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Ann Thorac Surg 1999;68:1330-1335
© 1999 The Society of Thoracic Surgeons
a Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Hannover, Germany
b Department of Anesthesia, Hannover Medical School, Hannover, Germany
c Department of Pharmacology, Hannover Medical School, Hannover, Germany
Address reprint requests to Dr Strüber, Division of Thoracic and Cardiovascular Surgery, Hannover Medical School, Carl Neuberg Str 1, 30623 Hannover, Germany
e-mail: strueber{at}thg.mh-hannover.de
| Abstract |
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Methods. Cytokine release and complement activation (interleukin-6 and interleukin-8, soluble tumor necrosis factor receptors 1 and 2, complement factor C3a, and C1 esterase inhibitor) were determined in 24 patients before and after CABG or MIDCABG. The maximum body temperature, chest drainage, and fluid balance were recorded for 24 hours after operation.
Results. Release of interleukin-6, interleukin-8, and tumor necrosis factor receptors 1 and 2 was significantly higher (p
0.005) in the CABG group than the MIDCABG group just after operation. After 24 hours, a significant increase in interleukin-6 was also found in the MIDCABG group (p = 0.001) compared with preoperative value. Body temperature and fluid balance were significantly higher after CABG (p
0.001).
Conclusions. Minimally invasive direct coronary artery bypass grafting represents a less traumatizing technique of surgical revascularization. The reduction in the inflammatory response may be advantageous for patients with a high degree of comorbidity.
| Introduction |
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Since the 1967 report by Kolessov [2], only a few surgeons have reported on bypass grafting without CPB. Recent attention has focused on this technique to avoid the adverse effects of CPB on very sick patients and to contain costs. To optimize access to the internal mammary artery (IMA) and improve epicardial stabilization, special retractors were designed (Cardiothoracic Systems, Inc, Cupertino, CA) for minimally invasive direct coronary artery bypass grafting (MIDCABG) through a minithoracotomy without CPB. This technique has been shown to be a safe and reliable method for revascularization of the left anterior descending coronary artery (LAD) [3]. Successful use in repeat coronary artery bypass procedures has also been reported [4]. One feature of this technique is the clamping of the LAD for up to 30 minutes for revascularization. Studies of cytokine responses to CPB reveal that cytokine release is triggered by ischemia and reperfusion and that the levels of cytokine release correlate with cardiac ischemia [5]. This study compares the perioperative cytokine release after MIDCABG with that after conventional CABG.
| Patients and methods |
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MIDCABG procedure
A left anterior minithoracotomy of 8 to 10 cm through the fifth intercostal space was performed. With the special retractor system (Cardiothoracic Systems, Inc), the left IMA was dissected as a pedicle up to the second rib. After harvest of the IMA, heparin (100 U/kg of body weight) was administered, and the pericardium was opened. The myocardial surface was stabilized at the site of anastomosis to the LAD with a special "horseshoe" retractor. Before the anastomosis was performed, the LAD was occluded proximally and distally using two tourniquet sutures. The vessel was incised between these sutures, and the IMA anastomosis was constructed in an end-to-side fashion. Heparin was not reversed by protamine sulfate. After fixation of the distal pedicle, the chest was closed. The patients were mechanically ventilated in the intensive care unit for 12 to 15 hours and transferred from that unit 24 hours after operation.
CABG procedure
All patients underwent standard surgical revascularization for three-vessel coronary artery disease through a median sternotomy. In every instance, the pedicled left IMA was used as an LAD graft. In addition, two to four vein graft anastomoses were performed. Cardiopulmonary bypass was done with a non-heparin-coated circuit, a roller pump (Stöckert Instrumentation, Munich, Germany), and a membrane oxygenator (Monolyth; Sorin Biomedica, Munich, Germany). During CPB, moderate hypothermia (30° to 32°C) was induced. Prior to CPB, high-dose heparin (300 U/kg) was given, and an activated clotting time of more than 400 seconds was maintained. Heparin was reversed completely after termination of CPB. St. Thomas cardioplegic solution, 1 to 1.5 L, was infused through the aortic root to achieve myocardial preservation during cross-clamping.
Anesthesia
Sodium thiopental, fentanyl, and pancuronium bromide were administered to all patients. In the MIDCABG group, hemodynamic monitoring was done with a thermodilution catheter. During the time of harvest of the IMA to completion of the anastomosis, a left bronchial occlusion catheter was used to reduce ventilation of the left lung. In the CABG group, a mean arterial pressure of 50 to 70 mm Hg was maintained during CPB.
Cytokine measurements
Blood samples were obtained on admission, immediately after the surgical procedure, and 2, 8, and 24 hours after arrival in the intensive care unit. Blood was drawn from arterial catheters only. Enzyme-linked immunosorbent assays were used for measurement of soluble tumor necrosis factor (TNF) receptors 1 and 2 (R&D Systems, Wiesbaden, Germany). Levels of interleukin (IL)-6 and IL-8 were also determined by enzyme-linked immunosorbent assay (Immulite, DPC Biermann, Bad Nauheim, Germany). C1 esterase inhibitor activity was measured functionally by a commercially available amidolytic test (Behring, Marburg, Germany). Complement factor C3a was determined by radioimmunoassay (Amersham International, Inc, Little Chalfont, UK).
