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1.
Vasc Health Risk Manag ; 15: 539-550, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827327

RESUMO

Background: Left ventricular hypertrophy (LVH), as assessed by measurement of left ventricular mass (LVM), is one of the most important cardiovascular risk factors. It is commonly present in patients with ischemic heart disease (IHD), irrespective of the level of blood pressure; recently, oxidative stress has been shown to be an important factor in its development. The question then arises: can this risk factor be modified by antioxidant treatment (e.g., with allopurinol, a xanthine oxidase inhibitor)? Methods: This is an observational study with a cross-sectional design which explored the association between long-term (>12 months) allopurinol therapy and LV mass index (LVMI) as well as geometry in patients generally receiving standard treatments for IHD. The primary endpoint was LVMI measurement (by 2D-echocardiography) and secondary endpoints included the association of allopurinol use with LV function (ejection fraction), blood pressure, glycemic control, and lipid profile. Results: Ninety-six patients on standard anti-ischemic drug treatment (control group) and 96 patients who were additionally taking allopurinol (minimum dose 100 mg/day) were enrolled. Both groups were matched for age, sex, height, and co-morbidities, but poorer kidney function in the allopurinol group required further sub-group analysis based on renal function. Allopurinol treatment was associated with the lowest LVMI in the patients with normal serum creatinine (median LVMI; 70.5 g/m2): corresponding values were 76.0 and 87.0 in the control group with, respectively, normal and elevated serum creatinine, and 89.5 in the allopurinol group with elevated serum creatinine (P=0.027). In addition, allopurinol was associated with better glycemic control (HbA1c) with a difference of 0.8% (95% CI; 1.3, 0.2) (P=0.004) as compared with control patients. Conclusion: In our population, treatment with allopurinol (presumably because of its anti-oxidant properties) has shown a tendency to be associated with smaller LVM in IHD patients with normal serum creatinine, along with better glycemic control.


Assuntos
Alopurinol/uso terapêutico , Antioxidantes/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Alopurinol/efeitos adversos , Antioxidantes/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Estudos de Casos e Controles , Creatinina/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
2.
Georgian Med News ; (295): 93-101, 2019 Oct.
Artigo em Russo | MEDLINE | ID: mdl-31804207

RESUMO

This a review article that describes the most important pharmacokinetic parameters of ß-blockers that determinate clinical importance of this group of medications, pharmacodynamics effects of this group and representative medications from the ß-blocker class. We substantiated the use of ß-blockers for cardio-vascular diseases using evidence base approach and founds of pharmacokinetic and pharmacodynamics effects.


Assuntos
Antagonistas Adrenérgicos beta , Hipertensão , Isquemia Miocárdica , Antagonistas Adrenérgicos beta/farmacologia , Humanos , Hipertensão/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico
3.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 376-380, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701727

RESUMO

OBJECTIVE: To investigate whether salidroside (Sal) plays a part in protecting myocardial cell through reducing the myocardial ischemia and the apoptosis pathway of both death receptors and mitochondria in acute exhausted rats. METHODS: Male SD rats were randomly divided into 4 groups (n=6): control group(Con), acute exhaustive swimming group (EE), low-dose and high-dose Sal pre-treatment exhaustive swimming group (SLE, SHE). Rats were treated with Sal solution (15 or 30 mg/(kg·d)) or 0.9%NaCl (3 ml/(kg·d)) by intraperitoneal injection for 15 d, respectively. The Con group did not carry out swimming training. The next day after the end of intraperitoneal administration, the rats in EE, SLE and SHE group were forced to swim until they were exhausted followed the standard of Thomas. After the end of exhaustive exercise, the rats were anesthetized and the blood samples and hearts were collected immediately. The myocardial ischemia and hypoxia area and myocardial apoptosis index (AI) were also observed. Serum ischemia modified albumin (IMA), cardiac troponin I (cTnI), brain natriuretic peptide(BNP) and myocardial cell Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) were determined. The expressions of myocardial TNF receptor superfamily member 6 (Fas), cytochrome C (Cyto-c), aspartate proteolytic enzyme-3(Caspase-3), aspartate proteolytic enzyme-8(Caspase-8), and aspartate proteolytic enzyme-9(Caspase-9) were detected. RESULTS: Compared with the Con group, the myocardial ischemia and hypoxia area in EE group was increased significantly. The serum levels of IMA, cTnI and BNP, AI and Bax levels and cardiac Fas, Cyto-C, Caspase-3, Caspase-8 and Caspase-9 protein expressions of EE group were also increased significantly (P<0.01), while the protein expression of Bcl-2 in cardiac tissues was decreased significantly (P<0.01). Compared with the EE group, the myocardial ischemia and hypoxia area, serum levels of IMA, cTnI and BNP, AI and Bax levels, and the protein expressions of cardiac Fas, Cyto-C, Caspase-3, Caspase-8 and Caspase-9 in Sal group were all decreased significantly(P<0.01). while the protein expression of cardiac Bcl-2 in Sal group were increased significantly (P<0.01). CONCLUSION: Sal plays a role in protecting myocardial cell through reducing the myocardial ischemia and inhibiting myocardial cell apoptosis in exhaustive exercise rats. The mechanism of reducing myocardial cell apoptosis may be related to inhibiting the expressions of Fas, Cyto-C, Caspase-3, Caspase-8, Caspase-9 and increasing the expression of Bcl-2.


