Metabolic model for laboratory control of anti-ischaemic therapy effectiveness: a case study of nicorandil

Scientific relevance. A key anti-ischaemic mechanism of some medicinal products involves their effects on the metabolism of endothelial vasodilators, particularly the synthesis of nitric oxide from arginine and its precursor citrulline.Aim. The study was aimed to determine whether the plasma time course of guanidine derivatives (arginine precursors) is applicable to laboratory control of anti-ischaemic therapy effectiveness using a single oral dose of nicorandil in patients with coronary heart disease as a case study.Materials and methods. The authors used high-performance liquid chromatography to determine metabolites. Blood samples for analysis were obtained from 30 patients with angina pectoris (Grade II–III, Canadian Cardiovascular Society) and 30 healthy donors. All the study participants received a single oral dose of 20 mg nicorandil after 10 h of fasting.Results. At baseline, patients showed significantly higher plasma citrulline levels than donors. However, the elevated levels decreased to the healthy range after nicorandil administration. Plasma arginine levels in patients showed a statistically significant increase following nicorandil administration. Plasma homoarginine levels in patients remained reduced both before and after dosing. Nicorandil did not influence elevated levels of the endogenous nitric oxide synthase inhibitor (asymmetrical dimethylarginine).Conclusions. In addition to the established mechanisms responsible for altering cell metabolism, nicorandil enhances the contribution of citrulline to arginine resynthesis. It is reasonable to include citrulline and arginine, which are involved in the vasodilator response, in model schemes for laboratory control of the effectiveness of anti-ischaemic therapy

Метаболическая модель для лабораторного контроля эффективности антиишемической терапии на примере использования никорандила

A key anti-ischaemic mechanism of some medicinal products involves their effects on the metabolism of endothelial vasodilators, particularly the synthesis of nitric oxide from arginine and its precursor citrulline.The aim of the study was to determine whether the plasma time course of guanidine derivatives (arginine precursors) is applicable to laboratory control of anti-ischaemic therapy effectiveness using a single oral dose of nicorandil in patients with coronary heart disease as a case study.Materials and methods. The authors used high-performance liquid chromatography to determine metabolites. Blood samples for analysis were obtained from 30 patients with angina pectoris (Grade II–III, Canadian Cardiovascular Society) and 30 healthy donors. All the study participants received a single oral dose of 20 mg nicorandil after 10 h of fasting.Results. At baseline, patients showed significantly higher plasma citrulline levels than donors. However, the elevated levels decreased to the healthy range after nicorandil administration. Plasma arginine levels in patients showed a statistically significant increase following nicorandil administration. Plasma homoarginine levels in patients remained reduced both before and after dosing. Nicorandil did not influence elevated levels of the endogenous nitric oxide synthase inhibitor (asymmetrical dimethylarginine).Conclusions. In addition to the established mechanisms responsible for altering cell metabolism, nicorandil enhances the contribution of citrulline to arginine resynthesis. It is reasonable to include citrulline and arginine, which are involved in the vasodilator response, in model schemes for laboratory control of the effectiveness of anti-ischaemic therapy.Важным механизмом антиишемического действия некоторых препаратов является их влияние на метаболизм эндотелиальных факторов вазодилатации, в частности на образование оксида азота из аминокислоты аргинина и его предшественника цитруллина.Цель работы: изучение возможности использования показателей динамики гуанидиновых производных — предшественников аргинина — в плазме крови для лабораторного контроля эффективности антиишемической терапии на примере однократного перорального приема никорандила у пациентов с ишемической болезнью сердца.Материалы и методы: метаболиты определяли методом высокоэффективной жидкостной хроматографии в образцах крови, взятых у 30 пациентов со стенокардией напряжения II–III функционального класса. Референтной группой являлись 30 здоровых доноров. Никорандил использовали перорально в разовой дозе 20 мг после 10-часового голодания.Результаты: у пациентов исходный уровень цитруллина был достоверно выше, чем у здоровых доноров. После приема никорандила содержание цитруллина снижалось до уровня, не отличающегося от уровня в плазме крови здоровых доноров группы сравнения. Содержание аргинина в плазме крови пациентов после приема препарата достоверно возрастало. При этом у них сохранялся пониженный уровень гомоаргинина как до, так и после приема никорандила. Обнаружено также отсутствие влияния приема никорандила на уровень эндогенного ингибитора синтазы оксида азота — асимметричного диметиларгинина.Вывод: в дополнение к известным механизмам воздействия никорандила на клеточный метаболизм показано усиление участия цитруллина в ресинтезе аргинина. При оценке эффективности антиишемической терапии в модельную схему для лабораторного контроля целесообразно включать цитруллин и аргинин, которые являются участниками вазодилатационного ответа

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

Perioperative myocardial injury in patients with coronary artery disease during elective lower limb surgery

