The controversy over the benefits of pulsatile and nonpulsatile perfusion during cardiopulmonary bypass (CPB) has been ongoing for more than half a century.1–4 In earlier times, nonpulsatile perfusion was regarded as routine perfusion practice during CPB compared with the disadvantages of the pulsatile pump (it could not generate enough pulsatility, was complicated to operate, and increased the possibility of hemolysis). It seemed to be an exciting and satisfying method for people who served in this field, because it saved the lives of thousands of people with heart diseases. However, we had to take into account how many patients were lost by choosing this suboptimal method and how many additional medical resources were required to eliminate the adverse effects. Could we let the situation remain unchanged?
The advent of biomedical engineering has facilitated the development of several safe, simple, reliable, and cost-effective pulsatile pumps5–11 that are easy to set up and operate. With the new heart-lung machines, “one button” is used to alternate two perfusion modes during CPB. Some pulsatile pumps can even be triggered by the electrocardiogram and offer pulsatility not only during cardiac arrest but also during natural heart beating.9,10 Over the past few decades, clinical investigations, as well as animal experiments, have produced overwhelming evidence that pulsatile perfusion during CPB is more beneficial to patients than nonpulsatile flow.9–27 Although it is true that many investigations have failed to determine any difference between the two perfusion modes, their conclusions many have been influenced by a number of issues, such as a lack of understanding of the precise quantification of pressure-flow waveforms, limitations of experimental designs, or the selection of components of the extracorporeal circuit (pumps, membrane oxygenators, and aortic cannulae), without any scientific justification.5–10,28–37
The objective of this investigation was to review the literature published between 1952 and 2006 and reported in the databases of Google and Medline in order to clarify the truths and dispel the myths regarding the mode of perfusion used during open-heart surgery in pediatric and adult patients.
Materials and Methods
A computerized search, covering the period between 1952 and February of 2006, of the Google and Medline databases was conducted. Titles were sought containing the keywords pulsatile CPB, pulsatile flow, and pulsatile perfusion. Literature included the original (written in English or other languages) clinical trials and animal or in vitro experimental studies or invited editorial and review manuscripts on the topic of pulsatile vs. nonpulsatile flow during CPB surgery. Outcomes cited included clinical results and conclusions. Publications reporting on chronic support with different modes of perfusion, some comments on other papers, and some case reports about this topic were excluded.
The search of Google and Medline databases produced a total of 194 papers with titles containing the keywords. Of the 194 publications, 74 were about animal experiments, 85 were about clinical investigations, and 35 were reviews, new device designs, or editorial letters. Direct comparisons of pulsatile and nonpulsatile flow during CPB in either animal or human studies were found in 159 reports.
Based on our literature search, we found considerable evidence that pulsatile flow is superior to nonpulsatile flow during CPB. Several results indicated that some forms of pulsatile flow are no more damaging to red blood cells and platelets than nonpulsatile flow.38–40 Some studies reported significantly lower pulmonary vascular resistance with pulsatile CPB than with nonpulsatile flow,1–4,41–43 and also showed that pulsatile flow generates more hemodynamic energy that improves microcirculation and metabolism when compared with nonpulsatile flow and inhibits edema formation.44–46 Many investigators found that pulsatile flow decreases levels of thyroid hormone,24 plasma vasopressin,47 adrenocortical hormone,48 cortisol,49 catecholamines,50 rennin, angiotensin II,51 and thromboxane. Moreover, we determined that pulsatile flow significantly improves blood flow of the vital organs including the brain,9,52–59 heart,60–63 liver,64 pancreas,65,66 kidney,67–72 and gastrointestinal system73,74; increases lung function75; reduces the systemic inflammatory response syndrome11,76–79; and decreases the incidence of postoperative deaths in pediatric and adult patients.1,12,16,80 Nonpulsatile investigators have claimed only that there is no difference between the pulsatile and nonpulsatile system in terms of end-organ recovery; however, none of them documented that pulsatile flow is worse than nonpulsatile flow.
