Antegrade/Retrograde Blood Cardioplegia to Ensure Cardioplegic Distribution: Operative Techniques and Objectives

This article details techniques of delivery of antegrade/retrograde blood cardioplegia to ensure its distribution to prevent ischemic damage during aortic clamping, and describes methods of using warm blood cardioplegia to "resuscitate" the heart when used to induce cardioplegia and "avoid reperfusion damage" when given just before aortic unclamping. A technique of rapid transatrial cannulation of the coronary sinus is described to permit safe, rapid, and simple use of retrograde cardioplegia and avoid right heart isolation. Theoretic objectives of these operative techniques are discussed, together with presentation of the specific methods of achieving the aforementioned goals of using blood cardioplegia for resuscitation, prevention, and avoidance of ischemic and reperfusion damage. The preliminary clinical experience with antegrade/retrograde cardioplegia is summarized, and these results have led to adoption of these techniques of blood cardioplegia as the preferred method of myocardial protection in all adult operations and in many pediatric cardiac procedures.     

Do we need hypothermia in myocardial protection?

BACKGROUND: Since the concept of "elective cardiac arrest" has been introduced by Melrose et al., rapid arrest, hypothermia and additional protection has been employed in surgical myocardial protection in clinical and experimental settings. And cardioplegia technique employed these components improved clinical results of open heart surgery except special cases which require longer cardiac arrest. In 1991, Salemo et al. offered striking impact on most of cardiac surgeon with the report of retrograde continuous warm blood cardioplegia. Since then several reports pointed out the benefit of warm blood cardioplegia although inherent disadvantage of continuous cardioplegia were the inadequate visualization of the operative field. These reports recently lead some cardiac surgeon to intermittent warm blood cardioplegia. METHODS: This review introduced and examined our experimental and clinical data with reference to establish new surgical myocardial protection. CONCLUSIONS: Experimental and clinical data might encourage us to employ intermittent tepid (29 ) blood cardioplegia as a practical cardioplegia in open heart surgery.     

Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery

Objective: The influence of the addition of magnesium on myocardial protection with intermittent antegrade warm blood hyperkalaemic cardioplegia in patients undergoing coronary artery surgery was investigated and compared with intermittent antegrade warm blood hyperkalaemic cardioplegia only. Methods: Twenty-three patients undergoing primary elective coronary revascularization were randomized to one of two different techniques of myocardial protection. In the first group, myocardial protection was induced using intermittent antegrade warm blood hyperkalaemic cardioplegia. In the second group, the same technique was used except that magnesium was added to the cardioplegia. Intracellular substrates (ATP, lactate and amino acids) were measured in left ventricular biopsies collected 5 min after institution of cardiopulmonary bypass, after 30 min of ischaemic arrest and 20 min after reperfusion. Results: There were no significant changes in the intracellular concentration of ATP or free amino acid pool in biopsies taken at the end of the period of myocardial ischaemia. However, the addition of magnesium prevented the significant increase in the intracellular concentration of lactate seen with intermittent antegrade warm blood hyperkalaemic cardioplegia. Upon reperfusion there was a significant fall in ATP and amino acid concentration when the technique of intermittent antegrade warm blood hyperkalaemic cardioplegia was used but not when magnesium was added to the cardioplegia. Conclusions: This work shows that intermittent antegrade warm blood hyperkalaemic cardioplegia supplemented with magnesium prevents substrate derangement early after reperfusion.     

Paediatric myocardial protection-strategies, controversies and recent developments

