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1.
Crit Care ; 24(1): 95, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32188462

RESUMO

BACKGROUND: Concomitant vasoactive drugs are often required to maintain adequate perfusion pressure in patients with acute myocardial infarction (AMI) and cardiogenic shock (CS) receiving hemodynamic support with an axial flow pump (Impella CP). OBJECTIVE: To compare the effect of equipotent dosages of epinephrine, dopamine, norepinephrine, and phenylephrine on cardiac work and end-organ perfusion in a porcine model of profound ischemic CS supported with an Impella CP. METHODS: CS was induced in 10 pigs by stepwise intracoronary injection of polyvinyl microspheres. Hemodynamic support with Impella CP was initiated followed by blinded crossover to vasoactive treatment with norepinephrine (0.10 µg/kg/min), epinephrine (0.10 µg/kg/min), or dopamine (10 µg/kg/min) for 30 min each. At the end of the study, phenylephrine (10 µg/kg/min) was administered for 20 min. The primary outcome was cardiac workload, a product of pressure-volume area (PVA) and heart rate (HR), measured using the conductance catheter technique. End-organ perfusion was assessed by measuring venous oxygen saturation from the pulmonary artery (SvO2), jugular bulb, and renal vein. Treatment effects were evaluated using multilevel mixed-effects linear regression. RESULTS: All catecholamines significantly increased LV stroke work and cardiac work, dopamine to the greatest extend by 341.8 × 103 (mmHg × mL)/min [95% CI (174.1, 509.5), p < 0.0001], and SvO2 significantly improved during all catecholamines. Phenylephrine, a vasoconstrictor, caused a significant increase in cardiac work by 437.8 × 103 (mmHg × mL)/min [95% CI (297.9, 577.6), p < 0.0001] due to increase in potential energy (p = 0.001), but no significant change in LV stroke work. Also, phenylephrine tended to decrease SvO2 (p = 0.063) and increased arterial lactate levels (p = 0.002). CONCLUSION: Catecholamines increased end-organ perfusion at the expense of increased cardiac work, most by dopamine. However, phenylephrine increased cardiac work with no increase in end-organ perfusion.


Assuntos
Débito Cardíaco/efeitos dos fármacos , Coração Auxiliar , Hemodinâmica/efeitos dos fármacos , Choque Cardiogênico/terapia , Animais , Catecolaminas/uso terapêutico , Modelos Animais de Doenças , Dopamina , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Norepinefrina , Fenilefrina , Choque Cardiogênico/fisiopatologia , Suínos
2.
BJOG ; 127(8): 1018-1025, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32133780

RESUMO

OBJECTIVE: To compare maternal haemodynamics in women at low and high risk for preterm pre-eclampsia (PE), and between those at high risk who are randomised to aspirin or placebo. DESIGN: Prospective, longitudinal observational study. SETTING: Maternity units in six UK hospitals. POPULATION: Women participating in the Aspirin for Prevention of Preterm Pre-eclampsia (ASPRE) trial. The population comprised three groups of women: low risk for preterm PE (n = 1362), high risk for preterm PE treated with aspirin (n = 208) and high risk for preterm PE on placebo (n = 220). METHODS: Women had four visits during pregnancy: 11-14, 19-24, 30-34, and 35-37 weeks' gestation. Blood pressure was measured with a device validated for pregnancy, and PE and maternal haemodynamics were assessed with a bioreactance monitor at each visit. A multilevel linear mixed-effects analysis was performed to examine longitudinal changes of maternal haemodynamic variables, controlling for demographic characteristics, past medical history and medication use. MAIN OUTCOME MEASURES: Longitudinal changes of cardiac output (CO), mean arterial pressure (MAP), and peripheral vascular resistance (PVR). RESULTS: The low-risk group demonstrated the expected changes with an increase in CO and reduction in MAP and PVR, with a quadratic change across gestation. In contrast, the high-risk groups had a declining CO, and higher MAP and PVR during pregnancy. The administration of aspirin did not appear to affect maternal haemodynamics. CONCLUSIONS: Women screened as high risk for preterm PE have a pathological cardiac adaptation to pregnancy and the prophylactic use of aspirin (150 mg oral daily from the first trimester) in this group may not alter this haemodynamic profile. TWEETABLE ABSTRACT: In women at high risk of pre-eclampsia, prophylactic use of aspirin may not alter the impaired maternal cardiac adaptation.


