Efeitos das cardioplegias sangüíneas hipotérmica e normotérmica nos substratos intracelulares em pacientes com corações hipertróficos. Rev Bras Cir Cardiovasc 2000; 15(2): 160-8. RESUMO: Objetivos: As cardioplegias sangüíneas normotérmica e hipotérmica, administradas de maneira anterógrada e intermitente, têm demonstrado serem eficientes na proteção miocárdica em cirurgias de revascularização miocárdica. Entretanto, pouco se conhece da eficiência dessas técnicas em corações hipertróficos. Dessa maneira, foram estudados seus efeitos nos substratos intracelulares miocárdicos em pacientes portadores de estenose aórtica, submetidos a cirurgia de troca valvar aórtica.Casuística e Métodos: A concentração intracelular miocárdica dos substratos (ATP, lactato, glutamato, aspartato e alanina) foi medida em biópsias de ventrículo esquerdo de 20 pacientes submetidos a troca valvar aórtica, usando, como método de proteção miocárdica, cardioplegia sangüínea normotérmica (n=10) ou hipotérmica (n=10), administradas de forma anterógrada e intermitente. As biópsias foram retiradas 5 minutos após o início da circulação extracorpórea (controle), 30 minutos após o pinçamento aórtico (isquemia) e 20 minutos após o despinçamento (reperfusão).Resultados: Não houve alterações significantes na concentração intracelular dos substratos nas amostras coletadas durante o período isquêmico, em comparação ao controle. Na reperfusão, entretanto, houve significante queda nos valores de ATP e aminoácidos em ambos os grupos, em relação ao grupo controle.Conclusão: Os dados sugerem que ambos os protocolos de proteção miocárdica empregados não foram eficientes na proteção miocárdica de corações hipertróficos. DESCRITORES: Parada cardíaca induzida. Soluções cardioplégicas. Valva aórtica, cirurgia. Miocárdio, patologia. Miocárdio, fisiologia. Hipotermia induzida.Walter J. GOMES*, Raimondo ASCIONE**, M-Saadeh SULEIMAN**, Alan J. BRYAN**, Gianni D. ANGELINI** INTRODUÇÃOAs técnicas e estratégias de proteção miocárdica em cirurgia cardíaca têm sido profundamente alteradas nas últimas décadas. Essa evolução com contínuo aprimoramento tem sido possível através de intenso trabalho baseado em estudos de metabolismo aeróbio e anaeróbio do coração, cuidadosa observação em laboratório e subseqüente aplicação clínica. Lesões miocárdicas decorrentes da

Introduction Cardiac surgery with cardiopulmonary bypass and cardioplegic arrest is known to be responsible for ischaemia and reperfusion organ injury. In a previous study, ProMPT, in patients undergoing coronary artery bypass or aortic valve surgery we demonstrated improved cardiac protection when supplementing the cardioplegia solution with propofol (6 mcg/ml). The aim of the ProMPT2 study is to determine whether higher levels of propofol added to the cardioplegia could result in increased cardiac protection. Methods and Analysis The ProMPT2 study is a multi-centre, parallel, three-group, randomised controlled trial in adults undergoing non-emergency isolated coronary artery bypass graft surgery with cardiopulmonary bypass. A total of 240 patients will be randomised in a 1:1:1 ratio to receive either cardioplegia supplementation with high dose of propofol (12 mcg/ml), low dose of propofol (6 mcg/ml) or placebo (saline). The primary outcome is myocardial injury, assessed by serial measurements of myocardial troponin T up to 48 hours after surgery. Secondary outcomes include biomarkers of renal function (creatinine) and metabolism (lactate). Ethics and Dissemination The trial received research ethics approval from South Central – Berkshire B Research Ethics Committee and Medicines and Healthcare products Regulatory Agency in September 2018. Any findings will be shared though peer-reviewed publications and presented at international and national meetings. Participants will be informed of results through patient organisations and newsletters. Trial Registration ISRCTN15255199. Registered in March 2019.

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IntroductionChanges in cardiac metabolites in adult patients undergoing open-heart surgery using ischemic cardioplegic arrest have largely been reported for non-ventricular tissue or diseased left ventricular tissue, with few studies attempting to assess such changes in both ventricular chambers. It is also unknown whether such changes are altered in different pathologies or linked to the degree of reperfusion injury and inflammatory response. The aim of the present work was to address these issues by monitoring myocardial metabolites in both ventricles and to establish whether these changes are linked to reperfusion injury and inflammatory/stress response in patients undergoing surgery using cold blood cardioplegia for either coronary artery bypass graft (CABG, n = 25) or aortic valve replacement (AVR, n = 16).MethodsVentricular biopsies from both left (LV) and right (RV) ventricles were collected before ischemic cardioplegic arrest and 20 min after reperfusion. The biopsies were processed for measuring selected metabolites (adenine nucleotides, purines, and amino acids) using HPLC. Blood markers of cardiac injury (Troponin I, cTnI), inflammation (IL- 6, IL-8, Il-10, and TNFα, measured using Multiplex) and oxidative stress (Myeloperoxidase, MPO) were measured pre- and up to 72 hours post-operatively.ResultsThe CABG group had a significantly shorter ischemic cardioplegic arrest time (38.6 ± 2.3 min) compared to AVR group (63.0 ± 4.9 min, p = 2 x 10−6). Cardiac injury (cTnI release) was similar for both CABG and AVR groups. The inflammatory markers IL-6 and Il-8 were significantly higher in CABG patients compared to AVR patients. Metabolic markers of cardiac ischemic stress were relatively and significantly more altered in the LV of CABG patients. Comparing diabetic and non-diabetic CABG patients shows that only the RV of diabetic patients sustained major ischemic stress during reperfusion and that diabetic patients had a significantly higher inflammatory response.DiscussionCABG patients sustain relatively more ischemic stress, systemic inflammatory response and similar injury and oxidative stress compared to AVR patients despite having significantly shorter cross-clamp time. The higher inflammatory response in CABG patients appears to be at least partly driven by a higher incidence of diabetes amongst CABG patients. In addition to pathology, the use of cold blood cardioplegic arrest may underlie these differences.