Assuntos
Apoptose , Fadiga/fisiopatologia , Glucosídeos/farmacologia , Coração/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Fenóis/farmacologia , Animais , Biomarcadores/sangue , Feminino , Masculino , Miocárdio/citologia , Condicionamento Físico Animal , Ratos , Ratos Sprague-Dawley
4.
Mater Sci Eng C Mater Biol Appl ; 104: 109954, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500027

RESUMO

Therapeutic angiogenesis is essential for rescuing necrotic tissues in cases of ischemic disease. The exogenous hydrogen sulfide (H2S) donor, diallyl trisulfide (DATS), has been investigated as a therapeutic agent that promotes angiogenesis. However, the short half-life of generated H2S limits its therapeutic efficacy. In an attempt to overcome this difficulty, a poly(D,L-lactic-co-glycolic acid) microparticle system that contains DATS (DATS@MPs) is prepared as an in situ depot for the controlled release of H2S, providing slow release and long-term effectiveness. The results of in vitro investigations indicate that the slow-released DATS from the DATS@MPs depot yields a longer intracellular production of H2S than that from a free DATS depot. The intracellular generation of H2S favors the translocation of the transcription factor, Nrf2, from the cytosol to nuclei, potentially upregulating the gene expressions of antioxidant enzymes, ultimately increasing cellular resistance to oxidative stress. Intramuscular injection of the slow-releasing H2S donor depot DATS@MPs in an ischemic limb that is experimentally generated in a mouse model promotes therapeutic angiogenesis and protects cells from apoptosis and tissues from necrosis, ultimately salvaging the limb. These analytical results reveal that DATS@MPs is potentially useful in H2S-based therapy for treating ischemic diseases.


Assuntos
Preparações de Ação Retardada/farmacologia , Sulfeto de Hidrogênio/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Compostos Alílicos/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Linhagem Celular , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sulfetos/farmacologia
5.
Eur J Med Chem ; 183: 111658, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31514063

RESUMO

Cardiovascular disorders are known as one of the main health problems which are associated with mortality worldwide. Myocardial ischemia (MI) is improper blood supply to myocardium which leads from serious complications to life-threatening problems like AMI, atherosclerosis, hypertension, cardiac-hypertrophy as well as diabetic associated complications as diabetic atherosclerosis/cardiomyopathy/hypertension. Despite several efforts, the current therapeutic platforms are not related with significant results. Hence, it seems, developing novel therapies are required. In this regard, increasing evidences indicated, curcumin (CRC) acts as cardioprotective agent. Given that CRC and its analogs exert their cardioprotective effects via affecting on a variety of cardiovascular diseases-related mechanisms (i.e., Inflammation, and oxidative stress). Herein, for first time, we have highlighted the protective impacts of CRC against MI. This review might be a steppingstone for further investigation into the clinical implications of the CRC against MI. Furthermore, it pulls in light of a legitimate concern for scientific community, seeking novel techniques and characteristic dynamic biopharmaceuticals for use against myocardial ischemia.


