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1.
PLoS One ; 15(8): e0238039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32853284

RESUMO

Sepsis is a global economic and health burden. Dipeptidyl peptidase 3 (DPP3) is elevated in the plasma of septic patients. The highest levels of circulating DPP3 (cDPP3) are found in non-survivor septic shock patients. The aim of this study was to evaluate the benefits of inhibiting cDPP3 by a specific antibody, Procizumab (PCZ), on cardiac function in an experimental model of sepsis, the caecal ligature and puncture (CLP) model. Rats were monitored by invasive blood pressure and echocardiography. Results are presented as mean ± SD, with p <0.05 considered significant. PCZ rapidly restored left ventricular shortening fraction (from 39 ± 4% to 51 ± 2% before and 30 min after PCZ administration (p = 0.004)). Cardiac output and stroke volume were higher in the CLP + PCZ group when compared to the CLP + PBS group (152 ± 33 mL/min vs 97 ± 25 mL/min (p = 0.0079), and 0.5 ± 0.1 mL vs 0.3 ± 1.0 mL (p = 0.009), respectively) with a markedly reduced plasma DPP3 activity (138 ± 70 U/L in CLP + PCZ group versus 735 ± 255 U/L (p = 0.048) in the CLP + PBS group). Of note, PCZ rapidly reduced oxidative stress in the heart of the CLP + PCZ group when compared to those of the CLP + PBS group (13.3 ± 8.2 vs 6.2 ± 2.5 UI, p = 0.005, 120 min after administration, respectively). Our study demonstrates that inhibition of cDPP3 by PCZ restored altered cardiac function during sepsis in rats.


Assuntos
Dipeptidil Peptidases e Tripeptidil Peptidases/antagonistas & inibidores , Dipeptidil Peptidases e Tripeptidil Peptidases/sangue , Inibidores Enzimáticos/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Sepse/sangue , Sepse/fisiopatologia , Animais , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Masculino , Estudo de Prova de Conceito , Ratos , Ratos Wistar , Sepse/enzimologia , Sístole/efeitos dos fármacos , Sístole/fisiologia
2.
Life Sci ; 259: 118290, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32822713

RESUMO

AIMS: Atrial fibrillation (AF) is a common arrhythmia which is associated with higher risk of stroke, heart failure and all-cause mortality. Abnormal Ca2+ handling in diabetes mellitus (DM) can cause delayed depolarization involved with increased NCX activity. Complicated mechanisms are involved in atrial remodeling, of which CaMKII may be a key node signal. Therefore, we intend to explore whether CaMKII activation induces atrial electrical remodeling by regulating NCX expression in this study. MAIN METHODS: Adult male SD rats were used to establish a diabetic rat model, divided into three groups: the control group, DM group and allopurinol group. Hemodynamic and ECG indicators were recorded, after which electrophysiological studies were conducted. The protein expression of CaMKII, p-CaMKII, XO, MnSOD and NCX was measured by Western blot and immunohistochemistry. H&E and Masson staining were applied for observing myocardial fibrosis. HL-1 cells were cultured for the measurement of ROS generation. KEY FINDINGS: The arrangement of atrial myocytes was disordered and the collagen volume fraction of the atrium tissue was elevated in the DM group compared with the control group, and improved by allopurinol. Higher incidence of inducible AF, reduced conduction velocity and higher conduction inhomogeneity were observed in diabetic rats. These electrophysiological abnormalities were accompanied by higher oxidative stress and protein expression of p-CaMKII and NCX. Allopurinol prevented the development of these abnormal changes. SIGNIFICANCE: Allopurinol can improve atrial electrical remodeling by inhibiting CaMKII activity and protein expression of NCX. These data indicate xanthine oxidase inhibition can reduce oxidative stress and ameliorate atrial electrical remodeling.


Assuntos
Alopurinol/farmacologia , Remodelamento Atrial/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Diabetes Mellitus Experimental/complicações , Cardiomiopatias Diabéticas/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Xantina Oxidase/antagonistas & inibidores , Animais , Western Blotting , Ecocardiografia , Hemodinâmica/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
3.
Int Heart J ; 61(4): 799-805, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32728000