Assuntos
Aspirina/uso terapêutico , Débito Cardíaco/efeitos dos fármacos , Inibidores da Agregação de Plaquetas/uso terapêutico , Pré-Eclâmpsia/prevenção & controle , Gravidez de Alto Risco/efeitos dos fármacos , Adulto , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Débito Cardíaco/fisiologia , Feminino , Idade Gestacional , Humanos , Estudos Longitudinais , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Gravidez de Alto Risco/fisiologia , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia
3.
Am J Physiol Gastrointest Liver Physiol ; 318(2): G313-G321, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31841026

RESUMO

Acute kidney injury and hepatorenal syndrome (HRS) are frequent complications in patients with cirrhosis and ascites. First-line treatment is terlipressin, which reverses HRS in ~40% of patients but also lowers cardiac output (CO). We aimed to investigate whether reversing the cardio-suppressive effect of terlipressin with the ß-adrenoceptor agonist dobutamine would increase CO and thereby increase the glomerular filtration rate (GFR). We randomized 25 patients with cirrhosis, ascites, and impaired renal function (2:2:1): group A received terlipressin followed by the addition of dobutamine; group B received dobutamine and terlipressin as monotherapies; and group C received placebo. Renal and cardiac functions were assessed during 8 clearance periods of 30 min, and concentrations of vasoactive hormones were measured. Dobutamine as a monotherapy increased CO (1.03 L/min, P < 0.01) but had no significant effects on GFR. Renin (P < 0.05), angiotensin II (P < 0.005), and aldosterone (P < 0.05) increased after dobutamine infusion. Terlipressin as a monotherapy improved GFR (18.9 mL·min-1·m-2, P = 0.005) and mean arterial pressure (MAP) (14 mmHg, P = 0.001) but reduced CO (-0.92 L/min, P < 0.005) and renin (P < .005). A combined treatment of dobutamine and terlipressin had a positive effect on CO (1.19 L/min, P < 0.05) and increased renin (P < 0.005), angiotensin II (P < 0.005), and aldosterone (P < 0.05), but it had no significant effects on MAP or GFR. Dobutamine reversed the cardio-suppressive effect of terlipressin in cirrhosis, ascites, and impaired renal function. However, dobutamine reduced peripheral vascular resistance, activated renin-angiotensin-aldosterone system, and did not improve GFR compared with terlipressin as a monotherapy. Therefore, dobutamine cannot be recommended in cirrhosis and ascites.NEW & NOTEWORTHY This study shows that the cardio-suppressive effects of the vasopressin receptor agonist terlipressin can be reversed by dobutamine. This is a novel observation in patients with decompensated cirrhosis. Furthermore, we show that dobutamine reduced the peripheral vascular resistance and activated the renin-angiotensin system, whereas renal function was not further improved by terlipressin alone.


Assuntos
Agonistas Adrenérgicos beta/uso terapêutico , Ascite/metabolismo , Dobutamina/uso terapêutico , Nefropatias/prevenção & controle , Cirrose Hepática/metabolismo , Terlipressina/efeitos adversos , Terlipressina/uso terapêutico , Lesão Renal Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Pressão Arterial/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Feminino , Implantes para Drenagem de Glaucoma , Síndrome Hepatorrenal/tratamento farmacológico , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Renina/urina , Terlipressina/antagonistas & inibidores , Adulto Jovem
4.
Best Pract Res Clin Anaesthesiol ; 33(2): 199-209, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31582099

RESUMO

As the operating room and intensive care settings become increasingly complex, the required vigilance practitioners must dedicate to a wide array of clinical systems has increased concordantly. The resulting shortage of available attention to these various clinical tasks creates a vacuum for the introduction of systems that can administer well-established goal-directed therapies without significant provider feedback. Recently, there has been an explosion of academic exploration into creating such automated systems, with a strong specific focus on hemodynamic control. Within this field, the largest focus has been on goal-directed fluid therapy as systems automating vasopressor administration have only recently become viable options. Our goal in this review article is to summarize the validity of the relevant goal-directed hemodynamic systems and explore the expanding role of automation within these systems.


Assuntos
Débito Cardíaco/fisiologia , Hidratação/métodos , Hemodinâmica/fisiologia , Monitorização Intraoperatória/métodos , Débito Cardíaco/efeitos dos fármacos , Humanos , Vasoconstritores/administração & dosagem
5.
Am J Vet Res ; 80(10): 912-922, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31556714

RESUMO

OBJECTIVE: To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467). ANIMALS: 8 purpose-bred, 2-year-old Beagles. PROCEDURES: A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 µg/kg) or MED mixed with 400 µg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 µg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis. RESULTS: Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole-treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Cães , Hipnóticos e Sedativos/farmacologia , Imidazóis/farmacologia , Medetomidina/farmacologia , Quinolizinas/farmacologia , Anestesia/veterinária , Animais , Débito Cardíaco/efeitos dos fármacos , Estudos Cross-Over , Dexmedetomidina/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Injeções Intramusculares/veterinária , Masculino , Medetomidina/administração & dosagem , Medetomidina/antagonistas & inibidores , Quinolizinas/antagonistas & inibidores , Distribuição Aleatória , Método Simples-Cego
6.
Vet J ; 251: 105346, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31492384

