Remote ischaemic preconditioning: is it a flag on the field?

Ischaemic preconditioning is one of several different techniques that have been proposed to render the heart more resistant to ischaemia/reperfusion injuries. A significant reduction of troponin release is 'proof of concept', however, whether ischaemic preconditioning leads to improved clinical outcomes is still to be proven. Moreover, the exact mechanism of action still remains unknown since very few studies have investigated the signal transmission in humans.

Understanding innovations in the evolving practice of blood and crystalloid cardioplegia.

The use of cardioplegia solution has substantially increased the safety of cardiac surgery. It protects the myocardium by inducing a rapid and complete diastolic arrest, minimizing myocardial energy requirements, preventing ischaemic damage during the arrest phase and minimizing or preventing reperfusion injury once coronary blood flow is restored. This article is a summary of important information that has accumulated in the literature about cardioplegia and describes how our understanding of cardioplegia has evolved. The basic principles of myocardial ischaemia and reperfusion injury and how they relate to myocardial protection are described. Blood and crystalloid cardioplegia are compared with respect to biochemical and physiological differences. Recent patient demographic changes, with surgeons operating on older, more complex patients who have more severe and diffuse disease, are discussed. This cohort of patients potentially requires prolonged elective ischaemia; hence, improved myocardial protection would be of benefit. We highlight areas of study that have demonstrated a new concept of myocardial protection, known as polarized arrest. Many pharmacological agents have been shown (in experimental studies) to have the ability to induce a polarized arrest and to provide improved protection.

Haemolysis: the harbinger of recurrent mitral regurgitation after mitral valve repair.

We present a case of severe haemolysis post mitral valve repair that presented within the first week of operation. Despite assurance of a good repair, with initial postoperative echocardiographic evidence, the patient subsequently developed haemolysis and required forty units of blood over three months. We emphasize that an unexplained anaemia post mitral valve repair should trigger suspicion for mechanical haemolysis and suggest disease progression or failure of repair.

Miniaturized extracorporeal circulation vs. off-pump coronary artery bypass grafting: what the evidence shows?

Recognition of the potentially deleterious effects of esxtracorporeal circulation led to off-pump coronary artery surgery (OPCAB) experiencing a surge in popularity in the initial decade after its conception. However, OPCAB has its own limitations and technical difficulties, such as coronary access, increased left ventricular size and reduced function, which may lead to the potential for suboptimal revascularization. As an alternative technique, miniaturized extracorporeal circulation (mECC) may provide a more controlled operative field in which the heart may be manipulated whilst minimizing the inflammatory, coagulopathic and haemodilutional effects of cardiopulmonary bypass. In this review, we outline the proposed benefits of the mECC system, discuss the pitfalls associated with mECC, and directly compare mECC to 'off-pump' coronary surgery for a variety of clinical and non-clinical outcomes.

Surgical reconstruction of the mitral valve.

From Cutler's first attempt to treat the mitral valve by inserting a tenotomy knife through the left ventricle, to Carpentier's introduction of several repair techniques and a functional classification for assessing mitral valve lesions, the history of mitral valve treatment is exciting. Mitral diseases may be degenerative, ischaemic, infective or rheumatic, with or without superimposed impaired left ventricular function and calcification. Understanding the underlying pathological features is also important in determining whether mitral valve repair is feasible, how the valve should be repaired and the prospect for long-term durability of the repair. Recent advances in minimally invasive mitral valve surgery are promising but more effort is needed to ensure timely mitral valve repair.

Lipomatous hypertrophy of the interatrial septum: a commonly misdiagnosed mass often leading to unnecessary cardiac surgery.

Lipomatous hypertrophy of the interatrial septum is a benign cardiac mass that should be considered as part of the differential diagnosis for any atrial cardiac tumour. In the reported case, this lesion was initially suspected to be malignant and the patient was thus referred directly to cardiac surgeons for surgical removal. Unnecessary surgical intervention was swiftly averted because the cardiac surgeon promptly referred the patient for an expert echocardiogram that confirmed the diagnosis of lipomatous hypertrophy. The authors discuss the characteristic features of this lesion and how the diagnosis may be made based on several non-invasive imaging modalities without the need for a tissue biopsy. This condition is more common than initially thought and remains under-recognised by most clinicians. In such cases an increased awareness of this lesion along with the opinion of a specialist echocardiologist would help to avoid a misdiagnosis and unnecessary intervention.

Clinical inhibition of the seven-transmembrane thrombin receptor (PAR1) by intravenous aprotinin during cardiothoracic surgery.

BACKGROUND: Protease-activated receptor-1 (PAR1) is the principal thrombin receptor in the vasculature, and antagonists against this receptor are in preclinical trials. Aprotinin, already approved for clinical use to reduce transfusion requirements in cardiopulmonary bypass (CPB) surgery, has been shown to inhibit PAR1 activation in vitro. Here, we exploit CPB as a model for thrombin generation in humans to examine whether aprotinin can inhibit platelet PAR1 activation clinically. METHODS AND RESULTS: PAR1 expression and function on platelets was examined in coronary artery bypass grafting (CABG) patients randomized into 2 groups: (1) those receiving saline infusion during CPB (n=17) and (2) those receiving aprotinin (2x10(6) kallikrein inhibitor units [KIU] in pump prime, 2x10(6) KIU loading dose, followed by 0.5x10(6) KIU/h [n=13]). Platelets in the saline group showed loss of PAR1-specific function at 2 hours after CPB, but this was preserved in the aprotinin group (P<0.001). These effects were most likely targeted at PAR1 receptor cleavage, because (1) the level of thrombin generated during CPB did not vary significantly between groups, (2) expression of SPAN12, which detects only uncleaved PAR1 receptors, was preserved in the aprotinin but not the placebo group (P<0.05), and (3) supporting evidence in vitro showed reduced thrombin-induced PAR1 cleavage (P<0.001) and platelet aggregation (P<0.001) in the presence of aprotinin. CONCLUSIONS: This study demonstrates that platelet PAR1 activation by thrombin can be inhibited by aprotinin. Our results extend the clinical mechanism of action of aprotinin and provide the first proof of principle that PAR1 can be inhibited clinically. This has implications beyond cardiac surgery for the development of therapeutic PAR1 blockade.

Role of aprotinin in the management of patients during and after cardiac surgery.

Management of patients undergoing cardiac surgery has evolved in recent years as more is understood about the physiological changes and responses that occur during and after cardiopulmonary bypass (CPB). In particular, our understanding of the mechanisms involved in haemostasis and in the inflammatory response to bypass surgery, has allowed significant refinements in patient management. Improvements in the pharmacological conservation of blood loss have been striking, particularly with the development of the serine protease inhibitor, aprotinin (Trasylol, Bayer). Aprotinin represents a significant improvement, especially for patients at high risk, since it reduces the need for allogeneic and (sometimes scarce) blood products. However, in view of its cost, making an appropriate selection of patients most at risk of serious blood loss is a major consideration in the use of aprotinin. While its mechanisms of action are not well understood, the use of aprotinin also appears to reduce inflammatory response to CPB.