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1.
Purinergic Signal ; 20(2): 163-179, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37402944

RESUMO

Sustained pressure overload and fibrosis of the right ventricle (RV) are the leading causes of mortality in pulmonary arterial hypertension (PAH). Although the role of adenosine in PAH has been attributed to the control of pulmonary vascular tone, cardiac reserve, and inflammatory processes, the involvement of the nucleoside in RV remodelling remains poorly understood. Conflicting results exist on targeting the low-affinity adenosine A2B receptor (A2BAR) for the treatment of PAH mostly because it displays dual roles in acute vs. chronic lung diseases. Herein, we investigated the role of the A2BAR in the viability/proliferation and collagen production by cardiac fibroblasts (CFs) isolated from RVs of rats with monocrotaline (MCT)-induced PAH. CFs from MCT-treated rats display higher cell viability/proliferation capacity and overexpress A2BAR compared to the cells from healthy littermates. The enzymatically stable adenosine analogue, 5'-N-ethylcarboxamidoadenosine (NECA, 1-30 µM), concentration-dependently increased growth, and type I collagen production by CFs originated from control and PAH rats, but its effects were more prominent in cells from rats with PAH. Blockage of the A2BAR with PSB603 (100 nM), but not of the A2AAR with SCH442416 (100 nM), attenuated the proliferative effect of NECA in CFs from PAH rats. The A2AAR agonist, CGS21680 (3 and 10 nM), was virtually devoid of effect. Overall, data suggest that adenosine signalling via A2BAR may contribute to RV overgrowth secondary to PAH. Therefore, blockage of the A2AAR may be a valuable therapeutic alternative to mitigate cardiac remodelling and prevent right heart failure in PAH patients.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Animais , Humanos , Ratos , Adenosina-5'-(N-etilcarboxamida) , Modelos Animais de Doenças , Fibroblastos/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Receptor A2B de Adenosina/metabolismo
2.
Clin Sci (Lond) ; 136(1): 1-14, 2022 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-34939089

RESUMO

The urocortins (Ucns) belong to the corticotropin-releasing factor (CRF) family of peptides and have multiple effects within the central nervous and the cardiovascular systems. With growing evidence indicating significant cardioprotective properties and cardiovascular actions of these peptides, the question arises as to whether the plasma profiles of the Ucns are altered in pathologic settings. While reports have shown conflicting results and findings have not been corroborated in multiple independent cohorts, it seems likely that plasma Ucn concentrations are elevated in multiple cardiovascular conditions. The degree of increase and accurate determination of circulating values of the Ucns requires further validation.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Urocortinas/sangue , Animais , Humanos
3.
Animals (Basel) ; 14(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731304

RESUMO

The favourable geo-climatic conditions in Portugal have made it highly conducive to the development of Dirofilaria immitis in dogs, leading to its identification as an endemic region. This nematode is rapidly spreading across Europe, particularly in northeastern countries. The objective of this study was to provide an updated assessment of the prevalence of this disease in Portuguese dogs, analysing the results in relation to epidemiological and geo-environmental factors, and to identify potential risk factors. A total of 1367 dogs from all continental and insular districts were included in the study and tested for D. immitis antigens. The overall prevalence was found to be 5.9%. It was observed that the disease is spreading northward, with previously unaffected districts now reporting cases, and that the prevalence in coastal districts exceeded that of inland ones. Notably, the Aveiro district exhibited a significant increase in D. immitis prevalence, while in certain districts such as Setúbal, Santarém, Madeira, or Faro, a stabilisation or decrease in prevalence was noted. Furthermore, outdoor and older dogs were found to be at a higher risk of infection. No positive cases were detected in the Azores. Most of the infected dogs were located in areas of high and medium risk of infection. This study underscores the importance of implementing pharmacological prophylaxis, vector control strategies, and public awareness programs to control the spread of this zoonotic disease.