During the past decades, with the development of improved techniques in cardiac surgery and refinement of CPB instruments, the mortality rates following CPB procedures have been significantly decreased.81,82 To date, morbidity is still primarily a clinical problem, especially in high-risk cardiac patients. Major factors include deep-hypothermia circulatory arrest, ischemia/reperfusion, systemic inflammatory response syndrome, and nonpulsatile flow. The mode of perfusion could influence the result of vital organ recovery after CPB.
Based on the literature we reviewed about pulsatile vs. nonpulsatile flow during CPB, results very clearly showed that pulsatile flow is more effective than nonpulsatile flow during pediatric and adult CPB procedures. Despite the growing evidence for the possible benefits of pulsatile perfusion, the nonpulsatile mode has been chosen for routine clinical practice during open-heart surgery in the majority of institutions. The problem of clinical acceptance of pulsatile perfusion rests heavily on the controversy reported in the literature, which revolves around some key issues.
Lack of Common Definition or Precise Quantification
To date, we do not have a common definition or precise quantification of pulsatile flow, without which direct and meaningful comparisons of different perfusion modes are impossible.5–10,29–32 Investigators who focus on the topic of pulsatile vs. nonpulsatile flow need a definition because it is commonly believed that pulse pressure is sufficient for direct comparisons. Quantification of pulsatility in terms of pulse pressure is inadequate because the generation of pulsatile flow depends on an energy gradient.5–10,29–32 Therefore, the pump flow and arterial pressure must be included in quantification of different perfusion modes.
The Energy Equivalent Pressure Formula (EEP) is based on the ratio between the area beneath the hemodynamic power curve (∫ fpdt) and the area beneath the pump flow curve (∫ fdt) during each pulse cycle29:
Where f is the pump flow rate, p is the arterial pressure (mm Hg), and dt indicates that the integration is performed over time (t). The unit of the EEP is millimeters of mercury. Therefore, it is possible to compare the EEP with the mean arterial pressure (MAP). The difference between the EEP and MAP is the extra energy generated by each pulsatile or nonpulsatile device. The difference between EEP and MAP in the normal human heart is approximately 10%.
The Surplus Hemodynamic Energy (SHE) formula is calculated by multiplying the difference between the EEP and the MAP by 1332. The SHE equals the extra energy in terms of energy units.
Limitations of Experimental Designs in Some Investigations
In order to make clinically meaningful comparisons, every single component of the bypass circuit must be selected based on its previous performance in different perfusion modes, because not only the pulsatile pump but also the oxygenator and aortic cannula have a direct impact on the quality of the pulsatility during bypass.5–10,83–87
In the pulsatile extracorporeal circulation system, undoubtedly, the pump is the key to the whole system. In view of improved technological advancements, one might have anticipated the development of pumps able to deliver adjustable and reliable pulsatile flow. In the United States, only pumps that have been approved by the US Food and Drug Administration (FDA) can be applied during clinical bypass. All of them generate only diminished pulsatility, not physiologic pulsatility.9,30 We previously tested almost all of the heart-lung machines that have been approved by the FDA in terms of hemodynamic energy levels in the piglet model and found that the pulsatile roller pump with a diminished pulsatile flow is significantly better than nonpulsatile perfusion to recover the vital organs during and after CPB. A detailed investigation of different pumps and hemodynamic energy levels can be found in our previous publications.6–8
Because the membrane oxygenator is regularly placed after the pump, the pressure drop of the membrane has a direct impact on the quality of the pulsatility delivered by the pulsatile pumps.83–86 Hollow-fiber membrane oxygenators have significantly lower pressure drops and are more suitable for use with pulsatile pumps than flat-sheet membrane oxygenators. However, the structure and engineering designs of hollow-fiber membrane oxygenators may also have a direct impact on the quality of the pulsatility.83–86 The pressure drop of the membrane is extremely important for pediatric CPB procedures, because the pump flow rates are significantly higher in neonates and infants than in adult patients (150–200 ml/kg/min vs. 50 ml/kg/min).87,88
The quality of the pulsatility is greatly affected by the length of the arterial cannula tip. An arterial cannula with a shorter tip allows better pulsatility.84 Because the sizes of the cannulas are significantly smaller for pediatric patients, the geometry of the cannula has a direct impact on the quality of the pulsatility.
