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Rapid progressive central cooling to 29 degrees C by extracorporeal circuit preserves cardiac function and hemodynamics in immature swine.

ABSTRACT: The International Liaison Committee on Resuscitation (ILCOR) consensus statement includes recommendations and guidelines for therapeutic hypothermia in infants and children. The information supporting these recommendations is sparse, and reveals a need for target temperature and cooling mode data in age-appropriate animal models. Accordingly, we determined cardiac function and hemodynamic indices in immature piglets (<28 days) undergoing graded and rapid central cooling from 36 to 20 degrees C over 20 min by directing cardiac output through an extracorporeal circuit. Functional parameters were recorded continuously using aortic flow probes and left ventricular (LV) pressure capacitance catheters. Stroke volume and work increased during temperature reduction, peaking at 29 degrees C, while systemic vascular resistance did not change. Although, heart rate decreased steadily, cardiac output, power, and LV dP/dt(max) was maintained until 29 degrees C. All function parameters decreased below 29 degrees C, implying a critical threshold had been exceeded at lower temperatures. These data show that the temperature range (30+/-1) degrees C maintains cardiac function and that this target should be further evaluated as a target for therapeutic hypothermia.

SUBMITTER: Ning XH

PROVIDER: S-EPMC2350210 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Rapid progressive central cooling to 29 degrees C by extracorporeal circuit preserves cardiac function and hemodynamics in immature swine.

Ning Xue-Han XH Hyyti Outi O Ge Ming M Anderson David L DL Portman Michael A MA

Resuscitation 20071031 3

The International Liaison Committee on Resuscitation (ILCOR) consensus statement includes recommendations and guidelines for therapeutic hypothermia in infants and children. The information supporting these recommendations is sparse, and reveals a need for target temperature and cooling mode data in age-appropriate animal models. Accordingly, we determined cardiac function and hemodynamic indices in immature piglets (<28 days) undergoing graded and rapid central cooling from 36 to 20 degrees C o ...[more]

PMID: 17976893

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Project description:BackgroundExtracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65-75 vs 80-90 mmHg) in a porcine model.MethodsPigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120-min after ROSC.ResultsSix animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC.ConclusionsDuring early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.

Project description:ObjectivesLung remains the least-utilized solid organ for transplantation. Efforts to recover donor lungs with reversible injuries using ex vivo perfusion systems are limited to <24 hours of support. Here, we demonstrate the feasibility of extending normothermic extracorporeal lung support to 4 days using cross-circulation with conscious swine.MethodsA swine behavioral training program and custom enclosure were developed to enable multiday cross-circulation between extracorporeal lungs and recipient swine. Lungs were ventilated and perfused in a normothermic chamber for 4 days. Longitudinal analyses of extracorporeal lungs (ie, functional assessments, multiscale imaging, cytokine quantification, and cellular assays) and recipient swine (eg, vital signs and blood and tissue analyses) were performed.ResultsThroughout 4 days of normothermic support, extracorporeal lung function was maintained (arterial oxygen tension/inspired oxygen fraction >400 mm Hg; compliance >20 mL/cm H2O), and recipient swine were hemodynamically stable (lactate <3 mmol/L; pH, 7.42 ± 0.05). Radiography revealed well-aerated lower lobes and consolidation in upper lobes of extracorporeal lungs, and bronchoscopy showed healthy airways without edema or secretions. In bronchoalveolar lavage fluid, granulocyte-macrophage colony-stimulating factor, interleukin (IL) 4, IL-6, and IL-10 levels increased less than 6-fold, whereas interferon gamma, IL-1α, IL-1β, IL-1ra, IL-2, IL-8, IL-12, IL-18, and tumor necrosis factor alpha levels decreased from baseline to day 4. Histologic evaluations confirmed an intact blood-gas barrier and outstanding preservation of airway and alveolar architecture. Cellular viability and metabolism in extracorporeal lungs were confirmed after 4 days.ConclusionsWe demonstrate feasibility of normothermic maintenance of extracorporeal lungs for 4 days by cross-circulation with conscious swine. Cross-circulation approaches could support the recovery of damaged lungs and enable organ bioengineering to improve transplant outcomes.

Dataset Information

Rapid progressive central cooling to 29 degrees C by extracorporeal circuit preserves cardiac function and hemodynamics in immature swine.

Publications

Rapid progressive central cooling to 29 degrees C by extracorporeal circuit preserves cardiac function and hemodynamics in immature swine.

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