PHARMACODYNAMIC INTERACTION OF TINOSPORA CORDIFOLIA WITH ATENOLOL AND PROPRANOLOL IN ISOPROTERENOL INDUCED CARDIAC NECROSIS IN RATS

Objective: The present study was carried out to evaluate the combined cardioprotective effect of standardized extract of Tinospora cordifolia extract (TCE) with atenolol (AT) and propranolol (PP) in isoproterenol (ISO) induced cardiac necrosis in rats. Methods: Myocardial infarction (MI) or cardiac necrosis was induced by subcutaneous administration of ISO for two days consecutively at an interval of 24 h. Rats were pre-administered with test drugs for 21 d followed by ISO was administration on 20 and 21st day. 24 h after final ISO administration, mean arterial blood pressure (MAB), Heart rate (HR), electrocardiogram (ECG), heart bio-marker enzyme, and histopathological study of cardiac tissue were evaluated from control and experimental groups and analyzed statistically by one-way ANOVA followed by Tukeys’s test. Results: Rats administered with ISO showed significant (p<0.001) changes in ECG, HR, MAB, heart bio-marker enzyme, antioxidant parameters, and histopathology of the heart. The activities of biomarkers have reduced in serum and there is a significant (p<0.001) increase in antioxidants in the heart tissue of animals treated with drug combination. Similarly, ECG, MAB, and HR were restored to normalcy in drug-treated animals. Conclusion: It may be concluded that the herb-drug combinations i. e TCE (500 mg/kg)+AT (10 mg/kg) and TCE (500 mg/kg)+PP (10 mg/kg) has shown increased cardioprotective activity than they were used alone.

Ivabradine Induces Cardiac Protection against Myocardial Infarction by Preventing Cyclophilin-A Secretion in Pigs under Coronary Ischemia/Reperfusion

In response to cardiac ischemia/reperfusion, proteolysis mediated by extracellular matrix metalloproteinase inducer (EMMPRIN) and its secreted ligand cyclophilin-A (CyPA) significantly contributes to cardiac injury and necrosis. Here, we aimed to investigate if, in addition to the effect on the funny current (I(f)), Ivabradine may also play a role against cardiac necrosis by reducing EMMPRIN/CyPA-mediated cardiac inflammation. In a porcine model of cardiac ischemia/reperfusion (IR), we found that administration of 0.3 mg/kg Ivabradine significantly improved cardiac function and reduced cardiac necrosis by day 7 after IR, detecting a significant increase in cardiac CyPA in the necrotic compared to the risk areas, which was inversely correlated with the levels of circulating CyPA detected in plasma samples from the same subjects. In testing whether Ivabradine may regulate the levels of CyPA, no changes in tissue CyPA were found in healthy pigs treated with 0.3 mg/kg Ivabradine, but interestingly, when analyzing the complex EMMPRIN/CyPA, rather high glycosylated EMMPRIN, which is required for EMMPRIN-mediated matrix metalloproteinase (MMP) activation and increased CyPA bonding to low-glycosylated forms of EMMPRIN were detected by day 7 after IR in pigs treated with Ivabradine. To study the mechanism by which Ivabradine may prevent secretion of CyPA, we first found that Ivabradine was time-dependent in inhibiting co-localization of CyPA with the granule exocytosis marker vesicle-associated membrane protein 1 (VAMP1). However, Ivabradine had no effect on mRNA expression nor in the proteasome and lysosome degradation of CyPA. In conclusion, our results point toward CyPA, its ligand EMMPRIN, and the complex CyPA/EMMPRIN as important targets of Ivabradine in cardiac protection against IR.

Digoxin-specific antibody fragments for the treatment of suspected Nerium oleander toxicosis in a cat

Case summary A 6-year-old castrated male domestic shorthair cat presented for lethargy and gastrointestinal signs after possible exposure to Nerium oleander leaves. The cat developed a ventricular arrhythmia that responded positively to the administration of digoxin-specific antibody fragments. Underlying hypertrophic cardiomyopathy was also diagnosed after the development of congestive heart failure. Humane euthanasia was elected owing to a lack of significant response to continued therapy. Relevance and novel information To our knowledge, this is the first report to describe the use of digoxin-specific antibody fragments in a cat. Nerium oleander toxicosis is associated with significant morbidity and mortality, and digoxin-specific antibody fragments have been used effectively in humans and animals. The development of cardiac necrosis may have contributed to worsening arrhythmias and highlights the importance of early intervention. The use of digoxin-specific antibody fragments for suspected N oleander toxicosis in a cat resulted in a rapid response and appeared to be well tolerated.