Both pulsatile and nonpulsatile groups must include patients with similar characteristics including age, weight, body surface area, and severity of surgery.5,10,32,83 It is well documented that more significant vital organ injury occurs in the population of high-risk patients as compared with the low-risk patients during CPB. An effective comparison between pulsatile and nonpulsatile perfusion during clinical practice should focus on the high-risk patients.
In published literature, there is no evidence documenting the adverse effects of pulsatility during pediatric or adult patient CPB. Pro-nonpulsatile investigators can claim only that there is no difference between pulsatile and nonpulsatile perfusion in terms of vital organ recovery. However, we found dozens of papers in the databases reporting that pulsatile flow is better than nonpulsatile flow during CPB. Based on results, we believe that pulsatile perfusion only minimizes these adverse effects; it does not eliminate them totally. When the two perfusion modes are compared in animal models or clinical work, components of the CPB circuit must be carefully chosen for optimal pulsatile flow, and arterial pressure and pump flow waveforms must be quantified in terms of energy equivalent pressure, surplus hemodynamic energy, and total hemodynamic energy levels. When these factors are accounted for, the comparison becomes clinically meaningful. The results in the literature clearly suggest that pulsatile flow is superior to nonpulsatile flow during and after open-heart surgery in pediatric and adult patients.
The authors would like to thank Elizabeth Breach for editorial assistance during preparation of this manuscript.
1. Taylor KM: Pulsatile perfusion, in: Taylor KM (ed): Cardiopulmonary Bypass
, Baltimore: Williams & Wilkins, 1986, pp. 85–114.
2. Hickey PR, Buckley MJ, Philbin DM: Pulsatile and nonpulsatile cardiopulmonary bypass: review of a counterproductive controversy. Ann Thorac Surg
36: 720–737, 1983.
3. Hornick P, Taylor KM: Pulsatile and nonpulsatile perfusion: the continuing controversy. J Cardiothorac Vasc Anesth
11: 310–315, 1997.
4. Taylor KM: The present status of pulsatile perfusion. Curr Med Lit Cardiovasc Med
3: 66–69, 1984.
5. Ündar A: Myths and truths of pulsatile and nonpulsatile perfusion during acute and chronic cardiac support. Artif Organs
28: 439–443, 2004.
6. Ündar A, Eichstaedt HC, Masai T, et al: Precise quantification of pulsatility is a necessity for direct comparisons of six different pediatric heart-lung machines in a neonatal CPB model. ASAIO J
51: 600–603, 2005.
7. Ündar A, Eichstaedt HC, Masai T, et al: Comparison of six pediatric cardiopulmonary bypass pumps during pulsatile and nonpulsatile perfusion. J Thorac Cardiovasc Surg
122: 827–829, 2001.
8. Ündar A, Frazier OH, Fraser CD Jr: Defining pulsatile perfusion: quantification in terms of energy equivalent pressure. Artif Organs
23: 712–716, 1999.
9. Ündar A: Pulsatile versus nonpulsatile cardiopulmonary bypass procedures in neonates and infants: from bench to clinical practice. ASAIO J
51: vi–x, 2005.
10. Ündar A: Benefits of pulsatile flow during and after cardiopulmonary bypass procedures. Artif Organs
29: 688–690, 2005.
11. Sezai A, Shiono M, Nakata K, et al: Effects of pulsatile CPB on interleukin-8 and endothelin-1 levels. Artif Organs
29: 708–713, 2005.
12. Murkin JM, Martzke JS, Buchan AM, et al: A randomized study of the influence of perfusion technique and pH management strategy in 316 patients undergoing coronary artery bypass surgery. I. Mortality and cardiovascular morbidity. J Thorac Cardiovasc Surg
110: 340–348, 1995.
13. Minami K, Dramburg W, Notohamiprodjo G, Körfer R: Effects of pulsatile perfusion on perioperative morbidity and mortality in high-risk patients, in: Minami K, Körfer R, Wada J (eds), Cardio-thoracic Surgery: What Is New in Current Practice
. Amsterdam, Elsevier; 1992, pp. 67–75.
