Joseph P. Ornato

Background: Heart disease is the leading cause of death in the United States with a disproportionate impact in rural America, and health worker shortages contribute to these disparities. Team‐based heart disease care models can help mitigate health worker shortages, but lack of role clarity and restrictive scope of practice laws can be a barrier to their implementation. Methods: To better understand the intersection of licensed scope of practice laws with rural heart disease care, we performed a legal epidemiology analysis to identify and describe licensed scope of practice laws for 9 health worker cadres in 13 state and federal jurisdictions for 8 heart disease services. Results: We found substantial ambiguity, variation, and some important gaps, which may undermine the predictability of regulatory and reimbursement environments and hinder implementation of innovative team‐based care models. Conclusions: Three policy opportunities to address the identified gaps include: (1) linking licensed scope of practice definitions to the scope of accredited training curricula, (2) shifting away from collaborative practice agreements to define licensed scope of practice, and (3) prohibiting insurance plans from conditioning reimbursement based solely on provider cadre.

Background: Post‐resuscitation syndrome, involves a severe inflammatory response following successful cardiopulmonary resuscitation. The potential mechanism of Vitamin C (VitC) after cardiopulmonary resuscitation on myocardial and cerebral function, duration of survival is undefined. Methods and Results: A first set of experiments were done in 18 male Sprague‐Dawley rats for the investigation of short‐term follow‐up, randomized into 3 groups: (1) sham; (2) controls; (3) VitC. Ventricular fibrillation was electrically induced and untreated for 6 minutes. Cardiopulmonary resuscitation including chest compression and mechanical ventilation were then initiated and continued for 8 minutes followed by defibrillation. At 5 minutes after return of spontaneous circulation, either VitC (200 mg/kg) or placebo was administered by intravenous infusion with a syringe pump for half an hour. There were significant improvements in myocardial function and buccal microcirculation in rats treated with VitC after return of spontaneous circulation 4 hours compared with controls. VitC inhibited proinflammatory cytokines (interleukin‐6 and tumor necrosis factor‐α), SDC‐1 (Syndecan‐1), and hyaluronic acid in plasma compared with controls ( P <0.01). VitC decreased reactive oxygen species production and inhibited p38/MAPK (mitogen‐activated protein kinase) pathway phosphorylation. A second set with 20 animals was used for assessing the neurological deficit score after return of spontaneous circulation 72 hours, randomized into 2 groups: 1) controls; 2) VitC. The survival rate and neurological deficit score after return of spontaneous circulation 72 hours were improved in VitC‐treated animals compared with those of the control group. Conclusions: VitC reduces the severity of post‐resuscitation myocardial and cerebral dysfunction and improves the survival. The mechanisms may involve inhibiting transcription of inflammatory cytokines and oxidative stress, thus protecting the integrity of the vascular endothelium. Meanwhile VitC reduces shedding of SDC‐1 and alters p38/MAPK phosphorylation and microcirculation.

Purpose: To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR). Methods: Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups. Results: Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05). Conclusion: Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.

Background: To investigate the therapeutic potential of combined therapy with polyethylene glycol‐20k (PEG‐20k) and MCC950 on post‐resuscitation myocardial function in a rat model of cardiac arrest.Methods and Results: Thirty rats were randomized into 5 groups: Sham, Control, PEG‐20k, MCC950, PEG‐20k+ MCC950. Except for sham, animals were subjected to 6 minutes of ventricular fibrillation followed by 8 minutes cardiopulmonary resuscitation. Two milliliters PEG‐20k was administered by intravenous injection coincident with the start of cardiopulmonary resuscitation; MCC950 (10 mg/kg), a highly selective NLRP3 inflammasome inhibitor, was delivered immediately after restoration of spontaneous circulation. Myocardial function, sublingual microcirculation, mitochondrial function, plasma cardiac troponin I, and interleukin‐1β, expression of proteins in SIRT1 (sirtuin 1)/PGC‐1α (peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha) and NLRP3 (the NOD‐like receptor family protein 3) inflammasome pathways were evaluated. Following cardiopulmonary resuscitation, myocardial function was compromised with a significantly decreased cardiac output, ejection fraction, and increased myocardial performance index, cardiac troponin I. Sublingual microcirculation was disturbed with impaired perfused vessel density and microvascular flow index. Cardiac arrest reduced mitochondrial routine respiration, Complex I‐linked respiration, respiratory control rates and oxidative phosphorylation coupling efficiency. PEG‐20k or MCC950 alone restored mitochondrial respiratory function, restituted sublingual microcirculation, and preserved myocardial function, whereas a combination of PEG‐20k and MCC950 further improved these aspects. PEG‐20k restored the expression of SIRT1 and PGC‐1α, and blunted activation of NLRP3 inflammasomes. MCC950 suppressed expression of cleaved‐caspase‐1/pro‐caspase‐1, ASC (apoptosis‐associated speck‐like protein), GSDMD [gasdermin d], and interleukin‐1β.Conclusions: Combined therapy with PEG‐20k and MCC950 is superior to either therapy alone for preserving post‐resuscitated myocardial function, restituting sublingual microcirculation at restoration of spontaneous circulation at 6 hours. The responsible mechanisms involve upregulated expression of SIRT1/PGC1‐α in tandem with inhibition of NLRP3 inflammasomes.

