Animal model for investigation of spinal cord injury caused by aortic cross-clamping.

The objective of this experimental protocol was to design a large animal model that could simulate the ischemic condition caused by aortic cross-clamping during the operation for intrathoracic and thoraco-abdominal aneurysm. Domestic swine weighing 25 to 30 kg were used for this model. The thoracic cavity was opened through the fourth intercostal space. Cross-clamp was applied below the left subclavian artery. Duration of cross-clamp was 30 min and the reperfusion period was 24 h. Methods of assessment included Tarlov's criteria, histology transmission electron microscopy, and spinal cord perfusion with microspheres. This model is reproducible. The results of experimental protocols completed using this model are referenced. This article discusses the details of the experimental protocol with steps toward reproduction of the model and rationalization. This animal model can be used for the evaluation of the pathophysiology of spinal cord injury and sensory- and motor-evoked potentials, and most importantly it can also be used for the examination of pharmacological interventions for prevention and treatment of ischemia reperfusion injury caused by aortic cross-clamping.

Comparison of new iron chelating agents in the prevention of ischemia/reperfusion injury: a swine model of heart-lung transplantation.

The preservation of the heart and lung for transplantation remains a major concern in extended ischemic intervals. This experimental endeavor evaluates and compares the efficacy of iron chelating agents such as high molecular weight deferoxamine and 21-aminosteroid (U74006F) in a swine model of heart-lung transplantation. Heat-lung blocks were exposed to 4 h and 45 min of ischemia and 2 h of reperfusion. Animals were divided into three groups. Group A was a control without pharmacological intervention. In groups B and C, 21-aminosteroid (U74006F), 10 mg/kg, and high molecular weight deferoxamine, 50 mg/kg, were used, respectively. The results of functional parameters (cardiac index, stroke index, lung water, PO2, PCO2, alveolar-arterial gradient, and alveolar-arterial ratio) demonstrated superior heart and lung function for group C, where high molecular weight deferoxamine was used. Alterations of heart and lung function were significantly more (p less than .001) for control animals and for group B where U74006F was used. This study suggests that formation of hydroxyl radicals was affected by chelation of iron with high molecular weight deferoxamine, which reflects better heart and lung function and consequently less damage to this group of animals. The compound 21-aminosteroid U74006F failed to protect the heart and lung from ischemic-reperfusion injury in this model of heart-lung transplantation.

Comparison of functional and metabolic assessments in preservation techniques for heart transplantation.

The present study compares simple hypothermic storage and hypothermic perfusion in a swine model of heart transplantation using metabolic and functional assessments. In both groups the hearts were initially protected with iso-osmolar potassium Tyers' cardioplegia. The donor hearts of group A were placed in simple hypothermic storage for 5 h. The donor hearts of group B were placed onto a perfusion apparatus for 5 h with perfusion pressure maintained at 28 cm of H2O and a myocardial temperature of 8-10 degrees C. The perfustate consisted of Tyers' solution with the addition of 2 mg/L of mannitol, 12.5 mg/L of glucose, 5 units/L of insulin, and 95% oxygen. The ischemic interval within both groups was 6 h, including orthotoipic transplantation. Investigation was conducted at three time periods: prepreservation (T1) in the donor, and postpreservation (T2) and immediately after loading (T3) in the recipient. Following volume loading for the hypothermic perfusion group there was significant improvement of myocardial function (cardiac index, p less than .05; stroke index, p less than .05) with no significant change in systemic vascular resistance, systemic blood pressure, and heart rate. There was also significant improvement in myocardial performance (p less than .05) for the hypothermic perfusion group following volume loading. Results of fatty acid turnover using 15-p-iodo (123I)-phenylpentodecanoic acid indicate significantly greater increase in metabolic rate for the perfusion group than for the hypothermic storage group. (p less than .05). This indicates improved metabolic status of the heart treated with the hypothermic perfusion technique. We conclude that a combination of functional and metabolic assessments is a good method for deduction of ischemic-reperfusion injury. We also conclude that hypothermic perfusion is superior to hypothermic storage for in vitro preservation of hearts for heart transplantation.

Swine as a model for cardiovascular research: improved cardiopulmonary bypass techniques.

A large-animal model is essential for the assessment of functional parameters in cardiovascular surgical research. To date the canine model has been used successfully because of its availability and tolerance to cardiopulmonary bypass. However, because of decreased availability and increased cost, an alternative animal model is now needed. The swine model has been used in experimental cardiac procedures, but complications during cardiopulmonary bypass have presented a formidable challenge. These complications include enormous fluid shifts from the vascular bed, increased metabolic acidosis, and marked hemoglobinuria. To eliminate these deleterious complications within the swine model, a number of technical alterations were achieved. The priming solution used for the extracorporeal circuit was altered to consist of 1000 mL lactated Ringer's solution. 500 mL 20% mannitol, 500 mL 6% dextran in 5% detrose solution. 50 mEq sodium bicarbonate, and 10,000 IU heparin. The extracorporeal circuit employed the use of membrane oxygenation. Three different blood flow rates (150, 175, and 200 mL/kg min-1) were studied. We conclude that the optimum blood flow rate for cardiopulmonary bypass in swine is in the range of 175-200 mL/kg min-1. Membrane oxygenation results in less damage to blood during cardiopulmonary bypass. The asanguinous hyperosmolar priming solution is beneficial for cardiopulmonary bypass in swine to greatly reduce fluid shifts, prevent metabolic acidosis, and eliminate hemoglobinuria.

Creation of a pedicle valve unit (PVU) for establishment of enteric continence. Experimental observations.

The aim of this study was to develop a natural tissue valve that could be anastomosed into any area of the gastrointestinal (GI) tract to act as a fecal "brake" and so establish enteric continence at that site. A 4-cm-long valve created from an intussuscepted small bowel pedicle was anastomosed into the cecum and brought out through the abdominal wall as a stoma in 11 rabbits. The animals were re-explored five weeks later for assessment of valve viability and continence and microscopic appearance. In all cases, the valve was fully continent in vivo. All valves were viable, and there was no anastomotic leakage. Pressure testing of the valve at reoperation revealed that 7 of 10 valves tested withstood pressures of 30 mmHg before and after catheterization and 6 of 10 were fully continent to cecal "blanching" pressure (50 mmHg). Valve failure was due to deintussusception in three cases. In four cases, valves were continent over 50 mmHg and showed no tendency to incontinence to bursting pressure of the cecum. We conclude that a continent pedicle valve unit (PVU) for placement in a variety of locations in the GI tract is feasible. The PVU has implications in the management of short-gut syndrome, incontinent ileostomy, continent cecostomy, and as a continent valve placed in the perineum for restoration of perineal defecation following proctectomy.