Advances In Myocardial Protection Research Articles

WITHDRAWN: Cardioplegia and Cardiac surgery: A comprehensive literature review

Abstract Myocardial protection is an essential component of cardiac surgery. Cardioplegic solutions induce cardiac arrest in order to optimise operative conditions. Importantly, cardioplegia enhances myocardial recovery and improves clinical outcomes. There have been considerable advances in myocardial protection since the concept of chemical cardioplegia was first introduced in 1955. Methods can be characterised according to solution, temperature, additives and delivery methods. In spite of significant research, there is still no clear consensus on the cardioplegic method or solution associated with optimum clinical outcomes. This is a comprehensive and comparative overview of the available and upcoming methods in the field of myocardial protection.

Postconditioning the Heart of ST-Elevation Myocardial Infarction Patients

Over the past decade, the therapeutic strategies for acute myocardial infarction have changed considerably. Progress in experimental models, as well as noninvasive myocardial imaging techniques, has identified myocardial reperfusion injury as a significant contributor to the final infarct size in human patients. Following 3 decades devoted to the improvement of reperfusion therapy, recent major advances in myocardial protection after reperfusion slowly move the attention from the vessel to the muscle. In the past 20 years, several pharmacologic treatments or techniques applied at early reperfusion have been tested in experimental models and in the clinical setting. Numerous promising therapies in experimental models have failed to show significant benefit in the clinical realm. But to date, ischemic postconditioning applied at the onset of reperfusion is among the most promising therapies to treat reperfusion injury in myocardial infarction patients, with a 35% significant reduction of final infarct size in small groups of patients and different settings. However, clinical evidence in large population studies is still lacking for their widespread usage in the catheter laboratory at the time of reperfusion. After a brief review of the underlying molecular mechanisms of ischemic postconditioning, this review will focus on the clinical studies assessing the postconditioning effect in STEMI patients and review the findings and explore the future of this technique.

Surgical patch angioplasty of the left main coronary artery

Isolated ostial stenosis of the left main coronary artery (LMCA) is rare, occurring in <1% of the patients undergoing coronary angiography. Surgical patch angioplasty (SPA) offers an alternative to conventional coronary artery bypass grafting (CABG) in such cases and is advantageous in restoring more physiological myocardial perfusion, maintaining ostial patency and preserving conduit material. However, a number of early technical failures and high perioperative mortality have limited the generalized uptake of this procedure, and only recently have advances in myocardial protection and novel surgical approaches to the LMCA resulted in a resurgence of the technique. A systematic literature search identified 45 studies incorporating 478 patients undergoing SPA. A variety of patch materials were used, including the pericardium, saphenous vein and internal mammary and pulmonary arteries. Patients were followed up for a mean of 54.4 months. The 30-day mortality was 1.7% and cardiac specific mortality 3.3% at last follow-up. Encouragingly, 92.4% of reported cases (n = 182) showed complete angiographic patency at last follow-up. Our results indicate that SPA may be a viable alternative to CABG in the surgical management of isolated ostial LMCA stenosis. However, no randomized trials have been performed, and it is clear that careful patient selection is essential in minimizing morbidity and mortality in the short- and long-term. Further research is required to allow a direct comparison of SPA to techniques with a more substantial evidence base such as CABG and percutaneous coronary intervention, and to define the optimal patch graft material, elucidating that any beneficial effects arterial patches may have on long-term patency.

The Short‐term Pulsatile Ventricular Assist Device for Postcardiotomy Cardiogenic Shock: A Clinical Trial in China

