Asian Cardiovasc Thorac Ann 2005;13:65-69
© 2005 Asia Publishing EXchange Ltd
Demonstration and Operative Influence of Low Prime Volume Closed Pump
Hideaki Takai, MD,
Kiyoyuki Eishi, MD,
Shiro Yamachika, MD,
Shiro Hazama, MD,
Tsuneo Ariyoshi, MD,
Katsuo Nishi, MD
Department of Cardiovascular Surgery, Nagasaki University School of Medicine, Nagasaki, Japan
For reprint information contact: Hideaki Takai, MD Tel: 81 95 849 7307 Fax: 81 95 849 7311 Email: shinge{at}net.nagasaki-u.ac.jp, Department of Cardiovascular Surgery, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
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ABSTRACT
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Various improvements have been made in cardiopulmonary bypass (CPB) in the past few decades. We designed a new type of CPB to reduce the secretion of systemic inflammatory markers. We used a low prime volume pump (LPVP), completely closed CPB circuit and examined coagulant factors and inflammatory cytokines. In this study, we demonstrate the efficacy of LPVP using molecular biological data. Fourteen patients were randomized prospectively into two groups: Group L patients underwent LPVP (n = 8) and Group N patients underwent normal prime volume CPB (n = 6). We measured thrombin-antithrombin III complex (TAT), complement factor (C3a), and interleukin (IL)-10 levels at four time points. TAT (66.1 ± 15.1 ng·mL–1), C3a (1895 ± 282 ng·mL–1) and IL-10 (486 ± 114 pg·mL–1) levels in Group N were significantly higher than in Group L (TAT, 19.5 ± 4.4 ng·mL–1; IL-10, 105 ± 24.6 pg·mL–1; C3a, 1349 ± 369 ng·mL–1) immediately following CPB. LPVP demonstrated a lower systemic inflammatory response compared to normal prime volume CPB, as assessed using a molecular biological approach.
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INTRODUCTION
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A significant advance in coronary artery revascularization was reported by Favarolo1 in 1968. Further improvements in operative techniques and devices have continued since then. The influence of cardiopulmonary bypass (CPB) has been reported in several articles.2–4 After undergoing CPB, some patients exhibit various homeostasis dysfunctions (involving respiratory function, renal function and the clotting system) that have been described as "post-perfusion syndrome". To reduce the deleterious effects of CPB, various improvements have been made.5–8 Utilizing these improvements, we devised a less invasive CPB (low prime volume closed CPB; LPVP). In this article, we demonstrate the decreased invasiveness and improved efficacy of LPVP using molecular biological techniques.
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PATIENTS AND METHODS
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After approval by the institutional review board, we studied 14 patients undergoing isolated coronary artery bypass grafting (CABG). Patients were randomized into two groups prospectively: patients undergoing LPVP, Group L (8 cases), and those with normal prime volume CPB, Group N (6 cases).
The exclusion criteria were as follows: emergent and urgent cases, renal dysfunction cases (serum creatinine > 1.5 mg·dL–1), low ejection fraction cases (EF < 35%), single bypass cases, on-pump beating-heart CABG cases, patients with severe chronic obstructive pulmonary disease or uncontrolled asthma, preoperative use of steroids and previous heart surgery.
The characteristics of the two types of CPB are showed in Table 1
. A CAPIOX EBS (Terumo Co., Tokyo, Japan) with a heparin-coated circuit was used in the LPVP circuit. A needle vent was placed in the aortic root and connected to the vent circuit and the cardioplegic solution circuit. A removable soft reservoir bag (500 mL capacity) was fixed in the middle of the blood removal circuit and the vent circuit, and was primed with Ringer’s lactate solution without blood (Figure 1). The priming solution (total volume 590 mL) was drained through the circuit (Figure 1), before starting CPB. The soft reservoir collected the blood that remained in the circuit after CPB, which was subsequently used for autologous transfusion. Suction was provided using the cell saver (Medtronic Inc., Blood Management Business Electromedics, Parker, CO, USA). The cell saver was set up independently and not connected to the LPVP circuit. Each patient was administered an initial pre-bypass bolus dose of heparin (100 IU·kg–1). During CPB, activated clotting time (ACT) was maintained at 250–300 sec. Protamine sulfate was administered at a rate of 100 IU·kg–1 in LPVP. Myocardial protection was provided by intermittent antegrade injection of warm blood cardioplegia, according to the protocol of Calafiore et al 9 in which cardioplegia flows into every anastomosis.
A CAPIOX-SX (HP) (Terumo Co., Tokyo, Japan) with a heparin-coated circuit was used in the normal prime volume open CPB circuit. This type of CPB was primed with 1.5 liters of 6% hydroxyethylated starch (10 mL·kg–1) and Ringer’s lactate solution without blood. A Sarns 9000 roller pump (Terumo Cardiovascular Systems, Ann Arbor, MI, USA) was used. Myocardial protection was provided by intermittent, antegrade injection of cold (4°C) cardioplegic solution (St. Thomas solution). Each patient was administered an initial pre-bypass bolus dose of heparin (150 IU·kg–1). ACT was kept > 400 sec during CPB. Protamine sulfate was administered at a rate of 150 IU·kg–1 in the standard prime volume open CPB.
