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OBJECTIVE: Ischemic preconditioning is an increased tolerance to myocardial ischemia during the second of two consecutive exercise tests. ATP-sensitive K(+) channel blockers, such as glinides and sulfonylurea drugs, can induce loss of ischemic preconditioning. This study aimed to investigate the effects of repaglinide, a hypoglycemic agent with an affinity for myocardial ATP-sensitive K (+)channels, on the results of consecutive exercise tests in patients with diabetes and multivessel coronary artery disease. METHODS: Forty-two patients with type 2 diabetes and chronic stable angina pectoris, and two-vessel or three-vessel disease participated in this study. The patients underwent two consecutive treadmill exercise tests (phase 1). On the day after these exercise tests, 2 mg of oral repaglinide was given to the patients. One week later, two exercise tests were repeated consecutively (phase 2). RESULTS: All patients achieved 1.0-mm ST-segment depression during the four exercise tests (T1, T2, T3, and T4). In phase 2, seven patients improved in time to onset of 1.0-mm ST-segment depression. The worsening of the time to onset of 1.0-mm ST-segment depression in phase 2 demonstrated ischemic preconditioning block in 83.3% of patients (P=0.0001). Even the postexercise electrocardiographic parameters (ST-segment depression morphology and magnitude and arrhythmias) were significantly different between the groups with and without pharmacologic ischemic preconditioning block (P=0.031). CONCLUSIONS: Repaglinide, an oral hypoglycemic agent with ATP-sensitive K(+) channel-blocker activity, eliminated the myocardial ischemic preconditioning in patients with coronary disease and diabetes.

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BACKGROUND: The warm-up phenomenon observed after the second of two sequential exercise tests is characterized by an increased time to ischemia and ischemic threshold, and the latter is related to ischemic preconditioning. Previous studies have demonstrated that a single dose of glibenclamide, a cardiac ATP-sensitive K (K(ATP)) channel blocker, prevents ischemic preconditioning. This study aimed to investigate the effects of chronic treatment with glibenclamide during two sequential exercise tests. METHODS: Forty patients with angina pectoris were divided into three groups: 20 nondiabetics (NDM), 10 patients with diabetes in treatment with glibenclamide (DMG) and 10 diabetic patients with other treatments (DMO). All patients underwent two consecutive exercise tests. RESULTS: Heart rate and rate-pressure product at 1.0 mm ST-segment depression significantly increased during the second exercise test in NDM group (121.3+/-16.5 vs 127.3+/-15.3 beats/min, P<0.001, and 216.7+43.1 vs 232.1+/-43.0 beats.min-1.mmHg.10(2), P<0.001), and in DMO group (114.1+/-19.6 vs 119.6+/-18.1 beats/min, P=0.001, and 199.8+/-36.6 vs 222.2+/-29.2 beats.min-1.mmHg.10(2), P=0.019), but it did not change in patients in DMG group (130.7+/-14.5 vs 132.1+/-4.7 beats/min, P=ns, and 251.7+/-47.2 vs 250.3+/-42.8 beats.min-1.mmHg.10(2), P=ns). In the three groups, NDM, DMO, and DMG, the time to 1.0 mm ST-segment depression during the second exercise test was greater than during the first (225.0+/-112.5 vs 267.0+/-122.3 seconds, P=0.006; 187.5+/-54.0 vs 226.5+/-74.6 seconds, P=0.029 and 150.0+/-78.7 vs 186.0+/-81.9 seconds, P<0.001). CONCLUSION: The chronic use of glibenclamide may have mediated the loss of preconditioning benefits in the warm-up phenomenon, probably through its KATP channel-blocker activity, but without acting upon the tolerance to exercise.

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PURPOSE: To study the correlation between magnetic resonance imaging of the heart and right ventricle endomyocardial biopsy results in chronic Chagas' heart disease. METHODS: Ten patients with Chagas' disease, mean age 47 +/- 7 years, all males, in congestive heart failure with New York Heart Association class II (2 patients), III (6) and IV (2) were studied. Mean left ventricular ejection fraction was at echocardiogram 36 +/- 6. The patients were submitted to right ventricular endomyocardial biopsy and magnetic resonance imaging of the heart. The results of this group were compared with a control group of patients with idiopathic dilated cardiomyopathy, with mean age of 46 +/- 10 years and left ventricular ejection fraction of 30 +/- 4, in heart failure with functional class II (1 patient), III (5) and IV (1). RESULTS: All patients with Chagas' heart disease presented an increase in magnetic ressonance imaging signal of the heart after gadolinium use. The septal signal intensity changed from 0.87 +/- 0.06 to 1.54 +/- 0.16 (p < 0.001). In the control group the mean septal signal intensity was 0.93 +/- 0.07 before and 0.89 +/- 0.06 after the gadolinium (p = ns). Eight patients of the Chagas' disease group had biopsy proven myocarditis and two had borderline myocarditis. However, only one patient of the control group had diagnosis of borderline myocarditis. CONCLUSION: Myocarditis is frequently found in Chagas' heart disease patients and who unlike controls present a significant increase in myocardial signal intensity after gadolinium infusion. The magnetic resonance imaging of the heart seems a promising alternative method for the diagnosis of an inflammatory process in Chagas' heart disease.

Objetivo - Estudar a correlação entre a imagem por ressonância magnética e a biopsia endomiocárdica do ventrículo direito (VD) na cardiopatia da doença de Chagas. Métodos - Comparação de 10 pacientes com cardiopatia da doença de Chagas, idade média de 47 ± 7 anos, todos do sexo masculino, com insuficiência cardíaca em classe funcional (CF) II NYHA (2 pacientes), III (6) e IV (2); fração de ejeção do ventrículo esquerdo (FEVE) média pelo ecocardiograma 36 ± 6%; e 6 pacientes com cardiomiopatia dilatada idiopática, idade média de 46 ± 10 anos, FEVE média pelo ecocardiograma 30 ± 4% e insuficiência cardíaca CF II (1 paciente), III (5) e IV (1). Todos os pacientes foram submetidos a biopsia endomiocárdica do VD e exame do coração através de ressonância magnética (RM) com e sem uso do contraste gadolíneo. Resultados - Todos os pacientes com cardiopatia chagásica apresentaram aumento da intensidade de sinal na imagem pela RM após o uso de gadolíneo. A intensidade média do sinal variou de 0,87 ± 0,06 antes a 1,54 ± 0,16 após o uso do contraste (p < 0,001). No grupo controle, antes do uso do gadolíneo a intensidade média septal foi de 0,93 ± 0,07 e, após, o valor médio foi de 0,89 ± 0,06 (p = ns). Oito pacientes no grupo de cardiopatia chagásica tiveram biopsia provando miocardite e 2 com resultado bordeline, contudo no grupo controle, somente um teve diagnóstico duvidoso para miocardite. Conclusão - A miocardite é freqüentemente encontrada na doença de Chagas, os pacientes com cardiomiopatia chagásica, ao contrário do grupo controle, apresentam aumento significativo da intensidade de sinal de ressonância após o uso do gadolíneo. A imagem por RM parece ser método alternativo e com boa acurácia para diagnóstico de processo inflamatório cardíaco na doença de Chagas

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