Passive Infusion

Abstract

Some damage to the capillaries and increase in myocardial edema have been shown when retrograde cardioplegia perfusion pressure exceeds 40–50 mmHg, or possibly when it falls within this pressure interval. To avoid these complications, we designed a very simple delivery method for retrograde cardioplegia: passive continuous infusion by gravitational force alone.

From August 2002 through April 2003, 147 patients undergoing elective coronary artery bypass surgery were randomly allocated into 2 groups. In both groups, isothermic blood cardioplegic solution was infused continuously in a retrograde fashion, after antegrade cardioplegic arrest. Group 1 (n = 76) received retrograde infusion passively by gravitational force, while Group 2 (n = 71) received retrograde infusion from a manually controlled pressure bag, with the pressure maintained at about 40 mmHg. Myocardial biopsy specimens were taken just before the aorta was declamped, and myocardial edema was scored upon histopathologic examination. Postoperative myocardial damage was evaluated with periodic measurements of CK-MB isoenzyme and cardiac troponin T levels. We recorded cardioplegic infusion pressures and rates, and the total amount of potassium administered.

The mean cardioplegic infusion pressures and rates, total potassium levels, and cardioplegic solution amounts were significantly lower in Group 1 than Group 2. Histologic observations revealed significantly less myocardial edema in Group 1. There were no differences between groups in CK-MB isoenzyme or cardiac troponin T levels, mortality, or morbidity.

Retrograde continuous infusion of isothermic blood cardioplegic solution by gravitational force alone appears to provide satisfactory myocardial protection and to eliminate the harmful effects of higher pressures upon the myocardium.

Many studies have been performed to determine the optimal pressure for retrograde cardioplegic infusion. Gott and colleagues¹ observed ecchymosis when the mean coronary sinus pressure exceeded 40 mmHg. Hammond and coworkers² reported the risk of damage to capillaries and venules when the perfusion pressure in the coronary sinus rose above 60 mmHg. About 40 mmHg of perfusion pressure has become, by consensus, the standard for retrograde cardioplegia.^3–5 Myocardial edema and increases in left ventricular stiffness have been reported even within this pressure limit, especially in patients with acute coronary syndromes.^6,7 On the other hand, some level of perfusion pressure is necessary to drive adequate cardioplegic solution through the coronary vascular bed. Gravity might provide this driving force without the risks of higher pressures on the coronary vasculature. In this report, we present a very simplified delivery method for retrograde cardioplegia, as passive infusion by means of gravitational force. The protective effects of this method on the myocardium were evaluated and compared with those provided by a conventional delivery method from a pressure bag.

Patients and Methods

Patients

From August 2002 through April 2003, 147 patients undergoing elective coronary artery bypass grafting (CABG) for multivessel coronary artery disease were selected at random (within the parameters described below) for inclusion in the study or control group. Patients received retrograde continuous infusion of isothermic blood after antegrade cardioplegic arrest. The pressure at the tip of the retrograde cardioplegia cannula was monitored. In Group 1 (n = 76), retrograde cardioplegic solution was infused passively by means of gravitational force, gained by hanging the bag 1 meter above the patient. In Group 2 (n = 71), a manually controlled pressure bag was used to maintain the pressure at about 40 mm. We excluded from the study patients in need of urgent operation, reoperation, or valvular operation, as well as patients who had significant systemic disease (chronic renal failure or severe chronic obstructive pulmonary disease, for example) or a history of myocardial infarction (MI) during the preceding 15 days.

Surgical Technique

The operations were performed via a median sternotomy and with the patient on cardiopulmonary bypass. The left internal mammary artery (LIMA) was used for revascularization of the left anterior descending coronary artery, and saphenous vein grafts were used for the others. After 2-stage atrial cannulation and aortic cannulation, a 14F retrograde coronary sinus perfusion catheter (Edwards Lifesciences Research Medical Corporation; Midvale, Utah) with a self-inflating balloon was inserted by palpation of the coronary sinus, just before restoration of cardiopulmonary bypass (CPB). If necessary, the catheter was repositioned until the middle cardiac vein was filled, when cardioplegic solution was administered. Cardiopulmonary bypass was instituted using moderate hemodilution with a hematocrit level of 20% to 25% and mild systemic hypothermia (rectal temperature, 30–32 °C). Pump flows were 2.0 to 2.2 L/min/m², and the mean arterial pressure was maintained between 50 and 60 mmHg, with administration of sodium nitroprusside or phenylephrine hydrochloride as required. There was no interruption of retrograde administration of cardioplegic solution during the distal anastomosis. In order to obtain good visualization during construction of the coronary anastomoses, carbon dioxide (CO₂) was blown onto the anastomotic field. The left ventricle was consistently vented through the ascending aorta. All proximal anastomoses were performed on the aorta, which was side-clamped.