The association of systemic inflammatory markers with indicators of stress and cardiac necrosis in patients undergoing aortic valve replacement and revascularization surgeries

The aim was to investigate: changes of inflammatory, stress and cardiac response in patients undergoing open heart surgeries up to five days after the procedure; the association between inflammatory, stress and cardiac response and whether changes in a certain marker can predict short-term patient outcome. Ninety patients were divided into three groups, 30 participants each (on-pump, off-pump revascularization and valve replacement group). The following markers were measured: complete blood count, CRP, IL-6, IL-10, leptin, resistin, monocyte chemoattractant protein-1 (MCP-1), cortisol, CK and hsTnT in 5 points. Resistin increased in all three groups. Lower IL-10 levels were found after the surgery and higher levels of leptin and MCP-1 in the off-pump than in the on-pump group. Off-pump group had higher values of IL-6, IL-10, leptin, resistin and MCP-1 and lower levels of CK and hsTnT 24 after surgery than the on-pump group. We found significant correlation between MCP-1 and resistin. The difference between resistin at time points 2 and 3 significantly predicted transfusion needs; while the difference between CRP and resistin before and at the end of the surgery together with the difference between leukocytes at the end and 24 hours after the surgery predicted the use of inotropic agents/vasopressors. Cardiac surgeries cause an increase of inflammatory, stress and cardiac markers. Only resistin correlated with MCP-1 which confirms the link between resistin secreted form infiltrated macrophages and enhanced release of MCP-1.

1639 Echocardiographic photorealistic imaging of leiomyomatosis intravascularis

39-years old female patient was admitted to the Department of Cardiac Surgery because of the suspicion of additional mass in the right atrium (RA). She had no symptoms. Two weeks before she underwent surgery because of the tumours of the uterus and the bladder. Moreover, she was treated for papillary thyroid carcinoma 1 year before. D-dimer levels, NTproBNP and markers of cardiac necrosis weren’t elevated. In histopathological examination leiomyomatosis intravascularis was diagnosed. In the transthoracic echocardiography (TTE) we confirmed the presence of additional inhomogeneous, mobile mass in the RA with morphology corresponding to thrombus. Moreover the inferior vena cava (IVC) was also involved. We decided to perform transesophageal echocardiography (TEE). Bicaval view showed that the structure enters through the IVC to the RA and protrude across the tricuspid valve throughout the cardiac cycle. In the photorealistic imaging we could exactly see huge mass that was elongated, mobile, inhomogeneous, had no adhesion with the wall of heart and vein and waved along with the heartbeat (figure 1 A,B). The surgery was performed through median sternotomy. A huge mass with about 30cm length was excised through RA oblique incision, on beating heart with cardiopulmonary bypass (figure 1C). Abstract 1639 Figure. Leiomyomatosis intravascularis

Intravenous epinephrine overdose in prehospital management of suspected anaphylaxis

A 65-year-old woman called paramedics for stridor and neck swelling following an insect bite with a possible anaphylactic reaction. On arrival paramedics administered intramuscular epinephrine without any observed improvement in stridor. Paramedics then prepared 5 mg of 1:1000 epinephrine for nebulised administration, which was inadvertently given intravenously. The patient developed tachycardia, anxiety and a severe headache, with biochemical evidence of cardiac necrosis without any haemodynamic compromise. The patient recovered over the next 24 hours and no long-term sequelae were identified on CT coronary angiogram, electrocardiography (ECG) echocardiography or invasive angiography. This case highlights the risk of cardiac ischaemia during epinephrine administration and the importance of protocols to ensure appropriate dosing. This case also raises questions regarding appropriate management of epinephrine overdose and shines a light on the absence of guidelines on the prevention of complications from epinephrine administration.