During the past several years, we repeatedly suggested that the lack of precise quantification of pressure-flow waveforms is one of the major factors for the controversy over the benefits of pulsatile perfusion in pediatric and adult open-heart procedures.1–5 Different types of pulsatile pumps (roller vs. hydraulically driven) produce significantly different hemodynamic energy levels at the same pump flow rate and arterial pressure.6,7 Quantification of pulsatile and nonpulsatile pressure-flow waveforms in terms of pulse pressure is inadequate because the generation of pulsatility depends on an energy gradient.1–5,8,9 We have already shown that with identical pulse pressure levels, two different pulsatile pumps generated significantly different hemodynamic energy levels.7 There is a direct correlation between the morphology (shape and size) of the waveforms and the hemodynamic energy levels.7 Waveforms with a more physiological morphology contain more energy when compared with less physiological waveforms at identical pulse pressure, and pump flow rates.7 We have also documented that when there was extra hemodynamic energy in the circuit and in subjects, vital organ perfusion improved dramatically under pulsatile flow conditions.10–14
Generation of pulsatile flow depends on an energy gradient.1–5,8,9 Surplus hemodynamic energy (SHE) is the extra hemodynamic energy generated by a pulsatile device when the adequate pulsatility is achieved.8,9,15 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.
Materials and Methods
Thirty-nine piglets (average weight, 3 kg) were subjected to cardiopulmonary bypass (CPB) with a hydraulically driven physiologic pulsatile pump (PPP; n = 7), Jostra-HL 20 pulsatile roller pump (Jostra-PR; n = 6), Stockert SIII pulsatile roller pump (SIII-PR; n = 6), Stockert SIII mast-mounted pulsatile roller pump with a miniature roller head (Mast-PR; n = 7), Stockert SIII mast-mounted nonpulsatile roller pump (Mast-NP; n = 7), or Stockert CAPS nonpulsatile roller pump (CAPS-NP; n = 7).
Anesthesia and surgery protocols have been described in significant detail in our previous publications.6,10–14 All animals received humane care, as described in the Guide for the Care and Use of Laboratory Animals of the National Research Council (National Academy Press, revised 1996). Each piglet was premedicated with intramuscular ketamine hydrochloride (20 mg/kg) and acepromazine maleate (1 mg/kg). Once an intravenous line was established, a 3-mm endotracheal tube was inserted for mechanical ventilation. Intravenous boluses of fentanyl citrate (100 μg/kg) and pancuronium bromide (0.3 mg/kg) were then given. After a median sternotomy was performed, the ascending aorta and the right atrium were cannulated with a 10F aortic cannula (DLP, Inc., Grand Rapids, MI) and a 21F single-stage venous cannula (Polystan A/S, Varlose, Denmark), respectively. The extracorporeal circuit was primed with heparinized fresh blood and lactated Ringer’s solution. The priming volume for the whole circuit was approximately 600 ml. During CPB, the hematocrit level was maintained at 20%. In all the experiments, a hollow-fiber membrane oxygenator (Capiox SX10; Terumo Corp, Tokyo, Japan) and a pediatric arterial filter (Terumo Corp) were used. During pulsatile CPB, the pump rate was maintained at 150 bpm, and the stroke volume was maintained at 1 ml/kg. Pump flow was maintained at 150 ml·kg–1·min–1 in all the groups. An ultrasonic flow probe (T109; Transonic Systems, Inc., Ithaca, NY) was placed in the circuit beyond the membrane oxygenator to measure blood flow. During CPB, the mean arterial pressure (MAP) was maintained at approximately 45 mm Hg by adding isoflurane through the oxygenator gas-inflow conduit. Arterial pH and Pco2 were maintained at 7.35–7.45 and 35–45 mm Hg, respectively. A 40 ml dose of crystalloid cardioplegia (modified Kirklin solution) was manually administered in to the ascending aorta at the beginning of DHCA. During the 60-minute aortic cross-clamping period, the temperature was kept at 18ºC in both groups. At the end of each experiment, the piglet was euthanized with a 0.22-mg/kg intravenous bolus of pentobarbital sodium and phenytoin sodium (Beuthanasia-D).
Once CPB was begun, each animal underwent 20 minutes of hypothermia, 60 minutes of deep hypothermic circulatory arrest (DHCA), 10 minutes of cold reperfusion, and 40 minutes of rewarming. During cooling and rewarming, alpha-stat acid-base management was used. In all experiments phenoxybenzamine (1 mg/kg), a potent vasodilator and α-adrenergic blocker, was used 5 minutes before the initiation of CPB.
The pump flow rate was maintained at 150 ml·kg–1·min–1 and the 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.
Precise Quantification of Pulsatile and Nonpulsatile Pressure-Flow Waveforms
The SHE (ergs/cm3) = 1,332 ([(∫ fpdt) / (∫ fdt)] – MAP) was calculated at each experimental stage (where f = pump flow rate, p = arterial pressure, and dt = increment in time).
Waveforms of the femoral artery pressure (MAP), precannula extracorporeal circuit pressure, and pump flow were collected during three experimental stages: 1) normothermic CPB (after 15 minutes on pump at 36°C); 2) deep hypothermic CPB (immediately before DHCA at 18°C); and, 3) the postrewarming period (after 60 minutes of DHCA, 10 minutes of cold reperfusion, and 40 minutes of rewarming).
