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3 results on '"anti-ischemic drugs"'

1. Anti-ischemic properties of a new spiro-cyclic benzopyran activator of the cardiac mito-KATP channel

Author

Calderone, Vincenzo, Testai, Lara, Martelli, Alma, Rapposelli, Simona, Digiacomo, Maria, Balsamo, Aldo, and Breschi, Maria C.

Subjects
*BENZOPYRANS, *POTASSIUM channels, *ADENOSINE triphosphate, *MITOCHONDRIA, *LABORATORY rats, *MYOCARDIAL infarction, *CARDIOTONIC agents, *CYCLOSPORINE
Abstract

Abstract: Many activators of KATP channels exhibit cardioprotective effects, mainly mediated by channels expressed on mitochondria (mito-KATP). Previous results showed anti-ischemic effects of the spiro-cyclic derivative A, on isolated rat hearts. In this work this molecule was more extensively studied and diazoxide was used as reference mito-KATP opener. The studies were performed on an in vivo rat model of myocardial infarct and on heart-derived H9c2 cells exposed to an anoxic environment. The mechanism of action was further investigated on isolated rat heart mitochondria. In the model of myocardial infarct compound A and diazoxide produced significant cardioprotective effects, antagonised by the selective mito-KATP blocker 5-hydroxydecanoic acid (5-HD). Compound A, like diazoxide, produced modest and non-significant hypotensive responses, while the hyperglycaemic effects of diazoxide were not observed for the new compound. Protective effects of compound A and diazoxide were also recorded in H9c2 cells and again were inhibited by 5-HD. Compound A and diazoxide caused swelling of cardiac mitochondria, in agreement with the profile of mito-KATP openers. Both compounds evoked concentration-dependent Ca2+-release from Ca2+-preloaded mitochondria, prevented mitochondrial Ca2+-uptake and caused mitochondrial membrane depolarisation. These effects were antagonised by ATP, the endogenous KATP inhibitor. In conclusion, compound A exhibits a promising profile of an anti-ischemic agent, with a mechanism likely to be linked to the activation of mito-KATP channels, and, because of its chemical characteristics such as structural rigidity and chirality due to the spiro-cyclic moiety, represents an interesting template for development of analogues further improved in activity and selectivity. [Copyright &y& Elsevier]

Published
2010
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2. Chronobiology and chronotherapy of ischemic heart disease

Author

Portaluppi, Francesco and Lemmer, Björn

Subjects
*CORONARY disease, *CIRCADIAN rhythms, *CALCIUM channels, *BETA adrenoceptors
Abstract

Abstract: The occurrence of the clinical manifestations of ischemic heart disease (IHD) – myocardial ischemia and angina pectoris, acute myocardial infarction, and sudden cardiac death – is unevenly distributed during the 24 h with greater than expected events during the initial hours of the daily activity span and in the late afternoon or early evening. Such temporal patterns result from circadian rhythms in pathophysiological mechanisms plus cyclic environmental stressors that trigger ischemic events. Both the pharmacokinetics (PK) and pharmacodynamics (PD) of many, though not all, anti-ischemic oral nitrate, calcium channel blocker, and β-adrenoceptor antagonist medications have been shown to be influenced by the circadian time of their administration. The requirement for preventive and therapeutic interventions varies predictably during the 24 h, and thus therapeutic strategies should also be tailored accordingly to optimize outcomes. During the past decade, two first generation calcium channel blocker chronotherapies have been developed, trialed, and marketed in North America for the improved treatment of IHD. Nonetheless, there has been relatively little investigation of the administration-time (circadian rhythm) dependencies of the PK and PD of conventional anti-ischemic medications, and there has been little progress in the development of new generation IHD chronotherapies. Available epidemiologic, pharmacologic, and clinico-therapeutic evidence demonstrates how the chronobiologic approach to IHD can contribute new insight and opportunities to improve drug design and drug delivery to enhance therapeutic outcomes. [Copyright &y& Elsevier]

