Quantitative studies on the influence of leukocytes on the vascular resistance in a skeletal muscle preparation

Braide, Magnus; Amundson, Björn; Chien, Shu; Bagge, U.

doi:10.1016/0026-2862(84)90064-5

Cited by 114 publications

(35 citation statements)

References 17 publications

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“…The 45% increase in WBC count (Table I) could contribute to a significant rise in microvascular resistance due to increased margination and adherence of leukocytes to the venular endothelium (34). Studies on WBC-endothelium adhesion in mesentery (cat) (35) have demonstrated a twofold increase in venular resistance attendant to adhesion induced by a chemoattractant, with washout times comparable with the time to attain Vpk found here.…”

Section: Discussionsupporting

confidence: 68%

Intravital microscopy of capillary hemodynamics in sickle cell disease.

Lipowsky¹,

Sheikh

Katz

1987

J. Clin. Invest.

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Crisis subjects exhibited a significantly depressed PORH with the ratio of peak red cell velocity to resting values reduced by 15% due to a loss of vasodilatory reserve, whereas crisis-free subjects exhibited a normal response. A 55% increase in the time to attain peak Vrbc was attributed to resistance increases, possibly resulting from red cell and leukocyte-to-endothelium adhesion during the induced ischemia.

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Section: Discussionsupporting

confidence: 68%

Intravital microscopy of capillary hemodynamics in sickle cell disease.

Lipowsky¹,

Sheikh

Katz

1987

J. Clin. Invest.

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“…Data from white blood cell perfusion studies on isolated muscle and kidney preparations show that leukocytes alone may obstruct the microcirculation under low-flow states, increasing the resistance by 30%. 27 This leukocyte capillary plugging also may be the major mechanism of the "no-reflow phenomenon." This phenomenon, first described in the CNS by Ames et al, 24 is defined as the incomplete restoration of normal blood flow after a period of ischemia.…”

Section: Discussionmentioning

confidence: 99%

Reduction of central nervous system ischemic injury in rabbits using leukocyte adhesion antibody treatment.

Clark

Madden

Rothlein

et al. 1991

Stroke

183

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Activated leukocytes appear to be directly involved in ischemic central nervous system injury. A surface glycoprotein (CD18) on the leukocyte is required for endothelial adherence and subsequent function and can be blocked with leukocyte adhesion antibody treatment. We used two animal models to determine the efficacy of anti-CD18 antibody treatment in preserving neurologic function after central nervous system ischemia. We gave a dose of 1 mg/kg anti-CD18 to treatment rabbits 30 minutes before inducing irreversible ischemia in the brain with intraarterial microspheres or in the spinal cord using reversible aortic occlusion. Treatment with anti-CD18 produced a significant reduction in neurologic deficits in the reversible spinal cord model, but not in the irreversible microsphere model. This protective effect supports the active role of leukocytes in central nervous system reperfusion ischemic injury and offers potential for future therapy. {Stroke 1991;22:877-883) T he appearance of leukocytes in injured ischemic tissue traditionally has been believed to represent a pathophysiologic response to existing injury. Recent evidence indicates they also may be important in the pathogenesis and extension of ischemic injury. "4 Two proposed mechanisms of leukocyte potentiation of ischemia are 1) microvascular occlusion from direct mechanical obstruction and cytotoxic effects on the endothelium, and 2) central nervous system (CNS) tissue infiltration and neuronal cytotoxic injury. "7 The leukocyte-mediated tissue damage may be irreversible even if blood flow is restored. Leukocyte adhesion is an early step in both of these mechanisms.Recent studies have identified a specific leukocyte membrane glycoprotein complex (CD 18) that is critically important for adherence. Monoclonal antibodies (anti-CD 18) to these glycoproteins have been Received October 1, 1990; accepted March 27, 1991. shown to inhibit adherence-dependent leukocyte functions in vitro. 89 In vivo studies using anti-CD18 have shown a reduction of ischemic injury and decreased leukocyte tissue infiltration in heart, lung, intestinal, and systemic shock models.10 -14 These data indicate that leukocyte endothelial adhesion is probably a critical early event in the process leading to neutrophil-mediated tissue reperfusion injury. To date, there have been no published studies using anti-CD 18 to reduce CNS ischemic injury. It is not known how the blood-brain barrier influences leukocyte adhesion and migration or if it would alter anti-CD 18 effects. Because neutrophil infiltratiori is present early in CNS ischemic injury, 15 -17 it is anticipated that leukocytes also will have a critical role in CNS ischemic injury. To test this hypothesis, we evaluated the therapeutic efficacy of anti-CD18 in two models of selective CNS ischemia in rabbits. These models were chosen to compare the treatment efficacy of anti-CD 18 in a reperfusion model versus an irreversible microemboli model. Materials and MethodsWe used male New Zealand White rabbits weighing 2-3 kg. We select...