Despite the recent advances in myocardial protection, surgical techniques, intra-aortic balloon therapy, and maximal pharmacological support, postoperative ventricular dysfunction continues to occur in 0.5-1.0% of all patients undergoing cardiac surgery. Ventricular assist device (VAD) is an important therapeutic adjunct in treating patients with profound ventricular dysfunction with postcardiotomy cardiogenic shock. The purpose of this report was to describe the clinical results with the China-made Luo-Ye VAD as a short-term circulatory support. From May 1998 to December 2006, 17 patients with postcardiotomy cardiogenic shock were supported by the Luo-Ye VAD. Of these patients, 10 were males and seven were females with a mean age of 49.6 years (range 36-68 years). All cases were supported by left VAD (LVAD). Mean duration of support was 46.3 h (range 13-113 h). A criteria of insertion was established to standardize implantation criteria. Among the 17 patients treated with LVAD, eight (47.1%) patients were weaned from support and seven (41.2%) patients were discharged from hospital. Ten (58.8%) patients died while on LVAD support (nine cases) or shortly after weaning (one case). The causes of death in the entire group were cardiac (40%), renal failure (20%), neurologic (10%), sepsis (10%), and multiple organ system failure (20%). The complications were represented by bleeding, renal failure, neurologic event, infection, ventricular arrhythmias, etc. The Luo-Ye VAD functioned well and proved to be useful in patients with postcardiotomy cardiogenic shock. It carries a less-postoperative anticoagulant and a low incidence of VAD-related complications. The survival rate was encouraging in our small cohort of patients.

Nontransplant surgical alternatives for heart failure

Heart failure is a tremendous burden on society, and on the health care system in particular. Historically, medical treatments have been the only therapies available because patients were felt to be too high risk to undergo conventional cardiac surgical procedures. Cardiac transplantation remains an established therapy for certain patients with end-stage heart failure but it is limited by donor availability and the need for lifelong immunosuppression. Recent advances in myocardial protection, operative techniques, and perioperative care have made it possible for conventional surgery, such as coronary bypass, ventricular reconstruction, and valve repair, to be offered to many patients with advanced heart failure with good short- and long-term results. In 2005, few patients are inoperable.

Impact of Left Ventricular Dysfunction on Outcome in Aortic Stenosis Patients After Aortic Valve Replacement

Surgical treatment for aortic stenosis includes aortic valve replacement, which alleviates symptoms and increases longevity. The purpose of this study was to evaluate the prevalence of left ventricular dysfunction after aortic valve replacement. Left ventricular function was assessed by a retrospective review of preoperative and postoperative ejection fractions (EF) using echocardiography. The prevalence of left ventricular dysfunction after aortic valve replacement was 17.39% with an odds ratio of 4.37 for low preoperative EF. Despite advances in myocardial protection and cardiothoracic surgical care, preoperative EF remains a strong predictor of outcome in patients undergoing aortic valve replacement.

Patient Selection and Technical Considerations for Off-Pump Coronary Surgery

The first successful operations on the coronary arteries were done without the assistance of extracorporeal circulation. Many published reports described operations performed while the heart continued beating (1–8). Advances in cardiopulmonary bypass (CPB) technology, myocardial protection, and cardiopulmonary support allowed surgeons to operate on these arteries with greater precision. It is widely accepted that the single most important development in cardiac surgery was the introduction and refinement of extracorporeal circulation via CPB. Event-free survival rates in cardiac surgery dramatically improved with advancements in myocardial protection that allowed operating in a quiet, motionless, and bloodless field. More recently, advances in 2 competing strategies, coronary artery bypass grafting (CABG) surgery and catheter-based intervention, have led to many debates regarding the optimal treatment of ischemic coronary artery disease. CABG has resulted in longer survival, better quality of life, and long-term event-free survival in patients with multivessel coronary artery disease (9–11). But what is old is new again. The option of not using the pump was the underlying assumption in the development of the concept of minimally invasive coronary surgery. Reports regarding systemic effects of CPB abound in the literature of the past 17 years. Such effects include hematologic, metabolic, pulmonary, cardiac, and cognitive dysfunctions (12–21).

Cecilie Greig memorial lecture 2002. Myocardial protection: an expanding or contracting discipline?

For the past thirty years cardiac surgeons have had a unique opportunity to study the consequences of myocardial ischemia and reperfusion. With the advent of an ability to intervene in acute myocardial syndromes, cardiologists have vigorously joined that effort as have fundamental scientists. Exogenous myocardial protective strategies have emerged as have novel strategies that take advantage of endogenous mechanisms of myocardial protection. As a consequence of improved myocardial protection, operative mortality and morbidity, in particular the low output syndrome, have diminished. However, despite important increases in the knowledge base referable to myocardial ischemia and reperfusion, major advances in myocardial protection have slowed in the past several years. This article explores potential untapped options for augmenting myocardial protection and focuses on the potential adverse interactions between cardiopulmonary bypass and myocardial protection as a prime target for future investigations leading to improved myocardial management during heart operations.