RESUMO

The aim of this study was to compare the sedative and cardiovascular effects of dexmedetomidine (DEX) administrated via intranasal (IN) and intramuscular (IM) routes. This masked, randomised, crossover study used six male beagle dogs, receiving 0.02 mg/kg dexmedetomidine either IN (DEX-IN) or IM (DEX-IM), and an equal volume of saline by the alternative route. Dexmedetomidine plasma concentration was measured before (TB) and at time points (T) 2, 5, 10, 15, 30, 45, 60, 90 and 120 min after drug administration (T0). Physiological variables, sedation scores and sedation times were recorded until recovery. Echocardiography was performed at TB and between T20-T40. Repeated data over time were analysed using a Scheirer-Ray-Hare test. Other data were compared using a Wilcoxon or Student's t test. Times from T0 to sternal position and from lateral to sternal position were longer for DEX-IN than DEX-IM (P = 0.018 and P = 0.009, respectively). Time from sternal to standing position was shorter for DEX-IN than DEX-IM (P = 0.03). Dexmedetomidine plasma concentrations were significantly lower for DEX-IN than DEX-IM from T10 to T120. Heart rate was significantly lower for DEX-IM than DEX-IN from T5 to T20. Echocardiography showed a decrease in systolic function and calculated cardiac output in DEX-IM as compared to baseline. The DEX concentration-sedation curve for DEX-IN as compared to DEX-IM was leftward shifted, whereas the IN and IM DEX concentration-variation-in-heart-rate curves overlapped. Although reaching lower plasma concentrations, IN dexmedetomidine produced similar sedation to IM dexmedetomidine without affecting cardiovascular function.


Assuntos
Administração Intranasal/veterinária , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacocinética , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacocinética , Injeções Intramusculares/veterinária , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Estudos Cross-Over , Dexmedetomidina/sangue , Cães , Ecocardiografia/veterinária , Frequência Cardíaca/efeitos dos fármacos , Masculino , Distribuição Aleatória
7.
Int Heart J ; 60(5): 1222-1225, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484879

RESUMO

Bradycardia is a common complication at the early postoperative period after heart transplantation (HT). The heart rate (HR) usually recovers within a few weeks; however, several patients need a temporary pacemaker or chronotropic agents to stabilize their hemodynamics. Here, we report the first case of transient bradycardia associated with hemodynamic deterioration following HT, which was successfully treated with cilostazol, a phosphodiesterase-3-inhibiting agent. A 59-year-old man received HT for advanced heart failure due to ischemic cardiomyopathy. General fatigue persisted even after the HT. His HR was around 60 beats per minute (bpm) with sinus rhythm. Echocardiography showed no abnormal findings. Right heart catheterization showed that the cardiac index (CI) was 1.9 L/minute/m2. Continuous intravenous infusion of isoproterenol (0.003 µg/kg/minute) increased the HR to 80 bpm and CI to 2.7 L/minute/m2 and improved his symptoms. Isoproterenol was switched to oral administration of cilostazol (100 mg, twice a day), which maintained the HR at around 80 bpm and CI of 2.5 L/minute/m2. The patient's HR gradually recovered and cilostazol could be discontinued three months after the HT. Oral administration of cilostazol can be a therapeutic option for patients with sinus bradycardia following HT, who need positive chronotropic support.


Assuntos
Bradicardia/tratamento farmacológico , Cilostazol/uso terapêutico , Insuficiência Cardíaca/cirurgia , Transplante de Coração/efeitos adversos , Bradicardia/diagnóstico por imagem , Bradicardia/etiologia , Débito Cardíaco/efeitos dos fármacos , Eletrocardiografia/métodos , Seguimentos , Insuficiência Cardíaca/diagnóstico , Transplante de Coração/métodos , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/etiologia , Edema Pulmonar/fisiopatologia , Radiografia Torácica/métodos , Fatores de Tempo , Resultado do Tratamento
8.
J Am Coll Cardiol ; 74(7): 889-901, 2019 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-31416533