14. Watarida S, Mori A, Onoe M, et al: A clinical study on the effects of pulsatile cardiopulmonary bypass on the blood endotoxin levels. J Thorac Cardiovasc Surg
108: 620–625, 1994.
15. Mori A, Watanabe K, Onoe M, et al: Regional blood flow in the liver, pancreas and kidney during pulsatile and nonpulsatile perfusion under profound hypothermia. Jpn Circ J
52: 219–227, 1988.
16. Huddy SP, Joyce WP, Pepper JR: Gastrointestinal complications in 4473 patients who underwent cardiopulmonary bypass surgery. Br J Surg
78: 293–296, 1991.
17. Son HS, Sun K, Fang YH, et al: The effects of pulsatile versus non-pulsatile extracorporeal circulation on the pattern of coronary artery blood flow during cardiac arrest. Int J Artif Organs
28: 609–616, 2005.
18. Herreros J, Berjano EJ, Sola J, et al: Injury in organs after cardiopulmonary bypass: a comparative experimental morphological study between a centrifugal and a new pulsatile pump. Artif Organs
28: 738–742, 2004.
19. Nakamura K, Harasaki H, Fukumura F, et al: Comparison of pulsatile and non-pulsatile cardiopulmonary bypass on regional renal blood flow in sheep. Scand Cardiovasc J
38: 59–63, 2004.
20. Ündar A, Masai T, Yang SQ, et al: Pulsatile perfusion improves regional myocardial blood flow during and after hypothermic cardiopulmonary bypass in a neonatal piglet model. ASAIO J
48: 90–95, 2002.
21. Ündar A, Masai T, Yang SQ, et al: Effects of perfusion mode on regional and global organ blood flow in a neonatal piglet model. Ann Thorac Surg
22. Song Z, Wang C, Stammers AH: Clinical comparison of pulsatile and nonpulsatile perfusion during cardiopulmonary bypass. J Extra Corpor Technol
29: 170–175, 1997.
23. Watanabe T, Orita H, Kobayashi M, Washio M: Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass: Comparative study of circulatory arrest, nonpulsatile low-flow perfusion, and pulsatile low-flow perfusion. J Thorac Cardiovasc Surg
97: 396–401, 1989.
24. Buket S, Alayunt A, Ozbaran M, et al: Effect of pulsatile flow during cardiopulmonary bypass on thyroid hormone metabolism. Ann Thorac Surg
58: 93–96, 1994.
25. Taylor KM, Bain WH, Davidson KG, Turner MA: Comparative clinical study of pulsatile and non-pulsatile perfusion in 350 consecutive patients. Thorax
37: 324–330, 1982.
26. Yasui H, Yonenaga K, Kado H, et al: Open-heart surgery in infants using pulsatile high-flow cardiopulmonary bypass. J Cardiovasc Surg (Torino)
30: 661–668, 1989.
27. Bregman D, Bowman FO Jr, Parodi EN, et al: An improved method of myocardial protection with pulsation during cardiopulmonary bypass. Circulation
): II157–II160, 1977.
28. Ündar A, Rosenberg G, Myers JL: Major factors in the controversy of pulsatile versus nonpulsatile flow during acute and chronic cardiac support. ASAIO J
51: 173–175, 2005.
29. Shepard RB, Simpson DC, Sharp JF: Energy equivalent pressure. Arch Surg
93: 730–740, 1966.
30. Wright G: Mechanical simulation of cardiac function by means of pulsatile blood pumps. J Cardiothorac Vasc Anesth
11: 299–309, 1997.
31. Wright G: Hemodynamic analysis could resolve the pulsatile blood flow controversy. Ann Thorac Surg
58: 1199–204, 1994.
32. Ündar A: The ABCs of research on pulsatile versus nonpulsatile perfusion during cardiopulmonary bypass [editorial]. Med Sci Monit
8: ED21–ED24, 2002.
