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Ann Thorac Surg 2006;81:1109-1111
© 2006 The Society of Thoracic Surgeons


Case report

Arteriolar Blood Flow Pulsatility in a Patient Before and After Implantation of an Axial Flow Pump

Helmut Habazettl, MD a , * , Marian Kukucka, MD b , Yu G. Weng, MD c , Wolfgang M. Kuebler, MD a , Roland Hetzer, MD c , Hermann Kuppe, MD b , Axel R. Pries, MD a

a Institute of Physiology, Charité Campus Benjamin Franklin, Berlin, Germany
b Institute of Anesthesiology, Deutsches Herzzentrum, Berlin, Germany
c Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum, Berlin, Germany

Accepted for publication December 21, 2004.

* Address correspondence to Dr Habazettl, Institute of Physiology, Charité Campus Benjamin Franklin, Arnimallee 22, Berlin, 14195 Germany (Email: helmut.habazettl{at}charite.de).


    Abstract
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 Abstract
 Introduction
 Comment
 References
 
In a patient with end stage ischemic heart failure scheduled for implantation of an axial flow pump small arteriolar flow pattern was recorded using a novel intravital microscope. Preoperative arteriolar blood flow velocity was highly pulsatile, ranging from about 7 to 16 mm per second in a 12.8 µm diameter arteriole. After implantation of the pump, this pulsatility was abrogated and arteriolar blood flow velocity changed instantaneously with changes in pump speed (eg, 2 mm/s at 5,000 rpm vs 3.5 mm/s at 8,000 rpm in an 8.9 µm diameter arteriole). This lack of flow velocity oscillations may have profound long-term effects on shear stress regulated arteriolar remodeling.


    Introduction
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 Abstract
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Left ventricular assist devices (LVADs) producing continuous flow are increasingly implanted into patients (for review see reference [1]). Although the effects of these devices on central hemodynamics are well characterized, little information is available about their impact on the microcirculation. Maintenance of hepatic and renal function in sheep and patients suggests that microvascular perfusion of these organs was preserved for up to 6 months, despite reduced pulsatility of pressure and flow [2, 3]. In calves, during short-term exposure to an axial flow LVAD, physiological regulation of tissue perfusion seemed to remain intact [4]. However, prolonged nonpulsatile perfusion in sheep and goats induced thinning of the aortic media layer and atrophy of smooth muscle cells [3, 5]. Similar effects seem to occur in arteriolar resistance vessels after 4 weeks of nonpulsatile perfusion in pigs [6].

These effects are attributed to the lack of pressure pulse in the blood vessels. However, axial flow LVADs would also abolish the pulsatility of flow in the microcirculation, which may have profound effects on endothelial cells that seem to respond differently to oscillatory versus continuous shear stress even at the same mean value [7]. Because it is unknown how pulsatile flow is transmitted from the aorta and great arteries to downstream small resistance arterioles in patients before and after implantation of an axial LVAD, we used a novel intravital microscopic technique to directly observe diameters and blood flow velocity in sublingual microvessels in a patient scheduled for LVAD implantation.

A 62-year old man with end stage heart failure due to ischemic cardiomyopathy presented with acute deterioration of cardiac function and was scheduled for implantation of an axial flow pump [8] (Incor, Berlin Heart, Berlin Germany). Immediately before and after surgery, video sequences from sublingual microvessels were recorded using an orthogonal polarization spectral imaging device [9] (Cytoscan Lekam, Devon, UK) additionally equipped with a double flash illumination technique to allow for off-line analysis of arteriolar blood flow velocity by spatial correlation [10].

Figure 1 shows an example of the patient's sublingual microvessels. Figure 2A shows preoperative blood flow velocity in a 12.8 µm diameter arteriole. At this time, heart rate was 92 bpm, blood pressure was 115/62 mm Hg, cardiac output was 4.04 L/min, and left ventricular and right ventricular ejection fraction determined by echocardiography was 20% and 45%, respectively. Flow velocity exhibits a large, rhythmic oscillation showing that pulsatility of blood flow is effectively transmitted from large arteries to pre-capillary arterioles. Power spectral analysis revealed that the largest fraction of total oscillation energy resides in the peak representing the patient's heart rate (Fig 2B).


Figure 1
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Fig 1. Example of human sublingual microvessels visualized by our OPS imaging device. V denotes collecting venule, the arrows from A point at a distributing arteriole. The scale bar with a length of 100 µm is given.

 

Figure 2
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Fig 2. Results of off-line continuous blood flow velocity measurements in sublingual arterioles (top) and of power spectral density of these signals as obtained by Fast Fourier Transformation (bottom) are given for two arterioles of the same patient before (A, B) and after implantation of the axial flow pump (C, D). Please note the different x- and y-axis scalings in panel C as compared to panel A. After implantation of the pump, the rhythmic oscillations of small arteriole blood flow velocity in synchrony with heart rate (HR) are lost (C, D). Instead blood flow velocity instantly changes with the pump speed (rpm = rotations per minute).

