modified to serve primarily as large-bore shunts between the dorsal branch of the ventral aorta and the dorsal aorta. In many filaments from arches 3 and 4, the respiratory lamellae are condensed and have only 1-3 large channels. In some instances in arch 4, shunt vessels arise from the afferent branchial artery and connect directly with the efferent filamental artery. The filamental nutrient and interlamellar systems are poorly developed or absent. The respiratory and systemic pathways in Anabas are arranged in parallel. Blood flows from the ventral branch of the ventral aorta, through gill arches 1 and 2, into the accessory respiratory organs, and then returns to the heart. Blood, after entering the dorsal branch of the ventral aorta, passes through gill arches 3 and 4 and proceeds to the systemic circulation. This arrangement optimizes oxygen delivery to the tissues and minimizes intravascular pressure in the branchial and air-breathing organs. The efficiency of this system is limited by the mixing of respiratory and systemic venous blood at the heart.

Air↗

The microcirculation of bone and marrow in the diaphysis of the rat hemopoietic long bones.

The nature of the microcirculation of the diaphyseal portion of long bones and the adjacent bone marrow is poorly understood. The purpose of this study was to describe the blood supply in the diaphyseal cortex and the relationship of the bone vascular circulation to that of the bone marrow in the growing rat. India ink-gelatin was infused in the arterial system of 3-month-old rats and the vascularization was determined from histological sections. In some studies the periosteal circulation was blocked but the nutrient and metaphyseal arteriole systems were left intact. In the growing rat, most of the vascular flow appears to be centripetally through the diaphyseal cortex and this appears to be the primary blood supply for the adjacent bone marrow. The India ink traversed the cortex and entered the marrow through osteal canals at the endocortical surface. At the marrow-endocortical bone surface interface, ink exiting from the osteal canals filled the adjacent marrow sinusoids in what appeared as "bush-like" structures. From the bone marrow the ink appeared to drain into the central vein. Some arterioles from the nutrient system were found to penetrate the inner two thirds of the cortical bone and then re-enter the bone marrow. The centripetal flow of blood and the importance of the cortical flow for perfusion of the hemopoietic tissue was further documented when periosteal flow was obstructed. In this situation, the cortical bone and adjacent bone marrow were not perfused while the nutrient system and central vein were filled with ink.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Development of the microcirculation of the secondary ossification center in rat humeral head.

This work investigated the origin and development of microcirculation in the rat humeral head and the expression of vascular endothelial growth factor (VEGF) as a factor supporting the vascular growth and the development of the secondary ossification centers. Sixty rats aging 1, 3-4, 6-8, 11, and 21 days, 5 weeks, and 4 and 8 months were used. Samples of humeral head were collected for histology and immunohistochemistry for VEGF. Some animals were perfused with Mercox resin in order to obtain vascular corrosion casts (vcc) observed by scanning electron microscopy (SEM). No cartilage canals were present at birth. At 6 days postnatal, blood vessels coming from the perichondrium and the region near the capsule attachment invaded the cartilage; at 11 days postnatal, signs of calcification were present and within the third week some bone trabeculae were formed. Just before the vascular invasion of the epiphysis, a positive reaction for VEGF was localized in chondrocytes of the epiphyseal cartilage close to the capsule insertion. During the development and expansion of the secondary ossification center, VEGF expression was higher in chondrocytes but decreased when epiphysis was diffusely ossified. VEGF was expressed also by mesenchymal cells present in and around the fibrous tissue where the secondary ossification center will develop. SEM vcc confirmed that vessels penetrating into the epiphysis arose merely from the periosteal and the capsular networks, and vascular connections with the diaphyseal circulation were not evident. These observations demonstrated that VEGF production by chondrocytes begun some days after birth, supported the rapid vascular growth from the surrounding soft tissues, and was chronologically related to the development of the secondary ossification center in rat proximal humerus. Finally, the possible role of VEGF as mediator of angiogenesis and, at least indirectly, as a trigger factor also in the ossification and the bone remodeling of the secondary ossification centers has been discussed.

