A review of leukofiltration in cardiac surgery: the time course of reperfusion injury may facilitate study design of anti-inflammatory effects.

The systemic inflammatory response syndrome (SIRS) is a well-recognized phenomenon attending cardiopulmonary bypass (CPB) surgery. SIRS leads to costly complications and several strategies intended to ameliorate the symptoms have been studied, including leukocyte reduction using filtration. Although the body of work suggests that leukoreduction attenuates SIRS, discrepancies remain within the literature.

Conditioned blood reperfusion during angioplasty (CoBRA) treatment of acute myocardial infarction.

Acute myocardial infarct (MI) results in ischemia distal to lesions which puts heart muscle at risk for reperfusion injury (RI). Neutrophils, platelets and complement are putative mediators of RI. Recent advances in filtration technology provide integrated neutrophil and platelet removal together with complement-attenuating properties in a single blood-conditioning device.

Aprotinin inhibits thrombin formation and monocyte tissue factor in simulated cardiopulmonary bypass.

Background: Aprotinin reduces perioperative bleeding after open heart surgery, primarily by inhibiting fibrinolysis. In addition, the drug has both procoagulant and anticoagulant effects that involve complex reactions of coagulation proteins and cells that are incompletely understood. This study tests the hypothesis that aprotinin has an anticoagulant effect on the extrinsic coagulation pathway.

Enoxaparin suppresses thrombin formation and activity during cardiopulmonary bypass in baboons.

Objective: This study tests the hypotheses that enoxaparin, a low molecular weight heparin and potent inhibitor of factor Xa, alone or in combination with standard heparin, inhibits thrombin formation and activity and modulates complement activation and neutrophil elastase release during cardiopulmonary bypass in baboons.

Methods: After preliminary studies to determine doses and possible species differences to anticoagulants and protamine, 27 anesthesized baboons had normothermic cardiopulmonary bypass with standard, unfractionated, porcine intestinal heparin, enoxaparin, or a combination of heparin and enoxaparin. Protamine in appropriate doses was used to reverse anticoagulation.

Papillary muscle discoordination rather than increased annular area facilitates mitral regurgitation after acute posterior myocardial infarction.

Background: Acute posterior myocardial infarction that produces immediate mitral regurgitation alters the mitral annulus and its spatial relationship with both papillary muscles. The precise deformations that cause valve insufficiency are not understood and impair efforts to repair the valve.

Methods And Results: In six Dorsett hybrid sheep, sonomicrometry transducers were placed around the mitral annulus (6) and at the tips and bases of both papillary muscles (4).

A baboon model for hematologic studies of cardiopulmonary bypass.

Objective investigation of new inhibitors of blood protein or cellular systems that are activated during cardiopulmonary bypass (CPB) is impeded by the absence of a satisfactory animal model. Because most baboon hematologic proteins immunologically cross-react with those used for human assays, we developed a robust, reusable baboon model of CPB. Blood samples were obtained from adult baboons at six time intervals before, during, and after 60 minutes of partial CPB at 37 degrees C with peripheral cannulas.

Distortions of the mitral valve in acute ischemic mitral regurgitation.

Background: In the absence of papillary muscle rupture, the precise deformations that cause acute postinfarction mitral valve regurgitation are not understood and impair reparative efforts.

Methods: In 6 Dorsett hybrid sheep, sonomicrometry transducers were placed around the mitral annulus (n = 6) and at the tips and bases of both papillary muscles (n = 4). Later, specific circumflex coronary arteries were occluded to infarct approximately 32% of the posterior left ventricle and produce acute 2 to 3+ mitral regurgitation.

Tirofiban provides "platelet anesthesia" during cardiopulmonary bypass in baboons.

Objective: Tirofiban (Aggrastat) is a reversible, nonpeptide inhibitor of platelet glycoprotein II/IIIa receptors. We tested the hypothesis that tirofiban preserves platelet number and function and shortens postoperative bleeding times in baboons after cardiopulmonary bypass.

