Delayed administration of allogeneic cardiac stem cell therapy for acute myocardial infarction could ameliorate adverse remodeling: experimental study in swine.

BACKGROUND: The optimal timing of cardiac stem cells administration is still unclear. We assessed the safety of same-day and delayed (one week) delivery and the possible influence of the timing on the therapeutic outcomes of allogeneic porcine cardiac stem cells administration after acute myocardial infarction in a closed-chest ischemia-reperfusion model. METHODS: Female swine surviving 90 min occlusion of the mid left anterior descending coronary artery received an intracoronary injection of 25x10(6) porcine cardiac stem cells either two hours (n = 5, D0) or 7 days (n = 6, D7) after reperfusion. Controls received intracoronary injection of vehicle on day 7 (n = 6, CON). Safety was defined in terms of absence of major cardiac events, changes to the ECG during injection, post-administration coronary flow assessed using the TIMI scale and cardiac troponin I determination after the intervention. Cardiac Magnetic Resonance was performed for morphological and functional assessment prior to infarction, before injection (D7 and CON groups only), at one and 10 weeks. Samples were taken from the infarct and transition areas for pathological examination. RESULTS: No major adverse cardiac events were seen during injection in any group. Animals receiving the therapy on the same day of infarction (D0 group) showed mild transient ST changes during injection (n = 4) and, in one case, slightly compromised coronary flow (TIMI 2). Cardiac function parameters and infarct sizes were not significantly different between groups, with a trend towards higher ejection fraction in the treated groups. Ventricular volumes indexed to body surface area increased over time in control animals, and decreased by the end of the study in animals receiving the therapy, significantly so when comparing End Diastolic Volume between CON and D7 groups (CON: 121.70 ml/m(2) ± 26.09 ml/m(2), D7: 98.71 ml/m(2) ± 8.30 ml/m(2), p = 0.037). The treated groups showed less organization of the collagenous scar, and a significantly (p = 0.019) higher amount of larger, more mature vessels at the infarct border. CONCLUSIONS: The intracoronary injection of 25x10(6) allogeneic cardiac stem cells is generally safe, both early and 7 days after experimental infarction, and alleviates myocardial dysfunction, with a greater limitation of left ventricular remodeling when performed at one week.

[Intra-abdominal hypertension: effects on the splanchnic circulation. Preliminary study in a model of ascites]. / Hipertensión intraabdominal: consecuencias sobre la circulación esplácnica. Estudio preliminar en un modelo de ascitis.

INTRODUCTION: Intra-abdominal hypertension is defined as a rise in intra-abdominal pressure leading to progressive dysfunction of the abdominal organs. OBJECTIVE: To evaluate the effects of intra-abdominal hypertension on the splanchnic circulation in a porcine animal model with a view to determining the diagnostic method of choice. MATERIAL AND METHODS: A total of 10 swine were divided into 2 groups: a control group and a group with an ascites pressure of 20mmHg. Transvesical and transperitoneal intra-abdominal pressures were registered, and the correlation between the measurements obtained was determined. Concentrations of lactic acid, alanine aminotransferase, glucose and gastric mucosal pH were also obtained. We registered the mean arterial and abdominal perfusion pressures, and the correlation of the latter with gastric mucosal pH and lactic acid concentrations. The parameters were registered for a total of 3hours. RESULTS: We observed a high correlation between transvesical and transperitoneal measurements of intra-abdominal pressure (R(2)=0.98). In the 20mmHg pressure group, lactic acid concentrations increased significantly at 180min (p<0.011). Gastric mucosal pH differed significantly between the 2 groups from the beginning of the study (p=0.004) and significantly decreased from 120min onward. Mean arterial and abdominal perfusion pressures gradually decreased during the trial, with early significant changes in the abdominal perfusion pressure (p=0.001), and a good correlation with the remaining study parameters. There were no significant changes in hepatic indicators. CONCLUSIONS: We believe the transvesical approach to be the technique of choice to determine intra-abdominal pressure. Abdominal perfusion pressure is a sensitive marker of intra-abdominal hypertension, and gastric mucosal pH is the first parameter to be affected.

