Influence of intermittent fasting on myocardial infarction-induced cardiac remodeling.

BACKGROUND: Information on the role of intermittent fasting (IF) on pathologic cardiac remodeling is scarce. We compared the effects of IF before and after myocardial infarction (MI) on rat cardiac remodeling and survival. METHODS: Wistar rats were intermittently fasted (food available every other day) or fed ad libitum for 12 weeks and then divided into three groups: AL - fed ad libitum; AL/IF - fed AL before MI and IF after MI; and IF - fed IF before and after MI. Echocardiogram was performed before MI and 2 and 12 weeks after surgery. Isolated hearts were evaluated in Langendorff preparations. RESULTS: Before surgery, body weight (BW) was lower in IF than AL. Final BW was lower in AL/IF and IF than AL. Perioperative mortality did not change between AL (31.3%) and IF (27.3%). Total mortality was lower in IF than AL. Before surgery, echocardiographic parameters did not differ between groups. Two weeks after surgery, MI size did not differ between groups. Twelve weeks after MI, left ventricular (LV) diastolic posterior wall thickness was lower in AL/IF and IF than AL. The percentage of variation of echocardiographic parameters between twelve and two weeks showed that MI size decreased in all groups and the reduction was higher in IF than AL/IF. In Langendorff preparations, LV volume at zero end-diastolic pressure (V0; AL: 0.41 ± 0.05; AL/IF: 0.34 ± 0.06; IF: 0.28 ± 0.05 mL) and at 25 mmHg end-diastolic pressure (V25; AL: 0.61 ± 0.05; AL/IF: 0.54 ± 0.07; IF: 0.44 ± 0.06 mL) was lower in AL/IF and IF than AL and V25 was lower in IF than AL/IF. V0/BW ratio was lower in IF than AL and LV weight/V0 ratio was higher in IF than AL. Myocyte diameter was lower in AL/IF and IF than AL (AL: 17.3 ± 1.70; AL/IF: 15.1 ± 2.21; IF: 13.4 ± 1.49 µm). Myocardial hydroxyproline concentration and gene expression of ANP, Serca 2a, and α- and ß-myosin heavy chain did not differ between groups. CONCLUSION: Intermittent fasting initiated before or after MI reduces myocyte hypertrophy and LV dilation. Myocardial fibrosis and fetal gene expression are not modulated by feeding regimens. Benefit is more evident when intermittent fasting is initiated before rather than after MI.

Food restriction induces in vivo ventricular dysfunction in spontaneously hypertensive rats without impairment of in vitro myocardial contractility

Cardiac structures, function, and myocardial contractility are affected by food restriction (FR). There are few experiments associating undernutrition with hypertension. The aim of the present study was to analyze the effects of FR on the cardiac response to hypertension in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Five-month-old SHR were fed a control or a calorie-restricted diet for 90 days. Global left ventricle (LV) systolic function was evaluated in vivo by transthoracic echocardiogram and myocardial contractility and diastolic function were assessed in vitro in an isovolumetrically beating isolated heart (Langendorff preparation). FR reduced LV systolic function (control (mean ± SD): 58.9 ± 8.2; FR: 50.8 ± 4.8 percent, N = 14, P < 0.05). Myocardial contractility was preserved when assessed by the +dP/dt (control: 3493 ± 379; FR: 3555 ± 211 mmHg/s, P > 0.05), and developed pressure (in vitro) at diastolic pressure of zero (control: 152 ± 16; FR: 149 ± 15 mmHg, N = 9, P > 0.05) and 25 mmHg (control: 155 ± 9; FR: 150 ± 10 mmHg, N = 9, P > 0.05). FR also induced eccentric ventricular remodeling, and reduced myocardial elasticity (control: 10.9 ± 1.6; FR: 9.2 ± 0.9 percent, N = 9, P < 0.05) and LV compliance (control: 82.6 ± 16.5; FR: 68.2 ± 9.1 percent, N = 9, P < 0.05). We conclude that FR causes systolic ventricular dysfunction without in vitro change in myocardial contractility and diastolic dysfunction probably due to a reduction in myocardial elasticity.