RESUMO

BACKGROUND: Phosphodiesterase-9 (PDE9) reduces natriuretic peptide (NP) signaling and may be involved in the pathophysiology of heart failure (HF). OBJECTIVES: This study investigated for the first time the integrated hemodynamic, endocrine, and renal effects of phosphodiesterase-9 inhibition (PDE9-I). METHODS: A total of 8 normal sheep and 8 sheep with pacing-induced HF received incremental intravenous boluses of PDE9-I (30, 100, and 300 mg PF-04749982 at 1-h intervals). RESULTS: PDE9-I dose-dependently increased plasma cyclic guanosine monophosphate (cGMP) in normal sheep (p < 0.05) while concurrently reducing circulating atrial natriuretic peptide levels (p < 0.01). Similar trends were evident in HF, resulting in significant elevations in the cGMP/NP ratio in both states (p < 0.001 and p < 0.05, respectively). PDE9-I also produced progressive falls in arterial pressure (HF: p < 0.001), atrial pressure (Normal: p < 0.001; HF: p < 0.001), and peripheral resistance (HF: p < 0.001), and transiently increased cardiac output at the top dose (Normal: p < 0.05; HF: p < 0.001). Inhibition of PDE9 had a negligible effect on circulating hormones at the lower doses, but post-high dose, acutely increased renin activity (Normal: p < 0.001; HF: p < 0.05), vasopressin (Normal: p < 0.001; HF: p < 0.01), and cyclic adenosine monophosphate (HF: p < 0.001). Plasma aldosterone increased briefly after high-dose PDE9-I in normal sheep, and fell following the top dose in HF. PDE9-I dose-dependently increased urinary cGMP in both states (both p < 0.001). In HF, this was associated with increases in urine volume (p < 0.01), sodium excretion (p < 0.01), and creatinine clearance (p < 0.001). CONCLUSIONS: PDE9-I improves NP efficacy in conjunction with beneficial hemodynamic and renal effects in experimental HF. These results support a role for PDE9 in HF pathophysiology and suggest its inhibition may constitute a novel therapeutic approach to this disease.


Assuntos
3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Fosfodiesterase/administração & dosagem , Monofosfato de Adenosina/sangue , Aldosterona/sangue , Animais , Fator Natriurético Atrial/sangue , Pressão Atrial/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Creatinina/urina , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Esquema de Medicação , Guanosina Monofosfato/sangue , Guanosina Monofosfato/urina , Renina/sangue , Ovinos , Sódio/urina , Urina , Resistência Vascular/efeitos dos fármacos , Vasopressinas/sangue
9.
Crit Care ; 23(1): 264, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358025

RESUMO

BACKGROUND: Bedside functional hemodynamic assessment has gained in popularity in the last years to overcome the limitations of static or dynamic indexes in predicting fluid responsiveness. The aim of this systematic review and metanalysis of studies is to investigate the reliability of the functional hemodynamic tests (FHTs) used to assess fluid responsiveness in adult patients in the intensive care unit (ICU) and operating room (OR). METHODS: MEDLINE, EMBASE, and Cochrane databases were screened for relevant articles using a FHT, with the exception of the passive leg raising. The QUADAS-2 scale was used to assess the risk of bias of the included studies. In-between study heterogeneity was assessed through the I2 indicator. Bias assessment graphs were plotted, and Egger's regression analysis was used to evaluate the publication bias. The metanalysis determined the pooled area under the receiving operating characteristic (ROC) curve, sensitivity, specificity, and threshold for two FHTs: the end-expiratory occlusion test (EEOT) and the mini-fluid challenge (FC). RESULTS: After text selection, 21 studies met the inclusion criteria, 7 performed in the OR, and 14 in the ICU between 2005 and 2018. The search included 805 patients and 870 FCs with a median (IQR) of 39 (25-50) patients and 41 (30-52) FCs per study. The median fluid responsiveness was 54% (45-59). Ten studies (47.6%) adopted a gray zone analysis of the ROC curve, and a median (IQR) of 20% (15-51) of the enrolled patients was included in the gray zone. The pooled area under the ROC curve for the end-expiratory occlusion test (EEOT) was 0.96 (95%CI 0.92-1.00). The pooled sensitivity and specificity were 0.86 (95%CI 0.74-0.94) and 0.91 (95%CI 0.85-0.95), respectively, with a best threshold of 5% (4.0-8.0%). The pooled area under the ROC curve for the mini-FC was 0.91 (95%CI 0.85-0.97). The pooled sensitivity and specificity were 0.82 (95%CI 0.76-0.88) and 0.83 (95%CI 0.77-0.89), respectively, with a best threshold of 5% (3.0-7.0%). CONCLUSIONS: The EEOT and the mini-FC reliably predict fluid responsiveness in the ICU and OR. Other FHTs have been tested insofar in heterogeneous clinical settings and, despite promising results, warrant further investigations.