 
After implantation of the axial flow pump cardiac output was completely dependent on the pump as evidenced by echocardiographic monitoring of the continuously closed aortic valve. At this time the pump speed was varied to optimize the patient's hemodynamics. Blood pressure and pump flow were 87/64 mm Hg and 3.2 L/min at 5,000 rpm and 91/87 mm Hg and 5.1 L/min at 8,000 rpm, respectively. During such a switch from 5,000 to 8,000 and back to 5,000 rpm, blood flow velocity was recorded in an arteriole of 8.9 µm in diameter for about 85 seconds (Fig 2C). Oscillation of blood flow velocity is considerably reduced and only a very small component of total spectral power can be attributed to the patient's beating heart (Fig 2D). The 60% increase in pump speed directly translated into a similar increase (76 %) in mean arteriolar blood flow velocity, whereas mean arterial pressure increased by only 21%, indicating that microvascular perfusion in this patient largely depends on the performance of the pump and is not reflected directly by arterial pressure. Although the initial postoperative course of the patient was uneventful (extubated after 6 days and fully mobilized on a normal ward of our hospital), he died of cerebral infarction and subsequent hemorrhage 6 weeks after pump implantation.


    Comment
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 Abstract
 Introduction
 Comment
 References
 
Blood flow velocity is sensed by endothelial cells by wall shear stress that elicits numerous responses in these cells. Acute responses include release of nitric oxide and prostacyclin that induce vasorelaxation and have anti-thrombotic and anti-inflammatory properties [11]. Long-term changes in shear stress alter endothelial gene expression and modulate vessel growth and regression [12]. However, endothelial cells seem to respond differently to continuous versus oscillatory shear stress [7]. Thus, the observed abrogation of blood flow pulsatility in small resistance arterioles after implantation of an axial flow LVAD, may have profound long-term effects on endothelial-mediated vascular adaptive mechanisms.


    References
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 Abstract
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 Comment
 References
 

  1. Song X, Throckmorton AL, Untaroiu A, et al. Axial flow blood pumps ASAIO J 2003;49(4):355-364.[Medline]
  2. Letsou GV, Myers TJ, Gregoric ID, et al. Continuous axial-flow left ventricular assist device (Jarvik 2000) maintains kidney and liver perfusion for up to 6 months Ann Thorac Surg 2003;76:1167-1170.[Abstract/Free Full Text]
  3. Saito S, Westaby S, Piggot D, et al. End-organ function during chronic nonpulsatile circulation Ann Thorac Surg 2002;74:1080-1085.[Abstract/Free Full Text]
  4. Tuzun E, Eya K, Chee HK, et al. Myocardial hemodynamics, physiology, and perfusion with an axial flow left ventricular assist device in the calf ASAIO J 2004;50(1):47-53.[Medline]
  5. Nishimura T, Tatsumi E, Takaichi S, et al. Prolonged nonpulsatile left heart bypass with reduced systemic pulse pressure causes morphological changes in the aortic wall Artif Organs 1998;22(5):405-410.[Medline]
  6. Nishimura T, Tatsumi E, Nishinaka T, et al. Diminished vasoconstrictive function caused by long-term nonpulsatile left heart bypass Artif Organs 1999;23(8):722-726.[Medline]
  7. Barakat A, Lieu D. Differential responsiveness of vascular endothelial cells to different types of fluid mechanical shear stress Cell Biochem Biophys 2003;38(3):323-343.[Medline]
  8. Hetzer R, Weng Y, Potapov EV, et al. First experiences with a novel magnetically suspended axial flow left ventricular assist device Eur J Cardiothorac Surg 2004;25(6):964-970.[Abstract/Free Full Text]
  9. Groner W, Winkelman JW, Harris AG, et al. Orthogonal polarization spectral imaginga new method for study of the microcirculation. Nat Med 1999;5(10):1209-1212.[Medline]
  10. Lindert J, Werner J, Redlin M, Kuppe H, Habazettl H, Pries AR. OPS imaging of human microcirculationa short technical report. J Vasc Res 2002;39(4):368-372.[Medline]
  11. Tedgui A, Mallat Z. Anti-inflammatory mechanisms in the vascular wall Mol Cell 2001;88(9):877-887.
  12. Brown MD, Hudlicka O. Modulation of physiological angiogenesis in skeletal muscle by mechanical forcesinvolvement of VEGF and metalloproteinases. Angiogenesis 2003;6(1):1-14.[Medline]



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