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Ann Thorac Surg 2000;69:171-175
© 2000 The Society of Thoracic Surgeons

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Original Articles

Perfusion-assisted direct coronary artery bypass: selective graft perfusion in off-pump cases

^a Division of Cardiothoracic Surgery, Department of Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, Georgia, USA
^b Division of Cardiothoracic Surgery, Department of Anesthesiology, Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, Georgia, USA

Address reprint requests to Dr Guyton, Division of Cardiothoracic Surgery, The Emory Clinic, 1365 Clifton Rd, Atlanta, GA 30322
e-mail: rguyton{at}emory.org

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
Background. Hemodynamic instability during multivessel off-pump coronary artery bypass grafting can lead to hypotension, progressive myocardial ischemia, further hypotension, and the need for urgent cardiopulmonary bypass.

Methods. In 10 patients undergoing off-pump coronary artery bypass grafting, a novel technique of pressure-controlled blood delivery has been used that allows the immediate restoration of arterial blood to distal coronary beds after distal coronary anastomosis. This technique utilizes a servo-controlled pump to allow delivery of blood at systemic or suprasystemic pressures, and provides the option for infusion of supplemental additives for myocardial resuscitation, myocardial vasodilation, and enhancement of myocardial performance.

Results. Myocardial perfusion was successfully enhanced via one or two grafts in all 10 patients with an average graft flow of 98 ± 8 mL/min. In 3 patients, a 27% increase in perfusion pressure led to a 59% increase in perfusate flow. All patients were hemodynamically stable after initiation of selective graft perfusion.

Conclusions. Based on this preliminary patient series, the selective perfusion of grafted vessels seems to facilitate multivessel off-pump coronary artery bypass grafting by promoting rapid recovery of grafted segments, by enhanced hemodynamic stability during subsequent anastomoses, and by providing increased flexibility in the sequence of grafting.

	Introduction

Top Abstract Introduction Material and methods Results Comment References

 
Within the last 4 years, there has been a resurgence of coronary artery bypass grafting without cardiopulmonary bypass. Refinements in retraction techniques and the development of improved stabilizing devices have been enabling technologies allowing successful off-pump coronary artery bypass (OPCAB) in many patients with multivessel coronary artery disease [1–3]. However, hemodynamic deterioration during retraction and stabilization, and especially during temporary occlusion of an important target vessel, remains a recurrent threat to the patient and a primary concern for the surgeon. A second matter of concern for the surgeon in multivessel OPCAB is the need for rapid recovery of any impairment in myocardial function after each anastomosis before occlusion of subsequent target vessels. If such recovery does not occur, cumulative regional impairment may become so extensive that pump function fails in a catastrophic manner. These concerns have prompted the use of intraluminal stents, arterial shunts, and "proximal first" grafting strategies to decrease ischemic impairment and promote early recovery of the grafted myocardial region. Measures such as ischemic preconditioning of target vascular beds have been advocated to reduce injury from transient occlusion [1] with mixed benefit [4].

We have utilized an adjunctive technology in multivessel OPCAB that promotes early reperfusion and rapid recovery of grafted segments that may diminish ischemia during subsequent anastomoses. Arterial blood is removed from the aorta and pumped into the target vessel via saphenous vein and radial artery grafts after distal anastomoses are completed. A servo-controlled pump allows pressure control at systemic or suprasystemic levels, while computer-controlled additive circuits allow the simultaneous addition of substrates for myocardial resuscitation, vascular dilation, and/or enhancement of myocardial performance via perfusate blood. This is a report of the first 10 patients in whom this selective graft perfusion technology was used.

	Material and methods

Top Abstract Introduction Material and methods Results Comment References

 
Perfusion-assisted direct coronary artery bypass (PADCAB) utilizes a simple circuit and a computer-controlled delivery system [5]. Standard median sternotomy and standard conduit harvesting techniques were utilized. Before division of the internal mammary artery, 400 U/kg of heparin sodium was administered. Additional heparin was given during the procedure in order to maintain an activated clotting time greater than 400 seconds. Epivascular echocardiography was utilized in all patients over 65 years of age with left main disease or with peripheral or cerebrovascular disease to evaluate the ascending aorta. Via a purse-string suture in a nondiseased site in the ascending aorta, a DLP aortic root cannulae (9 gauge, 11 French; Medtronic DLP, Grand Rapids, MI) was inserted into the aorta and connected to the Myocardial Protection System (MPS) cardioplegia and perfusion delivery system (Quest Medical Inc, Allen, TX) (Fig 1). The MPS delivery system allows monitoring of delivery line pressure (mm Hg), vein graft infusion pressure (mm Hg), and flow (mL/min). Furthermore, the MPS delivery console computes a retrievable log of the amounts of blood or additive infused.

