Cardioplegic Induction Research Articles

Direct Procurement of Thoracic Organs Along with Abdominal Normothermic Regional Perfusion in Donation After Circulatory Death

<h3>Purpose</h3> Direct procurement of thoracic organs as compared to using abdominal normothermic regional perfusion (aNRP) is the preferred method for thoracic organ procurement in donors after circulatory death (DCD). The use of aNRP improves outcomes from liver transplantation. We have developed a technique for thoracic organ isolation during aNRP that allows successful co-procurement of thoracic and abdominal organs. <h3>Methods</h3> In order to achieve successful thoracic isolation both the brain perfusion and volume loss must be prevented. After certification of circulatory death and a standoff period the thoraco-abdominal incision is performed. Blood is collected from the donor right atrium or a side-arm of the aNRP circuit to prime the organ care system (OCS) before isolation of vascular structures in a systematic way. 1. The left pleura is opened, and the lung retracted to allow identification and clamping of the descending thoracic aorta above the diaphragm. 2. The ascending aorta is clamped, and the aortic arch vented cranial to the clamp. Abdominal NRP can then commence. 3. The inferior vena-cava is clamped within the pericardium. 4. The superior vena-cava and azygos vein are tied off. 5. The heart is vented on the left and right side before induction of cardioplegia. The diagram illustrates complete vascular isolation of the thoracic cavity enabling explantation of the heart and lung after delivery of selective antegrade pneumoplegia while abdominal organs continue to be perfused for 2-hours before the start of abdominal procurement. <h3>Results</h3> Between 2019-21 we successfully performed seven such procurements. Three heart and lungs, three lungs and one heart procurement alone. All organs were successfully implanted with successful immediate outcome in all thoracic and abdominal recipients. <h3>Conclusion</h3> Direct procurement of thoracic organs is a feasible option during aNRP. This will potentially expand the thoracic organ donor pool and improve outcome of liver transplantation.

Blood Cardioplegia Induction, Perfusion Storage and Graft Dysfunction in Cardiac Xenotransplantation.

BackgroundPerioperative cardiac xenograft dysfunction (PCXD) describes a rapidly developing loss of cardiac function after xenotransplantation. PCXD occurs despite genetic modifications to increase compatibility of the heart. We report on the incidence of PCXD using static preservation in ice slush following crystalloid or blood-based cardioplegia versus continuous cold perfusion with XVIVO© heart solution (XHS) based cardioplegia.MethodsBaboons were weight matched to genetically engineered swine heart donors. Cardioplegia volume was 30 cc/kg by donor weight, with del Nido cardioplegia and the addition of 25% by volume of donor whole blood. Continuous perfusion was performed using an XVIVO © Perfusion system with XHS to which baboon RBCs were added.ResultsPCXD was observed in 5/8 that were preserved with crystalloid cardioplegia followed by traditional cold, static storage on ice. By comparison, when blood cardioplegia was used followed by cold, static storage, PCXD occurred in 1/3 hearts and only in 1/5 hearts that were induced with XHS blood cardioplegia followed by continuous perfusion. Survival averaged 17 hours in those with traditional preservation and storage, followed by 11.47 days and 15.03 days using blood cardioplegia and XHS+continuous preservation, respectively. Traditional preservation resulted in more inotropic support and higher average peak serum lactate 14.3±1.7 mmol/L compared to blood cardioplegia 3.6±3.0 mmol/L and continuous perfusion 3.5±1.5 mmol/L.ConclusionBlood cardioplegia induction, alone or followed by XHS perfusion storage, reduced the incidence of PCXD and improved graft function and survival, relative to traditional crystalloid cardioplegia-slush storage alone.

Normothermic blood cardioplegia. Alternative or adjunct?

Normothermic blood cardioplegia was developed originally to be used during cardioplegic induction and reperfusion as an adjunct for enhancing metabolic reversal of biochemical alterations occurring before, during, and after total myocardial ischemia. This adjunct was introduced clinically after extensive experimental testing. By contrast, continuous normothermic blood cardioplegia without hypothermia was introduced clinically without a scientific infrastructure and has generated great interest because of its simplicity and encouraging early results, but has caused substantial confusion. This report is written to (1) clarify the role of normothermic blood cardioplegia as an adjunct to available hypothermic and antegrade and retrograde methods of myocardial protection, rather than as an alternative to them, (2) call attention to the misconception that continuous coronary perfusion avoids ischemia inasmuch as "unintentional ischemia" may occur despite continuous coronary perfusion, (3) identify theoretic and practical limitations of warm continuous retrograde blood cardioplegia exposed by testing after its clinical introduction, (4) enumerate the unanswered questions posed after clinical use of this method, and (5) focus on the self-imposed inflexibility created by adoption of adversarial positions in regard to cardioprotective strategies that impedes our ability to combine, rationally, the spectrum of approaches to myocardial protection that have evolved from the recognized limitations of individual methods.

