Objectives: When used as a cardioplegic solution, Custodiol® HTK solution is typically administered in a single-dose, allowing the operation to be performed continuously. This is an advantage over alternative cardioplegic solutions that may have to be re-administered every 20-30 minutes. Although Custodiol is widely used as a cardioplegic solution in Europe, its use for myocardial protection remains an off-label indication in the United States. Thus, the aim of this study is to compare the efficacy of Custodiol to standard 4:1 blood cardioplegia in adult cardiac cases. METHODS: This study was a single-center retrospective review of prospectively collected data. Adult cardiac cases performed between November 2011 and August 2013 using Custodiol® were compared to cases using standard Plegisol® 4:1 blood cardioplegia. Twenty-six primary intra-operative and post-operative endpoints were compared including 30-day mortality, 30-day hospital readmission, prolonged mechanical ventilation time, and renal failure. RESULTS: Of the 229 cases identified, 63 cases used Custodiol and 166 used 4:1 blood cardioplegia. Demographics were similar in both groups with a mean patient age of 65.27±15.07 years for Custodiol and 66.72±12.85 years for 4:1 blood cardioplegia. The average cardiopulmonary bypass time for Custodiol and 4:1 blood cardioplegia was 124.76±61.45 and 137.93±54.05 minutes respectively. The Custodiol group had a greater incidence of prolonged ventilation (>24 hours), 20.6% versus 15.1% respectively, and this approached statistical significance with a p value of 0.052. Intra-operative blood usage was significantly higher in the Custodiol group compared to the blood cardioplegia group, with 44.4% of patients receiving fresh frozen plasma during the operation compared to only 25.3% in the blood cardioplegia group (p=0.005). The results revealed no statistically significant difference in 30-day mortality, 30-day hospital readmission, renal failure, and stroke. CONCLUSION: Despite the distinct advantage of long-term ischemic tolerance, Custodiol use was associated with an increased requirement for fresh frozen plasma during the perioperative period when compared to blood cardioplegia.

Resistin, an adipocyte-derived hormone, is thought to represent a link between obesity and insulin-resistant diabetes. The potential role of resistin as a cardioprotective agent has not been explored. Our hypothesis is that resistin has a cardioprotective effect that is mediated by the resistin receptor-coupled activation of PI3K/Akt/PKC/KATP dependent pathways. Our studies demonstrated that pretreatment of mouse hearts with 10 nM resistin for 5 min protected the heart against I/R injury in a mouse heart perfusion model. When mouse hearts were subjected to 60 min of LAD ligation followed by 4 h of reperfusion, resistin pretreatment (33 μg/kg) for 30 min or 24 h before ligation was able to significantly reduce the infarct size/risk area. The protective effect of resistin was abolished by wortmannin, as well as by an Akt inhibitor, triciribine. Resistin's protective effect was absent in Akt kinase-deficient mutant mice. The protective effect was also blocked by chelerythrine, a PKC inhibitor, and εV1-2, a PKCε inhibitor. Finally, the protective effect was blocked by 5-hydroxydecanoate, which blocks the opening of mitoKATP channels. Resistin-induced Akt phosphorylation in HL-1 cells was inhibited by wortmannin and triciribine. Resistin also induced PKCε phosphorylation, which was blocked by triciribine. These studies demonstrate that resistin's cardioprotective effect is mediated by PI3K/Akt/PKC dependent pathways. In addition to cardiomyocytes, resistin also induced Akt phosphorylation in endothelial cells and smooth muscle cells, suggesting that resistin receptors are present in these cells. The effect of resistin on apoptosis was assessed in hearts subjected to 30 min of ischemia and 3 h of reperfusion. There were significantly fewer in situ oligo ligation-positive myocyte nuclei in mice treated with resistin. Our results show that resistin can dramatically reduce apoptosis and infarct size, thus protecting the heart against I/R injury.