33. Ündar A, Masai T, Frazier OH, Fraser CD Jr: Pulsatile and nonpulsatile flows can be quantified in terms of energy equivalent pressure during cardiopulmonary bypass for direct comparisons. ASAIO J
34. Ündar A: Universal and precise quantification of pulsatile and non-pulsatile pressure-flow waveforms is necessary for direct and adequate comparisons among the results of different investigators [letter]. Perfusion
18: 135–136, 2003.
35. Ündar A, Fraser CD Jr: The relation between pump flow rate and pulsatility on cerebral hemodynamics during pediatric cardiopulmonary bypass [letter]. J Thorac Cardiovasc Surg
116: 530–531, 1998.
36. Ündar A, Calhoon JH: Stockert roller pump generated pulsatile flow: cerebral metabolic changes in adult cardiopulmonary bypass [letter]. Perfusion
13: 215–216, 1998.
37. Ündar A, Fraser CD Jr: Balloon pump-induced pulsatile perfusion during cardiopulmonary bypass does not improve brain oxygenation [letter]. J Thorac Cardiovasc Surg
38. Taylor KM, Bain WH, Maxted KJ, et al: Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. I. Pulsatile system employed and its hematologic effects. J Thorac Cardiovasc Surg
75: 569–573, 1978.
39. Salerno TA, Charrette EJ, Keith FM: Hemolysis during pulsatile perfusion: clinical evaluation of a new device. J Thorac Cardiovasc Surg
79: 579–581, 1980.
40. Ündar A, Henderson N, Thurston GB, et al: The effects of pulsatile versus nonpulsatile perfusion on blood viscoelasticity before and after deep hypothermic circulatory arrest in a neonatal piglet model. Artif Organs
23: 717–721, 1999.
41. Chiu IS, Chu SH, Hung CR: Pulsatile flow during routine cardiopulmonary bypass. J Cardiovasc Surg
25: 530–536, 1984.
42. Jacobs LA, Klopp EH, Seamone W, et al: Improved organ function during cardiac bypass with a roller pump modified to deliver pulsatile flow. J Thorac Cardiovasc Surg
58: 703–712, 1969.
43. Philbin DM, Levine FH, Emerson CW, et al: Plasma vasopressin levels and urinary flow during cardiopulmonary bypass in patients with valvular heart disease: effect of pulsatile flow. J Thorac Cardiovasc Surg
78: 779–783, 1979.
44. Matsumoto T, Wolferth CC Jr, Perlman MH: Effects of pulsatile and non-pulsatile perfusion upon cerebral and conjunctival microcirculation in dogs. Am Surg
37: 61–64, 1971.
45. Fukae K, Tominaga R, Tokunaga S, et al: The effects of pulsatile and nonpulsatile systemic perfusion on renal sympathetic nerve activity in anesthetized dogs. J Thorac Cardiovasc Surg
111: 478–484, 1996.
46. Silverman NA, Levitsky S, Kohler J, et al: Prevention and reperfusion injury following cardioplegic arrest by pulsatile flow. Ann Thorac Surg
35: 493–499, 1983.
47. Kaul TK, Swaminathan R, Chatrath RR, Watson DA: Vasoactive pressure hormones during and after cardiopulmonary bypass. Int J Artif Organs
13: 293–299, 1990.
48. Kono K, Philbin DM, Coggins CH, et al: Adrenocortical hormone levels during cardiopulmonary bypass with and without pulsatile flow. J Thorac Cardiovasc Surg
85: 129–133, 1983.
49. Taylor KM, Wright GS, Reid JM, et al: Comparative studies of pulsatile and nonpulsatile flow during cardiopulmonary bypass. II. The effects on adrenal secretion of cortisol. J Thorac Cardiovasc Surg
75: 574–578, 1978.
50. Philbin DM, Levine FH, Kono K, et al: Attenuation of the stress response to cardiopulmonary bypass by the addition of pulsatile flow. Circulation
64: 808–812, 1981.
51. Taylor KM, Bain WH, Morton JJ: The role of angiotensin II in the development of peripheral vasoconstriction during open-heart surgery. Am Heart J
100: 935–937, 1980.
52. Ündar A, Masai T, Yang SQ, et al: Global and regional cerebral blood flow in neonatal piglets undergoing pulsatile cardiopulmonary bypass with continuous perfusion at 25 degrees C and circulatory arrest at 18 degrees C. Perfusion
16: 503–510, 2001.