Assuntos
Cardiotônicos/farmacologia , Curcumina/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/prevenção & controle , Animais , Cardiotônicos/uso terapêutico , Curcumina/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Isquemia Miocárdica/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos
7.
Lancet ; 394(10199): 697-708, 2019 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-31448741

RESUMO

Atherosclerosis and its clinical manifestation as ischaemic heart disease remains a considerable health burden. Given that many factors contribute to ischaemic heart disease, a multifactorial approach to prevention is recommended, starting with lifestyle advice, smoking cessation, and control of known cardiovascular risk factors, such as blood pressure and lipids. Within the lipid profile, the principal target is lowering LDL cholesterol, firstly with lifestyle interventions and subsequently with pharmacological therapy. Statins are the recommended first-line pharmacological treatment. Some individuals might require further lowering of LDL cholesterol or be unable to tolerate statins. Additional therapies targeting different pathways in cholesterol metabolism are now available, ranging from small molecules taken orally, to injectable therapies. Examples include ezetimibe, which targets Niemann-Pick C1-like protein, and monoclonal antibodies that target PCSK9. Phase 3 trials have also been completed for bempedoic acid (targeting ATP-citrate lyase) and inclisiran (an interference RNA-based therapeutic targeting hepatic PCSK9 synthesis). In addition to LDL cholesterol, mendelian randomisation studies support a causal role for lipoprotein(a) and triglycerides in ischaemic heart disease. In this Series paper, we appraise currently available and emerging therapies for lowering LDL cholesterol, lipoprotein(a), and triglycerides for prevention of ischaemic heart disease.


Assuntos
Anticorpos Monoclonais/farmacologia , Anticolesterolemiantes/farmacologia , LDL-Colesterol/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Lipoproteínas/efeitos dos fármacos , Isquemia Miocárdica/prevenção & controle , LDL-Colesterol/sangue , Humanos , Lipoproteínas/sangue , Isquemia Miocárdica/tratamento farmacológico , Pró-Proteína Convertase 9 , Fatores de Risco , Triglicerídeos/sangue
8.
Biomed Res Int ; 2019: 7587451, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31380437

RESUMO

Nowadays, the prevention of severe myocardium injury resulting from myocardial ischemia/reperfusion injury (I/R) has been recognized as an important subject in the field of ischemic heart disease. In this study, H9c2 cardiomyocytes were exposed to cycles of hypoxia/reoxygenation (H/R) to mimic myocardial I/R injury. Western blot analysis and qRT-PCR were performed to detect the expression of Cox-2, Akt and p-Akt. Cell viability, LDH release and activity of Caspase-3 were assessed to determine the protective effect of propofol. The results proved that the protective effect of propofol for H/R challenged cardiomyocytes was associated with Akt phosphorylation. We also revealed that treatment of propofol suppressed the expression of Cox-2 in cardiomyocytes which was up-regulated after H/R treatment. Conversely, the over-expression of Cox-2 inhibited Akt phosphorylation while enhancing cardiomyocytes apoptosis. Interestingly, Akt activator exhibited similar protective effect with propofol and could diminish the influences brought by over-expression of Cox-2. Thus, it could be concluded that Cox-2 negatively affects the protective effect of propofol against hypoxia/reoxygenation induced cardiomyocyte apoptosis by suppressing Akt phosphorylation.


Assuntos
Ciclo-Oxigenase 2/genética , Proteína Oncogênica v-akt/genética , Propofol/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Isquemia Miocárdica/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fosforilação , Ratos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos
9.
Lakartidningen ; 1162019 Jul 17.
Artigo em Sueco | MEDLINE | ID: mdl-31334816

RESUMO

Elevation of troponin reflects myocardial infarction. The underlying causes should be assessed, as treatment and prognosis may differ widely. Myocardial damage with non-obstructive coronary arteries requires further evaluation including magnetic resonance tomography. We report a case of significant myocardial ischemia which was unnoticed by myocardial scintigraphy but detected by positron emission tomography (PET). The 15O-water tracer allows for quantitative assessment of myocardial perfusion including regional abnormalities and may thus diagnose microvascular dysfunction.