4.
Vet Sci ; 10(8)2023 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-37624305

RESUMO

The Lusitano horse is gaining popularity in the equestrian world, and as a result, the significance of applied sports medicine for this breed is growing. As cardiology plays a crucial role in this field, numerous studies have been conducted to establish electrocardiographic reference values in various breeds to ensure a more accurate evaluation. However, studies regarding healthy Lusitano horses are lacking. So, this study aimed to establish electrocardiographic reference values for Lusitano horses, utilizing a sample of 82 clinically healthy animals. The evaluation involved lead II and base-apex lead measurements, with a median heart rate of 39 beats per minute being recorded. The P wave demonstrated a predominantly bifid configuration, while the QRS complex exhibited various forms. The most common QRS configurations were QR and R in lead II, and RS in the base-apex lead. Additionally, most T waves displayed a biphasic shape in both methods. Furthermore, statistically significant differences were noted based on age and gender. Some of the electrocardiographic values obtained differed from those previously published for other breeds. Given the relevance of electrocardiogram in cardiovascular evaluation, these findings bring valuable insights regarding the specific parameters for Lusitano horse and emphasize the importance of obtaining breed-specific electrocardiographic reference values.

5.
Proc Natl Acad Sci U S A ; 106(5): 1512-7, 2009 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-19164539

RESUMO

The thymus represents the "cradle" for T cell development, with thymic stroma providing multiple soluble and membrane cues to developing thymocytes. Although IL-7 is recognized as an essential factor for thymopoiesis, the "environmental niche" of thymic IL-7 activity remains poorly characterized in vivo. Using bacterial artificial chromosome transgenic mice in which YFP is under control of IL-7 promoter, we identify a subset of thymic epithelial cells (TECs) that co-express YFP and high levels of Il7 transcripts (IL-7(hi) cells). IL-7(hi) TECs arise during early fetal development, persist throughout life, and co-express homeostatic chemokines (Ccl19, Ccl25, Cxcl12) and cytokines (Il15) that are critical for normal thymopoiesis. In the adult thymus, IL-7(hi) cells localize to the cortico-medullary junction and display traits of both cortical and medullary TECs. Interestingly, the frequency of IL-7(hi) cells decreases with age, suggesting a mechanism for the age-related thymic involution that is associated with declining IL-7 levels. Our temporal-spatial analysis of IL-7-producing cells in the thymus in vivo suggests that thymic IL-7 levels are dynamically regulated under distinct physiological conditions. This IL-7 reporter mouse provides a valuable tool to further dissect the mechanisms that govern thymic IL-7 expression in vivo.


Assuntos
Interleucina-7/metabolismo , Timo/metabolismo , Animais , Células Cultivadas , Cromossomos Artificiais Bacterianos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Genes Reporter , Interleucina-7/genética , Proteínas Luminescentes/genética , Camundongos , Camundongos Transgênicos , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Timo/citologia , Timo/imunologia
6.
Vet Sci ; 9(10)2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36288146

RESUMO

Over the last years, the importance of microRNAs (miRNAs) has increasingly been recognised. Each miRNA is a short sequence of non-coding RNA that influences countless genes' expression and, thereby, contributes to several physiological pathways and diseases. It has been demonstrated that miRNAs participate in the development of many cardiovascular diseases (CVDs). This review synopsises the most recent studies emphasising miRNA's influence in several CVDs affecting dogs and cats. It provides a concise outline of miRNA's biology and function, the diagnostic potential of circulating miRNAs as biomarkers, and their role in different CVDs. It also discusses known and future roles for miRNAs as potential clinical biomarkers and therapeutic targets. So, this review gives a comprehensive outline of the most relevant miRNAs related to CVDs in Veterinary Medicine.

7.
Front Pharmacol ; 12: 724320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34489711

RESUMO

Heart failure with preserved ejection fraction (HFpEF) roughly represents half of the cardiac failure events in developed countries. The proposed 'systemic microvascular paradigm' has been used to explain HFpHF presentation heterogeneity. The lack of effective treatments with few evidence-based therapeutic recommendations makes HFpEF one of the greatest unmet clinical necessities worldwide. The endogenous levels of the purine nucleoside, adenosine, increase significantly following cardiovascular events. Adenosine exerts cardioprotective, neuromodulatory, and immunosuppressive effects by activating plasma membrane-bound P1 receptors that are widely expressed in the cardiovascular system. Its proven benefits have been demonstrated in preclinical animal tests. Here, we provide a comprehensive and up-to-date critical review about the main therapeutic advantages of tuning adenosine signalling pathways in HFpEF, without discounting their side effects and how these can be seized.

