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Coronary flow velocity immediately after reperfusion reflects myocardial microcirculation in canine models of acute myocardial infarction.

Recent reports indicate that the coronary microcirculation is sometimes injured, despite successful reperfusion in acute myocardial infarction (AMI). However, it is difficult to evaluate the coronary microcirculation immediately after reperfusion by using only angiography. The purpose of this study was to examine the relationship between the pattern of coronary blood flow velocity and myocardial microcirculatory injury immediately after reperfusion in AMI. The authors recorded the left circumflex coronary flow velocity by using the Doppler guide wire method 10 minutes after reperfusion in a canine model of AMI. In addition, myocardial contrast echocardiography was performed with the injection of contrast medium into the left circumflex coronary artery before clamping of the coronary artery and 15 minutes after release of the clamp. From these images, the ratio of the normalized gray-level postreperfusion to preclamping in the contrast-enhanced area was determined. It was compared with coronary flow velocity variables. In the 10 dogs with a diastolic-to-systolic velocity ratio (DSVR) < 4.0, this velocity ratio 10 minutes after reperfusion correlated positively (r = 0.75, p < 0.01) with the normalized gray-level ratio. However, the remaining three dogs with a DSVR > or = 4.0 markedly deviated from this pattern. Coronary flow velocities in the three dogs were characterized by a greater decrease in systolic flow velocity and occurrence of early systolic retrograde flow. Myocardial contrast echocardiographic images in these three dogs demonstrated a lower normalized gray-level ratio. In conclusion, the coronary flow velocity pattern immediately after reperfusion may reflect myocardial microcirculatory injury.

Albumins↗

A contribution to the physiology of the perilymph. Part IV: Effect of histamine on the cochlear microcirculation.

Summary--Because of the topography of the perilymphatic vascular network, the cochlear microcirculation is especially sensitive to the effect of vasoactive substances reaching the perilymphatic space. The cochlear microcirculation is mainly controlled humorally, via the activity of the metarterioles and changes in the flow properties of the blood. Intracochlear histamine reduces the cochlear circulation even more markedly than after intracarotid administration. No systematic effects of parenteral administration of vasoactive substances can be expected on the cochlear circulation. Reversible auditory disorders after stapedectomy may be explicable by the intracochlear release of histamine. The internal release of histamine after sunstroke and cold stress may play a part in sudden dusturbances of hearing.

Animals↗

In vivo observation of tracheal microcirculation in dogs.

Tracheal microcirculation was studied in six healthy anesthetized adult mongrel dogs. A transparent balloon was used to apply pressure to the tracheal mucosa during observation of the microcirculation. Pressures of microvascular occlusion were measured using an electrically callibrated silicone, envelope placed on the observation balloon. The different vessel sizes were measured and classified using the operating microscope. Capillary occlusion pressures ranged from 10 to 40 msurements of tracheal diameter were performed. Progressive local and generalized dilatation occurred. Capillary occlusion pressure was lower in the more dilated specimens. The lower than expected occlusion pressures are thought to be a result of the tracheal dilatation and may be related to the administration of drugs or other factors.

Animals↗

Changes of Achilles midportion tendon microcirculation after repetitive simultaneous cryotherapy and compression using a Cryo/Cuff.

BACKGROUND: Cryotherapy and compression have been shown to decrease pain and improve function. The dosage and timing of these options remain unclear. PURPOSE: To examine the effects of a standardized compression and cryotherapy device (Cryo/Cuff) on midportion Achilles tendon microcirculation during intermittent administration. STUDY DESIGN: Descriptive laboratory study. METHODS: Twenty-six subjects were included (13 men and 13 women; age, 32.3 +/- 12 years; body mass index, 25.4 +/- 5 kg/m(2)). Each underwent three 10-minute applications of the device, followed by a 10-minute recovery period. A continuous real-time assessment of parameters of Achilles tendon midportion microcirculation was performed with a laser Doppler spectrophotometry system. RESULTS: Superficial tendon oxygen saturation dropped significantly from 35.9 +/- 21 arbitrary units (AU) to 13.5 +/- 15, 15.9 +/- 16, and 11.1 +/- 11 AU (P = .0001) during each period of cryo-compression, respectively. There was significant increase during the recovery period (55.4 +/- 29, 65.2 +/- 26, and 65.7 +/- 27 AU; P = .003), up to +83% of the baseline level. At 8-mm tendon depth, cryo-compression preserved local oxygen with -4% (P = .001) of the baseline level and small but significant increased oxygen saturation of up to +13% (P = .0001). Relative postcapillary venous tendon filling pressures were favorably reduced both superficially (57% +/- 34%, 67% +/- 27%, and 64% +/- 38%, respectively; P = .0004) and deep (76% +/- 13%, 79% +/- 11%, and 78% +/- 18%, respectively; P = .0002). Superficial capillary blood flow was reduced from 48.4 +/- 48 to 5 +/- 7, 4 +/- 5, and 3 +/- 4 AU at each period, respectively (-94%, P = .0003), with increased flow during recovery periods of up to 58 +/- 64, 58 +/- 79, and 47 +/- 71 AU, respectively (+20%, P = .265). Deep flow was reduced from 197 +/- 147 to 66.7 +/- 64, 55 +/- 46, and 43 +/- 39 AU, respectively (-78%, P = .0002) without increase during recovery periods. CONCLUSION: Cryo/Cuff exerts beneficial effects on the microcirculatory level of the midportion Achilles tendon with decreased capillary blood flow, preserved deep tendon oxygen saturation, and facilitated venous capillary outflow.

