Figure 5 - uploaded by José Gustavo Padrão Tavares
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Histograms showing the incidence of ventricular arrhythmia (VA), atrio-ventricular blockade (AVB) and lethality (LET) in rats submitted to cardiac I/R, before (white bars) and after (colored bars) treatment with L-type Ca 2+ channel blocker nifedipine (1 mg/kg and 30 mg/kg, EV, before ischemia).
Source publication
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 ventilatio...
Context in source publication
Context 1
... 2 Serum concentrations of CK-MB (U/L) and troponin I (ng/mL) obtained in rats of cardiac I/R and SHAM-operated groups. Figure 5 shows that treatment of rats with nifedipine 1 mg/kg and 30 mg/kg IV before ischemia significantly reduced incidence of VA from 85% to 28%, AVB from 79% to 14%, and LET from 70% to 14%, ...
Citations
... However, in cases of Research, Society and Development, v. 11, n. 11, e509111133978, 2022 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v11i11.33978 patients with hypertension who still with elevated blood pressure despite optimization therapy, the dihydropyridine calcium channel blockers may be used (Tavares et al., 2017;Heidenreich et al., 2022 ). ...
To evaluate, describe and compare the pharmacological treatments available for heart failure (HF). This is a literature review about the pharmacological treatment of HF based on articles selected from the PubMed database, as well as relevant guidelines, using pertinent keywords and application of inclusion and exclusion criteria. Chronic heart failure is a common condition that, if untreated, harms quality of life and is associated with a high risk of mortality, morbidity, and recurrent hospitalization. However, the prognosis of patients with this condition has been improved with knowledge of the pathophysiology of HF and, therefore, assertive application of both non-pharmacological and pharmacological treatment recommendations. Pharmacotherapy is based on neurohormoral inhibition of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system to improve the health status and survival of these patients. Currently, the recommendation for the treatment of HF with reduced ejection fraction (HFrEF) includes 4 drug classes: an angiotensin/neprilysin receptor inhibitor (ANRi), beta-blockers, mineralocorticoid receptor antagonists (MRA) and SGLT2 inhibitors (SGLT2ii). Mortality-reducing pharmacotherapy in HF currently includes ANRi, beta-blockers, MRA and SGLT2. Therefore, the challenge is to transform the results achieved in clinical studies into reality for the majority of patients with HF. This path must be promoted through multidisciplinary care with improved access to recommended drugs, close monitoring of patients, healthy habits, control of comorbidities and therapeutic adherence.
... Surgical procedures used for induction of CIR in rats were made in accordance with methodology previously described [17][18][19] . Rats were anesthetized with urethane (1.25 g/kg), and fixed in the supine position. ...
... After of 10 min of cardiac ischemia, the tourniquet was removed to allow coronary recirculation for 75 min (cardiac reperfusion). The cardiac electrical activity in all groups studied was monitored by electrocardiogram (ECG) system using a method previously described [17][18][19] . ECG analysis was performed during 100 min of duration (stabilization for 15 min, cardiac ischemia for 10 min and cardiac reperfusion for 75 min). ...
... The ECG was recorded using a biopotential amplifier by means of needle electrodes placed subcutaneously on the limbs. Successful surgical obstruction of the coronary artery was validated by ECG alterations (increase in R wave and ST segment) caused by cardiac ischemia [17][18][19] . The body temperature was maintained at 37.5 ºC with a heated operating platform and appropriate heating lamps and was evaluated routinely via a rectal thermometer. ...
Purpose
To evaluate the preventive cardioprotective effects of resveratrol and grape products, such as grape juice and red wine, in animal model of cardiac ischemia and reperfusion.
Methods
Male Wistar rats orally pretreated for 21-days with resveratrol and grape products were anesthetized and placed on mechanical ventilation to surgically induce cardiac ischemia and reperfusion by obstruction (ischemia) followed by liberation (reperfusion) of blood circulation in left descending coronary artery. These rats were submitted to the electrocardiogram (ECG) analysis to evaluate the effects of pretreatment with resveratrol and grape products on the incidence of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) resulting from cardiac ischemia and reperfusion.
