The chemokine (C-X-C motif) receptor 4 inhibitor AMD3100 accelerates blood flow restoration in diabetic mice

Intracoronary thrombus resulting in acute myocardial ischemia can be lysed by thrombolytic agents, such as, streptokinase or t-PA. We examined the potential of a recombitant tissue-plasminogen activator (rt-PA)and a fibrin (ogen)-degradation productpentapeptide 6A, Ala-Arg-Pro-Ala-Lys, corresponding to aminoacids 43-47 in the BB-chain of fibrinogen, which causes marked increase in coronary blood flow and stimulates prostacyclin release, in restoring coronary blood flow in dqgs with experimentally-induced thrombus. An occlusive thrombus was created in the circumflex (Cx) coronary artery in 8 dcgs by electricalstimulation of the endothelial surface. The electrically-induced Cx thrombus consisted primarily of platelets and fibrin. After the occlusive thrcmbus was stable without electrical currant, rt-PA (10ug/kg/minute for 30 minutes intravenously)or peptide 6A (5 unoles/minute for 20 minutes intracorcnary) were randomly administered. Infusion of t-PA restored coronar blood flow (peak 22 ±12 ml/minute, mean ±SD) in five of seven animlas. The time to flow restoration was 12.3 ± 9.1 minutes and the reflow persistedfor20.0 ± 10.9 minutes. Peptide 6A administration also restored coronary blood flow (peak 20 ± 4 ml/ minute) in seven of eight animals with occlusive coronary thrombus. Mean time to blood flow restoration (4.3 ±2.9 minutes) wasshorter(P>0.05) than with rt-PA, but thereflow persisted only for the duration of tine infusion (16.3 ± 10.2 minutes).Peptide 6A adninistration was associatedwith a significant (P±0.05) increase in plasma 6-keto-PGF1α indicating stimulation of prostacyclin release. In addition, plasma t-PA concentrations also increased (F>0.01) at the peak effect of peptide 6A indicating releaseof endogenous t-PA as another potentialmechanism of the thrombolytic effects of peptide 6A. This study demonstrates that peptide 6A exerts coronary thrombolytic effectsccmpa rable to those of t-PA in a canine model of coronary thrombosis.

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Role of Delayed Neuroglial Activation in Impaired Cerebral Blood Flow Restoration Following Comorbid Injury

Cellular and Molecular Neurobiology ◽

10.1007/s10571-019-00735-y ◽

2019 ◽

Vol 40 (3) ◽

pp. 369-380 ◽

Cited By ~ 1

Author(s):

Zareen Amtul ◽

Jasmine Randhawa ◽

Abdullah N. Najdat ◽

David J. Hill ◽

Edith J. Arany

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Flow Restoration

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Prediction of cerebral blood flow restoration after extracranial-intracranial bypass surgery using superficial temporal artery duplex ultrasonography (STDU)

Acta Neurochirurgica Supplements - New Trends of Surgery for Stroke and its Perioperative Management ◽

10.1007/3-211-27911-3_26 ◽

2005 ◽

pp. 159-163 ◽

Cited By ~ 3

Author(s):

T. Inoue ◽

S. Fujimoto

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Bypass Surgery ◽

Superficial Temporal Artery ◽

Temporal Artery ◽

Duplex Ultrasonography ◽

Flow Restoration

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Plasmin-induced endothelium-dependent vasodilatation versus fibrinolysis — Two pathways of blood flow restoration in the thrombotically occluded vessels?

Fibrinolysis and Proteolysis ◽

10.1016/0268-9499(94)90267-4 ◽

1994 ◽

Vol 8 ◽

pp. 113-115 ◽

Cited By ~ 1

Author(s):

S.Y. Mashina ◽

G.V. Bashkov

Keyword(s):

Blood Flow ◽

Flow Restoration

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Microvascular remodeling and accelerated hyperemia blood flow restoration in arterially occluded skeletal muscle exposed to ultrasonic microbubble destruction

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00144.2004 ◽

2004 ◽

Vol 287 (6) ◽

pp. H2754-H2761 ◽

Cited By ~ 35

Author(s):

Ji Song ◽

Patrick S. Cottler ◽

Alexander L. Klibanov ◽

Sanjiv Kaul ◽

Richard J. Price

Keyword(s):

Skeletal Muscle ◽

Blood Flow ◽

Arterial Occlusion ◽

Pulsed Ultrasound ◽

Medial Region ◽

Lateral Region ◽

Microvascular Remodeling ◽

Flow Restoration ◽

Normal Rat ◽

Ultrasound Microbubbles

We showed previously that microbubble destruction with pulsed 1-MHz ultrasound creates a bioeffect that stimulates arteriogenesis and a chronic increase in hyperemia blood flow in normal rat muscle. Here we tested whether ultrasonic microbubble destruction can be used to create a microvascular remodeling response that restores hyperemia blood flow to rat skeletal muscle affected by arterial occlusion. Pulsed ultrasound (1 MHz) was applied to gracilis muscles in which the lateral feed artery was occluded but the medial feed artery was left intact. Control muscles were similarly occluded but did not receive ultrasound, microbubbles, or both. Hyperemia blood flow and number of smooth muscle (SM) α-actin-positive vessels, >30-μm arterioles, and capillaries per fiber were determined 7, 14, and 28 days after treatment. In ultrasound-microbubble-treated muscles, lateral region hyperemia blood flow was increased at all time points and restored to normal at day 28. The number of SM α-actin vessels per fiber was increased over control in this region at days 7 and 14 but decreased by day 28, when larger-diameter arterioles became more prevalent in the medial region. The number of capillaries per fiber was increased over control only at day 7 in the lateral region and only at days 7 and 14 in the medial region, indicating that the angiogenesis response was transient and likely did not contribute significantly to flow restoration at day 28. We conclude that ultrasonic microbubble destruction can be tailored to stimulate an arteriogenesis response that restores hyperemia blood flow to skeletal muscle in a rat model of arterial occlusion.

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