A retrospective observational study evaluating the association between vasoactive-inotropic score and mortality after major abdominal surgery.

The relationship between VISmax and mortality in patients undergoing major abdominal surgery remains unclear. This study aims to evaluate the association between VISmax and both short-term and long-term all-cause mortality in patients undergoing major abdominal surgery, VISmax was calculated (VISmax = dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min] + 10 × milrinone dose [µg/kg/min] + 10,000 × vasopressin dose [units/kg/min] + 100 × norepinephrine dose [µg/kg/min]) using the maximum dosing rates of vasoactives and inotropics within the first 24 h postoperative ICU admission. The study included 512 patients first admitted to the intensive care unit (ICU) who were administered vasoactive drugs after major abdominal surgery. The data was extracted from the medical information mart in intensive care-IV database. VISmax was stratified into five categories: 0-5, > 5-15, > 15-30, > 30-45, and > 45. Compared to patients with the lowest VISmax (≤ 5), those with the high VISmax (> 45) had an increased risk of 30-day mortality (hazard ratio [HR] 3.73, 95% CI 1.16-12.02; P = 0.03) and 1-year mortality (HR 2.76, 95% CI 1.09-6.95; P = 0.03) in fully adjusted Cox models. The ROC analysis for VISmax predicting 30-day and 1-year mortality yielded AUC values of 0.69 (95% CI 0.64-0.75) and 0.67 (95% CI 0.62-0.72), respectively. In conclusion, elevated VISmax within the first postoperative 24 h after ICU admission was associated with increased risks of both short-term and long-term mortality in patients undergoing major abdominal surgery.

Shen'ge Formula Protects Cardiac Function in Rats with Pressure Overload-Induced Heart Failure.

Background: In China, Shen'ge formula (SGF), a Traditional Chinese Medicine blend crafted from ginseng and gecko, holds a revered place in the treatment of cardiovascular diseases. However, despite its prevalent use, the precise cardioprotective mechanisms of SGF remain largely uncharted. This study aims to fill this gap by delving deeper into SGF's therapeutic potential and underlying action mechanism, thus giving its traditional use a solid scientific grounding. Methods: In this study, rats were subjected to abdominal aortic constriction (AAC) to generate pressure overload. Following AAC, we administered SGF and bisoprolol intragastrically at specified doses for two distinct durations: 8 and 24 weeks. The cardiac function post-treatment was thoroughly analyzed using echocardiography and histological examinations, offering insights into SGF's influence on vital cardiovascular metrics, and signaling pathways central to cardiac health. Results: SGF exhibited promising results, significantly enhanced cardiac functions over both 8 and 24-week periods, evidenced by improved ejection fraction and fractional shortening while moderating left ventricular parameters. Noteworthy was SGF's role in the significant mitigation of myocardial hypertrophy and in fostering the expression of vital proteins essential for heart health by the 24-week mark. This intervention markedly altered the dynamics of the Akt/HIF-1α/p53 pathway, inhibiting detrimental processes while promoting protective mechanisms. Conclusion: Our research casts SGF in a promising light as a cardioprotective agent in heart failure conditions induced by pressure overload in rats. Central to this protective shield is the modulation of the Akt/HIF-1α/p53 pathway, pointing to a therapeutic trajectory that leverages HIF-1α promotion and p53 nuclear transport inhibition.

Growth/differentiation factor 15 (GDF15) expression in the heart after myocardial infarction and cardioprotective effect of pre-ischemic rGDF15 administration.

Growth/differentiation factor-15 (GDF15) is considered an unfavourable prognostic biomarker for cardiovascular disease in clinical data, while experimental studies suggest it has cardioprotective potential. This study focuses on the direct cardiac effects of GDF15 during ischemia-reperfusion injury in Wistar male rats, employing concentrations relevant to patients at high cardiovascular risk. Initially, we examined circulating levels and heart tissue expression of GDF15 in rats subjected to ischemia-reperfusion and sham operations in vivo. We then evaluated the cardiac effects of GDF15 both in vivo and ex vivo, administering recombinant GDF15 either before 30 min of ischemia (preconditioning) or at the onset of reperfusion (postconditioning). We compared infarct size and cardiac contractile recovery between control and rGDF15-treated rats. Contrary to our expectations, ischemia-reperfusion did not increase GDF15 plasma levels compared to sham-operated rats. However, cardiac protein and mRNA expression increased in the infarcted zone of the ischemic heart after 24 h of reperfusion. Notably, preconditioning with rGDF15 had a cardioprotective effect, reducing infarct size both in vivo (65 ± 5% in control vs. 42 ± 6% in rGDF15 groups) and ex vivo (60 ± 4% in control vs. 45 ± 4% in rGDF15 groups), while enhancing cardiac contractile recovery ex vivo. However, postconditioning with rGDF15 did not alter infarct size or the recovery of contractile parameters in vivo or ex vivo. These novel findings reveal that the short-term exogenous administration of rGDF15 before ischemia, at physiologically relevant levels, protects the heart against ischemia-reperfusion injury in both in vivo and ex vivo settings. The ex vivo results indicate that rGDF15 operates independently of the inflammatory, endocrine and nervous systems, suggesting direct and potent cardioprotective properties against ischemia-reperfusion injury.