Invited commentary

Sheil and colleagues have described a method that purportedly detects coronary artery endothelial dysfunction during controlled cardiac ischemia. The technique, which involves imaging sonicated albumin microbubbles, has been previously used in adult cardiac surgery. Prior studies in the laboratory showed that these microbubbles attach to neutrophils. Their persistence in coronary arteries indicates adherence of neutrophils to the vascular endothelium, which implies endothelial injury. This paper’s contribution is to demonstrate the safety and efficacy of this technique in the clinical pediatric population. While vascular endothelial dysfunction has been shown to be part of the spectrum of myocardial injury following ischemia, it is unlikely to account entirely for ischemic myocardial dysfunction, with direct myocyte injury being the other important consideration. How tightly does this qualitative measure of endothelial dysfunction correlate with subsequent clinical myocardial dysfunction following controlled ischemia or prolonged exposure to cardiopulmonary bypass? Even if this correlation is tight, the method’s clinical utility is unproven. What does one do with the result during an actual clinical case? The better home for the method may be in the laboratory, where it might serve as a real-time indicator of endothelial dysfunction in studies of strategies for protecting the myocardium from ischemic injury. The next questions to answer are as follows: (1) What is the detailed mechanism underlying the phenomenon? (2) In controlled studies of myocardial ischemia, what is the relationship between microbubble transit time and post-ischemic ventricular function (as measured, eg, by load-independent indices of contractility)? (3) Do specific interventions (eg, cardioplegia administration) that improve ventricular function also shorten transit time? Depending upon these answers, the method may prove to be a simple, real-time way of evaluating myocardial protective strategies in the laboratory or in clinical studies. This paper’s other impact is that it reopens the book on the problem of pediatric myocardial protection. While the literature is rife with contributions on the subject from the early 1990’s, the contributions recently have diminished. The clinical impact of decade-old strategies such as blood cardioplegia, leukocyte depletion, Na+–H+ exchange inhibition, K+–ATP channel activation, Ca++ channel blockade, PAF antagonism, Mg++ supplementation, nitric oxide, or amino acid enhancement in pediatric cardiac surgery remains unclear. While overall results of congenital cardiac surgery have improved dramatically in the past decade, a cadre of operations requiring longer ischemic times or involving the preoperatively impaired myocardium have been introduced. Clinically demonstrated advances in myocardial protection would enhance improvement in the outcome following these most difficult operations. The topic should be resurrected. Contrast echocardiography: potential for the in-vivo study of pediatric myocardial preservationThe Annals of Thoracic SurgeryVol. 75Issue 5PreviewMyocardial contrast echocardiography (MCE) has been used successfully during adult cardiac surgery to image myocardial perfusion. Recently it has been suggested this technique is capable of detecting microvascular injury and inflammation because sonicated albumin microbubbles adhere to activated neutrophils and, in the presence of denuded or inflamed endothelium, they persist within the microvasculature rather than passing unimpeded, which results in profound slowing of their transit rates. The technique has not previously been used during congenital heart surgery; however significant potential is suggested in this setting in which myocardial inflammation may contribute to postoperative myocardial dysfunction, a leading cause of morbidity and mortality. Full-Text PDF

Advances in myocardial protection.

The success of cardiac surgery is due in large part to the myocardial protection techniques employed to maintain cardiac viability during the period of induced ischemic arrest. As the number of older, high-risk cardiac surgical patients increases, advances in myocardial protection have become necessary to achieve a quiet, bloodless operative field without the production of irreversible intraoperative myocardial damage. Current efforts to provide optimal myocardial protection have focused on the effects of cardioplegic perfusate temperature, distribution of cardioplegia flow, and components of the arresting solution. Minimally invasive techniques have expanded surgical options and have led to the development of new methods to protect the myocardium.

Is an Integrated Approach Warranted for Concomitant Carotid and Coronary Artery Disease?