View larger version (50K): [in this window] [in a new window]   Fig 1. Perfusion-assisted direct coronary artery bypass system. Aortic blood is directed from the aortic cannula (A) through the Quest MPS to the multiple perfusion set (B), and finally the proximal vein or arterial grafts (C). The vein infusion pressure is monitored by the MPS system from a feedback line (D) located at the proximal portion of the multiple perfusion set.

In these 10 patients, the flow of blood through the vein grafts and delivery pressure of the reperfusate were measured and recorded. One to two grafts were perfused in each patient. After completion of all saphenous vein or radial artery distal anastomoses in most cases, the left internal mammary was anastomosed to the left anterior descending coronary artery. Proximal anastomoses of the vein and/or radial artery grafts were then performed to the ascending aorta utilizing a side-biting clamp. Perfusion to each graft was terminated while proximal anastomoses were completed. A half-reversal dose of protamine sulfate (calculated from the presumed level of plasma heparin at the time of reversal) was administered before chest closure, and the activated clotting time (ACT) was reduced to ~180 seconds. The DLP cannula was removed from the aorta and the purse-string suture was tied. The chest was closed in a routine manner.

Values in this report are presented as mean ± standard error of the mean.

	Results

Top Abstract Introduction Material and methods Results Comment References

 
Case 1
An asymptomatic 57-year-old male with a medical history of hyperlipidemia, hypertension, and a strong family history of coronary artery disease underwent routine cardiac workup, which revealed coronary artery disease. Cardiac catheterization revealed severe three-vessel disease with left main coronary artery disease and a near total occlusion of the right coronary artery. PADCAB times three was performed on July 27, 1999. Arterial conduits were chosen for the left anterior descending and circumflex systems, and a reverse saphenous vein graft was chosen for the left ventricular branch of the right coronary artery. The heart was elevated and stabilized with a Cohn Cardiac Stabilizer (Genzyme Surgical Products, Cambridge, MA). The native vessel was occluded proximal and distal to the proposed site of arteriotomy. As the vein graft anastomosis was being performed to the left ventricular branch of the right coronary artery, 0.8 mm of ST elevation developed in the inferior leads (AS/3 Monitoring System; Datex, Helsinki, Finland). The native vessel was reopened after completion of the anastomosis, but the ST elevation persisted. Distal perfusion through the vein graft with unsupplemented blood from the aortic site was performed using the MPS system with a flow of 65 mL/min and a perfusion pressure of 96 mm Hg. The ST segments promptly resolved. While maintaining reperfusate flow through the vein graft, the radial artery was used to graft the circumflex marginal vessel, and the left internal mammary artery was used to graft the left anterior descending coronary artery. An aortic side-biting clamp was used to perform the radial artery and vein graft proximal anastomoses. Perfusion of the vein graft perfusion was discontinued when the last proximal anastomosis was begun. No recurrence of ST segment elevation was observed during this final period of nonperfusion of the left ventricular branch of the right coronary artery. The remainder of the operative procedure and subsequent patient recovery were uneventful.

Case 2
A 78-year-old male presented with unstable angina of 1-week duration superimposed on chronic class II angina. Cardiac catheterization revealed 90% stenosis of the right coronary artery at the origin of the posterior descending artery, 95% stenosis of the left anterior descending artery, 90% stenosis of a small diagonal vessel, and 90% stenosis of a very small circumflex branch. PABCAB times three was performed on September 17, 1999. After completion of the distal anastomosis of the posterior descending coronary artery with a vein graft, perfusion using the MPS system was initiated. This vessel was perfused during the construction of the remaining distal anastomoses. After the heart was positioned for the left anterior descending anastomosis, flow through the vein graft stabilized at 55 mL/min with a perfusion pressure of 88 mm Hg. After nitroglycerin was added to the reperfusate (100 µg/L), flow increased to 70 mL/min while the perfusion pressure remained minimally changed (90 mm Hg). When the perfusion pressure was increased to 125 mm Hg, flow was increased to 120 mL/min. As the left anterior descending anastomosis was being completed, perfusate flow was decreased to 5 mL/min for 2 minutes. Anterior-apical hypokinesis worsened as evaluated by transesophageal echocardiography at the end of these 2 minutes. Restoration of flow through the vein graft to 146 mL/min at a pressure of 122 mm Hg led to prompt improvement in anteroapical function. The internal mammary anastomosis was completed and the graft was opened. A final, difficult anastomosis was constructed to the small diagonal vessel with a second vein graft. The circumflex vessel was not grafted. The two proximal anastomoses were constructed with an aortic side-biting clamp. The remainder of the operation and subsequent recovery were uneventful.