Epigallocatechin Gallate Reduces Ischemia/Reperfusion Injury in Isolated Perfused Rabbit Hearts.

Cardioplegic arrest during heart operations is often used in cardiac surgery. During cardioplegia, the heart is subjected to a global ischemia/reperfusion-injury. (−)-epigallocatechin gallate (EGCG), one of the main ingredients of green tea, seems to be beneficial in various cardiac diseases. Therefore, the aim of our study was to evaluate EGCG in a rabbit model of cardioplegic arrest. Twenty four mature Chinchilla rabbits were examined. Rabbit hearts were isolated and perfused according to Langendorff. After induction of cardioplegia (without and with 20 µmol/L EGCG, n = 6 each) the hearts maintained arrested for 90-min. Thereafter, the hearts were re-perfused for 60 min. During the entire experiment hemodynamic and functional data were assessed. At the end of each experiment, left ventricular samples were processed for ATP measurements and for histological analysis. Directly after cessation of cardioplegia, all hearts showed the same decline in systolic and diastolic function. However, hearts of the EGCG-group showed a significantly faster and better hemodynamic recovery during reperfusion. In addition, tissue ATP-levels were significantly higher in the EGCG-treated hearts. Histological analysis revealed that markers of nitrosative and oxidative stress were significantly lower in the EGCG group. Thus, addition of EGCG significantly protected the cardiac muscle from ischemia/reperfusion injury.

Improved cardiac protection with Sabax cardioplegia in Langendorff isolated rat hearts

Abstract Objective: Cardioplegia is an important step to facilitate cardiac surgery while limiting intraoperative myocardial injury. Although recent advances in cardioplegic arrest methods have significantly contributed to better postoperative outcomes, there is still controversy regarding the optimal composition and temperature of the cardioplegic solution. Accordingly, we aimed to assess whether cold or lukewarm Sabax cardioplegia offer improved myocardial protection compared with the classical Krebs-Henseleit solution. Methods: The hearts of 40 male Wistar rats were isolated and submitted to constant-flow retrograde perfusion using a Langendorff perfusion apparatus. The hearts were randomly assigned to cold Krebs-Henseleit (K-H), cold Sabax, or lukewarm Sabax cardioplegia. The ECG, heart rates, and left ventricular systolic pressures (LVSP) were recorded pre- and post-cardioplegia. The time needed for cardioplegia induction and post-cardioplegia recovery were also noted. Results: Both cold and lukewarm Sabax cardioplegia insured faster induction and faster recovery following isothermic reperfusion compared to the standard K-H solution (both p&lt; 0.01). With K-H cardioplegia, the hearts presented a 21.7% force loss after reperfusion (p&lt; 0.001), whilst Sabax cardioplegia was associated with a slight increase in ventricular mechanical activity (3% LVSP increase with lukewarm Sabax cardioplegia, p&lt; 0.001 and 2% LVSP increase with cold Sabax cardioplegia, p = 0.02). With Sabax cardioplegia the hearts displayed considerably less major arrhythmic events and presented less significant bradycardia. Conclusions: The present data suggest that Sabax cardioplegia may be superior to the classical cold crystalloid K-H solution in preserving mechanical activity of the heart and may provide superior protection against major arrhythmias.

