Dynamic and differential changes in myocardial and plasma endothelin in patients undergoing cardiopulmonary bypass.

OBJECTIVE: The bioactive peptide endothelin modulates left ventricular function by changing afterload, coronary vascular tone, and myocardial contractility. However, whether increased plasma endothelin levels observed in patients during and after coronary revascularization and cardiopulmonary bypass reflect actual myocardial interstitial levels are unknown. METHODS: A microdialysis probe (outer diameter: 0.77 mm; length: 4 mm) was placed in the left ventricular apical midmyocardium in 20 patients and myocardial interstitial fluid was collected (2.5 microL/min) at baseline and up to 30 minutes after cardiopulmonary bypass. Myocardial interstitial and systemic arterial endothelin were measured by radioimmunoassay. RESULTS: Baseline myocardial interstitial endothelin was over 6-fold higher than plasma (20.11 +/- 2.07 vs 3.19 +/- 0.25 fmol/mL, P < .05). Plasma endothelin increased by 23% +/- 12% at 60 minutes of cardiopulmonary bypass whereas myocardial interstitial endothelin increased by 105% +/- 24%, P < .05), and this change was higher than in the plasma ( P < .05). Although no further change in plasma endothelin occurred during cardiopulmonary bypass, myocardial interstitial levels increased further after crossclamp removal (400% +/- 75%) and remained significantly higher than plasma at separation from cardiopulmonary bypass. CONCLUSION: The unique findings of this study were 2-fold: First, significant compartmentalization of endothelin exists within the human myocardium. Second, a significantly higher and temporally disparate change in myocardial interstitial endothelin occurs during and after cardiopulmonary bypass when compared with systemic levels. These dynamic changes in myocardial endothelin likely influence coronary vascular tone and contractility.

The effects of leukocyte reduction on matrix metalloproteinase release in cardiopulmonary bypass.

Matrix metalloproteinases (MMPs) are a family of enzymes responsible for degrading the extracellular matrix, a process that likely contributes to the development of altered vascular permeability. Past studies in patients undergoing cardiopulmonary bypass (CPB) have documented increased levels of MMPs with CPB. The purpose of this study was to evaluate the effect of leukocyte reduction on MMP release during CPB. Patients (n = 17) undergoing elective coronary revascularization requiring CPB were randomly assigned to either a leukocyte-reducing filter (LRF) group (n = 9) or the standard CPB circuit with no LRF (n = 8). White blood cell (WBC) counts, MMP-2, and MMP-9 levels were serially measured at baseline and up to 12 hours post CPB. MMP levels were measured by enzyme-linked immunoassay. ProMMP-2 levels increased in both the non-LRF and LRF groups but to a higher degree in the LRF group. ProMMP-9 levels increased by 40% in the non-LRF group. In contrast, proMMP-9 decreased by 30% in the LRF group. The addition of leukocyte-reducing filters in the CPB circuit attenuated the release of MMP-9 but increased release of MMP-2 post-CPB. Because MMPs can degrade the extracellular matrix, leading to increased vascular permeability, attenuation of MMPs may have decreased the local tissue injury known to occur as a result of these enzymes. However, future prospective studies to test this hypothesis directly are warranted.

Fresh frozen plasma in the pediatric pump prime: a prospective, randomized trial.

BACKGROUND: The aim of this study was to determine whether the use of fresh frozen plasma (FFP) in the infant pump prime can avoid dilution of fibrinogen, decrease the need for blood product transfusion after bypass, and decrease exposure to donor blood products. METHODS: Twenty infants weighing less than 8 kg were prospectively randomized to receive either 1 U of FFP (10 patients) or no FFP (10 patients) in the pump prime. Mean age (4.2 +/- 2.8 months), weight (4.3 +/- 1.1 kg), total prime volume (641 +/- 96 ml), cardiopulmonary bypass time, cross-clamp time, lowest temperature on bypass, and preoperative coagulation parameters did not differ between the two groups. RESULTS: At the end of bypass, the mean fibrinogen level was significantly higher in the FFP than the no FFP group (123 +/- 20 versus 58 +/- 17 mg/dL; p < 0.0001), whereas the mean platelet count did not differ (60 +/- 25 versus 52 +/- 26 K/mm(3); p = 0.5). Patients in the FFP group received significantly fewer units of cryoprecipitate (0.4 +/- 0.8 versus 2.0 +/- 0.9 U/patient; p < 0.001), and had a mean total donor exposure of 4.1 +/- 1.5 U/patient versus 5.4 +/- 1.4 U/patient in the no FFP group (p = 0.06). The mean chest tube output over the first 24 hours did not differ between groups. CONCLUSIONS: The use of FFP in the pump prime significantly limited dilutional hypofibrinogenemia, decreased the transfusion of cryoprecipitate after bypass, and tended to decrease the overall mean patient exposure to blood products.