8.
Vet Sci ; 8(12)2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34941833

RESUMO

This study aimed to evaluate maternal left ventricular (LV) systo-diastolic function using conventional and TDI echocardiography and included 10 healthy Saint-Bernard pregnant bitches. M-mode, peak transmitral flow velocities during early diastole (E) and atrial contraction (A), aortic and pulmonic flow, myocardial performance index (MPI), TDI studies (peak myocardial velocities during early diastole (E'), atrial contraction (A') and peak systole (S')), and blood pressure were measured at 21 to 28 (T1), 40 (T2) and 60 (T3) days of gestation and four to eight weeks postpartum (T4). Cardiac output and heart rate were 20% and 9% higher at T3, respectively, compared to T4 (p < 0.01). Lateral S' was 36% higher at T3 than at T1 (p < 0.05). Changes in diastolic function were demonstrated by 10% lower E wave and 15% A wave at T1, compared to T4 (p < 0.05). E' and A' were 23% and 42% higher at T3 compared to T4 (p < 0.01). Both lateral E/E' and E'/A' were 6% and 19% lower at T3 compared to T1 (p < 0.01 and p < 0.05, respectively). At T3, MPI was 51% and 34% lower when compared to T1 or T2 (p < 0.05). The echocardiographic evaluation of maternal cardiac function is important, as structural, and functional changes occur throughout pregnancy.

9.
Vet J ; 265: 105549, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33129554

RESUMO

Atrial fibrillation (AF) is the most common non-physiological arrhythmia in dogs and humans. Its high prevalence in both species and the impact it has on survival time and quality of life of affected patients, makes it a very relevant topic for medical research. In dogs, the diagnosis of AF is usually fairly straightforward, but optimal management can be complicated. Rate control is the most commonly used strategy; rhythm control can also be considered in very specific cases. Concurrent congestive heart failure is frequently identified, which represents an extra challenge for the clinicians. This article reviews the current recommendations for the diagnosis and management considerations of AF in dogs. Future perspectives, focusing on new drugs that may prevent development of AF based on recent discoveries, will also be discussed.


Assuntos
Fibrilação Atrial/veterinária , Doenças do Cão/diagnóstico , Animais , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Doenças do Cão/terapia , Cães , Cardioversão Elétrica/métodos , Cardioversão Elétrica/veterinária , Eletrocardiografia/métodos , Eletrocardiografia/veterinária , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/veterinária , Frequência Cardíaca/efeitos dos fármacos , Humanos , Prognóstico
10.
Vet J ; 265: 105548, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33129553

RESUMO

Atrial fibrillation (AF) is the most common non-physiological arrhythmia in dogs and humans. Its high prevalence in both species and the impact it has on survival time and quality of life of affected patients, makes it a very relevant topic of medical research. Significant developments in understanding the mechanisms underlying this arrhythmia in humans has occurred over the last decades and some of this knowledge is being applied to veterinary medicine, despite the many differences between species. This article reviews the current understanding of the pathophysiology of AF. The epidemiology and classification of AF in dogs will also be discussed.


Assuntos
Fibrilação Atrial/veterinária , Doenças do Cão/epidemiologia , Doenças do Cão/fisiopatologia , Animais , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/fisiologia , Dilatação Patológica , Doenças do Cão/classificação , Cães , Fenômenos Eletrofisiológicos , Átrios do Coração/patologia , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/veterinária , Fatores de Risco
11.
Surg Endosc ; 23(11): 2550-5, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19343424

RESUMO

BACKGROUND: Clinical applications of transvaginal Natural Orifice Transluminal Endoscopic Surgery (NOTES) are still limited in the literature, mostly case reports performed by hybrid procedures with laparoscopic assistance. Avoiding complications from incisions is the main goal for natural orifice surgery. This study reports on a technique developed at our institution that uses two endoscopes inserted into the vagina to perform a Totally NOTES (T-NOTES) transvaginal cholecystectomy, and describes preliminary results. METHODS: IRB approval was obtained at the institution for transvaginal NOTES clinical trials, and informed consent was obtained. The technique of T-NOTES transvaginal cholecystectomy was clinically applied in four female patients with symptomatic cholelithiasis, and data were prospectively documented. Transvaginal NOTES access was obtained by direct vaginal incision, and two endoscopes were simultaneously introduced in the abdominal cavity. Dissection was accomplished with available endoscopic instruments. Ligation of cystic duct and artery was performed using endoscopic clips. Vaginal closure was achieved using the direct-vision sutured technique. RESULTS: The technique was successfully performed in the four patients. Insufflation and spatial orientation was of good quality. Mean operative time was 210 min. There were no complications during the 30-day follow-up. Postoperative course was uneventful, and patients were released from the hospital on the first postoperative day. CONCLUSION: Tranvaginal T-NOTES using two endoscopes provides a feasible method for natural orifice cholecystectomy using available technology. Large-series studies are needed to evaluate the results with respect to safety of the approach.