The effect of tepid amino acid-enriched induction cardioplegia on the outcome of infants undergoing cardiac surgery

Despite promising experimental results, no information has been published on the clinical effects of amino acid-enriched induction cardioplegic solution on outcome in children undergoing cardiac surgery. This is a retrospective study of 185 consecutive patients younger than 12 months with one of the following defects undergoing open heart surgery: atrioventricular septal defect, transposition of the great arteries, tetralogy of Fallot or ventricular septal defect. Patients were divided into two groups according to the following myocardial protection approaches: tepid substrate-enriched induction cardioplegia followed by cold blood cardioplegia (n=113) or only cold blood induction cardioplegia (n=72). Patient allocation was determined by the anesthesiologist in charge of cardiopulmonary bypass (CPB). The primary outcome measure was postoperative myocardial injury assessed by troponin T level and inotrope score. Demographic data were similar for both groups. Cardioplegic induction had no overall effect for inotrope score (16.3 ± 9.2 vs.17.9 ± 10.0, p=0.276) or lactate release (1.8 ± 1.3 vs. 1.6 ± 0.8, p=0.110) on arrival to the paediatric intensive care unit. On the first postoperative day, there were no significant differences between the cardioplegia groups for inotrope score (13.7 ± 8.7 vs.14.3 ± 9.1, p=0.657), troponin T (2.4 ± 1.6 vs. 2.8 ± 2.7 μg/L, p=0.267), lactate (1.5 ± 2.0 vs. 1.5 ± 0.8, p=0.972), or any of the other clinical outcome measures. Compared to cold cardioplegia alone, the administration of tepid induction cardioplegia had no effect on the clinical outcome of infants who underwent cardiac surgery.

Adenosine Bolus Injection Prior to Cardioplegia Enhances Preservation of Heart Grafts in Rats

Introduction: Adenosine opens potassium channels leading to rapid cardiac arrest; has antioxidant, anti-inflammatory and vasodilative properties; and has been used as protective cardioplegia during cardiac surgery. However, adenosine is not administered during organ procurement for cardiac transplants. in this study, we hypothesized that bolus injection of adenosine prior to cardioplegic induction could be an effective adjunct to cardioplegia infusion after cross-clamping the aorta, and may be a clinically accessible alternative to current heart procurement practices.

Myocardial Protective Effect of Human Atrial Natriuretic Peptide in Cardiac Surgery - "hANP Shot" in Clinical Safety Trial -

We studied low-dose human atrial natriuretic peptide (hANP) infusion therapy during cardiac surgery and reported the cardiac and renal protective effects. The efficacy of a bolus injection of hANP (the "hANP shot") simultaneously with induction of cardioplegia has been proven in animal experiments. In the present study the clinical effects of this "hANP shot" were examined. The subjects were 67 patients undergoing Coronary artery bypass grafting. At the time of inducing cardioplegia, 1 group received a simultaneous bolus injection of 100 μg of hANP (hANP group) and the other group received an injection of physiological saline (placebo group). The primary endpoints were (1) operative mortality and complications, and (2) the creatine kinase isoenzyme MB (CPK-MB), troponin-I, and human heart fatty acid binding protein (H-FABP) levels. The secondary endpoints were (1) the incidence of arrhythmia, and levels of (2) atrial and B-type natriuretic peptides, and cyclic guanosine monophosphate (cGMP), and (3) renin, angiotensin II, and aldosterone. Postoperative CPK-MB, troponin-I, and H-FABP levels were significantly lower in the hANP group than in the placebo group. Postoperative arrhythmia was significantly less frequent in the hANP group than in the placebo group. It is possible to achieve cardioprotective effects based on the safety of the "hANP shot", as well as from biomarkers of ischemia and results related to arrhythmia. The "hANP shot" should also be evaluated as a safer and new cardioprotective method for cardiac surgery.

Clinical Study of ATP Cardioplegia On Myocardial Protection

目的 观察外源性ATP对心肌保护作用.方法将30例心脏手术患者随机分为实验组(A组)15例和对照组(B组)1 5例,A组采用含ATP的st.Thomas Ⅱ号停跳液,B组采用st.Thomas Ⅱ号停跳液,分别以临床效果、血中肌钙蛋白T(CTnT)评价两种诱导停跳液方法的心肌保护作用.结果(1)实验组停跳液能达到与对照组停跳液同样好的停跳效果;(2)心脏自动复跳率实验组(93.3%)明显高于对照组(66.7%),实验组拔管时间以及在ICU停留时间都明显短于对照组;(3)心肌形态学:实验组明显优于对照组.结论ATP停跳液较单纯晶体停跳液具有更好的心肌保护作用。

Blood cardioplegia

We present the technical details of blood cardioplegia as the standard clinical practice in most centers today. In addition, the contribution refers to the advanced strategies using blood cardioplegia in specific situations, including warm cardioplegia induction, controlled reperfusion in acute myocardial infarction, and the application of leucocyte filtration.

