The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The prototype of the pentraxin family is C reactive protein (CRP), a widely-used biomarker in human pathologies with an inflammatory or infectious origin. Data so far describe PTX3 as a multifunctional protein acting as a functional ancestor of antibodies and playing a regulatory role in inflammation. Cardiovascular disease (CVD) is a leading cause of mortality worldwide, and inflammation is crucial in promoting it. Data from animal models indicate that PTX3 can have cardioprotective and atheroprotective roles regulating inflammation. PTX3 has been investigated in several clinical settings as possible biomarker of CVD. Data collected so far indicate that PTX3 plasma levels rise rapidly in acute myocardial infarction, heart failure and cardiac arrest, reflecting the extent of tissue damage and predicting the risk of mortality.

Background—: This study sought to validate the ability of amplitude spectrum area (AMSA) to predict defibrillation success and long-term survival in a large population of out-of-hospital cardiac arrests. Methods and Results—: ECGs recorded by automated external defibrillators from different manufacturers were obtained from patients with cardiac arrests occurring in 8 city areas. A database, including 2447 defibrillations from 1050 patients, was used as the derivation group, and an additional database, including 1381 defibrillations from 567 patients, served as validation. A 2-second ECG window before defibrillation was analyzed, and AMSA was calculated. Univariable and multivariable regression analyses and area under the receiver operating characteristic curve were used for associations between AMSA and study end points: defibrillation success, sustained return of spontaneous circulation, and long-term survival. Among the 2447 defibrillations of the derivation database, 26.2% were successful. AMSA was significantly higher before a successful defibrillation than a failing one (13±5 versus 6.8±3.5 mV-Hz) and was an independent predictor of defibrillation success (odds ratio, 1.33; 95% confidence interval, 1.20–1.37) and sustained return of spontaneous circulation (odds ratio, 1.22; 95% confidence interval, 1.17–1.26). Area under the receiver operating characteristic curve for defibrillation success prediction was 0.86 (95% confidence interval, 0.85–0.88). AMSA was also significantly associated with long-term survival. The following AMSA thresholds were identified: 15.5 mV-Hz for defibrillation success and 6.5 mV-Hz for defibrillation failure. In the validation database, AMSA ≥15.5 mV-Hz had a positive predictive value of 84%, whereas AMSA ≤6.5 mV-Hz had a negative predictive value of 98%. Conclusions—: In this large derivation-validation study, AMSA was validated as an accurate predictor of defibrillation success. AMSA also appeared as a predictor of long-term survival.

Introduction Effects of postresuscitation treatment with argon on neurologic recovery were investigated in a porcine model of cardiac arrest (CA) with an underlying acute myocardial infarction. Methods The left anterior descending coronary artery was occluded in 12 pigs, and CA was induced. After 8 min of untreated CA, cardiopulmonary resuscitation was performed for 5 min before defibrillation. Following resuscitation, animals were subjected to 4-h ventilation with 70% argon/30% oxygen or 70% nitrogen/30% oxygen. Myocardial function was echocardiographically assessed, and serum neuron-specific enolase was measured. Animals were observed up to 72 h for assessment of survival and neurologic recovery. Results All the animals were resuscitated and survived for 72 h, except for a control pig. Ventilation with argon did not have any detrimental effects on hemodynamics and respiratory gas exchange. All the six argon-treated animals had a fast and complete 72-h neurologic recovery, in contrast to only two of the six controls (P < 0.05). Seventy-two-hour neurologic alertness score and neurologic deficit score were, respectively, 100 and 0 in the argon group and 79 and 29 in the control one (P < 0.01 and P < 0.05). Significantly lower increases in serum neuron-specific enolase (12% vs. 234%) and minimal histological brain injury (neuronal degeneration: 0 vs. 1) were also observed in argon-treated animals, in comparison to controls. Conclusions In this model, postresuscitation treatment with argon allowed for a faster and complete neurologic recovery, without detrimental effects on hemodynamics and respiratory gas exchanges.

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.