Myocardial Protection

The delivery system for cardioplegic solution is shown in Figure 1. A Y-shaped line was used for directing the cardioplegic solution from the aortic cannula antegrade to the aortic root or retrograde to the coronary sinus catheter. The temperature of the blood collected for cardioplegia was the same as that of the perfusate (∼25–28 °C), and the hematocrit level was the same as the perfusate level (∼20%–25%).

Fig. 1 The cardioplegic delivery system. One branch is for obtaining isothermic blood from the aortic cannula, and the other branch is for infusing the antegrade aortic root or the retrograde coronary sinus catheter.

The induction cardioplegic solution contained blood (1,000 mL), potassium (30 mEq/L), sodium bicarbonate (10 mEq/L), and magnesium sulphate (6 mEq/L), whereas the maintenance solution contained blood (500 mL), potassium (10–12 mEq/L), and sodium bicarbonate (5 mEq/L). After cross-clamping the ascending aorta, we accomplished cardiac arrest with an antegrade infusion of 500-mL induction cardioplegic solution given at a mean 70-mmHg aortic root pressure. Arrest was maintained by a continuous retrograde infusion of 500-cc induction cardioplegic solution, and this was followed with maintenance solution.

In Group 1, a cardioplegia bag was hung about 1 meter above the patient, and cardioplegic solution flowed passively against myocardial vascular resistance. The pressure was monitored at the tip of the retrograde cardioplegia cannula. In Group 2, additional pressure was applied to the retrograde cardioplegia bag until 40-mmHg infusion pressure was attained at the tip of the retrograde cardioplegia cannula. The mean flow rate of cardioplegic solution, total amount of solution, and total potassium administered were recorded for each patient. Potassium serum levels were measured from the venous blood samples at 15-minute intervals, and the peak potassium level for each patient was noted.

Markers of Myocardial Damage

At the beginning of the operation and 1, 4, 8, 12, 24, and 48 hours after chest closure, blood samples were collected in order to monitor CK-MB isoenzyme and cardiac troponin T levels. Serum CK-MB levels were studied by enzymatic immunoassay (AU640e® Chemistry Immuno Analyzer, Olympus America Inc.; Melville, NY). Troponin levels were assessed by electrochemiluminescence in immunoassay analysis (Modular Analytics E 170, Roche Diagnostics; Basel, Switzerland). Electrocardiographic (ECG) tracings were obtained before surgery, upon the patient's arrival in the intensive care unit, and during the first 5 postoperative days. Newly appearing Q-waves or the disappearance of R-waves on 2 consecutive postoperative ECG tracings or an increase in CK-MB levels of more than 100 IU/L (or any combination of these) was considered diagnostic of MI.

Myocardial Edema

Just before declamping the aorta, we used a needle to take myocardial biopsy specimens from the left ventricular anterior walls of the first 20 patients in each group. These specimens were fixed in 10% formalin. Paraffin blocks were cut at 5 μm and stained with hematoxylin-eosin, periodic acid-Schiff (PAS) with and without diastase, Masson trichrome, and Alcian blue. Myocardial edema was evaluated and scored by the same pathologist, who was blinded to the study.

Myocardial edema was scored as:

• Grade 0: No edema

• Grade 1: Mild – focal interstitial edema

• Grade 2: Moderate – intense focal interstitial edema

• Grade 3: Moderate – intense diffuse interstitial edema

Statistical Analysis

All data were collected in a prospective manner. Results were reported as the mean ± standard deviation. Analysis of continuous data was performed with Student's t-test, and that of repeated measures was performed with the 2-way analysis of variance test. Categorical measures were compared by χ² statistical analysis.