A prospective, randomized study of endothelin and postoperative recovery in off-pump versus conventional coronary artery bypass surgery.

OBJECTIVE: The objectives are 2-fold: (1). to serially determine endothelin (ET) levels in arterial vascular compartments in patients undergoing coronary artery bypass surgery using either cardiopulmonary bypass or off-pump techniques, and (2). to define potential relationships between endothelial levels and specific perioperative parameters of patient recovery. METHODS: In a prospective, randomized study, endothelin plasma content was measured from patients undergoing coronary artery bypass grafting using either off-pump techniques (OPCAB group, n = 25) or conventional cardiopulmonary bypass (CPB group, n = 25) before surgery, before and after coronary artery anastomosis, and 6 and 24 hours postoperatively. Specific indices of patient recovery including pulmonary artery pressures, ventilation requirement, and hospital stay were documented for patients in both study groups. RESULTS: Postoperative systemic arterial ET levels were significantly increased by 200% in the CPB group and 50% in the OPCAB group. ET levels remained significantly higher in the CPB group relative to the OPCAB group throughout the postoperative period of observation (p < 0.05). Pulmonary artery pressures, ventilation requirement, and hospital stay were significantly increased in patients in the CPB group. CONCLUSIONS: Postoperative ET levels were higher in patients who underwent CPB for coronary artery bypass surgery. Increased ET in the postoperative period may contribute to a more complex recovery from coronary artery bypass surgery in patients undergoing cardiopulmonary bypass.

The infant with single ventricle and excessive pulmonary blood flow: results of a strategy of pulmonary artery division and shunt.

BACKGROUND: The infant with a single ventricle and excessive pulmonary blood flow requires early protection of the pulmonary vascular bed to insure suitability for a subsequent Fontan procedure. The traditional approach, pulmonary artery banding, has had disappointing results. We have pursued an alternate strategy: division of the pulmonary artery, and placement of a systemic-to-pulmonary artery shunt. Potential sites of systemic outflow tract obstruction are simultaneously bypassed, by either a Damus-Kaye-Stansel, or modified Norwood procedure. METHODS: From January 1996 to June 2001, 22 infants were treated by this strategy. Patients with hypoplastic left heart syndrome were excluded. Median age was 18 days (range 2 days to 6 months). In addition to pulmonary artery division and shunt, 3 of 22 patients underwent a Damus-Kaye-Stansel procedure, and 13 of 22 patients underwent a modified Norwood procedure. RESULTS: There were no operative deaths, and one late death. Actuarial survival beyond 30 months was 90%. At follow-up catheterization in 22 patients, median transpulmonary gradient was 7 mmHg (range 4 to 18), and median pulmonary vascular resistance 1.9 Wood units (range 0.9 to 3.3). Twenty-one patients have undergone a subsequent bidirectional superior cavopulmonary connection, and 6 a Fontan procedure, with no deaths. No patient developed subaortic stenosis, or aortic arch obstruction. Neoaortic insufficiency was none or trivial in 12 patients, mild in 3, and moderate in 1. CONCLUSIONS: In patients with a functional single ventricle and excessive pulmonary flow, a strategy of pulmonary artery division and shunt, along with prophylactic bypass of systemic outflow obstruction, carries low operative and midterm mortality. It provides consistent protection of the pulmonary vascular bed, avoids subaortic stenosis and aortic arch obstruction, minimizes neoaortic insufficiency, and ensures suitability for progression along a Fontan pathway. These results provide a comparison for alternate strategies, including pulmonary artery banding.