Summary of 8 other patients
In addition to the 2 patients described above, 8 other patients underwent PADCAB between September 1 and 17, 1999. In these 10 patients, 10 internal mammary grafts, five radial artery grafts, and 14 reverse saphenous vein grafts were performed (2.9 ± 0.2 grafts per patient). Average time per anastomosis was 11.3 ± 0.8 minutes. One graft was perfused in each of 7 patients, and two grafts were perfused in each of 3 patients. Three patients had perfusion of radial grafts (nitroglycerin was added to the perfusate in 2 of these patients).

Perfusion of the grafts averaged 98.1 ± 7.6 mL/min in each patient with a mean perfusion pressure of 109 ± 2 mm Hg. The mean systemic arterial pressure during this interval was 78 ± 3 mm Hg. Total blood infusion volume per patient averaged 4,563 ± 725 mL over 45 ± 6 minutes.

Nitroglycerin was used as an additive in 6 patients. Two patients received moderate doses (perfusate concentrations of 10 to 40 µg/L) with no change in perfusate flow. Four patients received more generous concentrations of nitroglycerin (100 µg/L), leading to a modest 18% increase in perfusate flow (Fig 2). Because nitroglycerin was delivered directly into the coronary arteries, total systemic dose was low (range 1 to 17 µg/min) and no systemic effect on pressure was noted.

View larger version (16K): [in this window] [in a new window]   Fig 2. The changes in perfusate flow (at a constant infusion pressure) before and after initiation of nitroglycerin (100 µg/L) in 4 patients undergoing PADCAB are shown. (NTG = nitroglycerin.)

View larger version (16K): [in this window] [in a new window]   Fig 3. The relationship of infusion pressure (mm Hg) and perfusate flow (mL/min) during PADCAB is shown in 3 patients.

Hemodynamic instability was a problem during the construction of the first anastomosis (before perfusion assist) in 1 patient, requiring cardiac massage. This occurred during anastomosis to a small obtuse marginal vessel high on the lateral wall with a tight proximal stenosis. After perfusion was established to this vessel, the patient was hemodynamically stable throughout the remainder of the procedure, even during a very difficult anastomosis to a second obtuse marginal artery equally high on the lateral wall (the second vessel was larger than the first with a less tight proximal stenosis). Hemodynamic instability was notably absent during graft perfusion in all cases.

One patient suffered atheroembolism to the small bowel despite the use of intraoperative epivascular aortic echocardiography to identify a nondiseased site on the aorta for cannula insertion and placement of the side-biting clamp. In this case, the proximal anastomosis was constructed at the site of cannula insertion and, indeed, the aorta did not have atherosclerotic disease at this site by direct observation. This patient died 4 days after the operation. There were no other complications in the other 9 patients. Average postoperative length of stay was 5 ± 0.5 days.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
Our early experience with PADCAB leads us to predict that this technology will be combined with new retraction techniques and stabilization devices as enabling technologies that facilitate the application of off pump coronary artery bypass to an increasingly larger proportion of patients with multivessel coronary artery disease. The salutary advantages of this technique are: (1) immediate perfusion of grafted myocardial regions to meet oxygen demands and prevent cumulative ischemic dysfunction; (2) enhanced hemodynamic stability during multivessel grafting; (3) the potential for administration of cardioprotective or vasoactive additives in the perfusate that may facilitate myocardial recovery and function; and (4) a logistic advantage to the surgeon regarding the appropriate sequence of grafting.

The MPS is a sophisticated computer-controlled pump designed for flexible cardioplegia delivery that appears to be well suited for PADCAB application. The pressure and temperature of the perfusate are precisely controlled by a computer-enhanced servo-regulation system. Perfusate flow can be programmed to achieve target perfusion pressures. Furthermore, safeguards to prevent inadvertent high perfusion pressures or the introduction of air into the perfusate are employed. Two independent circuits are constructed within the console, thereby allowing the addition of two different additive solutions into the perfusate. These solutions are introduced into the perfusate automatically at preset concentrations that are held constant over variations in flow rate.

The use of target pressure-controlled perfusion offers unusual advantages to this methodology. In this preliminary series, the mean line perfusate pressure exceeded mean systemic pressure by 30 mm Hg. The advantages of this method over passive flow systems (such as aorto-graft shunts) are emphasized by the control that can be exercised over flow. In 3 patients, pressure was increased from 100 to 125 mm Hg; a 27% increase in pressure led to a 59% increase in flow rate. Passive flow systems necessarily deliver blood at pressures below systemic levels and do not allow adjustment of flow rate to maintain a balance in oxygen supply/demand balance. If the heart begins to fail, these passive flow systems will participate in a vicious spiral of progressive perfusion failure and progressive pump failure. This is the classic "crash on cardiopulmonary bypass" scenario. With the PADCAB heart, on the other hand, target vessels’ perfusate flow rates can be adjusted by varying perfusion pressure, thereby preventing regional dysfunction secondary to perfusion limitations. Hemodynamic stability after initiation of selective graft perfusion was a common feature of these 10 PADCAB patients.