The purpose of this study was to determine if del Nido cardioplegia provides superior protection for aged and young adult hearts. We used our isolated working heart model of cardioplegic arrest and reperfusion to compare functional recovery in both senescent and young adult rat hearts, with delivery of del Nido or our standard cardioplegia. In the aged hearts, use of del Nido cardioplegia prevented spontaneous contractions during arrest, reduced troponin release, and provided superior functional recovery during working heart. In contrast, in the young adult hearts, although stroke work was higher in the del Nido group, there were no significant differences in spontaneous activity, troponin release, and cardiac output between del Nido and standard cardioplegia, suggesting that del Nido cardioplegia did not provide superior functional recovery in the young adult heart. Del Nido cardioplegia has the potential to provide superior myocardial protection for elderly patients undergoing cardiac surgery.

Background: Combined valvular and coronary artery bypass grafting (CAB G) surgery requires a long period of cardioplegic arrest (CA) that predisposes the heart to ischaemiareperfusion injury, low cardiac output syndrome, reperfusion dysrhythmias, inhospital mortality and increased costs. Procedures that can reduce the duration of CA would be expected to reduce intraoperative and postoperative complications. Mehods: Adults undergoing combined valvular and CABG surgery were randomized to either coronary surgery performed on the beating heart with cardiopulmonary bypass (CPB) support followed by CA for the valvular procedure (hybrid group) or surgery with both procedures carried out under CA (conventional group). The primary outcome was a composite of in-hospital death, postoperative myocardial infarction, cardiac dysrhythmias, requirements for cardiac pacing for more than 12 hours and/or inotropic support for more than 12 hours postoperativeiy. Results: One hundred and sixty patients (80 hybrid, 80 conventional) were randomized between March 2008 and July 2012. Mean age was 66.5 years and 74% were male. Valvular procedures included aortic (61.8%) and mitral (33.1%) alone or in combination (5.l %). The primary outcome occurred in 64/80 of the conventional group patients and 67/80 of the hybrid group patients (odds ratio 1.24, 95% Cl 0.54 to 2.86, p=0.61). The CA time was, on average, 16% shorter in the hybrid group (median 98 minutes vs. 89 minutes, geometric mean ration (GMR) 0.84, 95% Cl 0.77 to 0.93 , p=0.0004), but the overall duration of CPB was on average 7% longer in the hybrid group (GMR 1.07, 95% Cl 0.98 to 1.16, p=0.12). Cardiac troponin T plasma concentrations and levels of metabolites measured in heart biopsies were similar between the two treatment groups. Conclusion: The hybrid technique reduced the CA time, but this did not result in a significant reduction in the frequency of the primary outcome. In this trial the clinical outcomes and the extent of the myocardial injury were similar between the two surgical methods.

Heme oxygenase (HO)-1 converts heme to bilirubin, carbon monoxide, and iron. Our prior work has suggested a cardioprotective role for HO-1 in heart failure. To test whether HO-1 (heat shock protein 32) prevents cardiomyocyte apoptosis and cardiac dysfunction after ischemia-reperfusion (I/R), we generated transgenic mice overexpressing HO-1 in the heart under the control of the α-myosin heavy chain promoter. HO-1 transcript and protein increased markedly in the heart only. In an isolated heart preparation, we observed an enhanced functional recovery during reperfusion after ischemia in the transgenic hearts compared with nontransgenic controls. I/R injury was also performed in intact animals by coronary ligation and reperfusion to assess the protective role of HO-1 overexpression on heart apoptosis. HO-1 overexpression reduced cardiac apoptosis, as evidenced by fewer terminal deoxynucleodidyl transferase-mediated dUTP nick-end labeling-positive or in situ oligo ligation-positive myocytes, compared with nontransgenic mice. Our results indicate that cardioselective overexpression of HO-1 exerts a cardioprotective effect after myocardial I/R in mice, and this effect is probably mediated via an antiapoptotic action of HO-1.

