Effect of extracorporeal membrane oxygenation on left ventricular function of swine.

BACKGROUND: Previous clinical and experimental investigations have produced inconsistent data describing the effects of veno-arterial extracorporeal membrane oxygenation (VA ECMO) on intrinsic left ventricular (LV) function. We report an animal model that allows investigation of the effects of VA ECMO on the mechanics of the LV using two load-insensitive indices: end-systolic pressure-minor axis dimension relationship (ESPDR) and preload recruitable dimensional stroke work (PRDSW). METHODS: Eight piglets (5 to 11 kg) were anesthetized, instrumented, and placed on VA ECMO. Throughout the experiment, systemic and left atrial partial pressure of oxygen were maintained between 100 to 200 mm Hg. At ECMO flow rate of 50% of baseline cardiac output, data were collected prior to ECMO, at 4 and 6 hours during ECMO, and after weaning from ECMO. Data measured or calculated for each time point included heart rate, LV pressures and minor axis dimensions at different pre-loads, first derivative of LV pressure with respect to time, velocity of circumferential fiber length shortening (VCF), LV shortening fraction (LVSF), ESPDR, and PRDSW. RESULTS: A significant (p < 0.05) decrease in LVSF and VCF was seen at 4 and 6 hours during ECMO when compared to baseline, but the ESPDR and PRDSW did not change during ECMO. CONCLUSIONS: VA ECMO alone changes some of the load-dependent parameters of contractility, but intrinsic function of the heart is not significantly affected as measured by load-insensitive indices of LV performance.

Cardiopulmonary bypass with deep hypothermic circulatory arrest for a patient with sickle cell anemia: a case report.

A 36-year-old sickle cell anemia patient undergoing a pulmonary thromboendarterectomy required the use of cardiopulmonary bypass incorporating deep hypothermic circulatory arrest. Being aware of reported incidences of sickling crises, a team of the surgeon, anesthesiologist, hematologist, and perfusionist met to devise a plan of treatment. Treatment included preoperative and intraoperative exchange transfusion, optimal blood gas management, and increased blood flows during bypass. The surgical procedure was performed and was successful in reducing pulmonary hypertension, incorporating a team approach and utilizing these techniques. No incidence of adverse sickling events was observed during this procedure.

Hyperthermic intraoperative intraperitoneal chemotherapy for peritoneal carcinomatosis and sarcomatosis using a cardioplegia heat exchanger and a two-pump system: a case report.

A 34-year-old male diagnosed with pseudomyxoma peritoneii presented for an exploratory laparotomy and hyperthermic intraoperative intraperitoneal chemotherapy. A circuit using two roller pumps and a cardioplegia administration set was assembled to deliver the chemotherapy perfusate at a consistent temperature. The authors discuss a case in which this treatment modality was used, describing the perfusionist's role and the circuit design.

Effects of hemofiltration on serum aprotinin levels in patients undergoing cardiopulmonary bypass.

OBJECTIVE: To determine the effects of hemofiltration on serum aprotinin levels during cardiopulmonary bypass (CPB) surgery. DESIGN: Prospective, randomized study. SETTING: University of Washington Medical Center, single institution. PARTICIPANTS: Patients undergoing cardiac surgery without contraindications to aprotinin administration. INTERVENTIONS: Patients were randomized to full-Hammersmith and half-Hammersmith dosing regimens of aprotinin and were further randomized to hemofiltration or no hemofiltration. MEASUREMENTS AND MAIN RESULTS: Serum aprotinin levels were studied before CPB, 60 and 120 minutes into CPB, and at the end of CPB before protamine administration. Each group experienced a decrease in serum aprotinin levels with the institution of CPB, attributable to hemodilution and redistribution of aprotinin outside of the vascular compartment. During CPB, aprotinin levels declined further, but no significant difference was observed between patients who received hemofiltration and those who did not. Hematocrit values were significantly higher at the end of CPB in the hemofiltration groups. Patients receiving half-Hammersmith dosing regimens maintained aprotinin levels throughout CPB, which have been shown to inhibit plasmin but were lower than levels previously shown to inhibit kallikrein. CONCLUSIONS: Hemofiltration during CPB did not significantly alter serum aprotinin levels in patients receiving half-Hammersmith and full-Hammersmith dosing regimens of aprotinin.

Angiographic and histological evaluation of porcine retinal vascular damage and protection with perfluorocarbons after massive air embolism.

