Effects of delta-opioid receptor agonist pretreatment on the cardiotoxicity of bupivacaine in rats

Background Delta-opioid receptor is widely expressed in human and rodent hearts, and has been proved to protect cardiomyocytes against ischemia/reperfusion and heart failure. The antagonist of delta-opioid receptor could block the rescue effect of lipid emulsion against local anesthetic cardiotoxicity. However, no evidence is available for the direct effect of delta-opioid-receptor agonists on the cardiotoxicity of local anesthetics. Methods Anesthetized Sprague Dawley rats were divided into five groups. Group NS received 2 ml·kg−1·min−1 normal saline, group LE received 2 ml·kg−1·min−1 30% lipid emulsion and group BW received 0.1, 1.0, or 5.0 mg/kg BW373U86, a delta-opioid-receptor agonist, for 5 min. Then 0.5% bupivacaine was infused intravenously at a rate of 3.0 mg·kg−1·min−1 until asystole. The time of arrhythmia, 50% mean arterial pressure-, 50% heart rate-reduction and asystole were recorded, and the dose of bupivacaine at each time point was calculated. Results All three different doses of BW373U86 did not affect the arrhythmia, 50% mean arterial pressure-reduction, 50% heart rate-reduction and asystole dose of bupivacaine compared with group NS. 30% LE significantly increased the bupivacaine threshold of 50% mean arterial pressure-reduction (17.9 [15.4–20.7] versus 7.2 [5.9–8.7], p = 0.018), 50% heart rate-reduction (18.7 ± 4.2 versus 8.8 ± 1.7, p < 0.001) and asystole (26.5 [21.0–29.1] versus 11.3 [10.7–13.4], p = 0.008) compared with group NS. There was no difference between group LE and group NS in the arrhythmia dose of bupivacaine (9.9 [8.9–11.7] versus 5.6 [4.5–7.0], p = 0.060). Conclusions Our data show that BW373U86 does not affect the cardiotoxicity of bupivacaine compared with NS control in rats. 30% LE pretreatment protects the myocardium against bupivacaine-induced cardiotoxicity.

Effect of short-acting b--blockers on heart rate and blood pressure in patients with acute coronary syndrome during percutaneous and coronary intervention

Background. The use of b- blockers in acute coronary syndrome (ACS) is recommended for all patients, who has not contraindications. The study of the effects of esmolol during percutaneous coronary intervention (PCI) remains relevant. Objective. To evaluate the features of the effect of esmolol (Biblock, “YURiA-PHARM”) on heart rate and blood pressure in patients with ACS during PCI.Materials and methods. The study included 30 patients, 15 men and 15 women, who were hospitalized in a specialized cardiology department with ACS with elevation of the ST segment. All patients underwent a general clinical examination, ECG recording in 12 leads, PCI according to the standard protocol with ECG and blood pressure monitoring. All patients were given infusion of esmolol before the standard therapy. The level of heart rate reduction, systolic blood pressure (SBP), diastolic blood pressure (DBP), the correlation of heart rate reduction during esmolol infusion with the clinical and functional parameters of patients and the degree of coronary artery (CA) damage were analyzed.Results. Decreased heart rate and blood pressure during infusion of esmolol in all patients. Before the infusion, the heart rate av-eraged (109.8 ± 4.0) beats per minute. After the infusion – (92.8 ± 3.2) beats per minute, (p < 0.001) with an average duration of infusion (18.2 ± 2.3) minutes. The decrease in SBP levels during infusion occurred on average by (22.8 ± 2.5) mm Hg, DBP – by (16.0 ± 2.1) mm Hg, no patient had hypotension. According to the results of correlation analysis, it was found that the decrease in heart rate with the use of esmolol has a correlation with the average age of patients (r = -0.47, p = 0.0012), with the presence of multivascular coronary artery disease (r = -0.38, p = 0.002). Weaker negative correlation was found with the initial level of SBP (r = -0.28, p = 0.015), the presence of a history of myocardial infarction (r = -0.27, p = 0.005), the presence of signs of left ventricular hypertrophy (LVH) on the ECG (r = -0.22, p = 0.008), and a history of arterial hypertension that was not treated according to current recommendations (r = -0.21, p = 0.032).Conclusions. The use of esmolol solution in patients with ACS who have supraventricular tachycardia and elevated blood pressure during PCI can improve control of heart rate, SBP and DBP, a significant decrease is observed after 10 minutes of dose titration. Careful titration of esmolol solution and monitoring of ECG and blood pressure revealed no side effects, including bradycardia and hypotension, which indicates a high safety profile of the drug.

Cirrhotic Cardiomyopathy

Cirrhotic cardiomyopathy (CCM), cardiac dysfunction in end-stage liver disease in the absence of prior heart disease, is an important clinical entity that contributes significantly to morbidity and mortality. The original definition for CCM, established in 2005 at the World Congress of Gastroenterology (WCG), was based upon known echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Subsequent advances in cardiovascular imaging and in particular myocardial deformation imaging have rendered the WCG criteria outdated. A number of investigations have explored other factors relevant to CCM, including serum markers, electrocardiography, and magnetic resonance imaging. CCM characteristics include a hyperdynamic circulatory state, impaired contractility, altered diastolic relaxation, and electrophysiological abnormalities, particularly QT interval prolongation. It is now known that cardiac dysfunction worsens with the progression of cirrhosis. Treatment for CCM has traditionally been limited to supportive efforts, but new pharmacological studies appear promising. Left ventricular diastolic dysfunction in CCM can be improved by targeted heart rate reduction. Ivabradine combined with carvedilol improves left ventricular diastolic dysfunction through targeted heart rate reduction, and this regimen can improve survival in patients with cirrhosis. Orthotopic liver transplantation also appears to improve CCM. Here, we canvass diagnostic challenges associated with CCM, introduce cardiac physiology principles and the application of echocardiographic techniques, and discuss the evidence behind therapeutic interventions in CCM.

ROLE OF HEART RATE REDUCTION WITH IVABRADINE IN LEFT VENTRICULAR FAILURE

Objective: To compare mean heart rate reduction in Ivabradine and placebo group in left ventricular failurepatients. Study Design: Quasi experimental study. Place and Duration of Study: Study was conducted at CMH, Kharian, from Jul 2018 to Dec 2018. Methodology: 64 patients participated in the study. They were randomly divided into two groups of 32each. One group was given Tab Ivabradine (10 mg twice a day) while second group received a placebo for aperiod of 4 weeks. After 4 weeks each patient was evaluated and heart rate, systolic and diastolic blood pressure were recorded. Mann-whitney U test selected to compare heart rate and ages of both groups t- test used to compare systolic and diastolic blood pressure among both groups. Chi-square test used to determine the association of heart rate between two groups. A p-value ≤0.05 was considered significant. Results: Median (IQR) heart rate was significantly lower in Ivabradine group 58.3 (4) as compared to placebo64.1(1) (p<0.01). Systolic blood pressure (132.8 ± 3.6) was significantly lower in ivabradine group as comparedto placebo group (137.1 ± 4.5) (p<0.01). Difference in diastolic blood pressure was insignificant in both groups (p=0.55). There was a significant association between heart rate of 55-60 beats per minute and ivabradine use(p<0.01). Conclusion: Ivabradine is safe and efficative drug in reducing heart rate and systolic blood pressure for patients suffering from left ventricular failure. Early detection and management of left ventricular failure with ivabradine use leads to better prognosis of the disease.