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Ann Thorac Surg 1996;62:1388-1391
© 1996 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Evidence of Improved Microvascular Perfusion When Using Antegrade and Retrograde Cardioplegia

Division of Cardiothoracic Surgery, Department of Surgery, University of California Los Angeles Medical Center, Los Angeles, California

Accepted for publication June 12, 1996.

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background. The maximum degree of microvascular distribution of cardioplegic solution is considered important to achieve optimum myocardial protection. This study attempts to demonstrate that the addition of retrograde cardioplegia to antegrade cardioplegia improves overall microvascular perfusion.

Methods. Explanted human hearts (n = 6) were treated with cold cardioplegic arrest and bicaval cardiectomy. Blood cardioplegia (37°C) containing colored microspheres (color A for antegrade, color B for retrograde) was simultaneously infused antegrade at a pressure of 80 mm Hg and retrograde at a pressure of 40 mm Hg for 2 minutes. The ventricular myocardium was then sampled at three sites to determine absolute and relative cardioplegic microvascular flow.

Results. Of the total microvascular capillary flow, 27% to 32% was found to be the contribution of retrogradely delivered cardioplegia.

Conclusions. Despite being delivered simultaneously and at a lower pressure, retrograde cardioplegia contributed substantially to overall microvascular perfusion. This suggests that antegrade cardioplegia alone does not perfuse all available myocardial capillaries and that the addition of retrograde cardioplegia enhances overall microvascular distribution and perfusion.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
The use of retrograde cardioplegia has gained wide acceptance as an important component of myocardial protection. The retrograde approach provides superior cardioplegic delivery to myocardium distal to complete coronary occlusions as compared with the antegrade approach [1–3]. Further, retrograde techniques greatly expedite and simplify the conduct of a variety of operations. Many reports have documented the clinical safety and effectiveness of properly used warm or cold retrograde cardioplegia [4–6].

But what of the combined use, either sequentially or simultaneous, of antegrade and retrograde cardioplegia? Buckberg and others [7–9] have suggested, even in hearts with normal coronary arteries, that the overall microvascular distribution of cardioplegic solution may be improved by using both antegrade and retrograde cardioplegia rather than one delivery technique alone. If this is true, one could anticipate improved myocardial protection when using both antegrade and retrograde cardioplegia on the basis of improved distribution. Based on clinical observations and studies using anatomic capillary markers, our group suggested previously that improved microvascular distribution may be achieved, even in patients with normal coronary arteries, by using both antegrade and retrograde cardioplegia [10]. In this study, we attempt to further substantiate this claim.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Six explanted human hearts were obtained for the study. These hearts were from heart transplant recipients with a histologic diagnosis of idiopathic cardiomyopathy with interstitial fibrosis. All patients had no history of thoracic or cardiac operations and had normal coronary artery anatomy without angiographic or pathologic evidence of atherosclerotic coronary artery disease. Use of explanted hearts was in accordance with hospital autopsy research guidelines and was approved by the Department of Pathology, University of California Los Angeles School of Medicine.

During orthotopic heart transplantation, explanted hearts were arrested in situ using 4°C antegrade blood cardioplegia delivered at 80 mm Hg for 2 minutes. The composition of the arresting solution was as described previously [11]. Hearts were excised in the standard bicaval cardiectomy fashion, leaving a slightly shorter inferior vena cava atrial cuff. This allowed the coronary sinus and its left and right ventricle venous drainage systems to remain intact. Hearts were immediately transferred to the laboratory on iced saline solution.

Each heart was weighed and prepared for antegrade and retrograde simultaneous perfusion. The left and right coronary ostia were identified and cannulated with heparin-saline filled intravenous tubing. Using end to end technique, we sutured a 10-mm Gore-Tex (W.L. Gore, Flagstaff, AZ) tube graft to the coronary sinus. This allowed delivery of retrograde cardioplegia to the coronary sinus without leakage or backflow. The free atrial resection line was then occluded with vascular clamps. After emptying the heart of any remaining fluid, we suspended the heart in air by a heavy silk suture placed through the aorta and pulmonary artery. During simultaneous left and right coronary artery and occluded coronary sinus perfusion, all cardioplegic effluent egressed from thebesian veins into the body of the ventricles, where it was collected.

