RESUMEN
BACKGROUND: Cardiopulmonary bypass (CPB) is known to induce systemic inflammation and cardiac dysfunction associated with a significant morbidity. Aim of the study was to develop an in vivo model of rat CPB with hypothermic cardiac arrest and the use of cardioplegia. MATERIAL AND METHODS: The CPB circuit consisted of a venous reservoir, membrane oxygenator, heat exchanger, and roller pump. CPB was instituted in adult male Wistar rats (400-500 g) for 60 min at a flow rate of 120 ml x kg(-1) x min(-1), including 15 min cooling to 32 degrees C, 30 min cardiac arrest with the use of cold crystalloid cardioplegia after aortic cross clamping, and 15 min of reperfusion and rewarming to 37 degrees C. Arterial blood pressure (MAP) and heart rate (HR) were monitored, arterial blood samples were analyzed. Left ventricular (LV) function parameters were assessed by intraventricular conductance catheter. Important technical aspects are: ventilation is required during partial bypass; anticoagulation should be performed immediately prior to CPB to reduce blood loss; active suction on venous drainage allows higher pump flows; and the small priming volume of the extracorporeal circuit (8 ml) avoids the need for donor blood. RESULTS: MAP remained stable prior to and during CPB.MAP and HR were significantly decreased 60 min after weaning from bypass. Hct was significantly lowered after hemodilution, but remained stable during CPB and 60 min after weaning from bypass. BE and pH remained stable throughout the experiment.Without inotropic support diastolic and systolic LV function parameters were impaired after 30 min of cardioplegic arrest followed by 15 min of reperfusion. Myocardial TNF-alpha mRNA levels were slightly increased (1.28-fold, p = 0.71), and IL-6 mRNA was significantly increased in the cardioplegia group (90.3-fold, p = 0.001). Both IL-6 and TNF-alpha plasma levels were significantly elevated in the cardioplegia group (TNF-alpha: 4.6-fold increase,p < 0.05; IL-6: 426.8-fold increase, p < 0.001). CONCLUSIONS: We have developed a rat CPB with mild hypothermic cardioplegic arrest. This rodent model is suitable to study clinically relevant problems related to CPB,myocardial protection and systemic inflammation.
Asunto(s)
Presión Sanguínea/fisiología , Cateterismo Cardíaco/métodos , Puente Cardiopulmonar/métodos , Paro Cardíaco Inducido/métodos , Frecuencia Cardíaca/fisiología , Corazón/fisiopatología , Modelos Animales , Animales , Ventrículos Cardíacos/fisiopatología , Hipotermia Inducida , Interleucina-6/metabolismo , Masculino , Miocardio/metabolismo , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Instrumentos Quirúrgicos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Cardiac performance is quantitatively and continuously assessed from pressure-volume signals by using the conductance catheter technique even in small animals. Conductivity of blood, however, is dependent on hematocrit (Hct). Interdependence between hematocrit and volume measurement by the conductance catheter has been evaluated. In 12 male Wistar rats weighing 400-475 g, anesthetized and artificially ventilated, Hct was gradually lowered by isovolumic hemodilution ranging from 50% to 7%. Heparinized blood samples were drawn at decreasing Hct levels for centrifugation, for automated Hct measurement by a blood gas analyzer, and for conductance catheter volume measurements (CCV) in calibrated cuvettes. Substitution of about 2 ml colloid solution lowered the Hct initially from 47 +/- 2% to 36 +/- 3%; at the same time, CCV output rose by 36 +/- 14% for definite blood volume. There is a strong inverse linear relationship (absolute value of r > 0.96; P < 0.0001) between relative volume units (RVU) displayed by the volume acquisition device and the hematocrit for any calibrated blood cuvette. Slopes of the regression lines increase proportionally to the calibration volumes (28.3 microl: -0.25; 63.6 microl: -0.57; 113.1 microl: -0.92). These data document the direct interdependence between Hct and CCV. Consequently, careful Hct correction of the RVU recordings is necessary especially in small animals where even small amounts of substituted solutions result in a marked decrease in Hct and, thus, in pronounced blood volume misreadings.
Asunto(s)
Algoritmos , Artefactos , Cateterismo Cardíaco/métodos , Hematócrito/métodos , Pletismografía de Impedancia/métodos , Volumen Sistólico/fisiología , Función Ventricular Izquierda/fisiología , Animales , Masculino , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The calcium sensitizer levosimendan (LEV) improves the function of stunned myocardium, cardiac performance in heart failure, and possibly the efficiency of myocardial work. The present experiments investigated the effect of LEV on myocardial contraction and metabolism of acutely ischaemic myocardium distal to a functionally effective coronary artery stenosis. Anaesthetised open chest pigs (n = 14) were instrumented to assess heart rate (HR), aortic pressure (AoP), cardiac output (CO), blood flow in the left descending (QLAD) and circumflex (QLCX) coronary artery, myocardial end-diastolic segment length and systolic shortening (edL, MSS by sonomicrometry) in the LAD- and LCX-territory. Systemic vascular resistance (SVR), and a myocardial power index (PowI) for the LAD- and LCX-region were calculated. Following obstruction of QLAD by an external snare proximal to the first diagonal branch LEV was given intravenously (10 + 20 + 30 microg/kg 15 min apart, n = 8) or the vehicle of LEV (n = 6). Following LEV haemodynamics and regional myocardial performance changed significantly: HR +22 min(-1), AoP -6 mmHg, CO +17%, SVR -21%; intact myocardium: QLCX +15%, RLCX -24%, PowILCX + 39%; ischaemic myocardium: QLAD -7%, MSSLAD -42%, PowILAD -27%. The data confirm the pharmacological profile of LEV: positive chronotropy, positive inotropy, and vasodilatation. The pump function of acutely ischaemic myocardium worsened following LEV. The efficiency of myocardial performance did not improve. A beneficial effect of LEV on the function of ischaemic myocardium was possibly outmanoeuvred by the increase in heart rate.