BACKGROUND AND PURPOSE: We have previously shown that perfluorocarbon emulsions (PFEs) reduce the severity of cerebral injury (indicated by infarct, reduced blood flow, and depressed EEG) induced by air embolism during cardiopulmonary bypass (CPB). This study used retinal fluorescein angiography to define the mechanisms of cerebral injury and to determine the efficacy of PFEs in cerebral protection. These angiographic findings were correlated to previously reported histologic findings. METHODS: Twenty domestic pigs underwent CPB with a prime of standard crystalloid or PFE (5 mg/kg) and crystalloid. After 10 minutes on CPB, a single (5 mL/kg) or double (2x2.5 mL/kg) bolus of room air or saline (control) was delivered via the right carotid artery. Retinal fluorescein angiograms were captured at 4 time points: baseline, air insult, postbypass, and postreperfusion. Following euthanasia, both eyes were removed and the retinas isolated for histological analysis with horseradish peroxidase (HRP), as previously reported. RESULTS: In control pigs, postreperfusion angiograms showed small nonperfused areas, and retinal whole mounts demonstrated vascular damage as previously reported. In 5 PFE-primed animals, postreperfusion angiograms showed hyperfluorescence, but angiograms and HRP mounts were otherwise not significantly different from baseline. Severely hyperfluorescent vessels observed angiographically also showed a correlation with HRP extravasation but were not consistently indicative of severe vascular damage. CONCLUSIONS: Retinal fluorescein angiography and retinal staining with HRP indicate that mechanisms of cerebral air embolism include nonperfusion, vascular leakage and spasm, red blood cell sludging, and hemorrhage. Priming with PFE prevented many of the sequelae associated with air embolism.

A second-generation blood substitute (perfluorodichlorooctane emulsion) does not activate complement during an ex vivo circulation model of bypass.

OBJECTIVES: To examine whether a second-generation perfluorocarbon (PFC) blood substitute added to the cardiopulmonary bypass (CPB) prime influences complement production. DESIGN: A prospective, randomized, single-blinded, ex vivo model. SETTING: A university hospital, laboratory, and clinics. PARTICIPANTS: Ten healthy adult consented volunteer blood donors (five men, five women). INTERVENTIONS: Ex vivo closed-loop extracorporeal circuit including membrane oxygenator, tubing, and filter primed with crystalloid or crystalloid plus PFC was circulated for 1 hour with the addition of 500 mL of heparinized fresh human whole blood. MEASUREMENTS AND MAIN RESULTS: Laboratory specimens were drawn from the circuit at 10-minute intervals for 1 hour and measured for complement (C3a, Bb fragment) concentrations, blood gases, fibrinogen concentration, platelet count, and hematocrit. In the PFC group, C3a and Bb fragments were equal to or less than those in the group that received crystalloid alone. CONCLUSION: The second-generation PFC added to the prime of a CPB circuit does not independently increase complement production.

Heparin-coated bypass circuits (Carmeda) suppress the release of tissue plasminogen activator during normothermic coronary artery bypass graft surgery.

OBJECTIVES: To study fibrinolysis in a homogeneous first-time coronary artery bypass surgery (CABG) population in whom heparin-coated circuits were used. DESIGN: A prospective, blinded, randomized, placebo-controlled study. SETTING: A university hospital, tertiary care, intraoperative and postoperative intensive care unit. PARTICIPANTS: Twenty-one adult elective primary CABG patients. INTERVENTIONS: Randomized circuit-type centrifugal pump, membrane oxygenator, rigid cardiotomy reservoir, either placebo (n = 10) or heparin-coated (n = 11) (Carmeda; Medtronic Inc., Anaheim, CA). MEASUREMENTS AND MAIN RESULTS: Blood samples were analyzed for tissue plasminogen activator (TPA) activity, TPA antigen, plasminogen activator inhibitor-1 (PAI-1) activity, prothrombin complex F1.2, and antithrombin III (AT-III) at the following times: before cardiopulmonary bypass (CPB), during CPB (30 and 60 minutes), post-CPB, and day 1 postsurgery. TPA activity and antigen increased fivefold in the placebo group during CPB, whereas it did not even double in the heparin-coated group. PAI-1, F1.2, and AT-III were not different between groups. CONCLUSIONS: Heparin-coated CPB circuits reduced TPA release in this homogeneous CABG population with routine heparin/protamine management.

An in vitro comparison of gas transfer and pressure drop of the Bentley Duraflo Coated Spiral Gold and the Medtronic Carmeda Coated Maxima hollow fiber membrane oxygenators.