Assuntos
Hemodinâmica/fisiologia , Respiração com Pressão Positiva/normas , Adulto , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Feminino , Hidratação/métodos , Hidratação/normas , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva/métodos , Curva ROC , Reprodutibilidade dos Testes
10.
Crit Care Nurs Clin North Am ; 31(3): 349-366, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31351555

RESUMO

This article reviews the use of vasoactive medications prescribed in the postoperative management of patients who have undergone cardiac surgery. With a focus on the influence these medications have on the physiologic contributors to cardiac output and blood pressure, insight into decision making related to use, titration, and discontinuation of these medications is provided. Case studies offer vignettes to demonstrate the application of knowledge gleaned from the article.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiotônicos/administração & dosagem , Cirurgia Torácica , Vasoconstritores/administração & dosagem , Vasodilatadores/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Enfermagem de Cuidados Críticos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Contração Miocárdica , Cuidados Pós-Operatórios
11.
PLoS One ; 14(7): e0213414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31291253

RESUMO

In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35-40 mm Hg; normal) and hypercapnia (ibid 90-110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 µg/kg/min (low), 0.6 µg/kg/min (middle), and 1.2 µg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33-7.42] and 7.01 [range 6.96-7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis.


Assuntos
Acidose Respiratória/tratamento farmacológico , Cardiotônicos/administração & dosagem , Colforsina/análogos & derivados , Acidose Respiratória/fisiopatologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Catecolaminas/sangue , Colforsina/administração & dosagem , Modelos Animais de Doenças , Dobutamina/administração & dosagem , Cães , Relação Dose-Resposta a Droga , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/fisiopatologia , Resistência Vascular/efeitos dos fármacos
12.
Biomed Res Int ; 2019: 6539050, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31309111

RESUMO

Objective: To determine whether the administration of intra-arrest cyclosporine (CCY) and methylprednisolone (MP) preserves left ventricular ejection fraction (LVEF) and cardiac output (CO) after return of spontaneous circulation (ROSC). Methods: Eleven, 25-30kg female swine were randomized to receive 10mg/kg CCY + 40mg MP or placebo, anesthetized and given a transthoracic shock to induce ventricular fibrillation. After 8 minutes, standard CPR was started. After two additional minutes, the experimental agent was administered. Animals with ROSC were supported for up to 12h with norepinephrine as needed. Echocardiography was performed at baseline, and 1, 2, 6 and 12h post-ROSC. Analysis was performed using generalized estimating equations (GEE) after downsampling continuously sampled data to 5 minute epochs. Results: Eight animals (64%) achieved ROSC after a median of 7 [IQR 5-13] min of CPR, 2 [ IQR 1-3] doses of epinephrine and 2 [IQR 1-5] defibrillation shocks. Animals receiving CCY+MP had higher post ROSC MAP (GEE coefficient -10.2, P = <0.01), but reduced cardiac output (GEE coefficient 0.8, P = <0.01) compared to placebo. There was no difference in LVEF or vasopressor use between arms. Conclusions: Intra-arrest cyclosporine and methylprednisolone decreased post-arrest cardiac output and increased mean arterial pressure without affecting left ventricular ejection fraction.


Assuntos
Cardiomiopatias/tratamento farmacológico , Ciclosporina/farmacologia , Parada Cardíaca/tratamento farmacológico , Metilprednisolona/farmacologia , Animais , Débito Cardíaco/efeitos dos fármacos , Reanimação Cardiopulmonar/métodos , Ecocardiografia/métodos , Cardioversão Elétrica/métodos , Epinefrina/farmacologia , Feminino , Ventrículos do Coração/efeitos dos fármacos , Suínos , Vasoconstritores/farmacologia , Fibrilação Ventricular/tratamento farmacológico
13.
Pediatr Cardiol ; 40(6): 1238-1246, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31309235

RESUMO

The oral triiodothyronine for infants and children undergoing cardiopulmonary bypass (OTICC) trial showed that Triiodothyronine (T3) supplementation improved hemodynamic and clinical outcome parameters. We tested the validity of low cardiac output syndrome (LCOS), derived using clinical parameters and laboratory data, by comparing the LCOS diagnosis with objective parameters commonly measured in a cardiac intensive care unit (CCU) setting. OTICC, a randomized, placebo-controlled trial included children younger than 3 years with an Aristotle score between 6 and 9. We used the existing trial data set to compare the LCOS diagnosis with echocardiographic hemodynamic parameters. Additionally, we determined if LCOS, prospectively assigned during a clinical trial, served as an early predictor of clinical outcomes. All LCOS subjects at 6 and 12 h after cross-clamp release later showed significantly lower pulse pressure, stroke volume and cardiac output, and higher systemic vascular resistance. These LCOS patients also had significantly longer time to extubation (TTE) and higher mortality rate. LCOS incidence was significantly lower in the T3 treatment group [n = 86 vs. 66, respectively, p < 0.001; OR (95% CI) 0.43 (0.36-0.52)] particularly at 6 h. Also, LCOS patients in the placebo group had significantly lower FT3 serum levels over time. These analyses confirm that early clinically defined LCOS successfully predicts cardiac dysfunction determined later by objective hemodynamic echocardiographic parameters. Furthermore, early LCOS significantly impacts TTE and mortality. Finally, the data support prior clinical trial data, showing that oral T3 supplementation decreases early LCOS in concordance with reducing TTE.