&lt;![CDATA[Myocardial metabolism after hypothermic retrograde continuous blood cardioplegia with anterograde warm cardioplegic induction]]&gt;

&lt;![CDATA[Myocardial metabolism after hypothermic retrograde continuous blood cardioplegia with anterograde warm cardioplegic induction]]&gt;

Metabolismo miocárdico após cardioplegia sangüínea hipotérmica retrógrada contínua com indução anterógrada normotérmica

OBJECTIVE: To determinate the alterations suffering by myocardium in the hypothermic retrograde continuous blood cardioplegia with antegrade warm cardioplegic induction. METHOD: A metabolic analysis of hypothermic retrograde continuous blood cardioplegia with antegrade warm cardioplegic induction was performed in a prospective study of 15 patients scheduled for elective coronary artery bypass grafting. Arterial and coronary sinus blood samples were simultaneously taken: before establishing cardiopulmonary bypass, after anterograde warm cardioplegic induction, when the aortic clamp was removed and 10, 30 and 60 minutes after reperfusion to analyze the oxygen content and lactate concentration. Four transmural left ventricular biopsy samples were obtained: before aortic clamping, immediately after the initial cardioplegia bolus, immediately before aortic declamping and 30 minutes after reperfusion to analyze the levels of ATP, ADP, AMP and lactate in the myocardium. The CK-MB isoenzyme was analysed in venous blood samples. RESULTS: There were no mortalities in the group. Inotropic support was not necessary in any patients and no peri- or post-operative myocardial infarction was detected. There was a decrease in the arterial-venous extraction of oxygen and lactate in the heart during reperfusion, a partial recovery occurred at 60 minutes of reperfusion. The levels of ATP and the other nucleotides in the myocardium were maintained during aortic clamping, but these levels decreased during the first 30 minutes of reperfusion. The lactate accumulated in the heart muscle during aortic clamping with a decrease occurring during reperfusion. CONCLUSIONS: From a metabolic point of view the method could not avoid an anaerobic metabolism during cross-clamping and only after 60 minutes of reperfusion there was a satisfactory metabolic recovery. These alterations are probably a reflection of cellular ischemic injury that occurs during cross-clamping and they seem to be of transitory effect. A better myocardium protection was observed with the addiction of anterograde warm induction cardioplegia.

Myocardial Protection of Warm Cardioplegic Induction on the Isolated Perfused Rat Heart Model

Myocardial protection through different cardioplegia approaches is an important issue for successful cardiovascular surgery. The objective of this prospective randomized study was to evaluate the effect of myocardial protection of warm (37°C) and cold (6°C) cardioplegic induction, respectively, using a Langendorff isolated rat heart perfusion model. Twenty-eight isolated rat hearts on the Langendorff perfusion model were randomly divided into two groups: group T (n 14) received warm (37°C) cardioplegic induction, followed by cold (6°C) cardioplegia after ECG showed straight line; alternatively, group C (n 14) received only cold cardioplegic induction. After undergoing ischemia for 80 min, both group T and group C received reperfusion with Krebs-Henseleit Buffer (KHB) for 40 min. An additional group A (n 7) received KHB continuously for 120 min and served as the control group for the assessment of Na+/K+ATPase activity. The coronary flow, concentration of creatine kinase (CK) in coronary effluent, and cardiac function were evaluated at different time periods. Na+/K+˚TPase activity was assessed at the end of reperfusion. The coronary flow, content of CK in coronary effluent, heart rate, dp/dtmax, and left ventricular peak pressure (LVPP) were significantly greater (p &lt; .05) in group T than group C during the reperfusion period. The negative value of -dp/dtmax and left ventricular end-diastolic pressure (LVEDP) was significantly lower (p &lt; .05) in group T than group C, during the reperfusion period. The Na+/K+-ATPase activity assessed at the end of reperfusion period was significantly higher (p &lt; .05) in group A and group T than group C, while no significant difference (p .13) was found between group T and group A. Compared with cold cardioplegic induction, warm cardioplegic induction provides superior myocardial protection by enhancing coronary flow, reducing myocardial injury, improving cardiac function, and preserving Na+/K+-ATPase activity.