Statistical analysis
All data are expressed as the mean ± the standard deviation. Analysis of variance for repeated measures was performed using an SPSS statistical program. A p value of less than 0.05 was considered significant.
| Results |
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All patients in both groups were extubated 6 to 12 hours after the operation and were transferred in hemodynamically stable condition from the intensive care unit to a regular ward on the first postoperative day. No sympathomimetic drugs were used during the postoperative course, and no signs of cardiac ischemia as determined by electrocardiographic criteria or creatine kinase or troponin T levels were found. Blood loss within 24 hours after operation was 580 ± 280 mL in the MIDCABG group and 720 ± 350 mL in the CABG group.
The concentration of C3a in the CABG group increased fivefold (p = 0.001) right after the surgical procedure compared with the preoperative value. The level then decreased steadily until a normal range was reached after 24 hours (Fig 1). In contrast, C3a concentration was unchanged in the MIDCABG group. There was a tendency for the activity of C1 esterase inhibitor to be reduced (p = 0.049) for the first 8 hours after CPB with normal values at 24 hours (Fig 2). No such changes were found in the MIDCABG group.
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| Comment |
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, IL-6, and IL-8 [11] and activation of the complement system [6]. This leads clinically to a postperfusion syndrome characterized by fever and fluid accumulation in the interstitium [12]. In addition, low systemic vascular resistance can develop [13]. Postperfusion organ dysfunction has been reported mainly for the lungs [14], the kidneys [15], and the central nervous system. Activation of the complement system by CPB is considered a first step in the inflammatory reaction and a main cause for organ dysfunction [16]. In our study, a significant increase in C3a characterized the activation of the complement system immediately after CABG. This was followed by a moderate decrease in activity of C1 esterase inhibitor, the main inhibitor of activation of the complement system by way of the classic pathway. This decrease may indicate consumption of this factor as a result of overstimulation of the pathway by CPB. In one instance, acquired C1 esterase inhibitor deficiency plus CPB was reported to cause pulmonary edema, circulatory collapse, and hemostatic disorder [17]. Such activation of the complement system by the classic pathway because of exposure of the blood to artificial surfaces was considered the initial step in the CPBinduced inflammatory response [6].
High circulating levels of proinflammatory cytokines such as TNF and IL-6 after cardiac operations are also associated with the postperfusion syndrome and a higher postoperative oxygen consumption [18]. Genes responsible for expression and production of TNF were activated during CPB in all patients and were highest when CPB exceeded 1.5 hours [19]. Reduction in circulating concentrations of complement factors (C3a and C5a) and cytokines (TNF and IL-6) by use of a polysulfone hemofilter during CBP resulted in improved early postoperative oxygenation and hemodynamics [20].
In our study, the soluble TNF receptors were used as a more stable indicator of TNF-
release [21, 22]. The postoperative increase in both receptors indicates a substantial release of TNF-
during CABG. The increase in the proinflammatory IL-6 and IL-8 follows the same pattern with substantially increased levels after CABG. In contrast, no significant increases in these cytokine levels were found after MIDCABG except for IL-6. Steadily increasing concentrations of this cytokine were measured up to 24 hours postoperatively. However, the peak level seen in the CABG group was not reached. This indicates an IL-6 release after the surgical procedure and may be due to anesthesia, blood loss, mechanical ventilation, or pain. Further clinical investigation is necessary to define the factors responsible for IL-6 release.
This study demonstrates that the inflammatory response seen with conventional CABG procedures with high circulating concentrations of activated complement products and proinflammatory cytokines is not found after MIDCABG operations. Procedural differences that might influence the inflammatory process include the use of the extracorporeal perfusion system during CABG, the extent of myocardial ischemia (local for MIDCABG and global for CABG), and the use of protamine sulfate and moderate hypothermia for CABG. In a similar study using the same MIDCABG technique, Gu and associates [23] found no activation of the complement system. In addition, they reported the elimination of leukocyte and platelet activation in the MIDCABG group. In our study, no fever was seen clinically after MIDCABG, and the interstitial fluid accumulation evidenced by positive fluid balances in the CABG group was not found after MIDCABG. Other studies [21] report that these advantages may lead to a shorter period of postoperative ventilatory support and a reduction in postoperative hospital stay. These observations were similar to those in a previous study in patients who underwent coronary bypass grafting without CPB [24].
A limitation of this study is that the procedures compared differed in the degree of coronary artery revascularization. In the CABG group, complete revascularization of three-vessel disease was performed. In contrast, with the MIDCABG technique, only coronary arteries of the anterior wall can be accessed. The conventional approach resulted not only in a longer surgical incision and the use of CBP, but also in longer operating and anesthesia times. However, in our experience, the lesser degree of invasiveness of MIDCABG, as evidenced by the elimination of an inflammatory response and the avoidance of a median sternotomy, led to the referral of patients with two- or three-vessel disease for this procedure. These patients had a high degree of comorbidity, such as advanced lung or kidney disease. In this group, the inflammatory response to CABG represents a high risk for postoperative organ dysfunction [25]. After MIDCABG, none of the patients experienced organ dysfunction. The MIDCABG approach offers surgical coronary revascularization to patients who can undergo CPB only at higher risk. Also, MIDCABG with subsequent angioplasty of the remaining lesions ("hybrid procedure") is applicable particularly for patients with a high degree of comorbidity.
In conclusion, this study shows that cytokine release with MIDCABG is significantly lower than that with conventional CABG with CPB. We confirmed other studies revealing high complement activation during CABG that is not found for MIDCABG. In addition, consumption of C1 esterase inhibitor was found in this study. The absence of complement activation and cytokine release leads to an improved clinical course and no postoperative inflammatory response. These findings are of special importance for patients with associated disease and coronary vessel disease that cannot be treated with angioplasty alone. Minimally invasive direct coronary artery bypass grafting represents another treatment strategy for these patients.
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