Le succès de la chirurgie cardiaque dépend essentiellement de la préservation des tissus durant l'opération. Afin d'optimiser cette dernière, une protection myocardique est appliquée à travers la perfusion d'une cardioplégie hypothermique lui permettant de tolérer l'ischémie provoquée par l'absence de vascularisation. Malgré ces progrès techniques et les connaissances accumulées, la chirurgie cardiaque reste une chirurgie à risque dont les complications sont parfois de nature inconnue. Il n'existe pourtant pas de suivi opérationnel de la protection myocardique et les seules indications disponibles pour le chirurgien sont l'arrêt contractile du cœur en début de cardioplégie ou l'apparition de fibrillations cardiaques dénonçant une inefficacité à long terme de la cardioplégie. Parmi les paramètres de mesure pouvant contribuer à la surveillance du myocarde sous cardioplégie, le suivi du changement de température induit par celle-ci pourrait devenir un indicateur pertinent. L'objectif de ce travail de thèse est donc de mettre en place un dispositif de suivi thermique du cœur permettant d'évaluer concrètement la diffusion et l'efficacité de perfusion cardioplégique durant la chirurgie cardiovasculaire.Parmi les méthodes de suivi thermique non invasives implantables en salle d'opération, la thermométrie par ultrasons (TUS) et la thermographie par infrarouges (TIR) ont retenu notre attention. Dans un premier temps, une méthode directe de thermométrie par ultrasons basée sur le principe "d'écho tracking" est expérimentée via un capteur ultrasonore $2,25 MHz mono-élément sur une gamme de température de 10 à 30°C. Cependant la caractérisation du muscle cardiaque par ultrasons et les expérimentations menées en laboratoire ont mis en avant la complexité du milieu nécessitant une calibration préalable, difficile à mettre en place en conditions opératoires. La technique présente tout de même une précision de mesure satisfaisante pour une variation de température inférieure à 10°C. Un modèle d'ajustement est alors proposé afin d'identifier la tendance de réchauffement interne du cœur à partir de la température de surface mesurable via une caméra thermique à infrarouge et par l'estimation volumique du milieu par ultrasons. Le modèle est validé dans un premier temps par simulation par éléments finis et dans un second temps durant des expérimentations sur fantômes et cœur in-vitro.Au final, le dispositif multi-physique TIR et TUS est expérimenté sur modèle in-vivo lors d'opérations, durant lesquelles des sessions de refroidissement par cardioplégie hypothermique sont effectuées. L'étude se conclut sur des premiers résultats de suivi thermique satisfaisants où les températures surfaciques acquises par TIR et l'estimation de l'épaisseur des parois ventriculaires par ultrasons permettent d'obtenir efficacement la tendance de réchauffement du myocarde. Le dispositif multi-physique a également démontré la possibilité d'appliquer une calibration directe de la thermométrie ultrasonore. Cette étude de faisabilité a démontré la possibilité d'un monitoring thermique du cœur de manière non invasive et applicable en temps réel. Ce dispositif pourrait être, après adaptation spécifique, implémenté durant les interventions cardio-vasculaire et fournir un indicateur précieux aux chirurgiens quant à l'efficacité de la protection myocardique. / The success of cardiac surgery essentially depends on tissue preservation. To optimize this latter, a myocardial protection is applied thanks to a hypothermic cardioplegia that confers a marked protective effect to the heart under ischemia. Despite these technical developments, cardiac surgery still presents risks and complications are sometimes of an unknown nature. However, no operational real-time monitoring of myocardial tissue exists. Among the metrics that could be analyzed, the temperature change measurement may be a relevant indicator. The objective of the present thesis is therefore to establish a thermal monitoring system of the heart in a way to evaluate the quality of the cardioplegia perfusion during cardiovascular surgery.Among the non-invasive thermal monitoring methods implantable in the operating room, the ultrasonic thermometry and infrared thermography caught our attention. In the first stages of the study, a direct method of ultrasonic thermometry based on the echo tracking is performed on in-vitro samples with 2.25 MHz ultrasonic sensor in a temperature range between 10 to 30°C. The ultrasonic characterization of the heart muscle and the laboratory experiments brought to the forth an environmental complexity requiring prior calibration that may be difficult to implement in operational conditions. However, the technique has a satisfactory measurement accuracy for temperature variations of less than 10°C.An adjustment model is then proposed to identify the in-depth warming trend of the heart thanks to the surface temperature measurement performed by thermal infrared camera and the medium thickness estimated by ultrasound. The model is validated by finite element simulations and experiments realized on ghosts and in-vitro heart samples.Finally, the device is experimented on in-vivo animal models while hypothermic cardioplegia were conducted. Conclusive results were obtained on the heart thermal monitoring. In particular, the surface temperatures acquired by infrared thermography and the thickness estimation of the ventricular walls by ultrasound allowed an estimation of the myocardial-warming trend.This feasibility study has demonstrated the possibility of heart thermal monitoring, noninvasively and appropriate in real time. After specific adaptation, this device could be implemented during cardiovascular interventions and provide a valuable indicator for the surgeons about the efficacy of myocardial protection.