Cardioplegic Induction with Adenosine Improves Post-Ischemic Function in Coronary Artery Bypass Surgery

Cardioplegic Induction with Adenosine Improves Post-Ischemic Function in Coronary Artery Bypass Surgery

Myocardial interstitial glucose and lactate before, during, and after cardioplegic heart arrest

The interstitial fluid of the human myocardium was monitored in 13 patients undergoing aortic valve and/or bypass surgery before, during, and after hypothermic potassium cardioplegia. The regulation of glucose and lactate was studied after sampling with microdialysis. The following questions were addressed. 1). Is the rate of transcapillary diffusion the limiting step for myocardial uptake of glucose before or after cardioplegia? 2). Does cold potassium cardioplegia induce a critical deprivation of glucose and/or accumulation of lactate in the myocardium? Before cardioplegia, interstitial glucose was approximately 50% of the plasma level (P < 0.001). Interstitial glucose decreased significantly immediately after induction of cardioplegia and remained low (1.25 +/- 0.25 mM) throughout cardioplegia. It was restored to precardioplegic levels 1 h after release of the aortic clamp. Interstitial glucose then decreased again at 25 and 35 h postoperatively to the levels observed during cardioplegia. Interstitial lactate decreased immediately after induction of cardioplegia but returned to basal level during the clamping period. At 25 and 35 h, interstitial lactate was significantly lower than before and during cardioplegia. Glucose transport over the capillary endothelium is considered rate limiting for its uptake in the working heart but not during cold potassium cardioplegia despite the glucose deprivation following perfusion of glucose-free cardioplegic solution. Lactate accumulated during cardioplegia but never reached exceedingly high interstitial levels. We conclude that microdialysis provides information that may be relevant for myocardial protection during open-heart surgery.

Delivery of a nonpotassium modified maintenance solution to enhance myocardial protection in stressed neonatal hearts: A new approach

Objectives: This study was undertaken to compare conventional cardioplegic strategies with a new approach that uses a modified nonpotassium maintenance solution between cardioplegia doses in stressed neonatal hearts. Methods: Thirty-five neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of ischemia on cardiopulmonary bypass. In 10 animals bypass was discontinued without further ischemia (stress control group). The other 25 received a warm blood cardioplegic induction and were separated into 5 groups. In 5 animals cardiopulmonary bypass was discontinued without further ischemia (cardioplegia control group); the remaining 20 underwent an additional 70 minutes of cold blood cardioplegic arrest. Five received only intermittent cardioplegia every 20 minutes, whereas 15 also received cold blood maintenance infusions between cardioplegic doses (integrated strategy). In 5 of these animals the blood was unmodified, whereas in 10 a modified nonpotassium “cardioplegia-like” solution was delivered either antegradely (n = 5) or retrogradely (n = 5). Myocardial function was assessed by pressure-volume loops (expressed as percentage of control); vascular function was assessed by coronary vascular resistance. Results: All piglets that underwent hypoxic ischemic stress alone (controls) died. Warm induction alone (cardioplegic controls) partially repaired the stress injury. Intermittent cardioplegia preserved the depressed systolic function (end-systolic elastance 40% vs 39%), increased diastolic stiffness (255% vs 239%), reduced adenosine triphosphate (10.6 vs 12.2 μg/g tissue), and elevated coronary vascular resistance at levels identical to warm induction alone; infusing unmodified blood between cardioplegia doses (standard integrated) improved results slightly. In contrast, infusion of a cold modified solution (antegrade or retrograde) between cardioplegia doses (modified integrated) completely restored systolic function (end-systolic elastance 100% and 97%, P <.001 vs intermittent and standard integrated), only minimally increased diastolic stiffness (159% and 156%, P <.001 vs intermittent and standard integrated), restored adenosine triphosphate (18.8 and 16.6 μg/g, P <.001 vs intermittent and standard integrated), and normalized coronary vascular resistance (P <.001 vs intermittent and standard integrated). This strategy was used in 72 consecutive hypoxic patients (21 arterial switch operations, retrograde; 51 Fontan procedures, antegrade) with a 2.8% mortality. Conclusions: Infusion of a cold modified solution between cardioplegic doses (modified integrated protection) significantly improved myocardial protection in the stressed neonatal heart, was effective delivered either antegradely or retrogradely, and was used successfully for hypoxic (stressed) pediatric patients.