Assuntos
Isquemia Miocárdica/diagnóstico por imagem , Radioisótopos de Oxigênio , Tomografia por Emissão de Pósitrons/métodos , Água , Ecocardiografia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/tratamento farmacológico , Imagem de Perfusão do Miocárdio , Radioisótopos de Oxigênio/farmacocinética , Oligoelementos/farmacocinética
10.
Dis Markers ; 2019: 4823156, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316680

RESUMO

Apelin plays important roles in cardiovascular homeostasis. However, its effects on the mechanoenergetics of heart failure (HF) are unavailable. We attempted to investigate the effects of apelin on the left ventricular-arterial coupling (VAC) and mechanical efficiency in rats with HF. HF was induced in rats by the ligation of the left coronary artery. The ischemic HF rats were treated with apelin or saline for 12 weeks. The sham-operated animals served as the control. The left ventricular (LV) afterload and the systolic and diastolic functions, as well as the mechanoenergetic indices were estimated from the pressure-volume loops. Myocardial fibrosis by Masson's trichrome staining, myocardial apoptosis by TUNEL, and collagen content in the aorta as well as media area in the aorta and the mesenteric arteries were determined. Our data indicated that HF rats manifested an increased arterial load (Ea), a declined systolic function (reduced ejection fraction, +dP/dtmax, end-systolic elastance, and stroke work), an abnormal diastolic function (elevated end-diastolic pressure, τ, and declined -dP/dtmax), and decreased mechanical efficiency. Apelin treatment improved those indices. Concomitantly, increased fibrosis in the LV myocardium and the aorta and enhanced apoptosis in the LV were partially restored by apelin treatment. A declined wall-to-lumen ratio in the mesenteric arteries of the untreated HF rats was further reduced in the apelin-treated group. We concluded that the rats with ischemic HF were characterized by deteriorated LV mechanoenergetics. Apelin improved mechanical efficiency, at least in part, due to the inhibiting cardiac fibrosis and apoptosis in the LV myocardium, reducing collagen deposition in the aorta and dilating the resistant artery.


Assuntos
Apelina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Animais , Apoptose , Pressão Sanguínea , Colágeno/metabolismo , Insuficiência Cardíaca/etiologia , Masculino , Isquemia Miocárdica/complicações , Ratos , Ratos Wistar , Sístole , Função Ventricular Esquerda
11.
Zhongguo Zhong Yao Za Zhi ; 44(11): 2244-2250, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359649

RESUMO

PUE@PEG-PLGA micelles has excellent characteristics such as small particle size, high drug loading and slow drug release. The results of TEM electron microscopy showed that PUE@PEG-PLGA micelles had obvious core-shell structure. The critical micelle concentration(CMC) of PEG-PLGA micelles determined by pyrene assay was about 4.8 mg·L~(-1). Laser confocal experiments showed that PEG-PLGA micelles can enhance the cellular uptake of coumarin-6 and aggregate around the mitochondria; quantitative results of extracellular drug residues also indirectly confirmed that PEG-PLGA micelles can promote cellular uptake of the drug. Acute ischemic myocardial model rats were prepared by coronary artery ligation, and then the model rats were randomly divided into six groups: Sham operation group, model group, puerarin(PUE) group, as well as low-, mid-, and high-dose PUE@PEG-PLGA micelles groups. Drugs were given by iv administration 5 min after the ligation. The ST segment changes in the electrocardiogram were monitored; serum creatine kinase(CK), lactate dehydrogenase(LDH), aspartate aminotransferase(AST), and malondialdehyde(MDA) levels were detected and myocardial infarct size was also measured. Both PUE and PUE@PEG-PLGA micelles can reduce the elevated ST segment, reduce serum CK, LDH, AST and MDA levels, and reduce myocardial infarct size. The efficacy of PUE@PEG-PLGA medium and high dose groups was significantly better than that in the PUE group, and the efficacy in PUE@PEG-PLGA low dose group was basically equivalent to that in the PUE group. PUE@PEG-PLGA micelles can greatly improve the cardiomyocytes uptake of PUE, enhance the anti-acute myocardial ischemia effect of drugs, and reduce its dosage.


Assuntos
Isoflavonas/farmacologia , Micelas , Isquemia Miocárdica/tratamento farmacológico , Animais , Poliésteres , Polietilenoglicóis , Distribuição Aleatória , Ratos
12.
Kardiologiia ; 59(6): 12-17, 2019 Jun 25.
Artigo em Russo | MEDLINE | ID: mdl-31242836

