Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-17T11:38:19.320Z Has data issue: false hasContentIssue false
  • English
  • Français

Abrupt oxygen decrease influences thrombosis and bleeding in stenosed and endothelium-injured rabbit carotid arteries

Published online by Cambridge University Press:  01 December 2008

J. Dellamonica ,
E. Mazoyer ,
J. P. Rosa ,
F. Cymbalista  and
ChM. Samama
J. Dellamonica
Affiliation:
Avicenne University Hospital, Department of Anaesthesiology and Intensive Care, Bobigny, Paris, France
E. Mazoyer
Affiliation:
Avicenne University Hospital, Laboratory of Haematology, Bobigny, Paris, France
J. P. Rosa
Affiliation:
Avicenne University Hospital, Lariboisière Hospital, INSERM U689, Paris, France
F. Cymbalista
Affiliation:
Avicenne University Hospital, Laboratory of Haematology, Bobigny, Paris, France
ChM. Samama*
Affiliation:
Avicenne University Hospital, Department of Anaesthesiology and Intensive Care, Bobigny, Paris, France Avicenne University Hospital, Lariboisière Hospital, INSERM U689, Paris, France
*
Correspondence to: Charles Marc Samama, Department of Anaesthesiology and Intensive Care, Hotel-Dieu University Hospital 1, place du Parvis de Notre-Dame, 75181 Paris Cedex 04, France. E-mail: marc.samama@htd.aphp.fr; Tel: +33 1 42 34 85 51; Fax: +33 1 42 34 89 60
Get access

Summary

Background and objective

Blood oxygen concentration decrease may be associated with haemostatic impairments. We aimed to study the effect of oxygen decrease in a rabbit model of thrombosis and bleeding.

Methods

A total of 44 rabbits were anaesthetized, ventilated and monitored for blood pressure, blood arterial gas, temperature and carotid blood flow. The Folts model was used: a stenosis (75%) and an injury were carried out on the carotid artery, inducing thrombosis. Blood flow decreased as thrombus size increased until the pressure gradient was such that the thrombus was released and local arterial blood flow was suddenly restored. This is known as a cyclic flow reduction. After counting baseline cyclic flow reductions during a 20-min period (P1), rabbits were randomized blindly to one of three groups: hyperoxic, FiO2=100%; normoxic, FiO2 was decreased to obtain a PaO2 between 80 and 120 mmHg; hypoxic, PaO2 < 80 mmHg. Then CFRs were recorded over a second 20-min period (P2). At the end of the experiment, a hepatosplenic section was done and the amount of blood loss was recorded. After each period, the following parameters were measured: blood gas, ear-immersion bleeding time, haemoglobin, platelet count, prothrombin time, activated partial thromboplastin time and fibrinogen.

Results

Oxygen decrease during hypoxic and normoxic periods was associated with a decrease in cyclic flow reductions. Bleeding time increased in the hypoxic group unless hepatosplenic bleeding remained stable. A slight increase in activated partial thromboplastin time was observed in the normoxic and hypoxic groups.

Conclusion

An abrupt decrease in oxygen administration was responsible for an antithrombotic effect. Increase in bleeding time occurred during hypoxia. No clinically relevant variation of any haemostasis parameters was observed.

