Disturbance Of Cerebral Microcirculation Research Articles

Effects of Mild Hypothermia on Cerebral Large and Small Microvessels Blood Flow in a Porcine Model of Cardiac Arrest.

The effect of mild hypothermia (MH) on microcirculation after resuscitation from cardiac arrest is controversial. The aim of this study was to determine whether MH improves or aggravates the disturbance of cerebral microcirculation. Twenty domestic male pigs were randomized into the MH group (n=8), non-hypothermia (NH) group (n=8) or sham operation group (n=4). In the MH group, the animals were initiated rapid intravascular cooling at 1h after return of spontaneous circulation (ROSC) from 8min ventricular fibrillation, and the core temperature was reduced to 33°C for 12h and then rewarmed to 37°C. In the NH group, animals did not receive hypothermia treatment after ROSC. In the sham operation group, the same surgical procedure was performed, but without inducing ventricular fibrillation and hypothermia treatment. The cerebral microvascular flow index (MFI) of large microvessel (diameter>20μm) and small microvessel (diameter<20μm) was measured after ROSC. Cerebral oxygen extraction ratio, internal jugular venous-artery lactate difference, and CO2 difference were also calculated. Cerebral MFI dramatically reduced after ROSC, and MH further aggravated the decrease in MFI of small microvessel compared with NH (p<0.05). Internal jugular venous-arterial lactate difference and CO2 difference, and oxygen extraction ratio were all significantly increased after ROSC. MH significantly decreased the values compared with NH (p<0.05). MH decreases cerebral small microvessel blood flow and cerebral metabolism after ROSC compared with NH. However, the total effect is that cerebral oxygen supply-demand relationship is improved during hypothermia.

The disturbances of cerebral microcirculation in severe head injury

The aim of the literature review was to present modern views on the possible mechanisms of the disturbances of capillary blood flow in severe brain injury (TBI). The critical analysis of the concept of secondary brain damage and possible mechanisms of the disturbances of cerebral microcirculation in TBI are presented. We also discuss modern methodologies for assessing capillary blood flow in patients with brain damage. The attention is focused on the causes of the disturbances of cerebral microcirculation in TBI, as well as in various forms of fat embolism in severe combined TBI. Possibilities of prevention and early correction of damaged capillary blood flow in brain injury, as well as the supposed reasons for the failure of some clinical trials, including the widely known CRASH, are analyzed. It is noted that an integrative approach to the assessment of cerebral microcirculation in conjunction with brain metabolism reflects not just the variability of cerebral blood flow and functional disorders of perfusion and metabolism coupling in traumatic brain injury. It is emphasized that ischemia is not the only cause of post-traumatic disorders of pial circulation. We highlight directions for future research of posttraumatic disturbances of cerebral microcirculation as a leading factor of secondary brain insults. The possibility of pharmacological and non-pharmacological correction of microcirculatory disorders in TBI is outlined.

Bradykinin antagonists reduce leukocyte-endothelium interactions after global cerebral ischemia.

The aim of the present study was to evaluate the influence of bradykinin on microcirculatory changes and outcome after global cerebral ischemia (15 minute) in Mongolian gerbils. The cerebral microcirculation was investigated by fluorescent intravital microscopy. Survival and functional outcome was evaluated up to 4 d after ischemia. Animals were treated with the selective B(1) and B(2) receptor antagonists B 9858 and CP 0597, respectively, and the nonselective B(1)/B(2) receptor antagonist B 9430. Leukocyte activation was significantly reduced by all antagonists as indicated by a significant decrease in the number of rolling (33 +/- 20, 6 +/- 8, 9 +/- 10, and 13 +/- 10) and adherent leukocytes (9 +/- 7, 3 +/- 4, 1 +/- 1, and 2 +/- 3. 100 microm(-1) x min(-1) in controls and in animals treated with B(1), B(2), and B(1)/B(2) antagonist, respectively). Arteriolar diameters were significantly reduced during reperfusion (35 +/- 11 before and 27 +/- 8 microm 40 minutes after ischemia) in animals treated with the B(2) antagonist. The postischemic hypoperfusion, however, was not affected. Mortality was significantly higher in animals treated with the B(1) and the B(1)/B(2) antagonist. The authors concluded that bradykinin is involved in postischemic disturbances of cerebral microcirculation. The therapeutic effect of specific bradykinin receptor antagonists on functional outcome, however, remains unclear.

Influence of platelet-activating factor on cerebral microcirculation in rats: part 2. Local application.

Platelet-activating factor (PAF) is involved in the development of secondary brain damage after ischemic and traumatic brain injury. On the basis of data from studies in peripheral organs, we hypothesized that PAF-mediated effects after cerebral injury could be secondary to alterations in cerebral microcirculation. Changes in cerebral microcirculation focusing on leukocyte-endothelium interactions were quantified with the use of a closed cranial window model in Sprague-Dawley rats (n=33) by means of intravital fluorescence microscopy. The brain surface was superfused with PAF in concentrations from 10(-3) (n=3) to 10(-12) mol/L (n=6) for 20 minutes (5 mL/h). PAF 10(-4) mol/L (n=4) increased the number of rolling and adherent leukocytes in venules from 9.7+/-0.4 to 19.7+/-2.3 cells/100 mm. min (P=NS versus control) and from 2.2+/-0.5 to 4.3+/-0.7 cells/100 mm. min (P<0.05 versus control), respectively. Lower concentrations did not elicit leukocyte-endothelium interactions. Vessel diameters remained unchanged except for a transient increase of arteriolar diameters during superfusion with PAF 10(-4) and 10(-6) mol/L (n=6). Although only a limited area of the brain surface was exposed to PAF, the mediator induced a significant dose-dependent transitory arterial hypotension and caused irreversible circulatory shock at the high concentration (PAF 10(-3) mol/L). Arterial hypotension after administration of PAF 10(-3) mol/L could be attenuated by the intravenous pretreatment with the PAF antagonist WEB 2170BS. PAF, when locally released after brain injury, can penetrate the blood-brain barrier and induce systemic effects, including arterial hypotension. Its role as a mediator in the development of secondary brain damage seems, at least in the initial phase, not to be associated with disturbances of cerebral microcirculation or activation of leukocytes.