Assuntos
Colecistectomia Laparoscópica/métodos , Colelitíase/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Adulto , Brasil , Colecistectomia Laparoscópica/efeitos adversos , Colelitíase/diagnóstico , Estudos de Coortes , Colonoscópios , Feminino , Seguimentos , Gastroscópios , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento , Vagina/cirurgia
12.
Vet J ; 181(3): 326-31, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18445537

RESUMO

Limited data are available on the use of more recent echocardiographic parameters in the rabbit. Echocardiographic examination, including conventional echocardiography and tissue Doppler imaging (TDI), was performed on 26 male New Zealand white rabbits under ketamine-midazolam sedation. Particular emphasis was placed on the more recent systolic and diastolic parameters, such as myocardial performance index (Tei index) and mitral annular motion (from septal and lateral sides of the left ventricle) obtained using pulsed TDI. Parameters that assessed systolic and diastolic function (fractional shortening, Tei index, and maximal mitral E- and A-wave velocities) were comparable to those reported in the literature for rabbits in the awake state. The less cardiodepressive anaesthetic protocol could offer a good alternative in performing echocardiographic evaluation whenever such caution is necessary. TDI is feasible in healthy rabbits and potentially suitable for the investigation of left ventricle systolic and diastolic function.


Assuntos
Ecocardiografia Doppler/veterinária , Coração/fisiologia , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Midazolam/farmacologia , Coelhos/fisiologia , Animais , Masculino
13.
Am J Vet Res ; 70(4): 464-71, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19335101

RESUMO

OBJECTIVE-To report reference values and examine the agreement in the myocardial performance (Tei) index of the left ventricle (LVTI) as measured by tissue Doppler imaging (TDI), pulsed-wave Doppler imaging (PWD), and M-mode echocardiography in clinically normal rabbits. ANIMALS-26 clinically normal male New Zealand White rabbits. PROCEDURES-Echocardiographic examinations that included TDI, PWD, and M-mode echocardiography were performed. Rabbits were sedated by SC administration of ketamine and midazolam. Intraclass correlation coefficients (ICCs) were used to measure absolute agreement among the 3 echocardiographic techniques. Intraclass correlation coefficients were computed for values a and b and for the equation (a - b)/b used to determine LVTI; value a equals the sum of isovolumic contraction time, ejection time, and isovolumic relaxation time, and value b equals the left ventricular ejection time. Values of ICC > 0.75 indicated good agreement between 2 echocardiographic techniques. RESULTS-For value a, Pearson correlation coefficients between pairs of techniques were all high (r r 0.7). However, only the septal TDI and the lateral wall TDI had good agreement (ICC, 0.86). For value b, correlations were generally low with the exception of the correlation between the septal and the lateral wall TDI. For value b, TDI was the only technique with good agreement (ICC, 0.77). For LVTI, only TDI techniques had a significantly positive correlation. All the other correlations were close to zero with a paradoxic moderate negative correlation between PWD-determined LVTI and lateral wall TDI-determined LVTI. CONCLUSIONS AND CLINICAL RELEVANCE-For LVTI, the absolute agreement was poor between all pairs of techniques.


Assuntos
Ecocardiografia/veterinária , Coelhos/fisiologia , Função Ventricular Esquerda/fisiologia , Animais , Ecocardiografia/normas , Masculino , Reprodutibilidade dos Testes
14.
Drug Discov Today ; 24(11): 2170-2180, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31430542