During the last two decades, there has been a phenomenal rise in the number of patients undergoing early primary repair for congenital heart defects. Repair of these intracardiac defects usually requires open heart surgery that necessitates cardiopulmonary bypass, aortic cross clamping and administered cardiac arrest. To achieve this goal, cardioplegia is administered at predetermined intervals to ensure a quiescent heart and protection of the myocardium from ischaemia at the same time. Cardioplegia administration is usually done in conjunction with hypothermia to decrease the metabolic demands of the arrested heart as hypothermia alone is inferior to the combination of hypothermia and cardioplegia in providing adequate myocardial protection. The types and methods of cardioplegia in use today are as diverse as individual surgeons; and most institutions have over time developed their own preferred myocardial protection techniques that have proven to be safe and effective. Most of the available literature and concepts in pediatric myocardial protection today have been borrowed from observations in adults and ex- vivo and in-vivo animal models. The extrapolation of these concepts to pediatric myocardium is inappropriate as immature myocardium is not simply a “small adult heart”. It has unique differences and susceptibilities. This review provides a synopsis of pediatric myocardial protection including types, mechanisms, composition and comparative features of pediatric cardioplegia solutions currently in use all over the world. As of now, there is no evidence favoring one technique or strategy over the other. Pediatric myocardial protection protocols in general are currently experience based.     

Intraoperative myocardial protection: current trends and future perspectives

BACKGROUND: The results of contemporary coronary artery bypass graft surgery (CABG) are excellent. However, recently changing trends in the population at risk have necessitated new measures to minimize perioperative morbidity and mortality. METHODS: We reviewed cardioplegic innovations developed, evaluated, and currently employed at the Toronto Hospital. In addition, we conducted an evaluation of novel cardioplegic formulations, with an eye towards future clinical applications. RESULTS: At the Toronto Hospital, we demonstrated that blood provided better protection than crystalloid cardioplegia. Subsequently, we found that a terminal infusion of warm blood cardioplegia repleted myocardial adenosine triphosphate (ATP) levels and improved postoperative ventricular function. Recently, we reported that tepid (29 degrees C) cardioplegia reduced lactate and acid production during cardioplegic arrest, and improved postoperative ventricular function. Combining antegrade and retrograde cardioplegic delivery reduced lactate production, preserved ATP stores, and improved metabolic recovery after cross-clamp release. Cardioplegic flows of at least 200 mL/min were required to washout detrimental metabolic end-products and improve ventricular function. To further optimize myocardial protection, attempts have been made to harness the beneficial effects of ischemic preconditioning using adenosine. Similarly, insulin cardioplegia has been employed in order to enhance ventricular performance by stimulating early postoperative aerobic metabolism. Finally L-arginine, a nitric oxide donor has been demonstrated to be beneficial in experimental studies and may represent a further option for the enhancement of intraoperative myocardial protection. CONCLUSIONS: Despite continued improvements in cardioplegic techniques, low output syndrome following high-risk CABG remains an ongoing concern. The development of novel additives with various protective properties may provide added protection, allowing for a reduction morbidity and mortality following CABG.     

Myocardial protection: some problems and recent progress]

One of the great advances in cardiac surgery in the past 20 years has been the concept of myocardial protection "cardioplegia". But even now, there are some controversies about the methods for myocardial protection. In this review, controversy between crystalloid and blood cardioplegia, between extracellular and intracellular cardioplegic solution are discussed. And then the recent advances in cardioplegia, terminal warm blood cardioplegia, retrograde infusion of cardioplegic solution and cardioplegia in infants are reviewed.     

Technical Considerations for Myocardial Protection during the Course of Coronary Artery Bypass Reoperation: The Impact of Functioning Saphenous Vein and Internal Mammary Artery Grafts

New technical challenges involving the delivery of cardioplegia during the course of coronary artery bypass operation continue to be presented to the surgeon. Functioning saphenous grafts at reoperation that are at risk for distal embolization, are managed by altering the standard cardioplegia delivery techniques. Management of patent internal mammary artery (IMA) grafts depends upon the status of the native circulation and coronary collateral. The reoperation may be performed with a fibrillating heart, standard cardioplegia with a clamped mammary graft, or cardioplegia delivered during simultaneous circulatory arrest. Myocardial temperature measurements, during the course of more complex operations, are useful in choosing the appropriate technique for myocardial protection.     

Myocardial injury in hypertrophic hearts of patients undergoing aortic valve surgery using cold or warm blood cardioplegia.