53. Hashimoto K, Onoguchi K, Takakura H, et al: Beneficial effect of balloon-induced pulsatility on brain oxygenation in hypothermic cardiopulmonary bypass. J Cardiovasc Surg (Torino)
42: 587–593, 2001.
54. Ündar A, Eichstaedt HC, Frazier OH, Fraser CD Jr: Monitoring regional cerebral oxygen saturation using near-infrared spectroscopy during pulsatile hypothermic cardiopulmonary bypass in a neonatal piglet model. ASAIO J
46: 103–106, 2000.
55. Mutch WA, Warrian RK, Eschun GM, et al: Biologically variable pulsation improves jugular venous oxygen saturation during rewarming. Ann Thorac Surg
69: 491–497, 2000.
56. Mutch WA, Lefevre GR, Thiessen DB, et al: Computer-controlled cardiopulmonary bypass increases jugular venous oxygen saturation during rewarming. Ann Thorac Surg
65: 59–65, 1998.
57. Onoe M, Mori A, Watarida S, et al: The effect of pulsatile perfusion on cerebral blood flow during profound hypothermia with total circulatory arrest. J Thorac Cardiovasc Surg
108: 119–125, 1994.
58. Nojima T, Mori A, Watarida S, Onoe M: Cerebral metabolism and effects of pulsatile flow during retrograde cerebral perfusion. J Cardiovasc Surg (Torino)
34: 483–492, 1993.
59. Watanabe T, Washio M: Pulsatile low-flow perfusion for enhanced cerebral protection. Ann Thorac Surg
56: 1478–1481, 1993.
60. Chiang BY, Ye CH, Gou XD, et al: Effects of pulsatile reperfusion on globally ischemic myocardium. ASAIO J
39: M438–M443, 1993.
61. Levine FH, Phillips HR, Carter JE, et al: The effect of pulsatile perfusion on preservation of left ventricular function after aortocoronary bypass grafting. Circulation
64(2 Pt 2): II40–II44, 1981.
62. Mori F, Ivey TD, Itoh T, et al: Effects of pulsatile reperfusion on post-ischemic recovery of myocardial function after global hypothermic cardiac arrest. J Thorac Cardiovasc Surg
93: 719–727, 1987.
63. Gu YJ, De Kroon TL, Elstrodt JM, et al: Augmentation of abdominal organ perfusion during cardiopulmonary bypass with a novel intra-aortic pulsatile catheter pump. Int J Artif Organs
28: 35–43, 2005.
64. Mori A, Tabata R, Nakamura Y, et al: Effects of pulsatile cardiopulmonary bypass on carbohydrate and lipid metabolism. J Cardiovasc Surg (Torino)
28: 621–626, 1987.
65. Murray WR, Mittra S, Mittra D, et al: The amylase-creatinine clearance ratio following cardiopulmonary bypass. J Thorac Cardiovasc Surg
82: 248–253, 1981.
66. Nagaoka H, Innami R, Watanabe M, et al: Preservation of pancreatic beta cell function with pulsatile cardiopulmonary bypass. Ann Thorac Surg
48: 798–802, 1989.
67. Ündar A, Masai T, Beyer EA, et al: Pediatric physiologic pulsatile pump enhances cerebral and renal blood flow during and after cardiopulmonary bypass. Artif Organs
26: 919–923, 2002.
68. Kim HK, Son HS, Fang YH, et al: The effects of pulsatile flow upon renal tissue perfusion during cardiopulmonary bypass: A comparative study of pulsatile and nonpulsatile flow. ASAIO J
51: 30–36, 2005.
69. Dalton ML Jr, Mosley EC, Woodward KE, Barila TG: The effect of pulsatile flow of renal blood flow during extracorporeal circulation. J Surg Res
51: 127–131, 1965.
70. Lodge AJ, Ündar A, Daggett CW, et al: Regional blood flow during pulsatile cardiopulmonary bypass and after circulatory arrest in an infant model. Ann Thorac Surg
63: 1243–1250, 1997.