Aim. To assess the prevalence of ischemic myocardial injury and the cardioprotective effect of nicorandil by assessing high-sensitivity cardiac troponin (hs-cTn) in patients with stable coronary artery disease (CAD) during elective lower limb surgery, as well as to identify predictors of adverse cardiac events.Material and methods. The study included 70 patients with stable coronary artery disease hospitalized for elective autogenous femoropopliteal bypass (FPB) surgery. After randomization, all patients were divided into two following groups: control group — 35 patients; main group — 35 patients, who, in addition to standard therapy, were prescribed nicorandil (Cordinic, PIQ-PHARMA) in a single dose of 20 mg 2 hours before surgery. In the postoperative period, the incidence of myocardial injury was assessed by hs-cTn increase. The obtained primary data were subjected to mathematical processing using the R-Studio software package (R language).Results. At baseline, patients in both groups were comparable in clinical characteristics, therapy, and duration of vascular surgery. In the main group of patients receiving nicorandil, a significant decrease in the incidence of perioperative myocardial injury was noted. In 5 patients of the control group, hs-cTn level 24 hours after surgery exceeded the threshold value, which indicated myocardial injury in the early postoperative period. In the nicorandil group, there was no hs-cTn increase (14% vs 0%, p=0,027). Regression analysis identified a predictor of perioperative myocardial injury — left ventricular ejection fraction (LVEF) <50%. LVEF <50% increases the risk of myocardial injury in the early postoperative period by 7,36 times (p=0,04) and 9,15 times (p=0,048) according to univariate and multivariate regression analysis, respectively.Conclusion. Perioperative myocardial injury is a common complication in patients with CAD undergoing lower extremity revascularization. The use of nicorandil (Cordinic, PIQ-PHARMA) before elective revascularization surgery helps reduce the incidence of ischemic myocardial injury in the early postoperative period and is not accompanied by adverse reactions, which rationales this approach to improve the clinical outcomes of lower extremity revascularization in patients with stable CAD. A predictor of myocardial injury, determined by hs-cTn, is a LVEF <50%

ACUTE ATORVASTATIN RECAPTURE THERAPY IN CORONARY ARTERY BYPASS GRAFTING

Aim. To assess the safety of the application of high-dose atorvastatin and its effect on metabolic parameters, such as the total level of nitric oxide and homocysteine in the blood plasma in patients with ischemic heart disease during a coronary artery bypass surgery (CABG).Material and methods. The study included 42 patients with stable effort angina II-IV functional class. A special criterion for selection was the taking atorvastatin at a dose of 20 mg/day for at least 30 days before patient was directed to surgical revascularization of the myocardium. Immediately before the intervention, the dose of atorvastatin was increased to the maximum allowed with subsequent taking of 40 mg/day. Complications after CABG, indicators of lipid metabolism and biochemical safety of statin use were analyzed. The duration of observation of results of the acute atorvastatin recapture therapy was 3 weeks during hospital period. We used modern enzymatic method for nitrogen oxides determination with the application of nitrate reductase. Determination of total homocysteine was performed by high performance liquid chromatography.Results. It was found that atorvastatin 80 mg for 12 hours and 2 hours before CABG in patients previously treated with atorvastatin 20 mg/day is well tolerated and leads to decrease in total levels of nitric oxide by 1.6 (0.18-10.8 ) μmol/l and homocysteine by 0.9 (0.17-2.69) μmol/l (p< 0.05 for both)Conclusion. It is assumed that the metabolic effects of high-dose therapy with atorvastatin may have a positive influence on the immediate postoperative period

ACUTE ATORVASTATIN RECAPTURE THERAPY IN CORONARY ARTERY BYPASS GRAFTING

Aim. To assess the safety of the application of high-dose atorvastatin and its effect on metabolic parameters, such as the total level of nitric oxide and homocysteine in the blood plasma in patients with ischemic heart disease during a coronary artery bypass surgery (CABG).Material and methods. The study included 42 patients with stable effort angina II-IV functional class. A special criterion for selection was the taking atorvastatin at a dose of 20 mg/day for at least 30 days before patient was directed to surgical revascularization of the myocardium. Immediately before the intervention, the dose of atorvastatin was increased to the maximum allowed with subsequent taking of 40 mg/day. Complications after CABG, indicators of lipid metabolism and biochemical safety of statin use were analyzed. The duration of observation of results of the acute atorvastatin recapture therapy was 3 weeks during hospital period. We used modern enzymatic method for nitrogen oxides determination with the application of nitrate reductase. Determination of total homocysteine was performed by high performance liquid chromatography.Results. It was found that atorvastatin 80 mg for 12 hours and 2 hours before CABG in patients previously treated with atorvastatin 20 mg/day is well tolerated and leads to decrease in total levels of nitric oxide by 1.6 (0.18-10.8 ) μmol/l and homocysteine by 0.9 (0.17-2.69) μmol/l (p< 0.05 for both)Conclusion. It is assumed that the metabolic effects of high-dose therapy with atorvastatin may have a positive influence on the immediate postoperative period