Tonometry as a predictor of inadequate splanchnic perfusion in an intra-abdominal hypertension animal model.

BACKGROUND: The gastrointestinal system is the most sensitive to the presence of intra-abdominal hypertension. We aimed to assess the early prognostic value of gastric air tonometry as a predictor of inadequate splanchnic perfusion and determine its relation with abdominal perfusion pressure (APP). METHODS: Twenty-five Large White swine were used for this study. A control group and two study groups were included, in which intra-abdominal pressure (IAP) was elevated with Co2 to 20 and 30 mmHg during 5 h. We measured the intramucosal gastric pH (pHim) and determined gastric luminal PCO2 (PgCO2) and PgCO2gap (gastric luminal CO2-arterial CO2) to evaluate gastric acidity. APP was indirectly obtained through IAP and mean arterial pressure. Additionally, histopathologic samples of small intestine were obtained and analyzed. RESULTS: pHim showed a decrease in IAP groups, with statistical significance in the 30 mmHg group, 90 min after stabilization period (P < 0.01). Serum lactate showed delayed alteration when compared with pHim, with significant increase, 180 min after stabilization (P < 0.05). The values of PgCO2 and PCO2gap were increased in IAP groups, being statistically significant in the 30 mmHg group, 120 and 150 min, respectively, after stabilization. In increased IAP groups, there was a time progressive decrease of APP, with statistically significant differences observed between groups at 20 min (P < 0.001). The histopathology study revealed parenchymal injury of the intestine at 30 mmHg. CONCLUSIONS: Tonometry is sensitive to the increase in IAP and relates to the reduction of APP generated by splanchnic hypoperfusion.

Common swine models of cardiovascular disease for research and training.

Cardiovascular diseases are a major health concern and therefore an important topic in biomedical research. Large animal models allow researchers to assess the safety and efficacy of new cardiovascular procedures in systems that resemble human anatomy; additionally, they can be used to emulate scenarios for training purposes. Among the many biomedical models that are described in published literature, it is important that researchers understand and select those that are best suited to achieve the aims of their research, that facilitate the humane care and management of their research animals and that best promote the high ethical standards required of animal research. In this resource the authors describe some common swine models that can be easily incorporated into regular practices of research and training at biomedical institutions. These models use both native and altered vascular anatomy of swine to carry out research protocols, such as testing biological reactions to implanted materials, surgically creating aneurysms using autologous tissue and inducing myocardial infarction through closed-chest procedures. Such models can also be used for training, where native and altered vascular anatomy allow medical professionals to learn and practice challenging techniques in anatomy that closely simulates human systems.

Intrapericardial administration of mesenchymal stem cells in a large animal model: a bio-distribution analysis.

The appropriate administration route for cardiovascular cell therapy is essential to ensure the viability, proliferative potential, homing capacity and implantation of transferred cells. At the present, the intrapericardial administration of pharmacological agents is considered an efficient method for the treatment of cardiovascular diseases. However, only a few reports have addressed the question whether the intrapericardial delivery of Mesenchymal Stem Cells (MSCs) could be an optimal administration route. This work firstly aimed to analyze the pericardial fluid as a cell-delivery vehicle. Moreover, the in vivo biodistribution pattern of intrapericardially administered MSCs was evaluated in a clinically relevant large animal model. Our in vitro results firstly showed that, MSCs viability, proliferative behavior and phenotypic profile were unaffected by exposure to pericardial fluid. Secondly, in vivo cell tracking by magnetic resonance imaging, histological examination and Y-chromosome amplification clearly demonstrated the presence of MSCs in pericardium, ventricles (left and right) and atrium (left and right) when MSCs were administered into the pericardial space. In conclusion, here we demonstrate that pericardial fluid is a suitable vehicle for MSCs and intrapericardial route provides an optimal retention and implantation of MSCs.