Delivery of a nonpotassium modified maintenance solution to enhance myocardial protection in stressed neonatal hearts: A new approach

This study was undertaken to compare conventional cardioplegic strategies with a new approach that uses a modified non-potassium maintenance solution between cardioplegia doses in stressed neonatal hearts. Thirty-five neonatal piglets underwent 60 minutes of ventilator hypoxia (inspired oxygen fraction 8%-10%) followed by 20 minutes of ischemia on cardiopulmonary bypass. In 10 animals bypass was discontinued without further ischemia (stress control group). The other 25 received a warm blood cardioplegic induction and were separated into 5 groups. In 5 animals cardiopulmonary bypass was discontinued without further ischemia (cardioplegia control group); the remaining 20 underwent an additional 70 minutes of cold blood cardioplegic arrest. Five received only intermittent cardioplegia every 20 minutes, whereas 15 also received cold blood maintenance infusions between cardioplegic doses (integrated strategy). In 5 of these animals the blood was unmodified, whereas in 10 a modified non-potassium "cardioplegia-like" solution was delivered either antegradely (n = 5) or retrogradely (n = 5). Myocardial function was assessed by pressure-volume loops (expressed as percentage of control); vascular function was assessed by coronary vascular resistance. All piglets that underwent hypoxic ischemic stress alone (controls) died. Warm induction alone (cardioplegic controls) partially repaired the stress injury. Intermittent cardioplegia preserved the depressed systolic function (end-systolic elastance 40% vs 39%), increased diastolic stiffness (255% vs 239%), reduced adenosine triphosphate (10.6 vs 12.2 microg/g tissue), and elevated coronary vascular resistance at levels identical to warm induction alone; infusing unmodified blood between cardioplegia doses (standard integrated) improved results slightly. In contrast, infusion of a cold modified solution (antegrade or retrograde) between cardioplegia doses (modified integrated) completely restored systolic function (end-systolic elastance 100% and 97%, P <.001 vs intermittent and standard integrated), only minimally increased diastolic stiffness (159% and 156%, P <.001 vs intermittent and standard integrated), restored adenosine triphosphate (18.8 and 16.6 microg/g, P <.001 vs intermittent and standard integrated), and normalized coronary vascular resistance (P <.001 vs intermittent and standard integrated). This strategy was used in 72 consecutive hypoxic patients (21 arterial switch operations, retrograde; 51 Fontan procedures, antegrade) with a 2.8% mortality. Infusion of a cold modified solution between cardioplegic doses (modified integrated protection) significantly improved myocardial protection in the stressed neonatal heart, was effective delivered either antegradely or retrogradely, and was used successfully for hypoxic (stressed) pediatric patients.

Myocardial Protection of Warm Blood Cardioplegic Induction during Cardiopulmonary Bypass

In his prospective randomized clinical study, we evaluated the myocardial protection of warm blood cardioplegic induction and cold blood cardioplegic induction, respectively, during cardiopulmonary bypass. Twenty-eight adult patients who underwent valve replacement were randomly divided into two groups: group T (14 cases) received cold (6–8°C) blood cardioplegic induction after ECG showed straight line induced by warm (35–37°C) blood cardioplegia; whereas, group C (14 cases) received cold blood cardioplegic induction only. The effects of myocardial protection of both cardioplegic inductions were evaluated by clinical outcomes, myocardial biochemistry index (cardiac troponin T, cTnT), and myocardial automorphology. The ratio of myocardial auto resuscitation was significantly higher in group T (93%) than that in group C (50%). Only one case in group T (7%) and three cases in group C (21%) needed temporary pacemakers. No case in group T (0%) and five cases (36%) in group C received dopamine. The postoperative mechanical ventilation time and ICU stay time of group T were shorter than those of group C. Myocardial biochemistry index— plasma level of cTnT in group T was lower than that of group C immediately and 6 h after cardiopulmonary bypass. Myocardial morphology—group T had comparably better outcomes than group C. We concluded that warm blood cardioplegic induction during cardiopulmonary bypass, compared with cold blood cardioplegic induction, provides better myocardial protection.

Improved preservation of coronary endothelial function with Celsior compared with blood and crystalloid solutions in heart transplantation

