External counterpulsation of a systemic-to-pulmonary artery shunt increases coronary blood flow in neonatal piglets.

BACKGROUND: Systemic-to-pulmonary artery shunt (SPS) palliation reduces coronary blood flow (CBF), which may precipitate myocardial ischemia postoperatively. HYPOTHESIS: Counterpulsation (CP) of SPS augments CBF. METHODS: Seven neonatal piglets (4.3 ± 0.23 kg) underwent sternotomy and ductus ligation. With a 5-mm polytetrafluoroethylene graft, SPS was created from innominate to pulmonary artery. A rigid shell holding a 9.5-mm diameter balloon was placed around the graft for CP. Using electrocardiographic signal, CP was initiated to trigger balloon inflation/deflation during the diastolic/systolic intervals, respectively. Instantaneous proximal and distal pulmonary artery and mid-anterior descending coronary artery flow rates were measured using transit time flow probes. Blood pressure and flow rates were recorded during three states: shunt closed, shunt open, and shunt open with CP. STATISTICAL COMPARISON: Friedman's test and repeated measures analysis of variance. RESULTS: Diastolic pressure decreased significantly with the shunt open (39 ± 8.4 to 28 ± 4.5 mm Hg, P = .05), then increased with CP (33 ± 2.3 mm Hg, P = .03). Median ratio of pulmonary to systemic flow (Qp/Qs) was 1.19, 1.9, and 1.53 with shunt closed, open, and open with CP, respectively. With CP, both diastolic coronary flow per minute (P = .018) and average diastolic flow rate per diastolic interval (P = .03) increased as well as total coronary flow per minute (P = .066; 19.6% ± 11.7%, 25.2% ± 17.0%, and 15.4% ± 13.9% change from shunt open, respectively). The percentage increase in average diastolic flow rate per diastolic interval correlated strongly with Qp/Qs (R (2) = .838). CONCLUSIONS: In this model of SPS, CP increased diastolic blood pressure and CBF while maintaining significant augmentation of pulmonary blood flow (Qp/Qs). Shunt CP may aid in early postoperative management of palliative congenital heart disease.

End-diastolic flow reversal limits the efficacy of pediatric intra-aortic balloon pump counterpulsation.

BACKGROUND: Counterpulsation with an intra-aortic balloon pump (IABP) has not achieved the same success or clinical use in pediatric patients as in adults. In a pediatric animal model, IABP efficacy was investigated to determine whether IABP timing with a high-fidelity blood pressure signal may improve counterpulsation therapy versus a low-fidelity signal. METHODS: In Yorkshire piglets (n = 19; weight, 13.0 ± 0.5 kg) with coronary ligation-induced acute ischemic left ventricular failure, pediatric IABPs (5 or 7 mL) were placed in the descending thoracic aorta. Inflation and deflation were timed with traditional criteria from low-fidelity (fluid-filled) and high-fidelity (micromanometer) blood pressure signals during 1:1 support. Aortic, carotid, and coronary hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption was calculated from coronary sinus and arterial blood samples. Left ventricular myocardial blood flow and end-organ blood flow were measured with microspheres. RESULTS: Despite significant suprasystolic diastolic augmentation and afterload reduction at heart rates of 105 ± 3 beats per minute, left ventricular myocardial blood flow, myocardial oxygen consumption, the myocardial oxygen supply/demand relationship, cardiac output, and end-organ blood flow did not change. Statistically significant end-diastolic coronary, carotid, and aortic flow reversal occurred with IABP deflation. Inflation and deflation timed with a high-fidelity versus low-fidelity signal did not attenuate systemic flow reversal or improve the myocardial oxygen supply/demand relationship. CONCLUSIONS: Systemic end-diastolic flow reversal limited counterpulsation efficacy in a pediatric model of acute left ventricular failure. Adjustment of IABP inflation and deflation timing with traditional criteria and a high-fidelity blood pressure waveform did not improve IABP efficacy or attenuate flow reversal. End-diastolic flow reversal may limit the efficacy of IABP counterpulsation therapy in pediatric patients with traditional timing criteria. Investigation of alternative deflation timing strategies is warranted.