A linear mixed-effects model, which accounts for the correlation among repeated measurements on an animal, was fit to the data to assess differences in SHE between pumps and stages. The between-subjects factor for the model was pump (PPP, Jostra PR, SIII-PR, Mast-PR, CAPS-NP, and Mast-NP). The within-subjects factor for the model was stage (normothermic CPB, pre-DHCA, and post-DHCA). All p values and 95% confidence intervals for mean difference SHE estimates were adjusted for pairwise comparison testing using Tukey’s multiple comparison procedure. All analyses were performed using the SAS statistical software package (SAS Institute Inc., Cary, NC).
Surplus Hemodynamic Energy Levels in Piglets
During normothermic CPB, the physiologic pulsatile pump produced the greatest extra energy (8,563 ± 1,918 ergs/cm3, p < 0.001). When compared with all the other pumps except the physiologic pulsatile pump, the Jostra HL-20 (2731 ± 374 ergs/cm3, p < 0.001) and SIII pulsatile roller (2,020 ± 441 ergs/cm3, p < 0.001) pumps produced a significantly higher amount of surplus hemodynamic energy. The SIII mast-mounted pulsatile roller pump failed to generate any more surplus hemodynamic energy (–114 ± 911 ergs/cm3) than the nonpulsatile pumps. None of the nonpulsatile roller pumps produced extra energy. During hypothermic CPB and after DHCA and rewarming, the results were extremely similar to those seen during normothermic CPB. Figures 1–3 summarize the results in detail.
Surplus Hemodynamic Energy Levels in Extracorporeal Circuits
Hemodynamic energy levels in extracorporeal circuits were significantly higher to those seen in piglets at all three experimental stages. However, the order in terms of energy generation was identical compared with that seen in piglets. During normothermic CPB, the physiologic pulsatile pump generated significantly higher hemodynamic energy when compared with all other pumps (42,909 ± 11,996 ergs/cm3, p < 0.001). The Jostra HL-20 pulsatile roller pump produced the second highest amount of surplus hemodynamic energy levels (11,233 ± 2,836 ergs/cm3), and the SIII pulsatile roller pump produced the third highest amount of surplus hemodynamic energy levels (7,726 ± 1,757 ergs/cm3). The SIII-mast mounted pulsatile roller pump did not generate any more surplus hemodynamic energy than the nonpulsatile pumps. Figures 4–6 summarize the results in detail.
Our results clearly confirm that the surplus hemodynamic energy formula is a novel tool to precisely quantify pressure-flow waveforms of different perfusion modes and different types of pulsatility. Our results also confirm that not all pulsatile pumps produce adequate pulsatile energy. In fact, one of the pulsatile roller pumps failed to produce any extra energy. Therefore, it is imperative that investigators quantify the hemodynamic energy levels before making direct comparisons for end organ recovery under different modes of perfusion.
What happens to this extra hemodynamic energy generated under adequate pulsatility? We have documented that when there was a significant difference between perfusion modes, then the vital organ recovery dramatically improved under pulsatile flow conditions.2,3,10–14 When there was no difference in terms of hemodynamic energy levels between the perfusion modes, then vital organ dysfunction was very similar between the two groups.16 So, there is a direct correlation between the extra hemodynamic energy levels and vital organ recovery under pulsatile flow conditions.
Every single component of the extracorporeal circuit has a direct impact on the quality of the pulsatility.17–20 In this study, the only difference among the six groups was the heart-lung machine. All other components of the extracorporeal circuit, including the membrane oxygenator and the arterial and venous cannulas, were identical in all six groups. All pulsatile and nonpulsatile pumps used in this study, except the physiological pulsatile pump, have already been approved by the US Food and Drug Administration for clinical use. The physiologic pulsatile pump produced the highest hemodynamic energy levels at all experimental stages. The Jostra HL-20 and SIII pulsatile roller pumps generated only one fourth of the hemodynamic energy generated by the PPP.
The only difference between the SHE and energy equivalent pressure (EEP) formulas is the units. The units of the EEP are mm Hg, whereas the units of SHE are ergs/cm3. Therefore, the surplus hemodynamic energy formula precisely quantifies the hemodynamic energy levels in terms of energy units. The units of EEP are mm Hg, and this allows us to directly compare the EEP with mean arterial pressure. If there is any extra energy, the EEP is always higher than the MAP. The difference between the EEP and the MAP is the extra energy. The difference between EEP and MAP in the normal human heart is approximately 10%.9 Several investigators have adopted EEP and SHE formulas for precise quantification of pressure-flow waveforms under pulsatile and nonpulsatile perfusion for acute and chronic support.15,21,22
The surplus hemodynamic energy formula is a novel method to precisely quantify different levels of pulsatility and nonpulsatility for direct and meaningful comparisons.
The physiologic pulsatile pump produced the greatest surplus hemodynamic energy. Most of the pediatric pulsatile pumps (except the Mast-PR) generated significant surplus hemodynamic energy. None of the nonpulsatile roller pumps generated adequate surplus hemodynamic energy.
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