OBJECTIVES: Myocardial protection techniques during cardiac surgery have been largely investigated in the clinical setting of coronary revascularisation. Few studies have been carried out on patients with left ventricular hypertrophy where the choice of delivery, and temperature of cardioplegia remain controversial. This study investigates metabolic changes and myocardial injury in hypertrophic hearts of patients undergoing aortic valve surgery using antegrade cold or warm blood cardioplegia. METHODS: Thirty-five patients were prospectively randomised to intermittent antegrade cold or warm blood cardioplegia. Left ventricular biopsies were collected at 5min following institution of cardiopulmonary bypass, 30min after cross-clamping the aorta and 20min after cross-clamp removal, and used to determine metabolic changes during surgery. Metabolites (adenine nucleotides, amino acids and lactate) were measured using high pressure liquid chromatography and enzymatic techniques. Postoperative myocardial troponin I release was used as a marker of myocardial injury. RESULTS: Ischaemic arrest was associated with significant increase in lactate and alanine/glutamate ratio only in the warm blood group. During reperfusion, alanine/glutamate ratio was higher than preischaemic levels in both groups, but the extent of the increase was considerably greater in the warm blood group. Troponin I release was markedly (P<0.05, Mean+/-SD) lower at 1, 24 and 48h postoperatively in the cold compared to the warm blood group (0.51+/-0.37, 0.37+/-0.22 and 0.27+/-0.19 vs. 0.75+/-0.42, 0.73+/-0.51 and 0.54+/-0.38ng/ml for cold vs. warm group, respectively). CONCLUSIONS: Cold blood cardioplegia is associated with less ischaemic stress and myocardial injury compared to warm blood cardioplegia in patients with aortic stenosis undergoing valve replacement surgery. Both cardioplegic techniques, however, confer sub-optimal myocardial protection.     

Multicentre investigation of myocardial protection with cold cardioplegia

In order to analyze factors of importance for the efficiency of myocardial protection during open-heart surgery, a study was made of 144 patients undergoing isolated aortic valve replacement with various cardioplegic techniques. The cardioplegia was of Bretschneider type in 54 cases, St Thomas in 31 and Ringer-potassium type in 11 cases. Single or multi-dose blood cardioplegia was used in 11 cases and continuous blood cardioplegia in 30 cases. Local cardiac hypothermia was additionally employed in all patients. The efficiency of myocardial protection was assessed mainly from the incidence of postoperative conduction disturbances, myocardial enzyme release and need for inotropic support. All patients survived the operation. In 20% surgery was followed by transient or persistent disturbance of conduction, in 9% by abnormally increased CK-MB release and in 5% by requirement for inotropic support. Preoperative risk factors such as high age or severe left ventricular (LV) hypertrophy or dysfunction had little influence on the results. Patients in whom aortic stenosis (AS) was dominant in the complex with aortic insufficiency (AS + AI) showed 20-hour postoperative CK-MB enzyme activity twice as high as those with pure aortic insufficiency. The most important factors in myocardial protection were the duration of aortic occlusion and the myocardial temperature during cardioplegia. When the aortic occlusion lasted more than 80 min there was a 32% incidence of conduction disturbances and 20-hour CK-MB activity thrice as high as after shorter occlusion. Patients with mean myocardial temperature below 18 degrees C during cardioplegia invariably had low enzyme activities, which indicated good myocardial protection. The best overall results were obtained in patients operated on during hypothermia at 25-27 degrees C, with single or multi-dose blood cardioplegia and with efficient local cooling of the heart.     

Improved myocardial protection with blood and crystalloid cardioplegia

Although the results of coronary artery bypass surgery have been excellent, recent studies have demonstrated transient alterations in myocardial function and metabolism in spite of apparently adequate cardioplegic protection. Blood cardioplegia may provide better protection than crystalloid cardioplegia, but clinical studies remain inconclusive. Critical coronary stenoses limit cardioplegic delivery, and myocardial protection would be improved with either blood or crystalloid cardioplegia if the solution could be delivered beyond the coronary stenosis. The construction of proximal as well as distal anastomoses during a prolonged cross-clamp period permits more uniform cardioplegic delivery and immediate reperfusion when the cross clamp is released. This technique was used in a prospective randomized trial comparing blood and crystalloid cardioplegia. The long cross-clamp technique eliminated temperature gradients induced when cardioplegia was delivered into the aortic root. The technique of cardioplegic delivery may be as important as the solution used for cardioplegic protection. (J VASC SURG 1984;1:656-9.)     