Results

Preoperative characteristics including age, sex, severity of angina, previous MI, and mean left ventricular ejection fraction (LVEF) were similar in both groups. There was no significant difference between the groups in the number of distal anastomoses, duration of aortic cross-clamping, and total CPB time (Table I).

TABLE I. Preoperative Characteristics and Operative Data

In Group 1, the cardioplegic infusion pressure was quite stable, at 11–28 mmHg (mean, 19.7 ± 8 mmHg); in Group 2, cardioplegic solution was administered at a pressure of 39 ± 2 mmHg (P < 0.05). The total cardioplegic volume was 1,950 ± 735 mL in Group 1 and 2,280 ± 610 mL in Group 2 (P < 0.05). The mean cardioplegic infusion rate was 96 ± 23 mL/min in Group 1 and 144 ± 30 mL/min in Group 2 (P < 0.05). The mean total potassium amount given was 37 ± 3 mEq in Group 1 and 44 ± 4 mEq in Group 2 (P < 0.05). There were no significant differences in peak serum potassium levels between the groups (Table I), nor were there any significant differences in CK-MB isoenzyme and cardiac troponin T levels between the groups (Table II).

TABLE II. Comparison of CK-MB and Troponin T Levels

The myocardial edema scores were significantly lower in Group 1 than in Group 2 (P < 0.05; Table III). Most specimens (60%) were evaluated as normal (grade 0: no edema) in Group 1, whereas only 5 patients (25%) presented with grade 0 edema in Group 2 (Fig. 2). Two of the 20 patients (10%) in Group 1 had grade 3 myocardial edema, while 7 of the 20 patients (35%) in Group 2 had grade 3 edema (Fig. 3).

TABLE III. Myocardial Edema Scores

Fig. 2 Grade 0 myocardial edema (H&E, orig. ×20).

Fig. 3 Grade 3 myocardial edema (H&E, orig. ×40).

Postoperative mortality and morbidity rates are shown in Table IV. No deaths occurred in this relatively low-risk study population. There was only 1 stroke, which occurred in Group 2. Perioperative MI occurred in 1 patient in Group 1 and in 2 patients in Group 2. There was no significant difference between the groups with regard to the need for postoperative pharmacologic or mechanical support. The incidence of supraventricular and ventricular arrhythmia was similar in both groups.

TABLE IV. Comparative Postoperative Mortality and Morbidity

Discussion

Important coronary stenoses or occlusions may limit antegrade delivery of cardioplegic solution to the entire myocardium. Retrograde cardioplegia enables delivery beyond an occluded or critically stenosed coronary artery. It is well known that myocardial oxygen consumption is decreased 80% by cardiac arrest.⁸ However, the achievement of cardiac arrest is much slower when induction cardioplegic solution is administered in a retrograde fashion.³ The early achievement of cardiac arrest by antegrade induction may be more prudent for preservation of energy stores. Therefore, retrograde cardioplegia should be reserved for the maintenance of cardiac arrest. In the present study, cardioplegia was induced by antegrade administration of solution in all cases.

The distribution of the retrograde cardioplegic solution should be evaluated by examining the middle cardiac vein and the anterior cardiac veins during perfusion, because retrograde administration may not perfuse all of the right ventricular free wall and septum.³ If the retrograde cardioplegia catheter is placed too far to the left, it must be repositioned until the middle cardiac vein is filled when the solution is administered.

The preferred method for retrograde cardioplegia is continuous infusion.^7,9–13 In almost all previous studies, however, retrograde cardioplegic infusion has been interrupted (“near continuous retrograde cardioplegia”¹²) to ensure adequate visualization of the coronary artery during each distal anastomosis. The total interruption time comprised more than 30% of the total cross-clamp time in most cases and as high as 50% in some cases.¹⁴ The interrupted retrograde administration of warm cardioplegic solution can cause warm ischemia and can lead to cellular injury.⁹ In the present study, blowing CO₂ onto the anastomotic fields provided good visualization, so that interruption of the flow was avoided. The method used in the present study can be described as “full continuous retrograde cardioplegia.”