Extracorporeal membrane oxygenation versus counterpulsatile, pulsatile, and continuous left ventricular unloading for pediatric mechanical circulatory support.

OBJECTIVES: Despite progress with adult ventricular assist devices, limited options exist to support pediatric patients with life-threatening heart disease. Extracorporeal membrane oxygenation remains the clinical standard. To characterize (patho)physiologic responses to different modes of mechanical unloading of the failing pediatric heart, extracorporeal membrane oxygenation was compared to intra-aortic balloon pump, pulsatile-flow ventricular assist device, or continuous-flow ventricular assist device support in a pediatric heart failure model. DESIGN: Experimental. SETTING: Large animal laboratory operating room. SUBJECTS: Yorkshire piglets (n = 47; 11.7 ± 2.6 kg). INTERVENTIONS: In piglets with coronary ligation-induced cardiac dysfunction, mechanical circulatory support devices were implanted and studied during maximum support. MEASUREMENTS AND MAIN RESULTS: Left ventricular, right ventricular, coronary, carotid, systemic arterial, and pulmonary arterial hemodynamics were measured with pressure and flow transducers. Myocardial oxygen consumption and total-body oxygen consumption were calculated from arterial, venous, and coronary sinus blood sampling. Blood flow was measured in 17 organs with microspheres. Paired Student t tests compared baseline and heart failure conditions. One-way repeated-measures analysis of variance compared heart failure, device support mode(s), and extracorporeal membrane oxygenation. Statistically significant (p < 0.05) findings included 1) an improved left ventricular blood supply/demand ratio during pulsatile-flow ventricular assist device, continuous-flow ventricular assist device, and extracorporeal membrane oxygenation but not intra-aortic balloon pump support, 2) an improved global myocardial blood supply/demand ratio during pulsatile-flow ventricular assist device and continuous-flow ventricular assist device but not intra-aortic balloon pump or extracorporeal membrane oxygenation support, and 3) diminished pulsatility during extracorporeal membrane oxygenation and continuous-flow ventricular assist device but not intra-aortic balloon pump and pulsatile-flow ventricular assist device support. A profile of systems-based responses was established for each type of support. CONCLUSIONS: Each type of pediatric ventricular assist device provided hemodynamic support by unloading the heart with a different mechanism that created a unique profile of physiological changes. These data contribute novel, clinically relevant insight into pediatric mechanical circulatory support and establish an important resource for pediatric device development and patient selection.

Effects of phentolamine infusion during selective cerebral perfusion in neonatal piglets.

BACKGROUND: An optimal selective cerebral perfusion protocol in pediatric cardiac surgery is unknown. Phentolamine is frequently used in pediatric cardiopulmonary bypass. We sought to determine the effects of continuous phentolamine infusion during selective cerebral perfusion. METHODS: Twenty-seven neonatal piglets (3.38 ± 0.32 kg) were randomly assigned to 3 groups; sham (n = 7, anesthesia alone, no surgery or bypass), control (n = 10, saline infusion), or experimental (n = 10, phentolamine infusion 0.1 mg/kg per hour). Animals underwent 90 minutes of selective cerebral perfusion. Cerebral vascular resistance index (CVRI) and metabolic rate of oxygen (CMRO2) were determined every 15 minutes. Standardized sections of hippocampus, basal ganglia, and neo-cortex were obtained. Tissue samples were stained for caspase-3 and analyzed for positive apoptotic cell count. Data were analyzed with repeated measures and one-way analysis of variance. RESULTS: The CVRI tended to increase over time in the control group and decrease over time in the experimental group, but difference was not statically significant (0.46 ± 0.24 vs 0.39 ± 0.10 mm Hg × min × kg(2/3)/mL, p = 0.15). Mean CMRO2 was higher in the control group compared with the experimental group (0.90 ± 0.27 vs 0.59 ± 0.12 mLO2/min × kg(2/3), p = 0.005) and decreased over time in both groups. The percentage of caspase-3 positive cells was significantly different among regions (hippocampus = 16.9 ± 8.8; basal ganglia = 14.6 ± 7.5; neocortex = 10.8 ± 6.3; p < 0.0001) but not significantly different among sham (11.8% ± 2.68%), control (14.4% ± 2.24%), and experimental (15.5% ± 2.24%) groups. CONCLUSIONS: A continuous infusion of phentolamine during selective cerebral perfusion significantly decreases CMRO2 and tends to decrease CVRI when compared with control. At the dose studied and at the time of tissue sampling, phentolamine does not appear to decrease apoptosis during or early after selective cerebral perfusion.