心肌保护临床研究和应用进展

心肌保护近年来的发展多注重基础研究紧密联系临床，积极转化为临床实践，心肌保护液的添加成分、减轻炎症反应的策略、缺血预调在临床方面的应用都是学者们高度关注的重要部分，能够转化到临床，成为有效的心肌保护措施。     

Myocardial protection with cold blood potassium cardioplegia: experimental and clinical studies

One hundred and eighty-one patients (101 men and 80 women) underwent 61 congenital and 120 acquired heart operations using cold blood potassium cardioplegia as the method of myocardial protection at Kagoshima University from August, 1978 to August, 1981. Hospital deaths occurred in 18 patients (9.8%), and 4 cases were late death (2.2%). Multivariate analysis revealed no significant relationship between type of heart disease and operative mortality or the occurrence of post-operative low output syndrome. To evaluate the superiority of cold blood cardioplegia for myocardial protection, we carried out 20 orthotopic heart transplants in dog; 16 transplanted grafts could maintain the circulation of recipient without cardiopulmonary bypass. Cardiac contractility following 90-minute ischemic time showed 97 to 100% of the control values without any inotropic drugs. These clinical and experimental findings suggest that cold blood potassium cardioplegia provides excellent myocardial protection during the ischemia of the heart.     

Evaluation of myocardial protection by combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia in aorto-coronary bypass grafting.

The concept of pretreatment of the myocardium with a pharmacological agent protecting the cell against ischemic and reperfusion injury is very attractive. Lidoflazine, a calcium overload blocker, predominantly membrane stabilizing, is able to prevent cell damage during ischemic arrest and reperfusion. The purpose of this study was to determine whether the combination of lidoflazine pretreatment and St. Thomas' Hospital cardioplegia can provide, in clinical practice, better myocardial protection in aorto-coronary bypass grafting than St. Thomas' Hospital cardioplegia alone. As indices for myocardial protection, recovery of cardiac function, enzyme release, and clinical outcome were registered. Ninety-three patients undergoing aorto-coronary bypass surgery were studied. These patients were randomized into two groups in a double blind fashion. Patients in group A (n = 48) received lidoflazine 1 mg/kg intravenously over a period of 20 min before initiation of cardiopulmonary bypass. Group B (n = 45) receiving placebo, acted as a control group. Myocardial protection consisted of intermittent infusion of cold 4 degrees C St. Thomas' Hospital cardioplegia, topical slush ice, and systemic hypothermia (28 degrees C rectal). No significant differences between the two groups were noted in terms of recovery of cardiac function, enzyme release, incidence of myocardial infarction, low cardiac output, rhythm, and conduction disturbances. In conclusion, our data suggest that the combination of intravenous pretreatment with lidoflazine and St. Thomas' Hospital cardioplegia did not provide significant additional myocardial protection in the clinical situation.     

Antegrade and retrograde blood cardioplegia

The article analyses the techniques of antegrade/retrograde blood cardioplegia which ensures even distribution of the solution in the heart so as to reduce the ischemic injury to the myocardium during compression of the aorta. The author describes methods of inducing cardioplegia by means of "warmed" blood for "reanimation" of the heart during cardioplegia and for the prevention of "reperfusion injuries" occurring immediately after the clamp is removed from the aorta. A method of rapid transatrial cannulation of the coronary sinus is described which provides for safe, rapid, and simple retrograde cardioplegia and helps to avoid isolation of the right heart. The theoretical basis of this operative technique is discussed as well as the specific methods for achieving the above mentioned purposes of using blood cardioplegia for resuscitation, avoidance, and prevention of ischemic and perfusion damages. Preliminary clinical experience in the use of antegrade/retrograde cardioplegia is generalized in this article. The results allowed us to introduce these methods of blood cardioplegia as an effective measure of myocardial protection during operations on adult patients and in some operations on children.     

