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Ann Thorac Surg 1999;68:1967-1970
© 1999 The Society of Thoracic Surgeons
a Division of Cardiovascular Surgery, University of Freiburg, Freiburg, Germany
Address reprint requests to Dr Schlensak, Department of Cardiovascular Surgery, University of Freiburg, Hugstetter Str 55, 79106 Freiburg, Germany
e-mail: schlensa{at}ch11.ukl.uni-freiburg.de
Presented at the International Symposium on Myocardial Protection From Surgical Ischemic-Reperfusion Injury, Asheville, NC, Sep 21–24, 1997.
Abstract
The goal of revascularization after acute occlusion of a coronary artery is the return of contractile function and the reduction of mortality. Although reperfusion of ischemic myocardium is a prerequisite for return of function, it may, in itself, cause further injury. Controlled blood cardioplegic reperfusion reduces this "reperfusion injury" and provides maximal myocardial protection. In this article, we review recent advances in surgically controlled reperfusion and speculate on future prospects for myocardial protective techniques in patients with acute coronary artery occlusion.
The goal of revascularization after acute occlusion of a coronary artery is the return of contractile function and the reduction of mortality. In practice, revascularization can be achieved by thrombolysis, percutaneous transluminal coronary angioplasty (emergency PTCA) or coronary artery bypass grafting (emergency CABG). Despite these possibilities to revascularize ischemic myocardium, the results are still disappointing. Surgical revascularization is associated with the worst outcome reaching a perioperative mortality of up to 17% [1, 2] compared to 9% with PTCA [3–7]. Therefore surgical revascularization procedures have generally been restricted to patients with acute coronary occlusion after failed PTCA.
Although reperfusion of ischemic myocardium is a prerequisite for return of function, it may, in itself, cause further injury. The severity of this "reperfusion injury" is related to the duration of ischemia [8]. Reduction of reperfusion injury is associated with improved outcome [9]. We have developed a strategy of "controlled reperfusion" of the acutely ischemic myocardium, in which both the composition of the reperfusate and the application pressure are predetermined [10–12]. We tested our strategy in patients undergoing emergency CABG and compared our results to those obtained from patients who underwent emergency PTCA [13]. We found that despite the worse prognosis of patients undergoing surgery, the mortality of surgically revascularized patients receiving controlled reperfusion was substantially lower than that of patients undergoing emergency PTCA. Our results suggest that a large amount of the perioperative or perinterventional mortality in these patients is associated with reperfusion injury, which may be limited by controlled reperfusion.
Rationale for controlled reperfusion
During ischemia, as well as during reperfusion, profound changes occur in both function and metabolism of the heart. Briefly, during ischemia aerobic metabolism becomes inhibited and anaerobic metabolism is activated. High-energy phosphates are broken down, intracellular lactate increases, and acidosis develops [14]. The citric acid cycle loses intermediates [15]. Contractile function is decreased or seizes. Upon reperfusion, lactate and protons are washed out of the ischemic tissue. The release of protons from the cells is associated with an increase in intracellular calcium. With the reinitiation of oxidative metabolism, a burst of oxygen free radicals is generated [16]. Contractile function may, but does not always, return [17]. Among the many changes associated with ischemia and reperfusion, generation of free radicals and accumulation of intracellular calcium during reperfusion have been suggested as the main candidates responsible for reperfusion injury [8, 16, 18, 19].
We have developed a strategy of "controlled reperfusion" of the acutely ischemic myocardium, in which both the composition of the reperfusate and the condition of application are predetermined. The reperfusate for controlled reperfusion consists of blood as oxygen carrier which is supplemented with the following substances (Table 1): Potassium chloride is added to keep the myocardium arrested, which avoids an increase in energy demand. Buffering capacity is increased to limit acidosis. Glucose, glutamate, and aspartate are added to provide ample substrate on reperfusion, to promote anaplerotic reactions for the replenishment of the citric acid cycle, and to increase osmolarity.
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After completion of the final distal anastomosis and after the aortic clamp is removed, the controlled blood cardioplegic solution is given at a flow rate of up to 50 ml/min per graft with a perfusion pressure not exceeding 50 mmHg for 20 minutes into the vein grafts only. Cannulation of a side branch of the vein graft may allow delivery of the controlled blood cardioplegic reperfusate while the proximal anastomosis is performed. The heart is vented during controlled reperfusion and for an additional 30 minutes after completion of controlled reperfusion.
Our experience with controlled reperfusion
Single-center
We used the approach of controlled reperfusion in 37 patients with acute coronary artery occlusion who underwent emergency surgical revascularization compared them to 36 patients with acute myocardium infarction who did not receive controlled reperfusion [12]. In all patients, cardiopulmonary bypass (CPB) was initiated as quickly as possible, with cannulation of the aorta and the right atrium with a single venous cannula, and venting of the left ventricle. Combined antegrade and retrograde delivery of blood cardioplegic solution for induction and maintenance was used. After completion of the final, distal anastomosis, the aortic clamp was removed and the hot shot was given [20]. The controlled blood reperfusate was now given antegradely into the grafts for 20 minutes. Regional wall motion was evaluated intraoperatively by the surgeon and postoperatively analyzed from either radionuclide ventriculography or echocardiography. The overall hospital mortality was 5% in the group of patients protected with controlled reperfusion compared to 11% in the group who did not receive controlled reperfusion, although aortic occlusion time (43 ± 3 minutes versus 34 ± 3 minutes) and bypass time (105 ± 6 minutes versus 69 ± 5 minutes) were significantly longer in the group with controlled reperfusion. Bypass time was prolonged in the reperfused group because of controlled reperfusion and the 30-minute period of subsequent venting. The prevalence of spontaneous sinus rhythm after removal of the aortic clamp was higher in the group with controlled reperfusion (81%) compared to the group with uncontrolled reperfusion (Table 2). Furthermore, controlled reperfusion decreased the perioperative mortality in patients with multivessel disease from 16% to 6% and in patients with preoperative shock from 50% to 15% (Table 3).
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The concept of controlled reperfusion without thoracotomy was first described by Okamoto and colleagues [22]. In an experimental study, they performed controlled blood reperfusion after 3 hours of coronary occlusion by connection of cardiopulmonary bypass through cannulation in the groin (Figs 2, 3). Two additional catheters were advanced through the aorta. One was placed in the left ventricle for venting, the other one was placed in the coronary artery distal to the stenosis for controlled reperfusion. The results were comparable to the results of controlled reperfusion with thoracotomy, and substantially better than those where coronary occlusion was not followed by controlled reperfusion [22].
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In conclusion, a large amount of the perioperative and perinterventional mortality in patients undergoing emergency revascularization for acute myocardial infarction is associated with reperfusion injury. Controlled blood cardioplegic reperfusion reduces reperfusion injury and provides maximal myocardial protection. We propose that every patient undergoing emergency CABG should be treated with controlled reperfusion. Controlled reperfusion for patients undergoing emergency PTCA is technically feasible, but still needs to be tested under clinical conditions.
References
This article has been cited by other articles:
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  F. Nicolini, C. Beghi, C. Muscari, A. Agostinelli, A. M. Budillon, I. Spaggiari, and T. Gherli Myocardial protection in adult cardiac surgery: current options and future challenges Eur. J. Cardiothorac. Surg., December 1, 2003; 24(6): 986 - 993. [Abstract] [Full Text] [PDF]
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