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Ann Thorac Surg 1995;60:78-82
© 1995 The Society of Thoracic Surgeons

Ventricular Effluent of Retrograde Cardioplegia in Human Hearts Has Traversed Capillary Beds

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

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Background:. In human hearts, as much as two thirds of retrograde cardioplegia is shunted through thebesian and arteriosinusoidal channels into the ventricular cavities. This ventricular effluent is believed to have bypassed the myocardial capillary beds and is therefore considered nonnutritive. Methods:. To test this hypothesis, we studied the explanted hearts from 9 cardiac transplant recipients with the diagnosis of idiopathic cardiomyopathy. These hearts were arrested in situ with cold blood cardioplegia and excised with the coronary sinus intact. The left and right coronary ostia and the coronary sinus then were cannulated. Colored microspheres (15 ± 5 µm) mixed in 37°C blood cardioplegia were administered through the coronary sinus at a pressure of 30 to 40 mm Hg. Effluents from the coronary arteries and ventricular chambers were collected and analyzed for microsphere concentration. Results:. Approximately 80% of retrograde cardioplegia solution was recovered in the ventricular chambers. Nearly 40% of this ventricular chambers effluent had traversed capillary beds and, thus, we believe has nutritive properties. Almost all of the coronary artery effluent of retrograde cardioplegia solution had traversed capillary beds. The total nutritive fraction of retrograde warm blood cardioplegia in this explanted human heart model was approximately 55%. Conclusions:. These findings suggest that the ventricular chamber effluent of retrograde blood cardioplegia contributes to the metabolic homeostasis of the arrested human heart.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
See also page 82.

Despite increasing popularity of retrogradely administered cardioplegic solution through the coronary sinus in clinical cardiac surgery, the adequacy of right ventricular protection remains a concern. Multiple experimental studies using canine models have questioned the protection of the right ventricle and posterior part of interventricular septum using this method of cardioplegia delivery [1–5]. Concomitantly, an abundance of clinical literature has accumulated attesting to the clinical efficacy of this route of cardioplegic delivery [6–8]. Using warm continuous retrograde blood cardioplegia, several reports have emerged demonstrating the safety of right ventricular protection in patients undergoing coronary bypass grafting, as well as patients undergoing mitral valve operations complicated with right ventricular hypertrophy [9–11]. Furthermore, intraoperative contrast echocardiography in human hearts has demonstrated a homogeneous distribution of retrograde cardioplegia to all regions of left and right ventricles [12]. Thus, the experimental observations do not completely reconcile the clinical success.

One potential explantation to this inconsistency may be the differences in the coronary venous anatomy of the human hearts and canine hearts. It is possible that the venous anatomy of the human heart is more suitable for perfusion through the coronary sinus. As much as 60% of retrogradely administered cardioplegia solution in canine hearts is recovered in ventricular chambers by shunting through the venovenous connections of myocardium [13]. It is believed that the ventricular cavity effluent in these experimental models has bypassed the microvasculature and is nonnutritive [13]. Such information is not known in human hearts. The purpose of this study was to assess and quantitate the nutritive property of the ventricular chambers effluent of retrograde warm blood cardioplegia in explanted human hearts.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Cardioplegic Solution
The blood cardioplegic solution was composed of ABO-compatible whole blood and crystalloid cardioplegia solution in a 4:1 ratio. The crystalloid cardioplegia solution was prepared by mixing 500 mL D5.2 NS with 200 mL 0.3 mol/L THAM (Abbott, Chicago, IL) and 50 mL of citrate-phosphate-dextrose (Abbott) solution. To this mixture, KCl (60 mEq), heparin (2,000 units/100 ml), calcium chloride (50 mg/100 mL), and sodium bicarbonate (approximately 8 mEq/100 mL) were added. The cardioplegia solution was oxygenated by bubbling with 100% oxygen for approximately 5 minutes. The final cardioplegia solution had the following approximate values: hematocrit 20%; oxygen tension, 150 mm Hg; carbon dioxide tension, less than 60 mm Hg; pH, 7.4; sodium, 170 mEq; potassium, 40 mEq; calcium, 0.5 mEq; chloride, 95 mEq; glucose, 800 mg/dL; and osmolality, 450 mOsm. The cardioplegic solution was prepared within 1 hour of the experimental procedure.

Explantation of the Human Hearts
This research protocol was reviewed and approved by the Institutional Review Board on the use of pathologic specimens. The explanted hearts of 9 heart transplant recipients were used for this study. These hearts lacked angiographic or pathologic evidence of coronary artery disease and demonstrated histologic evidence of idiopathic cardiomyopathy with interstitial fibrosis. At the time of orthotopic heart transplantation, 4°C blood cardioplegic solution was administered into the aortic root for 2 minutes leading to a diastolic arrest. The hearts then were explanted subatrially, ensuring intact removal of coronary sinus and venous drainage of both ventricles. The hearts were placed in iced saline solution and transported to the laboratory for the experimental procedure.

