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Ann Thorac Surg 1996;62:23-29
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Integrated Cardioplegia Allows Complex Valve Repairs in All Patients

Division of Cardiothoracic Surgery, University of Illinois, Chicago, Illinois

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Traditionally, most surgeons have taken adversarial positions with respect to whether cardioplegia should be given warm or cold, antegrade or retrograde, continuous or intermittent. Because each method has weaknesses, myocardial protection is compromised when only one method is employed. It is our contention that an "integrated" approach that combines all of the aforementioned principles will improve myocardial protection, allowing the time needed for complex valve repairs.

Methods. Thirty-four patients (25 undergoing complex mitral valve repairs and 9 undergoing Ross procedures) have undergone complex valve repair since we began using an integrated cardioplegic strategy that incorporates all of the techniques mentioned above and is based on the following principles: (1) Cardioplegia is infused antegrade and retrograde, warm and cold. (2) Surgical precision is optimized by a dry, bloodless field using cold intermittent arrest to limit ischemia when visualization is needed. (3) Continuous blood cardioplegia is used when visualization is not problematic, thereby avoiding unnecessary ischemia.

Results. Average age was 46 ± 4 years (range, 9 to 79 years), and 9 patients (26%) were having reoperations. All mitral patients had severe mitral regurgitation, 52% (13/25) had a preoperative ejection fraction less than 0.40, and 40% (10/25) had pulmonary artery pressures greater than 60 mm Hg. In the Ross patients 33% (3/9) had an ejection fraction less than 0.40, including 2 patients who concomitantly underwent complex mitral valve repair. Despite cross-clamp times of 187 ± 12 minutes (range, 138 to 267 minutes) in the Ross group and 139 ± 8 minutes (range, 92 to 218 minutes) in the complex mitral valve repair group with a predicted mortality (Parsonnet) of approximately 10%, no patients died, only 5 (15%) required inotropes, none required intraaortic balloon pumping, only 1 (3%) required antiarrhythmics, and the average postoperative hospital stay was 8 days in the mitral repair group and 5 days in the Ross group.

Conclusions. We believe an integrated approach incorporating the strategies of warm and cold blood cardioplegia, antegrade and retrograde delivery, and continuous and intermittent infusion affords better myocardial protection, avoids unnecessary ischemia, facilitates technical ease of operation, and results in a more stable postoperative course. Integrating these modalities into a comprehensive strategy (instead of relying on one) maximizes each method's strength while minimizing weaknesses, thereby allowing surgeons to perform complex valve repairs safely in all patients.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
See also page 29.

Preservation of a patient's native valve offers numerous advantages over replacement [1–4]. This knowledge has led to the development of increasingly complex surgical techniques to allow valve conservation in more patients. Unfortunately, these techniques often require prolonged periods of myocardial ischemia, resulting in a reluctance to attempt these procedures in patients with depressed hearts.

Traditionally, surgeons have taken adversarial positions with respect to whether cardioplegic solutions should be given warm or cold, antegrade or retrograde, continuous or intermittent. Because each method has inherent weaknesses, adherence to only one deprives the patient of the benefits of each of the aforementioned techniques [5–8]. Despite this limitation, most surgeons continue to rely on only one strategy, and resist the notion this may cause suboptimal myocardial protection. We believe an "integrated" approach that incorporates all of these principles will improve myocardial protection and allow all patients to safely undergo complex valve repair. We examined all patients at our institution who have undergone complex valve reconstruction since we began using an integrated cardioplegic strategy to investigate if prolonged cross-clamp times were detrimental in high-risk patients.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
We retrospectively reviewed the charts of all patients who underwent a complex valve reconstruction procedure since we began using an integrated cardioplegic strategy. Procedures considered to be complex were Ross procedures and mitral valve repairs that required more than a quadrangular resection or ring annuloplasty. There were 34 patients; 25 underwent complex mitral valve repairs, and 9 underwent Ross procedures. Data were collected with respect to age; previous operations; valve pathology; preoperative ejection fraction, left ventricular end-diastolic diameter, and pulmonary artery pressure; Parsonnet (severity) score; bypass, ischemic, and cross-clamp times; mortality; postoperative use of inotropes, intraaortic balloon counterpulsation, or antiarrhythmics; additional procedures; and postoperative length of stay (this information was available for all patients). Ischemic time was defined as the time the aorta was cross-clamped, and there was no antegrade or retrograde perfusion. Renal-dose dopamine (2 to 3 mg • kg^-1 • min^-1) was not considered positive for postoperative inotropic use. Left ventricular dilatation was defined as an end-diastolic dimension greater than 57 mm. Twenty-one patients also underwent intraoperative evaluation of right ventricular wall motion before and after bypass using transesophageal echocardiography. Wall motion was assessed by an independent observer and scored using a system previously described in which 0 is normal, 1 is mild hypokinesis, 2 is severe hypokinesis, 3 is akinesis, and 4 is dyskinesis [9].