RESUMO

Therapeutic strategies for pulmonary arterial hypertension (PAH) have made remarkable progress over the last two decades. Currently, 3 types of drugs can be used to treat PAH; prostacyclins, phosphodiesterase 5 inhibitors, and endothelin receptor antagonists (ERA). In Japan, the first generation ERA bosentan was reimbursed in 2005, following which the 2nd generation ERAs ambrisentan and macitentan were reimbursed in 2009 and 2015, respectively. The efficacy of each ERA on hemodynamics in PAH patients remains to be elucidated. The aims of this study were to evaluate the hemodynamic effects of ERAs and compare these effects among each generation of ERAs.We retrospectively examined the clinical parameters of 42 PAH patients who were prescribed an ERA (15 bosentan, 12 ambrisentan, and 15 macitentan) and who underwent a hemodynamic examination before and after ERA introduction at our institution from January 2007 to July 2019.In a total of 42 patients, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) were significantly decreased and cardiac index was significantly increased after ERA introduction (P < 0.001) and the World Health Organization-Functional class (WHO-Fc) was significantly improved after ERA introduction (P = 0.005). Next, in a comparison between 1st and 2nd generation ERAs, 2nd generation ERAs were found to have brought about greater improvements in hemodynamic parameters (mPAP and PVR. P < 0.01), heart rate, brain natriuretic peptide, arterial oxygen saturation, and mixed venous oxygen saturation than the 1st generation ERA bosentan.We conclude that all ERAs could successfully improve the hemodynamics of PAH patients and that the newer generation ERAs, ambrisentan and macitentan, seemed to be preferable to bosentan.


Assuntos
Bosentana/uso terapêutico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Fenilpropionatos/uso terapêutico , Hipertensão Arterial Pulmonar/tratamento farmacológico , Piridazinas/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Administração Oral , Adulto , Idoso , Bosentana/administração & dosagem , Estudos de Casos e Controles , Antagonistas dos Receptores de Endotelina/administração & dosagem , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenilpropionatos/administração & dosagem , Inibidores da Fosfodiesterase 5/uso terapêutico , Placebos/administração & dosagem , Prostaglandinas I/uso terapêutico , Hipertensão Arterial Pulmonar/fisiopatologia , Pressão Propulsora Pulmonar/efeitos dos fármacos , Piridazinas/administração & dosagem , Pirimidinas/administração & dosagem , Estudos Retrospectivos , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos
4.
Int J Nanomedicine ; 15: 4393-4405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606684

RESUMO

Aim: The effects of polyamidoamine (PAMAM) dendrimers on the mammalian heart are not completely understood. In this study, we have investigated the effects of a sixth-generation cationic dendrimer (G6 PAMAM) on cardiac function in control and diabetic rat hearts following ischemia-reperfusion (I/R) injury. Methods: Isolated hearts from healthy non-diabetic (Ctr) male Wistar rats were subjected to ischemia and reperfusion (I/R). LV contractility and hemodynamics data were computed digitally whereas cardiac damage following I/R injury was assessed by measuring cardiac enzymes. For ex vivo acute exposure experiments, G6 PAMAM was administered during the first 10 mins of reperfusion in Ctr animals. In chronic in vivo studies, nondiabetic rats (Ctr) received either vehicle or daily i.p. injections of G6 PAMAM (40 mg/kg) for 4 weeks. Diabetic (D) animals received either vehicle or daily i.p. injections of G6 PAMAM (10, 20 or 40 mg/kg) for 4 weeks. The impact of G6 PAMAM on pacing-postconditioning (PPC) was also studied in Ctr and D rats. Results: In ex vivo studies, acute administration of G6 PAMAM to isolated Ctr hearts during reperfusion dose-dependently impaired recovery of cardiac hemodynamics and vascular dynamics parameters following I/R injury. Chronic daily i.p. injections of G6 PAMAM significantly (P<0.01) impaired recovery of cardiac function following I/R injury in nondiabetic animals but this was not generally observed in diabetic animals except for CF which was impaired by about 50%. G6 PAMAM treatment completely blocked the protective effects of PPC in the Ctr animals. Conclusion: Acute ex vivo or chronic in vivo treatment with naked G6 PAMAM dendrimer can significantly compromise recovery of non-diabetic hearts from I/R injury and can further negate the beneficial effects of PPC. Our findings are therefore extremely important in the nanotoxicological evaluation of G6 PAMAM dendrimers for potential clinical applications in physiological and pathological settings.