Age Factors↗

Effect of 0.25 T static magnetic field on microcirculation in rabbits.

We showed previously in rabbits that 0.2 and 0.35 T static magnetic field (SMF) modulated systemic hemodynamics by arterial baroreceptors. We now have measured the effect of 0.25 T SMF on microcirculation within cutaneous tissue of the rabbit ear lobe by the rabbit ear chamber (REC) method. Forty experimental runs (20 controls and 20 SMF) were carried out in eight different rabbits with an equal number of control and SMF experiments on each individual. Rabbits were sedated by pentobarbital sodium (5 mg/kg/h, i.v.) during the entire 80 min experiment. SMF was generated by four neodium-iron-boron alloy (Nd2-Fe14-B) magnets (15 x 25 x 30 mm, Neomax, PIP - Tokyo Co., Ltd., Tokyo, Japan), positioned around the REC on the observing stage of an optical microscope. The direct intravital microscopic observation of the rabbit's ear microvascular net, along with simultaneous blood flow measurement by microphotoelectric plethysmography (MPPG), were performed PRE (20 min, baseline), DURING (40 min), and POST (20 min) magnetic field exposure. The control experiments were performed under the same conditions and according to the same time course, but without magnetic field. Data were analyzed comparing MPPG values and percent change from baseline in the same series, and between corresponding sections of control and SMF runs. In contrast to control series (100+/-0.0%-90.0+/-5.4%-87.7+/-7.1%, PRE-EXPOSURE-POST), after magnetic field exposure we observed increased blood flow (100+/-0.0%-117.8+/-9.6%*-113.8+/-14.0%, *P<0.05) which gradually decreased after exposure cessation. We propose that long exposure of a high level nonuniform SMF probably modifies microcirculatory homeostasis through modulation of the local release of endothelial neurohumoral and paracrine factors that act directly on the smooth muscle of the vascular wall, presumably by affecting ion channels or second messenger systems.

Animals↗

Hyperaemic response in the skin microcirculation of patients with chronic venous insufficiency.

The capacity of the microcirculation in the liposclerotic skin of patients with chronic venous insufficiency to vasodilate in response to pilocarpine electrophoresis was assessed using laser Doppler fluxmetry. Pilocarpine induces vasodilation by direct action on capillaries; other methods of vasodilatation, such as heating of the skin, act by a number of pathways including a neurogenic one. Thirty patients with lipodermatosclerosis and chronic venous insufficiency and 20 control subjects were studied. There was no difference in peak vasodilatation following pilocarpine electrophoresis in the two groups. The median (interquartile range) peak flux in patients was 665 (382-1025) units and in controls 765 (452-975) units (95 per cent confidence interval of difference--270 to 150 units, P = 0.5). This suggests that the capillaries in the liposclerotic skin of patients with chronic venous insufficiency have a normal capacity to vasodilate.

Aged↗

Arterialization of the portal vein improves hepatic microcirculation and tissue oxygenation in experimental cirrhosis.

BACKGROUND: Arterialization of the portal vein (APV) has shown beneficial effects on liver regeneration and function in selected patients undergoing liver resection and transplantation. Whether APV improves liver perfusion and function in cirrhosis is unclear. This study investigated the effect of APV on hepatic haemodynamics and liver function in a rat model of cirrhosis. METHODS: Male Sprague-Dawley rats (250-300 g) were divided into three groups: normal controls (n = 7), cirrhosis with sham laparotomy (sham; n = 7) and cirrhosis with APV (APV; n = 9). Portal venous blood flow, portal vein pressure and hepatic parenchymal microcirculation (HPM) were measured before and after APV. Hepatic parenchymal oxygenation was assessed by near-infrared spectroscopy and hepatocellular injury by standard liver function tests. Measurements were taken at baseline, after APV and 7 days after surgery. RESULTS: APV increased portal blood flow and pressure in cirrhotic rats without altering intrahepatic portal resistance. APV increased the HPM in cirrhotic rats by a mean(s.e.m.) of 28.5(0.1) per cent on day 0 and 54.6(0.1) per cent by day 7 (P = 0.001). Liver tissue oxygenation was increased by APV and the plasma gamma-glutamyltranspeptidase level was reduced (mean(s.e.m.) 6.0(0.5) versus 3.8(0.3) units/l before and after APV respectively; P = 0.006) at day 7. CONCLUSION: APV increases portal blood flow, tissue perfusion and oxygenation in cirrhosis.