RESUMO

PURPOSE: to assess drug therapy and achievement of target parameters of treatment in patients with ischemic heart disease (IHD) during 3-5 years of follow-up aſter coronary bypass surgery. MATERIALS AND METHODS: From the initial sample of the coronary bypass surgery registry (n=680) we selected for this study 111 men (mean age 61 [55; 65] years) hospitalized in 2011 with clinical picture of IHD for coronary artery bypass graſting (CABG). RESULTS: Mean duration of follow-up was 4.2 years. Mortality was 11.7 % (n=13), 11 deaths were cardiovascular, 2 - from unknown causes. End points defined as repeat hospitalizations and IHD progression were registered in 18 of 98 patients (18.4 %). Only in 25 % of patients during 3-5 years of observation aſter CABG there were no clinical signs of angina. Five patients (5.1 %) developed new type 2 diabetes. Drug therapy: 80 patients (81.6 %) received acetylsalicylic acid, 60 (61.2 %) - angiotensin converting enzyme inhibitors, 80 (81.6 %) - ß-adrenoblockers. Eighty-one men (82.6 %) received statins, but only 20 of 98 re-examined patients (20.4 %) took high doses. Target levels of low density lipoprotein cholesterolConclusion. Data of clinical practice illustrate insufficient quality of basic and antianginal therapy in patients with IHD aſter CABG. Indicators of control of angina, heart rate, achievement of target levels of parameters of lipid metabolism remain unsatisfactory.


Assuntos
Doença da Artéria Coronariana , Isquemia Miocárdica , Idoso , Angina Pectoris , Aspirina , Ponte de Artéria Coronária , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/tratamento farmacológico , Resultado do Tratamento
13.
Life Sci ; 231: 116569, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31202841

RESUMO

AIM: The IRE1 signaling pathway is implicated in I/R injury. However, little is known about the involvement of this pathway in low-dose LPS treatment of myocardial I/R injury. Thus, an attempt was made to determine the relationship between the IRE1 pathway and I/R injury using rats or in vitro H9C2 cell myocardial I/R injury models. MAIN METHODS: Sprague-Dawley rats and cultured H9C2 cells were pretreated with low-dose LPS and subjected to myocardial I/R injury models. KEY FINDINGS: Low-dose LPS did not affect normal rat or cellular function. Compared with the I/R group, treatment with LPS attenuated myocardial apoptosis, decreased plasma LDH and CK-MB activities, reduced myocardium infarct size, and downregulated caspase-3 expression. Moreover, the protein or mRNA expression levels of the IRE1 signaling pathway-related proteins Grp78, IRE1, p-ASK1, ASK1, p-JNK, and JNK were notably increased during I/R injury but significantly decreased by low-dose LPS treatment both in rats and in H9C2 cells. SIGNIFICANCE: Low-dose LPS exhibited therapeutic effects in myocardial I/R injury. Most importantly, the cardioprotective mechanism of low-dose LPS may be associated with the IRE1 signaling pathway.


Assuntos
Proteínas de Membrana/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Proteínas Serina-Treonina Quinases/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Proteínas de Choque Térmico/metabolismo , Lipopolissacarídeos/farmacologia , MAP Quinase Quinase Quinase 5/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Infarto do Miocárdio/metabolismo , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/efeitos dos fármacos
14.
Molecules ; 24(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067690

RESUMO

Out-of-hospital sudden cardiac arrest is a major public health problem with an overall survival of less than 5%. Upon cardiac arrest, cessation of coronary blood flow rapidly leads to intense myocardial ischemia and activation of the sarcolemmal Na+-H+ exchanger isoform-1 (NHE-1). NHE-1 activation drives Na+ into cardiomyocytes in exchange for H+ with its exchange rate intensified upon reperfusion during the resuscitation effort. Na+ accumulates in the cytosol driving Ca2+ entry through the Na+-Ca2+ exchanger, eventually causing cytosolic and mitochondrial Ca2+ overload and worsening myocardial injury by compromising mitochondrial bioenergetic function. We have reported clinically relevant myocardial effects elicited by NHE-1 inhibitors given during resuscitation in animal models of ventricular fibrillation (VF). These effects include: (a) preservation of left ventricular distensibility enabling hemodynamically more effective chest compressions, (b) return of cardiac activity with greater electrical stability reducing post-resuscitation episodes of VF, (c) less post-resuscitation myocardial dysfunction, and (d) attenuation of adverse myocardial effects of epinephrine; all contributing to improved survival in animal models. Mechanistically, NHE-1 inhibition reduces adverse effects stemming from Na+-driven cytosolic and mitochondrial Ca2+ overload. We believe the preclinical work herein discussed provides a persuasive rationale for examining the potential role of NHE-1 inhibitors for cardiac resuscitation in humans.


