Adriano Meneghini

Anti-hypertensive drugs have different effects on ventricular hypertrophy regression

OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH) and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed), Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor) and verapamil (Ca++ channel blocker) caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker) were similar. Indapamina (diuretic) had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1) receptor antagonist) produced better results than atenolol (selective β1 receptor antagonist) with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

Memantine prevents cardiomyocytes nuclear size reduction in the left ventricle of rats exposed to cold stress

OBJECTIVES Memantine is an N-methyl-d-aspartate (NMDA) glutamate receptor antagonist used to treat Alzheimer’s disease. Previous studies have suggested that receptor blockers act as neuroprotective agents; however, no study has specifically investigated the impact that these drugs have on the heart. We sought to evaluate the effects of memantine on nuclear size reduction in cardiac cells exposed to cold stress. METHOD We used male EPM-Wistar rats (n=40) divided into 4 groups: 1) Matched control (CON); 2) Memantine-treated rats (MEM); 3) Rats undergoing induced hypothermia (IH) and 4) Rats undergoing induced hypothermia that were also treated with memantine (IHM). Animals in the MEM and IHM groups were treated by oral gavage administration of 20 mg/kg/day memantine over an eight-day period. Animals in the IH and IHM groups were submitted to 4 hours of hypothermia in a controlled environment with a temperature of − 8°C on the last day of the study. RESULTS The MEM group had the largest cardiomyocyte nuclear size (151 ± 3.5 μm3 vs. CON: 142 ± 2.3 μm3; p<0.05), while the IH group had the smallest mean value of nuclear size. The nuclear size of the IHM group was preserved (125 ± 2.9 μm3) compared to the IH group (108 ± 1.7 μm3; p<0.05). CONCLUSION Memantine prevented the nuclear size reduction of cardiomyocytes in rats exposed to cold stress.

