Depression of Collateral Blood Flow Following Arterial Thrombosis

SummaryPermanent ligation of the feline aorta at the iliac bifurcation is followed by rapid opening of pre-existing collateral blood vessels. However, if ligation is combined with formation of a clot, these protective collateral vessels do not function. This study was undertaken to determine if drugs which alter serotonin function can improve collateral blood flow after arterial thrombosis. Permanent ligations were placed at the iliac bifurcation, circumflex iliac and sixth lumbar arteries in all cats. A clot was produced in the aorta of 27 cats by injection of 0.1 ml of thromboplastin. Ligated clot-occluded cats were untreated (10); had blood serotonin depleted using a single dose of reserpine (0.1 mg/kg i. m.) followed by para-chlorophenylanine (p-CPA) (100 mg/kg orally) every 3 days (9) ; or were treated prior to surgery with a serotonin antagonist cinanserin HC1 (4 mg/kg i. v.) (8). Control cats (18) were acutely ligated. 9 of these cats were untreated, 5 were cinanserin HC1-treated, and 4 were reserpine/p-CPA-treated. Extent of collateral development was assessed by aortograms 3 days after occlusion and by neurologic rating. Aortograms of acutely ligated cats indicated a significant collateral blood flow around the segment of ligated aorta, while ligated clot-occluded cats had a severely depressed hind-limb perfusion. Reserpine/p-CPA-treated ligation clot-occluded cats had aortograms similar to acutely ligated cats. The cinanserin HC1-treated ligation clot-occluded cats had aortograms which indicated hind-limb perfusion was not as adequate as the acutely ligated cats. However, the perfusion of these animals was improved over untreated ligation clot-occluded cats. Neurologic rating correlated with aortograms. These results suggest: 1) the clinical consequences of arterial thrombosis cannot be entirely attributed to mechanical occlusion of an artery, but may be due to depression of protective collateral blood flow induced by thrombosis, 2) serotonin is an important factor in this depression of collateral blood flow, and 3) isolation of the factors responsible for collateral inhibition could permit the development of therapeutic interventions.

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Depression of Collateral Blood Flow Following Arterial Thrombosis

10.1055/s-0039-1680605 ◽

1977 ◽

Author(s):

R.G. Schaub ◽

K.M. Meyers

Keyword(s):

Blood Flow ◽

Arterial Thrombosis ◽

Collateral Circulation ◽

Therapeutic Interventions ◽

Collateral Blood Flow ◽

Flow Measurements ◽

Clinical Consequences ◽

Blood Flow Measurements ◽

Collateral Vessels ◽

Iliac Bifurcation

Permanent ligation of the feline aorta at the iliac bifurcation is followed by rapid opening of pre-existing collateral blood vessels. However, if ligation is combined with formation of a clot these protective collateral vessels do not function. This study was undertaken to determine if drugs which alter serotonin (5-HT) function can improve collateral blood flow after arterial thrombosis. Permanent ligations were placed at the iliac bifurcation, circumflex iliac and sixth lumbar arteries in all cats. Control cats (8) were acutely ligated. In all other cats a clot was produced in the aorta by injection of 0.1 ml of thromboplastin. Clotted cats were untreated (8); had blood 5-HT depleted using a single dose of reserpine (0.1 mg/kg i.m.) followed by para-chlorophenylalanine (p-CPA) (100 mg/kg orally) every 3 days (9); or were treated prior to surgery with a 5-HT antagonist cinanserin HCl (4 mg/kg i.v.) (8). Collateral circulation was determined by blood flow measurements and aortograms 3 days after occlusion of the aorta. The hindlimb blood flow of untreated clotted animals was 20% of the acutely ligated control animals 3 days following aortic occlusion. However, hindlimb blood flow was 90% of control in reserpine and p-CPA treated cats and 60% of control in cinanserin HCl treated cats. Blood flow measurements correlated with aortograms. These results suggest: (1) The clinical consequences of arterial thrombosis cannot be entirely attributed to mechanical occlusion of an artery, but may be due to depression of protective collateral blood flow induced by thrombosis, (2) Serotonin is an important factor in this depression of collateral blood flow, and (3) Isolation of the factors responsible for collateral inhibition could permit the development of therapeutic interventions.

