Left ventricular dysfunction during extracorporeal membrane oxygenation in a hypoxemic swine model.

BACKGROUND: Perfusion of the coronary circulation with hypoxemic blood from the left ventricle has been postulated to cause myocardial dysfunction during venoarterial extracorporeal membrane oxygenation for respiratory support. METHODS: We investigated this hypothesis in 10 anesthetized open-chest piglets (7 to 9 kg) undergoing venoarterial extracorporeal membrane oxygenation after placement of minor-axis sonomicrometry crystals and left ventricular micromanometer. The left atrial partial pressure of oxygen was made hypoxemic (25 to 40 mm Hg) after initiation of extracorporeal membrane oxygenation by ventilation with a hypoxic gas mixture. Left ventricular contractile function, including peak LV pressure, shortening fraction, maximum rate of increase of left ventricular pressure, velocity of circumferential fiber shortening, end-systolic pressure-minor axis dimension relationship, and preload recruitable dimensional stroke work, was measured or calculated on extracorporeal membrane oxygenation before (baseline) and at 4 and 6 hours after rendering the left atrial blood hypoxemic. RESULTS: Left ventricular shortening fraction and velocity of circumferential fiber shortening were significantly lower (p < 0.05) at 4 and 6 hours when compared with baseline. The slope of the end-systolic pressure-minor axis dimension relationship decreased but was not significantly different at 4 and 6 hours when compared with baseline owing to poor linear correlation (r = 0.30 to 0.93). The preload recruitable dimensional stroke work was more linear (r = 0.87 to 0.99), and the slope was significantly lower (p < 0.01) at 4 and 6 hours when compared with baseline. CONCLUSIONS: Hypoxemic cardiac output from the left ventricle during venoarterial extracorporeal membrane oxygenation is associated with depression of left ventricular systolic function in this animal model. Current use of venoarterial extracorporeal membrane oxygenation for respiratory support may not provide adequate oxygen supply to the myocardium.

Acute mitral valve regurgitation created in sheep using echocardiographic guidance.

BACKGROUND AND AIM OF STUDY: This study was designed to determine: (i) Whether acute mitral valve regurgitation (MVR) due to chordal rupture can be reproducibly created under echocardiographic guidance; (ii) what degree of MVR can be created; (iii) what degree of acute regurgitation is survivable; and (iv) whether acute MVR due to chordal rupture progresses over time. METHODS: In a pilot group of six juvenile farm-bred sheep, selected chordae tendineae were ruptured using either a biopsy needle or endoscopic scissors under echocardiographic guidance, without need for cardiopulmonary bypass. Sheep were sacrificed acutely (n = 2), and at six weeks (n = 2) or eight weeks (n = 2). When the technique was optimized, five sheep entered a study group in which chords were ruptured using endoscopic scissors; the sheep were sacrificed 16 weeks after surgery. RESULTS: In the pilot study, acute MVR (grade 2-4+) was produced in all sheep, normal ventricular wall motion was maintained, with minimal progression of regurgitation over time. In one pilot sheep which did not survive, grade 4+ MVR was created acutely. Use of endoscopic scissors was preferable to the biopsy needle. In the study group, acute MVR (grade 2-4+) was produced in all five sheep, and was still present at 16 weeks, with progression in only one animal. CONCLUSIONS: This pilot study demonstrated that controlled degrees of survivable acute MVR due to chordal rupture can be created under echocardiographic guidance, with minimal progression of MVR over time. This animal model can be applied to investigate the pathogenesis of clinical MVR, and to suggest appropriate medical or surgical intervention.

Antibody to CD18 reduces neutrophil and T lymphocyte infiltration and vascular cell adhesion molecule-1 expression in cardiac rejection.

Most antirejection therapies target immune activation but may not reduce leukocyte infiltration into the graft. The leukocyte integrin CD18 has been shown to be important for leukocyte migration in vitro. We postulated that antibody blockade of CD18 might reduce the migration of different leukocyte subpopulations into myocardium during rejection. Using a rabbit model, we evaluated the effect of a monoclonal antibody to CD18 on the infiltration of neutrophils (polymorphonuclear leukocytes [PMNs]), T lymphocytes, and macrophages into cardiac grafts. In addition, vascular cell adhesion molecule-1 (VCAM-1) expression was assessed to determine the relationship between leukocyte infiltration and VCAM-1 expression, an unblocked alternate adhesion pathway. Donor hearts from Stauffland rabbits were transplanted heterotopically into the cervical position of New Zealand White recipients. Recipient rabbits received either monoclonal antibody to CD18 daily without other immunosuppression (n=51), saline injections as placebo controls (n=52), or nonfunctional isotype-matched antibody (n=4). Recipient rabbits were killed at 1 hr, 6 hr, 24 hr, 3 days, and 7 days after transplantation (10-12 rabbits per group at each time point). PMNs, T lymphocytes, and macrophages were differentiated by routine staining and immunocytochemistry, respectively, and quantified as the number of cells per standardized field. VCAM-1 expression was examined immunocytochemically in 30 treated and 30 control transplanted hearts. Monoclonal antibody to CD18 significantly reduced the infiltration of PMNs and T lymphocytes into myocardium during rejection, but did not affect the infiltration of macrophages. Blocking the CD18/intercellular adhesion molecule-1 adhesion pathway also resulted in a decrease in VCAM-1 expression, which correlated in time with the reduction in T lymphocyte infiltration.

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)