Assuntos
Baixo Débito Cardíaco/tratamento farmacológico , Débito Cardíaco/efeitos dos fármacos , Receptores dos Hormônios Tireóideos/administração & dosagem , Tri-Iodotironina/administração & dosagem , Baixo Débito Cardíaco/etiologia , Baixo Débito Cardíaco/mortalidade , Ponte Cardiopulmonar/efeitos adversos , Criança , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Masculino , Estudos Prospectivos , Resultado do Tratamento
14.
Crit Care ; 23(Suppl 1): 149, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200777

RESUMO

Catecholamines are used to increase cardiac output and blood pressure, aiming ultimately at restoring/improving tissue perfusion. While intuitive in its concept, this approach nevertheless implies to be effective that regional organ perfusion would increase in parallel to cardiac output or perfusion pressure and that the catecholamine does not have negative effects on the microcirculation. Inotropic agents may be considered in some conditions, but it requires prior optimization of cardiac preload. Alternative approaches would be either to minimize exposure to vasopressors, tolerating hypotension and trying to prioritize perfusion but this may be valid as long as perfusion of the organ is preserved, or to combine moderate doses of vasopressors to vasodilatory agents, especially if these are predominantly acting on the microcirculation. In this review, we will discuss the pros and cons of the use of catecholamines and alternative agents for improving tissue perfusion in septic shock.


Assuntos
Catecolaminas/efeitos adversos , Perfusão/normas , Pressão Arterial/fisiologia , Débito Cardíaco/efeitos dos fármacos , Catecolaminas/farmacologia , Catecolaminas/uso terapêutico , Humanos , Microcirculação/efeitos dos fármacos , Perfusão/métodos , Perfusão/tendências , Ressuscitação/métodos , Ressuscitação/tendências
15.
EuroIntervention ; 15(7): 586-593, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31147306

RESUMO

AIMS: The haemodynamic effects of primary implantation of an intra-aortic balloon pump (IABP) versus inotropes in decompensated heart failure and low output (DHF-LO), but without an acute coronary syndrome, have not been investigated. We therefore aimed to investigate the effect of primary IABP implantation as compared to inotropes on haemodynamics in DHF-LO with no acute ischaemia. METHODS AND RESULTS: Patients (n=32) with DHF-LO despite IV diuretics were randomised to primary 50 mL IABP or inotropes (INO: enoximone or dobutamine). The primary endpoint was the improvement of organ perfusion assessed by ∆ mixed-venous oxygen saturation (SvO2) at 3 hours; secondary endpoints included ∆ cardiac power output (CPO), NT-proBNP proportional change, cumulative fluid balance and ∆ dyspnoea severity score, all at 48 hours. Data are presented as median (IQR). Patients were 60 (48-69) years old and 72% were male. Baseline SvO2 was 44 (39-53)%. ∆SvO2 was higher in the IABP group (+17 [+9; +24] vs. +5 [+2; +9]%, p<0.05). IABP patients had a higher ∆CPO, a greater relative reduction in NT-proBNP, a more negative cumulative fluid balance, and a greater reduction in dyspnoea severity score. There were no IABP-related serious adverse events (SAEs). Thirty-day mortality was 23% (IABP) vs. 44% (INO). CONCLUSIONS: Primary circulatory support by IABP showed a significant increase in improved organ perfusion assessed by SvO2.