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Inhibitory effect of cardiac contraction on coronary collateral blood flow

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1977.233.5.h541 ◽

1977 ◽

Vol 233 (5) ◽

pp. H541-H546 ◽

Cited By ~ 3

Author(s):

R. E. Russell ◽

R. W. Chagrasulis ◽

J. M. Downey

Keyword(s):

Blood Flow ◽

Left Coronary Artery ◽

Constant Pressure ◽

Inhibitory Effect ◽

Cardiac Contraction ◽

Collateral Blood Flow ◽

Ischemic Region ◽

Perfusion Apparatus ◽

Collateral Vessels ◽

Coronary Collateral Blood Flow

The present study was undertaken to determine the effect of contraction on overall flow in an area supplied by collateral vessels. Changes in the distribution of blood flow across the wall of ischemic and normally perfused regions of the left ventricle were observed during normal beating and during vagal arrest. The main left coronary artery was cannulated and perfused at constant pressure (125 mmHg) using a servo pump apparatus. An ischemic area supplied by collaterals was created by ligating the left anterior descending artery. Radiomicrospheres (15 micrometer) were injected into the perfusion apparatus during beating. Then spheres with a different label were administered to the same heart during arrest. The results revealed that beating caused a gradient of blood flow inhibition from near zero at the epicardium to about 50% at the endocardium in both zones. Inhibition to flow at the mid wall of the ischemic zone, 71%, was significantly greater than that seen at the corresponding depth in the normally perfused region, 33%. These results indicate that contraction not only inhibits collateral blood flow to an ischemic region, but also that the inhibition is actually magnified at the mid wall.

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Vasomotor responses of newly developed coronary collateral vessels

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1996.271.2.h490 ◽

1996 ◽

Vol 271 (2) ◽

pp. H490-H497 ◽

Cited By ~ 2

Author(s):

J. W. Kinn ◽

J. D. Altman ◽

M. W. Chang ◽

R. J. Bache

Keyword(s):

Nitric Oxide ◽

Blood Flow ◽

Coronary Artery ◽

Retrograde Flow ◽

Collateral Blood Flow ◽

Coronary Collateral ◽

Retrograde Blood Flow ◽

Vasomotor Activity ◽

Collateral Vessels ◽

Oxide Synthase

Well-developed coronary collateral vessels contain an abundant muscular media and can undergo active vasomotion. However, early after coronary occlusion, coronary collateral vessels are thin walled with little smooth muscle, suggesting that vasomotor capability might be limited. Consequently, this study determined whether newly developed coronary collateral vessels have active vasomotor activity and whether endothelial function in these newly developed vessels is impaired. Retrograde blood flow was measured as an index of coronary collateral blood flow approximately 2 wk after embolic occlusion of the anterior descending coronary artery of dogs. Agonists were administered into the left main coronary artery to reach collaterals originating from the left coronary system. Baseline retrograde blood flow was 25.1 +/- 2.7 ml/min and increased to 36.7 +/- 3.7 ml/min after nitroglycerin (6 micrograms.kg-1.min-1, P < 0.05). Cyclooxygenase blockade with indomethacin (5 mg/kg i.v.) decreased retrograde collateral blood flow to 16.8 +/- 2.3 ml/min (P <a 0.05). Subsequent administration of acetylcholine increased retrograde flow to 29.4 +/- 3.7 ml/min (P < 0.05), indicating intact endothelium-mediated vasodilation. Inhibition of nitric oxide synthase with NG-nitro-L-arginine further decreased coronary collateral retrograde flow to 12.0 +/- 2.8 ml/min (P < 0.05) and markedly blunted the response to acetylcholine. These findings demonstrate substantial vasomotor capability even early during coronary collateral development and indicate that both nitric oxide and cyclooxygenase-dependent endothelial mechanisms are intact.

