Aim Adequate coronary perfusion pressure (CPP) during cardiopulmonary resuscitation (CPR) is essential for establishing return of spontaneous circulation. The objective of this study was to compare short-term survival using a hemodynamic directed resuscitation strategy versus an absolute depth-guided approach in a porcine model of asphyxia-associated cardiac arrest. We hypothesized that a hemodynamic directed approach would improve short-term survival compared to depth-guided care. Methods After 7 minutes of asphyxia, followed by induction of ventricular fibrillation, 19 female 3-month old swine (31 ± 0.4 kg) were randomized to receive one of three resuscitation strategies: 1) Hemodynamic Directed Care (CPP-20): chest compressions (CCs) with depth titrated to a target systolic blood pressure of 100 mmHg and titration of vasopressors to maintain CPP > 20 mmHg; 2) Depth 33mm (D33): target CC depth of 33mm with standard American Heart Association (AHA) epinephrine dosing; or 3) Depth 51mm (D51): target CC depth of 51mm with standard AHA epinephrine dosing. All animals received manual CPR guided by audiovisual feedback for 10 minutes before first shock. Results 45-minute survival was higher in the CPP-20 group (6/6) compared to D33 (1/7) or D51 (1/6) groups; p=0.002. Coronary perfusion pressures were higher in the CPP-20 group compared to D33 (p=0.011) and D51 (p=0.04), and in survivors compared to non-survivors (p<0.01). Total number of vasopressor doses administered and defibrillation attempts were not different. Conclusions Hemodynamic directed care targeting CPPs > 20 mmHg improves short-term survival in an intensive care unit porcine model of asphyxia-associated cardiac arrest.

Background-Increasing evidence, derived mainly from animal models, supports the existence of endogenous cardiac renewal and repair mechanisms in adult mammalian hearts that could contribute to normal homeostasis and the responses to pathological insults. Methods and Results-Translating these results, we isolated small c-kit ϩ cells from 36 of 37 human hearts using primary cell isolation techniques and magnetic cell sorting techniques. The abundance of these cardiac progenitor cells was increased nearly 4-fold in patients with heart failure requiring transplantation compared with nonfailing controls. Polychromatic flow cytometry of primary cell isolates (Ͻ30 m) without antecedent c-kit enrichment confirmed the increased abundance of c-kit ϩ cells in failing hearts and demonstrated frequent coexpression of CD45 in these cells. Immunocytochemical characterization of freshly isolated, c-kit-enriched human cardiac progenitor cells confirmed frequent coexpression of c-kit and CD45. Primary cardiac progenitor cells formed new human cardiac myocytes at a relatively high frequency after coculture with neonatal rat ventricular myocytes. These contracting new cardiac myocytes exhibited an immature phenotype and frequent electric coupling with the rat myocytes that induced their myogenic differentiation. Conclusions-Despite the increased abundance and cardiac myogenic capacity of cardiac progenitor cells in failing human hearts, the need to replace these organs via transplantation implies that adverse features of the local myocardial environment overwhelm endogenous cardiac repair capacity. Developing strategies to improve the success of endogenous cardiac regenerative processes may permit therapeutic myocardial repair without cell delivery per se.