BACKGROUND: Cardioplegic solutions have been used to enhance myocardial preservation during cardiac surgery. The benefits derived from preventing myocardial ischemia with cardioplegic solutions may, however, be countered by tissue damage that occurs when the myocardium is reperfused with oxygenated blood. Furthermore, cardioplegia-induced endothelial dysfunction may contribute to depressed myocardial function postoperatively. The endothelium of coronary arteries and vein grafts is damaged by crystalloid cardioplegic solutions. There is less known about the effects of cardioplegic solutions on the microvasculature. METHODS AND RESULTS: The hypothesis that microvascular damage occurs following perfusion with hyperkalemic, crystalloid, cardioplegic solutions and blood reperfusion, leading to decreased blood flow and increased neutrophil accumulation, was tested in a model system. Intravital microscopic observations were performed during a 20-minute perfusion of the hamster cremaster muscle with cardioplegic solutions (10 degrees C) via the femoral artery with the iliac occluded and during a subsequent 2-hour blood reperfusion period (iliac open). Arteriolar vasoconstriction (27% decrease in diameter, p less than 0.05) and a 25% decrease in the density of perfused capillaries (p less than 0.05) occurred during reperfusion in hamsters receiving crystalloid cardioplegic solution (16 meq K+) compared to control hamsters (no cardioplegic solution given). Neutrophils accumulated on venular endothelium in treated animals (250% increase, p less than 0.05) and extravascularly (myeloperoxidase levels 2.0 +/- 0.4 U/g versus 1.3 +/- 0.3 U/g in control, p less than 0.05). The addition of adenosine (10(-4) M) and albumin (2 g%) to the cardioplegic perfusate, accompanied by the administration of adenosine (10(-4) M) during reperfusion, produced arteriolar vasodilation (34% diameter increase, p less than 0.05) and inhibited extravascular neutrophil accumulation (myeloperoxidase level of 1.5 +/- 0.2 U/g, p greater than 0.05 versus control). Capillary perfusion, however, was still significantly diminished (28% decrease, p less than 0.05.) CONCLUSIONS: We conclude that injury manifest by decreased microvascular blood flow and increased neutrophil accumulation in tissues occurs after perfusion with hypothermic, hyperkalemic, crystalloid cardioplegic solutions and blood reperfusion. Adenosine seems to partially attenuate this injury by dilating arterioles and decreasing extravascular neutrophil accumulation.
BACKGROUND: Cardioplegic solutions have been used to enhance myocardial preservation during cardiac surgery. The benefits derived from preventing myocardial ischemia with cardioplegic solutions may, however, be countered by tissue damage that occurs when the myocardium is reperfused with oxygenated blood. Furthermore, cardioplegia-induced endothelial dysfunction may contribute to depressed myocardial function postoperatively. The endothelium of coronary arteries and vein grafts is damaged by crystalloid cardioplegic solutions. There is less known about the effects of cardioplegic solutions on the microvasculature. METHODS AND RESULTS: The hypothesis that microvascular damage occurs following perfusion with hyperkalemic, crystalloid, cardioplegic solutions and blood reperfusion, leading to decreased blood flow and increased neutrophil accumulation, was tested in a model system. Intravital microscopic observations were performed during a 20-minute perfusion of the hamster cremaster muscle with cardioplegic solutions (10 degrees C) via the femoral artery with the iliac occluded and during a subsequent 2-hour blood reperfusion period (iliac open). Arteriolar vasoconstriction (27% decrease in diameter, p less than 0.05) and a 25% decrease in the density of perfused capillaries (p less than 0.05) occurred during reperfusion in hamsters receiving crystalloid cardioplegic solution (16 meq K+) compared to control hamsters (no cardioplegic solution given). Neutrophils accumulated on venular endothelium in treated animals (250% increase, p less than 0.05) and extravascularly (myeloperoxidase levels 2.0 +/- 0.4 U/g versus 1.3 +/- 0.3 U/g in control, p less than 0.05). The addition of adenosine (10(-4) M) and albumin (2 g%) to the cardioplegic perfusate, accompanied by the administration of adenosine (10(-4) M) during reperfusion, produced arteriolar vasodilation (34% diameter increase, p less than 0.05) and inhibited extravascular neutrophil accumulation (myeloperoxidase level of 1.5 +/- 0.2 U/g, p greater than 0.05 versus control). Capillary perfusion, however, was still significantly diminished (28% decrease, p less than 0.05.) CONCLUSIONS: We conclude that injury manifest by decreased microvascular blood flow and increased neutrophil accumulation in tissues occurs after perfusion with hypothermic, hyperkalemic, crystalloid cardioplegic solutions and blood reperfusion. Adenosine seems to partially attenuate this injury by dilating arterioles and decreasing extravascular neutrophil accumulation.