Carbon monoxide releasing molecule-2 enhances coagulation in rat and rabbit plasma

Nielsen, Vance G.; Huneke, Richard B.; Khan, Ejaz

doi:10.1097/mbc.0b013e3283380c88

Cited by 8 publications

(12 citation statements)

References 6 publications

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“…Subsequent investigations that assessed changes in plasma kinetics in vitro and in vivo, were conducted to determine if CO exposure changed coagulation in various preclinical animal models [67][68][69][70]. Of interest, CO enhanced coagulation and attenuated fibrinolysis in rat, rabbit and horse plasma [67][68][69][70].…”

Section: In Vitro and Preclinical Evidence That Co Is A Procoagulant mentioning

confidence: 99%

“…Of interest, CO enhanced coagulation and attenuated fibrinolysis in rat, rabbit and horse plasma [67][68][69][70]. Further, using a sedated rabbit model measuring ear bleeding times, it was determined that intravenous administration of CORM-2 (10 mg/kg) reduced bleeding time to normal values in a model of aspirin/clopidogrel induced platelet inhibition [68].…”

Section: In Vitro and Preclinical Evidence That Co Is A Procoagulant mentioning

confidence: 99%

“…4), with methods used to generate these images as previously cited [84][85][86]. Considered together, these investigations involved conditions or disease states wherein increased CO would be expected to be present, resulting in thrombus ultrastructure (e.g., finer or matted fibers) consistent with enhanced clot strength demonstrated in vitro [48,[51][52][53][54][55][56][57]67,68,[70][71][72][73][74][75][76] or in vivo [68,69] following CO exposure.…”

Section: Ultrastructural Findings Supporting a Procoagulant Role For Comentioning

confidence: 99%

“…Platelets appear to respond to CO in a similar fashion among human and rodent studies [10][11][12]16,21,22], but plasmatic coagulation also appears to be enhanced in humans, rats and rabbits [48,[51][52][53][54][55][56][57][58][67][68][69]. In an effort to reveal potential sources of specie specific differences, one may consider the differences in thrombus ultrastructure between humans, rabbits, mice and rats [94,95].…”

Section: A Possible Species-specific Explanation Of Disparate Hemostamentioning

confidence: 99%

“…There is evidence that excessive CO exposure may result in decreased in vivo and in vitro hemostasis in humans and rodents [4][5][6][7][8][18][19][20][21][22][23], potentially by inhibition of platelet aggregation [9][10][11][12][13]15,16,[20][21][22][23]. However, there is also evidence that increased CO exposure can enhance platelet activation [14,17] and cause enhanced coagulation/decreased fibrinolysis in humans and other mammalian species [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][67][68][69][70]…”

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confidence: 99%

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Carbon monoxide: Anticoagulant or procoagulant?

Nielsen

Pretorius

2014

Thrombosis Research

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Within the past decade there have been several investigations attempting to define the impact of exogenous and endogenous carbon monoxide exposure on hemostasis.Critically, two bodies of literature have emerged, with carbon monoxide mediated platelet inhibition cited as a cause of in vitro human and in vitro/in vivo rodent anticoagulation. In contrast, interaction with heme groups associated with fibrinogen, α 2 -antiplasmin and plasmin by carbon monoxide has resulted in enhanced coagulation and decreased fibrinolysis in vitro in human and other species, and in vivo in rabbits. Of interest, the ultrastructure of platelet rich plasma thrombi demonstrates an abnormal increase in fine fiber formation and matting that are obtained from humans exposed to carbon monoxide.Further, thrombi obtained from humans and rabbits have very similar ultrastructures, whereas mice and rats have more fine fibers and matting present. In sum, there may be

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Section: In Vitro and Preclinical Evidence That Co Is A Procoagulant mentioning

confidence: 99%

Section: In Vitro and Preclinical Evidence That Co Is A Procoagulant mentioning

confidence: 99%

Section: Ultrastructural Findings Supporting a Procoagulant Role For Comentioning

confidence: 99%

Section: A Possible Species-specific Explanation Of Disparate Hemostamentioning

confidence: 99%

mentioning

confidence: 99%

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Carbon monoxide: Anticoagulant or procoagulant?

Nielsen

Pretorius

2014

Thrombosis Research

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Comparison of the effects of CORM-2, CORM-3 and CORM-A1 on coagulation in human plasma

Nielsen

Garza

2014

Blood Coagulation &Amp; Fibrinolysis

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Carbon monoxide derived from the catalytic action of heme oxygenase-1 or carbon monoxide-releasing molecules (CORMs) has been found to potentially be an anticoagulant or procoagulant agent. Of interest, two water-soluble CORMs, CORM-3 and CORM-A1, recently became commercially available. Thus, the purpose of the present study was to assess and compare the effects of the previously well studied CORM-2 to the effects of CORM-3 and CORM-A1 on coagulation in citrated human plasma with thrombelastography. Plasma exposed to CORMs was incubated at 37°C for at least one carbon monoxide release half-time, and then tissue factor-activated coagulation was commenced with calcium addition. CORM-2 and CORM-3 enhanced the velocity of clot formation and thrombus strength in a similar manner, whereas CORM-A1 did not affect coagulation. However, CORM-A1 did diminish tissue-type plasminogen activator initiated fibrinolysis. The similarity in effect on coagulation by CORM-2 and CORM-3 was likely secondary to the relatively inert effect of their ruthenium-containing carrier molecule, whereas the boron-containing CORM-A1 may have had no effect secondary to boron binding to fibrinogen, preventing carbon monoxide-mediated changes in fibrinogen protein structure via attached heme group(s). Future investigations with CORMs should have special attention to confounding effects of the carrier molecule.

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Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits

Nielsen¹,

Chawla²,

Mangla³

et al. 2011

Blood Coagulation &Amp; Fibrinolysis

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Administration of carbon monoxide derived from carbon monoxide-releasing molecules has been demonstrated to enhance coagulation in vitro at small concentrations (100-200 μmol/l) in human and rabbit plasma. We sought to determine if carbon monoxide-releasing molecule-2 [tricarbonyldichlororuthenium (II) dimer, CORM-2] would improve coagulation in rabbit plasma in vitro via thrombelastography and in an in vivo preclinical rabbit model of ear bleeding time following administration of clopidogrel (20 mg/kg) with aspirin (10 mg/kg) via gavage. Addition of 100 μmol/l CORM-2 to rabbit plasma significantly improved coagulation. This procoagulant effect was blocked by pre-exposure of plasma to an agent that converts hemefibrinogen to methemefibrinogen in human plasma, preventing carbon monoxide binding and enhancement of coagulation. Rabbit ear bleeding time was 5.8 ± 1.1 min 2-3 h after clopidogrel/aspirin administration. Bleeding time significantly decreased to 2.6 ± 0.6 min, 5 min after administration of CORM-2 (10 mg/kg; 279 μmol/l 'best-case' instantaneous concentration) intravenously. CORM-2 enhances plasmatic coagulation in a manner similar to that of human plasma in vitro, and plasmatic coagulation is enhanced in vivo by CORM-2 as well. Additional preclinical investigation of the effects of CORM-2 on coagulopathy (e.g. heparin or hemodilution mediated) utilizing this rabbit model is planned.

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Carbon monoxide releasing molecule-2 enhances coagulation in rat and rabbit plasma

Cited by 8 publications

References 6 publications

Carbon monoxide: Anticoagulant or procoagulant?

Carbon monoxide: Anticoagulant or procoagulant?

Comparison of the effects of CORM-2, CORM-3 and CORM-A1 on coagulation in human plasma

Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits

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