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This thesis is a step forward in evaluating insulin therapy and defining its role in cardiac surgery first described as Glucose-Insulin-Potassium (GIK) solution 40 years ago. / Chapter (I) includes a review of the literature on insulin therapy in cardiac surgery and illustrates the scientific bases and controversies in this therapy. / Chapter (II) entitled: "Myocardial Protection During Elective Coronary Artery Bypass Grafting Using High Dose Insulin Therapy" represents a manuscript that was presented in the following meetings: (A) Local meetings: (1) McGill cardiovascular research day, February 1/2007, Montreal, Canada. (2) Fraser Gurd annual research day, McGill surgery department, May 31/2007, Montreal, Canada. (B) National meetings: (1) 11th Annual Terrence Donnelly research day for Canadian cardiac surgery residents, May 26/2007, Toronto, Canada. (C) International meetings: (1) 43rd Annual meeting of the Society of thoracic surgeons (STS), January 30/2007, San Diego, United States. A full manuscript was submitted to "The Annals of Thoracic Surgery" for review. / Chapter (III) entitled: "High Dose Insulin Therapy Attenuates Systemic Inflammatory Response in Patients Undergoing Elective Coronary Artery Bypass Grafting" represents a manuscript that was presented in the following meetings: (A) Local meetings: (1) Fraser Guard McGill Surgery department annual research day, May 3/2006, Montreal, Canada. (B) National meetings: (1) 10th Annual Terrence Donnelly research day for Canadian cardiac surgery residents, May 26/2007, Toronto, Canada. (2) Young investigator forum, Canadian Society of Clinical Investigators (CSCI), September 28/2006, Ottawa, Canada. (3) 59 th annual meeting of Canadian Cardiovascular Society (CCS), October 21/2006, Vancouver, Canada. (C) International meetings: (1) American Heart Association (AHA), November 12/2006, Chicago, United states. / Abstracts from this work were published in the following journals: (1) Clinical and Investigative Medicine, Vol. 29, No. 4, August 2006. (2) The Canadian Journal of Cardiology, Vol. 22 supp D, October 2006 (3) Circulation, Vol. 114 supp, No. 18, October 2006. / A full manuscript was submitted to "the journal of thoracic and cardiovascular surgery" for review.

Orientador: Reinaldo Wilson Vieira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T23:28:36Z (GMT). No. of bitstreams: 1 SilveiraFilho_LindembergdaMota_M.pdf: 22765856 bytes, checksum: 1ca4bc9b50a4a81b4aff9a1c376e5d98 (MD5) Previous issue date: 2006 / Resumo: Introdução: A administração de diferentes agentes associados à cardioplegia tem sido realizada desde o surgimento da proteção miocárdica em Cirurgia Cardíaca. Qualquer medicamento que promova uma melhora na capacidade do coração operado resistir à isquemia, que se traduza em melhora hemodinâmica e de sobrevida, pode ter sua associação à cardioplegia justificada. O agente de manejo metabólico trimetazidine (TMZ), utilizado na prática clínica como agente anti-isquêmico, tem sido usado em pacientes cirúrgicos esporadicamente, não havendo comprovação de sua eficácia quando apenas associado à solução cardioplégica. Objetivo: Verificar em modelo experimental de coração isolado de suínos se a associação do trimetazidine à solução cardioplégica promove melhora no desempenho do coração Material e métodos: O modelo experimental utilizou suínos Large-White, com coração isolado perfundido por suporte de outro animal em modo de execução de trabalho ("working heart state"). Foram divididos em três grupos (n = 6), submetidos a isquemia regional seguido de isquemia global, que recebiam um dos três tratamentos: Solução St Thomas (ST), solução St Thomas acrescida de trimetazidine (TMZ) e grupo controle (Co). Durante período de reperfusão aos 30, 60 e 90 minutos foram medidos parâmetros hemodinâmicos de contratilidade e metabólicos, obtendo-se assim a elastância máxima (Emáx), o índice de trabalho sistólico pré-recrutável (PRSW), "dureza" do ventrículo (EDPRV), fluxo coronariano, consumo de oxigênio e dosagens de lactato e glicose. Os resultados foram analisados estatisticamente Resultados: Em relação aos parâmetros hemodinâmicos de contratilidade não houve diferença estatisticamente significante entre os três grupos. Houve produção crescente de lactato nos três grupos quanto maior o tempo de reperfusão de forma uniforme. O fluxo coronariano, o consumo de oxigênio e o consumo de glicose tiveram grande variação entre os diferentes tempos medidos mas sem diferença entre os três tratamentos. O peso final do ventrículo esquerdo foi significativamente menor no grupo trimetazidine (TMZ) que nos demais. Conclusão: A administração aguda do trimetazidine, associada simplesmente como adjuvante à solução cardioplégica não demonstrou benefício hemodinâmico ou metabólico em modelo experimental de coração isolado em porcos. Palavras-chave: Trimetazidine, coração isolado, solução cardioplégica / Abstract: Introduction: Many drugs have usually been associated to cardioplegia since beggining of myocardial protection in Cardiac Surgery in order to improve surgical outcome. Any medicine able to induce resistance to ischemia and better hemodinamic effects and survival may have its utilization justified. Trimetazidine is an agent currently available as anti-ischemic medicine for anginal symptoms acting by protective metabolic effects Its role to be used in heart surgical patients as an adjuvant to cardioplegia is yet not fully comprehended. Objective: Verify in an isolated working heart state animal model if the association of trimetazidine to cardioplegia improves heart performance. Materials and method: Swines were used in this working heart model. They were divided in three grups (n = 6) that underwent regional and global ischemia. Each group was selected to a different treatment. St Thomas Cardioplegia (ST), St Thomas associated to trimetazidine (TMZ) and control group (Co). Data was collected during reperfusion period at 30, 60 and 90 minutes and were measured: Hemodinamic parameters such as elastance contractility index (Emáx), preload recruitable stroke work relationship (PRSW) and heart "stiffness" (EDPRV). Other data included coronary flow, oxygen and glucose consumption and lactate. Results were statistically analysed. Results: All contractility data were not significantly different among three groups. Lactate became constantly higher according to time uniformly in all three groups Coronary flow, glucose consumption and oxygen consumption presented large variations during time periods but according to treatments showed no statistical differences in all three groups. Left ventricle final weight was significantly lower in trimetazidine group compared to both other groups. Conclusion: Acute administration of trimetazidine associated to cardioplegia as an adjuvant showed no hemodinamic or metabolic improvement in an isolated working heart experimental model in swines. Key-words: Trimetazidine; isolated working heart model; cardioplegia / Mestrado / Cirurgia / Mestre em Cirurgia