Background. The management of patients with severe, concomitant coronary and carotid artery occlusive disease is controversial. Methods. Between 1975 and 1996, 512 patients (mean age, 64.9 years; 70% male) were admitted for coronary revascularization; 316 (61.7%) had asymptomatic, severe carotid disease (stenosis >70%) and 196 (38.3%) had symptomatic carotid disease (159 [31.1%] with transient ischemia and 37 [7.2%] with completed stroke). In group 1, coronary revascularization and carotid endarterectomy were simultaneously performed in 255 patients (49.8%) with unstable angina. In group 2 (staged approach), carotid endarterectomy was performed before coronary revascularization in 257 patients (50.2%) without unstable angina. Results. Before 1986, the incidence of stroke and death was greater in group 1 (n = 149) than in group 2 (n = 156) (14 [9.4%] versus 4 [2.6%]; p < 0.01). Since 1986, outcomes in group 1 (n = 106) and group 2 (n = 101) have been similar for stroke (2 [1.9%] versus 2 [2.0%]), death (4 [3.8%] versus 3 [3.0%]), and myocardial infarction (4 [3.8%] versus 5 [5.0%]). Significant univariate and multivariate predictors of adverse outcome were primarily heart-related (reoperation, intraaortic balloon use, ejection fraction <0.50, and angina grade 4 for death; age >70 years and congestive heart failure for stroke). Conclusions. Despite highly selected populations, contemporary surgical results do not indicate that staged treatment of severe, concomitant coronary and carotid artery occlusive disease has an advantage over simultaneous treatment. Advances in myocardial protection and perioperative hemodynamic management may account for the low incidences of stroke and death in these operations.

The physiologic basis of warm cardioplegia

Advances in myocardial protection have been instrumental in making cardiac surgery safer. Debate exists over the optimal medium and the optimal temperature for cardioplegia. Currently blood cardioplegia is preferred over crystalloid; the optimal temperature, however, remains controversial. Both warm and cold blood cardioplegia use potassium-induced electromechanical arrest, thereby reducing oxygen consumption by 90% in the working heart. Hypothermic blood cardioplegia given every 15 to 30 minutes provides a bloodless operative field and reduces oxygen consumption an additional 5% to 20%. Continuous warm cardioplegia avoids the deleterious effects of hypothermic ischemia and minimizes reperfusion injury. Perfusion is often interrupted for 5 to 10 minutes to allow adequate visualization of the operative site. Both warm and cold cardioplegia can be given either antegrade or retrograde. Retrospective studies from Toronto support the safety and efficacy of warm cardioplegia. Two large prospective, randomized trials of warm cardioplegia versus intermittent cold blood or cold crystalloid cardioplegia demonstrated equally low incidences of death, perioperative myocardial infarction, and need of intraaortic balloon pump support. Warm blood cardioplegia represents the latest development in myocardial protection. Preliminary studies support its efficacy. Additional studies are needed to determine the ideal route of delivery and to identify any risks associated with the inherent warm cardiopulmonary bypass required.

Risk factors for stroke following coronary bypass surgery.

Improvements in surgical technique and advances in myocardial protection have resulted in low rates of morbidity and mortality despite a greater incidence of high-risk patients. Noncardiac morbidity prolongs hospital stays and increases the costs of cardiac surgery. This study examines the preoperative predictors of stroke following isolated coronary bypass surgery. The clinical records of 3910 consecutive patients who underwent isolated coronary bypass surgery at the University of Toronto were reviewed. Stepwise logistic regression identified six independent predictors of stroke following CABG (percent in parentheses) and calculated factor adjusted odds ratios (OR) for each risk factor. Triple vessel coronary artery disease was the most important predictor (1.9%, OR 5.71), followed by normothermic systemic perfusion (3.8%, OR 4.85), age > 70 years (3.2%, OR 3.88), a previous history of transient ischemic attacks or stroke prior to surgery (6.1%, OR 3.7), peripheral vascular disease (4.7%, OR 2.77), and diabetes mellitus (2.6%, OR 2.01). The mechanism of stroke is likely different between these high-risk groups and strategies to prevent postoperative stroke should focus on the mechanisms responsible in high-risk patients.

Elective cardiac arrest with a hyperpolarizing adenosine triphosphate–sensitive potassium channel opener: A novel form of myocardial protection?