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Improvement of Collateral Circulation after Arterial Thrombosis with Indomethacin Therapy

Thrombosis and Haemostasis ◽

10.1055/s-0038-1650086 ◽

1980 ◽

Vol 44 (02) ◽

pp. 069-071 ◽

Cited By ~ 4

Author(s):

Cecelia Helenski ◽

Robert G Schaub ◽

Royce Roberts

Keyword(s):

Blood Flow ◽

Platelet Activation ◽

Arterial Thrombosis ◽

Collateral Circulation ◽

Thromboxane A2 ◽

Collateral Flow ◽

Collateral Blood Flow ◽

Vasoactive Substance ◽

Aortic Thrombosis ◽

Platelet Counts

SummaryWe compared development of feline hindlimb collateral circulation and coagulation changes 3 hours following aortic thrombosis in five non-treated and five indomethacin treated (20 mg/kg) cats. Coagulation changes were monitored with the one stage prothrombin time (OSPT), partial thromboplastin time (PTT), protamine sulfate dilution test for fibrin monomer (PSD), and platelet counts. Collateral circulation was assessed with aortograms. Significant changes in coagulation parameters with the exception of platelet counts were not observed in either group. Platelet counts of non-treated cats were reduced to 63 ± 5% of control while platelet counts of treated cats were 96 ± 3% of control. Aortograms of non-treated cats indicated poor hindlimb perfusion around the thrombus, while aortograms of indomethacin treated animals indicated significant blood flow to the hindlimbs through collateral channels. These results support a role for the platelet in post thrombosis vasospasms and suggest that anti-platelet therapy could have positive effects in reducing the extent of ischemic damage which follows arterial thrombosis.Several studies, using cat and dog models, have demonstrated a significant reduction of collateral blood flow can occur following formation of an occlusive arterial thrombus (1–5). The collateral flow which developed after thrombosis was significantly less than when occlusion was accomplished with mechanical methods such as ligation (1, 3, 4). This suggested the presence of a thrombus produced effects on blood vessels more complex than simple mechanical obstruction. Imhoff originally suggested that the inhibition of collateral flow which followed thrombosis was related to the release or formation of a vasoactive substance which would induce constriction of collateral source or re-entry vessels (1). Butler, in later studies, suggested that it was serotonin which was responsible for the post thrombosis inhibition of collateral blood flow (2). The involvement of serotonin would seem logical, since the majority of blood serotonin is found in the platelet (6), is released upon platelet activation (7-9), and is a potent vasoconstrictor (10). A mechanism for serotonin involvement has proposed that the platelets in the flowing blood come into contact with the thrombus, are activated and release serotonin (2–4). Consideration of the biochemistry of platelet activation makes it apparent that serotonin is neither the only nor the most powerful vasoactive substance released by the platelet. Thromboxane A2 (TxA) is a critical substance in the activation, release, and aggregation of platelets (11, 12, 13). Thromboxane A2 is a particularly powerful vasoconstrictor which would be a more likely candidate to produce the type of long lasting vasospasm necessary to reduce collateral flow in the post thrombosis state (11, 12, 13). The relationship between thromboxane A2 and serotonin is suggested by recent studies which demonstrate that serotonin can initiate thromboxane A2 release from canine and feline platelets (14). Therefore, serotonin could be an intermediate mechanism in the process of collateral inhibition.If this hypothesis is correct, then inhibition of TxA synthesis should prove as beneficial in improving collateral flow after thrombosis as serotonin antagonists. To test this hypothesis we examined the effect of indomethacin treatment on development of collateral circulation following aortic thrombosis. Indomethacin is a non-steroidal, anti-inflammatory drug which inhibits cyclooxygenase, the major enzyme in the PG and TxA synthetic pathway (15–19).

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