Experimental Protocol
The hearts were weighed; right and left coronary ostia were cannulated with heparin saline-filled intravenous tubing and secured. A pursestring suture of O Prolene (Ethicon, Somerville, NJ) was placed around the coronary sinus; a 16F silicone perfusion cannula (DLP, Grand Rapids, MI) was barely introduced into the coronary sinus, and the pursestring was tied. The free atrial edges were occluded with vascular clamps, and the hearts were suspended by a heavy suture placed through the aorta and pulmonary artery. The previously prepared warm blood cardioplegia solution (37°C) was delivered at a pressure of 30 to 40 mm Hg for 2 minutes. Approximately 2.5 million colored microspheres (15 ± 5 µm) were injected into the coronary sinus infusion line during the first 30 seconds of cardioplegic administration. The effluents from right coronary ostium, left coronary ostium, right ventricular cavity, and left ventricular cavity were collected and measured. The microsphere concentration in a 5- to 7-mL sample of each effluent solution was measured using the previously described method of microsphere analysis [14]. The regional capillary distribution of retrograde cardioplegia in 6 of the explanted hearts has been reported previously [15].

Statistical Analysis
A paired t test was used to compare the mean values of different parameters. All values are reported as mean ± standard error of the mean. The mean values refer to the arithmetic mean of the values for the 9 explanted hearts. The mean percentages in Table 1 therefore may not add up to 100%.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment References

The inflow and effluent solution microsphere concentrations, as well as the rate of extraction of microspheres from the effluent solution (fraction of solution that has traversed capillary bed), are shown in Table 2. The concentration of microspheres in the effluent solution recovered in aortic root from both coronary ostia was very low (17 ± 8/mL), and the extraction of microspheres was nearly complete (0.997 ± 0.002). More interestingly, the microsphere concentration in the effluent solution recovered from the ventricular chambers was substantially lower than the concentration of microspheres in the cardioplegia solution. The extraction ratio of the ventricular chambers effluent was 0.404 ± 0.074, suggesting that nearly 40% of this effluent solution has traversed capillary beds. The extraction of microspheres in the left ventricular chamber effluent was slightly higher than in the right ventricular chamber effluent (0.507 ± 0.091 versus 0.338 ± 0.081; p = 0.064).

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment References

The anatomy of coronary venous system of the human heart, in comparison to the arterial system, is poorly understood. Hochberg and Austen [16] identified two interrelated venous systems that drain the myocardium. The greater system consists of venous channels that establish communication between the coronary arterial system/capillary network and coronary sinus/right atrium. This system drains approximately 73% of antegradely administered solution. The lesser system is a network of vessels that drain directly into ventricular cavities. This system consists of arteriosinusoidal channels (communication between the precapillary coronary arterial system and ventricular chambers) and thebesian veins (communication between coronary veins and ventricular chambers). The lesser system is anatomically more prominent within the right ventricular myocardium.

The retrogradely administered solution through the coronary sinus of the human heart has two general pathways of flow. The first is the greater venous system through the capillaries, coronary arteries, and then exiting into the aortic root. In the human heart, approximately one quarter of retrograde cardioplegia follows this pathway; not surprisingly, nearly all of the effluent in aortic root has traversed capillary beds. The other major avenue for retrogradely administered solution is through the venous channels that communicate with the ventricular chambers. In the clinical setting, it is noted commonly that a substantial fraction of retrograde cardioplegia is shunted into the ventricular chambers. In this experimental explanted human heart model, nearly 80% of the cardioplegia solution administered through the coronary sinus was recovered in the ventricular chambers (right ventricle > left ventricle). It was noteworthy that, contrary to the general belief that the ventricular chambers effluent is nonnutritive, approximately 40% of cardioplegia solution recovered in the ventricular chambers had traversed capillary beds. Figure 1 schematically illustrates the pathways of retrograde cardioplegia flow. Theoretically, it is possible that retrograde cardioplegia solution may traverse thebesian veins, bypassing capillary networks and drain into ventricular cavity. This fraction of the solution is nonnutritive and, in this experimental model, constituted the majority of the effluent. It is also anatomically feasible that retrograde cardioplegia may traverse capillary beds and then drain into the ventricular chambers through arteriosinusoidal channels. The findings of this study suggest that the effluent found in the ventricular cavities of the human heart does have nutritive properties and may contribute to the metabolic homeostasis of the arrested normothermic heart.

View larger version (35K): [in this window] [in a new window]   Fig 1. . Pathways that the cardioplegic solution administered through the coronary sinus may follow. (LV = left ventricular; RV = right ventricular.)