Introdução. A Aprotinina parece reduzir o uso de transfusões, o processo inflamatório e o dano miocárdico, pós-CEC. Material e Métodos. Estudo prospectivo randomizado em crianças de 30 dias a 4 anos de idade, submetidas à correção de cardiopatia congênita acianogênica, com CEC e divididas em dois grupos, um denominado Controle (n=9) e o outro, Aprotinina (n=10). Neste, a droga foi administrada imediatamente antes da CEC. A resposta inflamatória sistêmica e disfunções hemostáticas e multiorgânicas foram analisadas por marcadores clínicos e bioquímicos. Foram consideradas significantes as diferenças com p<0,05. Resultados. Os grupos foram semelhantes quanto às variáveis demográficas e intra-operatórias, exceto por maior hemodiluição no Grupo Aprotinina. Não houve benefício quanto aos tempos de ventilação pulmonar mecânica, permanência no CTIP e hospitalar, nem quanto ao uso de inotrópicos e função renal. A relação PaO2/FiO2 (pressão parcial de oxigênio arterial/fração inspirada de oxigênio) apresentou queda significativa com 24 h PO, no Grupo Controle. Ocorreu preservação da concentração plaquetária com a Aprotinina enquanto no grupo Controle houve plaquetopenia desde o início da CEC. As perdas sangüíneas foram semelhantes nos dois grupos. No grupo Aprotinina surgiu leucopenia significativa, em CEC, seguida de leucocitose. Fator de necrose tumoral alfa (TNF-) , Interleucinas (IL)-6, IL-8, IL-10, proporção IL-6/IL-10, troponina I cardíaca (cTnI), fração MB da creatinofosfoquinase (CKMB), transaminase glutâmico-oxalacética (TGO) e fração amino-terminal do peptídio natriurético tipo B (NT-proBNP) não apresentaram diferenças marcantes intergrupos. A proporção IL-6/IL-10 PO aumentou no grupo Controle. A lactatemia e acidose metabólica pós-CEC foi mais intensa no grupo Aprotinina. Não houve complicações com o uso da Aprotinina. Conclusão. A Aprotinina não minimizou as manifestações clínicas e os marcadores séricos de resposta inflamatória sistêmica e miocárdicos, mas preservou quantitativamente as plaquetas. / Introduction. Aprotinin seems to reduce the need for transfusion, the inflammatory process and myocardial damage after extracorporeal circulation (ECC). Material and Methods. A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered immediately before ECC and the systemic inflammatory response and hemostatic and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05. Results. The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the postoperative ICU and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/inspired oxygen fraction ratio (PaO2/FiO2) was significantly reduced 24 h after surgery in the Control Group. Platelet concentration was preserved with the use of Aprotinin, whereas thrombocytopenia occurred in the Control Group since the beginning of ECC. Blood loss was similar for both groups. Significant leukopenia was observed in the Aprotinin Group during ECC, followed by leukocytosis. Tumor necrosis factor alpha (TNF-), interleukins (IL)-6, IL-8, IL-10, IL-6/IL-10 ratio, cardiac troponin I (cTnI), creatine kinase MB fraction (CKMB), glutamic-oxaloacetic transaminase (GOT) and the aminoterminal fraction of natriuretic peptide type B (NT-proBNP) ndid not differ significantly between groups.The postoperative IL-6/IL-10 fraction increased significantly in the Control Group. Post-ECC blood lactate concentration and metabolic acidosis was more intense in the Aprotinin Group. There were no complications with the use of Aprotinin. Conclusion. Aprotinin did not minimize the clinical manifestations or serum markers of the inflammatory, systemic and myocardial response, but quantitatively preserved the platelets.