Myocardial protection in cardiac surgery: a historical review from the beginning to the current topics

Myocardial protection has become an essential adjunctive measure in cardiac surgery for a couple of decades, because since the 1950s, the methods of cardioprotection (cardioplegic solutions and related procedures) have been improved by the mechanism of myocardial ischemia/reperfusion-induced damage being unveiled through the untiring efforts of researchers and clinicians. The concept of myocardial protection in cardiac surgery was proposed along with introduction of hypothermic crystalloid potassium cardioplegia in the beginning and has been diversified by pharmacological additives, blood cardioplegia, temperature modulation (warm; tepid), retrograde cardioplegia, controlled reperfusion, integrated cardioplegia, and pre-and postconditioning. This historical review summarized experimental and clinical studies dealing with the methods and results of myocardial protection in cardiac surgery, introducing the newly developed concepts for the last decade and the current topics.     

心肌缺血的病理生理与心肌保护

心肌损伤是心脏手术引起的主要并发症之一。手术操作、全身炎性反应和心肌缺血-再灌注是造成心肌损伤的主要因素。轻柔而迅速的手术操作能减轻机械因素对心肌的损伤,缩短心肌缺血时间,从而减轻缺血-再灌注对心肌的损伤。良好的心肌保护效果是患者术后恢复的关键因素。近年来,通过调节心脏保护液的温度、成分、灌注方法而增加心肌氧供、降低氧耗、抑制炎性反应、清除氧自由基,并使用药物启动心肌细胞内源性保护机制,从而减轻心肌缺血-再灌注损伤,改善心肌保护效果。     

Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery.

The authors' recent experimental work has demonstrated that myocardial protection using continuous coronary perfusion with warm beta-blocker-enriched blood avoids myocardial ischaemia and minimizes myocardial oedema formation, thus completely preserving left ventricle function. The purpose of this clinical study was to compare this alternative technique in terms of structural and functional myocardial protection with the routinely used crystalloid Bretschneider cardioplegia. Sixty coronary artery surgery patients were randomized to receive either crystalloid cardioplegia or continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker esmolol. Cardiac function was evaluated using transoesophageal echocardiography (fractional area of contraction) and cardiac metabolism using arterial-coronary sinus lactate concentration difference (a - csD(LAC)). From left ventricular biopsies, the authors determined myocardial oedema, heat-shock-protein-70, intercellular-adhesion-molecule and actin pattern. Patients with crystalloid cardioplegia received 3.6 +/- 0.8 grafts during 64 +/- 20 min cross-clamp time (beta-blocker: 3.5 +/- 0.9 grafts during 68 +/- 22 min; NS). Following cross-clamp removal crystalloid cardioplegia hearts released significant lactate amounts (a- csD(LAC)) - 1.0 +/- 0.6 versus - 0.1 +/- 0.2 mmol/litre in beta-blocker hearts; P < 0.05). In crystalloid cardioplegia hearts, myocardial water content increased from 82.1 +/- 2.1% pre-cardiopulmonary bypass to 83.2 +/- 1.7% at the end of cardiopulmonary bypass (P < 0.05); in beta-blocker hearts myocardial water content remained unchanged (pre-cardiopulmonary bypass: 82.3 +/- 1.9%; end of cardiopulmonary bypass: 82.4 +/- 1.7%; NS). At the end of cardiopulmonary bypass, left ventricular biopsies of beta-blocker hearts showed less structural damage as determined by heat shock protein-70, intercellular adhesion molecule-I and deranged actin cross-striation pattern as compared with crystalloid cardioplegia hearts (P < 0.05). The post-cardiopulmonary bypass fractional area of contraction was similar in both groups (beta-blocker: 65 +/- 14%; crystalloid cardioplegia: 62 +/- 16%); however, beta-blocker patients required less inotropic stimulation (dopamine: beta-blocker: 2.9 +/- 2.5 versus crystalloid cardioplegia: 5.0 +/- 2.3 microg/kg per min; P < 0.05). The data suggest that continuous coronary perfusion with warm esmolol-enriched blood results in better myocardial protection compared with crystalloid cardioplegia. It is concluded that the concept of beta-blocker-induced cardiac surgical conditions may be a useful alternative for myocardial protection during coronary artery surgery.     