Evaluation of baroreflex function in young spontaneously hypertensive rats

FUNDAMENTO: A literatura tem descrito dados contraditorios em relacao ao inicio da diminuicao da funcao barorreflexa em ratos espontaneamente hipertensos. OBJETIVO:Este estudo foi realizado para avaliar a funcao barorreflexa em ratos jovens de 13 semanas espontaneamente hipertensos. METODOS:Foram estudados ratos machos Wistar Kyoto (WKY) (n=15) e ratos espontaneamente hipertensos (REH) de 13 semanas (n=15). Cânulas foram inseridas na arteria aorta abdominal atraves da arteria femoral direita para medir a pressao arterial media (PAM) e a frequencia cardiaca (FC). A funcao barorreflexa foi calculada como a derivada da variacao da FC em funcao da variacao da PAM (ΔFC/ΔPAM), quando submetida a teste com uma dose depressora de nitroprussiato de sodio (50µg/kg) e com uma dose pressora de fenilefrina (8µg/kg) atraves de cânula inserida na veia femoral direita em ratos espontaneamente hipertensos e WKY. Diferencas com um valor de p < 0.05 foram consideradas estatisticamente significantes. RESULTADOS:Ratos espontaneamente hipertensos: ΔPAM=43,5 mmHg±5,2, ΔFC=-59,7 ppm±17,9 e ΔFC/ΔPAM=1,3 ppm/mmHg±0,1 testados com fenilefrina; Wistar Kyoto: ΔPAM=&56mmHg±3, ΔFC=*-114,9ppm±11,3 e ΔFC /ΔPAM =#1,9ppm/mmHg±0,3 testados com fenilefrina; ratos espontaneamente hipertensos: ΔPAM=-45,6mmHg±8,1, ΔFC=40,1ppm±11,6 e ΔFC/ΔPAM=0,9ppm/mmHg±0,5 testados com nitroprussiato de sodio; Wistar Kyoto: ΔPAM=-39,8mmHg±6,2, ΔFC=51,9ppm±21,8 e ΔFC/ΔPAM=1,4ppm/mmHg±0,7 testados com nitroprussiato de sodio (*p<0,05; #p<0,01; &p<0,001). CONCLUSAO: Nossos resultados mostram que ratos espontaneamente hipertensos de 13 semanas apresentaram reducao da funcao barorreflexa quando testados com fenilefrina.BACKGROUND The literature describes contradictory data regarding the onset of the baroreflex reduction in spontaneously hypertensive rats. OBJECTIVE This investigation was undertaken to evaluate the baroreflex function in 13-week-old spontaneously hypertensive rats. METHODS Male Wistar Kyoto (n=15) and spontaneously hypertensive rats (n=15) aged 13 weeks were studied. Cannulas were inserted in the abdominal aortic artery through the right femoral artery to measure mean arterial pressure and heart rate. Baroreflex function was calculated as the derivative of the variation of HR in function of the MAP variation (Delta heart rate/Delta mean arterial pressure) tested with a depressor dose of sodium nitroprusside (50microg/kg) and with a pressor dose of phenylephrine (8microg/kg) in the right femoral venous approach through an inserted cannula in awake spontaneously hypertensive rats and Wistar-Kyoto. Differences with p values < 0.05 were considered statistically significant. RESULTS Spontaneously hypertensive rats: Delta mean arterial pressure=43.5mmHg+/-5.2, Delta heart rate=-59.7ppm+/-17.9 and Delta heart rate/Delta mean arterial pressure=1.3ppm/mmHg+/-0.1 tested with phenylephrine; Wistar Kyoto: Delta mean arterial pressure=&56mmHg+/-3, Delta heart rate=*-114.9ppm+/-11.3 and Deltaheart rate/Delta mean arterial pressure=#1.9ppm/mmHg+/-0.3 tested with phenylephrine; spontaneously hypertensive rats: Delta mean arterial pressure=-45.6mmHg+/-8.1, Delta heart rate=40.1ppm+/-11.6 and Delta heart rate/Delta mean arterial pressure=0.9ppm/mmHg+/-0.5 tested with sodium nitroprusside; Wistar Kyoto: Delta mean arterial pressure=-39.8mmHg+/-6.2, Delta heart rate=51.9ppm+/-21.8 and Delta heart rate/Delta mean arterial pressure=1.4ppm/mmHg+/-0.7 tested with sodium nitroprusside (*p<0.05; #p<0.01; &<0.001). CONCLUSION Our results showed that 13-week-old spontaneously hypertensive rats presented reduced baroreflex function when tested with phenylephrine.

Fluoxetine effects on mitochondrial ultrastructure of right ventricle in rats exposed to cold stress

OBJECTIVE To assess fluoxetine effects on mitochondrial structure of the right ventricle in rats exposed to cold stress. METHODS The experimental study procedures were performed in 250-300g male EPM-Wistar rats. Rats (n=40) were divided into four groups: 1) Control group (CON); 2) Fluoxetine (FLU); 3) Induced hypothermia (IH) and; 4) Induced hypothermia treated with fluoxetine (IHF). Animals of FLU group were treated by the administration of gavages containing 0.75 mg/kg/day fluoxetine during 40 days. The induced hypothermia was obtained by maintaining the groups 3 and 4 in a freezer at -8 degrees C for 4 hours. The animals were sacrificed and fragments of the right ventricle (RV) were removed and processed prior to performing electron microscopic analysis. RESULTS The ultrastructural changes in cardiomyocytes were quantified through the number of mitochondrial cristae pattern (cristolysis). The CON (3.85%), FLU (4.47%) and IHF (8.4%) groups showed a normal cellular structure aspect with preserved cardiomyocytes cytoarchitecture and continuous sarcoplasmic membrane integrity. On the other hand, the IH (34.4%) group showed mitochondrial edema and lysis in cristae. CONCLUSION The ultrastructural analysis revealed that fluoxetine strongly prevents mitochondrial cristolysis in rat heart, suggesting a protector effect under cold stress condition.