Blood cardioplegia at 37°C was prepared as described previously [12] and divided into aliquots for antegrade and retrograde cardioplegia. To each aliquot, 2.5 million (15 +/- 5 µm) colored microspheres (color A for antegrade, color B for retrograde) were added and continuously agitated before delivery. Simultaneous antegrade and retrograde cardioplegia was then given at 80 mm Hg and 40 mm Hg, respectively, for 2 minutes.

At the mid-ventricle level, 2-cm slices of the myocardium were made. A 2.5-g specimen was then taken from the mid-left ventricular free wall, the mid-interventricular septum, and the mid-right ventricular free wall. Tissue specimens were processed following EZ-Trac (Los Angeles, CA) guidelines, as described previously [12]. Microspheres recovered and regional flow in mL • g^-1 • min^-1 were also calculated as described previously [12]. Because two separate color microspheres were used, total microvascular flow in mL•mg^-1•min^-1 could be determined as well as to what degree the total flow was derived from antegradely or retrogradely delivered microspheres.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Antegrade (color A microspheres) cardioplegic flow in mL•mg^-1•min^-1 was 0.16 +/- 0.16 for the lateral right ventricular free wall, 0.16 +/- 0.16 for the mid-interventricular septum, and 0.14 +/- 0.17 for the lateral left ventricular free wall. Retrograde (color B microspheres) cardioplegic flow in mL•mg^-1•min^-1 was 0.07 +/- 0.15 for the lateral right ventricular free wall, 0.06 +/- 0.13 for the mid-interventricular septum, and 0.06 +/- 0.07 for the lateral left ventricular free wall. Total cardioplegic flow (color A + color B microspheres) in mL•g^-1•min^-1 was 0.23 +/- 0.25 for the lateral right ventricular free wall, 0.22 +/- 0.16 for the mid-interventricular septum, and 0.20 +/- 0.17 for the lateral left ventricular free wall (Fig 1).

View larger version (46K): [in this window] [in a new window]   Fig 1. . Antegrade and retrograde contributions to total regional blood flow during simultaneous antegrade and retrograde cardioplegia delivery, in mL•g-1•min-1. (IVS = interventricular septum; LV = left ventricle; RV = right ventricle.)

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

We have previously made the following clinical observations in patients without coronary artery disease [10]. During the delivery of an intermittent dose of antegrade cardioplegia, the initial coronary sinus effluent is dark and desaturated. With time, the effluent becomes red and no longer desaturated, as the oxygen debt is repaid and a steady state of excessive oxygen supply to demand is reached. However, if while at this steady state one immediately switches from giving antegrade to retrograde cardioplegia, one will notice that for a short and variable period of time, the initial coronary artery effluent is partially desaturated and then becomes more red until another steady state is reached. Why does this occur? One possible explanation is that antegrade cardioplegia fails to perfuse all possible microvascular beds, and the initial desaturation of the retrograde cardioplegia coronary artery effluent represents the oxygen debt being repaid in capillaries perfused exclusively by retrograde cardioplegia. Our group demonstrated recently in a piglet model, using glutaraldehyde perfusion fixation and the retrograde injection of an intracapillary marker, that the subsequent delivery of antegrade cardioplegia could not displace (wash out) 12.5% to 14% of capillaries containing the marker [10]. We speculated that this was due to the incomplete microvascular distribution of antegrade cardioplegia.

This experiment was designed to clarify the issue of whether retrograde cardioplegia could enhance overall microvascular perfusion and distribution when used with antegrade cardioplegia, even in patients with normal coronary arteries. The results indicate that when both antegrade and retrograde cardioplegia are delivered simultaneously (even with greater antegrade delivery pressure), 27% to 32% of capillary cardioplegic flow is the result of retrogradely delivered cardioplegia.