Achilles Tendon↗

Longitudinal studies on the microcirculation around the TheraCyte immunoisolation device, using the laser Doppler technique.

Encapsulation of cellular grafts in an immunoisolation membrane device may make it possible to perform transplantation without having to give immunosuppressive drugs. A common problem is the development of an avascular fibrotic zone around the implants, leading to impaired graft survival. The TheraCyte macroencapsulation device has therefore been designed to facilitate neovascularization of the device's surface. In this study, we evaluated the microcirculation around empty TheraCyte devices implanted SC in rats at various times after implantation, using a laser Doppler probe introduced via the device port. Studies were performed on day 1 or at 1, 2, and 4 weeks or at 2, 3, and 12 months after implantation. The mean flow was 158+/-42, 148+/-50, 133+/-28, 72+/-17, 138+/-41, 165+/-43, and 160+/-29 perfusion units (PU), respectively. Thus, the microcirculation around the device was significantly reduced at 4 weeks after implantation (p < 0.01) while, from 2 months onwards the circulation had improved and did not differ significantly from that on day 1. The present study shows time-related changes in the microcirculatory flow around TheraCyte macroencapsulation devices that agree with our previous microdialysis studies on in vivo exchange of insulin and glucose between the device and the circulation. Laser Doppler flowmetry seems to provide a reliable technique for screening blood perfusion around macroencapsulation devices.

Animals↗

An Internet multicast symposium concerning the microcirculation of the islets of Langerhans.

The Internet Globally-linked Computer System was used to conduct an international scientific symposium. The symposium was held at the VAMC-Long Beach and consisted of prepared lectures that were multicast over the Internet. The basic unit of hardware used for the Internet Multicast was the Silicon Graphics Indy Unix Workstation, which was equipped with a color video camera. The multicast required four additional pieces of software from the file transfer protocol. The multicast backbone protocol allowed for simultaneous audio and video signals (the presenter, the slides, and the videotape images of islet microcirculation studies) to be transmitted over the computer network. The faculty included 12 experts in microcirculation, who gave 15-min lectures that included a question and answer period. All lectures were received at 14 computer stations in six countries. Eleven of the faculty gave their lectures at the VAMC-Long Beach, and one gave her lecture at the Massachusetts Institute of Technology in Boston, MA. The presenter from Boston was able to receive and answer questions from the faculty at the VAMC-Long Beach. An estimated $12,000 was saved in travel, hotel, and food costs and an estimated 180 travel hours were saved by viewers who did not have to travel to the symposium. We have demonstrated that a scientific symposium can be conducted using the Internet. We propose that many of our future meeting will be organized over the computer network. This format of multiimage projections allows us to effectively communicate in a personal way with a reduction in expensive and time-consuming travel.

Animals↗

Correlation of microcirculation architecture with ultrasound backscatter parameters of uveal melanoma.

Ultrasound tissue characterization parameters of size and acoustic concentration can be used to sub-classify uveal melanoma and estimate the patient's risk of death. Histologically determined microcirculation patterns have also been found to sub-classify uveal melanoma and predict patient's risk of death. This study examines the spatial relationship between tumor features detected by the two techniques. Three dimensional ultrasound images that depict the size and relative concentration of scattering elements in uveal melanoma within a range of approximately 50-120 microns were compared with PAS (without hematoxylin) stained histological sections graded and localized according to tumor microvascular patterns. Both ultrasound parameter imaging and histopathology were accomplished by workers masked to the other procedure. In three of five patients vascular networks were identified histopathologically. The predominant ultrasound feature seen in the regions of the histologically identified networks were clusters of scatterers in the range of approximately 50-80 microns. In the two cases without a network vascular pattern, lower range scatterers dominated the tumor volume. All the cases could be distinguished by the size and distribution of contiguous spatial clusters of acoustic scatterers. Scatterer size features detected in three dimensional ultrasound parameter images can identify tumor regions containing a specific microvascular pattern. Ultrasound tissue characterization features used to sub-classify uveal melanoma may have a biophysical basis related to patterns of tumor microcirculation.