Cold stress effects on cardiomyocytes nuclear size in rats: light microscopic evaluation

INTRODUCTION Total body induced hypothermia and myocardial cooling are effective methods regarding myocardial protection during heart surgery and ischemia. It is described in previous studies that extreme low temperature exposure causes mitochondrial cristae and myofilament disarrangement in cardiomyocytes, however, no investigation has analyzed the effects of cold stress on nuclear size of cardiomyocytes. OBJECTIVES To evaluate the effects of acute cold stress exposure on the nuclear size of cardiomyocytes in rats. METHODS The experimental study procedures were performed on 300-310 g adult male Wistar rats. Rats (n=20) were divided into two groups: 1) Control (CON) and; 2) Induced hypothermic (IH) group. Animals of IH group were exposed during 4 hours once at a controlled temperature of - 8 degrees C. It was performed histological analysis of liver and adrenal gland to examine the stress condition of animals. Cardiomyocytes nucleus size were examined by three independent investigators with the same and standardized criteria and analyzed by Bartkos intra-class correlation coefficient (R>0.75 = positive concordance). Students t test was applied. The significance level was set at P<0.05. RESULTS The induced hypothermic group presented higher lipid depletion in adrenal gland cells (P<0.05) and higher glycogen depletion in liver glycogen (P<0.05). The experimental group showed lower cardiomyocytes nuclear volume (108 + 1.7 microm(3); P<0.05), it decreased in 76% compared to the control group (142 + 2.3 microm(3)). Bartkos correlation: CON=0.44; IH=0.96, variation analysis between groups means differences was significant. CONCLUSION These data suggest that acute cold stress exposure induces cardiomyocytes nucleus size reduction in rats.

Myocardium tissue changes caused by electrical transthoracic discharges in rats

Background Cardiomyocytes cytoarchitecture changes caused by transthoracic countershocks have been focused recently. We aimed to evaluate the effects of electrical discharge application in the mitochondria structure in atrial myocardium of rats. Methods An electrical cardioverter was adapted to small rodent animals for our research. Electrical discharges were applied to the precordial region of 30 albino rats: (1) control group - animals that remained on resting period and were afterwards sacrificed; (2) electrical discharge group - animals that remained on resting period, followed by ten electrical discharges of 300 mV and sacrificed, and; (3) electrical post-discharge group - animals that remained on a resting period and received ten electrical discharges like the electrical discharge group, but were sacrificed seven days subsequently. We examined liver, adrenal and left atrium tissue fragments of the three groups. Results It was observed in control and post-discharge groups a normal cellular structure aspect with preserved architecture of cardiomyocytes and continuous sarcoplasmic membrane integrity. On the other hand, cardiac muscle fibers with mitochondrial edema and lysis occurred in the discharge group. Glycogen and adrenal lipids were not depleted in all groups. Conclusion These data suggest that transthoracic electrical discharges induce mitochondrial injuries in atrial cardiac cells of rats.

A Randomized Trial of the Topical Effect of Antifibrinolytic Epsilon Aminocaproic Acid on Coronary Artery Bypass Surgery Without Cardiopulmonary Bypass

We assessed the effect of the topical application of epsilon-aminocaproic antifibrinolytic acid (EACA) on the pericardium of patients submitted to coronary artery bypass graft (CABG) without the use of cardiopulmonary bypass (CPB). This is a prospective, randomized, and double-blind study. We evaluated 26 patients with chronic coronary heart disease indicated for CABG without CPB (EACA and placebo groups). The analysis of the postoperative hematological results showed no difference between groups in hemoglobin and hematocrit. There was no difference between the groups regarding the postoperative bleeding through the drains in the first 24 hours, 48 hours, and accumulated loss until removal of drains. The use of EACA in patients undergoing CABG without CPB presented no difference in the reduction of the amount of bleeding and the need for blood transfusions.

