Capillary Erythrocyte Velocity Research Articles

Ivabradine Attenuates the Microcirculatory Derangements Evoked by Experimental Sepsis.

Experimental data suggest that ivabradine, an inhibitor of the pacemaker current in sinoatrial node, exerts beneficial effects on endothelial cell function, but it is unclear if this drug could prevent microcirculatory dysfunction in septic subjects, improving tissue perfusion and reducing organ failure. Therefore, this study was designed to characterize the microcirculatory effects of ivabradine on a murine model of abdominal sepsis using intravital videomicroscopy. Twenty-eight golden Syrian hamsters were allocated in four groups: sham-operated animals, nontreated septic animals, septic animals treated with saline, and septic animals treated with ivabradine (2.0 mg/kg intravenous bolus + 0.5 mg · kg · h). The primary endpoint was the effect of ivabradine on the microcirculation of skinfold chamber preparations, assessed by changes in microvascular reactivity and rheologic variables, and the secondary endpoint was its effects on organ function, evaluated by differences in arterial blood pressure, motor activity score, arterial blood gases, and hematologic and biochemical parameters among groups. Compared with septic animals treated with saline, those treated with ivabradine had greater functional capillary density (90 ± 4% of baseline values vs. 71 ± 16%; P < 0.001), erythrocyte velocity in capillaries (87 ± 11% of baseline values vs. 62 ± 14%; P < 0.001), and arteriolar diameter (99 ± 4% of baseline values vs. 91 ± 7%; P = 0.041) at the end of the experiment. Besides that, ivabradine-treated animals had less renal, hepatic, and neurologic dysfunction. Ivabradine was effective in reducing microvascular derangements evoked by experimental sepsis, which was accompanied by less organ dysfunction. These results suggest that ivabradine yields beneficial effects on the microcirculation of septic animals.

Influence of rheological parameters on the velocity of erythrocytes passing nailfold capillaries in humans

One thousand two hundred and fifty-six subjects (apparently healthy subjects and patients with cardiovascular diseases) were registered in a prospective study including demographical and clinical data, rheological parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte deformability) as well as the erythrocyte velocity in human nailfold capillaries under resting and postischemic conditions. A multivariate regression analysis showed that under resting conditions there was no correlation between rheological parameters and erythrocyte velocity in capillaries. The blood flow regulation seemed to be so effective, that pathological changes of the blood fluidity showed no effect on the velocity of an erythrocyte passing the capillaries. During vessel paralysis in the early phase of the postischemic hyperemia following a stasis of three minutes in the vasculature distal to a pressure cuff at the upper arm a very clear correlation between the plasma viscosity and the maximum postischemic erythrocyte velocity in ipsilateral cutaneous capillaries could be observed (p < 0.0001) while none of the other rheological parameters seemed to play a role. In a subgroup of diabetic patients the erythrocyte aggregation (measured during stasis) also correlated with the erythrocyte velocity (p = 0.0175) besides the plasma viscosity. This shows that a correlation of rheological parameters with the capillary perfusion could only be found during vessel paralysis. In of diabetic patients besides the plasma viscosity also the erythrocyte aggregation correlated with the mean capillary erythrocyte velocity. Theses results are in agreement with the hypothesis from Barras that plasma viscosity determines the perfusion of microvessels. Under certain conditions e.g. diabetic disorder, also the erythrocyte aggregation plays a role.

Long-Term in Vivo Investigation of Mouse Cerebral Microcirculation by Fluorescence Confocal Microscopy in the Area of Focal Ischemia

This study was designed to assess that mouse pial and cortical microcirculation can be monitored in the long term directly in the area of focal ischemia, using in vivo fluorescence microscopy. A closed cranial window was placed over the left parieto-occipital cortex of C57BL/6J mice. Local microcirculation was recorded in real time through the window using laser-scanning confocal fluorescence microscopy after intravenous injection of fluorescent erythrocytes and dextran. The basal velocity of erythrocytes through intraparenchymal capillaries was 0.53+/-0.30 mm/sec (n=121 capillaries in 10 mice). Two branches of the middle cerebral artery were topically cauterized through the window. Blood flow evaluated by laser-Doppler flowmetry in two distinct areas indicated the occurrence of an ischemic core (15.2%+/-5.9% of baseline for at least 2 h) and a penumbral zone. Magnetic resonance imaging and histology were used to characterize the ischemic area at 24 h after occlusion. The infarct volume was 7.3+/-3.2 mm(3) (n=6). Microcirculation was repeatedly videorecorded using fluorescence confocal microscopy over the next month. After the decrease following arterial occlusion, capillary erythrocyte velocity was significantly higher than baseline 1 week later, and attained 0.74+/-0.51 mm/sec (n=76 capillaries in six mice, P<0.005) after 1 month, while venous and capillary network remodeling was assessed, with a marked decrease in tortuosity. Immunohistochemistry revealed a zone of necrotic tissue into the infarct epicenter, with activated astrocytes at its border. Such long-term investigations in ischemic cortex brings new insight into the microcirculatory changes induced by focal ischemia and show the feasibility of long-term fluorescence studies in the mouse cortex.

