Attenuation of hypothermia-induced platelet activation and platelet adhesion to artificial surfaces in vitro by modification of hemoglobin to carry S-nitric oxide and polyethylene glycol.
Hypothermic cardiopulmonary bypass alters platelet function and hypothermia is associated with postoperative myocardial ischemia. Thrombogenic surfaces such as extracorporeal circuits, vascular graft materials, and components of atherosclerotic plaque induce activation of platelets. The effects of human hemoglobin (Hb) covalently modified to carry S-nitric oxide (NO) functional groups (SNO-Hb), polyethylene glycol (PEG-Hb), and SNO-PEG-Hb on platelet activation were studied. Platelet activation was assessed by cytometric analysis of GPIIb-IIIa activation and P-selectin expression at hypothermic condition (22 degrees C) after stimulation with Hb derivatives. Platelet adhesion and aggregation were measured in a parallel glass plate chamber coated with unmodified Hb, SNO-Hb, PEG-Hb, SNO-PEG-Hb, and collagen. Platelet binding of antibodies to GPIIb-IIIa and P-selectin was significantly enhanced by hypothermic condition and by unmodified Hb. There was significantly less platelet binding of antibodies to GPIIb-IIIa and P-selectin with SNO-Hb, PEG-Hb, and SNO-PEG-Hb compared with unmodified Hb. There was significantly less platelet attachment, adhesion, and aggregation on the SNO-Hb, PEG-Hb and SNO-PEG-Hb coated surfaces compared with unmodified Hb-coated and -uncoated surfaces. SNO-Hb, PEG-Hb, and SNO-PEG-Hb induced less platelet activation at hypothermic temperature, and induced less platelet adhesion and aggregation on thrombogenic surfaces compared with unmodified Hb. The inhibitory effect may be derived from antiadhesive properties of Hb, antiplatelet actions of NO, and molecular barrier action of PEG.
Fujii
H
H
Department of Anesthesiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Fujii
S
S
Togashi
H
H
Yoshioka
M
M
Nakai
K
K
Satoh
H
H
Sakuma
I
I
Kenmotsu
O
O
Kitabatake
A
A
D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D006454:Hemoglobins / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D007036:Hypothermia, Induced / Q000009:adverse effects*; D007700:Kinetics; D008297:Male; D009569:Nitric Oxide / Q000138:chemical synthesis / Q000494:pharmacology; D009603:Nitroso Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D013499:Surface Properties / Q000187:drug effects
D006454:Hemoglobins; D009603:Nitroso Compounds; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D009569:Nitric Oxide; D011092:Polyethylene Glycols