Electric countershock and cold stress effects on liver and adrenal gland

OBJECTIVES: Cold exposure induces glycogen and lipid depletion in the liver and the adrenal gland, respectively. However, no previous study has determined the effects of electrical countershock on those tissues. We aimed to evaluate the effects of electrical countershock on lipid depletion in the adrenal gland and on glycogen depletion in the liver. METHODS: We used 40 male Wistar rats divided into four groups: the control group, in which the animals were subjected to a resting period of seven days; the electrical discharge group, in which the animals were subjected to a resting period followed by administration of ten 300-mV electrical discharges; the electrical post-discharge group, in which the animals received ten electrical shocks (300 mV) followed by rest for seven consecutive days; and the cold stress group, in which the animals were subjected to a resting period and were then exposed to −8ºC temperatures for four hours. All animals underwent a laparotomy after treatment. The lipid and glycogen depletions are presented using intensity levels (where + = low intensity and ++++ = high intensity, with intermediate levels in between). RESULTS: The rats exposed to the cold stress presented the highest glycogen and lipid depletion in the liver and the adrenal gland, respectively. Furthermore, we noted that the electrical countershock significantly increased lipid depletion in the adrenal gland and glycogen depletion in the liver. One week after the electrical countershock, the liver and adrenal gland profiles were similar to that of the control group. CONCLUSION: Electrical countershock immediately increased the glycogen depletion in the liver and the lipid depletion in the adrenal gland of rats.

Efeito da denervação cardíaca ventral na incidência de fibrilação atrial após revascularização cirúrgica do miocárdio

OBJECTIVE To evaluate the effect of ventral cardiac denervation in the incidence of atrial fibrillation after coronary artery bypass surgery. METHODS Between September and November, 50 patients without history or previous diagnosis of atrial arrhythmia from the same institution presenting coronary heart disease with indication for coronary artery graft bypass surgery were enrolled in a prospective and randomized study. The exclusion criteria were: patients older than 75 years of age, previous history of atrial arrhythmia and associated heart surgeries. Denervation was performed before cardiopulmonary bypass and it was achieved by removing the adipose tissues around the superior vena cava, aorta and pulmonary artery. The groups were compared regarding demographic, clinical and operative variables. RESULTS There were no hospital mortalities. The additional time for the denervation was 7.64+/-2.33 minutes, and there were no associated complications. Postoperative atrial fibrillation was present in two (8%) patients of the Control Group and in three (12%) patients who underwent ventral cardiac denervation. The risk of postoperative atrial fibrillation in patients undergoing ventral cardiac denervation was 22% higher than in the Control Group (0.56-2.66,confidence interval); however, this outcome was not statistically significant (p=0.64). CONCLUSION Ventral cardiac denervation, despite being a fast and low-risk procedure, does not significantly reduce the incidence of atrial fibrillation after coronary artery bypass graft surgery.

Memantine effects on liver and adrenal gland of rats exposed to cold stress.

BACKGROUND Memantine attenuates heart stress due cold stress, however, no study focused its effects on liver and adrenal gland. We evaluated its effects on lipid depletion in adrenal gland and glycogen depletion in liver of rats exposed to cold stress. METHODS Male rats divided into 4 groups: 1)Control (CON); 2)Memantine (MEM); 3)Induced cold stress (IH) and; 4)Induced cold stress memantine (IHF). Memantine were administrated by gavage (20 mg/kg/day) during eight days. Cold stress were performed during 4 hours once at - 8°C. Lipid and glycogen depletion were presented as its intensity levels. RESULTS Rats exposed to cold stress presented the highest glycogen (p < 0.001) and lipid depletion (p < 0.001) in liver and adrenal gland, respectively. We noted that memantine significantly reduced lipid depletion in adrenal gland and glycogen depletion in liver. CONCLUSION Memantine prevented glycogen depletion in liver and lipid depletion in adrenal gland of rats under a cold stress condition.Background Memantine attenuates heart stress due cold stress, however, no study focused its effects on liver and adrenal gland. We evaluated its effects on lipid depletion in adrenal gland and glycogen depletion in liver of rats exposed to cold stress. Methods Male rats divided into 4 groups: 1)Control (CON); 2)Memantine (MEM); 3)Induced cold stress (IH) and; 4)Induced cold stress memantine (IHF). Memantine were administrated by gavage (20 mg/kg/day) during eight days. Cold stress were performed during 4 hours once at - 8°C. Lipid and glycogen depletion were presented as its intensity levels. Results Rats exposed to cold stress presented the highest glycogen (p < 0.001) and lipid depletion (p < 0.001) in liver and adrenal gland, respectively. We noted that memantine significantly reduced lipid depletion in adrenal gland and glycogen depletion in liver. Conclusion Memantine prevented glycogen depletion in liver and lipid depletion in adrenal gland of rats under a cold stress condition.