Thirty-day risk of digoxin toxicity among older adults co-prescribed trimethoprim-sulfamethoxazole versus amoxicillin: A population-based cohort study.

IMPORTANCE: Trimethoprim-sulfamethoxazole (TMP-SMX) may increase digoxin concentration, a medication with a narrow therapeutic index. Small changes in digoxin concentration could predispose individuals to the risk of toxicity. OBJECTIVE: To characterize the risk of digoxin toxicity in older adults taking digoxin following co-prescription of TMP-SMX compared with co-prescription of amoxicillin. DESIGN, SETTINGS, AND PARTICIPANTS: Retrospective population-based cohort study in Ontario, Canada (2002-2020) using linked health care data. Participants comprised 47,961 older adults taking digoxin (58% women; median age 80 years [interquartile range 74-86]) who were newly treated with TMP-SMX (n = 10,273) compared with those newly treated with amoxicillin (n = 37,688). EXPOSURE: Co-prescription of TMP-SMX versus amoxicillin in older adults concurrently taking digoxin. MAIN OUTCOME AND MEASURE: The primary outcome was a hospital encounter (i.e., hospital admission or emergency department visit) with digoxin toxicity within 30 days of the antibiotic prescription. Inverse probability of treatment weighting on the propensity score was used to balance comparison groups on indicators of baseline health. Weighted risk ratios (RR) were obtained using modified Poisson regression and weighted risk differences (RD) using binomial regression. The number needed to harm (NNH) was calculated as 1/RD. RESULTS: A hospital encounter with digoxin toxicity occurred in 49/10,273 (0.48%) patients treated with TMP-SMX versus 32/37,688 (0.08%) in those treated with amoxicillin (weighted RR, 5.71 [95% confidence interval (CI), 3.19 to 10.24]; weighted RD, 0.39% [95% CI, 0.25% to 0.53%]; NNH 256 [95% CI, 233 to 400]). CONCLUSION AND RELEVANCE: In older adults taking digoxin, the 30-day risk of a hospital encounter with digoxin toxicity was nearly 6 times higher in those co-prescribed TMP-SMX versus amoxicillin, although the absolute risk difference was low (0.4%). Physicians should prescribe an alternative antibiotic when clinically appropriate. If TMP-SMX must be co-prescribed with digoxin (if the benefit is believed to outweigh the risk), digoxin should be dose-reduced on an individual basis.

Cardiac index-guided therapy to maintain optimised postinduction cardiac index in high-risk patients having major open abdominal surgery: the multicentre randomised iPEGASUS trial.

BACKGROUND: It is unclear whether optimising intraoperative cardiac index can reduce postoperative complications. We tested the hypothesis that maintaining optimised postinduction cardiac index during and for the first 8 h after surgery reduces the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. METHODS: In three German and two Spanish centres, high-risk patients having elective major open abdominal surgery were randomised to cardiac index-guided therapy to maintain optimised postinduction cardiac index (cardiac index at which pulse pressure variation was <12%) during and for the first 8 h after surgery using intravenous fluids and dobutamine or to routine care. The primary outcome was the incidence of a composite outcome of moderate or severe complications within 28 days after surgery. RESULTS: We analysed 318 of 380 enrolled subjects. The composite primary outcome occurred in 84 of 152 subjects (55%) assigned to cardiac index-guided therapy and in 77 of 166 subjects (46%) assigned to routine care (odds ratio: 1.87, 95% confidence interval: 1.03-3.39, P=0.038). Per-protocol analyses confirmed the results of the primary outcome analysis. CONCLUSIONS: Maintaining optimised postinduction cardiac index during and for the first 8 h after surgery did not reduce, and possibly increased, the incidence of a composite outcome of complications within 28 days after surgery compared with routine care in high-risk patients having elective major open abdominal surgery. Clinicians should not strive to maintain optimised postinduction cardiac index during and after surgery in expectation of reducing complications. CLINICAL TRIAL REGISTRATION: NCT03021525.