Assuntos
Débito Cardíaco/fisiologia , Cardiotônicos/uso terapêutico , Dobutamina/uso terapêutico , Enoximona/uso terapêutico , Insuficiência Cardíaca/cirurgia , Hemodinâmica/fisiologia , Balão Intra-Aórtico/métodos , Idoso , Débito Cardíaco/efeitos dos fármacos , Feminino , Coração Auxiliar , Hemodinâmica/efeitos dos fármacos , Humanos , Balão Intra-Aórtico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
Med Hypotheses ; 128: 76-77, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31203914

RESUMO

Type A aortic dissection (TAAD) is a catastrophic condition with 24-48% mortality during the first day, if patients are not surgically treated. Due to old age and associated co-morbidities surgeons may be reluctant to operate and patients are administered medical therapy for the end of reducing systolic blood pressure and heart rate. Beta-blockers (BB) are the "medications of choice". Based on physical and physiological considerations, it was hypothesized that BB may actually exacerbate TAAD.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Aneurisma Dissecante/tratamento farmacológico , Contração Miocárdica/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Cardiologia/métodos , Comorbidade , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica , Humanos , Modelos Teóricos , Túnica Íntima/lesões
17.
Pediatr Cardiol ; 40(5): 1046-1056, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31065757

RESUMO

Acute heart failure (AHF) can cause low cardiac output and poor end-organ perfusion. Inotropic agents along with vasodilators can improve organ perfusion. Arginine vasopressin (AVP) and calcium chloride (CaCl) infusions are increasingly being used in low cardiac output states in pediatric AHF. We retrospectively reviewed 77 patients (0-18 years) with AHF admitted between January 2014 and May 2017 who received concurrent AVP and CaCl infusions. Surrogates of cardiac output and organ perfusion included hemodynamic vital signs, laboratory parameters, and urine output (UO). Organ dysfunction and vasopressor inotropic scores were also calculated. Median (IQR) age was 0.88 years (0, 3.75), and median weight was 6.62 kg (3.5, 13.7). Congenital heart disease was present in 70% (46/77) patients. Univentricular physiology was present in 25% (25/77) patients. None of the patients were in the immediate postoperative period. Median durations of AVP and CaCl were 2 days (1, 3) and 3 days (2, 6), respectively. Using Wilcoxon-signed rank test and Bonferroni correction, post hoc comparison showed that at 8 h post infusion, all systolic blood pressure (SBP) and diastolic blood pressure (DBP) results, and UO were greater than those 1 h prior to infusion. Median SBP increased from 79 mm Hg (71, 92) 1 h prior to 97 mm Hg (84, 107) 8 h post. Median DBP increased from 44 mm Hg (35, 52) 1 h prior to 54 mm Hg (44, 62) 8 h post. Heart rate showed a decrease between measurements 1 h prior to infusion and 8 h post, with median scores 146 (127, 162) and 136 (114, 150) beats per minute, respectively. Within first 8 h, median UO continuously increased from 6 mL/h. (0, 25) at 1 h post infusion to 20 mL/h. (2, 62) at 8 h post infusion. Median pediatric logarithmic organ dysfunction scores on days 4 through 7 post infusion were lower compared to day 1; median vasopressor inotropic scores on day 2 through 7 post infusion were lower compared to day 1. Serum lactate level, arterial pH, and base excess all showed favorable trend. Concurrent use of AVP and CaCl infusions may improve surrogates of cardiac output, and intensive care outcomes, and prevent organ dysfunction in children with AHF.


Assuntos
Arginina Vasopressina/uso terapêutico , Cloreto de Cálcio/uso terapêutico , Cardiopatias Congênitas/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Vasoconstritores/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Pré-Escolar , Quimioterapia Combinada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
18.
Nat Rev Cardiol ; 16(9): 555-574, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31123340

RESUMO

Testosterone is the main male sex hormone and is essential for the maintenance of male secondary sexual characteristics and fertility. Androgen deficiency in young men owing to organic disease of the hypothalamus, pituitary gland or testes has been treated with testosterone replacement for decades without reports of increased cardiovascular events. In the past decade, the number of testosterone prescriptions issued for middle-aged or older men with either age-related or obesity-related decline in serum testosterone levels has increased exponentially even though these conditions are not approved indications for testosterone therapy. Some retrospective studies and randomized trials have suggested that testosterone replacement therapy increases the risk of cardiovascular disease, which has led the FDA to release a warning statement about the potential cardiovascular risks of testosterone replacement therapy. However, no trials of testosterone replacement therapy published to date were designed or adequately powered to assess cardiovascular events; therefore, the cardiovascular safety of this therapy remains unclear. In this Review, we provide an overview of epidemiological data on the association between serum levels of endogenous testosterone and cardiovascular disease, prescription database studies on the risk of cardiovascular disease in men receiving testosterone therapy, randomized trials and meta-analyses evaluating testosterone replacement therapy and its association with cardiovascular events and mechanistic studies on the effects of testosterone on the cardiovascular system. Our aim is to help clinicians to make informed decisions when considering testosterone replacement therapy in their patients.