Microcirculation of the bulbar conjunctiva in the goat implanted with a total artificial heart: effects of pulsatile and nonpulsatile flow.

A new system to observe the microcirculation on the bulbar conjunctiva was developed using a digital high definition microscope to investigate the influence of the flow patterns on the microcirculation in a goat with a total artificial heart (TAH). The undulation pump TAH was implanted into the goat. When the whole body condition became stable, the flow pattern was modulated between the pulsatile and the nonpulsatile mode, and the changes in the microcirculation were observed. When the flow pattern was changed from pulsatile to nonpulsatile mode, the erythrocyte velocity in capillaries dropped from 526+/-83 to 132+/-41 microm/s and remained at a low level. The number of perfused capillaries decreased as well. Then the nonpulsatile flow mode was maintained for 20 minutes. After the flow pattern was returned to the pulsatile mode again, the erythrocyte velocity recovered to the initial level (433+/-71 microm/s). In many cases, the flow of the nonperfused capillaries in the nonpulsatile mode recovered to the initial level after the flow pattern was changed to the pulsatile mode again. The perfused capillary density in the nonpulsatile mode (19.7+/-4.1 number of capillaries/mm) was significantly lower than that in the pulsatile mode (34.7+/-6.3 number of capillaries/mm). It is thought that the basal and flow stimulated endothelium derived nitric oxide release in the microvessels decreased because of the disappearance of pulsatility and that the nitric oxide induced the constriction of arterioles after the flow pattern was changed to the nonpulsatile mode. At the same time, the baroceptors might sense the decrease in the arterial peak pressure or dp/dt, and the sympathetic nerve increases activities and induce the constriction of arterioles. Then, the erythrocyte velocity in capillaries would decrease. Because of the flow pattern further in the chronic phase, it is important to follow the change in the microcirculation.

Capillary flow and diameter changes during reperfusion after global cerebral ischemia studied by intravital video microscopy.

The reaction of cerebral capillaries to ischemia is unclear. Based on Hossmann's observation of postischemic "delayed hypoperfusion," we hypothesized that capillary flow is decreased during reperfusion because of increased precapillary flow resistance. To test this hypothesis, we measured cerebral capillary erythrocyte velocity and diameter changes by intravital microscopy in gerbils. A cranial window was prepared over the frontoparietal cortex in 26 gerbils anesthetized with halothane. The animals underwent either a sham operation or fifteen minutes of bilateral carotid artery occlusion causing global cerebral ischemia. Capillary flow velocities were measured by frame-to-frame tracking of fluorescein isothiocyanate labeled erythrocytes in 1800 capillaries after 1-hour reperfusion. Capillary flow velocities were decreased compared to control (0.25 +/- 0.27 mm/s vs. 0.76 +/- 0.45 mm/s; P<0.001). Precapillary arteriole diameters in reperfused animals were reduced to 76.3 +/- 6.9% compared to baseline (P<0.05). Capillary diameters in reperfused animals (2.87 +/- 0.97 microm) were reduced (P<0.001) compared to control (4.08 +/- 1.19 microm). Similar reductions of precapillary (24%) and capillary vessel diameters (30%) and absolute capillary flow heterogeneity indicate that delayed (capillary) hypoperfusion occurs as a consequence of increased precapillary arteriole tone during reperfusion.

Real-time microcirculatory changes due to spreading depression under focal ischemia

