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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.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.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,p0.05; IL-6: 426.8-fold increase, p0.001).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.

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.

Pressure-controlled intermittent coronary sinus occlusion has been reported to reduce infarct size in dogs with coronary artery occlusion, possibly because of increased ischemic zone perfusion and washout of toxic metabolites. The influence of this intervention on regional myocardial function was investigated in open and closed chest dogs. In six open chest dogs with severe stenosis of the left anterior descending coronary artery and subsequent total occlusion, a 10 minute application of intermittent coronary sinus occlusion increased ischemic myocardial segment shortening from 5.5 ± 1.2 to 8.2 ± 2.6% (NS) and from −0.1 ± 2.1 to 2.3 ± 1.2% (NS), respectively.In eight closed chest anesthetized dogs, intermittent coronary sinus occlusion was applied for 2.5 hours between 30 minutes and 3 hours of intravascular balloon occlusion of the proximal left anterior descending coronary artery. Standardized two-dimensional echocardio-graphic measurements of left ventricular function were performed to derive systolic sectional and segmental fractional area changes in five short-axis cross sections of the left ventricle. Fractional area change in all the severely ischemic segments (< 5% systolic wall thickening) was −4.0 ± 4.7% at 30 minutes after occlusion, and increased with subsequent 60 and 150 minutes of treatment to 13.1 ± 3.3 and 7.0 ± 3.3%, respectively (p < 0.05). At the most extensively involved low papillary muscle level of the ventricle, regional ischemic fractional area change was increased by intermittent coronary sinus occlusion between 30 and 180 minutes of coronary occlusion from −0.4 ± 0.1 to 14.4 ± 4% (p < 0.05), whereas a further deterioration was noted in untreated dogs with coronary occlusion.Continuous arterial and coronary venous blood density measurements were performed in seven open chest dogs to determine the influence of pressure-controlled intermittent coronary sinus occlusion on ischemic myocardial washout. The arteriovenous density gradient was 0.16 ± 0.05 g/Iiter during coronary artery occlusion, and decreased to 0.05 ± 0.08 g/liter (p < 0.05) as a result of the intervention, suggesting a significant fluid washout from the myocardium. It is concluded that pressure-controlled intermittent coronary sinus occlusion provides recovery of cardiac function and that this benefit might be associated with enhanced ischemic zone washout.