Assuntos
Dendrímeros/toxicidade , Coração/fisiopatologia , Mamíferos/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Nanopartículas/toxicidade , Poliaminas/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Pós-Condicionamento Isquêmico , Masculino , Contração Miocárdica/efeitos dos fármacos , Miocárdio/enzimologia , Ratos Wistar
5.
Isr Med Assoc J ; 7(22): 338-342, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32692493

RESUMO

BACKGROUND: Methylene blue (MB), an inhibitor of nitric oxide synthesis and its effects is a potentially effective treatment against distributive shock states such as septic shock and vasoplegic syndrome. MB has been shown to alleviate vasoplegia and promote an increase in blood pressure. It may reduce mortality. However, in the pediatric population, there are few case reports and only one controlled study on administration of MB use for vasoplegia, sepsis, or shock in general. OBJECTIVES: To summarize the experience of administering MB for vasoplegic shock in a tertiary care pediatric intensive care unit. METHODS: A retrospective chart review of seven pediatric cases treated with MB for vasoplegic shock was conducted. MB was administered as a bolus followed by continuous infusion. The authors measured blood pressure, vasopressor, and inotropic support. Patient outcome was monitored. RESULTS: The authors observed a favorable hemodynamic response with an increase in blood pressure and a reduction in vasopressor and inotropic support needed following MB administration in six patients. No side effects were observed. Three patients eventually died one to two days later, secondary to their underlying disease. CONCLUSIONS: This case series adds to the small body of evidence in the pediatric population supporting the use of MB for distributive shock states and emphasizes the need for larger, randomized trials evaluating its role in vasoplegic shock treatment.


Assuntos
Hemodinâmica/efeitos dos fármacos , Azul de Metileno/administração & dosagem , Choque Séptico/tratamento farmacológico , Vasoplegia/tratamento farmacológico , Pré-Escolar , Estado Terminal , Inibidores Enzimáticos/administração & dosagem , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Masculino , Estudos Retrospectivos , Resultado do Tratamento
6.
PLoS One ; 15(7): e0235084, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614837

RESUMO

Hemorrhagic shock is one of the leading causes of mortality and morbidity in pediatric trauma. Current treatment based on volume resuscitation is associated to adverse effects, and it has been proposed that vasopressors may be used in the pharmacological management of trauma. Terlipressin has demonstrated its usefulness in other pediatric critical care scenarios and its long half-life allows its use as a bolus in an outpatient critical settings. The aim of this study was to analyze whether the addition of a dose of terlipressin to the initial volume expansion produces an improvement in hemodynamic and cerebral perfusion at early stages of hemorrhagic shock in an infant animal model. We conducted an experimental randomized animal study with 1-month old pigs. After 30 minutes of hypotension (mean arterial blood pressure [MAP]<45 mmHg) induced by the withdrawal of blood over 30 min, animals were randomized to receive either normal saline (NS) 30 mL/kg (n = 8) or a bolus of 20 mcg/kg of terlipressin plus 30 mL/kg of normal saline (TP) (n = 8). Global hemodynamic and cerebral monitoring parameters, brain damage markers and histology samples were compared. After controlled bleeding, significant decreases were observed in MAP, cardiac index (CI), central venous pressure, global end-diastolic volume index (GEDI), left cardiac output index, SvO2, intracranial pressure, carotid blood flow, bispectral index (BIS), cerebral perfusion pressure (CPP) and increases in systemic vascular resistance index, heart rate and lactate. After treatment, MAP, GEDI, CI, CPP and BIS remained significantly higher in the TP group. The addition of a dose of terlipressin to initial fluid resuscitation was associated with hemodynamic improvement, intracranial pressure maintenance and better cerebral perfusion, which would mean protection from ischemic injury. Brain monitoring through BIS was able to detect changes caused by hemorrhagic shock and treatment.


Assuntos
Hemodinâmica/efeitos dos fármacos , Solução Salina/uso terapêutico , Choque Hemorrágico/terapia , Terlipressina/uso terapêutico , Vasoconstritores/uso terapêutico , Animais , Animais Recém-Nascidos , Circulação Cerebrovascular/efeitos dos fármacos , Modelos Animais de Doenças , Hidratação , Masculino , Ressuscitação , Choque Hemorrágico/sangue , Choque Hemorrágico/fisiopatologia , Suínos
7.
Life Sci ; 259: 118162, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32730836