RESUMO

Urotensin II (UII) is a vasoactive peptide that interacts with a specific receptor called the UT receptor. UII has been implicated in cardiovascular regulation, with promising therapeutic applications based on UT receptor antagonism. The endogenous ligands of the UT receptor: UII and urotensin-related peptide (URP), differentially bind and activate this receptor. Also, the receptor localization is not restricted to the plasma membrane, possibly inducing different physiological responses that could support its inconsistent, but potent, vasoactive activity. These properties could explain the disappointing outcomes in clinical studies, in contrast to the positive preclinical results regarding heart failure, pulmonary hypertension, atherosclerosis and diabetes mellitus. These aspects should be considered in future investigations to a better comprehension of the role of UII as a potential therapeutic target.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Descoberta de Drogas/métodos , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Urotensinas/antagonistas & inibidores , Animais , Fármacos Cardiovasculares/química , Fármacos Cardiovasculares/farmacologia , Modelos Animais de Doenças , Humanos , Ligantes , Receptores Acoplados a Proteínas G/genética , Transdução de Sinais , Distribuição Tecidual , Urotensinas/biossíntese
15.
Front Pharmacol ; 10: 1103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611793

RESUMO

Background: Mounting evidence indicate that reducing the sinoatrial node (SAN) activity may be a useful therapeutic strategy to control of heart failure. Purines, like ATP and its metabolite adenosine, consistently reduce the SAN spontaneous activity leading to negative cardiac chronotropy, with variable effects on the force of myocardial contraction (inotropy). Apart from adenosine A1 receptors, the human SAN expresses high levels of ATP-sensitive ionotropic P2X4 receptors (P2X4R), yet their cardiac role is unexplored. Methods: Here, we investigated the activity of P2 purinoceptors on isolated spontaneously beating atria (chronotropy) and on 2 Hz-paced right ventricular (RV, inotropy) strips from Wistar rats. Results: ATP (pEC 50 = 4.05) and its stable analogue ATPγS (pEC 50 = 4.69) concentration-dependently reduced atrial chronotropy. Inhibition of ATP breakdown into adenosine by NTPDases with POM-1 failed to modify ATP-induced negative chronotropy. The effect of ATP on atrial rate was attenuated by a broad-spectrum P2 antagonist, PPADS, as well as by 5-BDBD, which selectively blocks the P2X4R subtype; however, no effect was observed upon blocking the A1 receptor with DPCPX. The P2X4R positive allosteric modulator, ivermectin, increased the negative chronotropic response of ATP. Likewise, CTP, a P2X agonist that does not generate adenosine, replicated the P2X4R-mediated negative chronotropism of ATP. Inhibition of the Na+/Ca2+ exchanger (NCX) with KB-R7943 and ORM-10103, but not blockage of the HCN channel with ZD7288, mimicked the effect of the P2X4R blocker, 5-BDBD. In paced RV strips, ATP caused a mild negative inotropic effect, which magnitude was 2 to 3-fold increased by 5-BDBD and KB-R7943. Immunofluorescence confocal microscopy studies confirm that cardiomyocytes of the rat SAN and RV co-express P2X4R and NCX1 proteins. Conclusions: Data suggest that activation of ATP-sensitive P2X4R slows down heart rate by reducing the SAN activity while increasing the magnitude of ventricular contractions. The mechanism underlying the dual effect of ATP in the heart may involve inhibition of intracellular Ca2+-extrusion by bolstering NCX function in the reverse mode. Thus, targeting the P2X4R activation may create novel well-tolerated heart-rate lowering drugs with potential benefits in patients with deteriorated ventricular function.

16.
Drug Discov Today ; 23(6): 1285-1292, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29747005

RESUMO

Pulmonary arterial hypertension (PAH) is a maladaptive disorder characterized by increased pulmonary vascular resistance leading to right ventricular failure and death. Adenosine released by injured tissues, such as the lung and heart, influences tissue remodeling through the activation of adenosine receptors. Evidence regarding activation of the low-affinity A2BAR by adenosine points towards pivotal roles of this receptor in processes associated with both acute and chronic lung diseases. Conflicting results exist concerning the beneficial or detrimental roles of the A2B 'biased' receptor in right ventricular failure secondary to PAH. In this review, we discuss the pros and cons of manipulating A2BARs as a putative therapeutic target in PAH.


Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Receptor A2B de Adenosina/metabolismo , Animais , Transporte Biológico , Membrana Celular , Humanos , Hipertensão Pulmonar/metabolismo , Ligantes , Pulmão/irrigação sanguínea , Pulmão/metabolismo , Miocárdio/metabolismo , Transdução de Sinais
17.
Naunyn Schmiedebergs Arch Pharmacol ; 376(1-2): 107-15, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17701026

RESUMO

Urotensin II (U-II) is a cyclic peptide that may be involved in cardiovascular dysfunction. In the present study, the acute effects of U-II on diastolic properties of the myocardium were investigated. Increasing concentrations of U-II (10(-8) to 10(-6) M) were added to rabbit papillary muscles in the absence (n = 15) or presence of: (1) damaged endocardial endothelium (EE; n = 9); (2) U-II receptor antagonist, urantide (10(-5) M; n = 7); (3) nitric oxide (NO) synthase inhibitor, N(G)-Nitro-L-Arginine (10(-5) M; n = 9); (4) cyclooxygenase inhibitor, indomethacin (10(-5) M; n = 8); (5) NO synthase and cyclooxygenase inhibitors, N(G)-Nitro-L-Arginine (10(-5) M) and indomethacin (10(-5) M), respectively, (n = 8); or (6) protein kinase C (PKC) inhibitor, chelerythrine (10(-5) M; n = 9). Passive length-tension relations were constructed before and after a single concentration of U-II (10(-6) M; n = 3). U-II concentration dependently decreased inotropy and increased resting muscle length (RL). At 10(-6) M, active tension decreased 13.8 +/- 5.4%, and RL increased to 1.007 +/- 0.001 L/L (max). Correcting RL to its initial value resulted in an 18.1 +/- 3.0% decrease in resting tension, indicating decreased muscle stiffness, which was also suggested by the down and rightward shift of the passive length-tension relation. This effect remained unaffected by EE damage and PKC inhibition. In contrast, the presence of urantide and NO inhibition abolished the effects of U-II on myocardial stiffness, while cyclooxygenase inhibition significantly attenuated them. U-II decreases myocardial stiffness, an effect that is mediated by the urotensin-II receptor, NO, and prostaglandins. This represents a novel mechanism of acute neurohumoral modulation of diastolic function, suggesting that U-II is an important regulator of cardiac filling.


Assuntos
Diástole , Contração Miocárdica , Urotensinas/fisiologia , Remodelação Ventricular , Análise de Variância , Animais , Diástole/efeitos dos fármacos , Elasticidade , Humanos , Técnicas In Vitro , Masculino , Contração Miocárdica/efeitos dos fármacos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/fisiologia , Músculos Papilares/efeitos dos fármacos , Músculos Papilares/fisiologia , Prostaglandinas/fisiologia , Coelhos , Receptores Acoplados a Proteínas G/fisiologia , Urotensinas/farmacologia , Vasoconstritores/farmacologia , Remodelação Ventricular/efeitos dos fármacos
18.
Exp Biol Med (Maywood) ; 231(6): 893-8, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16741019

RESUMO

Inotropic effects of selective ET(B) receptor stimulation depend on the functional integrity of the endocardial endothelium (EE), which is negative when it is intact and positive when it is damaged. These results have been attributed to the existence of two subtypes of ET(B) receptors in the heart: (i) ET(B1), located on the EE, decreases inotropy; (ii) ET(B2), located on myocardial cells, increases inotropy. In the present study we investigated the functional integrity of the EE in a heart failure (HF) model (doxorubicin-induced cardiomyopathy) by evaluating the contractile response to ET(B1) receptor stimulation. New Zealand White rabbits were treated with doxorubicin (DOX-HF, 1 mg/kg, iv, twice weekly for 8 weeks) or with saline. Contractile effects of increasing doses of a selective agonist of endothelial ET(B) receptors, IRL-1620 (10(-9) to 10(-6) M), were studied in papillary muscles (Krebs-Ringer: 1.8 mM CaCl2, 35 degrees C) from control (n = 10) and DOX-HF rabbits (n = 7). Isotonic and isometric twitches were recorded and analyzed. Reported parameters included active tension (AT) and maximum velocities of tension rise (dT/dt(max)) and decline (dT/dt(min)). On echocardiography, DOX-HF rabbits had increased left ventricular (LV) end-diastolic and end-systolic diameters and reduced ejection fraction (52% +/- 2% vs. 61% +/- 1%). Contrary to control papillary muscles, DOX-HF muscles showed a steady decrease in contractility between 1 and 4 Hz. In the control group, IRL-1620 induced dose-dependent negative inotropic and lusitropic effects that decreased at 10(-6) M: 26% +/- 3%, AT; 17% +/- 3%, dT/dt(max); and 16% +/- 5%, dT/dt(min). In the DOX-HF group, these effects were significantly reduced. At the same concentration, IRL-1620 decreased AT (8% +/- 3%) and dT/dt(max) (8% +/- 3%), without significantly affecting dT/dt(min). This study showed an impaired response to endothelial ET(B) receptor stimulation, providing for the first time strong evidence of the occurrence of EE dysfunction in the failing heart and further highlighting the potential use of ET(B) receptor stimulation as a marker of EE function.