71. Canivet JL, Larbuisson R, Damas P, et al: Plasma renin activity and urine beta 2-microglobulin during and after cardiopulmonary bypass: Pulsatile vs non-pulsatile perfusion. Eur Heart J
11: 1079–1082, 1990.
72. Matsuda H, Hirose H, Nakano S, et al: Results of open heart surgery in patients with impaired renal function as creatinine clearance below 30 ml/min: The effects of pulsatile perfusion. J Cardiovasc Surg (Torino)
27: 595–599, 1986.
73. Ohri SK, Bowles CW, Mathie RT, et al: Effect of cardiopulmonary bypass perfusion protocols on gut tissue oxygenation and blood flow. Ann Thorac Surg
64: 163–170, 1997.
74. Gaer JA, Shaw AD, Wild R, et al: Effect of cardiopulmonary bypass on gastrointestinal perfusion and function. Ann Thorac Surg
57: 371–375, 1994.
75. Clarke PC, Kahn DR, Dufek JH, Sloan H: The effects of non-pulsatile blood flow on canine lungs. Ann Thorac Cardiovasc Surg
57: 190–195, 1968.
76. Orime Y, Shiono M, Hata H, et al: Cytokine and endothelial damage in pulsatile and nonpulsatile cardiopulmonary bypass. Artif Organs
23: 508–512, 1999.
77. Neuhof C, Wendling J, Dapper F, et al: Endotoxemia and cytokine generation in cardiac surgery in relation to flow mode and duration of cardiopulmonary bypass. Shock
1: 39–43, 2001.
78. Vedrinne C, Tronc F, Martinot S, et al: Better preservation of endothelial function and decreased activation of the fetal renin-angiotensin pathway with the use of pulsatile flow during experimental fetal bypass. J Thorac Cardiovasc Surg
120: 770–777, 2000.
79. Driessen JJ, Dhaese H, Fransen G, et al: Pulsatile compared with nonpulsatile perfusion using a centrifugal pump for cardiopulmonary bypass during coronary artery bypass grafting: Effects on systemic haemodynamics, oxygenation, and inflammatory response parameters. Perfusion
10: 3–12, 1995.
80. Fumero R, Montevecchi FM, Scuri S, et al: Clinical experience with a new pulsatile pump for infant and pediatric cardiopulmonary bypass. Int J Artif Organs
12: 314–320, 1989.
81. McKhann GM, Grega MA, Borowicz LM Jr, et al: Stroke and encephalopathy after cardiac surgery: An update. Stroke
37: 562–571, 2006.
82. Allen SW, Gauvreau K, Bloom BT, Jenkins KJ: Evidence-based referral results in significantly reduced mortality after congenital heart surgery. Pediatrics
112: 24–28, 2003.
83. Ündar A: Principles and practice of pulsatile perfusion in pediatric and adult open-heart surgery. Turkish J Thorac Cardiovasc Surg
12: 215–219, 2004.
84. Ündar A, Lodge AJ, Daggett CW, et al: The type of aortic cannula and membrane oxygenator affect the pulsatile waveform morphology produced by a neonate-infant cardiopulmonary bypass system in vivo. Artif Organs
22: 681–686, 1998.
85. Ündar A, Koenig KM, Frazier OH, Fraser CD Jr: Impact of membrane oxygenators on pulsatile versus nonpulsatile perfusion in a neonatal model. Perfusion
15: 111–120, 2000.
86. Gourlay T, Taylor KM: Pulsatile flow and membrane oxygenators. Perfusion
9: 189–196, 1994.
87. Ündar A, Owens WR, McGarry MC, et al: Comparison of hollow-fiber membrane oxygenators in terms of pressure drop of the membranes during normothermic and hypothermic cardiopulmonary bypass in neonates. Perfusion
20: 135–138, 2005.
88. Dubois J, Jamaer L, Mees U, et al: Ex vivo evaluation of a new neonatal/infant oxygenator: Comparison of the Terumo CAPIOX Baby RX with Dideco Lilliput 1 and Polystan Safe Micro in the piglet model. Perfusion
19: 315–321, 2004.