To understand better the implications of this finding, it is important to review possible pathways of both antegrade and retrograde cardioplegic flow. Antegrade blood flow is under many autoregulatory control loops. Antegrade blood may flow directly through capillaries to the venous system of the heart. The left ventricular veins empty predominantly through the coronary sinus, whereas right ventricular veins have rich networks connecting them to the anterior cardiac vein and thebesian veins. Thus, much of the right ventricle antegrade blood flow eventually drains directly into the body of the right ventricle [13]. Not all antegrade blood flow must traverse capillaries to empty into the heart. Arteriosinusoids may exist, which could allow blood to flow from the coronary arteries through arteriosinusoids directly into the body of the ventricle without first traversing capillaries [14]. The existence of such arteriosinusoids has been questioned recently, and their anatomic presence must be considered debatable [15]. In addition, arteriolar autoregulation can allow selective arteriovenous shunting past some capillary beds [16]. Thus, there are both anatomic and physiologic conditions that would allow dynamic changes in the percentage of total possible capillary beds perfused and the absolute flow through them of antegradely delivered cardioplegia.

Retrogradely delivered cardioplegia has many potential pathways of flow as well. Upon entry into the coronary sinus, cardioplegia flows into epicardial veins of both the left and right heart. The cardioplegia may then flow across capillary beds into coronary arterioles and then eventually out the coronary artery ostium. Some cardioplegia, however, is shunted through venous connections to thebesian veins, which then empty into the body of the ventricles without traversing capillary beds. For ease of recall, we will call the pathway of coronary sinus to epicardial veins to capillaries to arterioles to out the coronary ostea the "classic" pathway of nutrient retrograde cardioplegia flow. In situations in which the coronary sinus ostium is occluded and cardioplegia is delivered directly into the coronary sinus, 61.3% +/- 7.9% traverses capillaries and exits the coronary arteries (the classic pathway), whereas 34.5% +/- 4.6% is found to be shunted through thebesian veins into the body of the ventricles [12]. These pathways are summarized in Figure 2. But what occurs if the coronary artery ostium or aortic root is occluded during retrograde cardioplegia delivery? Does all nutrient flow cease and all cardioplegia flow through thebesian veins into the body of the ventricle? The answer to this question is not known. However, it is anatomically possible that some retrograde cardioplegia could follow the pathway of coronary sinus to epicardial veins to capillaries to arterioles to arteriovenous shunts or arteriosinusoids and into the body of the ventricle. We will call this hypothetic pathway the "alternate" pathway of nutrient retrograde cardioplegia flow.

View larger version (47K): [in this window] [in a new window]   Fig 2. . Classic and alternate pathways of retrograde cardioplegia flow. (Reprinted with permission from The Society of Thoracic Surgeons [Ann Thorac Surg 1993;56:410–7].)

There are limits to this model that are worthy of discussion. Because both antegrade and retrograde cardioplegia were delivered simultaneously, it is possible that this in itself leads to decreased antegrade capillary perfusion. And, if only antegrade cardioplegia were delivered, all capillary beds would be perfused. Although this is possible, we believe it is unlikely because the antegrade cardioplegia was delivered at 80 mm Hg and the retrograde was delivered at 40 mm Hg. Thus, any capillary capable of being perfused by antegrade cardioplegia should have been perfused on the basis of superior perfusion pressure. If no capillaries were available for retrograde perfusion, this cardioplegia could have coursed from the coronary sinus to epicardial veins to thebesian veins, and into the body of the ventricles without traversing capillaries. But this, in fact, did not occur, thus supporting our suggestion that overall enhanced microvascular distribution and perfusion occur when both antegrade and retrograde cardioplegia are used.

