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Background and Purpose: Cerebral cavernous malformations (CCM) present as mulberry-like malformations of the microvasculature of the central nervous system. Current medical treatment of CCM lesions is limited to surgical removal of the vascular malformations. It is, therefore, important to identify therapeutic drug treatments for patients with CCM. Propranolol has shown great benefit in the treatment of infantile hemangioma. In addition, patients with CCM who receive propranolol have demonstrated a reduction of their lesions. Our investigation set out to provide preclinical data to support propranolol as a therapeutic treatment. Methods: An inducible endothelial-specific Ccm3 knockout murine model (CCM3(iECKO)) was used, with assessment of lesion quantity and size following oral treatment with propranolol. Scanning and transmission electron microscopy were used to characterize the CCM3(iECKO) lesions and the effects of propranolol on the disease. Immunofluorescent imaging was used to investigate pericyte coverage in the propranolol-treated CCM3(iECKO) mice. Results: With propranolol treatment, the lesion quantity, size, and volume decreased in both the brain and retina in the CCM3(iECKO) model. Novel characteristics of the CCM3(iECKO) lesions were discovered using electron microscopy, including plasmalemmal pits and thickening of the endothelial-pericyte basal membrane. These characteristics were absent with propranolol treatment. Pericyte coverage of the CCM3(iECKO) lesions increased after propranolol treatment, and vascular leakage was reduced. Conclusions: This study supports the concept that propranolol can be used to reduce and stabilize vascular lesions and can, therefore, be suggested as a pharmaceutical treatment for CCM.

Rationale: Cardiopulmonary resuscitation is the cornerstone of cardiac arrest (CA) treatment. However, lung injuries associated with it have been reported. Objectives: To assess 1) the presence and characteristics of lung abnormalities induced by cardiopulmonary resuscitation and 2) the role of mechanical and manual chest compression (CC) in its development. Methods: This translational study included 1) a porcine model of CA and cardiopulmonary resuscitation (n = 12) and 2) a multicenter cohort of patients with out-of-hospital CA undergoing mechanical or manual CC (n = 52). Lung computed tomography performed after resuscitation was assessed qualitatively and quantitatively along with respiratory mechanics and gas exchanges. Measurements and Main Results: The lung weight in the mechanical CC group was higher compared with the manual CC group in the experimental (431 6 127 vs. 273 6 66, P = 0.022) and clinical study (1,208 6 630 vs. 837 6 306, P = 0.006). The mechanical CC group showed significantly lower oxygenation (P = 0.043) and respiratory system compliance (P, 0.001) compared with the manual CC group in the experimental study. The variation of right atrial pressure was significantly higher in the mechanical compared with the manual CC group (54 6 11 vs. 31 6 6 mm Hg, P = 0.001) and significantly correlated with lung weight (r = 0.686, P = 0.026) and respiratory system compliance (r = 20.634, P = 0.027). Incidence of abnormal lung density was higher in patients treated with mechanical compared with manual CC (37% vs. 8%, P = 0.018). Conclusions: This study demonstrated the presence of cardiopulmonary resuscitation–associated lung edema in animals and in patients with out-of-hospital CA, which is more pronounced after mechanical as opposed to manual CC and correlates with higher swings of right atrial pressure during CC.