Myocardial Protection in Pediatric Cardiac Surgery

The combination of hypothermia and potassium cardioplegic arrest has become the most common method of myocardial protection in the evolution of myocardial protection. This review focuses on myocardial protection in pediatric cardiac surgery. In the 1980s, blood was added to cardioplegia solution in order to supply the myocardium with oxygen, nutrients, and for buffering purposes. Similar myocardial protection methods have been used in adult and pediatric groups for many years. However, the immature heart in the pediatric group differs in many ways from the mature hearts in adults. Low cardiac output is more often observed in pediatric patients. Most cardiac operations are performed under cardioplegic arrest in pediatric cardiac surgery. Today there are a lot of different types of cardioplegia solutions and methods used in pediatric cardiac surgery. Soon after normothermic perfusion was used in the adult cardiac surgery in the beginning of the 1990s, normothermic perfusion and cardioplegia began to be used in pediatric myocardial protection. Myocardial protection is more challenging in particular cases such as: (i) long and complex cases in which repetitive cardioplegia administration through the aortic root is difficult; (ii) newborn patients; and (iii) cases with preoperative damaged myocardium. If the mortality and morbidity rates of the centers in complex and long procedures are higher than the reported rates in literature, the myocardial protection method must be suspected and reorganized.     

Myocardial preservation in the neonate. Beneficial effects of cardioplegia and systemic hypothermia on piglets undergoing cardiopulmonary bypass and myocardial ischemia

This study examined anatomic differences between the adult and the newborn heart as they relate to myocardial preservation and compared standard techniques of myocardial preservation used in operations for congenital heart disease. The biventricular endocardial surface area/ventricular mass ratios were calculated in 10 neonatal (2.5 +/- 0.2:1) and 10 adult (0.6 +/- 0.1:1) pigs (p less than 0.001). Three groups of neonatal pigs underwent 1 hour of global myocardial ischemia while being supported by cardiopulmonary bypass. Myocardial protection was by deep systemic hypothermia (group 1), moderate systemic hypothermia and cardioplegia (group 2), or by deep systemic hypothermia and cardioplegia (group 3). Left ventricular end-systolic pressure-dimension and end-diastolic pressure-dimension relationships were measured before and after cardiopulmonary bypass. Septal temperatures remained below 20 degrees C in groups 1 and 3 but rose above 20 degrees C in group 2. Groups 1 and 2 had moderate and mild ventricular stiffening, respectively, whereas group 3 showed no diastolic dysfunction. Ventricular contractility was increased (p less than 0.05) in group 3. Techniques for myocardial preservation used during operations for congenital heart disease must consider the large endocardial surface area/mass ratio and the rewarming effects of systemic blood. The combination of deep systemic hypothermia and cardioplegia provided superior myocardial protection compared with the other techniques tested.     

Retrograde continuous warm blood cardioplegia: a new concept in myocardial protection

This report presents the results in our first clinical series of patients receiving continuous warm blood cardioplegia through the coronary sinus. Warm oxygenated blood cardioplegia has certain theoretical advantages, such as continuously supplying oxygen and substrates to the arrested heart while avoiding the side effects of hypothermia. Retrograde infusion of cardioplegia also offers certain advantages (eg, in valve operations and in patients with severe coronary artery disease) that are complementary to warm blood cardioplegia. Retrograde warm blood cardioplegia was used in 113 consecutive patients (85 men and 28 women with a mean age of 61 years) undergoing various procedures. Three percent of the patients died, 7% needed transient intraaortic balloon pump support, 6% had evidence of perioperative myocardial infarction, and 96% had spontaneous return of rhythm. There were no coronary sinus injuries. This new technique of retrograde continuous warm blood cardioplegia is a simple, safe, and reliable method of myocardial protection that may change the way we currently protect the heart intraoperatively.