Surgical Techniques
All patients undergoing the Ross procedure had the pulmonary autograft inserted as a root replacement using techniques previously described [10, 11]. The only deviation was the tying of the proximal suture line over a strip of gludaldehyde (0.6%)-fixed pericardium, which we believe is extremely important to limit bleeding and prevent future annular dilatation. Mitral repair was done using the techniques of Carpentier and David [4, 12, 13]. The repair techniques used, as well as the number of patients requiring each technique, are as follows:

• Complex mitral valve repair
  
• 14 Leaflet resection or sliding annuloplasty
  
• 12 Creation of new chordae tendineae using Gore- Tex (W.L. Gore & Assoc, Flagstaff, AZ) suture
  
• 8 Chordal shortening
  
• 8 Glutaraldehyde-treated pericardial leaflet exten sion
  
• 3 Commissurotomy
  
• 2 Decalcification
  
• 5 Other repair procedures
  
• Ross procedure
  
• 9 Autograft root replacement
  

All patients undergoing mitral valve repair received an annuloplasty ring (16 Carpentier-Edwards and 9 Duran).

Cardioplegia Administration
The operation was conducted using a cardioplegic strategy similar to that described previously [5,14–16]. The details, however, are summarized to illustrate variations as well as basic concepts. Cardioplegic solutions are listed in Tables 1 and 2. All patients had antegrade and retrograde (Research Medical, Salt Lake City, UT) cardioplegia cannulas placed using methods previously described [5, 8]. The cardioplegic setup is depicted in Figure 1 and uses a switch to allow the infusion pressure to be monitored directly in the aorta or coronary sinus. After systemic heparinization, cannulas were placed in the ascending aorta and both venae cavae, and connected to a pump primed with 2 L of lactated Ringer's solution. The aorta was cross-clamped, and except for patients with severe aortic insufficiency, all patients received a 4-minute warm (37°C) induction using amino acid-enriched blood cardioplegia (see Table 1). Warm induction was always begun antegrade at 350 mL/min and approximately 4 mEq of additional KCl was quickly injected into the top of the Blood Cardioplegia Device to transiently raise the potassium concentration to produce myocardial arrest. Once electromechanical activity stopped, the infusion rate was decreased to 200 mL/min (for 2 minutes) keeping the pressure less than 50 mm Hg. This was followed by a 2-minute retrograde infusion at 200 mL/min (pressure <50 mm Hg). All patients then received cold blood cardioplegia (see Table 2) at 200 mL/min (2 minutes antegrade and 2 minutes retrograde). In patients with severe aortic insufficiency the heart was arrested with cold retrograde (200 to 300 mL/min; pressure <50 mm Hg) blood cardioplegia (see Table 2), followed by antegrade cardioplegia infusion delivered directly into each coronary ostium (2 minutes each).

View larger version (42K): [in this window] [in a new window]   Fig 1. . Clinical method of delivering antegrade/retrograde cardioplegia to ensure distribution to the entire myocardium. Note that this system allows for antegrade or retrograde delivery, and simultaneous pressure monitoring is easily accomplished. (Reprinted by permission of Research Medical, Inc, Salt Lake City, UT.)

After the mitral valve had been repaired, or the pulmonary autograft insertion was complete (Ross procedures), a 5- to 6-minute infusion (200 mL/min) of warm 37°C substrate-enriched (see Table 1) blood cardioplegia ("hot shot") was given antegrade. In patients with coronary artery disease or left ventricular hypertrophy half of the warm cardioplegic reperfusate was given retrograde to ensure distribution. During this time the left atrial closure or the proximal pulmonary homograft anastomosis was completed. If a longer period of cardiac arrest was required for atrial closure or homograft insertion, the cardioplegic infusion was simply continued. We switched to noncardioplegic blood approximately 1 to 2 minutes before removing the aortic cross-clamp to wash out the cardioplegia and allow the heart to start beating immediately upon removal of the aortic clamp. Bypass was then able to be discontinued almost immediately. The operation was completed in the standard fashion.