Participação do estado contrátil e do relaxamento miocárdico na disfunção ventricular durante a transição hipertrofia-falência cardíaca / Myocardial function during the transition from compensated left ventricular hypertrophy to failure

OBJETIVO - Avaliar a participação do estado contrátil e do relaxamento miocárdico na disfunção do músculo cardíaco durante a transição hipertrofia-falência cardíaca em ratos espontaneamente hipertensos (SHR). MÉTODOS - Músculos papilares isolados do ventrículo esquerdo de SHR com insuficiência cardíaca (SHR-IC) e sem falência (SHR) e de ratos normotensos controle Wistar-Kyoto (WKY) foram estudados em contraçöes isométrica e isotônica, em solução de Krebs-Henseleit (1,25 mM Ca 'elevado a +2', 28 'graus Celsius'). RESULTADOS - Os valores da tensão máxima desenvolvida (TD) e da velocidade máxima de encurtamenton (V máx) foram menores nos SHR-IC e SHR, em relação aos WKY (p<0,05). TD e V máx foram semelhantes nos SHR-IC e SHR (p>0,05). A rigidez passiva do músculo aumentou significantemente nos SHR-IC (p<0,05 vs WKY e SHR); esta variável não diferiu entre WKY e SHR (p>0,05). CONCLUSÄO - Os dados obtidos mostram que a transição da fase de hipertrofia estável para insuficiência cardíaca nos ratos espontaneamente hipertensos está associado ao aumento da rigidez passiva do miocárdio e näo à piora da funçäo contrátil do músculo cardíaco.

The rate of force generation by the myocardium is not influenced by afterload

The influence of afterload on the rate of force generation by the myocardium was investigated using two types of preparations: the in situ dog heart (dP/dt) and isolated papillary muscle of rats (dT/dt). Thirteen anesthetized, mechanically ventilated and thoracotomized dogs were submitted to pharmacological autonomic blockade (3.0 mg/kg oxprenolol plus 0.5 mg/kg atropine). A reservoir connected to the left atrium permitted the control of left ventricular end-diastolic pressure (LVEDP). A mechanical constriction of the descending thoracic aorta allowed to increase the systolic pressure in two steps of 20 mmHg (conditions H1 and H2) above control values (condition C). After arterial pressure elevations (systolic pressure C: 119 + 8.1; H1: 142 + 7.9; H2: 166 + 7.7 mmHg; P<0.01), there were no significant differences in heart rate (C: 125 + 13.9; H1: 125 + 13.5; H2: 123 + 14.1 bpm; P>0.05) or LVEDP (C:6.2 + 2.48; H1: 6.3 + 2.43; H2: 6.1 + 2.51 mmHg; P>0.05). The values of dP/dt did not change after each elevation of arterial pressure (C:3,068 + 1,057; H1: 3,112 + 996; H2: 3,086 + 980 mmHg/s; P>0.05). In isolated rat papillary muscle, an afterload corresponding to 50 percent and 75 percent of the maximal developed tension did not alter the values of the maximum rate of tension development (100 percent: 78 + 13; 75 percent: 80 + 13; 50 percent: 79 + 11 g mm-2 s-1, P>0.05). The results show that the rise in afterload per se does not cause changes in dP/dt or dT/dt.

Disfunção arterial como possível mecanismo de agressão cardíaca empacientes com Diabetes Mellitus tipo II: estudo doppler-ecocardiográfico / Arterial dysfunction as a possible mechanism od cardiac injury in type II Diabetic Patients: a doppler-echocardiography study

Objetivo - Avaliar a estrutura e função do ventrículo esquerdo (VE) e a rigidez arterial em portadores de diabetes mellitus tipo II. Métodos - Foram estudados 13 doentes diabéticos de ambos os sexox (55 "mais ou menos" 8 anos) sem outras doenças. A estrutura e funçäo do VE foram avaliadas por meio de ecodopplercardiografia associada à monitorizaçäo näo invasiva da pressäo arterial (PA). Os resultados foram comparados aos obtidos em grupo de indivíduos normais de mesma idade (n=12). Resultados - Näo houve diferenças entre os grupos quanto a PA diastólica, dimensöes das câmaras esquerdas e índices de funçäo sistólica e diastólica. Os pacientes diabéticos apresentaram índice de massa do VE (101 "mais ou menos" 10 vs 80 "mais ou menos" 14 g/m2; p "menor" 0,001) e índice de rigidez arterial sistêmica ( 0,86 "mais ou menos" 0,26 vs 0,69 "mais ou menos" 0,19 mmHg/mL; P "menor" 0,05) significantemente maiores que os controles. Conclusäo - O diabets mellitus está associado a aumento da rigidez arterial sistêmica e esse fator poderia contribuir para seus efeitos adversos sobre o VE.

