Benjamín Erranz

Regenerative Potential of Mesenchymal Stromal Cells: Age-Related Changes

Preclinical and clinical studies have shown that a therapeutic effect results from mesenchymal stromal cells (MSCs) transplant. No systematic information is currently available regarding whether donor age modifies MSC regenerative potential on cutaneous wound healing. Here, we evaluate whether donor age influences this potential. Two different doses of bone marrow MSCs (BM-MSCs) from young, adult, or old mouse donors or two doses of their acellular derivatives mesenchymal stromal cells (acd-MSCs) were intradermally injected around wounds in the midline of C57BL/6 mice. Every two days, wound healing was macroscopically assessed (wound closure) and microscopically assessed (reepithelialization, dermal-epidermal junction, skin appendage regeneration, granulation tissue, leukocyte infiltration, and density dermal collagen fibers) after 12 days from MSC transplant. Significant differences in the wound closure kinetic, quality, and healing of skin regenerated were observed in lesions which received BM-MSCs from different ages or their acd-MSCs compared to lesions which received vehicle. Nevertheless, our data shows that adults BM-MSCs or their acd-MSCs were the most efficient for recovery of most parameters analyzed. Our data suggest that MSC efficacy was negatively affected by donor age, where the treatment with adults BM-MSCs or their acd-MSCs in cutaneous wound promotes a better tissue repair/regeneration. This is due to their paracrine factors secretion.

Mild hypothermia attenuates lung edema and plasma interleukin-1β in a rat mechanical ventilation-induced lung injury model

ABSTRACT Recent data suggest that deep hypothermia has protective effects on experimental induced lung injury. It is not well known if these effects persist with mild hypothermia. The authors hypothesized that mild hypothermia may attenuate lung injury and decrease local and systemic proinflammatory cytokines in a rat model of injurious mechanical ventilation (MV). Twelve Sprague-Dawley male adult rats were anesthetized, intubated, and randomly allocated to normothermia group (37°C) (NT) or mild hypothermia group (34°C) (MH). After 2 hours of deleterious MV (peak inspiratory pressure [PIP] 40 cm H2O, zero end-expiratory pressure [ZEEP], and inspiratory fraction of oxygen [Fio2] 100%), arterial blood gases, lung gravimetry, and histological study were obtained. Protein content, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α were measured in plasma and bronchoalveolar lavage (BAL) fluid. Subjects that underwent MH had a significant lower wet-to-dry lung weight ratio (8.32 ± 0.28 vs. 10.8 ± 0.49, P = .01), IL-1β plasma concentration (0.6 ± 0.6 vs. 10.27 ± 2.80 pg/mL, P = .0048) and Paco2. There were no differences in terms of Pao2, histological injury, or BAL protein content. In this model of injurious mechanical ventilation, subjects treated with mild hypothermia had less lung edema and lower plasma IL-1β. Some of known beneficial effects of deep hypothermia can be obtained with mild hypothermia.

Surfactant deactivation in a pediatric model induces hypovolemia and fluid shift to the extravascular lung compartment.

Surfactant deficiency is the pivotal abnormality in Neonatal and Acute Respiratory Distress Syndrome. Surfactant deactivation can produce hypoxemia, loss of lung compliance, and pulmonary edema, but its circulatory consequences are less understood.

Mild hypothermia increases pulmonary anti-inflammatory response during protective mechanical ventilation in a piglet model of acute lung injury

The effects of mild hypothermia (HT) on acute lung injury (ALI) are unknown in species with metabolic rate similar to that of humans, receiving protective mechanical ventilation (MV). We hypothesized that mild hypothermia would attenuate pulmonary and systemic inflammatory responses in piglets with ALI managed with a protective MV.

Decreased lung compliance increases preload dynamic tests in a pediatric acute lung injury model

BACKGROUND Preload dynamic tests, pulse pressure variation (PPV) and stroke volume variation (SVV) have emerged as powerful tools to predict response to fluid administration. The influence of factors other than preload in dynamic preload test is currently poorly understood in pediatrics. The aim of our study was to assess the effect of tidal volume (VT) on PPV and SVV in the context of normal and reduced lung compliance in a piglet model. MATERIAL AND METHOD Twenty large-white piglets (5.2±0.4kg) were anesthetized, paralyzed and monitored with pulse contour analysis. PPV and SVV were recorded during mechanical ventilation with a VT of 6 and 12mL/kg (low and high VT, respectively), both before and after tracheal instillation of polysorbate 20. RESULTS Before acute lung injury (ALI) induction, modifications of VT did not significantly change PPV and SVV readings. After ALI, PPV and SVV were significantly greater during ventilation with a high VT compared to a low VT (PPV increased from 8.9±1.2 to 12.4±1.1%, and SVV from 8.5±1.0 to 12.7±1.2%, both P<0.01). CONCLUSIONS This study found that a high VT and reduced lung compliance due to ALI increase preload dynamic tests, with a greater influence of the latter. In subjects with ALI, lung compliance should be considered when interpreting the preload dynamic tests.

Effect of a Lung Rest Strategy During Ecmo in a Porcine Acute Lung Injury Model

ECMO is used to treat patients who develop refractory hypoxemia and to provide a more protective ventilation. Several guidelines recommend “lung rest” strategies based on variable ventilatory parameters. However, there is limited evidence to support this strategy.

Diferencia veno-arterial de dióxido de carbono como predictor de gasto cardiaco disminuido en modelo pediátrico experimental

Background: Cardiac output (CO) measurement is not a standard of care for critically ill children, but it can be estimated by indirect methods such as veno-arterial pCO2 difference (ΔVACO2). Aim: To determine the correlation between CO and ΔVACO2 and evaluate the usefulness of ΔVACO2 in the diagnosis of low CO in an experimental pediatric model. Materials and Methods: Thirty piglets weighing 4.8 ± 0.35 kg were anesthetized and monitored with transpulmonary thermodilution. Lung injury was induced with tracheal instillation of Tween 20®. Serial measurements of central venous and arterial blood gases, as well as CO, were obtained at baseline, 1, 2 and 4 h after lung injury induction. Low cardiac output (LCO) was defined as CO lower than 2.5 Llminlm2. Results: There was an inverse correlation between CO and ΔVACO2 (r = -0.36, p < 0.01). ΔVACO2 was 14 ± 8 mmHg in LCO state and 8 ± 6 mmHg when this condition was not present (p < 0.01). Area under the receiver operating characteristic (ROC) curves of ΔVACO2 and LCO state was 0.78 (0.68-0.86). The best cut-point was 8.9 mmHg to determine LCO with a sensibility 0.78, specificity 0.7, positive predictive value 0.27 and negative predictive value 0.96. Conclusions: In this model there was an inverse correlation between ΔVACO2 and CO. The best cutoff value to discard LCO was ΔVACO2 of 8.9 mmHg, indicating that under this value the presence of LCO is very unlikely.