In addition to the differences in the nutritive properties of the ventricular chambers effluents, the total nutritive fractions of retrograde cardioplegia in the human and canine hearts also differ. The total nutritive fraction is the sum percentage of retrograde cardioplegia that has traversed capillary beds and has nutritive properties. Using a vented, nonworking dog heart model, Solorzano and colleagues [13] observed that 26% ± 7% (mean ± standard error of the mean) of retrogradely administered microspheres were trapped in myocardium. Similarly, Stirling and associates [2] calculated an overall nutritive fraction of 36% for cold retrograde blood cardioplegia in a dog heart model. In contrast to these studies, Partington and co-workers [3] estimated that 65% of the retroperfused microspheres mixed in cold cardioplegic solution were trapped in the myocardium of a canine model. To address the issue of temperature-associated alteration in retroperfusion pattern, Calderone and associates [17] administered warm cardioplegic solution through the coronary sinus of swine hearts and observed an overall nutritive fraction of 33%. In our explanted human heart model, approximately 55% of all of the cardioplegia solution that was infused through the coronary sinus traversed capillary beds. These observations in the explanted human heart support the hypothesis that the coronary venous anatomy of the human heart may be different from the canine heart and that it appears more suitable for retrograde perfusion. Based on our findings, we believe that extrapolation of data obtained in canine experiments to the clinical situations should be done cautiously.

Recent clinical reports have demonstrated that excellent results can be obtained using retrograde warm blood cardioplegia [8–10]. However, based on experimental studies, the theoretical concern about right ventricular protection persists [1–5, 18]. Using the explanted human heart model, our group has reported previously that the capillary perfusion to the right ventricle with warm retrograde blood cardioplegia is barely adequate to meet its theoretical metabolic requirement [15, 19]. Due to lack of a margin of safety and data on homogenity of distribution, caution needs to be exercised in clinical application of warm continuous retrograde blood cardioplegia for myocardial protection. The findings of the present study neither support nor refute the clinical application of retrograde warm blood cardioplegia. However, the data presented in this experimental study provide an explanation for the observed clinical efficacy of warm retrograde cardioplegia. In the clinical setting, a substantial fraction of retrograde cardioplegia is recovered in the ventricular chambers. This study suggests that this ventricular chamber effluent has partly traversed capillary beds and has nutritive properties. This finding is in contrast to the previously held belief that the ventricular chamber effluent is shunted through venovenous channels and has bypassed the microvasculature. This study provides a basis to one of the speculations as the rationale for the clinical success of retrograde warm blood cardioplegia [20].

Two aspects of the methodology of this study deserve special emphasis: the size of microspheres and the placement of a pursestring around the coronary sinus. Capillary flow (ie, nutritive flow) is especially important in devising strategies for myocardial protection because the exchange of oxygen and metabolites occurs at the capillary level [21]. Trapping of 15 ± 5-µm microspheres conventionally has been used as a measure of capillary flow [2–4]. Entrapment of ``large'' microspheres in the venous network may overestimate capillary flow if drainage channels exist between the level of trapped microspheres and capillary beds. These drainage channels may serve to drain the perfusate before reaching the capillary beds. The optimal size of microspheres for being trapped at the level of capillaries (to measure the capillary flow) is not known. It has been reported that microspheres measuring 3.5 µm in diameter completely traverse the capillary bed, whereas 10-µm or larger microspheres do not traverse capillary networks and are trapped adjacent to capillary beds [17]. Thus the possibility of overestimation of capillary flow in this study due to infusion of 15 ± 5-µm microspheres cannot be excluded.

In the experimental preparation of this study, a pursestring suture was placed around the coronary sinus and snared around the catheter to ensure near-complete delivery of cardioplegic solution. This maneuver appears to enhance the delivery of cardioplegic solution through the few proximal branches of coronary sinus and may improve the distribution of the solution to the right ventricle [22]. Because a pursestring suture around the coronary sinus commonly is not employed clinically, the distribution of capillary flow and total nutritive fraction of retrograde cardioplegia in clinical situations may be different.

In summary, the majority of retrograde cardioplegic solution in explanted human hearts is recovered in the ventricular chamber; some of this effluent has traversed capillary beds and, therefore, has some nutritive properties. The nutritive fraction of retrograde blood cardioplegia in this model was approximately 55%. These findings underscore the differences in the coronary venous anatomy of human and canine hearts and provide an explanation for the discrepancy between experimental studies and the clinical success of warm continuous retrograde blood cardioplegia.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment References

 
Address reprint requests to Dr Laks, Division of Cardiothoracic Surgery, UCLA Medical Center, CHS 62-182A, 10833 LeConte Ave, Los Angeles, CA 90024.

Presented at the Thirty-first Annual Meeting of The Society of Thoracic Surgeons, Palm Springs, CA, Jan 30–Feb 1, 1995.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment 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): Abbas Ardehali Hillel Laks Davis C. Drinkwater, Jr Richard N. Gates Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ardehali, A. Articles by Kaczer, E. Search for Related Content PubMed PubMed Citation Articles by Ardehali, A. Articles by Kaczer, E. Related Collections Related Article