Paolo Ruggero Errante

Cardioprotective effect of lipstatin derivative orlistat on normotensive rats submitted to cardiac ischemia and reperfusion

PURPOSE To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. METHODS Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). RESULTS Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. CONCLUSION The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.

Cardioprotective effect of preconditioning is more efficient than postconditioning in rats submitted to cardiac ischemia and reperfusion

PURPOSE To investigate the cardioprotective effects of ischemic preconditioning (preIC) and postconditioning (postIC) in animal model of cardiac ischemia/reperfusion. METHODS Adult rats were submitted to protocol of cardiac ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG) analysis. RESULTS After reestablishment of coronary blood flow, we observed variations of the ECG trace with increased incidence of ventricular arrhythmia (VA) (85%), atrioventricular block (AVB) (79%), and increase of lethality (70%) in cardiac I/R group. The comparison between I/R + preIC group with I/R group demonstrated significant reduction in VA incidence to 28%, AVB to 0% and lethality to 14%. The comparison of I/R + postIC group with I/R group was observed significance reduction in AVB incidence to 25% and lethality to 25%. CONCLUSION The preconditioning strategies produce cardioprotection more efficient that postconditioning against myocardial dysfunctions and lethality by cardiac ischemia and reperfusion.

A Simple and Efficient Methodology for the Study of Cardioprotective Drugs in Animal Model of Cardiac Ischemia-Reperfusion

To study cardioprotective drugs, we developed a simple and efficient methodology to evaluate effects of drugs on cardiac electrical activity using electrocardiogram (ECG) in rats submitted to cardiac ischemia-reperfusion (I/R). Using adult male Wistar rats (14 - 16-week-old) anesthetized (urethane 1.25 g/kg, i.p.) and kept under mechanical ventilation, we used surgical procedures to induce cardiac I/R by means mechanical occlusion of left anterior descendent coronary artery for 10 min (ischemia) with silk suture (tourniquet) followed by its removal to allow coronary recirculation (reperfusion). To evaluate the effects of surgical process, a group of rats (SHAM-operated) was submitted to surgical procedures previously described, but without coronary occlusion. To evaluate cardiac electrical activity in rats submitted to cardiac I/R and SHAM-operated, the ECG system was coupled to animal body to determine the incidence of ventricular arrhythmia (VA), atrio-ventricular blockade (AVB) and lethality (LET). To evaluate injury biomarkers production in rats submitted to cardiac I/R and SHAM-operated, serum concentrations of creatine kinase fraction (MB/CK-MB) and troponin I were determined by biochemical techniques. Using the methodology proposed in this work, we observed that VA, AVB and LET incidence was significantly higher in cardiac I/R group (85%, 79% and 70%, respectively) than in SHAM-operated group (0%, 0% and 0%, respectively). Serum levels of CK-MB and troponin I were also significantly higher in cardiac I/R (1,850 ± 222 U/L and 0.031 ± 0.009 ng/mL, respectively) compared to SHAM-operated group (808 ± 72 U/L and 0.200 ± 0.027 ng/mL). To evaluate efficiency of methodology proposed in this work to study the effect of cardioprotective drugs, the effects of the L-type Ca2+ channel blocker (CCB) nifedipine (30 mg/kg, intravenously - IV) in rats submitted to cardiac I/R were studied. The treatment with nifedipine (before ischemia) significantly reduced the incidence of VA (from 85% to 28%), AVB (from 79% to 14%), and LET (from 70% to 14%). These results indicate that the methodology described in the present work is simple, and efficient, to evaluate cardiac functional and biochemical alterations induced by cardiac I/R, and also the study of cardioprotective drugs in rats. This methodology could contribute to the development of new pharmacological cardioprotective strategies for to treatment of ischemic cardiac diseases in humans, such as myocardial infarction.

The Pharmacological Modulation of Ca2+/Camp Intracellular Signaling Pathways and Traditional Antitumoral Pharmaceuticals: A Plausible Multi-target Combined Therapy?

Cancer is a major public health issue worldwide, affecting both developed and developing countries, thus leading to the rise of a large annual expenses every fiscal year. Surgery, radiotherapy, chemotherapy, immunotherapy and multitarget pharmaceutical therapies are the current strategies for cancer treatment. Generally, cancer treatments are based on the clinical history of the patients, including histological type and the presence of molecular biomarkers. Nonetheless, new options are clearly needed to increase survival and improve the patients’ quality of life, especially for those in advanced stages of this disease. Thus, the increased knowledge of the mechanisms responsible for growth, invasion and metastasis of cancer, including development of intrinsic resistance, is critical.

Effect of atenolol pre-treatment in heart damage in a model of intestinal ischemia-reperfusion

PURPOSE To investigate the effects of atenolol in inflammatory mediator and oxidative stress in a myocardial injury by intestinal ischemia/reperfusion in rat model. METHODS Adult Wistar male rats were randomly (n=8), anesthetized and divided in: Sham: submitted to operation only; group SS+IR: intravenous saline infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); group AT+IR: intravenous atenolol infusion (2 mg/kg) following superior mesenteric artery occlusion during 60 minutes (ischemia) and open for 120 minutes (reperfusion); and group AT+I+AT+R: intravenous atenolol infusion following superior mesenteric artery occlusion during 60 minutes (ischemia) and in the time 45 minutes other atenolol doses were administrated and the artery was open for 120 minutes (reperfusion), all animals were submitted to muscular relaxation for mechanical ventilation. In the end of experiment the animals were euthanized and the hearts tissue were morphology analyzed by histology and malondialdehyde by ELISA, and the plasma were analyzed for tumor necrosis factor-alpha by ELISA. RESULTS The group SS+IR demonstrated the higher malondialdehyde levels when compared with the atenolol treated-groups (p=0.001) in the heart tissue. The tumor necrosis factor-alpha level in plasma decrease in the treated groups when compared with SS+IR group (p=0.001). Histology analyses demonstrate pyknosis, edema, cellular vacuolization, presence of inflammatory infiltrate and band contraction in the heart tissue of the rats. CONCLUSION Atenolol significantly reduce the degree of cardiac damage after intestinal ischemia-reperfusion.