The relationship between pulmonary system impedance and right ventricular function in normal sheep.

Right ventricular (RV) afterload is a key determinant of RV function and is increased in many cardiopulmonary pathologies. Pulmonary circulation input impedance has been used to quantify afterload previously but due to its complexity has not been widely applied. This study examines the effect of a subset of the impedance spectrum, the zeroth and first harmonic impedance moduli (Z (0), Z (1)), on RV performance in large animals. An artificial circuit with adjustable resistance and compliance (C) was implanted into the pulmonary circulation of five sheep. Resistance was varied to increase Z (0) in increments of 2 mmHg/(L/min) until Z (0) was 8 mmHg/(L/min) above baseline. At each Z (0), C was adjusted between 0, 0.5 and 2 mL/mmHg or 0, 1, and 5 mL/mmHg. Fourier transforms of the pulmonary artery pressure and flow in each situation were used to calculate the pulmonary impedance. Results show that the percent change in cardiac output (ÞltaCO) is linearly related to the change in Z (0) (DeltaZ (0)). Increases in Z (1) (DeltaZ (1)) decreased ÞltaCO but to a much smaller degree, with the effect of DeltaZ (1) increasing with DeltaZ (0). Regression of these results produce the equation: ÞltaCO = (-0.0829DeltaZ (1) - 3.65)DeltaZ (0) - 9.02 (R (2) = 0.69). Blood flow and pressure moduli are small at harmonics higher than the first and are unlikely to affect RV function. Therefore, during acute, high afterload states, Z (0) is the primary determinant of CO, while the effect of Z (1) is minor.</p

Organ donation after cardiac determination of death (DCD): a swine model.

Donors after Cardiac Death (DCD) may reduce the organ scarcity; however, their use is limited because of warm ischemia time. Fortunately, this is less important in a subclass of DCD called expected (e-DCD), those with irreversible but incomplete brain injury. This study analyzed hemodynamic/pulmonary data to establish a clinically relevant model of cardiac death that would simulate an e-DCD setting. Hemodynamics, pulmonary artery flows, arterial blood gasses, and left atrial pressure were recorded q 5 minutes in anesthetized swine. After baseline data collection, the ventilator was discontinued and heparin was administered. Cardiac death was defined: as asystole, or mean arterial presusure < or = 25 mm Hg with a pulse pressure < or = 20 mm Hg. The time to death was approximately 14.8 minutes. Within 5 minutes of removal of the ventilator, there was a hyperdynamic period. Blood gases throughout the apneic time showed a rapid hypercapnia and acidosis. The hyperdynamic reflex response was followed by hypotension, bradycardia, and finally asystole or ventricular fibrillation. The protocol of withdrawal of ventilation, systemic anticoagulation, determination of death was developed to closely resemble the clinical e-DCD scenario. The physiologic changes that happen before death in DCD were described. An e-DCD model that can be used in studies related to organ transplantation was established.</p

In-parallel artificial lung attachment at high flows in normal and pulmonary hypertension models.

BACKGROUND: End-stage lung disease patients who require a thoracic artificial lung (TAL) must be extubated and rehabilitated prior to lung transplantation. The purpose of this study is to evaluate hemodynamics and TAL function under simulated rest and exercise conditions in normal and pulmonary hypertension sheep models. METHODS: The TAL, the MC3 Biolung (MC3, Inc, Ann Arbor, MI), was attached between the pulmonary artery and left atrium in nine normal sheep and eight sheep with chronic pulmonary hypertension. An adjustable band was placed around the distal pulmonary artery to control the percentage of cardiac output (CO) diverted to the TAL. Pulmonary system hemodynamics and TAL function were assessed at baseline (no flow to the TAL) and with approximately 60%, 75%, and 90% of CO diverted to the TAL. Intravenous dobutamine (0, 2, and 5 mcg . kg(-1). min(-1)) was used to simulate rest and exercise conditions. RESULTS: At 0 and 2 mcg . kg(-1). min(-1), CO did not change significantly with flow diversion to the TAL for both models. At 5 mcg . kg(-1). min(-1), CO decreased with increasing TAL flow up to 28% +/- 5% in normal sheep and 23% +/- 5% in pulmonary hypertension sheep at 90% flow diversion to the artificial lung. In normal sheep, the pulmonary system zeroth harmonic impedance modulus, Z(0), increased with increasing flow diversion. In hypertensive sheep, Z(0) decreased at 60% and 75% flow diversion and returned to baseline levels at 90%. The TAL outlet blood oxygen saturation was 95% or greater under all conditions. CONCLUSIONS: Pulmonary artery to left atrial TAL use will not decrease CO during rest or mild exercise but may not allow more vigorous exercise.</p