RESUMO

OBJECTIVE: The inhaled sevoflurane (sevo) is known to protect against myocardial ischemia/reperfusion (I/R) injury (MIRI), in which the functions of microRNAs (miRNAs) have been uncovered. However, the effect of sevo regulating miR-204 on this disease remains unknown. This research aims to explore the roles of sevo and miR-204 in the progression of MIRI. METHODS: The MIRI mice models induced by coronary artery ligation were treated by sevo, miR-204 mimics or silenced coactosin-like protein-1 (Cotl1). The pathology of mice myocardial tissues, apoptosis and ultrastructure of cardiomyocytes were observed. The expression of miR-204, Cotl1, Bax and Bcl-2 was determined. The contents of oxidative stress-related factors and inflammatory factors in mouse myocardial tissues were assessed, and the serum levels of indicators that correlated with myocardial infarction were determined as well. The target relation between miR-204 and Cotl1 was confirmed. RESULTS: MiR-204 was down-regulated, and Cotl1 was up-regulated in myocardial tissues of MIRI mice, and Cotl1 was targeted by miR-204. Sevo, elevated miR-204 and inhibited Cotl1 could promote cardiac function of MIRI mice, and protect myocardial tissue against MIRI by repressing the cardiomyocyte apoptosis, oxidative stress and inflammation reaction in MIRI mice. CONCLUSION: We found that sevo could up-regulate miR-204 to ameliorate MIRI in mice by inhibiting Cotl1 expression, which may provide candidates for the MIRI treatment.


Assuntos
Anestésicos Inalatórios/farmacologia , MicroRNAs/biossíntese , Proteínas dos Microfilamentos/antagonistas & inibidores , Isquemia Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Sevoflurano/farmacologia , Animais , Progressão da Doença , Hemodinâmica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
8.
Ther Adv Cardiovasc Dis ; 14: 1753944720934937, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32611276

RESUMO

Ivabradine is a pure heart-rate lowering drug that is nowadays used, accordingly to the last ESC Guidelines, to reduce mortality and heart failure (HF) hospitalization in patients with HF with reduced ejection fraction and in symptomatic patiens with inappropriate sinus tachycardia. Moreover, interesting effect of ivabradine on endothelial and myocardial function and on oxidative stress and inflamation pathways are progressively emerging. The aim of this paper is to highlight newer evidences about ivabradine effect (and consequently possible future application of the drug) in pathological settings different from guidelines-based clinical practice.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Ivabradina/uso terapêutico , Animais , Função Atrial/efeitos dos fármacos , Fármacos Cardiovasculares/efeitos adversos , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Ivabradina/efeitos adversos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Função Ventricular/efeitos dos fármacos
9.
Am J Physiol Heart Circ Physiol ; 319(2): H456-H467, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706261

RESUMO

Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the leg arteries, which causes claudication. This may be in part due to vascular mitochondrial dysfunction and excessive reactive oxygen species (ROS) production. A mitochondrial-targeted antioxidant (MitoQ) has been shown to improve vascular mitochondrial function that, in turn, led to improved vascular function in older adults and animal models. However, the roles of vascular mitochondria in vascular function including endothelial function and arterial stiffness in patients with PAD are unknown; therefore, with the use of acute MitoQ intake, this study examined the roles of vascular mitochondria in endothelial function, arterial stiffness, exercise tolerance, and skeletal muscle function in patients with PAD. Eleven patients with PAD received either MitoQ or placebo in a randomized crossover design. At each visit, blood samples, brachial and popliteal artery flow-mediated dilation (FMD), peripheral and central pulse-wave velocity (PWV), blood pressure (BP), maximal walking capacity, time to claudication (COT), and oxygen utility capacity were measured pre- and-post-MitoQ and placebo. There were significant group by time interactions (P < 0.05) for brachial and popliteal FMD that both increased by Δ2.6 and Δ3.3%, respectively, and increases superoxide dismutase (Δ0.03 U/mL), maximal walking time (Δ73.8 s), maximal walking distance (Δ49.3 m), and COT (Δ44.2 s). There were no changes in resting heart rate, BP, malondialdehyde, total antioxidant capacity, PWV, or oxygen utility capacity (P > 0.05). MitoQ intake may be an effective strategy for targeting the vascular mitochondrial environment, which may be useful for restoring endothelial function, leg pain, and walking time in patients with PAD.NEW & NOTEWORTHY The results of this study reveal for the first time that acute oral intake of mitochondrial-targeted antioxidant (MitoQ, 80 mg) is effective for improving vascular endothelial function and superoxide dismutase in patients with peripheral artery disease (PAD). Acute MitoQ intake is also effective for improving maximal walking capacity and delaying the onset of claudication in patients with PAD. These findings suggest that the acute oral intake of MitoQ-mediated improvements in vascular mitochondria play a pivotal role for improving endothelial function, the redox environment, and skeletal muscle performance in PAD.


