Precise quantification of pulsatility is a necessity for direct comparisons of six different pediatric heart-lung machines in a neonatal CPB model.

Generation of pulsatile flow depends on an energy gradient. Surplus hemodynamic energy (SHE) is the extra hemodynamic energy generated by a pulsatile device when the adequate pulsatility is achieved. The objective of this study was to precisely quantify and compare pressure-flow waveforms in terms of surplus hemodynamic energy levels of six different pediatric heart-lung machines in a neonatal piglet model during cardiopulmonary bypass (CPB) procedures with deep hypothermic circulatory arrest (DHCA). Thirty-nine piglets (average weight, 3 kg) were subjected to CPB with a hydraulically driven physiologic pulsatile pump (PPP; n=7), Jostra-HL 20 pulsatile roller pump (Jostra-PR; n=6), Stockert Sill pulsatile roller pump (SIII-PR; n=6), Stockert Sill mast-mounted pulsatile roller pump with a miniature roller head (Mast-PR; n=7), Stockert Sill mast-mounted nonpulsatile roller pump (Mast-NP; n=7), or Stockert CAPS nonpulsatile roller pump (CAPS-NP, n=7). Once CPB was begun, each animal underwent 20 minutes of hypothermia, 60 minutes of DHCA, 10 minutes of cold reperfusion, and 40 minutes of rewarming. The pump flow rate was maintained at 150 ml x kg(-1) x min(-1) and the mean arterial pressure (MAP) at 45 mm Hg. In the pulsatile experiments, the pump rate was kept at 150 bpm and the stroke volume at 1 ml/kg. The SHE (ergs/cm3) = 1,332 ([(integral fpdt) / (integral fdt)] - MAP) was calculated at each experimental stage. During normothermic CPB (15 minutes on pump), the physiologic pulsatile pump generated the highest surplus hemodynamic energy (8563 +/- 1918 ergs/cm3, p < 0.001) compared with all other pumps. The Jostra HL-20 and Stockert Sill pulsatile roller pumps also produced adequate surplus hemodynamic energy. Nonpulsatile roller pumps and the Stockert Sill mast-mounted pulsatile roller pump did not generate any extra hemodynamic energy. During hypothermic CPB and after DHCA and rewarming, the results were extremely similar to those seen during normothermic CPB. The surplus hemodynamic energy formula is a novel method to precisely quantify different levels of pulsatility and nonpulsatility for direct and meaningful comparisons. The PPP produced the greatest surplus hemodynamic energy. Most of the pediatric pulsatile pumps (except Mast-PR) generated significant surplus hemodynamic energy. None of the nonpulsatile roller pumps generated adequate surplus hemodynamic energy.

Anesthetic induction with ketamine inhibits platelet activation before, during, and after cardiopulmonary bypass in baboons.

The objective of this study was to investigate the effects of antifactor D monoclonal antibody (Mab) 166-32 on platelet activation during and after hypothermic cardiopulmonary bypass (CPB) in baboons. Fourteen baboons (mean weight, 15 kg) underwent hypothermic CPB. Seven of them were treated with a single injection of antifactor D Mab 166-32 (5 mg/kg) and the other seven animals were given saline as control. Each baboon was sedated with an intramuscular injection of 10 mg/kg of ketamine hydrochloride. A 20-gauge angiocatheter was placed in the cephalic vein, and 5 mg of diazepam was administered intravenously. Anesthesia was maintained with 0.80% to 2.25% isoflurane, 100% O2, and an inspiratory tidal volume of 13 mL/kg at a rate of 13 breaths per minute throughout the surgical procedure except during CPB. Pancuronium bromide, 0.1 mg/kg, was administered to achieve adequate muscle paralysis. Blood samples were collected before CPB, during CPB, and 1, 2, 3, and 6 h after CPB. Assays were performed to measure platelet activation [CD62P (P-selectin)] using immunofluorocytometric methods. There were no significant differences on CD62P expression of platelets between control and antibody groups before CPB (105 +/- 12% vs. 99 +/- 8%, P=NS), during normothermic CPB (62 +/- 6% vs. 63 +/- 19%, P=NS), during hypothermic CPB (55 +/- 8% vs. 54 +/- 13%, P=NS), and 1, 3, or 6 h after CPB (74 +/- 20% vs. 81 +/- 11%, P=NS). Anesthetic induction with ketamine caused significant reduction in the platelet activation in both groups. Ketamine did not affect complement, neutrophil, and monocyte activation or cytokine production. Further studies on the mechanisms of platelet inhibition by ketamine are warranted.