Elevated perfusion pressure may help diminish ischemia in remote myocardium as well as perfusing the primary myocardial zone. The use of suprasystemic perfusion pressures will likely enhance collateral flow to regions other than the primary grafted region, providing an additional safety margin for subsequent coronary occlusion in multivessel grafting. The second case study is an example of perfusion of an inferior vessel with preservation of function in the anterior descending region. The extent to which perfusion pressure can be safely elevated without inducing microvascular injury and tissue edema is unknown, especially in vulnerable myocardium, and caution must be used until experimental studies can be conducted. In this regard, it is particularly notable that the primary perfusion area may be minimally damaged during the initial anastomotic time interval and therefore may be more susceptible to hyperbaric perfusion injury [6]. Although normal myocardium may be tolerant of hyperbaric perfusion pressures, vulnerable myocardium is less resilient to higher perfusion pressure [7, 8].

The ease with which additives can be "dialed in" to the perfusate is a particularly positive attribute of the perfusion system used in these patients. The additive utilized in this early series was nitroglycerin. Nitroglycerin led to only a small increase in perfusion rate. Other vasodilators certainly might be more potent. The use of potent vasodilators in a passive flow system (such as a passive aorto-graft shunt) might be harmful, as a real threat of flow maldistribution (coronary steal) exists with limited inflow. With the pressure-controlled inflow of this PADCAB procedure, potent vasodilators are likely to be beneficial because the rate of perfusion as well as the concentration of vasodilator can be continuously adjusted for effect.

A second group of additives might be envisioned for the initial reperfusion of ischemic myocardium. Adenosine, oncotically active additives, nitric oxide generators, platelet and leukocyte adhesion inhibitors, membrane stabilizing drugs, and beta-blocking drugs all offer potential clinical advantage and deserve experimental evaluation [9–14].

A third group of additives present possibilities for enhanced myocardial function. If one needs to give epinepherine or milrinone, does it not make sense to deliver the inotropic agent preferentially to the region of the heart that is abundantly perfused? Glucose-insulin-potassium and triiodothyroxine are other additives that may provide considerable benefit with low risk. In addition to the potential use of additives to improve regional myocardial function, the supranormal regional myocardial blood flow during PADCAB is very likely to enhance regional function. Experimentally, progressive supranormal increases in myocardial blood flow have been associated with progressive improvement in function (the Gregg effect) [15]. This ability to perfuse at suprasystemic pressures is an advantage of PADCAB over "proximals-first" OPCAB strategies, as these strategies only deliver blood at systemic pressures.

Flexibility in the sequence of graft construction is another advantage of PADCAB. Although the "proximals-first" OPCAB technique offers immediate perfusion of grafted segments, this technique has disadvantages relative to subsequent retraction for difficult distal coronary grafts on the high lateral wall. The mammary graft must be made extra long if the apex of the heart is to be rolled over into the right chest for a high lateral anastomosis. This requirement for extra length is also true for grafts to the distal right coronary system if proximal and distal anastomoses of these grafts are to be completed before extreme retraction of the heart for lateral wall anastomoses. PADCAB allows the mammary graft to the anterior descending artery to be constructed last, utilizing a shorter and better segment of mammary artery and avoiding excessive traction on the in situ left interior mammary artery pedicle. The mammary artery can then be opened with the heart back in its physiologic position during construction of proximal anastomoses in PADCAB. The vein and radial artery graft lengths can be measured without regard to a need for subsequent extreme retraction of the heart. Judgment of appropriate graft length is further facilitated by observing the perfused grafts under MPS pressure with the heart in normal anatomic position.

In summary, we believe perfusion of grafted vessels may prove to be a facilitating factor in the performance of off-pump coronary artery bypass in selected patients with multivessel coronary artery disease. Although not needed in less complex surgical patients, in difficult patients, PADCAB seems to improve hemodynamic stability for multiple grafting and allows flexibility in the sequence of grafting. As appropriate cardioprotective perfusate additives are determined in experimental studies, the utility of PADCAB is likely to expand, perhaps providing reperfusion advantages even in patients requiring only one or two grafts, and enabling the application of off-pump coronary artery bypass to increasingly complex patients.

	Acknowledgments

 
We would like to acknowledge Scott Bodell for the artistic rendition of the PADCAB circuitry.

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