Laser-scanning confocal fluorescence microscopy was used to investigate microcirculatory influences of spreading depression (SD)-like depolarizations elicited by occlusion of the rat middle cerebral artery (MCA). Six rats underwent halothane anesthesia and mechanical ventilation. A closed cranial window was implanted over their frontoparietal cortex. They were placed under a Biorad Viewscan confocal microscope and intravenously given fluorescein isothiocyanate (FITC)-Dextran and FITC-labeled erythrocytes. The capillaries were visualized down to 200 μm below the brain surface and the images were video recorded (50/s). The MCA was occluded under the microscope using an intraluminal remotely controlled method and the reperfusion was induced 2 h later. Furthermore, the brains were histologically examined 24 h later. Under ischemia, the erythrocyte velocity through the capillaries was depressed by 35% and venous blood became highly sluggish. The arteriole diameter did not change significantly, however, the direction of arteriolar blood flow was episodically and transiently reversed. During spontaneous SD-like depolarization, the arteriole diameter significantly increased (+19% vs. MCAO) while capillary erythrocyte velocity was further depressed by 15%. This decrease in velocity was more pronounced (25%) when depolarization were associated with transient reversal of arteriolar flow. Following reperfusion, microcirculatory variables rapidly returned to the baseline. All rats exhibited infarcts 24 h after the occlusion. These results indicate that SD-like depolarizations have an adverse influence on penumbral microcirculation, i.e., a reduction in capillary perfusion by erythrocytes, despite arteriolar dilatation.

Penumbral microcirculatory changes associated with peri-infarct depolarizations in the rat.

This study was designed to investigate the influence of peri-infarct depolarization elicited by occlusion of the middle cerebral artery on the dynamics of the microcirculation. The microcirculation in the frontoparietal cortex of 9 rats was visualized in real time through a closed cranial window with the use of laser-scanning confocal fluorescence microscopy combined with intravenous fluorescein isothiocyanate (FITC)-dextran and FITC-labeled erythrocytes. The direct current potential/electrocorticogram was continuously monitored. Intraluminal focal ischemia was induced for 2 hours in 6 rats anesthetized with halothane and mechanically ventilated. Reperfusion was monitored for 1 hour. Three rats underwent sham operation. Brains were removed 24 hours after occlusion and processed for histology. In control conditions, the velocity of fluorescent erythrocytes through capillaries was 0.51+/-0.19 mm/s (mean+/-SD), and the diameter of the arterioles studied was 33+/-12 microm. Under ischemia, erythrocyte velocity through capillaries was significantly decreased to 0.33+/-0.14 mm/s, while arteriole diameter did not change significantly. During spontaneous peri-infarct depolarizations, arteriole diameter was significantly increased (119+/-23% of baseline), while capillary erythrocyte velocity was further decreased by 14+/-34%. The direction of arteriolar blood flow episodically and transiently reversed during approximately half of the peri-infarct depolarizations. The decrease in capillary erythrocyte velocity was more pronounced (23+/-37%) in these cases. After reperfusion, the microcirculatory variables rapidly returned to baseline. All rats in the ischemic group had infarcts 24 hours after occlusion. Peri-infarct depolarization has an adverse influence on penumbral microcirculation, reducing capillary perfusion by erythrocytes, despite dilatation of arterioles. These findings suggest that a steal phenomenon contributes to the deleterious effect of these depolarizations.

Primary Cutaneous Microangiopathy in Heart Recipients

In this study we investigated whether a disturbance in microcirculation is detectable in heart recipients with cardiac allograft vasculopathy (CAV) and severe hypercholesterolemia (n = 11) and in 7 heart recipients without CAV in comparison to patients with severe coronary artery disease (n = 49) and age-matched apparently healthy subjects (n = 100). For this purpose, the flow velocity of erythrocytes through cutaneous capillaries at the nail fold of the finger was measured under resting conditions. In addition, reactive hyperemia in the same capillaries after a 3-min ischemia was determined. Patients with CAV and severe lipid disorder showed a pathological reduction in mean capillary erythrocyte velocity under resting conditions with vRBC = 0.10 ± 0.07 mm/s. The latter was significantly and relevantly lower than in patients with coronary three-vessel disease (vRBC = 0.46 ± 0.35 mm/s). It was notable that under resting conditions temporary cessation of flow occurred in 8 of the 11 patients which did not occur in healthy subjects and rarely in patients with three-vessel disease (1 of 49 patients). In comparison to age-matched healthy subjects (vmax = 1.46 ± 0.52 mm/s), the patients with three-vessel disease showed a significant reduction in postischemic maximum erythrocyte velocity (vmax = 0.85 ± 0.55 mm/s), with a considerable shortening of the duration of reactive hyperemia. Patients with CAV demonstrated a total loss of postischemic reactive hyperemia (only 1 of the 11 patients presented a weak reactive hyperemia). Since no macroangiopathy was detectable in the upstream arm arteries, primary cutaneous microangiopathy can be assumed in patients with cardiac allograft vasculopathy and severe hypercholesterolemia.