Expanded pediatric cardiovascular simulator for research and training.

A mock circulation system has been developed to approximate key anatomic features and simulate the pressures and flows of an infant. Pulsatile flow is generated by 10 cc pulsatile ventricles (Utah infant ventricular assist device). Systemic vasculature is mimicked through the use of 3/8" ID bypass tubing with two flexible reservoirs to provide compliance. Vascular resistance, including pulmonary, aortic, and major branches, is controlled via a series of variable pinch clamps. The coronary branch has a dynamic resistor so that the majority of flow occurs during diastole. The system is instrumented to measure key pressures and flows. Right atrial pressure, left atrial pressure, pulmonary artery pressure, and mean aortic pressure are measured with high-fidelity pressure catheters (Millar Instruments, Houston, TX). Flows are measured by transit time ultrasonic flow probes (Transonic Systems, Ithaca, NY) in the pulmonary artery, aorta, coronary artery, and brachiocephalic artery along with assist device flow. The system can be tuned to create the hemodynamic values of a pediatric patient under normal or heart failure conditions. Once tuned to the desired hemodynamic conditions, the loop may be used to test the performance of various circulatory support systems including the intra-aortic balloon pump, left and right ventricular assist devices, or cardiopulmonary support systems such as extracorporeal membrane oxygenation.

Human, bovine and porcine systematic vascular input impedances are not equivalent: implications for device testing and xenotransplantation in heart failure.

BACKGROUND: Advanced therapies for heart failure (HF), such as mechanical circulatory support (MCS) devices and xenotransplantation, are usually tested in bovine and porcine models. This approach assumes a priori that animal (patho)physiology will closely match that of humans. Systemic aortic input impedance (Z(ART)) is an important physiologic determinant of left ventricular (LV) performance. We tested the hypothesis that Z(ART) is lower in bovine and porcine than in humans with normal or failing hearts. METHODS: High-fidelity aortic pressure and flow waveforms were recorded intra-operatively at native and paced heart rates of 100 beats per minute (bpm) in adult human patients with normal LV function (n = 13) or end-stage HF (n = 15), and normal calves (n = 10) and pigs (n = 18). Fast Fourier transformation was used to calculate Z(ART), and arterial resistance and compliance were estimated using a 4-element Windkessel model. RESULTS: Humans with HF had greater Z(ART) than those with normal LV function, characterized by higher resistance (1.16 +/- 0.12 vs 1.00 +/- 0.10 mm Hg x s/ml, p < 0.05) and lower compliance (1.53 +/- 0.21 vs 1.88 +/- 0.33 ml x mm Hg, p < 0.05). Healthy calves and pigs had significantly lower resistance (calf: 0.63 +/- 0.07 mm Hg x s/ml; pig: 0.90 +/- 0.07 mm Hg x s/ml) and higher compliance (calf: 2.79 +/- 0.37 ml x mm Hg; pig: 2.80 +/- 0.64 ml x mm Hg) when compared to humans (p < 0.05) with normal or failing hearts. CONCLUSIONS: Z(ART) is significantly lower in calves and pigs than in humans with or without HF. This finding has important implications for the pre-clinical testing of MCS devices and xenotransplants, which are usually examined in bovine and porcine models, respectively. Specifically, these therapies may respond differently in humans than animals due to non-equivalence of systemic after-load.

Technique of single-stage repair of coarctation of the aorta with ventricular septal defect.