Two models of heparin coated, hollow fiber membrane oxygenators were tested in vitro to compare gas transfer and transoxygenator pressure drop using an established protocol. Oxygen and carbon dioxide transfer rates were measured at blood flows of 2.5 and 5.0 liters per minute with gas flow: blood flow ratios of 1:1 and 2:1 at both blood flows. All testing was performed under normothermic conditions. The data shows that oxygen transfer increases as blood flow is increased in both oxygenators. Similarly, carbon dioxide transfer is increased by both increased blood and gas flows. Finally, the pressure drop was dependent on blood flow rate alone. This study demonstrated these two oxygenators to be comparable in both oxygen and carbon dioxide transfer and also in transoxygenator pressure drop.

Horseradish peroxidase as a histological indicator of mechanisms of porcine retinal vascular damage and protection with perfluorocarbons after massive air embolism.

BACKGROUND AND PURPOSE: This laboratory has previously shown that a second-generation perfluorocarbon emulsion (PFE) reduces the severity of cerebral injury induced by air embolism during cardiopulmonary bypass (CPB). Horseradish peroxidase examines vascular permeability and was used in this study of the mechanisms of cellular protection afforded by the PFE. METHODS: Twenty domestic pigs underwent CPB with a prime of standard crystalloid or PFE (5 mg/kg) and crystalloid. After 10 minutes on CPB, a 5-mL/kg bolus of room air or saline (control) was delivered via the right carotid artery. The air insult was delivered as either a single bolus or double bolus. After 1 hour of CPB and 1 hour of spontaneous reperfusion, horseradish peroxidase was injected intravenously and circulated for 15 minutes. After euthanasia, both eyes were removed, and the retinas were isolated for histological analysis. RESULTS: Total length of retinal vessels exhibiting horseradish peroxidase extravasation was significantly less in PFE pigs (P < .05). Vascular spasm and red blood cell hemorrhages were unaffected by PFE. PFE pigs exhibited mild to moderate vascular nonperfusion and red blood cell sludging; crystalloid groups demonstrated severe nonperfusion and sludging. CONCLUSIONS: Histological staining with horseradish peroxidase indicated that mechanisms of cerebral air embolism include vascular endothelial leakage, vascular nonperfusion, and red blood cell sludging and hemorrhage. Pretreatment with PFE prevented some sequelae associated with massive air embolism and CPB.

An in vitro evaluation of an automatic clamp for use with centrifugal pumps.

The risk of air emboli is a concern for all perfusionists. A new clamping device for use with centrifugal pumps is designed to clamp both the arterial and venous lines at the first indication of air or retrograde flow, thereby allowing the perfusionist to evaluate the situation and correct the problem before entraining air into the arterial pump head. After evaluating this device in our lab, we conclude that this new safety device should be added to the heart lung machine by all perfusionists using centrifugal pumps.

Perfluorocarbon emulsion in the cardiopulmonary bypass prime reduces neurologic injury.

BACKGROUND: Perfluorocarbon emulsion has proved beneficial in the prevention and amelioration of experimental air embolism. We examined whether the addition of perfluorocarbon to the prime solution could lead to a reduction in the incidence and severity of neurologic injury after the formation of a massive air embolism during cardiopulmonary bypass. METHODS: Fourteen pigs underwent bypass in which either a crystalloid prime solution or a perfluorocarbon prime solution (10 mL/kg) was used. Ten minutes into bypass a bolus (5 mL/kg) of air or saline (control) was delivered via the carotid artery. The resulting cerebral infarcts were graded on the basis of the findings in triphenyltetrazolium chloride-stained cerebral sections. Colored microspheres were used to measure cerebral blood flow. Bitemporal electroencephalography was used to evaluate cerebral function. RESULTS: Cerebral infarction was not found in the perfluorocarbon-air group (0 to 5 animals), as compared with its occurrence in 3 of the 5 animals in the crystalloid-air group. Cerebral blood flow was also maintained or increased in the perfluorocarbon-air group (p < 0.05), and the electroencephalogram total power showed less of a decrease and recovered more completely (p < 0.05) than it did in the crystalloid-air group. CONCLUSIONS: The addition of perfluorocarbon emulsion to the cardiopulmonary bypass prime solution leads to a reduction in the incidence and severity of neurologic injury after the formation of a massive air embolism during bypass.

A perfluorocarbon emulsion prime additive improves the electroencephalogram and cerebral blood flow at the initiation of cardiopulmonary bypass.

