Abstract

Major blood loss during cardiac surgery is associated with increased morbidity and mortality. Clinical pilot studies indicated that preoperative fibrinogen supplementation reduces postoperative blood loss without increasing thrombotic complications. However, an increase in fibrinogen concentration might rather aggravate pre-existing thrombosis than increase the incidence of thrombotic events. Therefore, we investigated, in the present study, whether fibrinogen supplementation influences (1) arterial thrombus formation, (2) the extent of myocardial infarction and (3) the cardioprotective effect of ischaemic preconditioning. Arterial thrombogenesis of the femoral artery was induced by topic FeCl3 treatment in anaesthetised Wistar rats after pretreatment with 60 mg/kg (Fiblow), 120 mg/kg (Fibhigh) or vehicle (Con). Vessel blood flow was monitored, and time to vessel occlusion was analysed as a marker for arterial thrombogenesis. In addition, regional myocardial I/R injury was induced by temporary left coronary artery occlusion in rats pretreated with or without fibrinogen supplementation. In additional groups, ischaemic preconditioning (IPC) was induced by 3 cycles of 5 min of ischaemia/reperfusion. In all groups, myocardial infarct size was determined by triphenyltetrazoliumchlorid staining. Arterial thrombogenesis was not affected by fibrinogen pretreatment. No differences in time until vessel occlusion between Con, Fiblow and Fibhigh groups were observed. In addition, fibrinogen supplementation in low and high concentrations had no effect on infarct size after regional myocardial ischaemia and reperfusion (Fiblow: 66 ± 10%, Fibhigh: 62 ± 9%; each ns vs. Con). IPC reduced infarct size from 62 ± 14% to 34 ± 12% (p < 0.05 vs. Con). Furthermore, both fibrinogen concentrations did not affect cardioprotection by ischaemic preconditioning (Fiblow + IPC: 34 ± 11%, Fibhigh + IPC: 31 ± 13%; each ns vs. IPC). Haemotherapy with fibrinogen did not affect arterial thrombogenesis, myocardial infarction and the cardioprotective effect of ischaemic preconditioning.

Highlights

  • Severe bleeding during cardiac surgery is associated with increased morbidity and mortality [1,2]

  • Fibrinogen supplementation in low and high concentrations had no effect on infarct size after regional myocardial ischaemia and reperfusion (Fiblow: 66 ± 10%, Fibhigh: 62 ± 9%; each ns vs. Con)

  • Fibrinogen levels were determined at baseline and after the surgical procedure, including thoracotomy and myocardial ischaemia/reperfusion injury in rats in vivo

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Summary

Introduction

Severe bleeding during cardiac surgery is associated with increased morbidity and mortality [1,2]. Patients with pre-existing ischaemic diseases such as perioperative myocardial infarction might be at risk following fibrinogen supplementation. Perioperative elevation in fibrinogen concentration may delay or diminish reperfusion of the ischaemic myocardium by extended thrombus formation due to increased coagulation or platelet linkage. Prophylactic treatment with fibrinogen could affect cardioprotection by ischaemic preconditioning (IPC), a setting in which the myocardium is protected against deleterious consequences of prolonged ischaemia and reperfusion by preceding short periods of myocardial ischaemia [11]. Therapeutic interventions to elevate the fibrinogen plasma concentration might counteract the anti-aggregatory effects of IPC, resulting in an attenuation of its cardioprotective potential. We hypothesised that haemotherapy with fibrinogen in the rat in vivo (1) promotes arterial thrombus formation and stability, (2) increases myocardial infarct size and (3) counteracts the cardioprotective potency of ischaemic preconditioning

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