Effect of mechanical ventilation on carotid artery thrombosis induced by photochemical injury in mice

Abstract

Increasing use of transgenic and gene targeting techniques for the investigation of hemostasis and vascular biology has generated interest in experimental models of carotid artery thrombosis in mice. We tested the hypothesis that hypoventilation in anesthetized mice may cause hypercapnia, increased carotid artery blood flow, and altered thrombotic responses to photochemical injury of the carotid artery. Arterial blood gases and carotid artery blood flow were measured in pentobarbital-anesthetized BALB/c or C57BL/6 J mice with and without mechanical ventilation. Photochemical injury of the carotid artery was induced using the rose bengal method. Compared with ventilated mice, unventilated mice had a 45% increase in carotid artery blood flow (0.74 +/- 0.04 vs. 0.41 +/- 0.03 mL min-1; P < 0.001) that was associated with an elevation of arterial PCO2 (58 +/- 4 vs. 33 +/- 4 mmHg; P < 0.05) and a decrease in arterial pH (7.18 +/- 0.05 vs. 7.32 +/- 0.03; P < 0.05). Time to first occlusion of the carotid artery after photochemical injury was shorter in ventilated than in unventilated mice (29 +/- 6 vs. 73 +/- 9 min; P < 0.001). Time to stable occlusion was also shorter in ventilated mice (49 +/- 8 vs. 81 +/- 6 min; P < 0.05). Elevated carotid artery blood flow, hypercarbic acidosis, and prolonged occlusion times also were observed in mice ventilated with supplemental carbon dioxide. General anesthesia without mechanical ventilation has the potential to confound studies of experimental thrombosis in vivo by producing hypoventilation, hypercapnia, acidosis, and altered carotid artery blood flow. Mechanical ventilation with maintenance of normal blood gases may enhance the physiological insight gained from experimental models of carotid artery thrombosis in mice.