Systemic tolerance of intravenous milrinone administration for cerebral vasospasm secondary to non-traumatic subarachnoid hemorrhage.

PURPOSE: Delayed cerebral ischemia (DCI) is a severe subarachnoid hemorrhage (SAH) complication, closely related to cerebral vasospasm (CVS). CVS treatment frequently comprises intravenous milrinone, an inotropic and vasodilatory drug. Our objective is to describe milrinone's hemodynamic, respiratory and renal effects when administrated as treatment for CVS. METHODS: Retrospective single-center observational study of patients receiving intravenous milrinone for CVS with systemic hemodynamics, oxygenation, renal disorders monitoring. We described these parameters' evolution before and after milrinone initiation (day - 1, baseline, day 1 and day 2), studied treatment cessation causes and assessed neurological outcome at 3-6 months. RESULTS: Ninety-one patients were included. Milrinone initiation led to cardiac output increase (4.5 L/min [3.4-5.2] at baseline vs 6.6 L/min [5.2-7.7] at day 2, p < 0.001), Mean Arterial Pressure decrease (101 mmHg [94-110] at baseline vs 95 mmHg [85-102] at day 2, p = 0.001) norepinephrine treatment requirement increase (32% of patients before milrinone start vs 58% at day 1, p = 0.002) and slight PaO2/FiO2 ratio deterioration (401 [333-406] at baseline vs 348 [307-357] at day 2, p = 0.016). Milrinone was interrupted in 8% of patients. 55% had a favorable outcome. CONCLUSION: Intravenous milrinone for CVS treatment seems associated with significant impact on systemic hemodynamics leading sometimes to treatment discontinuation.

Time-Varying Clearance in Milrinone Pharmacokinetics from Premature Neonates to Adolescents.

BACKGROUND AND OBJECTIVES: Milrinone is an inotrope and vasodilator used for prophylaxis or treatment of low cardiac output syndrome after weaning from cardiopulmonary bypass (CPB). It is renally eliminated and has an acceptable therapeutic range of 100-300 µg/L, but weight-based dosing alone is associated with poor target attainment. We aimed to develop a population pharmacokinetic model for milrinone from premature neonates to adolescents, and to evaluate how age, renal function and recovery from CPB may impact dose selection. METHODS: Fifty paediatric patients (aged 4 days to 16 years) were studied after undergoing cardiac surgery supported by CPB. Data from 29 premature neonates (23-28 weeks' postmenstrual age) treated for prophylaxis of low systemic blood flow were available for a pooled pharmacokinetic analysis. Population parameters were estimated using non-linear mixed effects modelling (NONMEM 7.5.1). RESULTS: There were 369 milrinone measurements available for analysis. A one-compartment model with zero-order input and first-order elimination was used to describe milrinone disposition. Population parameters were clearance 17.8 L/70 kg [95% CI 15.8-19.9] and volume 20.4 L/h/70 kg [95% CI 17.8-22.1]. Covariates included size, postmenstrual age and renal function for clearance, and size and postnatal age for volume. Milrinone clearance is reduced by 39.5% [95% CI 24.0-53.7] immediately after bypass, and recovers to baseline clearance with a half-time of 12.0 h [95% CI 9.7-15.2]. Milrinone volume was 2.07 [95% CI 1.87-2.27] times greater at birth than the population standard and decreased over the first days of life with a half-time of 0.977 days [95% CI 0.833-1.12]. CONCLUSION: Milrinone is predominately renally eliminated and so renal function is an important covariate describing variability in clearance. Increasing clearance over time likely reflects increasing cardiac output and renal perfusion due to milrinone and return to baseline following CPB.

Evaluation of Ouabain's Tissue Distribution in C57/Black Mice Following Intraperitoneal Injection, Using Chromatography and Mass Spectrometry.