Assuntos
Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Terapia de Reposição Hormonal , Testosterona/sangue , Testosterona/uso terapêutico , Animais , Aterosclerose/diagnóstico por imagem , Plaquetas/fisiologia , Débito Cardíaco/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Vasos Coronários , Progressão da Doença , Prescrições de Medicamentos/estatística & dados numéricos , Endotélio/fisiopatologia , Tolerância ao Exercício/efeitos dos fármacos , Glucose/metabolismo , Humanos , Metabolismo dos Lipídeos , Lipoproteínas/sangue , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Testosterona/farmacologia , Resistência Vascular/efeitos dos fármacos
19.
Crit Care ; 23(1): 179, 2019 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097012

RESUMO

BACKGROUND: Fluid challenge (FC) is one of the most common practices in Intensive Care Unit (ICU). The present study aimed to evaluate whether echocardiographic assessment of the response to FC at the end of the infusion or 20 min later could affect the results of the FC. METHODS: This is a prospective, observational, multicenter study including all ICU patients in septic shock requiring a FC of 500 mL crystalloids over 10 min. Fluid responsiveness was defined as a > 15% increase in stroke volume (SV) assessed by velocity-time integral (VTI) measurements at baseline (T0), at the end of FC (T10), then 10 (T20) and 20 min (T30) after the end of FC. RESULTS: From May 20, 2014, to January 7, 2016, a total of 143 patients were enrolled in 11 French ICUs (mean age 64 ± 14 years, median IGS II 53 [43-63], median SOFA score 10 [8-12]). Among the 76/143 (53%) patient responders to FC at T10, 37 patients were transient responders (TR), i.e., became non-responders (NR) at T30 (49%, 95%CI = [37-60]), and 39 (51%, 95%CI = [38-62]) patients were persistent responders (PR), i.e., remained responders at T30. Among the 67 NR at T10, 4 became responders at T30, (6%, 95%CI = [1.9-15.3]). In the subgroup analysis, no statistical difference in hemodynamic and echocardiographic parameters was found between groups. CONCLUSIONS: This study shows that 51.3% of initial responders have a persistent response to fluid 30 min after the beginning of fluid infusion and only 41.3% have a transient response highlighting that fluid responsiveness is time dependent. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02116413 . Registered on April 16, 2014.


Assuntos
Hidratação/métodos , Sepse/terapia , Fatores de Tempo , Idoso , Pressão Arterial/efeitos dos fármacos , Pressão Arterial/fisiologia , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Soluções Cristaloides/uso terapêutico , Ecocardiografia/métodos , Feminino , França , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sepse/fisiopatologia
20.
Cell Physiol Biochem ; 52(4): 922-934, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30964609

RESUMO

BACKGROUND/AIMS: In a previous study, we reported that cardiomyocytes were equipped with non-neuronal cardiac cholinergic system (NNCCS) to synthesize acetylcholine (ACh), which is indispensable for maintaining the basic physiological cardiac functions. The aim of this study was to identify and characterize a pharmacological inducer of NNCCS. METHODS: To identify a pharmacological inducer of NNCCS, we screened several chemical compounds with chemical structures similar to the structure of S-nitroso-N-acetyl-DL-penicillamine (SNAP). Preliminary investigation revealed that SNAP is an inducer of non-neuronal ACh synthesis. We screened potential pharmacological inducers in H9c2 and HEK293 cells using western blot analysis, luciferase assay, and measurements of intracellular cGMP, NO2 and ACh levels. The effects of the screened compound on cardiac function of male C57BL6 mice were also evaluated using cardiac catheter system. RESULTS: Among the tested compounds, we selected S-nitroso-Npivaloyl-D-penicillamine (SNPiP), which gradually elevated the intracellular cGMP levels and nitric oxide (NO) levels in H9c2 and HEK293 cells. These elevated levels resulted in the gradual transactivation and translation of the choline acetyltransferase gene. Additionally, in vitro and in vivo SNPiP treatment elevated ACh levels for 72 h. SNPiP-treated mice upregulated their cardiac function without tachycardia but with enhanced diastolic function resulting in improved cardiac output. The effect of SNPiP was dependent on SNPiP nitroso group as verified by the ineffectiveness of N-pivaloyl-D-penicillamine (PiP), which lacks the nitroso group. CONCLUSION: SNPiP is identified to be one of the important pharmacological candidates for induction of NNCCS.


Assuntos
Acetilcolina/biossíntese , Débito Cardíaco/efeitos dos fármacos , GMP Cíclico/metabolismo , Miócitos Cardíacos/metabolismo , Doadores de Óxido Nítrico , Sistema Colinérgico não Neuronal/efeitos dos fármacos , Animais , Células HEK293 , Humanos , Masculino , Camundongos , Óxido Nítrico/biossíntese , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/farmacologia
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