Depression in electroencephalogram (EEG) has been documented clinically and is reproducible in swine at the initiation of cardiopulmonary bypass (CPB) utilizing a crystalloid prime. The physiological cause of this transient alteration in electrical brain activity appears to be associated with the transient drop in arterial pressure. The etiology is unknown but may be attributable to the bolus of the crystalloid prime or micro emboli, either air or fibrin-platelet. Thirteen swine (17-26 kg) were anesthetized and received 4 mg/kg dexamethasone, and following a tracheotomy were ventilated with halothane in 100% O2. Surgical preparation included: sternotomy and preparation for right atrial-aortic CPB. The CPB circuit consisted of a hollow fiber membrane oxygenator, a hard-shell venous reservoir, a roller pump, and PVC tubing. The circuit was randomly primed with either 1200 ml Plasmalyte-A or 10 ml/kg perfluorocarbon emulsion (PFE) and Plasmalyte-A to total 1200 ml. The animals were monitored continuously for systemic hemodynamics and electrocardiogram, and cerebral monitoring included blood flow and bitemporal EEG. Arterial blood gases were measured and PaCO2 was kept between 30-45 mmHg both before and during CPB. Cerebral blood flow (CBF) was measured pre-CPB and at 10 minutes after initiation of CPB. Bitemporal computerized EEG was analyzed every 60 seconds. Total power of each hemisphere, power in frequency bands, and spectral edge were recorded. All animals demonstrated a relative decrease in EEG total power at the onset of CPB. Animals that received PFE demonstrated a more stable arterial blood pressure, an increased CBF, and a lesser decrease and an earlier recovery of the EEG power.(ABSTRACT TRUNCATED AT 250 WORDS)

Infusion of autologous platelet rich plasma does not reduce blood loss and product use after coronary artery bypass. A prospective, randomized, blinded study.

Prior nonblinded studies have suggested dramatic hemostatic effects and decreased plasma after cardiopulmonary bypass. Platelet rich plasma (8 to 10 ml/kg total body weight) was obtained (Haemonetics Plasma Saver; Haemonetics Corp., Natick, Mass.) from 51 patients undergoing primary coronary artery bypass grafting before heparinization. After double-blinded randomization, the platelet rich plasma was reinfused immediately in the control group or after heparin reversal in the treatment group. Homologous blood product usage, blood loss, and the surgeon's intraoperative subjective assessment of coagulation were evaluated. Additionally, thromboelastography, prothrombin time, partial thromboplastin time, activated clotting time, fibrinogen, platelet counts, and hematocrit values were evaluated before the operation, after heparin reversal, after infusion of platelet rich plasma or control solution, and 2 hours after infusion. The surgeon's subjective assessment of coagulation was not different between control and treatment groups (p = 0.78). According to specific predetermined transfusion guidelines, no statistically significant differences were found in the use of whole blood (p = 0.07), packed red blood cells (p = 0.62), platelets (p = 0.11), total units of blood products (p = 0.45), or in the percentage of patients receiving transfusions (control group 70%, treatment group 71%, p = 0.97). Cumulative amount of blood shed through the chest tube was not significantly different between the groups at any interval but tended toward significance at 4, 6, and 12 hours (p = 0.09, 0.07, and 0.09). The prothrombin time immediately after reinfusion of platelet rich plasma was significantly lower in the treatment group (p = 0.03), but all other laboratory studies were similar at each time interval. Infusion of platelet rich plasma after cardiopulmonary bypass in patients having uncomplicated primary coronary artery bypass grafting has minimal effects on the surgeon's assessment of coagulation, total transfusion requirements, mediastinal drainage, and laboratory studies of coagulation.

An in vitro protocol for evaluation and comparison of membrane oxygenators.

With the trend in open heart surgery toward normothermic bypass and warm blood cardioplegia, greater demand is being placed on the perfusionist to select an oxygenator that will perform safely and efficiently under a variety of conditions. While manufacturers report performance parameters for their products, the data is often not comparable due to widely differing conditions. Recent in vitro evaluation techniques employed to characterize membrane oxygenators do not simulate the actual oxygenator conditions observed during cardiopulmonary bypass. Biocompatibility and drug delivery are reported but comparisons of different oxygenator performance parameters are not completely addressed. We have designed a test circuit and an evaluation protocol to simultaneously characterize the performance of multiple oxygenators under identical conditions. The test circuit is designed to simulate clinical conditions and to evaluate gas exchange, blood path pressures, gas path pressures, and hemolysis. Previously reported studies have relied on a comparison of a single membrane oxygenator and a single bubble oxygenator. Our protocol will compare multiple membrane oxygenators, in vitro, under similar clinically relevant conditions. Such testing would be done prior to animal or clinical trials. Furthermore in vitro tests should be more reproducible and more discriminating than are ex vivo tests.