Results
It was observed that the incidence of AVB was significantly lower in rats pretreated with resveratrol (25%), grape juice (37.5%) or red wine (12.5%) than in rats treated with saline solution (80%) or ethanol (80%). Similarly, incidence of LET was also significantly lower in rats pretreated with resveratrol (25%), grape juice (25%) or red wine (0%) than in rats treated with saline solution (62.5%) or ethanol (75%).
Conclusions
These results indicate that the cardioprotective response stimulated by resveratrol and grape products prevents the lethal cardiac arrhythmias in animal model of ischemia and reperfusion, supporting the idea that this treatment can be beneficial for prevention of severe cardiac arrhythmias in patients with ischemic heart disease.
... CIR protocol was performed as previously described [9][10][11][12][13] . After anesthesia with urethane (1.25 g/ kg) and under mechanical ventilation, the rats were submitted to left-thoracotomy. ...
Abstract:
Purpose: To evaluate whether the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of mitochondrial Ca2+ uniporter (MCU) protects the myocardium against injuries caused by cardiac ischemia and reperfusion (CIR).
Methods: CIR was induced in adult male Wistar rats (300-350 g) by
occlusion of the left anterior descendent coronary artery (10 min), followed by reperfusion (120 min). Rats were treated with different
doses of MCU blocker ruthenium red (RuR), administered 5 min before ischemia or reperfusion.
Results: In untreated rats, the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB) and the lethality (LET) induced by CIR were 85%, 79% and 70%, respectively. In rats treated with RuR before ischemia, the incidences of VA, AVB and LET were significantly reduced to 62%, 25% and 25%, respectively. In rats treated with RuR after ischemia, the incidences of VA, AVB and LET were significantly reduced to 50%, 25% and 25%, respectively.
Conclusion: The significant reduction of the incidence of CIR-induced VA, AVB and LET produced by the treatment with RuR indicates that the attenuation of mitochondrial Ca2+ overload produced by pharmacological blockade of MCU can protect the myocardium against injuries caused by CIR.
Key words: Myocardial Reperfusion Injury. Ischemia. Calcium. Rats.
... It is important to highlight that ionic and energetic collapse in cardiomyocytes deregulates CECC, leading to systolic dysfunction and heart failure, and increases the production of free radicals, stimulates the persistent opening of the MPTP, and favors the formation of Ca 2+ phosphate crystals that severely compromise the functional integrity of MIT (27)(28)(29). Some studies suggest that the collapse of MIT caused by Ca 2+ overload could be attenuated or prevented by drugs capable of selectively blocking the MUC (29,32,33). ...
... Recently, we demonstrated in our laboratory that cardiac arrhythmias due to the collapse of MIT generated by Ca 2+ overload can be attenuated or prevented by treatment with selective MUC blockers (32). As previously mentioned, cardiac IR injury produces severe arrhythmias due to the collapse of MIT generated by Ca 2+ overload in cardiomyocytes (24,(27)(28)(29). ...
... As previously mentioned, cardiac IR injury produces severe arrhythmias due to the collapse of MIT generated by Ca 2+ overload in cardiomyocytes (24,(27)(28)(29). Thus, we evaluated the effects of the MUC blocker ruthenium red (RR) on the incidence of ventricular arrhythmias, especially atrioventricular blockade (AVB) and lethality (LET), in rats subjected to cardiac IR injury (32). For this experimental protocol, rats were anesthetized and subjected to cardiac ischemia for 10 min followed by reperfusion for 75 min (32). ...