Assuntos
Antioxidantes/uso terapêutico , Artéria Braquial/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Tolerância ao Exercício/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Claudicação Intermitente/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Compostos Organofosforados/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Artéria Poplítea/efeitos dos fármacos , Ubiquinona/análogos & derivados , Idoso , Antioxidantes/metabolismo , Pressão Arterial/efeitos dos fármacos , Artéria Braquial/metabolismo , Artéria Braquial/fisiopatologia , Estudos Cross-Over , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/metabolismo , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Contração Muscular/efeitos dos fármacos , Nebraska , Compostos Organofosforados/metabolismo , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/metabolismo , Artéria Poplítea/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Ubiquinona/metabolismo , Ubiquinona/uso terapêutico , Rigidez Vascular/efeitos dos fármacos , Caminhada
11.
Br J Anaesth ; 125(2): 192-200, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32563492

RESUMO

BACKGROUND: Anaesthesia-induced changes in renal perfusion are dependent on the choice of anaesthetic agent. However, the effects of varying inspired oxygen fraction (FiO2) on renal perfusion and oxygenation during TIVA (propofol + fentanyl) or volatile anaesthesia (VA; isoflurane) are unknown. METHODS: In 16 Merino ewes, we surgically implanted a renal artery flow probe and laser-Doppler and oxygen-sensing probes in the renal medulla and cortex. We compared the systemic and renal effects of graded alterations in FiO2 (0.21, 0.40, 0.60, and 1.0) during TIVA or VA and compared the changes with those in the non-anaesthetised state. RESULTS: Compared with the non-anaesthetised state, TIVA and VA decreased renal blood flow (-50% vs -75%), renal oxygen delivery (-50% vs -80%), and renal cortical (-40% vs -60%) and medullary perfusion (-50% vs -75%). At an FiO2 of 0.21, both anaesthetic regimens induced similar reductions in cortical (-58 vs -65%) and medullary (-37% vs -38%) oxygenation. At higher concentrations of FiO2, renal blood flow and renal tissue perfusion were not changed, but intrarenal oxygenation improved similarly under TIVA and VA. In particular, at an FiO2 of ≥0.40 and ≤0.60, cortical and medullary oxygen tension were similar to the non-anaesthetised state. CONCLUSIONS: Irrespective of FiO2, TIVA decreased renal and intrarenal perfusion less than VA, but at low FiO2 concentrations both led to equivalent reductions in renal cortical and medullary oxygenation. However, with FiO2 between 0.40 and 0.60 during TIVA or VA, both cortical and medullary oxygenation was maintained at normal physiological levels.


Assuntos
Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Hemodinâmica/efeitos dos fármacos , Oxigênio/metabolismo , Circulação Renal/efeitos dos fármacos , Animais , Feminino , Fentanila , Isoflurano/farmacologia , Modelos Animais , Propofol/farmacologia , Ovinos
12.
Vet Res Commun ; 44(2): 73-81, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32500313

RESUMO

BACKGROUND: Sildenafil improves autonomic dysfunction caused by pulmonary hypertension (PH) in humans, but its effect is unknown in dogs with PH. This prospective study aimed to evaluate the autonomic nervous system function of a canine model of chronic embolic PH (CEPH) and the autonomic nervous system function of a canine model of CEPH in which sildenafil was administered. METHODS: This study used five clinically healthy female beagle dogs. Evaluation parameters included hemodynamic parameters, heart rate (HR) and heart rate variability (HRV). Each evaluation parameter was compared before and after creating the CEPH model (before, BL; after, CEPHBL) and between the CEPHBL model and after the administration of sildenafil (1 mg/kg, BID) in the CEPH model dogs (CEPHSil). RESULTS: In the CEPHBL model, the hemodynamic parameters indicated cardiac hypofunction, and HR was significantly increased and HRV was significantly decreased compared with BL. Further, in the CEPHSil model, the hemodynamic parameters suggested improvement in cardiac function, and HRV was significantly increased. CONCLUSIONS: From the results of the CEPH model dogs, autonomic dysfunction was shown to occur in PH dogs. In addition, the administration of 1 mg/kg of sildenafil to CEPH model dogs may improve autonomic dysfunction.


Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/farmacologia , Animais , Sistema Nervoso Autônomo/fisiopatologia , Doença Crônica , Modelos Animais de Doenças , Cães , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/fisiopatologia
13.
PLoS One ; 15(6): e0234653, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32579577

RESUMO

We previously demonstrated that hexokinase II (HK2) dissociation from mitochondria during cardiac ischemia correlates with cytochrome c (cyt-c) loss, oxidative stress and subsequent reperfusion injury. However, whether HK2 release is the primary signal mediating this ischemia-induced mitochondrial dysfunction was not established. To investigate this, we studied the effects of dissociating HK2 from isolated heart mitochondria. Mitochondria isolated from Langendorff-perfused rat hearts before and after 30 min global ischemia ± ischemic preconditioning (IPC) were subject to in vitro dissociation of HK2 by incubation with glucose-6-phosphate at pH 6.3. Prior HK2 dissociation from pre- or end-ischemic heart mitochondria had no effect on their cyt-c release, respiration (± ADP) or mitochondrial permeability transition pore (mPTP) opening. Inner mitochondrial membrane morphology was assessed indirectly by monitoring changes in light scattering (LS) and confirmed by transmission electron microscopy. Although no major ultrastructure differences were detected between pre- and end-ischemia mitochondria, the amplitude of changes in LS was reduced in the latter. This was prevented by IPC but not mimicked in vitro by HK2 dissociation. We also observed more Drp1, a mitochondrial fission protein, in end-ischemia mitochondria. IPC failed to prevent this increase but did decrease mitochondrial-associated dynamin 2. In vitro HK2 dissociation alone cannot replicate ischemia-induced effects on mitochondrial function implying that in vivo dissociation of HK2 modulates end-ischemia mitochondrial function indirectly perhaps involving interaction with mitochondrial fission proteins. The resulting changes in mitochondrial morphology and cristae structure would destabilize outer / inner membrane interactions, increase cyt-c release and enhance mPTP sensitivity to [Ca2+].


Assuntos
Hexoquinase/metabolismo , Mitocôndrias Cardíacas/enzimologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Isquemia Miocárdica/enzimologia , Animais , Respiração Celular/efeitos dos fármacos , Dinaminas/metabolismo , Glucose-6-Fosfato/farmacologia , Hemodinâmica/efeitos dos fármacos , Concentração de Íons de Hidrogênio , Precondicionamento Isquêmico , Ligantes , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/ultraestrutura , Dinâmica Mitocondrial/efeitos dos fármacos , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Isquemia Miocárdica/patologia , Ligação Proteica/efeitos dos fármacos , Ratos Wistar
16.
PLoS One ; 15(6): e0234714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584842

RESUMO

As a consequence of a hormonal imbalance, Prostatic Hyperplasia (PH) is characterized by increased prostate volume, along with higher local angiogenesis and vascularization. Orchiectomy is the common treatment for dogs, however it is not an option for breeding animals. Thus, finasteride arises as the drug of choice for stud dogs. Therefore, the aim of this study was to evaluate the effects of orchiectomy or finasteride therapies on hormonal and vascular dynamics of PH dogs. Fifteen dogs, aged 6-13 years were assigned to: Untreated Group (dogs diagnosed with PH-n = 5), Finasteride treated group (PH dogs treated with finasteride-n = 5) and Orchiectomy treated group (PH dogs submitted to orchiectomy-n = 5). Evaluations were performed in a monthly interval (first day of treatment; after 30 and 60 days). Doppler ultrasonography was performed to measure prostatic volume, vascularization and hemodynamic profile of prostatic artery. Dihydrotestosterone, estrogen and testosterone concentrations were measured. At day 60, prostatic biopsy was performed for histological, immunohistochemical and qPCR analysis for VEGF-A expression. At day 60, vascularization score was higher in untreated compared to treated groups (finasteride and orchiectomy). Furthermore, VEGF-A expression was lower in the Orchiectomy Treated Group, but VEGF-A was immunohistochemically lower in both treated groups (finasteride and orchiectomy) compared to the Untreated Group. The efficiency of finasteride treatment in reducing clinical signs, prostate volume and vascularization appears to be similar to orchiectomy. In conclusion, both PH medical and surgical therapy lead to reduction in prostate dimension and VEGF-A expression and, consequently, lower local vascularization. However, orchiectomy promotes marked hormonal changes, which ultimately lead to prostate atrophy.