Statistics
Statistical data were analyzed with the use of JMP V2.0 (SAS Institute Inc, Cary, NC) on a MacIntosh IIVX computer (Apple Inc, Cupertino, CA). Group data are expressed as mean ± the standard error of the mean.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Mean age was 46 ± 4 years (range, 7 to 79 years) and the unmodified Parsonnet (severity) score averaged 16 in the mitral valve patients. Preoperative risk factors are listed in Table 3. All 25 patients undergoing complex mitral valve repair had 3 or 4+ mitral valve regurgitation documented by transesophageal echocardiography and catheterization, 3 with some degree of mitral stenosis. Fifteen of these 25 patients underwent concomitant procedures:

• Complex mitral valve repair
  
• 12 Tricuspid annuloplasty
  
• 4 Atrial septal defect closure
  
• 2 Coronary artery bypass grafting
  
• 1 Maze procedure
  

In the 9 Ross patients, 7 underwent operation for aortic insufficiency and 2 for aortic stenosis. Three patients with aortic insufficiency also underwent a mitral valve repair for regurgitation:

• Ross procedure
  
• 2 Mitral valve repair
  
• 1 Mitral valve repair and maze procedure
  

Preoperative ejection fractions in these patients were 0.34, 0.36, and 0.42. This last patient also underwent a maze procedure resulting in a3. cross-clamp time of 267 minutes.

Bypass, cross-clamp, and ischemic times are depicted in Figures 2 and 3. Despite cross-clamp times of 187 ± 12 minutes (range, 138 to 267 minutes) in the Ross group and 139 ± 8 minutes (range, 92 to 218 minutes) in the complex mitral repair group, no patients died, only 5 (15%) required inotropes (all being discontinued by 30 hours postoperatively), none required an intraaortic balloon pump, 1 (3%) required antiarrhythmics (lidocaine for 16 hours), and the average postoperative hospitalization was 8 ± 1 days (range, 5 to 21 days) in the mitral patients and 5 ± 1 days (range, 4 to 7 days) in the Ross patients. In patients undergoing evaluation of their right ventricular wall motion by intraoperative transesophageal echocardiogram, there was no change between the prebypass and postbypass wall motion scores (0.9 versus 0.7; 0 = normal, 1 = mild hypokinesis).

View larger version (14K): [in this window] [in a new window]   Fig 2. . Bypass, cross-clamp, and ischemic times in the 25 patients undergoing complex mitral valve repairs. Note that the bypass and cross-clamp times are relatively similar, indicating that bypass was able to be discontinued very shortly after removing the aortic cross-clamp. Also, despite the prolonged cross-clamp times, the myocardial ischemic time is extremely short (see text for description).

View larger version (16K): [in this window] [in a new window]   Fig 3. . Bypass, cross-clamp, and ischemic times in the 9 patients undergoing a Ross procedure. Note that the bypass time is a quite a bit longer than cross-clamp time because of the need to complete construction of the pulmonary homograft. Also note the extremely short ischemic times, despite the prolonged period of aortic cross-clamping (see text for description).

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

Cardioprotective strategies, like cardiac operations, have evolved to the point where it is essential to understand and use various techniques to ensure optimal myocardial protection. The surgeon must refrain from using simplistic solutions for the very reason that simplicity may not always afford the best result. For example, valve preservation may be an improvement over replacement, despite the increased complexity required of surgical techniques. By integrating all the aforementioned techniques of warm and cold, antegrade and retrograde, and continuous and intermittent cardioplegia, the surgeon is able to overcome the limitations and weaknesses of each strategy, thereby ensuring optimal myocardial protection.

The integrated cardioplegic strategy is based on the following principles: (1) All patients receive antegrade and retrograde delivery to ensure cardioplegic distribution. (2) Except for those with aortic insufficiency, all patients receive warm induction with amino acid-enriched cardioplegia to resuscitate the heart before surgically imposed cardiac ischemia. (3) Surgical precision is optimized by a dry, bloodless field (no perfusion) using cold intermittent blood cardioplegic arrest during those times when optimal visualization is required. (4) Ischemia is unnecessary when visualization is not problematic (most of the operative procedure), and so continuous perfusion is always delivered whenever possible. (5) Continuous blood perfusion of the cold arrested heart does not require cardioplegia. (6) All hearts receive a warm substrate-enhanced blood cardioplegia reperfusate to limit a reperfusion injury. It is imperative the surgeon understand and use all of these principles to ensure optimal protection while facilitating technical ease of operation.