Blood Vessels↗

The microcirculation in venous hypertension.

Venous ulceration is a common problem in western countries and results in large costs to healthcare systems. A number of hypotheses of the mechanisms of development of venous ulceration have been advanced, but this question has not been fully resolved. In recent years research effort has focused on the microcirculation of the skin and many methods of investigation have been employed to study this. Some of the principal findings described in published work are reviewed in this article. It seems unlikely from the available evidence that venous ulceration is attributable solely to failure of diffusion of oxygen and other small nutritional molecules to the tissues of the skin. The microvascular changes in the skin are characterised by activated endothelium and perivascular inflammatory cells. It is much more likely that leucocytes attach themselves to the cutaneous microcirculation, become activated and produce endothelial injury. Repeated over many months or years, this chronic inflammatory process leads to be tissues changes of lipodermatosclerosis. Although there is evidence of leucocyte involvement in the pathogenesis of venous ulceration, the exact mechanisms remain to be resolved. Improved treatment for patients may be devised once a better understanding of the basic causes of this condition has been reached.

Blood Gas Monitoring, Transcutaneous↗

Gene expression profile and synovial microcirculation at early stages of collagen-induced arthritis.

A better understanding of the initial mechanisms that lead to arthritic disease could facilitate development of improved therapeutic strategies. We characterized the synovial microcirculation of knee joints in susceptible mouse strains undergoing intradermal immunization with bovine collagen II in complete Freund's adjuvant to induce arthritis (i.e. collagen-induced arthritis [CIA]). Susceptible DBA1/J and collagen II T-cell receptor transgenic mice were compared with CIA-resistant FVB/NJ mice. Before onset of clinical symptoms of arthritis, in vivo fluorescence microscopy of knee joints revealed marked leucocyte activation and interaction with the endothelial lining of synovial microvessels. This initial inflammatory cell response correlated with the gene expression profile at this disease stage. The majority of the 655 differentially expressed genes belonged to classes of genes that are involved in cell movement and structure, cell cycle and signal transduction, as well as transcription, protein synthesis and metabolism. However, 24 adhesion molecules and chemokine/cytokine genes were identified, some of which are known to contribute to arthritis (e.g. CD44 and neutrophil cytosolic factor 1) and some of which are novel in this respect (e.g. CC chemokine ligand-27 and IL-13 receptor alpha1). Online in vivo data on synovial tissue microcirculation, together with gene expression profiling, emphasize the potential role played by early inflammatory events in the development of arthritis.

Animals↗

Bench-to-bedside review: sepsis is a disease of the microcirculation.

Microcirculatory perfusion is disturbed in sepsis. Recent research has shown that maintaining systemic blood pressure is associated with inadequate perfusion of the microcirculation in sepsis. Microcirculatory perfusion is regulated by an intricate interplay of many neuroendocrine and paracrine pathways, which makes blood flow though this microvascular network a heterogeneous process. Owing to an increased microcirculatory resistance, a maldistribution of blood flow occurs with a decreased systemic vascular resistance due to shunting phenomena. Therapy in shock is aimed at the optimization of cardiac function, arterial hemoglobin saturation and tissue perfusion. This will mean the correction of hypovolemia and the restoration of an evenly distributed microcirculatory flow and adequate oxygen transport. A practical clinical score for the definition of shock is proposed and a novel technique for bedside visualization of the capillary network is discussed, including its possible implications for the treatment of septic shock patients with vasodilators to open the microcirculation.

Critical Illness↗

Neural and endothelial control of the microcirculation in diabetic peripheral neuropathy.

