Postresuscitation Cerebral Vasospasm and Capillary Failure After Experimental Asphyxial Cardiac Arrest

Abstract

BACKGROUND: Disrupted cerebral blood flow is suggested to contribute to secondary brain injury after cardiac arrest (CA). This study aimed to investigate cerebral microcirculation after return of spontaneous circulation (ROSC) following asphyxial CA. We hypothesized that contraction of pericytes after ROSC compromises cerebral capillary blood flow. METHODS: Transgenic C57BL/6NRj mice (n=19) of both sexes were studied. Mice were expressing tdTomato as a fluorescent reporter under the control of the platelet-derived growth factor receptor β promoter to label pericytes. Chronic cranial windows were implanted 3 weeks before the experiment. Four minutes of asphyxial CA was followed by cardiopulmonary resuscitation. Two-photon microscopy assessed cerebral hemodynamics in the same cohort of mice at both 3 and 24 hours after ROSC. RESULTS: Of 13 mice in the CA group, 9 achieved ROSC; 6 and 5 mice survived to 3 and 24 hours after ROSC, respectively. Arterial blood pressure was similar between groups 3 and 24 hours after ROSC. At 3 hours after ROSC, pial arteries and penetrating arterioles were constricted in the CA group compared with sham (arteriole diameter, 12.2 μm [95% CI, 10.9–13.4] versus 15.6 μm [95% CI, 13.8–17.5] in CA and sham; P=0.003). Similarly, first-and second-to third-order capillaries showed reduced diameters 3 hours after ROSC (first-order diameter, 3.9 μm [95% CI, 3.5–4.2] versus 5.3 μm [95% CI, 4.8–5.9] in CA and sham; P=0.002). The vasoconstriction was associated with slower red blood cell velocities throughout the capillary network (for second-to third-order capillaries upstream from venule; 0.78 mm/s [95% CI, 0.46–1.09] versus 2.14 mm/s [95% CI, 1.73–2.55]; P<0.001) and increased capillary flow stalling. Artery-to-vein mean transit time was increased and relative transit-time heterogeneity was decreased 3 hours after ROSC. By 24 hours after ROSC, vessel diameters, blood flow velocity, transit time, and capillary stalling were not different compared with sham. CONCLUSIONS: Cerebrovascular vasospasm 3 hours after ROSC was associated with impaired cerebral microcirculation and increased capillary flow stalling.