The assurance of adequate cardioplegic distribution is essential. Studies have shown that it is safer to clamp the aorta for 4 hours with good cardioplegic distribution than for as little as 30 minutes when the same solution is given without attempts to deliver it beyond coronary stenosis [5]. Antegrade delivery avoids right ventricular ischemia and limits cardioplegic volumes by producing prompt myocardial arrest [5, 8, 19]. However, it is distributed poorly in the presence of coronary artery stenosis or aortic insufficiency [5, 8, 20]. Other limitations include the need to interrupt mitral valve procedures to remove retractors, and ostial damage during aortic valve operations [5, 8]. Retrograde (coronary sinus) cardioplegia offsets some of these problems by improving distribution (especially to the subendocardium) in the settings of coronary stenosis and aortic valve regurgitation. Retrograde delivery also avoids trauma to the coronary ostium and interferes minimally with surgical procedures. However, experimental and clinical studies have demonstrated that only antegrade delivery provides adequate right ventricular perfusion [6, 7, 20–22]. Therefore, both routes of administration are required to maximize the benefits of each method. We believe adopting a rigid approach of using of only one method of delivery is unwarranted and potentially harmful, because it does not ensure distribution to all areas of the heart.

Cardiac operations on energy-depleted hearts pose more difficult problems in myocardial protection. It is now apparent that most hearts requiring operation are energy depleted as decreased levels of adenosine triphosphate have been reported in hypertrophied hearts and those with coronary artery disease [14, 23, 24]. In this setting, warm (37°C) induction with substrate-enhanced blood cardioplegia (see Table 1) acts as a form of "active resuscitation" allowing the myocardium to better tolerate the obligatory period of aortic cross-clamping [5, 25]. We have recently shown that even hemodynamically stable hearts have increased metabolic uptake during warm cardioplegic induction, especially in patients with left ventricular hypertrophy, congestive heart failure, hypertension, a high severity (Parsonnet) score, or multivessel coronary artery disease [14]. Therefore, warm induction is given for 4 to 5 minutes in all patients undergoing valve operations to ensure repayment of the energy debt. Warm induction is always given over time, because oxygen is taken up over time. The infusion is usually split between antegrade and retrograde to ensure distribution. However, in the absence of coronary artery disease or severe left ventricular hypertrophy, retrograde delivery may not be necessary. Only in patients with aortic insufficiency is warm induction not indicated because of the large volumes usually required to produce arrest. In these patients we start cold cardioplegia retrograde, open the aorta, and infuse cardioplegia into each coronary ostium.

Cold cardioplegia always follows warm induction to (1) produce hypothermia to reduce metabolic demands and (2) create an environment that allows continuous anaerobic energy production during intervals between cardioplegia [5, 25]. Further reduction in the metabolic requirements makes the heart better able to tolerate any ischemic interval. Cold ischemic arrest (no myocardial perfusion) is only used when optimal visualization of the operative field is required, such as when working on the posterior mitral valve leaflet, or the left coronary ostium in Ross procedures. If coronary flow must be interrupted for more than 15 minutes, an intermittent cardioplegic infusion is given to maintain hypothermia and myocardial arrest.

Ischemia is unnecessary when visualization is not problematic (most of the operative procedure) and so continuous perfusion is always delivered whenever possible. Most of the time this is accomplished by continuous retrograde delivery because it avoids the need to remove valve retractors or ostial cannulation, thereby allowing the surgeon to continue to operate without stopping to give cardioplegia. Both experimental and clinical studies have now documented that retrograde delivery provides inadequate right ventricular nutritional flow, as it is mostly shunted through venovenous collaterals [6, 7, 20–22]. However, if cold (4°C) perfusion is used, retrograde perfusion still cools the right ventricule, reducing demands. Therefore, although retrograde delivery may not provide adequate right ventricular perfusion at 37°C, it may be adequate at a lower temperature because the demands are reduced. We still try to deliver an antegrade infusion approximately every 30 minutes to ensure adequate right ventricular perfusion. In the Ross patients, this is easily done by cannulating the right coronary ostium. In the mitral patients, the interval is usually extended to 40 minutes to limit removing the retractor, and is probably well tolerated because the right ventricle is kept cold by continuous perfusion. Evidence for the adequacy of right ventricular protection using the integrated strategy is derived from the transesophageal echocardiogram, which demonstrated complete preservation of postbypass right ventricular wall motion in all patients.