It is important to emphasize that our anatomic explanations for how simultaneously delivered retrograde cardioplegia resulted in capillary blood flow are speculation; the data presented do not directly support such hypotheses. Further experimentation is necessary to determine precise anatomic pathways. Another limitation to this model is that it is not a functional preparation. Thus, although it is possible to suggest that improved overall microvascular distribution and perfusion occur when both antegrade and retrograde cardioplegia are used, this may or may not translate into clinically improved myocardial protection. Further, whether these proposed benefits of antegrade and retrograde cardioplegia can be achieved when delivered sequentially (not simultaneously, as done in this experiment) has not been determined. Nonetheless, the results of this experiment merit further clinical investigation to compare antegrade cardioplegia alone with the combination of antegrade and retrograde cardioplegia for patients with normal coronary artery anatomy. One can anticipate that if differences are present, they would most likely be evident in procedures involving poor ventricular function, ventricular hypertrophy, or extended cross-clamp times. We hope to see such clinical experimentation in the near future.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Address reprint requests to Dr Laks, Division of Cardiothoracic Surgery, UCLA Medical Center, Box 951741, Los Angeles, CA 90095-1741.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 

1. Partington MY, Acar C, Buckberg GD, Julia P, Kofsky ER, Bugyi HI. Studies of retrograde cardioplegia. I. Capillary blood flow distribution to myocardium supplied by open and occluded arteries. J Thorac Cardiovasc Surg 1989;97:605–12.[Abstract]
2. Haan C, Lazar HL, Bernard S, Rivers S, Zallnick J, Shemin RJ. Superiority of retrograde cardioplegia after acute coronary artery occlusion. Ann Thorac Surg 1991;51:408–12.[Abstract]
3. Menasché P, Subayi JB, Veyssie L, Le Dref O, Chevret S, Piwnica A. Efficacy of coronary sinus cardioplegia in patients with complete coronary artery occlusions. Ann Thorac Surg 1991;51:418–23.[Abstract]
4. Diehl JT, Eichhorn EJ, Konstam MA, et al. Efficacy of retrograde coronary sinus perfusion in patients undergoing myocardial revascularization: a prospective randomized trial. Ann Thorac Surg 1988;45:595–602.[Abstract]
5. Drinkwater DC Jr, Cushen CK, Laks H, Buckberg GD. The use of combined antegrade-retrograde infusion of blood cardioplegic solution in pediatric patients undergoing heart operations. J Thorac Cardiovasc Surg 1992;104:1349–55.[Abstract]
6. Salerno TA, Houck JP, Barrozo CAM, et al. Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection. Ann Thorac Surg 1991;51:245–7.[Abstract]
7. Buckberg GD, Beyersdorf F, Kato NS. Technical considerations and logic of antegrade and retrograde blood cardioplegia delivery. Semin Cardiovasc Surg 1993;5:125–33.
8. Ihnken K, Morita K, Buckberg GD, et al. The safety of simultaneous arterial and coronary sinus perfusion: experimental background and initial clinical results. J Cardiac Surg 1994;9:15–25.[Medline]
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10. Gates RN, Laks H, Drinkwater DC Jr, et al. Can improved microvascular perfusion be achieved using both antegrade and retrograde cardioplegia? Ann Thorac Surg 1995;60:1308–11.[Abstract/Free Full Text]
11. Gates RN, Laks H, Drinkwater DC, et al. Gross and microvascular distribution of retrograde cardioplegia in explanted human hearts. Ann Thorac Surg 1993;56:410–7.[Abstract]
12. Rudis E, Gates RN, Laks H, et al. Coronary sinus osteal occlusion during retrograde delivery of cardioplegic solution significantly improves cardioplegic distribution and efficacy. J Thorac Cardiovasc Surg 1995;109:941–7.[Abstract]
13. Hochberg MS, Austen WG. Selective retrograde coronary venous perfusion. Ann Thorac Surg 1980;29:579–88.
14. Hamond GL, Austen WG. Drainage patterns of coronary arterial flow as determined from the isolated heart. Am J Physiol 1967;212:1435–48.[Free Full Text]
15. Tsang JC, Chiu RC-J. The phantom of "myocardial sinusoids": a historical reappraisal. Ann Thorac Surg 1995;60:1831–5.[Abstract/Free Full Text]
16. Kaley G, Altura BM, ed. Microcirculation. Baltimore: University Park Press, 1977:121–256.

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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): Richard N. Gates Hillel Laks Davis C. Drinkwater, Jr Alon S. Aharon Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gates, R. N. Articles by Chang, P. A. Search for Related Content PubMed PubMed Citation Articles by Gates, R. N. Articles by Chang, P. A.