... Nifedipine is clinically used as antihypertensive, vasodilator and tocolytic agent, and is indicated for the treatment of systemic and pulmonary arterial hypertension, and stable angina pectoris [76,77]. In animal models of cardiac I/R injury, administration of nifedipine before ischemia (10-15 min) reduces the incidence of ventricular tachyarrhythmias, ventricular fibrillation, and lethality [78][79][80][81]. Nicardipine and nimodipine also reduce the incidence of arrhythmias in different models of cardiac I/R injury when given prior to ischemia [80]. ...
... Our studies have showed that treatment with nifedipine before ischemia or reperfusion reduces the incidence of ventricular arrhythmias, atrioventricular blockade and lethality in animals submitted to cardiac I/R injury due to attenuation in cytosolic Ca 2+ overload in cardiac cells [81,82]. When administrated before reperfusion, this cardioprotective effect of nifedipine was lower in comparison to administration before ischemia [81,82]. ...
... Our studies have showed that treatment with nifedipine before ischemia or reperfusion reduces the incidence of ventricular arrhythmias, atrioventricular blockade and lethality in animals submitted to cardiac I/R injury due to attenuation in cytosolic Ca 2+ overload in cardiac cells [81,82]. When administrated before reperfusion, this cardioprotective effect of nifedipine was lower in comparison to administration before ischemia [81,82]. This result is due to cytosolic Ca 2+ overload generated during ischemia and increased depolarization of cardiomyocytes at the onset of reperfusion, which reduces the cardioprotective efficacy of nifedipine [81][82][83][84][85]. Clinical studies suggest that post-ischemia treatment with nifedipine in patients with acute myocardial infarction reduced the incidence of ventricular arrhythmias, but was unable to reduce lethality [86][87][88][89][90][91]. ...
Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these cells to protect themselves against injury including ischemia and reperfusion (I/R), has been termed "cardioprotection". This protective response can be stimulated by pharmacological agents (adenosine, catecholamines and others) and non-pharmacological procedures (conditioning, hypoxia and others). Several intracellular signaling pathways mediated by chemical messengers (enzymes, protein kinases, transcription factors and others) and cytoplasmic organelles (mitochondria, sarcoplasmic reticulum, nucleus and sarcolemma) are involved in cardioprotective responses. Therefore, advancement in understanding the cellular and molecular mechanisms involved in the cardioprotective response can lead to the development of new pharmacological and non-pharmacological strategies for cardioprotection, thus contributing to increasing the efficacy of IHD treatment. In this work, we analyze the recent advances in pharmacological and non-pharmacological strategies of cardioprotection.
... The method for induction of CIR has previously been described by our lab 11,[13][14][15] . Rats were anesthetized with urethane (1.25 g/kg), and fixed in the supine position. ...
... After of 10 min of cardiac ischemia, the tourniquet was removed to allow coronary recirculation for 75 min (cardiac reperfusion). The cardiac electrical activity in all groups studied was monitored by electrocardiogram (ECG) system using a method previously described by our lab 11,[13][14][15] . ECG analysis was performed during 100 min of duration (stabilization for 15 min, cardiac ischemia for 10 min and cardiac reperfusion for 75 min). ...
Purpose:
To evaluate the cardioprotective response of the pharmacological modulation of β-adrenergic receptors (β-AR) in animal model of cardiac ischemia and reperfusion (CIR), in spontaneously hypertensive (SHR) and normotensive (NWR) rats.
Methods:
CIR was induced by the occlusion of left anterior descendent coronary artery (10 min) and reperfusion (75 min). The SHR was treated with β-AR antagonist atenolol (AT, 10 mg/kg, IV) 5 min before CIR, and NWR were treated with β-AR agonist isoproterenol (ISO, 0.5 mg/kg, IV) 5 min before CIR.
Results:
The treatment with AT increased the incidence of VA, AVB and LET in SHR, suggesting that spontaneous cardioprotection in hypertensive animals was abolished by blockade of β-AR. In contrast, the treatment with ISO significantly reduced the incidence of ventricular arrhythmia, atrioventricular blockade and lethality in NWR (30%, 20% and 20%, respectively), suggesting that the activation of β-AR stimulate cardioprotection in normotensive animals. Serum CK-MB were higher in SHR/CIR and NWR/CIR compared to respective SHAM group (not altered by treatment with AT or ISO).