Myocyte necrosis is the basis for fibrosis in renovascular hypertensive rats

The pathogenesis of fibrosis and the functional features of pressure overload myocardial hypertrophy are still controversial. The objectives of the present study were to evaluate the function and morphology of the hypertrophied myocardium in renovascular hypertensive (RHT) rats. Male Wistar rats were sacrificed at week 4 (RHT 4) and 8 (RHT8) after unilateral renal ischemia (Goldblatt II hypertension model). Normotensive rats were used as controls. Myocardial function was analyzed in isolated papillary muscle preparations, morphological features were defined by light microscopy, and myocardial hydroxyproline concentration (HOP) was determined by spectrophotometry. Renal artery clipping resulted in elevated systolic arterial pressure (RHT4: 178 + 19 mmHg and RHT8: 194 + 24 mmHg, P<0.05 vs control: 123 + 7 mmHg). Myocardial hypertrophy was observed in both renovascular hypertensive groups. The myocardial HOP concentration was increased in the RHT8 group (control: 2.93 + 0.38 mug/mg; RHT4: 3,02 + 0.40 mug/mg; RHT8: 3,44 + 0.45 mug/mg of dry tissue, P<0.05 vs control and RHT4 groups). The morphological study demonstrated myocyte necrosis, vascular damage and cellular inflammatory response throughout the experimental period. The increased cellularity was more intense in the adventitia of the arterioles. As a consequence of myocyte necrosis, there was an early, local conjunctive stroma collapse with disarray and thickening of the argyrophilic interstitial fibers, followed scarring. The functional data showed an increased passive myocardial stiffness in the RHT4 group. We conclude that renovascular hypertension induces myocyte and arteriole necrosis. Reparative fibrosis occurred as a consequence of the inflammatory response to necrosis. The mechanical behavior of the isolated papillary muscle was normal, except for an early increased myocardial passive stiffness.

Patologia do coraçäo na AIDS. Estudo de 73 necropsias consecutivas / Pahtology of the heart in AIDS. A study of 73 consecutive necropsies

Objetivo - estudar a incidência e a etiologia das lesöes cardíacas na AIDS. Métodos - foram analisadas, retrospectivamente, 72 necropsias consecutivas de portadores de AIDS. Os relatórios das autopsias e os cortes histológicos foram revistos. As lâminas foram coradas por hematoxilina-eosina e quando necessário, estudaram-se,ainda, cortes corados por Ziehl-Nielsen, Gomori Grocott e Gram. Resultados - em nenhum paciente o óbito foi considerado de comprometimento cardíaco. Alteraçöes macro e/ou microspicas foram encontradas em 90 por cento dos casos. Atrofia das fibras cardíacas, associadas ou näo a edema intersticial e lipomatose difusa foi verificada em 51 por cento das autopsias. Infiltrado inflamatório miocárdico foi observado em 38 necropsias em , em 13 casos, um provável agente etiológico foi demonstrado: cryptococcus neoformans em 3 casos e mycobacteria tuberculosis, micobactéria atípica, toxoplasma gondii, trupanosoma cruzi e citomegalovírus em 2 casos cada. Em um paciente foi encontrado metsases de sarcoma de Kaposi e, em 4, endocardite bacteriana. Comprometimento do pericárdio foi verificado em 22 casos. Conclusäo - o exame do coraçào revela a alta incidência de alteraçöes patológicas que podem ser encotradas na AIDS.

Purpose - To study the incidence and the etiology of the cardiac lesions in AIDS patients. Methods - The autopsy protocols and the filled slides of the heart from 73 consecutive AIDS patients were reviewed. There were, at least, 2 slides of each heart stained by haematoxylin-eosin; when indicated, Ziehl Nielsen, Gram and Gomori Grocott stains were used. Results - No cause of death was assigned to the heart. There was involvement of the heart in 66 (90%) cases. Marked atrophy of cardiac fibers with or without lipomatosis was observed in 38 patients. Interstitial infiltrates of myocardium were present in 38 necropsies and in 13 of these cases a probable pathogen was demonstrated: cryptococcus neoforms in three cases and mycobacteria tuberculosis, atypical mycobacteria, toxoplasma gondii, trypanosoma cruzi and cytomegalovirus in two cases each. Bacterial endocarditis was found in 4 autopsies and Kaposi sarcome in one. The pericardium was involved in 22 cases; in 12 there was only non specific mononuclear infiltration. Conclusion - Autopsy examination of the heart from AIDS patients revealed frequent pathologic involvement