Ex Vivo Heart Perfusion

Heart transplantation offers the best prognostic results for patients with end stage heart failure. However, there is a much greater demand for donor hearts than there is adequate supply. Cold static storage (CSS) is the current standard protocol for donor heart procurement. CSS has excellent prognosis but subjects the organ to ischemic reperfusion injury (IRI) and induces tissue inflammation due to anoxic conditions and oxidative stress. Hearts from older donors or patients that have a history of previous heart disease can’t withstand the anoxic stressors and make for poor donor candidates with the CSS protocol since they are associated with worse prognostic outcomes, which restricts the donor pool for acceptable hearts. Ex vivo heart perfusion, a novel method for heart transport, is a potential solution to expanding the donor pool and reducing the IRI and anoxic insults. This protocol continuously perfuses the donor heart and has been shown to reduce ischemic injury, increase ex vivo viability time and improve the biochemical and cellular profile of the donor heart. These factors collectively open the door for the possibility of expanding the acceptable pool of donor hearts since this protocol places fewer stressors on the myocardial tissue. We review the limitations of the cold static storage protocol and evaluate the benefits, drawbacks and practicality of the ex vivo heart perfusion for use in clinical practice by examining both human and animal studies

Cardioplegia between evolution and revolution: from depolarized to polarized cardiac arrest in adult cardiac surgery

Despite current advances in perioperative care, intraoperative myocardial protection during cardiac surgery has not kept the same pace. High potassium cardioplegic solutions were introduced in the 1950s, and in the early 1960s they were soon recognized as harmful. Since that time, surgeons have minimized many of the adverse effects by lowering the temperature of the heart, lowering K+ concentration, reducing contact K+ time, changing the vehicle from a crystalloid solution to whole-blood, adding many pharmacological protectants and modifying reperfusion conditions. Despite these attempts, high potassium remains a suboptimalway to arrest the heart. We briefly review the historical advances and failures of finding alternatives to high potassium, the drawbacks of a prolonged depolarized membrane, altered Ca2+ intracellular circuits and heterogeneity in atrial-ventricular K+ repolarization during reanimation. Many of these untoward effects may be alleviated by a polarized membrane, and we will discuss the basic science and clinical experience from a number of institutions trialling different alternatives, and our institution with a non-depolarizing adenosine, lidocaine and magnesium (ALM) cardioplegia. The future of polarized arrest is an exciting one and may play an important role in treating the next generation of patients who are older, and sicker with multiple comorbidities and require more complex operations with prolonged cross-clamping times

Adenosine and its role in cardioplegia : experimental evaluation in the isolated rat heart and in an-vivo primate model

This study was designed to investigate the role of adenosine, an endogenous cardioprotectant agent, without high potassium and as cardioplegic additive to high potassium solutions. Adenosine cardioplegia and potassium cardioplegia supplemented by adenosine (K + ADO) were investigated in terms of hemodynamic, metabolic and ultrastructural recovery in the isolated rat heart and in the in-vivo baboon model during periods of global myocardial ischemia, simulating the clinical situation during open heart surgery. The results obtained in both models show that adenosine improved postischemic hemodynamic function when used without high potassium cardioplegia. The combination of adenosine and high potassium was less effective in both models in terms of hemodynamic recovery; however, improved rhythm stability and coronary vasodilatation were still present. In addition adenosine alone was able to induce fast electromechanical arrest in the isolated rat heart. However, failure of even high concentrations of adenosine to limit ventricular fibrillation in the baboon exclude its use as cardioplegic agent on its own without additional interventions. It appears likely that adenosine without high potassium is cardioprotective via activation of A₁ receptors and opening of ATP-sensitive potassium channels, a mechanism which is probably non-functional in a high potassium environment. In view of the limited cardioprotection achieved with the combination of adenosine and high potassium further studies should aim for additional interventions to induce cardioplegia with adenosine and normokalemic solutions

Myocardial protection to the hypertrophied heart: the eternal challenge

The myocardial protection allowed great advance in cardiac surgery, decreasing the mortality and making more feasible complex surgeries. Latterly, the patient population elected for cardiac procedures has been changing towards elderly patients with ventricular function depressed and myocardial hypertrophy. The myocardial hypertrophy condition represents a great challenge since the beginning of the cardiac surgery. Several techniques have been described to protect the myocardial hypertrophy, however with no satisfactory results. In this manuscript we present the state of the art technique of myocardial protection.A proteção miocárdica permitiu enorme avanço na moderna cirurgia cardíaca, reduzindo a mortalidade e permitindo que operações cada vez mais complexas pudessem ser realizadas. A alteração na população eleita para procedimentos cirúrgicos cardiológicos mudou significativamente nas últimas décadas, com o aumento de pacientes mais idosos, com função ventricular deprimida e miocárdio hipertrofiado. Essa última condição, desde os primórdios da cirurgia cardíaca, constituiu-se em grande desafio. Diversas técnicas de proteção ao miocárdio hipertrofiado foram descritas, porém com resultados não alentadores. As características da hipertrofia miocárdica no adulto com cardiopatia cirúrgica apresentam particularidades desafiadoras. Nesse artigo, procuramos atualizar o estado da arte sobre a proteção miocárdica ao coração hipertrofiado.9710