Influence of a New Monomeric Nonionic Radiographic Contrast Medium (Iobitridol-350 versus NaCl) on Cutaneous Microcirculation: Single-Center, Prospective, Randomized, Double-Blind Phase IV Study in Parallel Group Design

This single-center, prospective, randomized, double-blind phase IV study with parallel-group design was performed to test whether injection of a newly designed non-ionic monomeric radiographic contrast medium in the axillary artery influences the ipsilateral cutaneous microcirculation. Twenty patients with coronary heart disease or suspected coronary heart disease were investigated. Ten patients received iobitridol and 10 normal saline solution. The confirmatory target variable was the capillary erythrocyte velocity (vRBC). The vRBC was continuously recorded before and up to 3 min after the injection of iobitridol or normal saline solution and subsequently evaluated off-line. Thirty seconds after injection of 20 ml iobitridol, vRBC was reduced by 32% (P < 0.05). This was the strongest reduction, but vRBC was reduced at all time points measured up to 180 s following the injection (P < 0.05 up to 180 s). The overall reduction in vRBC was also statistically significant (P 0.0446). In contrast, there was a tendency toward an increase in vRBC following injection of 20 ml normal saline (P 0.0512). There was also a tendency toward a difference in the time course of changes in vRBC following injection of iobitridol compared to normal saline (P 0.0607). The decrease in vRBC following iobitridol injection (standardized difference (SD) according to Cohen, 0.67) can be regarded as biometrically weak, and the increase following normal saline injection (SD, 0.24) as very weak. The microcirculatory disturbance induced by iobitridol injection is less severe than that due to comparable high-viscosity contrast media.

Small-volume resuscitation restores hemorrhage-induced microcirculatory disorders in rat pancreas.

Pancreatic hypoxia/ischemia, as a consequence of shock-induced microcirculatory failure, is considered a causative factor in the initiation and/or progression of pancreatic tissue injury. The aim of this study was to compare the effects of "small volume resuscitation" with conventional isovolemic colloid and hypervolemic crystalloid resuscitation on pancreatic microcirculation after hemorrhagic shock. Randomized, controlled intervention trial. University laboratory. Twenty-three male Sprague-Dawley rats anesthetized with á-chloralose mechanically and ventilated. Rats subjected to 1 hr of hemorrhagic shock (mean arterial pressure of 40 mm Hg) were resuscitated with lactated Ringer's solution (four-fold shed volume/20 mins), 10% hydroxyethyl starch (shed volume/5 mins), or 7.2% sodium chloride-10% hydroxyethyl starch (10% shed volume/2 mins). The microcirculation of pancreatic acinar tissue was studied by means of intravital fluorescence microscopy and laser Doppler flowmetry. At 1 hr after resuscitation, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux were found to be significantly increased when compared with those values in the shock state. However, mean arterial pressure, pancreatic capillary erythrocyte velocity, and erythrocyte flux did not completely return to preshock values, regardless of the type of fluid used for resuscitation. At 15 mins and 1 hr after resuscitation, shock-induced capillary perfusion failure (reduction of functional capillary density) was restored to 91% to 94% of baseline values in all groups. Pancreatic capillary narrowing, indicating microvascular endothelial cell swelling, was abolished by resuscitation with both isotonic hydroxyethyl starch and hypertonic hydroxyethyl starch (p<.05 vs. lactated Ringer's solution). Despite replacement of only 10% of actual blood loss, small-volume resuscitation with hypertonic hydroxyethyl starch is as effective as the ten-fold volume of isotonic hydroxyethyl starch and, due to prevention of microvascular endothelial cell swelling, superior to the 40-fold volume of isotonic lactated Ringer's solution in regard to restoration of the shock-induced microcirculatory disturbances of rat pancreatic acinar tissue.

Impaired microcirculation in mild-to-moderate essential arterial hypertension

The aim of this study was to correlate capillary morphology and erythrocyte velocity to blood pressure in mild-to-moderate essential arterial hypertension. Ambulatory blood pressure measurement may provide more precise information about a patient's mean blood pressure than office measurements. Fifteen patients with recently diagnosed, previously untreated mild-to-moderate essential hypertension underwent 24-h ambulatory blood pressure recording and a capillaroscopic examination of finger microcirculation. Erythrocyte velocity was determined by the flying spot technique. Both mean 24-h ambulatory systolic blood pressure (SBP) and mean 24-h ambulatory diastolic blood pressure (DBP) were significantly inversely correlated with capillary erythrocyte velocity. However, the correlation between erythrocyte velocity and office SBP and office DBP was less significant. Capillary length was related to 24-h ambulatory DBP but not to office DBP. Capillary number was not related to any blood pressure parameter. These results indicate that, in patients with mild-to-moderate essential hypertension, erythrocyte velocity is significantly lower than for matched controls. It is also inversely related to mean 24-h ambulatory SBP and 24-h ambulatory DBP.