Assuntos
Parada Cardíaca/tratamento farmacológico , Isquemia Miocárdica/genética , Trocadores de Sódio-Hidrogênio/genética , Fibrilação Ventricular/tratamento farmacológico , Cálcio/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/genética , Parada Cardíaca/genética , Parada Cardíaca/patologia , Humanos , Modelos Animais , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Sarcolema/metabolismo , Sarcolema/patologia , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Trocadores de Sódio-Hidrogênio/metabolismo , Fibrilação Ventricular/genética , Fibrilação Ventricular/patologia
15.
Chem Biol Interact ; 308: 20-44, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31067438

RESUMO

Ischemic heart disease (IHD) is a major cause of cardiovascular morbidity and mortality worldwide, which is characterized by an imbalance between cardiac oxygen supply and demand predominantly due to obstruction of coronary arteries. Activation of the innate immune system and the consequent inflammatory response plays a role in the pathogenesis of IHD. Where an excessive inflammatory response may contribute to adverse cardiac remodeling and fibrosis, making inflammation an important therapeutic target for improving outcomes of IHD. While there are many discrepancies in the literature, evidence from both bench and clinical research demonstrate important effects of n-3 polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), toward IHD. N-3 PUFAs, and their metabolites, have been demonstrated to modulate various components of the immune system, including regulation of chemokines and cytokines, leukocyte chemotaxis and inflammasome formation. In this article, we provide an overview of the role the innate immune system has in IHD and focus on the immunomodulatory effects of n-3 PUFAs and their biologically active metabolites.


Assuntos
Cardiotônicos/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Imunidade Inata , Isquemia Miocárdica/tratamento farmacológico , Alarminas/metabolismo , Cardiotônicos/farmacologia , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Ciclo-Oxigenase 1/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Humanos , Imunidade Inata/efeitos dos fármacos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Isquemia Miocárdica/imunologia , Isquemia Miocárdica/patologia , Proteína-Lisina 6-Oxidase/metabolismo
16.
Pak J Pharm Sci ; 32(2): 647-650, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31081778

RESUMO

Aspirin is widely used as an antiplatelet agent . Many patients have been noticed with recurrence of major ischemic events in- spite of antiplatelet therapy. The objective of this study was to determine frequency of aspirin non-responsiveness /resistance in patients of ischemic heart disease. Seventy one patients of IHD were selected from out-patient department of Punjab Institute of Cardiology Lahore. Whole Blood Platelet aggregation studies were performed on Diamed Impact R. Aspirin response assay was performed with DiaChidon (Arachidoinc Acid 16mmol/L). Non responders to aspirin were assessed on the basis of software generated results: Surface covered (SC) >2.5% was considered as response to aspirin and SC <2.5% was considered as no response (or resistance) to Aspirin. Chi-square test was applied to measure statistical significance. Non-response to Aspirin was observed in 11% (8 out of 71). There was significant association (p=0.045) between resistance to aspirin and Diabetes mellitus. Treatment resistance was also significantly associated with female gender (p=0.015). We concluded that non response to Aspirin is seen in significant number of patients of IHD. Diabetes mellitus and female gender are strong risk factors of developing failure to aspirin therapy.


Assuntos
Aspirina/uso terapêutico , Isquemia Miocárdica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Estudos Transversais , Resistência a Medicamentos/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Isquemia Miocárdica/sangue , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária
17.
Zhongguo Zhong Yao Za Zhi ; 44(7): 1357-1362, 2019 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-31090292

RESUMO

In this study, solid dispersion technology was used to develop volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills(VOA-SNEDDS-DP) and its protective effect on acute myocardial ischemia injury was evaluated. Taking exterior quality, weight variation and the resolving time as comprehendsive evaluation indexes, the preparation process and formulation of the dropping pills were optimized by orthogonal design, and the dissolution rate in vitro of the optimized VOA-SNEDDS-DP was investigated. The rat model of acute myocardial ischemia was induced by intraperitoneal injection of isoproterenol hydrochloride and the serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), creatine kinase(CK) and pathological changes of myocardial tissue were determined to evaluate therapeutic effect of the dropping pills on acute myocardial ischemia. The results showed that the optimal formulation and preparation process of VOA-SNEDDS-DP were as follows: PEG6000-PEG8000 was 1∶1, proportion of VOA-SNEDDS and matrix was l∶2.5, the temperature of drug fluids was 75 ℃, drop rate was 35 drops/min, drop distance was 5 cm, the condensing agent temperature was 2-10 ℃. The content of ß-asarone in the dropping pills was 42.46 mg·g~(-1). The accumulated dissolution rate of the dropping pills reached 93.85% in 10 min. The results of pharmacodynamic experiments showed that VOA-SNEDDS-DP could significantly increase the SOD content(P<0.05), reduce the levels of MDA and CK(P<0.05) in serum, and effectively improve the pathological morphology of myocardial tissue. These results revealed that the preparation of VOA-SNEDDS-DP by solid dispersion technology was stable and feasible, and VOA-SNEDDS-DP had protective effect on acute myocardial ischemia injury.