The ability of emergency care research (ECR) to produce meaningful improvements in the outcomes of acutely ill or injured patients depends on the optimal configuration, infrastructure, organization, and support of emergency care research networks (ECRNs). Through the experiences of existing ECRNs, we can learn how to best accomplish this. A meeting was organized in Washington, DC, on May 28, 2008, to discuss the present state and future directions of clinical research networks as they relate to emergency care. Prior to the conference, at the time of online registration, participants responded to a series of preconference questions addressing the relevant issues that would form the basis of the breakout session discussions. During the conference, representatives from a number of existing ECRNs participated in discussions with the attendees and provided a description of their respective networks, infrastructure, and challenges. Breakout sessions provided the opportunity to further discuss the strengths and weaknesses of these networks and patterns of success with respect to their formation, management, funding, best practices, and pitfalls. Discussions centered on identifying characteristics that promote or inhibit successful networks and their interactivity, productivity, and expansion. Here the authors describe the current state of ECRNs and identify the strengths, weaknesses, and potential pitfalls of research networks. The most commonly cited strengths of population‐ or disease‐based research networks identified in the preconference survey were access to larger numbers of patients; involvement of physician experts in the field, contributing to high‐level study content; and the collaboration among investigators. The most commonly cited weaknesses were studies with too narrow a focus and restrictive inclusion criteria, a vast organizational structure with a risk of either too much or too little central organization or control, and heterogeneity of institutional policies and procedures among sites. Through the survey and structured discussion process involving multiple stakeholders, the authors have identified strengths and weaknesses that are consistent across a number of existing ECRNs. By leveraging the strengths and addressing the weaknesses, strategies can be adopted to enhance the scientific value and productivity of these networks and give direction to future ECRNs.

Baseline electrocardiogram abnormalities and market elevations not associated with myocardial necrosis make accurate diagnosis of myocardial infarction (MI) difficult in patients with cocaine‐associated chest pain. Troponin sampling may offer greater diagnostic utility in these patients. Objective: To assess outcomes based on troponin positivity in patients with cocaine chest pain admitted for exclusion of MI. Methods: Outcomes were examined in patients admitted for possible MI after cocaine use. All patients underwent a rapid rule‐in protocol that included serial sampling of creatine kinase (CK), CK‐MB, and cardiac troponin I (cTnI) over eight hours. Outcomes included CK‐MB MI (CK‐MB ≥ 8 ng/mL with a relative index [(CK‐MB × 100)/total CK] ≥ 4, cardiac death, and significant coronary disease (≥50%). Results: Of the 246 admitted patients, 34 (14%) met CK‐MB criteria for MI and 38 (16%) had cTnI elevations. Angiography was performed in 29 of 38 patients who were cTnI‐positive, with significant disease present in 25 (86%). Three of the four patients without significant disease who had cTnI elevations met CK‐MB criteria for MI, and the other had a peak CK‐MB level of 13 ng/mL. Sensitivities, specificities, and positive and negative likelihood ratios for predicting cardiac death or significant disease were high for both CK‐MB MI and cTnI and were not significantly different. Conclusions: Most patients with cTnI elevations meet CK‐MB criteria for MI, as well as have a high incidence of underlying significant disease. Troponin appears to have an equivalent diagnostic accuracy compared with CK‐MB for diagnosing necrosis in patients with cocaine‐associated chest pain and suspected MI.