Published
2007
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3. Pharmacotherapy of acute myocardial infarction

Author

Grgat, Krešimir, Samardžić, Jure, Bulj, Nikola, and Skorić, Boško

Subjects
pharmacotherapy, treatment, anticoagulant drugs, acute myocardial infarction, anti-ischemic drugs, antiplatelet drugs, fibrinolytic drugs
Abstract

Kardiovaskularne bolesti su vodeći uzrok smrtnosti u svijetu, a najčešće ljudi umiru od ishemijske bolesti srca. Akutni infarkt miokarda (AIM) kao najopasnija manifestacija ishemijske bolesti srca najčešće nastaje rupturom aterosklerotskog plaka na stjenci koronarne arterije kojeg slijedi prianjanje, aktivacija i agregacija trombocita, te aktivacija koagulacijske kaskade i formiranja tromba. Temelj liječenja AIM je koronarna revaskularizacija kojom se uspostavlja i poboljšava koronarni protok kako bi se sačuvalo čim više zdravog miokarda, a u načelu se postiže perkutanom koronarnom intervencijom (PCI), fibrinolizom ili aortokoronarnim premoštenjem. Farmakoterapija ima također ključnu ulogu u liječenju infarkta miokarda jer bez adekvatne primjene lijekova sama revaskularizacija neće ispoljiti značajan benefit za bolesnike. Dio bolesnika s AIM niti ne bude podvrgnut revaskularizaciji te je liječen strategijom baziranom dominantno na farmakoterapiji. Lijekovi u infarktu miokarda između ostaloga imaju zadaću da smanje ishemiju srčanog mišića, preveniraju koronarni tromboembolizam, poboljšaju protok krvi kroz stenotičke lezije i ugrađene stentove, smanje zahtjev miokarda za kisikom, održavaju otvorenost krvne žile i kontroliraju bol. Dugoročni ciljevi liječenja su prevencija novih ishemijskih događaja, kontrola rizičnih čimbenika te poboljšanje i produljenje života bolesnika. U ovom radu prikazan je pregled suvremene farmakoterapije AIM u prehospitalnom, hospitalom i posthospitalnom razdoblju uz osvrt na samu bolest i aktualna klinička istraživanja u ovom području koja traže nove načine da se reduciraju katastrofalne posljedice infarkta miokarda koji je već desetljećima jedan od najvećih javnozdravstvenih i društvenih problema., Cardiovascular diseases are the leading cause of death worldwide, and most people die from ischemic heart disease. Acute myocardial infarction is the most dangerous manifestation of ischemic heart disease and is usually caused by atherosclerotic plaque disruption in the coronary artery wall. Subsequently, platelet adherence, activation and aggregation occur, leading to the activation of the clotting cascade and clot formation. Coronary revascularization is the cornerstone treatment in myocardial infarction management to preserve and maintain as much myocardium as possible. It can be performed with percutaneous coronary intervention, fibrinolysis or coronary artery bypass grafting. Pharmacotherapy also plays a key role in myocardial infarction management because coronary revascularization cannot achieve desired benefit without concomitant medications. Part of the patients with myocardial infarction do not undergo revascularization and are treated predominantly with pharmacotherapy. Drugs used in patients with myocardial infarction, amongst other positive effects, reduce myocardial ischemia, prevent coronary thromboembolism, increase blood flow through stenotic lesions and implanted stents, reduce myocardial oxygen demand, preserve patency of the coronary artery and control pain. Long-term goals in treating myocardial infarction with medications are prevention of new ischemic events, risk factors control and improvement in patients' survival and quality of life. This graduate thesis reviews contemporary acute myocardial infarction pharmacotherapy in prehospital, hospital and posthospital setting, with reference to the disease itself and the ongoing clinical research in this area which is exploring new ways to reduce catastrophic consequences of this disease which has for decades been one of the major issues in public health and society in general.

Published
2017

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