Cardiotonic steroids (CTSs), such as digoxin, are used for heart failure treatment. However, digoxin permeates the brain-blood barrier (BBB), affecting central nervous system (CNS) functions. Finding a CTS that does not pass through the BBB would increase CTSs' applicability in the clinic and decrease the risk of side effects on the CNS. This study aimed to investigate the tissue distribution of the CTS ouabain following intraperitoneal injection and whether ouabain passes through the BBB. After intraperitoneal injection (1.25 mg/kg), ouabain concentrations were measured at 5 min, 15 min, 30 min, 1 h, 3 h, 6 h, and 24 h using HPLC-MS in brain, heart, liver, and kidney tissues and blood plasma in C57/black mice. Ouabain was undetectable in the brain tissue. Plasma: Cmax = 882.88 ± 21.82 ng/g; Tmax = 0.08 ± 0.01 h; T1/2 = 0.15 ± 0.02 h; MRT = 0.26 ± 0.01. Cardiac tissue: Cmax = 145.24 ± 44.03 ng/g (undetectable at 60 min); Tmax = 0.08 ± 0.02 h; T1/2 = 0.23 ± 0.09 h; MRT = 0.38 ± 0.14 h. Kidney tissue: Cmax = 1072.3 ± 260.8 ng/g; Tmax = 0.35 ± 0.19 h; T1/2 = 1.32 ± 0.76 h; MRT = 1.41 ± 0.71 h. Liver tissue: Cmax = 2558.0 ± 382.4 ng/g; Tmax = 0.35 ± 0.13 h; T1/2 = 1.24 ± 0.7 h; MRT = 0.98 ± 0.33 h. Unlike digoxin, ouabain does not cross the BBB and is eliminated quicker from all the analyzed tissues, giving it a potential advantage over digoxin in systemic administration. However, the inability of ouabain to pass though the BBB necessitates intracerebral administration when used to investigate its effects on the CNS.

Comparative Effectiveness and Safety of Intermittent, Repeated, or Continuous Use of Levosimendan, Milrinone, or Dobutamine in Patients With Advanced Heart Failure: A Network and Single-Arm Meta-analysis.

ABSTRACT: The aim of this study was to synthesize the available evidence regarding differences in the long-term safety and efficacy of intermittent, repeated, or continuous palliative inotropic therapy among patients with advanced heart failure. We systematically searched the PubMed, Embase, and Cochrane Library electronic databases, with a cutoff date of November 23, 2023, for studies reporting outcomes in adult patients with advanced heart failure treated with intermittent, repeated, or continuous levosimendan, milrinone, or dobutamine. Forty-one studies (18 randomized controlled trials and 23 cohort studies) comprising 5137 patients met the inclusion criteria. The results of the network meta-analysis of randomized controlled trials showed that levosimendan had significant advantages over milrinone or dobutamine in reducing mortality and improving left ventricular ejection fraction. A single-arm meta-analysis also indicated that levosimendan had the lowest mortality and significantly improved B-type brain natriuretic peptide and left ventricular ejection fraction. Regarding safety, hypotension events were observed more frequently in the levosimendan and milrinone groups. However, the current evidence is limited by the heterogeneity and relatively small sample size of the studies.

Safety and efficacy of levosimendan in patients with cardiac amyloidosis.

BACKGROUND: Patients with cardiac amyloidosis (CA) often experience heart failure (HF) episodes. No evidence is available on inotropic therapy. This study aims to fill this gap by examining the safety and efficacy of levosimendan. METHODS: We retrieved all HF patients receiving ≥1 levosimendan infusion from 2013 to 2023. CA patients were matched with HF patients without CA (controls) based on sex, age, and left ventricular ejection fraction (LVEF). The response to levosimendan was measured as changes in daily urinary output, body weight, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR). RESULTS: CA patients (median age 77 years, 73% men, 59% with ATTR-CA) and controls were compared. Levosimendan infusion was stopped because of hypotension in 2 cases with CA and (in 1 case) worsening renal function, and in 2 controls because of ventricular tachycardia episodes and (in 1 case) hypotension. CA patients showed a trend toward increased daily urinary output (p = 0.078) and a significant decrease in body weight (p < 0.001), without significant changes in NT-proBNP (p = 0.497) and eGFR (p = 0.732). Both CA patients and controls displayed similar changes in urinary output, weight, and eGFR, but NT-proBNP decreased more significantly among controls (p < 0.001). No differences were noted in rehospitalization rates, but CA patients experienced higher mortality at 6 and 12 months (p = 0.003 and p = 0.001, respectively). CONCLUSIONS: Levosimendan appears safe for CA patients needing inotropic support. The diuretic response and weight decrease during hospitalization were comparable between CA patients and matched HF patients, despite the greater mortality of CA patients after discharge.

Aminophylline in combination with caffeine citrate in neurodevelopmental treatment and follow-up of high-risk preterm infants using GMs assessment.