Keywords

CAROTID ARTERY THROMBOSISHAEMORRHAGEPLATELET AGGREGATIONOXYGENATIONHYPOXIARABBIT
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 12 , December 2008 , pp. 1002 - 1008
Copyright
Copyright © European Society of Anaesthesiology 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Kietzmann, T, Roth, U, Jungermann, K. Induction of the plasminogen activator inhibitor-1 gene expression by mild hypoxia via a hypoxia response element binding the hypoxia-inducible factor-1 in rat hepatocytes. Blood 1999; 94: 4177–4185.CrossRefGoogle Scholar
2.Leo, R, Pratico, D, Iuliano, L et al. Platelet activation by superoxide anion and hydroxyl radicals intrinsically generated by platelets that had undergone anoxia and then reoxygenated. Circulation 1997; 95: 885–891.CrossRefGoogle ScholarPubMed
3.Pinsky, DJ, Liao, H, Lawson, CA et al. Coordinated induction of plasminogen activator inhibitor-1 (PAI-1) and inhibition of plasminogen activator gene expression by hypoxia promotes pulmonary vascular fibrin deposition. J Clin Invest 1998; 102: 919–928.CrossRefGoogle ScholarPubMed
4.Lehmann, T, Mairbäurl, H, Pleisch, B, Maggiorini, M, Bärtsch, P, Reinhart, WH. Platelet count and function at high altitude and in high-altitude pulmonary edema. J Appl Physiol 2006; 100: 690–694.CrossRefGoogle ScholarPubMed
5.Folts, JD, Crowell, EB Jr, Rowe, GG. Platelet aggregation in partially obstructed vessels and its elimination with aspirin. Circulation 1976; 54: 365–370.CrossRefGoogle ScholarPubMed
6.Samama, CM, Bonnin, P, Bonneau, M et al. Comparative arterial antithrombotic activity of clopidogrel and acetyl salicylic acid in the pig. Thromb Haemost 1992; 68: 500–505.Google ScholarPubMed
7.Ouaknine-Orlando, B, Samama, CM, Riou, B et al. Role of the hematocrit in a rabbit model of arterial thrombosis and bleeding. Anesthesiology 1999; 90: 1454–1461.CrossRefGoogle Scholar
8.Delaporte-Cerceau, S, Samama, CM, Riou, B, Bonnin, P, Guillosson, JJ, Coriat, P. Ketorolac and enoxaparin affect arterial thrombosis and bleeding in the rabbit. Anesthesiology 1998; 88: 1310–1317.CrossRefGoogle ScholarPubMed
9.Golino, P, Ragni, M, Cirillo, P et al. Effects of recombinant active site-blocked activated factor VII in rabbit models of carotid stenosis and myocardial infarction. Blood Coagul Fibrinolysis 2000; 11 (Suppl. 1): S149–S158.Google ScholarPubMed
10.Fattorutto, M, Tourreau-Pham, S, Mazoyer, E et al. Recombinant activated factor VII decreases bleeding without increasing arterial thrombosis in rabbits. Can J Anaesth 2004; 51: 672–679.CrossRefGoogle ScholarPubMed
11.Yan, SF, Mackman, N, Kisiel, W, Stern, DM, Pinsky, DJ. Hypoxia/hypoxemia-induced activation of the procoagulant pathways and the pathogenesis of ischemia-associated thrombosis. Arterioscler Thromb Vasc Biol 1999; 19: 2029–2035.CrossRefGoogle ScholarPubMed
12.Oude Egbrink, MG, Tangelder, GJ, Slaaf, DW, Weijmer-van Velzen, S, Reneman, RS. Influence of hypercapnia and hypoxia on rabbit platelet aggregation. Thromb Res 1990; 57: 863–875.CrossRefGoogle ScholarPubMed
13.Kerry, PJ, Paton, CJ. Increased sensitivity of arachidonic acid-induced platelet aggregation in the presence of carbon dioxide. Br J Pharmacol 1984; 81: 125–130.CrossRefGoogle ScholarPubMed
14.Michelson, AD, MacGregor, H, Barnard, MR, Kestin, AS, Rohrer, MJ, Valeri, CR. Reversible inhibition of human platelet activation by hypothermia in vivo and in vitro. Thromb Haemost 1994; 71: 633–640.Google ScholarPubMed
15.Toff, WD, Jones, CI, Ford, I et al. Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation. JAMA 2006; 295: 2251–2261. Erratum in: JAMA 2006; 296: 46.CrossRefGoogle ScholarPubMed
16.Marret, E, Bonnin, P, Mazoyer, E et al. The effects of a polymerized bovine-derived hemoglobin solution in a rabbit model of arterial thrombosis and bleeding. Anesth Analg 2004; 98: 604–610.CrossRefGoogle Scholar
17.Postma, S, Emara, M, Obaid, L, Johnson, ST, Bigam, DL, Cheung, PY. Temporal platelet aggregatory function in hypoxic newborn piglets reoxygenated with 18%, 21%, and 100% oxygen. Shock 2007; 27: 448–454.CrossRefGoogle ScholarPubMed
18.Ikeda, H, Koga, Y, Oda, T et al. Free oxygen radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured canine coronary arteries. J Am Coll Cardiol 1994; 24: 1749–1756.CrossRefGoogle ScholarPubMed
19.Thom, SR, Fisher, D, Stubbs, JM. Platelet function in humans is not altered by hyperbaric oxygen therapy. Undersea Hyperb Med 2006; 33: 81–83.Google Scholar
20.Dube, B, Das, BK, Kolindewala, JK, Dube, RK, Bhargava, V. Hemostatic changes in neonates with anoxia and sepsis. Indian Pediatr 1989; 26: 26–31.Google ScholarPubMed
21.Fink, T, Kazlauskas, A, Poellinger, L, Ebbesen, P, Zachar, V. Identification of a tightly regulated hypoxia-response element in the promoter of human plasminogen activator inhibitor-1. Blood 2002; 99: 2077–2083.CrossRefGoogle ScholarPubMed
22.Liao, H, Hyman, MC, Lawrence, DA, Pinsky, DJ. Molecular regulation of the PAI-1 gene by hypoxia: contributions of Egr-1,HIF-1alpha, and C/EBPalpha. FASEB J 2007; 21: 935–949.CrossRefGoogle Scholar
23.Vogel, JA, Hartley, LH, Cruz, JC, Hogan, RP. Cardiac output during exercise in sea-level residents at sea level and high altitude. J Appl Physiol 1974; 36: 169–172.CrossRefGoogle ScholarPubMed