The results of single-stage and two-stage repair of coarctation of the aorta (CoA) with ventricular septal defect (VSD) have improved, but the optimal treatment strategy remains controversial. This article emphasizes the technical details for performing the single-stage repair of CoA with VSD and compares the results of this technique with the two-stage approach. A retrospective analysis of 46 patients who underwent completed surgical repair of CoA with VSD at Children's Hospital of Michigan, either using the single-stage (N=23) or the two-stage (N=23) techniques, was performed. The postoperative complications, hospital mortality, freedom from cardiac re-interventions, and actuarial survival were the same in both groups. The advantages of single-stage over two-stage repair include an earlier age at completion of repair, fewer operations, and fewer incisions. The one disadvantage of a single-stage repair was the increased need for delayed sternal closure compared with the two-stage approach, but this disadvantage has been neutralized in the recent era.

Single-stage versus 2-stage repair of coarctation of the aorta with ventricular septal defect.

OBJECTIVE: The results of single-stage and 2-stage repair of coarctation of the aorta with ventricular septal defect have improved, but the optimal treatment strategy remains controversial. This study compares our results with these 2 approaches. METHODS: We performed a retrospective analysis of 46 patients, 23 with single-stage repair and 23 with 2-stage repair, who underwent completed surgical treatment of coarctation of the aorta with a ventricular septal defect at the Children's Hospital of Michigan between March 1994 and June 2006. RESULTS: The average number of operations in the single-stage group was 1.5 +/- 0.6, and in the 2-stage group it was 2.2 +/- 0.4 (P < or = .0001). Postoperative complications were similar, except for the number of planned reoperations to perform delayed sternal closure in the single-stage operation (n = 7) compared with the 2-stage operation (n = 1, P = .023). The patient age in the single-stage group at the time of discharge (completed repair time) was a median of 39.0 days (range, 19-250 days) compared with a median of 113.0 days (range, 26-1614 days) in the 2-stage group after stage 2 (P < or = .0001). Freedom from cardiac reintervention was 89.8% in the single-stage group versus 84.9% in the 2-stage group (P = .33). The hospital mortality was 4.4% (1 patient) in each group. The actuarial survival rate was 95.7% in the single-stage group versus 90.6% in the 2-stage group (P = .38). CONCLUSIONS: The advantages of single-stage over 2-stage repair of a ventricular septal defect with coarctation of the aorta include an earlier age at completion of repair, fewer operations, and fewer incisions. Postoperative complications and hospital mortality are similar. The one disadvantage of a single-stage repair was the increased need for delayed sternal closure compared with the 2-stage approach.

The effect of heart rate, preload, and afterload on the viscoelastic properties of the swine myocardium.

Experiments were performed to test the hypothesis that viscoelastic properties of the swine myocardium are independent of heart rate (HR), preload (PL), and afterload (AL). Left ventricular pressure and aortic flow (AoF) waveforms were recorded in 13 swine. At different paced heart rates, an inferior vena caval occlusion (IVC) was used to reduce PL, then the IVC was released and simultaneously the aorta was clamped to increase AL. Equivalent left ventricular pressure waveform pairs consisting of an ejecting waveform (denoted as LVP) and isovolumic waveform (denoted as hydromotive pressure, HMP) were selected according to specified criteria resulting in 371 equivalent waveform pairs. From the selected waveform pairs and corresponding aortic flow waveforms, the viscoelastic properties (k and epsilon1) were estimated by HMP = LVP + epsilon1 V(EJ) + k x LVP x AoF. Here epsilon1 is the parallel elastance, k is the myocardial friction, and V(EJ) is the integral of AoF over ejection. Next, using k, epsilon1, LVP, and AoF waveforms, HMP was estimated using the equation above. To validate the model, the measured HMP and model-calculated HMP were compared for 371 matched waveform pairs (R2 = 0.97, SEE = 3.7 mmHg). The viscoelastic parameters (k and epsilon1) did not exhibit any clear or predictable dependence on HR, PL, and AL.