To explore the application effect of aminophylline combined with caffeine citrate and GMs in the evaluation of neurodevelopmental treatment and follow-up in high-risk preterm infants. A retrospective analysis of 66 high-risk preterm infants admitted to Hengshui People's Hospital from January 2020 to June 2021 was conducted. The children who received only conventional treatment were set as the control group, while those who received aminophylline and caffeine citrate on the basis of conventional treatment were set as the experimental group, 33 cases each group; GMs were used to evaluate the neurodevelopmental function of the children, and the treatment effect was analyzed. The normal proportion of GMs assessment results in the twisting phase and restless movement phase of the experimental group was superior to the control group (P<0.05); The proportion of children with normal neurodevelopment in the experimental group was significantly higher than that in the control group (P<0.05). Aminophylline in combination with caffeine citrate can help promote the neurodevelopment of children and improve their physical health using GMs assessment in the treatment and follow-up of high-risk preterm infants.

Integrated chemical profiling, network pharmacology and pharmacological evaluation to explore the potential mechanism of Xinbao pill against myocardial ischaemia-reperfusion injury.

CONTEXT: Xinbao pill (XBW), a traditional Chinese herbal formula, is widely used in clinical treatment for cardiovascular diseases; however, the therapeutic effect of XBW on myocardial ischaemia-reperfusion injury (MI/RI) is unclear. OBJECTIVE: This study evaluates the cardioprotective effect and molecular mechanism of XBW against MI/RI. MATERIALS AND METHODS: A phytochemistry-based network pharmacology analysis was used to uncover the mechanism of XBW against MI/RI. Ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry method was used to identify chemicals. MI/RI-related targets of XBW were predicted using TargetNet database, OMIC database, etc. Sprague-Dawley (SD) rats under anterior descending artery ligation model were divided into Sham, MI/RI and XBW (180 mg/kg, intragastric administration). After 30 min ischaemia and 24 h reperfusion, heart tissues were collected for measurement of myocardial infarct size. After oxygen glucose deprivation for 6 h, H9c2 cells were treated with XBW (60, 240 and 720 µg/mL) and diazoxide (100 µM) for 18 h of reperfusion. RESULTS: Thirty-seven chemicals were identified in XBW; 50 MI/RI-related targets of XBW were predicted using indicated databases. XBW significantly reduced infarct size and creatine kinase MB (CK-MB) level after MI/RI; XBW protected H9c2 cells against OGD/R injury. Gene ontology (GO) and KEGG pathway enrichment analyses by String database showed that the cardioprotective effect of XBW was associated with autophagy and apoptosis signalling pathways. Experimental investigation also verified that XBW suppressed apoptosis, autophagy and endoplasmic reticulum (ER) stress. CONCLUSIONS: XBW showed therapeutic effects against MI/RI mainly via attenuating apoptosis though suppressing excessive autophagy and ER stress.

Nerolidol attenuates isoproterenol-induced acute myocardial infarction in rats.

Cardiovascular diseases have high morbidity and mortality rates, and their treatment is not effective in reducing the damage caused by myocardial infarction (MI). This study aimed to investigate whether nerolidol (NRD), a sesquiterpene alcohol, could attenuate MI in an isoproterenol-treated rat model. MI was induced by the administration of two doses of isoproterenol (ISO, 100 mg/kg, i.p.) with an interval of 24 h between doses.The animals were divided into four groups: control (CTR) (vehicle - NaCl 0.9% + Tween 80 0.2%), MI (ISO + vehicle), MI + NRD (50 mg/kg) and MI + NRD (100 mg/kg). An electrocardiogram was performed, and contractile parameters, cardiac enzymes, infarction size, and antioxidant parameters in the heart were measured to evaluate the effects of NRD. The ISO group showed a significant rise in ST segment, QTc, and heart rate associated with a reduction in left ventricular developed pressure (LVDP), + dP/dt, and -dP/dt. In addition, there were increases in levels of creatine kinase (CK), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and thiobarbituric acid (TBARS); reductions in superoxide dismutase (SOD) and catalase (CAT) activities; and an increase in the infarction size. Interestingly, NRD significantly attenuated almost all the parameters of ISO-induced MI mentioned above. Our results suggest that nerolidol attenuates MI caused by ISO by a marked reduction in myocardial infarct size and suppression of oxidative stress. CK total, creatine kinase total; CK-MB, creatine kinase myocardial band; LDH, lactate dehydrogenase; SOD, superoxide dismutase; CAT, catalase. CTR (vehicle group), MI (100 mg/kg of isoproterenol), ISO + NRD 50 (50 mg/kg of nerolidol), and ISO + NRD 100 (100 mg/kg of nerolidol).