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The present project investigated the effect of glucose, high dose insulin and normoglycemia (GIN) therapy in patients undergoing coronary revascularization surgery. A reduction in myocardial injury as measured by cardiac troponin I was the primary end point. Cardiac function based on hemodynamics and vasoactive drug requirements as well as clinical outcome were evaluated. Hormones and metabolites and cardiac metabolism were investigated concurrently as potential mechanisms of GIN therapy. The major findings of the present study are that GIN therapy reduced post-operative myocardial injury and myocardial dysfunction leading to a decrease in major complications following coronary artery bypass grafting surgery. The mechanism of the overall improvement in cardiac function and decreased morbidity following CABG with GIN therapy is likely to be multi-factorial, but from the present results, is influenced by improved myocardial metabolism. GIN therapy is thus an effective diet for the ischemic heart.

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Paraplegia or paraparesis caused by temporary cross-clamping of the aorta is a devastating sequela in patients after surgery of the thoracoabdominal aorta. No effective clinical method is available to protect the spinal cord from ischemic reperfusion injury. A small animal (rat) model of spinal cord ischemia is established to better understand the pathophysiological events and to evaluate potential treatments. Eighty-one male Sprague-Dawley rats weighing 300 g to 350 g were used for model development (45) and treatment evaluation (36). The heparinized and anesthetized rat was supported by a respirator following tracheostomy. The thoracic aorta was cannulated via the left carotid artery for post-clamping intra-aortic treatment solution administration. After thoracotomy, the aorta was freed and temporarily clamped just distal to the left subclavian artery and just proximal to the diaphragm for different time intervals: 0, 5, 10, 15, 20, 25, 30, 35, and 40 minutes (five animals per group). The motor function of the lower extremities postoperatively showed consistent impairment after 30 minutes clamping (5/5 rats were paralyzed), and this time interval was used for treatment evaluation. For each treatment, six animals per group were used, and direct local intra-aortic infusion of physiologic solution (2 mL) at different temperatures with or without buffer substances was given immediately after double cross-clamp to protect the ischemic spinal cord. Arterial blood (2 mL) was infused in the control group. The data indicate that the addition of HCO3-(20 mM) to the hypothermic (15 degrees C) solution offered complete protection of the spinal cord from ischemic injury.(ABSTRACT TRUNCATED AT 250 WORDS)