Assuntos
Coração/fisiologia , Receptor de Endotelina B/fisiologia , Animais , Relação Dose-Resposta a Droga , Doxorrubicina/farmacologia , Ecocardiografia , Endocárdio/fisiologia , Endotelinas/farmacologia , Endotélio/fisiologia , Insuficiência Cardíaca/etiologia , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Contração Isotônica/efeitos dos fármacos , Masculino , Músculos Papilares/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Coelhos , Fatores de Tempo
19.
Am J Vet Res ; 67(10): 1725-9, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17014323

RESUMO

OBJECTIVE: To determine M-mode and Doppler echocardiographic reference values in healthy New Zealand white rabbits. ANIMALS: 52 healthy male rabbits. PROCEDURES: The rabbits were anesthetized and M-mode measurements of the left ventricle, left atrium, and aorta and Doppler measurements of pulmonary and aortic outflow and mitral inflow were recorded. RESULTS: Mean +/- SD heart rate during echocardiographic examination was 155 +/- 29 beats/min. Mean +/- SD measurements in diastole and systole for the interventricular septum thickness, left ventricular internal diameter, and left ventricular free wall thickness were 2.03 +/- 0.37 mm and 3.05 +/- 0.45 mm; 14.37 +/- 1.49 mm and 10.25 +/- 1.22 mm; and 2.16 +/- 0.25 and 3.48 +/- 0.55 mm, respectively. Mean +/- SD left atrial-to-aortic diameter ratio was 1.17 +/- 0.14, and mean +/- SD mitral valve E-point-to-septal separation interval was 1.71 +/- 0.29 mm. Mean +/- SD for fractional shortening and ejection fraction were 30.13 +/- 2.98% and 61.29 +/- 4.66%, respectively. Mean +/- SD maximal aortic and pulmonary artery outflow velocities were 0.85 +/- 0.11 m/s and 0.59 +/- 0.10 m/s, respectively, and the peak E-to-peak A wave velocity ratio of the mitral valve was 2.19 +/- 0.46. CONCLUSIONS AND CLINICAL RELEVANCE: Results provide echocardiographic reference values for young adult male New Zealand white rabbits anesthetized with ketamine and medetomidine. Values obtained from unanesthetized rabbits, rabbits sedated with other agents, or rabbits of different size may differ from those reported here.


Assuntos
Ecocardiografia Doppler/veterinária , Ecocardiografia/veterinária , Coração/anatomia & histologia , Animais , Masculino , Coelhos , Valores de Referência
20.
Acta Ortop Bras ; 21(4): 223-5, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24453673

RESUMO

OBJECTIVE: To investigate the prevalence of adolescent idiopathic scoliosis in school children from 10 to 14 years in public schools in Goiânia, GO, Brazil. METHODS: In a cross-sectional study, 476 students were randomly selected from 5 public schools, from a total of 33,343 students distributed in 162 schools. These subjects received the informed consent prior, which was returned after being signed by parents on physical examination day. We evaluated the symmetry of the shoulders, the scapulae, the triangle-cut, the hip evenness and the Adams test. In suspected cases, students were referred to panoramic radiographs of the spine. RESULTS: 418 students participated in the study (adjusted sampling error of 3.2%). Of this total, 31 students were suspected of scoliosis (17 males and 14 females). Twenty-eight students took radiographs, of which 18 were diagnosed with adolescent idiopathic scoliosis (11 female and 7 male), determining the prevalence of 4.3%. The chi-square test suggested no statistical difference in prevalence between the sexes. One student had congenital scoliosis. CONCLUSION: The prevalence of adolescent idiopathic scoliosis in the public schools of Goiânia is 4.3%. Level of Evidence III, Study of Nonconsecutive Patients.

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