OBJECTIVE: To examine the role played by endothelium-dependent and endothelium-independent vasodilation of the cutaneous microcirculation and their relationship to neural microcirculatory control in type 1 and type 2 diabetic patients. METHODS: Acetylcholine and sodium nitroprusside were iontophoresed using a dose-response technique. Endothelium-dependent, endothelium-independent, and C-fiber-mediated vasodilation were measured with a laser Doppler device. RESULTS: Endothelium-dependent vasodilation of the forearm cutaneous microcirculation was attenuated in diabetic subjects. The response was less in type 2 diabetic subjects than in controls (p < 0.005). In contrast, there was no significant difference between type 1 diabetic subjects and controls. There was no significant abnormality in endothelium-independent vasodilation in either diabetic group. The C-fiber-mediated axon reflex in the forearm was impaired in both type 1 and type 2 diabetics, which is consistent with a small-fiber neuropathy (p < 0.005). The duration of diabetes in type 2 diabetics was a significant predictor of the maximum endothelium-mediated vasodilation. CONCLUSION: Changes in cutaneous blood flow are seen relatively early in the course of diabetic peripheral neuropathy and are characterized by endothelial and neural but not smooth muscle dysfunction. The presence of significant C-fiber impairment in both diabetic groups, together with significantly greater dysfunction in endothelium-dependent vasodilation in type 2 diabetics, suggests that the endothelial function and nitric oxide may play a greater role in the pathogenesis of diabetic peripheral neuropathy in type 2 diabetic patients.

Adult↗

Orthogonal polarization spectral imaging of the microcirculation during acute hypervolemic hemodilution and epidural lidocaine injection.

We used Orthogonal Polarization Spectral Imaging to examine the microcirculation of the vaginal mucosa in nine anesthetized patients during two consecutive anesthetic interventions: hypervolemic hemodilution using hydroxyethyl starch followed by thoracic epidural lidocaine. Images taken before and after each intervention were compared. During hypervolemic hemodilution, systolic blood pressures increased significantly, but functional capillary density remained unchanged. Epidural anesthesia decreased systolic and diastolic blood pressures, but there was no change in capillary density, venular diameter, or flow velocity. We concluded that when using Orthogonal Polarization Spectral imaging, no consistent effects on the microcirculation of the vaginal wall can be detected.

Adult↗

Transcranial Doppler and cortical microcirculation at increased intracranial pressure and during the Cushing response: an experimental study on rabbits.

The effect of increased intracranial pressure on the flow velocity of the basilar artery was measured with transcranial ultrasonic Doppler in New Zealand White rabbits under alpha-chloralose anesthesia and artificial respiration. Laser Doppler flowmetry served to study changes of the cortical microcirculation. The results confirm a high inverse correlation of the diastolic flow velocity, the pulsatility index, and the resistance index with the cerebral perfusion pressure (CPP). During acute intracranial hypertension, however, these parameters do not show a good correlation with the local cortical blood flow. The absence of a correlation was evident over a wide CPP range down to values of 35 mm Hg. Only at CPP values below this critical threshold is the microcirculation impaired. The threshold is reached at pulsatility index values of more than 2.0 and at resistance index values of more than 0.8. Therefore, transcranial Doppler indices permit the detection of critical reductions of microcirculatory blood flow. The Cushing reaction occurred with a constant time lag of 5.5 +/- 0.7 seconds after the loss of CPP. The Cushing reaction did not establish systolic blood flow, which remained below the functional threshold, as concluded from the temporary loss of somatosensory evoked potentials.

Animals↗

Relations between disturbances in microcirculation and accumulation of lipids in the aortic wall.

For the purpose of unraveling the relations between disturbances in microcirculation and deposition of lipids in the aortic wall, 9 rabbits were fed a 1% cholesterol and 5% coconut oil at intervals up to 16 weeks, and 4 rabbits were used as controls. After microangiography of vasa vasorum, the same specimens were studied histochemically. The distribution of vasa vasorum became poorer on sacrifice by microangiography. However, it could not be thought that disturbances in vasa vasorum was a cause in the early deposition of lipids, because lesions were histologically mild in the greater parts of vasa vasorum. The sites of prediction for the vascular lesions were initially the branching part, and then the thoracic aorta. Thickness and numbers of the elastic lamina in the media decreased straightly in the distal direction, and the degree of intimal thickening and accumulation of lipids were parallel with the degree of the medial thickness. The intimal cells tended to be arranged radially with wide intercellular spaces in the cross section, suggesting the convenience for the passage of fluids. From the above facts, it may be reasonable to presume that the difference in severity of disturbances of microcirculation resulted in the difference in the site of predilection.

Angiography↗

Effects of low doses of endothelin-1 on basal vascular tone and autoregulatory vasodilation in canine coronary microcirculation in vivo.