Development of an artificial placenta I: pumpless arterio-venous extracorporeal life support in a neonatal sheep model.

PURPOSE: Effective treatment of respiratory failure in premature infants remains an unsolved problem. The development of an artificial placenta, in the form of a pumpless arteriovenous extracorporeal life support (AV-ECLS) circuit that maintains fetal circulation, is an appealing alternative. METHODS: A near-term (140 d/term = 145 days) neonatal lamb model was used (n = 7). Fetuses were exposed by hysterotomy, and flow probes were placed on the ductus arteriosus, aorta, and carotid artery. Catheters were placed into the umbilical vessels, and pumpless AV-ECLS was initiated. Fetuses were submerged in a warm saline bath, and support was maintained for up to 4 hours. RESULTS: Mean initial device flow was 383 mL/min but steadily declined to 177 mL/min at 4 hours. Mean initial pO(2) was 24 mm Hg and 18 mm Hg at 4 hours. Initial mean pCO(2) was 60 mm Hg and declined to 42 mm Hg at 4 hours. Mean arterial pressure was initially 43 mm Hg and decreased to 34 mm Hg at 4 hours. Flow in the ductus arteriosus was maintained for 4 hours. Of 7 fetuses, 5 survived 4 hours of support. CONCLUSIONS: Pumpless AV-ECLS can support gas exchange and maintain fetal circulation in a neonatal lamb model for a 4-hour period. Prolonged support (>4 hours) is hampered by high cannula resistance and declining device flow.</p

Lung physiology during ECS resuscitation of DCD donors followed by in situ assessment of lung function.

Extracorporeal cardiopulmonary support (ECS) of donors after cardiac death (DCD) has been shown to improve abdominal organs for transplantation. This study assesses whether pulmonary congestion occurs during ECS with the heart arrested and describes an in vivo method to assess if lungs are suitable for transplantation from DCD donors after ECS resuscitation. Cardiac arrest was induced in 30 kg pigs, followed by 10 min of warm ischemia. Cannulae were placed into the right atrium (RA) and iliac artery, and veno-arterial ECS was initiated for 90 min with lungs inflated, group 1 (n = 5) or deflated, group 2 (n = 3). Left atrial pressures were measured as a marker for pulmonary congestion. After 90 min of ECS, lung function was evaluated. Cannulae were placed into the pulmonary artery (PA) and left ventricle (LV). A second pump was included, and ECS was converted to a bi-ventricular (bi-VAD) system. The RVAD drained from the RA and pumped into the PA, and the LVAD drained the LV and pumped into the iliac. This brought the lungs back into circulation for a 1-hr assessment period. The oxygenator was turned off, and ventilation was restarted. Flows, blood gases, PA and left atrial pressures, and compliance were recorded. In both the groups, LA pressure wasperiod, PA flows were 1.4-2.2 L/min. PO2 was >300 mm Hg, with normal PCO2. Extracorporeal cardiopulmonary support resuscitation of DCD donors is feasible and allows for assessment of function before procurement. Extracorporeal cardiopulmonary support does not cause pulmonary congestion, and the lungs retain adequate function for transplantation. Compliance correlated with lung function.</p