Part 2: Principles of Research on Pulsatile and Nonpulsatile Perfusion

Dear Editor, Our previous Letter to the Editor titled “Part 1: Principles of Research on Pulsatile and Nonpulsatile Perfusion During Chronic Support” started with following two sentences:1 To make valid comparisons between pulsatile and nonpulsatile flow during chronic cardiac support, the experimental designs must be very close (or ideally identical) to the clinical set up. Investigations that have no similarity to the clinical scenario will only make this continuing debate more controversial. Based upon these statements, we have suggested that if any pulsatile pump is implanted in a patient, only that particular pulsatile device should be used continuously during the entire duration of support. Changing the perfusion mode with different pulsatile and nonpulsatile power levels with 30 minute durations and 10 minute intervals between each mode is a serious design error. One selected perfusion mode with an identical power level (70% or 100%, but only one of them) should be used. To compare pulsatile and nonpulsatile perfusion in their particular design, there should be four different groups, not just one group. This is a serious design error. In their reply to our letter, the authors of the referenced article wrote, “We would like to remind them that, unlike the CPB setting, where the arrested native heart is prevented from contributing a pulse to the pressure waveform, the LVAD setting almost always allows for the imprint of the native pulse.” We agree with this statement. In our Letter to the Editor titled, “Physiology of Nonpulsatile Circulation: Acute Versus Chronic Support, published in 2000 in the ASAIO Journal, we wrote, “During chronic circulatory support with a nonpulsatile left or right ventricle assist device, several investigators reported the presence of the pulse pressure in patients, because the natural heart is still beating.”2 This was more than 5 years ago. In 2002, we published the following in the Annals of Thoracic Surgery: “In a clinical scenario, however, pulse pressure is about 15 to 20 mm Hg, or even higher during mechanical circulatory support using a nonpulsatile left ventricular assist device because the natural heart is still beating.”3 In 2003, we wrote, “It is well documented that the continuous flow (nonpulsatile) pumps generate diminished pulsatility because the native heart is also working,” again published in the Annals of Thoracic Surgery.4 In 2004, in the invited editorial titled “Myths and Truths of Pulsatile and Nonpulsatile Perfusion During Acute and Chronic Cardiac Support,”5 we included the following statement: “Although the pump flow is 100% nonpulsatile, arterial waveforms have some degree of pulsatility because the natural heart is also pumping. If the patient's heart recovers well, then it is possible to achieve near physiologic arterial pressure waveforms.” In 2005, we wrote, “The native heart of patients who are supported by nonpulsatile pumps typically undergoes partial recovery and begins to eject after a few weeks of support. In this particular scenario, even though the nonpulsatile pump produces no pulsatility, there is diminished pulsatility because the native heart is pumping.”6 In our letter, we have not compared cardiopulmonary bypass with chronic mechanical circulatory support.1 In fact, in the Discussion section of their article, they stated that there were inconsistent results in terms of cerebral benefits of pulsatility during hypothermic cardiopulmonary bypass. We have disputed this statement and explained our previous investigations in this area of research including references in our earlier letter.1 The following is another misleading statement. “Prof. Undar and his colleagues stress the importance of designing experiments that are ‘very close or ideally identical to the clinical set up. But later, they criticize our study because ‘during 70% and 100% nonpulsatile perfusion, pressure waveforms clearly show pulsatility.” We criticized this particular study because of significant scientific design errors, not because they have seen pulsatility with 70% or 100% nonpulsatile flow. In their particular design, there are four different types of pulsatile flow.1 The use of pulse pressure for quantification is inadequate because the generation of pulsatile flow depends upon an energy gradient.7–10 We have already documented that with an identical pulse pressure the difference in extra energy levels in two types of pulsatility is more than 100%.9 The morphology (shape and size) of the waveforms with an identical pulse pressure shows different energy levels. All of these data were published in the ASAIO Journal in 1999.9 Several investigators, including our group, have used different formulas to precisely quantify the pressure-flow waveforms during acute and chronic support.7–13 Energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) formulas are adequate to precisely quantify the waveforms during acute or chronic support.6,8–10,14,15 Based upon the scientific data published on the importance of EEP,9,10,16,17 several leading pediatric and adult heart centers in the United States and abroad have already started clinical trials with pulsatile perfusion. Several investigators have also adopted the EEP for precise quantification.18,19 Akif Ündar Gerson Rosenberg John L.Myers Departments of Pediatrics, Surgery, and Bioengineering, Penn State College of Medicine, Penn State Children's Hospital, Milton S. Hershey Medical Center, Hershey, Pennsylvania.