Methods: Four groups were studied: control, n = 12; low-dose tirofiban (0.

Effect of factor Xa inhibitors on thrombin formation and complement and neutrophil activation during in vitro extracorporeal circulation.

Background: Even when large doses of heparin are administered during cardiopulmonary bypass, thrombin is produced. Thrombin is a powerful protease that is associated with the thrombotic and bleeding complications of open heart surgery and is produced by cleavage of prothrombin by factor Xa. This study assessed the ability of a specific inhibitor of factor Xa, recombinant tick anticoagulant peptide (rTAP), alone or in combination with standard heparin and a low-molecular-weight heparin, enoxaparin, to suppress thrombin formation and activity during in vitro extracorporeal circulation.

Pericardial blood activates the extrinsic coagulation pathway during clinical cardiopulmonary bypass.

Background: Coagulation during cardiopulmonary bypass (CPB) traditionally has been attributed to activation of the contact system of plasma proteins and the intrinsic coagulation pathway by blood contact with negatively charged surfaces not lined by endothelium. Recent studies have focused on the possible role of the extrinsic coagulation pathway during cardiac surgery. We postulated that the wound activates the extrinsic coagulation pathway during CPB by producing procoagulant cells and enzymes that enter the general circulation.

Nafamostat mesilate, a broad spectrum protease inhibitor, modulates platelet, neutrophil and contact activation in simulated extracorporeal circulation.

Activation of humoral and cellular participants in inflammation enhances the risk of postoperative bleeding and multiple organ damage in cardiopulmonary bypass (CPB). We now compare the effects of heparin alone in combination with nafamostat mesilate (NM), a protease inhibitor with specificity of trypsin-like enzymes, in an extracorporeal circuit which simulates CPB. NM significantly inhibits the release of platelet beta-thromboglobulin (beta TG) at 60 and 120 min.

Surface-bound heparin fails to reduce thrombin formation during clinical cardiopulmonary bypass.

The hypothesis that heparin-coated perfusion circuits reduce thrombin formation and activity; fibrinolysis; and platelet, complement, and neutrophil activation was tested in 20 consecutive, randomized adults who had cardiopulmonary bypass. Twenty identical perfusion systems were used; in 10, all blood-contacting surfaces were coated with partially degraded heparin (Carmeda process; Medtronic Cardiopulmonary, Anaheim, Calif.).

Reversal of heparin anticoagulation by recombinant platelet factor 4 and protamine sulfate in baboons during cardiopulmonary bypass.

The ability of recombinant platelet factor 4 and protamine to neutralize heparin after cardiopulmonary bypass was compared in anesthestized baboons. Clotting titration curves of heparinized baboon blood demonstrate an anticoagulant effect of protamine that is not seen with recombinant platelet factor 4. Neither drug caused meaningful changes in central pressures or cardiac output within 30 minutes after injection.

Iloprost and echistatin protect platelets during simulated extracorporeal circulation.

Temporary, reversible inhibition of platelets during cardiopulmonary bypass is an attractive strategy to protect platelets and normalize postoperative bleeding times. Iloprost, an analogue of prostacyclin, and the disintegrins reversibly inhibit platelets by different mechanisms. We tested the hypothesis that reduced doses of iloprost and either echistatin, a natural disintegrin, or RO43-5054, a peptidomimetic, in combination provide better platelet protection than any drug alone during simulated extracorporeal circulation.

Upregulation of Mac-1 surface expression on neutrophils during simulated extracorporeal circulation.

The leukocyte integrin Mac-1 (alpha m beta 2, CD11b/18 CR3, MO1), in addition to binding iC3b, has been shown to be the receptor for the coagulation proteins fibrinogen, factor X, and high molecular weight kininogen. Mac-1 is known to be upregulated by agonists that stimulate neutrophils or monocytes. Previous studies from this laboratory have documented neutrophil activation during cardiopulmonary bypass.