Assuntos
Acorus/química , Medicamentos de Ervas Chinesas/farmacologia , Isquemia Miocárdica/tratamento farmacológico , Óleos Voláteis/farmacologia , Óleos Vegetais/farmacologia , Animais , Creatina Quinase/sangue , Malondialdeído/sangue , Ratos , Superóxido Dismutase/sangue
18.
Am J Clin Nutr ; 109(4): 1197-1206, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30949673

RESUMO

BACKGROUND: Evolutionary biology suggests reproduction trades off against longevity. Genetic selection in favor of fertility and ischemic heart disease (IHD) exists in humans. Observationally, soy protects against IHD. Soy amino acids, glutamate and aspartate, may lower androgens. No large randomized controlled trials testing their health effects exist. OBJECTIVE: Using Mendelian randomization, we assessed how genetically predicted glutamate and aspartate affected IHD, blood pressure, and diabetes. METHODS: A separate sample instrumental variable analysis with genetic instruments was used to obtain unconfounded estimates using genetic variants strongly (P < 5 × 10(-8)) and solely associated with glutamate or aspartate applied to an IHD case (n ≤76,014)-control (n ≤ 264,785) study (based on a meta-analysis of CARDIoGRAMplusC4D 1000 Genomes, UK Biobank CAD SOFT GWAS and Myocardial Infarction Genetics and CARDIoGRAM Exome), blood pressure from the UK Biobank (n ≤ 361,194), and the DIAbetes Genetics Replication And Meta-analysis diabetes case (n = 26,676)-control (n = 132,532) study. A weighted median and MR-Egger were used for a sensitivity analysis. RESULTS: Glutamate was not associated with IHD, blood pressure, or diabetes after correction for multiple comparisons. Aspartate was inversely associated with IHD (odds ratio (OR) 0.92 per log-transformed standard deviation (SD); 95% confidence interval (CI) 0.88, 0.96) and diastolic blood pressure (-0.03; 95% CI -0.04, -0.02) using inverse variance weighting, but not diabetes (OR 1.00; 95% CI 0.91, 1.09). Associations were robust to the sensitivity analysis. CONCLUSIONS: Our findings suggest aspartate may play a role in IHD and blood pressure, potentially underlying cardiovascular benefits of soy. Clarifying the mechanisms would be valuable for IHD prevention and for defining a healthy diet.


Assuntos
Ácido Aspártico/administração & dosagem , Ácido Glutâmico/administração & dosagem , Isquemia Miocárdica/genética , Isquemia Miocárdica/fisiopatologia , Pressão Sanguínea , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Suplementos Nutricionais/análise , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Isquemia Miocárdica/tratamento farmacológico , Polimorfismo de Nucleotídeo Único
19.
Eur J Pharm Sci ; 134: 1-6, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30959104