Animals↗

Induction of adhesion molecule expression in liver ischaemia-reperfusion injury is associated with impaired hepatic parenchymal microcirculation.

BACKGROUND: Activated neutrophils may be important mediators in liver ischaemia-reperfusion injury (I/R). Adhesion of leucocytes to the endothelial cell surface is a result of activation of cell adhesion molecules. The aim of this study was to investigate the effect of I/R on the hepatic microcirculation (HM) and intercellular adhesion molecule (ICAM) 1 expression. METHODS: Four groups of six Sprague-Dawley rats underwent laparotomy for liver exposure. Group 1 acted as controls, and groups 2-4 underwent partial liver ischaemia for 30, 45 and 60 min respectively followed by reperfusion for 60 min. Flow in the HM was measured by laser Doppler flowmetry. Liver biopsies were taken at the end of the reperfusion period. ICAM-1 expression was assessed by immunohistochemistry (graded 0-3). RESULTS: Mean flow in the HM was significantly reduced with I/R (mean(s.e.m.) red cell flux 140(21), 52(3) and 43(2) with 30, 45 and 60 min ischaemia compared with control 230(17); all P < 0.001). ICAM-1 expression was significantly induced (mean(s.e.m.) 1.30(0.21), 2.50(0.22) and 2.80(0.17) with 30, 45 and 60 min ischaemia versus control 0.50(0.22); all P < 0.001). CONCLUSION: I/R produced a significant upregulation of ICAM-1 expression which correlated with impaired flow in the HM.

Animals↗

The effect of mouse hepatitis virus infection on the microcirculation of the liver.

Mouse hepatitis virus type 3 infection results in strain-dependent liver disease. The effects of mouse hepatitis virus type 3 on the microcirculation of the liver in both fully susceptible (Balb/cJ) and fully resistant (A/J) mice were studied. In Balb/cJ mice, 6 to 12 hr following infection, abnormalities in liver blood flow were observed which consisted of granular blood flow in both terminal hepatic and terminal portal venules. In addition, sinusoidal microthrombi were present predominantly in periportal areas. By 24 to 48 hr, liver cell edema and small focal lesions were prominent. At 48 hr, thrombi and hepatocellular necrosis were widespread, and blood was shunted from damaged areas into patent sinusoids. In sharp contrast to these abnormal findings, normal streamlined blood flow was present in the resistant A/J animals at all time points following infection. Since large amounts of virus were demonstrated by immunofluorescene in and by recovery and growth from livers of both resistant and susceptible strains, the presence of the virus per se cannot explain the abnormalities observed.

Animals↗

Morphology of gastric microcirculation in cirrhosis.

Morphologic alterations in the gastric microcirculation in cirrhosis were investigated following infusion of a silicone rubber compound into vessels of the excised stomach which was then cleared with methyl salicylate. In cirrhosis, arteriovenous anastomoses 15 to 50 micron in diameter were present in 5 of 10 patients; spiral arterioles were less than one-tenth as numerous as in stomachs from noncirrhotic patients. The arterioles mainly had a straight pattern and precapillaries, capillaries, and submucosal and subserosal veins were dilated in cirrhotics (p less than 0.05). The number of arteriovenous anastomoses was unrelated to the degree of vascular dilatation and the number of spiral arterioles. These morphological alterations are consistent with decreased arteriovenous flow resistance in the stomach of cirrhotic patients.

Adult↗