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(Circulation. 1996;93:327-332.)
© 1996 American Heart Association, Inc.

Articles

Enhancement of Platelet Deposition by Cross-Linked Hemoglobin in a Rat Carotid Endarterectomy Model

Stephen B. Olsen, MD; Douglas B. Tang, PhD; Mark R. Jackson, MD; Edward R. Gomez, MD; Benjamin Ayala; Barbara M. Alving, MD

From the Department of Hematology and Vascular Biology, the Department of Biometrics and Statistics, Walter Reed Army Institute of Research, and the Peripheral Vascular Surgery Service, Walter Reed Army Medical Center, Washington, DC.

Correspondence to Barbara Alving, MD, Chief, Department of Hematology and Vascular Biology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.

Background Purified human cross-linked hemoglobin, which is now being used in clinical trials, increases mean arterial pressure through binding of nitric oxide (NO). We postulated that binding of NO by cross-linked hemoglobin (Hb) could also increase platelet deposition at sites of subintimal injury.

Methods and Results Male Sprague-Dawley rats were infused with Hb (0.88 g/kg, n=8) or with the NO synthase inhibitor N^G-monomethyl-L-arginine (L-NMMA, 30 mg/kg, n=7) before undergoing microsurgical carotid endarterectomy. ¹¹¹In-labeled platelets were infused after endarterectomy, and platelet deposition was measured 20 minutes later. In control endarterectomized rats (n=8), mean platelet deposition was 7.7±0.7x10⁶/mm². Platelet deposition was significantly increased above controls in rats that received Hb (13.2±0.9x10⁶/mm², P=.0004) and in rats infused with L-NMMA (13.9±1.0x10⁶/mm², P=.0002). The increase was prevented by infusion of L-arginine (150 mg/kg) immediately after Hb or L-NMMA. To determine whether aspirin (ASA) blocked the increased deposition induced by Hb, rats received oral ASA (10 mg/kg) 18 hours before endarterectomy. Platelet deposition in animals receiving ASA alone was 6.4±0.9x10⁶/mm² (n=8). This was significantly increased to 10.8±0.8x10⁶/mm² (P=.002) for the ASA-treated group that received Hb at the time of endarterectomy (n=8). The prolonged bleeding times induced by ASA were unaffected by the infusion of Hb.

Conclusions These data suggest that in a rat endarterectomy model, Hb increases platelet deposition at sites of subintimal injury by binding NO. Increased deposition induced by Hb can be prevented by administration of L-arginine but not by pretreatment with aspirin.

Key Words: hemoglobin • nitric oxide • platelets • surgery

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