Martin and associates⁷ concluded that retrograde warm cardioplegia provides excellent myocardial protection. Kaukoranta's group¹⁵ found that mild hypothermic (29 °C) cardioplegia reduced myocardial oxygen consumption and the release of lactic acid and CK-MB, compared with normothermic (37 °C) cardioplegia. Similar results were achieved when mild hypothermic cardioplegia was compared with cold cardioplegia.¹¹ In the present study, blood obtained from the arterial circuit was the same temperature as the perfusate (25–28 °C).

The appropriate pressure for retrograde continuous administration of cardioplegic solution is arguable. A coronary sinus pressure greater than 40 mmHg has been reported to result in perivascular hemorrhage and myocardial edema, as well as direct coronary sinus injury.^1,16 In addition, Gott and associates¹ showed an increase in thebesian venous flow with increasing coronary venous pressures, which may lead to increased shunt fraction to the right heart.^17,18 Therefore, about 40 mmHg has become common.3–5,11,12,19 On the other hand, Huang and coworkers²⁰ found that increases in coronary sinus perfusion pressure from 20 mmHg to 30 mmHg and then to 40 mmHg have no significant effects on the distribution of cardioplegic solution. Although retrograde cardioplegia may meet the energy requirements of the arrested heart, perfusion through the coronary sinus under high pressure carries the risk of tissue edema, which may compromise the oxygen supply and result in partial myocardial ischemia or anoxia. For this reason, it is difficult to determine whether any ischemic changes that occur during retrograde cardioplegia are a direct result of insufficient cardioplegic solution delivery or a side effect (edema).²¹ The present study demonstrates that retrograde cardioplegia—with the solution given passively by means of gravitational force (mean pressure, 20 mmHg)—provides effective myocardial protection and avoids myocardial edema. Infusion of cardioplegic solution with a volume pump necessitates careful, continuous pressure monitoring, while passive infusion with gravitational force is a safe and reliable method of avoiding high pressures on the myocardium, which can occur with the occlusion of vascular passages during manipulation of the heart.

Although the suggested flow rate for retrograde continuous cardioplegia is about 200 mL/min in most studies, about 100-mL/min provided sufficient myocardial protection in the present study of retrograde continuous blood cardioplegia. Ikonomidis and colleagues²² found that a flow rate of less than 200 mL/min during normothermic (37 °C) retrograde cardioplegia resulted in an accumulation of lactate and acid during the cross-clamp period. On the other hand, lowering the temperature from 37 to 29 °C reduced myocardial oxygen consumption by almost 50%.²³ Rao and co-authors¹² claimed that a flow rate of 100 mL/min was inadequate when using tepid (29 °C) blood cardioplegic solution for myocardial protection and that a flow rate of 200 mL/min was required to ensure adequate washout of the accumulated metabolites. However, interruption of the cardioplegic flow consumed more than 30% of the total cross-clamp time in that study. During retrograde cardioplegia, it is difficult to provide a flow rate of around 200 mL/min without exceeding a perfusion pressure of 40 mmHg. Salerno and associates²⁴ deliberately maintained retrograde cardioplegic perfusion pressures in the coronary sinus below 40 mmHg, with a flow rate of only 122 mL/min. They concluded that this flow rate was sufficient to maintain oxygen and nutrient supply. In Group 2 of the present study, cardioplegic solution was administered retrogradely at 40-mmHg pressure, yielding a mean flow rate of about 145 mL/min. We believe that the production of a mean 200-mL/min flow rate may necessitate a mean coronary sinus pressure of more than 40 mmHg.

Although myocardial edema was significantly less in Group 1 in this study, there were no statistical differences between the groups with regard to myocardial damage and postoperative outcomes. This may be due to the relatively short cross-clamp periods in both groups. The total amounts of cardioplegic solution and potassium administered were significantly less in Group 1 than in Group 2. Although the difference between the peak serum potassium levels of the groups did not reach statistical significance, we speculate that there is a higher risk of hyperkalemia in Group 2, especially in patients with relatively long cross-clamp times.

We conclude that the retrograde continuous administration of isothermic blood cardioplegic solution under pressure produced by gravitational force eliminates the harmful effects of high pressures on the myocardial vasculature and provides satisfactory myocardial protection.