Hyperkalemic depolarized cardiac arrest has been the cornerstone of myocardial protection during cardiac surgery for more than 30 years. Many of the advances in myocardial protection seek to minimize the cellular damage and to reduce the ongoing metabolic processes occurring as a direct consequence of the depolarized state. Ideally, cardiac arrest at hyperpolarized cellular membrane potentials--the natural resting state of the heart--will meet all the requirements of modern cardioplegia, namely, electromechanical asystole and cardiac relaxation, while preserving the vital integrity of the heart itself. To determine whether activation of adenosine triphosphate-sensitive potassium channels by pharmacologic agents could produce hyperpolarized cardiac arrest, we tested the ability of aprikalim, a known adenosine triphosphate-sensitive potassium channel opener, to arrest the intact beating heart. In a normothermic (37 degrees C) isolated rabbit heart preparation, aprikalim was found to rapidly shorten the action potential duration and produce cardiac asystole that was maintained during 20 minutes of "no-flow" global ischemia without a rise in end-diastolic pressure. Cardiac rhythm and function were fully restored by reperfusion alone (developed pressure was 100.6% +/- 7.9% of prearrest value after 30 minutes of reperfusion). In contrast, 20 minutes of unprotected normothermic global ischemia resulted in a 2.7 +/- 0.55 mmHg rise in end-diastolic pressure and only 58.2% +/- 3.8% recovery of developed pressure after 30 minutes of reperfusion. By way of comparison, 20 minutes of standard hyperkalemic depolarized normothermic rest was accompanied by a 1.2 +/- 0.6 mmHg rise in end-diastolic pressure and only 80.8% +/- 2.6% recovery of developed pressure after 30 minutes of reperfusion. To directly compare hyperkalemic depolarized cardiac arrest to hyperpolarized cardiac arrest induced by potassium channel openers and to better define the characteristics of such hyperpolarized arrest, we studied a fixed (4 mmHg rise in end-diastolic pressure--contracture) ischemic injury model. The time to development of the contracture was prolonged by hyperkalemic arrest (35.8 +/- 1.7 minutes) and significantly more so by hyperpolarized arrest (47.0 +/- 3.3 minutes) when compared with that of unprotected hearts (24.0 +/- 1.2 minutes). Moreover, aprikalim resulted in significantly better postischemic recovery of function (developed pressure was 69.0% +/- 6.7% of prearrest value after 30 minutes of reperfusion) than after no cardioplegia (45.4% +/- 7.5%) or standard hyperkalemic cardioplegia (44.3% +/- 5.7%). Pharmacologic activation of adenosine triphosphate-sensitive potassium channels can result in predictable and sustainable hyperpolarized cardiac arrest that is reversible by reperfusion. This method of myocardial protection was found to fully preserve cardiac electromechanical function after a 20-minute period of global normothermic ischemia. Furthermore, hyperpolarized arrest induced by potassium channel openers significantly prolonged the period to the development of contracture and afforded a significantly better postischemic recovery of function than obtained in either hearts protected with hyperkalemic depolarized arrest or those not protected by any form of cardioplegia.

Serial assessment of left ventricular performance following coronary artery bypass grafting: Early postoperative results with myocardial protection afforded by multidose hypothermic potassium crystalloid cardioplegia

Forty patients who recently underwent coronary artery bypass graft (CABG) operations had serial hemodynamic and scintigraphic studies. Multidose hypothermic potassium crystalloid cardioplegia was used for myocardial protection and newer techniques in anesthetic management and perioperative patient care were also employed. The method of equilibrium cardiac gated blood pool (GBP) scintigraphy was used to obtain perioperative changes in global ejection fraction (EF) and regional wall motion (RWM). Ninety percent of patients displayed a decrease in EF 2 hours postoperatively when compared to their preoperative values. This change was also associated with a fall in cardiac index (CI) and left ventricular stroke work index (LVSWI). Twenty-four hours postoperatively, EF and CI recovered to preoperative levels, but LVSWI remained depressed. Seven days postoperatively, global EF had improved to a value greater than the preoperative one (50% ± 3% versus 57% ± 4%, p < 0.05). Perioperative changes in RWM followed the same pattern as EF, but recovery in this index of regional contractility was faster than EF, since maximal improvement was observed 24 hours postoperatively. Thus transient left ventricular dysfunction is common immediately after CABG, but recent advances in myocardial protection and perioperative management are associated with short-term increases in regional and global left ventricular function documented by noninvasive GBP imaging.