Proteção miocárdica ao coração hipertrofiado: o eterno desafio Myocardial protection to the hypertrophied heart: the eternal challenge

Abstract The myocardial protection allowed great advance in cardiac surgery, decreasing the mortality and making more feasible complex surgeries. Latterly the patient population elected for cardiac procedures has been changing towards elderly patients with ventricular function depressed and myocardial hypertrophy. The myocardial hypertrophy condition represents a great challenge since the beginning of the cardiac surgery. Several techniques have been described to protect the myocardial hypertrophy, however with no satisfactory results. In this manuscript we present the state of the art technique of myocardial protection. 98 CRESSONI, ES ET AL -Myocardial protection to the hypertrophied heart: the eternal challenge Bras Cir Cardiovasc 2008; 23(1): 97-107 Re

Clinical Impact of Custodiol Cardioplegic Solution on Patients Undergoing Complex Cardiac Surgery With Mild to Moderate Impairment of Left Ventricular Systolic Function

Background: The Bretschneider HTK solution is used widely for multiorgan preservation for transplantation, as well as a cardioplegic agent that allows single dose administration which is an attractive option for lengthy complex cardiac surgery. It was proved that it is simple to use, safe and practical. Moreover, it is considered to confer sufficient myocardial protection for more than 2 h of cardiac arrest. We undertook this descriptive study to analyze the performance of HTK solution in patients undergoing complex cardiac surgery with mild to moderate impairment of left ventricular systolic function. Patients and methods: A total of 50 patients underwent different complex cardiac surgery at national heart institute from January 2015 to November 2016 using single dose Custodiol cardioplegia as the primary and sole cardioplegic agent, their data was prospectively collected and their hospital outcome was analyzed as regards to ten study endpoints namely Prolonged ventilation, return to theatre for bleeding, renal failure, stroke, 30 days mortality, postoperative MI, need for inotropes, time on inotropes, ICU stay and hospital stay. Pre- and postoperative echocardiography was done to compare and evaluate the change of LV function using the parameters of End Systolic Dimension, End Diastolic Dimension, Fraction Shortening and Ejection Fraction of the left ventricle. Results: Half of the patients were males. Their age ranged between 16 – 65 years with a mean (standard deviation) of 47.46(11.10). preoperative ejection fraction ranged from 30 % to 49% with a mean (standard deviation) of 41.8 (6.32), the majority of them (64%) had NYHA class of 3 and half of them had CCS of 3. all patients were done electively. The most common procedure done was redo DVR 24% (12 patients) followed by Bentall operation 22%(11 patients). This is followed by CABG + MVR 7 patients (14%), then an equal number of 6 patients (12%) who underwent redo MVR post-infective endocarditis and CABG+ MVrep. The repair of tricuspid valve was done for 14 patients (28%) either with MVR or DVR. 4 patients (8%) had CABG +AVR for their combined lesions and another equal number of two patients (4%) underwent redo CABG and AVR + conduit (valve separate tube graft operation). prolonged ventilation occurred in 20% of the cases. An equal percentage of 6% of the patients had to return to the operative room and had postoperative MI. Renal failure occurred in 4% of the patients and as far as 30-day mortality is concerned, a similar 4% of patients died within this period. EF and FS were very similar when compared together (41.8 ± 6.32 %, 20.8 ± 2.35 % preoperatively compared to 41.92 ± 7.49%, 20.85 ± 3.25% postoperatively). P value was insignificant (0.937 and 0.929) respectively. Conclusion: A single dose of an HTK cardioplegic solution provides good myocardial protection in complex cardiac surgery with mild to moderate impairment of LV function and has a good immediate postoperative outcome

Polarizing versus depolarizing blood cardioplegia: An experimental study of myocardial function, metabolism and ultrastructure following cardiopulmonary bypass and cardioplegic arrest