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“…For example, in a skeletal muscle preparation with a buffer flow of 0.9 ml/min-100 g, infusion of 9x 10 6 leukocytes/100 g, which resulted in a circulating level of 9xlO 6 cells/ml, caused a 72% increase in precapillary resistance. 19 In the setting of myocardial ischemia and reperfusion, an incomplete return of blood flow has been observed. 13 In addition, granulocyte plugging of capillaries occurs in no-reflow capillaries after 1,3, or 5 hours of ischemia and reperfusion.…”

Section: Discussionmentioning

confidence: 99%

“…Circulation Research Vol 63, No 2, August 1988 resistance of the microcirculation of skeletal muscle 19 ; 3) granulocyte depletion during myocardial ischemia reduces microvascular resistance, edema, and arrhythmias 11 ; 4) intravital microscopy in heart muscle has shown mechanical obstruction of capillaries by granulocytes 12 ; 5) granulocytes cause a capillary noreflow phenomenon after myocardial ischemia and reperfusion 20 ; and 6) granulocytes can produce superoxides and initiate oxygen free-radical injury in the myocardium. 21 ' 22 Although myocardial ischemia activates the complement cascade and promotes localization of Clq and C3 to regions of ischemia, 1 • 2324 there is no information on the effect of C5a on granulocyte trapping in the coronary circulation, on coronary blood flow, or on myocardial function in the normal heart in vivo subjected to normal perfusion pressures.…”

mentioning

confidence: 99%

C5a decreases regional coronary blood flow and myocardial function in pigs: implications for a granulocyte mechanism.

Martin

Chenoweth

Engler

et al. 1988

Circulation Research

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Granulocytes cause some of the pathophysiological effects associated with the capillary no-reflow phenomenon during ischemia and in ischemia-reperfusion injury. However, no study has examined the consequences of in vivo granulocyte activation during normal perfusion pressures. In this study, we examined the effects of intracoronary administration of the complement component C5a, which is known to be a potent granulocyte activating factor. Nine open-chest, anesthetized pigs were instrumented to monitor regional coronary blood flow and segment shortening, left ventricular dP/dt, heart rate, and pulmonary artery and aortic blood pressures and to sample arterial and regional coronary venous blood for oxygen content and complete blood counts. Intracoronary infusion of human or porcine C5a in doses ranging from 10 to 500 ng produced a significant reduction in regional coronary blood flow and myocardial function. Although perfusion pressure and heart rate remained constant, venous oxygen content fell, indicating an imbalance between myocardial oxygen supply and demand. In addition, the arteriovenous difference of white blood cells was increased significantly after anaphylatoxin infusion, indicating intravascular trapping in the myocardium. Granulocytes accounted entirely for the differences in leukocyte counts because no significant changes in platelet, lymphocyte, or hematocrit levels were observed. Injection of vehicle alone did not alter any of the monitored variables. Serial sampling indicated that granulocyte extraction was increased before the reductions in coronary blood flow and myocardial function and that all effects of C5a had resolved within 2 minutes of injection. In separate studies, we examined the effects of C5a on isolated epicardial coronary arteries (750-1,000 fim diameter) of pigs. There was no vasoconstriction after exposure to C5a in buffer or in whole blood. These studies indicate that, in the presence of normal perfusion pressures, C5a activation of granulocytes results in intravascular trapping in the myocardium. Furthermore, coronary blood flow is decreased to the extent that an imbalance between myocardial oxygen supply and demand occurs, resulting in impairment of myocardial function. (Circulation Research 1988:63:483-491)

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Quantitative studies on the influence of leukocytes on the vascular resistance in a skeletal muscle preparation

Cited by 114 publications

References 17 publications

Intravital microscopy of capillary hemodynamics in sickle cell disease.

Intravital microscopy of capillary hemodynamics in sickle cell disease.

Reduction of central nervous system ischemic injury in rabbits using leukocyte adhesion antibody treatment.

C5a decreases regional coronary blood flow and myocardial function in pigs: implications for a granulocyte mechanism.

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