Conclusion:
The pharmacological modulation of β-AR could be a new cardioprotective strategy for the therapy of myocardial dysfunctions induced by CIR related to cardiac surgery and cardiovascular diseases.
... Nifedipine is clinically used as antihypertensive, vasodilator and tocolytic agent, and is indicated for the treatment of systemic and pulmonary arterial hypertension, and stable angina pectoris [76,77]. In animal models of cardiac I/R injury, administration of nifedipine before ischemia (10-15 min) reduces the incidence of ventricular tachyarrhythmias, ventricular fibrillation, and lethality [78][79][80][81]. Nicardipine and nimodipine also reduce the incidence of arrhythmias in different models of cardiac I/R injury when given prior to ischemia [80]. ...
... Our studies have showed that treatment with nifedipine before ischemia or reperfusion reduces the incidence of ventricular arrhythmias, atrioventricular blockade and lethality in animals submitted to cardiac I/R injury due to attenuation in cytosolic Ca 2+ overload in cardiac cells [81,82]. When administrated before reperfusion, this cardioprotective effect of nifedipine was lower in comparison to administration before ischemia [81,82]. ...
... Our studies have showed that treatment with nifedipine before ischemia or reperfusion reduces the incidence of ventricular arrhythmias, atrioventricular blockade and lethality in animals submitted to cardiac I/R injury due to attenuation in cytosolic Ca 2+ overload in cardiac cells [81,82]. When administrated before reperfusion, this cardioprotective effect of nifedipine was lower in comparison to administration before ischemia [81,82]. This result is due to cytosolic Ca 2+ overload generated during ischemia and increased depolarization of cardiomyocytes at the onset of reperfusion, which reduces the cardioprotective efficacy of nifedipine [81][82][83][84][85]. Clinical studies suggest that post-ischemia treatment with nifedipine in patients with acute myocardial infarction reduced the incidence of ventricular arrhythmias, but was unable to reduce lethality [86][87][88][89][90][91]. ...
Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these cells to protect themselves against injury including ischemia and reperfusion (I/R), has been termed "cardioprotection". This protective response can be stimulated by pharmacological agents (adenosine, catecholamines and others) and non-pharmacological procedures (conditioning, hypoxia and others). Several intracellular signaling pathways mediated by chemical messengers (enzymes, protein kinases, transcription factors and others) and cytoplasmic organelles (mitochondria, sarcoplasmic reticulum, nucleus and sarcolemma) are involved in cardioprotective responses. Therefore, advancement in understanding the cellular and molecular mechanisms involved in the cardioprotective response can lead to the development of new pharmacological and non-pharmacological strategies for cardioprotection, thus contributing to increasing the efficacy of IHD treatment. In this work, we analyze the recent advances in pharmacological and non-pharmacological strategies of cardioprotection.
... All experimental procedures used to induce cardiac I/R in this study were previously described in other studies published by our lab 13,14 . After anesthesia with urethane (1.25 g/kg), rats were submitted to orotracheal intubation and adapted in mechanical ventilator apparatus (Insight, model EFF 312, Brazil) with room air (volume of 10 mL/kg and 70 breaths/min). ...
... To evaluate cardiac electrical activity, the ECG system was adapted in rats submitted to cardiac I/R. Cardiac electrical activity were measured during 10 min ischemia and 120 min reperfusion 13,14 . The ECG was recorded from the beginning of the stabilization period using a data acquisition system (AqDados 7.02; Lynx Tecnologia Ltda, Brazil). ...
... To simplify the presentation of the results, ventricular fibrillation, torsades de pointes, and ventricular tachycardia parameters were considered only as VA. ECG measurements were evaluated according to Lambeth conventions 13,14 . ...
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.
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.