In cardiothoracic surgery, the use of the heart-lung machine for cardiopulmonary bypass (CPB) and induced cardiac arrest, cardioplegia, is required for performing the majority of the surgical procedures. Myocardial protection is essential during the ischemic period of cardioplegia. The aim of this project is to evaluate and verify if a recently developed routine for myocardial protection is feasible, safe and suited for use in clinical practice. This pre-clinical translational animal research project is designed to bridge the gap between basic research and new routines that may benefit the patient. In three different protocols, two groups of animals (10 in each group) are randomized to polarized or depolarized cardioplegic arrest. The novel and unexplored cardioplegic solution with esmolol, adenosine and magnesium; St Thomas’ Hospital polarizing cardioplegia (STH-POL) is compared with today’s gold standard; potassium-based St Thomas’ depolarizing solution (STH-2), both administered as repeated, cold, oxygenated blood. Left ventricular regional and global function in the early hours after weaning from CPB are evaluated together with myocardial ultrastructure and metabolism. Our hypothesis is that STH-POL improves myocardial protection demonstrated as better preserved postoperative cardiac function in a large animal translational model. This knowledge is essential before initiating clinical studies and implementation. An optimal myocardial protection is important when performing cardiac surgery in an ageing population with increased occurrence of more complex heart diseases and comorbidity. Paper I demonstrated improved regional and global contractility following 60 min of cardioplegic arrest with STH-POL compared to STH-2 blood cardioplegia. After weaning from CPB and following reperfusion, left ventricular dP/dtmax, Preload Recruitable Stroke Work and radial peak systolic strain rate were maintained 180 min after declamping in the group with polarized arrest and decreased with depolarized arrest. Paper II focused on energy metabolism and ultrastructure with the STH-POL compared to the STH-2 cardioplegia during 60 min of cardiac arrest and at early reperfusion. The study demonstrated increased levels of creatine phosphate in left ventricular myocardial tissue samples at the end of the period of cardioplegic arrest and early after reperfusion in the STH-POL compared to the STH-2 group. Furthermore, the adenosine triphosphate content was increased and the mitochondrial surface-to-volume ratio decreased with polarizing compared to depolarizing cardioplegia 20 min after reperfusion. However, at 180 min after reperfusion these group differences were negligible. Paper III addressed myocardial function after prolonged cardioplegic arrest for 120 min. A temporary increase in the load-independent contractility variable Preload Recruitable Stroke Work was seen in the STH-POL compared to the STH-2 group 150 min after declamping. Neither regional nor global left ventricular function differed between groups up to 240 min after declamping. However, compared to the STH-2 group, the left ventricular myocardial tissue blood flow rate decreased in the STHPOL group at 150 and 240 min compared to 60 min after declamping. The relationship between the left ventricular total pressure-volume area and blood flow rate was maintained after declamping in the STH-POL group and decreased in the STH-2 group. Thus, cardioplegic arrest with STH-POL alleviated the mismatch between myocardial function and perfusion after weaning from CPB compared to STH-2. Conclusion: In a porcine model, cardioplegic arrest with St. Thomas´ Hospital polarizing solution offered comparable myocardial protection and improved myocardial function (Paper I), preserved energy status (Paper II) and enhanced contractile efficiency (Paper III) in the early hours after weaning from cardiopulmonary bypass compared to St. Thomas´ Hospital No 2 blood cardioplegia

Propofol cardioplegia: A single-center, placebo-controlled, randomized controlled trial

OBJECTIVES: Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is an effective treatment for coronary artery and aortic valve diseases. However, the myocardium sustains reperfusion injury after ischemic cardioplegic arrest. Our objective was to assess the benefits of supplementing cardioplegia solution with the general anesthetic propofol in patients undergoing either coronary artery bypass grafting (CABG) or aortic valve replacement (AVR). METHODS: A single-center, double-blind randomized controlled trial was carried out to compare cardioplegia solution supplemented with propofol (concentration 6 μg/mL) versus intralipid (placebo). The primary outcome was cardiac troponin T release over the first 48 hours after surgery. RESULTS: We recruited 101 participants (51 in the propofol group, 50 in the intralipid group); 61 underwent CABG and 40 underwent AVR. All participants were followed to 3 months. Cardiac troponin T release was on average 15% lower with propofol supplementation (geometric mean ratio, 0.85; 95% confidence interval [CI], 0.73-1.01; P = .051). There were no differences for CABG participants but propofol-supplemented participants undergoing AVR had poorer postoperative renal function (geometric mean ratio, 1.071; 95% CI, 1.019-1.125; P = .007), with a trend toward longer intensive care stay (median, 89.5 vs 47.0 hours; hazard ratio, 0.58; 95% CI, 0.31-1.09; P = .09) and fewer with perfect health (based on the EQ-5D health utility index) at 3 months (odds ratio, 0.26; 95% CI, 0.06-1.05; P = .058) compared with the intralipid group. Safety profiles were similar. There were no deaths. CONCLUSIONS: Propofol supplementation in cardioplegia appears to be cardioprotective. Its influence on early clinical outcomes may differ between CABG and AVR surgery. A larger, multicenter study is needed to confirm or refute these suggestions