RESUMO

Rotigotine is a dopamine receptor agonist that can improve motor function in Parkinson's disease (PD) patients. Rotigotine extended-release microsphere (RoMS) is an extended-release intramuscular formulation that exhibits a sustained release of rotigotine over a 14-day period. The clinical trials of RoMS has been carried out in USA and China. The purpose of this study is to observe the effects of RoMS therapy on myocardial ischemic injury in mice, to know whether RoMS alleviate or deteriorate the myocardial ischemic injury while PD patient has onset of myocardial ischemia concurrent after administered with RoMS. A mouse model of myocardial ischemia was established using isoproterenol, and mice were pretreated with rotigotine or RoMS before inducing myocardial ischemic injury. The effects of rotigotine or RoMS therapy on the degree of myocardial ischemic injury were studied by evaluating troponin I level, creatine kinase-MB (CK-MB) activity, and histopathological changes in cardiomyocytes. The dopamine receptor blocker chlorpromazine was used to further investigate the effects of rotigotine or RoMS on myocardial ischemic injury. Furthermore, serum rotigotine concentrations were also assayed. When myocardial ischemia occurred during rotigotine or RoMS administration, troponin I level and CK-MB activity were decreased, and ischemia-induced histopathological changes in cardiomyocytes were alleviated. The effects of rotigotine were maintained only 12 h and after that no protective effect was observed. RoMS releases continuously into the circulation after intramuscular injection. The cardioprotective effects of RoMS were maintained 14 days after a single RoMS administration. When combined with chlorpromazine, the protective effects of rotigotine on myocardial ischemic injury were eliminated, and the protective effects of RoMS were also partially abolished. In the animal model of myocardial ischemia, pretreatment with rotigotine or RoMS does not deteriorate, but can alleviate cardiomyocyte injury. Furthermore, RoMS pretreatment show long-term and continuous protective effects on cardiomyocyte injury. RoMS therapy in PD patients at high risk for cardiovascular diseases may attenuate the degree of cardiomyocyte injury caused by ischemia.


Assuntos
Cardiotônicos/farmacocinética , Agonistas de Dopamina/farmacocinética , Microesferas , Isquemia Miocárdica/tratamento farmacológico , Tetra-Hidronaftalenos/farmacocinética , Tiofenos/farmacocinética , Animais , Cardiotônicos/administração & dosagem , Cardiotônicos/uso terapêutico , Clorpromazina/antagonistas & inibidores , Creatina Quinase Forma MB/efeitos dos fármacos , Creatina Quinase Forma MB/metabolismo , Agonistas de Dopamina/administração & dosagem , Agonistas de Dopamina/uso terapêutico , Isoproterenol/farmacologia , Masculino , Camundongos , Modelos Animais , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Doença de Parkinson/tratamento farmacológico , Tetra-Hidronaftalenos/administração & dosagem , Tetra-Hidronaftalenos/uso terapêutico , Tiofenos/administração & dosagem , Tiofenos/uso terapêutico , Troponina I/efeitos dos fármacos , Troponina I/metabolismo
20.
Life Sci ; 227: 8-19, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30986447

RESUMO

AIMS: Cardiac ischemic conditioning has been shown to decrease ischemic injury in experimental models and clinically. Activation of survival pathways leading to heat shock proteins (HSP) modulation is an important contributor to this effect. We have previously shown that celastrol, an HSP90 modulator, achieves cardioprotection through activation of cytoprotective HSP's and heme-oxygenase-1 (HO-1). This is the first comparative evaluation of several modulators of HSP90 activity for cardioprotection. Furthermore, basic celastrol structure-activity relationship was characterized in order to develop novel potent infarct sparing agents suitable for clinical development. MAIN METHODS: Combining in vitro cell culture using rat myocardial cell line exposed to ischemic and ischemia/reperfusion (I/R) stresses, and ex vivo Langendorff rat heart perfusion I/R model, we evaluated cardioprotective effects of various compounds. Selected signalling pathways were evaluated by western blot and reporter gene activation. KEY FINDINGS: From a variety of HSP90 modulator chemotypes, the celastrol family was most efficient in inducing cytoprotective HSP70 and HO-1 protein overexpression and cell survival in vitro. Celastrol and two synthetic analogs were protective against ischemia and prevented ischemia/reperfusion (I/R) injury when given as pre-treatment or at time of reperfusion, increasing viability and reducing mitochondrial permeability transition pore opening. Ex vivo experiments demonstrated that the two synthetic analogs show cardioprotective activity at lower concentrations compared to celastrol, with activation of multiple survival pathways. SIGNIFICANCE: Celastrol backbone is essential for cardioprotection through HSP90 activity modulation. These compounds hold promise as novel adjunct treatment to improve outcome in the clinical management of I/R injury.


Assuntos
Cardiotônicos/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Triterpenos/farmacologia , Animais , Cardiotônicos/uso terapêutico , Linhagem Celular , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Coração , Proteínas de Choque Térmico/metabolismo , Masculino , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Ratos , Ratos Endogâmicos Lew , Transdução de Sinais/efeitos dos fármacos , Triterpenos/metabolismo
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