Continuous perfusion of the cold arrested heart does not require cardioplegia. Therefore, we use primarily cold (4°C) noncardioplegic blood during continuous cold perfusion. This is done by having the perfusionist simply remove the cardioplegic line from the roller pump. Limiting the quantity of cardioplegia reduces postoperative hyperkalemia and avoids hemodilution. Cold cardioplegia is intermixed each 10 to 15 minutes, or whenever continuous flow is interrupted, to ensure maintenance of myocardial asystole.

Until recently, aortic cross-clamp time was synonymous with myocardial ischemic time. Surgeons therefore equated a shorter period of aortic cross-clamping with less myocardial damage, and felt compelled to try to perform the intracardiac portion of the repair as quickly as possible. This concept (that cross-clamp and ischemic times are synonymous) continues to persist and has resulted in a reluctance to attempt complex procedures in patients with depressed myocardium. However, continuous perfusion avoids myocardial ischemia during the period of aortic cross-clamping. Therefore, cross-clamp time is no longer an important determinant in predicting myocardial damage. Instead, a new variable, which we call "ischemic time," becomes the major predictor of potential myocardial injury.

Ischemic time is defined as the time when the aorta is cross-clamped and there is no myocardial perfusion. Continuous perfusion of the myocardium with an oxygenated solution (blood cardioplegia or noncardioplegic blood) limits myocardial ischemia, and therefore damage, so long as the solution is adequately distributed. In our patients continuous perfusion was used during almost the entire operative procedure. This resulted in relatively short ischemic times despite prolonged periods of aorta cross-clamping (see Figs 2, 3). In addition, hypothermia was used whenever perfusion was interrupted, further reducing metabolic demands and limiting myocardial damage. We believe the concept of limiting ischemic time by using continuous perfusion whenever possible is extremely important in explaining our results.

Reperfusion injury is defined as the functional, metabolic, and structural alteration caused by reperfusion after a period of temporary ischemia [5]. The potential for this damage exists during all cardiac operations because the aorta must be cross-clamped to produce a quiet, bloodless field, thereby ensuring ischemia. Our studies show that the fate of the myocardium jeopardized by global ischemia is determined more by careful control of the conditions of reperfusion and composition of the reperfusate then by the duration of the ischemia itself [5, 9, 15]. We therefore always deliver a 5- to 6-minute infusion of warm amino acid-enriched blood cardioplegic solution (see Table 1) before aortic unclamping. The infusion is extended by several minutes if for any reason we believe myocardial protection has been suboptimal. In patients with coronary artery disease or left ventricular hypertrophy, the infusion is split between antegrade and retrograde to ensure distribution to all areas of the ischemic myocardium. We often switch to a warm noncardioplegic blood infusion just before finishing the left atrial closure (mitral valve operation) or proximal pulmonary homograft insertion (Ross procedure). This washes out the cardioplegia so the heart resumes electromechanical activity immediately upon removal of the aortic cross-clamp; thereby allowing bypass to be discontinued quickly. Although early discontinuation of bypass was accomplished in the mitral valve repair group (see Fig 2), the Ross patients still had to have their distal pulmonary artery anastomosis completed, and so bypass was extended (see Fig 3).

In summary, we believe an integrated approach incorporating the strategies of warm and cold blood cardioplegia, antegrade and retrograde delivery, and continuous and intermittent infusion affords better myocardial protection, avoids unnecessary ischemia, facilitates technical ease of operation, and results in a more favorable postoperative course. Integrating these modalities into a comprehensive strategy, instead of relying on one, maximizes each method's strengths while minimizing inherent weaknesses, thereby allowing surgeons to perform complex valve repairs safely in all patients despite the prolonged cross-clamp times that often are required.

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
We thank Mr Greg Mork, Mr Jim Murray, and Ms Nancy Bourtsos for technical support, and Ms Felicia Mitchell and Ms Peggy Burse for organizational assistance.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Presented at the Thirty-second Annual Meeting of The Society of Thoracic Surgeons, Orlando, FL, Jan 29–31, 1996.

Address reprint requests to Dr Allen, Division of Cardiothoracic Surgery, University of Illinois, 840 S Wood St, 515 CSN (M/C 958), Chicago, IL 60612.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Bradley S. Allen Renee S. Hartz Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Allen, B. S. Articles by Hartz, R. S. Search for Related Content PubMed PubMed Citation Articles by Allen, B. S. Articles by Hartz, R. S. Related Collections Related Article