Background Endothelial injury from preservation solutions has been implicated in acute coronary vasospasm and pathologic activation of the endothelium, which can contribute to the development of graft coronary vasculopathy after heart transplantation. Preservation solutions with a powerful antioxidant capacity may decrease the occurrence of these complications. Materials and methods This study was designed to evaluate the effect of Celsior (an anti-oxidant solution specifically designed for cardiac preservation) in a model of heart preservation (4 hours at 4° C to reproduce the situation encountered in clinical heart transplantation) compared two commonly used cardioplegic and preservation strategies on coronary endothelial function. Endothelium-dependent relaxation of normal porcine epicardial coronary arteries to serotonin (5-HT, an agonist that activates 5-HT 1d receptors coupled to Gi proteins) and bradykinin (BK, which activates B2 receptors coupled to Gq proteins) was studied in standard organ chamber experiments in the following groups: a control group was submitted to immediate excision without cardioplegia and preserved in saline solution (0.9% NaCl) for 4 hours (Group 1); two groups had cardioplegia induced with a crystalloid solution and were stored for 4 hours in saline (Group 2) or 4 hours in Celsior solution (Group 3); and two groups had cardioplegia induced with normothermic blood cardioplegia and were stored for 4 hours in the saline (Group 4), or 4 hours in Celsior solution (Group 5). Finally, two groups underwent cardioplegia with Celsior and were stored for 4 hours in saline (Group 6), or 4 hours in the Celsior solution (Group 7). All cardioplegia solutions were at 4° C (except blood cardioplegia at 37° C) and all preservations solutions were at 4° C. Results Endothelium-dependent relaxations to serotonin were significantly decreased in all groups except the Celsior + Celsior group compared with the control group. There were no significant differences in relaxation to bradykinin except in one group. Use of the Celsior solution for induction of cardioplegia and storage better preserved endothelium-dependent G-protein–mediated relaxation compared with the other arrest and preservation strategies. Conclusions The observed effect may be associated with an improvement in both short- and long-term outcome in heart transplantation, especially because these alterations may be further compounded by reperfusion.

The role of cardioplegia induction temperature and amino acid enrichment in neonatal myocardial protection

Background. Warm cardioplegic induction improves the ischemically “stressed” adult heart. However, it is rarely used in infants, despite the fact that many newborn hearts are stressed by other factors such as hypoxia. The need for amino acids as well as their mechanism of action has also not been studied. Methods. We first assessed the role of cardioplegic induction temperature in 10 nonhypoxic neonatal piglets undergoing 70 minutes of multidose blood cardioplegic arrest. Five piglets (group 1) received a cold (4°C) induction, and 5 (group 2) a warm (37°C) induction. Twenty-six other piglets underwent ventilator hypoxia (fraction of inspired oxygen, 8% to 10%) for 60 minutes before cardiopulmonary bypass (stress). Six piglets (group 3) then underwent 70 minutes of cardiopulmonary bypass without ischemia (hypoxia controls), and 20 underwent 70 minutes of cardioplegic arrest. Five of these (group 4) received cold cardioplegic induction, and 15 received warm induction; in 5 of these (group 5), the warm cardioplegic solution contained amino acids, in 5 others (group 6), it was unsupplemented, and in the remaining 5 (group 7), nitroglycerin was added to determine the role of vasodilation. Myocardial function was assessed by pressure-volume loops (expressed as a percent of control), and coronary vascular resistance was measured with cardioplegic infusions. Results. In nonhypoxic (normal) piglets, cold (group 1) and warm (group 2) induction completely preserved systolic function (end-systolic elastance, 100% versus 104%) and preload recruitable stroke work (100% versus 102%), with minimal increase in diastolic compliance (162% versus 156%). Hypoxia–reoxygenation alone (group 3) depressed systolic function (end-systolic elastance, 51% ± 2%) and preload recruitable stroke work (54% ± 3%), and raised diastolic stiffness (260% ± 15%). The detrimental effects of reoxygenation persisted (unchanged from reoxygenation alone) with cold induction (group 4) or warm induction without amino acids (groups 6 and 7). In contrast, warm induction with amino acids (group 5) restored systolic function (end-systolic elastance, 105% ± 3%; p < 0.001 versus groups 3, 4, 6, and 7) and preload recruitable stroke work (103% ± 2%; p < 0.001 versus groups 3, 4, 6, and 7), and decreased diastolic stiffness (154% ± 7%; p < 0.001 versus groups 3, 4, 6, and 7). However, there was no difference in myocardial oxygen consumption in hypoxic hearts receiving a warm induction (6.9 versus 6.5 versus 7.3 mL/g per 5 minutes) (groups 5, 6, 7), and coronary vascular resistance was lowest with nitroglycerin (group 7). Conclusions. Cardioplegic induction can be given either warm or cold in nonhypoxic neonatal hearts. In contrast, only warm induction with amino acids repairs the hypoxic injury, but the primary mechanism of action is not related to increased metabolic activity or vasodilation.