Assuntos
Doenças do Cão/fisiopatologia , Finasterida/farmacologia , Hemodinâmica/efeitos dos fármacos , Hormônios/sangue , Neovascularização Patológica , Orquiectomia , Hiperplasia Prostática/veterinária , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Doenças do Cão/cirurgia , Cães , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Hiperplasia Prostática/patologia , Hiperplasia Prostática/fisiopatologia , Hiperplasia Prostática/terapia , Ultrassonografia Doppler , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Mymensingh Med J ; 29(2): 341-350, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32506088

RESUMO

Noxious stimuli during craniotomy may encourage hypertension and tachycardia, which may rise to morbidity in patients with intracranial hypertension. After craniotomy a moderate level of postoperative pain observed. The objective of this study was to observe the effect of intravenous paracetamol with bupivacaine scalp nerve block (SNB) on haemodynamics response as well as anaesthetic & analgesic requirements during supratentorial craniotomies. This is a single-blind, placebo-controlled, randomized clinical trial carried out in the Neurosurgery operation theatre from August 2015 to July 2017 under supervision of Department of Anaesthesia, Analgesia and Intensive Care Medicine of Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. A total of 40 patients aged 18-60 years with supratentorial space occupying lesion undergoing craniotomy under general anaesthesia who were attended in the department of Neurosurgery, BSMMU were enrolled in this study and they were divided randomly into two groups, 20 patients in each. The Group A received 100ml normal saline infusion and 0.25% bupivacaine (20ml) in scalp block, while the Group B received intravenous injection paracetamol (1gm) and 0.25% bupivacaine (total 20ml) in scalp block. Statistical analyses were obtained Statistical Packages for Social Sciences (SPSS-22). The mean systolic blood pressure varied within the normal range in both groups. The mean DBP of Group B remained significantly lower than that of Group A in different follow up except at 30 minutes and 60 minutes after dura incision. However, mean MAP of Group B remained significantly lower than that of Group A in different time interval. The mean heart rate of Group B remained significantly lower than that of Group A. The mean intraoperative propofol as well as fentanyl requirements were significantly decreased in Group B in comparison to Group A. The combination of intravenous paracetamol with bupivacaine scalp nerve block provides better intra-operative haemodynamic stability and neurosurgical compliances for the patients undergoing supratentorial craniotomies under general anaesthesia.


Assuntos
Bupivacaína , Bloqueio Nervoso , Acetaminofen/farmacologia , Adolescente , Adulto , Anestésicos Locais , Bangladesh , Craniotomia , Método Duplo-Cego , Hemodinâmica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Dor Pós-Operatória , Couro Cabeludo/cirurgia , Método Simples-Cego , Adulto Jovem
18.
Hipertens. riesgo vasc ; 37(2): 72-77, abr.-jun. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-189194

RESUMO

El sistema renina-angiotensina (SRA) es una cascada hormonal que regula presión arterial, electrólitos y balance hídrico. La angiotensinaII (AII) ejerce sus efectos a través de los receptores AT1 y AT2. El AT1 se encuentra en el sincitiotrofoblasto; el AT2 predomina durante el desarrollo fetal y su estimulación inhibe el crecimiento celular, aumenta la apoptosis, causa vasodilatación y regula el desarrollo del tejido fetal. Existe además un SRA en la placenta, y la generación local de AII es responsable de la activación de los receptores AT1 del trofoblasto. En el embarazo normal, concomitantemente con reducción de los niveles de presión arterial, se produce un aumento del SRA circulante, pero la presión arterial no sube porque existe refractariedad a la AII, cosa que no ocurre en la preeclampsia. Revisamos la función del SRA en el embarazo normal y en la preeclampsia


The renin-angiotensin system (ARS) is a hormonal cascade that regulates blood pressure, electrolytes and water balance. AngiotensinII (AII) exerts its effects through the AT1 and AT2 receptors. AT1 is found in the syncytiotrophoblast, AT2 predominates during foetal development and its stimulation inhibits cell growth, increases apoptosis, causes vasodilation and regulates the development of foetal tissue. There is also an SRA in the placenta. The local generation of AII is responsible for the activation of AT1 receptors in the trophoblast. In normal pregnancy, concomitantly with reduction of blood pressure the circulating RAS increases, but blood pressure does not rise due to AII refractoriness, which does not occur in preeclampsia. We review the role of the SRA in normal pregnancy and preeclampsia


Assuntos
Humanos , Feminino , Gravidez , Sistema Renina-Angiotensina/efeitos dos fármacos , Pré-Eclâmpsia/metabolismo , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Hemodinâmica/efeitos dos fármacos , Albumina Sérica/efeitos dos fármacos , Índice de Gravidade de Doença , Espaço Extracelular/efeitos dos fármacos , Homeostase/efeitos dos fármacos
19.
Am J Physiol Heart Circ Physiol ; 319(2): H262-H270, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32559135

