Effects of diabetes on myocardial infarct size and cardioprotection by preconditioning and postconditioning

Abstract

In spite of the current optimal therapy, the mortality of patients with ischemic heart disease (IHD) remains high, particularly in cases with diabetes mellitus (DM) as a co-morbidity. Myocardial infarct size is a major determinant of prognosis in IHD patients, and development of a novel strategy to limit infarction is of great clinical importance. Ischemic preconditioning (PC), postconditioning (PostC) and their mimetic agents have been shown to reduce infarct size in experiments using healthy animals. However, a variety of pharmacological agents have failed to demonstrate infarct size limitation in clinical trials. One of the possible reasons for the discrepancy between the results of animal experiments and clinical trials is that co-morbidities, including DM, modified myocardial responses to ischemia/reperfusion and to cardioprotective agents. Here we summarize observations of the effects of DM on myocardial infarct size and ischemic PC and PostC and discuss perspectives for protection of DM hearts.

Rapid ventricular pacing‐induced postconditioning attenuates reperfusion injury: effects on peroxynitrite, RISK and SAFE pathways

“…A possible explanation for the controversial results could be that the outcome of postconditioning may depend on several factors, such as failure to achieve complete reperfusion during application of brief I/R cycles, the duration of index ischaemia, the algorithm of postconditioning manoeuvre, gender, age and temperature (Skyschally et al, 2009b). In addition, co-morbidities, such as hyperlipidaemia (Kupai et al, 2009) and diabetes (Miki et al, 2012), may interfere with the infarct size-limiting effect of postconditioning. These confounding factors indicate the necessity to develop new alternative methods and models to induce postconditioning.…”

Durable Benefits of Cellular Postconditioning: Long‐Term Effects of Allogeneic Cardiosphere‐Derived Cells Infused After Reperfusion in Pigs with Acute Myocardial Infarction

“…Second, to produce AMI, we used an iatrogenic balloon occlusion model without any thrombus or atherosclerotic plaque in the absence of comorbidities, such as diabetes, and pigs were pretreated with amiodarone to prevent loss of animals attributable to ventricular arrhythmia. These do not reflect the real clinical situation; indeed, the preadministration of amiodarone has the potential to mask a possible effect of CDCs on arrhythmogenesis,39 and diabetes is known to interfere with some classical forms of cardioprotection 40. In addition, pigs were not receiving medical therapy, such as beta‐blockers or renin‐angiotensin system inhibitors, which are established as optimal medical therapy for preventing adverse remodeling and progression to heart failure.…”

Expressão do precondicionamento isquêmico em pacientes com diabetes mellitus tipo 2 e doença arterial coronariana

“…Entretanto, os resultados dos trabalhos experimentais são conflitantes (39) . Há trabalhos que sugerem que o diabetes interfere negativamente sobre o PI (37,(42)(43)(44)50,51) , enquanto outros indicam a preservação deste mecanismo cardioprotetor em modelos com diabetes (39,40,43,52,53) .…”

“…Especula-se que, em modelos experimentais, a normalização de alterações metabólicas possa restabelecer mecanismos de sinalização intracelulares protetores em animais com diabetes (39) . Além disso, apesar da suspensão dos medicamentos hipoglicemiantes previamente à realização dos testes ergométricos sequenciais, o efeito crônico de seu uso sobre o PI é desconhecido e possível (61) .…”

“…Assim, muitos autores têm estudado esta possível associação. Ainda que alguns trabalhos experimentais demonstrem que o diabetes pode alterar algumas vias intracelulares do PI, como as vias da quinase 3 do fosfatidil-inositol (37) ou a função dos canais de potássio dependentes de ATP (38) , prejudicando a expressão do PI, o conjunto destes estudos experimentais tem demonstrado resultados conflitantes (39) . Mesmo que alguns trabalhos demonstrem que o diabetes não interfere substancialmente no PI (40,41) , muitos sugerem influência negativa (42)(43)(44) .…”