Transient cerebral ischemia. Association of apoptosis induction with hypoperfusion.

Apoptosis is thought to be important in the pathogenesis of cerebral ischemia. The mechanism of apoptosis induction remains unclear but several studies suggest that it is preferentially triggered by mild/moderate microcirculatory disturbances. We examined in cats whether induction of apoptosis after 2.5 h of unilateral middle cerebral artery occlusion plus 10 h of reperfusion is influenced by the degree of cerebral microcirculatory disturbance. Quantitative monitoring over time of the disturbances of cerebral microcirculation in ischemic brain areas and evaluation of cytotoxic edema associated with perfusion deficits was achieved by using two noninvasive magnetic resonance imaging techniques: (a) high-speed echo planar imaging combined with a bolus of magnetic susceptibility contrast agent; and (b) diffusion-weighted imaging. Apoptosis-positive cells were counted in anatomic areas with different severity of ischemic injury characterized by magnetic resonance imaging, triphenyltetrazolium chloride, and hemotoxylin and eosin staining. The number of apoptosis-positive cells was significantly higher in anatomic areas with severe perfusion deficits during occlusion and detectable histologic changes 10 h after reperfusion. In contrast, in areas where perfusion was reduced but maintained during occlusion there were no detectable histological changes and significantly fewer apoptosis-positive cells. A similar number of cells that undergo apoptosis were shown in regions with transient or prolonged subtotal perfusion deficits. These results suggest that the apoptotic process is induced in the ischemic core and contributes significantly in the degeneration of neurons associated with transient ischemia.

Second report of an experimental study of cerebrocardiopulmonary resuscitation (CCPR) in dogs with reference to a new continuous brain cooling method, using a Resusci Pump TM-1.

In our previous report, the effect of CCPR (an intracarotid hypothermic infusion combined with the existing CPR) has been described by the authors on dogs in which cardiac arrest had been induced by the inhalation of nitrous oxide. This report contains a new continuous brain cooling method, using a Resusci Pump TM-1 which has been newly devised by us and which has a carotid-carotid bypass in order to reduce oxygen consumption and cerebral metabolism while maintaining a continuous cerebral blood flow. Cardiac arrest was induced experimentally by electrical stimulation. The duration of cardiac arrest was 5 to 10 min duration. The continuous brain cooling was carried out during the period of 10-30 min. Through the experiment, we have investigated vital signs, acid base balance, cardiac output, carotid arterial blood flow, oxygen availability of the brain tissue, and regional cerebral blood flow in both groups of CPR and CCPR . As for the clinical signs and cardiac output, there were no significant differences between two groups. Oxygen availability of the brain tissue and regional blood flow were much more improved in CCPR group than in CPR group. The brain was selectively cooled by means of the continuous brain cooling. This resulted in the minimum effect on circulatory and respiratory system as compared to the effects caused by general hypothermia. Furthermore, the continuous brain cooling decreased cerebral metabolism and CMRO2, and prevented a progressive development of cerebral hypoxia Cerebral perfusion at a given constant pressure may protect the brain tissue from the disturbance of cerebral microcirculation. Therefore, we might expect the continuous brain cooling to have a beneficial effect on cerebral respiration, circulation and metabolism.

The role of platelets and erythrocytes in disturbance of cerebral microcirculation (author's transl)

The mechanism of no-reflow phenomenon (NRP) is still in dispute. The present study was undertaken to evaluate the role of the intravascular component, i.e., platelets and red blood cells (RBC) in the post-ischemic period. Cerebral ischemia was induced in mechanically ventilated dogs by infusion of physiological saline into the cisterna magna at the pressure of 150-200 mmHg for 10-20 minutes. The local cortical CBF (1 CBF) was recorded with a double-needle type thermocouple. The systemic arterial pressure, cisterna magna pressure and cerebral impedance were also monitored. Blood samples were obtained from the superior sagittal sinus (SSS) and the femoral vein. The three dimensional changes of platelets and RBC were observed by scanning electron microscope and the platelet aggregability to ADP was recorded by Evans aggregometer. The course of 1 CBF was divided into two patterns in the post-ischemic period. In the first, reactive hyperemia was pronounced and in the second, it was only slight or none. In the latter group with apparent NRP, the changes of platelets and RBC were remarkable especially in the SSS. Platelets took the activated forms, i.e., pseudopod formation, spreading, surface folds and irreversible membrane fusion (platelet aggregation). Concerning RBC, discocytic shapes were transformed into echinocyte, keratocyte, schizocyte and so on, but no RBC aggregates were found. Platelet aggregability to ADP became lower after cerebral ischemia, being especially prominent in the no-reflow group. It is concluded that activation of platelet aggregability as well as the morphological change of platelets and RBC are induced by cerebral ischemia, both of which may contribute to the pathogenesis of no-reflow phenomenon.