Introdução. A Aprotinina parece reduzir o uso de transfusões, o processo inflamatório e o dano miocárdico, pós-CEC. Material e Métodos. Estudo prospectivo randomizado em crianças de 30 dias a 4 anos de idade, submetidas à correção de cardiopatia congênita acianogênica, com CEC e divididas em dois grupos, um denominado Controle (n=9) e o outro, Aprotinina (n=10). Neste, a droga foi administrada imediatamente antes da CEC. A resposta inflamatória sistêmica e disfunções hemostáticas e multiorgânicas foram analisadas por marcadores clínicos e bioquímicos. Foram consideradas significantes as diferenças com p<0,05. Resultados. Os grupos foram semelhantes quanto às variáveis demográficas e intra-operatórias, exceto por maior hemodiluição no Grupo Aprotinina. Não houve benefício quanto aos tempos de ventilação pulmonar mecânica, permanência no CTIP e hospitalar, nem quanto ao uso de inotrópicos e função renal. A relação PaO2/FiO2 (pressão parcial de oxigênio arterial/fração inspirada de oxigênio) apresentou queda significativa com 24 h PO, no Grupo Controle. Ocorreu preservação da concentração plaquetária com a Aprotinina enquanto no grupo Controle houve plaquetopenia desde o início da CEC. As perdas sangüíneas foram semelhantes nos dois grupos. No grupo Aprotinina surgiu leucopenia significativa, em CEC, seguida de leucocitose. Fator de necrose tumoral alfa (TNF-) , Interleucinas (IL)-6, IL-8, IL-10, proporção IL-6/IL-10, troponina I cardíaca (cTnI), fração MB da creatinofosfoquinase (CKMB), transaminase glutâmico-oxalacética (TGO) e fração amino-terminal do peptídio natriurético tipo B (NT-proBNP) não apresentaram diferenças marcantes intergrupos. A proporção IL-6/IL-10 PO aumentou no grupo Controle. A lactatemia e acidose metabólica pós-CEC foi mais intensa no grupo Aprotinina. Não houve complicações com o uso da Aprotinina. Conclusão. A Aprotinina não minimizou as manifestações clínicas e os marcadores séricos de resposta inflamatória sistêmica e miocárdicos, mas preservou quantitativamente as plaquetas. / Introduction. Aprotinin seems to reduce the need for transfusion, the inflammatory process and myocardial damage after extracorporeal circulation (ECC). Material and Methods. A prospective randomized study was conducted on children aged 30 days to 4 years submitted to correction of acyanogenic congenital heart disease with ECC and divided into two groups: Control (n=9) and Aprotinin (n=10). In the Aprotinin Group the drug was administered immediately before ECC and the systemic inflammatory response and hemostatic and multiorgan dysfunctions were analyzed on the basis of clinical and biochemical markers. Differences were considered to be significant when P<0.05. Results. The groups were similar regarding demographic and intraoperative variables, except for a greater hemodilution in the Aprotinin Group. The drug had no benefit regarding time of mechanical pulmonary ventilation, permanence in the postoperative ICU and length of hospitalization, or regarding the use of inotropic drugs and renal function. The partial arterial oxygen pressure/inspired oxygen fraction ratio (PaO2/FiO2) was significantly reduced 24 h after surgery in the Control Group. Platelet concentration was preserved with the use of Aprotinin, whereas thrombocytopenia occurred in the Control Group since the beginning of ECC. Blood loss was similar for both groups. Significant leukopenia was observed in the Aprotinin Group during ECC, followed by leukocytosis. Tumor necrosis factor alpha (TNF-), interleukins (IL)-6, IL-8, IL-10, IL-6/IL-10 ratio, cardiac troponin I (cTnI), creatine kinase MB fraction (CKMB), glutamic-oxaloacetic transaminase (GOT) and the aminoterminal fraction of natriuretic peptide type B (NT-proBNP) ndid not differ significantly between groups.The postoperative IL-6/IL-10 fraction increased significantly in the Control Group. Post-ECC blood lactate concentration and metabolic acidosis was more intense in the Aprotinin Group. There were no complications with the use of Aprotinin. Conclusion. Aprotinin did not minimize the clinical manifestations or serum markers of the inflammatory, systemic and myocardial response, but quantitatively preserved the platelets.