The plasma level of endothelin-1 (ET-1) increases in several cardiovascular disorders. The present study examined whether threshold doses of ET-1 affect vascular tone and autoregulatory vasodilation during a reduction in perfusion pressure in the coronary microcirculation in vivo. In anesthetized open-chest dogs, arterial microvessels in the epimyocardium were observed through a microscope equipped with a floating objective. In 6 dogs, ET-1 (10(-13) to 10(-8)mol/L) was superfused onto the epimyocardium in a cumulative fashion. In another set of dogs (n= 16), the perfusion pressure of the observed vascular bed was reduced to 60 mmHg (mild stenosis) and to 40 mmHg (severe stenosis) by a hydraulic occluder, and the microvascular responses were observed in the presence (n=9) or absence (n=7) of ET-1 (10(-12) or 10(-11) mol/L). ET-1 > or =10(-11) mol/L constricted coronary arterioles (< or =100 microm in diameter) and small arteries (>100 microm in diameter) in a dose-dependent fashion. ET-1 of 10(-12) mol/L affected neither the basal diameters nor the dilation of vessels during the pressure reduction. ET-1 of 10(-11) mol/L decreased the diameters of arterioles and small arteries before and during the mild and severe stenosis. However, ET-1 did not attenuate the percentage dilation of arterioles from the baseline in response to the mild and severe stenosis. The data indicates the following: (1) ET-1 at doses > or =10(-11) mol/L similarly constricts coronary arterioles and small arteries; (2) ET-1 at 10(-11) mol/L, which is slightly higher than the pathophysiological plasma level, increases the basal vascular tone, but does not attenuate the autoregulatory vasodilation of the coronary microcirculation.

Animals↗

[In vivo visualization of renal microcirculation using hydronephrotic rat kidney].

A number of neurohumoral factors participate in the regulation of renal hemodynamics. Several methods have been developed to study directly the regulation of renal microcirculation. Here, we introduce an in vivo method to visualize renal microcirculation by using hydronephrotic rat kidney, a unique method originally developed by Steinhausen et al. More than 10 weeks after unilateral ureteral ligation in rats, the renal parenchyme becomes thinner and suitable for transillumination. After anesthesia, the hydronephrotic kidney was split at the greater curvature with a thermal cautery and then fixed in a water chamber containing Kreb's solution. The renal tissue was transilluminated and microscopically visualized using water immersion objectives. Renal microvessels including arcuate and interlobular arteries, afferent and efferent arterioles and glomerular capillaries could be easily observed on a display monitor at a final magnification of 2,700 times. Topical application of angiotensin II elicited constriction of the interlobular artery and afferent and efferent arterioles dose-dependently. Thus, this preparation is a unique model allowing visualization of the whole renal vascular tree in vivo.

Animals↗

Effects of vasodilators on microcirculation of the rat cremaster muscle: a microscopic method for screening drugs.

Effects of vasodilating drugs on microcirculation of the rat cremaster muscle were investigated microscopically. Topical application and intravenous injection of papaverine produced dilatation of arterioles. Cyclandelate applied topically dilated the arterioles to a considerable extent. Topical application of bamethan induced arteriolar dilatation while bamethan given intravenously constricted the arterioles. Kallikrein applied topically induced a slight dilatation of arterioles, and intravenous administration of kallikrein produced an appreciable vasodilatation. Topical administration of bradykinin produced a vasodilatation of arterioles of the rat cremaster muscle. These results indicate that direct action of a drug on the microcirculation can be properly evaluated by the microscopic method in the rat cremater muscle, if the drug is applied topically, in the vicinity of small vessels under study.

Acetylcholine↗

Effect of ibudilast on microcirculation thrombosis in rat inner ear.

The effect of ibudilast (0.1, 0.3 mg/kg), which has cerebral vasodilating and antiplatelet effects, was evaluated in two models of rat inner ear microcirculation thrombosis by using the photochemical reaction between green light (wave length: 540 nm) and intravenous injection of rose bengal. Furthermore, the inner ear blood flow was measured by a laser-Doppler flowmeter. In the hearing disturbance model, under anesthesia, the compound action potential of the cochlear nerve (AP) was measured by an electrocochleogram. The sound stimulus was an 8-kHz sine wave at 80 dB SPL. The AP was calculated 128 times. In the controls, the AP disappeared about 4 min after the intravenous injection of rose bengal (20 mg/kg). The time required to completely suppress the AP in the animals treated with ibudilast (0.1, 0.3 mg/kg) was significantly prolonged as compared with that in the controls. In the equilibrium dysfunction model, ibudilast (0.1, 0.3 mg/kg) reduced the time of abnormal swimming in the swimming test 24 hr after the completion of photo-illumination. Ibudilast (0.3 mg/kg) increased the inner ear blood flow during the 10-min observation period as compared with the controls, while it did not affect the mean blood pressure. In conclusion, ibudilast increased the inner ear blood flow and was effective in two models of rat inner ear microcirculation thrombosis.

Animals↗