Metabolically controlled reperfusion in acute myocardial infarction: should the polarizing solution be given subselectively?

BACKGROUND: In working rat hearts, metabolic support of injured tissue enhances recovery after acute myocardial infarction. Clinical experience with a systemic "polarizing solution" supports this claim. OBJECTIVES: In a dog model of ischemia/reperfusion, we tested the feasibility of subselectively supplying adapted metabolic substrates before instituting blood reperfusion. METHODS: Thirty-five dogs underwent ligation of the proximal left anterior descending artery and collaterals for 90 minutes. The animals were randomly assigned to receive direct blood reperfusion (Group I), intracoronary glucose, insulin, and potassium (Group II), or intracoronary glucose, insulin, and potassium plus propionyl-L-carnitine (PLC) (Group III). After 30 minutes of artificial reperfusion, prograde blood flow was resumed in groups II and III. A routine necropsy was performed 3 to 5 days later. Primary endpoints were severe arrhythmias, death, markers of infarct size, and specific histologic features. RESULTS: We excluded 4 dogs for technical reasons and 2 others for preexisting cardiomyopathy. In the remaining 29 animals, large apical infarctions were documented ventriculographically during arterial ligation. One dog died of irreversible ventricular fibrillation during the initial ischemic period, and 9/28 dogs (32.1%) died during early reperfusion. Ventricular fibrillation was more common with 10% (versus 5%) dextrose concentrations and was eliminated by PLC. Irreversibly injured (versus jeopardized) areas of myocardium were more common in Group III (85.9 19.3%) than in Groups I and II (16.9 10.8%). CONCLUSION: Subselective infusion of metabolically supportive solutions during acute myocardial infarction is technically feasible. To prevent osmotic endothelial damage, the perfusate must have a low (< 5%) dextrose content.

Novel anti-factor D monoclonal antibody inhibits complement and leukocyte activation in a baboon model of cardiopulmonary bypass.

BACKGROUND: Adverse outcomes after cardiopulmonary bypass (CPB) are often related to systemic inflammation triggered by complement and leukocyte activation. To determine how inhibition of the alternative complement pathway affects systemic inflammation and tissue injury, we studied a novel monoclonal antibody (Mab), anti-human factor D murine Mab 166-32, in baboons. METHODS: Fourteen baboons (mean weight, 15 kg) underwent hypothermic CPB. The treatment group (n = 7) received a single injection of anti-factor D Mab 166-32 (5 mg/kg), and the control group (n = 7) was given saline solution. After initiation of CPB, all animals were subjected to 20 minutes of core cooling (rectal temperature, 27 degrees C), followed by 60 minutes of aortic cross-clamping, 25 minutes of rewarming, and 30 minutes of normothermic CPB. Blood samples were collected before CPB, during CPB, and 1, 2, 3, 6, and 18 hours after CPB. To measure neutrophil and monocyte activation, we performed flow cytometry for CD11b expression, ELISA for complement activation (Bb, C3a, C4d, and sC5b-9) and interleukin-6 (IL-6) production, and tissue injury studies for creatine kinase MB isoenzymes (CK-MB), creatine kinase (CK), and lactic dehydrogenase (LDH) levels. RESULTS: Anti-factor D Mab almost completely inhibited plasma Bb, C3a, and sC5b-9 production during CPB (P < .001). CD11b expression on neutrophils (129 +/- 5% vs. 210 +/- 42%; P = .0006) and on monocytes (139 +/- 14% vs. 245 +/- 43%; P = .0002) was also lower in the treatment group during CPB. The treated animals had a significantly smaller increase in plasma IL-6 concentrations than did the control animals (71 +/- 27 pg/mL vs. 104 +/- 54 pg/mL; P = .0002). CK-MB levels were also lower in the treatment group 6 hours after the end of CPB (204 +/- 30 vs. 335 +/- 59 IU/L; P = .003) and 18 hours after the end of CPB (P < .05). Creatine kinase levels (6 and 18 hours after the end of CPB) and LDH levels (3 and 6 hours after the end of CPB) showed patterns similar to those of CK-MB (P < .05). CONCLUSIONS: The alternative complement pathway plays a major role in systemic inflammation during CPB. Inhibition of complement activation via the alternative pathway by anti-factor D Mab 166-32 significantly reduces leukocyte activation and tissue injury in our baboon model.