RESUMO

Electronic cigarettes (ECs) and tobacco cigarettes (TCs) both release nicotine, a sympathomimetic drug. We hypothesized that baseline heart rate variability (HRV) and hemodynamics would be similar in chronic EC and TC smokers and that after acute EC use, changes in HRV and hemodynamics would be attributable to nicotine, not non-nicotine, constituents in EC aerosol. In 100 smokers, including 58 chronic EC users and 42 TC smokers, baseline HRV and hemodynamics [blood pressure (BP) and heart rate (HR)] were compared. To isolate the acute effects of nicotine vs. non-nicotine constituents in EC aerosol, we compared changes in HRV, BP, and HR in EC users after using an EC with nicotine (ECN), EC without nicotine (EC0), nicotine inhaler (NI), or sham vaping (control). Outcomes were also compared with TC smokers after smoking one TC. Baseline HRV and hemodynamics were not different in chronic EC users and TC smokers. In EC users, BP and HR, but not HRV outcomes, increased only after using the ECN, consistent with a nicotine effect on BP and HR. Similarly, in TC smokers, BP and HR but not HRV outcomes increased after smoking one TC. Despite a similar increase in nicotine, the hemodynamic increases were significantly greater after TC smokers smoked one TC compared with the increases after EC users used the ECN. In conclusion, chronic EC and TC smokers exhibit a similar pattern of baseline HRV. Acute increases in BP and HR in EC users are attributable to nicotine, not non-nicotine, constituents in EC aerosol. The greater acute pressor effects after TC compared with ECN may be attributable to non-nicotine, combusted constituents in TC smoke.NEW & NOTEWORTHY Chronic electronic cigarette (EC) users and tobacco cigarette (TC) smokers exhibit a similar level of sympathetic nerve activity as estimated by heart rate variability. Acute increases in blood pressure (BP) and heart rate in EC users are attribute to nicotine, not non-nicotine, constituents in EC aerosol. Acute TC smoking increased BP significantly more than acute EC use, despite similar increases in plasma nicotine, suggestive of additional adverse vascular effects attributable to combusted, non-nicotine constituents in TC smoke.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Fumar Cigarros/efeitos adversos , Sistemas Eletrônicos de Liberação de Nicotina , Hemodinâmica/efeitos dos fármacos , Nicotina/efeitos adversos , Sistema Nervoso Simpático/efeitos dos fármacos , Simpatomiméticos/efeitos adversos , Vaping/efeitos adversos , Adulto , Aerossóis , Pressão Sanguínea/efeitos dos fármacos , Sistema Cardiovascular/fisiopatologia , Estudos Cross-Over , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Exposição por Inalação/efeitos adversos , Masculino , Pessoa de Meia-Idade , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Distribuição Aleatória , Medição de Risco , Sistema Nervoso Simpático/fisiopatologia , Simpatomiméticos/administração & dosagem , Fatores de Tempo , Adulto Jovem
20.
Medicina (B Aires) ; 80(3): 271-274, 2020.
Artigo em Espanhol | MEDLINE | ID: covidwho-344356

RESUMO

Due to the coronavirus disease 2019 (COVID-19) pandemic, a wide number of compounds are under scrutiny regarding their antiviral activity, one of them being hydroxychloroquine. Cardiac aspects of the use of chloroquine and hydroxychloroquine are reviewed in this manuscript. A non-systematic review of the medical literature was performed. Information about their safety and efficacy as antimalarials, antivirals, as well as in the long-term treatment of rheumatic diseases was collected. We found an anti-inflammatory effect with reduction of longterm cardiovascular events, a very infrequent heart disease due to a lysosomal effect of the drug, and at the hemodynamic level hypotension, tachycardia, and QT interval prolongation, exacerbated when combined with azithromycin. However, the rate of adverse cardiac events of hydroxychloroquine (and chloroquine) was low.


Assuntos
Antivirais/efeitos adversos , Betacoronavirus , Doenças Cardiovasculares/induzido quimicamente , Cloroquina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/efeitos adversos , Pneumonia Viral/tratamento farmacológico , Anti-Inflamatórios/efeitos adversos , Antirreumáticos/efeitos adversos , Coração/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Pandemias , Fatores de Risco
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