Major Factors in the Controversy of Pulsatile Versus Nonpulsatile Flow During Acute and Chronic Cardiac Support

During the past 50 years, the controversy over the benefits of pulsatile versus nonpulsatile flow in cardiac surgery has not been solved.1 A detailed investigation in all published literature reveals that in a majority of publications, the investigators could not show any differences between perfusion modes during acute or chronic cardiac support. However, in more than 20 articles, it appears clear that pulsatile flow causes significantly less vital organ injury and systemic inflammation during cardiopulmonary bypass (CPB) procedures and chronic cardiac circulatory support.1–23 To the best of our knowledge, there is not a single publication that clearly shows the benefits of nonpulsatile perfusion over pulsatile perfusion in acute or chronic clinical or animal settings. The pro-nonpulsatile flow investigators can only claim that there is no difference between perfusion modes, whereas the pro-pulsatile investigators have documented clear benefits.1–23 The objective of this editorial is to examine the major causes for this continuing controversy and suggest potential solutions to end it. Following are the two major causes for the controversy, and both are valid for acute or chronic settings. Limitations of Experimental Designs One major cause for this controversy is the significant design limitations in clinical and experimental research on pulsatile and nonpulsatile flow.24–32 To make a valid and meaningful comparison between perfusion modes, there must be two distinct groups: pulsatile and nonpulsatile. Each group must be subjected to only one perfusion mode. The mode of perfusion used should not change in each subject during the entire duration of support. In other words, if a patient or animal is included in the pulsatile group, investigators must use pulsatile flow throughout in that particular subject. Changing the perfusion mode in the same subject is a serious design error. Unfortunately, a significant number of investigations that cannot show any differences between perfusion modes fall into this design error category.24–29 When comparing pulsatile and nonpulsatile flow in either the acute or chronic setting, the only difference between the two groups must be the mode of perfusion. Everything else, including patient demographics, severity of surgery, anesthesia and perfusion protocols, temperature, duration of support, and postoperative management must be the same or as similar as possible. During CPB, investigators must choose identical perfusion circuits including the same oxygenator, filter, venous and arterial cannulae, and coating material.30–32 During chronic support, the only difference must be the pump, and nothing else. Animal experiments must correlate with a clinical scenario. Experimental protocols that have no similarity to clinical practice can only dilute the controversy more.24–26,29 Precise Quantification of Pressure-Flow Waveforms The second major cause of the controversy is the use of pulse pressure for quantification of pressure flow waveforms during acute or chronic cardiac/cardiopulmonary support.33–40 Pulsatile and nonpulsatile pressure-flow waveforms should be quantified in terms of hemodynamic energy levels because generation of pulsatile flow depends upon an energy gradient.33–40 We have clearly documented that, with identical pulse pressures, the difference in terms of extra energy between two different pulsatile pumps can be more than 100%.37 The cause of this difference is the energy contained in each pulsatile cycle. The morphology (shape and size) of the waveforms with identical pulse pressure has different energy levels.36,37 Because of significant variances among different pulsatile and nonpulsatile systems used during acute or chronic support, the precise quantification of the pressure-flow waveforms is a necessity, not an option. We have suggested that energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) formulas are adequate to precisely quantify pressure-flow waveforms during acute and chronic cardiac support.33–40 Energy Equivalent Pressure Shepard's EEP formula is based upon the ratio between the area beneath the hemodynamic power curve (∫ fpdt) and the area beneath the pump flow curve (∫ fdt) during each pulse cycle:35 where f is the pump flow rate, p is the arterial pressure (mm Hg), and dt is the increment in time. The EEP is calculated in mm Hg. Under adequate pulsatility, EEP is always higher than mean arterial pressure (MAP). The difference between the EEP and MAP is the extra energy. Under 100% nonpulsatile flow conditions, the EEP becomes the MAP. Therefore, the extra energy is zero. Total Hemodynamic Energy Using Shepard's total hemodynamic energy formula, the constant 1,332 changes pressure from units of millimeters of mercury to units of dynes per cm2.35 Surplus Hemodynamic Energy Surplus hemodynamic energy is calculated by multiplying the difference between the EEP and the mean arterial pressure (MAP) by 1,332. SHE is the “extra energy” that exists only if there is some degree of pulsatility in the pressure or flow. Under 100% nonpulsatile conditions, the SHE is zero. At equal mean arterial pressures and pump flow rates, adequate pulsatile flow always generates significantly more extra energy when compared with the nonpulsatile flow.33–40 This is a serious disadvantage when nonpulsatile devices are used for either acute or chronic support. Several investigators have recently started using EEP for precise pressure-flow waveform quantification during pulsatile and nonpulsatile perfusion. Prof. Kyung Sun from Korea University, Seoul, South Korea, Prof. Y.J. Gu from University of Groningen, Netherlands, and Dr. Richard Tallman from the Ohio State University are a few examples.41 In addition, several perfusion schools in the United States have shown significant interest in adopting the EEP for precise quantification under pulsatile and nonpulsatile flow conditions. In conclusion, we suggest that investigators who are involved in pulsatile versus nonpulsatile research 1) review the limitations of their experimental designs (if any), and 2) precisely quantify the pulsatility in terms of EEP and SHE for direct and meaningful comparisons.