All samples were measured for thrombin-antithrombin III complex (TAT), complement factor (C3a), and interleukin (IL)-10 levels prior to the initiation of CPB (the beginning of operation; T1), just after the end of CPB (the end of total anastomosis; T2), 4 hours after the end of CPB (total anastomosis; T3), and 24 hours after the end of CPB ( total anastomosis; T4).
All samples were stored at –80°C until analysis by enzyme-linked immunosorbent assay: IL-10 (CytoscreenUS hIL-10 Ultra Sensitive; Biosource International, Camarillo, CA, USA), TAT (Enzygnost TAT micro; Dade Behring, Liederbach, Germany), or radioimmunoassay C3a (Human Complement C3a des Arg (125I) assay system; Amersham, Buckinghamshire, UK). The limits of sensitivity were 0.5 pg·mL–1 (IL-10), 20 ng·mL–1 (C3a), and 0.5 ng·mL–1 (TAT).
All values are expressed as the mean ± standard deviation (SD). The non-repeated analysis of variance (ANOVA) and Mann-Whitney U-test were used for intragroup comparisons. All computations were performed using SPSS statistical software packages version 11.0 (SPSS Inc., Chicago, IL, USA). A p-value < 0.05 was considered statistically significant.
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RESULTS
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The progress of all patients was uneventful during the perioperative and postoperative course. Preoperative values between the 2 groups were not statistically different (Table 2).
The value of intraoperative minimum hematocrit (Hct) in Group L was significantly higher than that in Group N ( p < 0.05). The preoperative Hct percent ratio and the intraoperative minimum Hct value (% R-Hct) were determined as an index of hemodilution. The value of % R-Hct in Group N was lower (67.2%) than in Group L (76.3%). Blood transfusion was usually performed after weaning off CPB for Hct > 20%. The number of packed red blood cells was greater in Group N than that in Group L. Postoperative blood loss over 24 hours was less in Group L (348 ± 51 mL) than that in Group N (685 ± 34 mL), however this was not significantly different.
TAT concentrations reached peak values at T2 (Group N, 66.1 ± 3.7 ng·mL–1; Group L, 19.5 ± 13.1 ng·mL–1) and decreased gradually thereafter. There were no significant differences between the two groups except at T2.
C3a concentrations were similar between the two groups. The value of C3a in Group L at T2 (1349 ± 1106 ng·mL–1) was lower than that of Group N (1895 ± 630 ng·mL–1).
A significant increase in IL-10 concentrations was observed in Group N (486 ± 255 pg·mL–1) at T2. However, only a small increase was observed in Group L (105 ± 65.1 ng·mL) at T2.
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DISCUSSION
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Several studies examining less invasive procedures for CPB have been reported.10–12 Two noteworthy methods of LPVP are commonly performed: one utilizes a completely closed CPB with a reservoir bag, the other utilizes a low priming volume and low volume cardioplegia. LPVP is similar to the MECC system reported by Fromes et al 12. However, there is one distinct difference between LPVP and the MECC system: LPVP is achieved with a reservoir bag and vent circuit. By installing this soft reservoir and connecting a vent circuit during CPB we are able to drain the blood into the soft reservoir and reserve it. Therefore, it is possible to freely control both the size of the heart and the visual field of the target bypass area more effectively.
The advantages of high Hct during CPB have been reported.5,13,14 Hemodilution was avoided by reducing the priming volume in the CPB circuit and by maintaining a low priming volume during cardioplegia. This results in blood conservation and a reduction in blood surface area contact. LPVP was effective at maintaining a high Hct compared to normal prime volume CPB.
The levels of TAT were examined as an indicator of coagulant activity. There were statistically significant differences in TAT at T2. As shown in Table 4, the transition of TAT in Group L was more stable than in Group N. It would appear that the system of coagulation activity was very stable during the perioperative period in Group L.
The damaging effects of CPB, related in part to complement activation by foreign surfaces, have been reported.2 Similarly, CABG is associated with a systemic inflammatory response which has been attributed to human cytokine response.15 IL-10 plays an anti-inflammatory role by suppressing T-cell activity.16 A significant increase in the values of C3a and IL-10 at T2 in Group N was demonstrated, as opposed to only a slight increase in Group L. Therefore, LPVP elicited a reduced inflammatory response in comparison with that of normal prime volume open CPB.
The most significant challenge encountered with LPVP is air elimination. The future safe clinical use of LPVP will depend on the incorporation of a device, such as an arterial filter, in the venous line to remove air. If such a device that can remove air efficiently was available, it might be possible to perform aortic valve replacement using LPVP. This study was designed to be a small-scale pilot study to evaluate a possible positive effect of LPVP. LPVP should be further investigated in a larger cohort.
In conclusion, the value of Hct was maintained higher in LPVP than with normal prime volume CPB. This study showed that the transitions of TAT in LPVP were more stable than those found in normal prime volume CPB. The inflammatory reaction in LPVP, as evidenced by C3a and IL-10, was preferable to that demonstrated with normal prime volume CPB. We believe that LPVP, as a new device for on-pump CABG, is less invasive than normal prime volume CPB.
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TOP
ABSTRACT
INTRODUCTION