The Effect of Diet on Cardiovascular Disease, Heart Disease, and Blood Vessels.

The Effect of Diet on Cardiovascular Disease, Heart Disease, and Blood Vessels [...].

Uso y seguridad de levosimendan en una unidad de cuidados intermedios: revisión de la experiencia de 3 años / Use and safety of Levosimendan in an Intermediate Care Unit: 3-year experience review

Introduction: Levosimendan is an inodilator with positive inotropiceffect whose demonstration of hemodynamic and clinical benefits hasnot always been consistent. The most recent meta-analyzes show stronger evidence of it, especially in some subgroups. The objective wasto evaluate the experience in the use of levosimendan, characterizingthe mode of prescription, the target population, clinical benefits andadverse effects.Materials and Methodologies: All patients who took Levosimendan in anIntermediate Care Unit during three full years were included. Generalclinical and analytical parameters, co-morbidities and characteristics ofhospitalization were obtained, as well as readmissions up to 6 months.Results: There were 39 events. Thirteen admissions were scheduled.Only 4 patients tolerated the maximum recommended levosimendanspeed. All completed 12.5 mg of levosimendan, 10 of which requiredaminergic support. In-hospital mortality was 15.4%. For all the patientswho died, admission was urgent.Conclusions: No patient with scheduled admission required aminergic support or died during hospitalization. It is not possible to inferwhether it would be possible to perform the same dose in a shorterperiod of time, even because of the small number that tolerated themaximum speed. Results of ongoing studies may help assess safetyand propose selection criteria for patients suitable for day hospitaladministration. Particularly in patients with advanced HF, intermittentand repeated administration, as occurred in this study, is a promising option. However, there are still important gaps, namely which isthe ideal cumulative dose and the frequency with which it shouldbe performed.

Introducción: El levosimendan es un sensibilizador de calcio con efectoinotrópico positivo cuya demostración de beneficios hemodinámicos yclínicos no siempre ha sido consistente. Los metanálisis más recientesmuestran pruebas más contundentes de ello, especialmente en algunossubgrupos. El objetivo fue evaluar la experiencia en el uso de levosimendan, caracterizando el modo de prescripción, la población, los beneficiosclínicos y los efectos adversos.Materiales y Metodologías: Se incluyeron todos los pacientes que tomaron Levosimendan en una Unidad de Cuidados Intermedios durante tresaños. Se obtuvieron parámetros clínicos y analíticos generales, comorbilidades y características de la hospitalización, así como reingresos hastalos 6 meses.Resultados: Hubo 39 eventos. Se programaron trece ingresos. Solo 4 pacientes toleraron la velocidad máxima recomendada de levosimendan.Todos completaron 12,5 mg de levosimendan, 10 de los cuales requirieron apoyo aminérgico. La mortalidad hospitalaria fue del 15,4%. Paratodos los pacientes que fallecieron, el ingreso fue urgente.Conclusiones: Ningún paciente con ingreso programado requirió apoyoaminérgico ni falleció durante la hospitalización. No es posible inferirsi sería posible realizar la misma dosis en un período de tiempo máscorto, incluso por el pequeño número que toleró la velocidad máxima.Los resultados de los estudios en curso pueden ayudar a evaluar la seguridad y proponer criterios de selección para pacientes adecuados para laadministración en un hospital de día. Particularmente en pacientes conIC avanzada, la administración intermitente y repetida, como ocurrió eneste estudio, es una opción prometedora. Sin embargo, existen lagunasimportantes, a saber, cuál es la dosis acumulativa ideal y la frecuenciacon la que debe realizarse.

Sinapic acid ameliorates cardiac dysfunction and cardiomyopathy by modulating NF-κB and Nrf2/HO-1 signaling pathways in streptozocin induced diabetic rats.

Hyperglycemia and hyperlipidemia-arbitrated mitochondrial oxidative insult is key reason for cardiac dysfunction and cardiomyopathy. Sinapic acid (SA) is a hydroxycinnamic acid (a polyphenolic acid) present in multiple plants and possesses several pharmacological activities. In this study, we examined the cardio protective effects of SA on streptozotocin (STZ)-induced cardiac insults. STZ and both STZ induced diabetes and normal control rats were administered with 20 and 40 mg/kg SA for 12 weeks. STZ rats demonstrated hyperglycemia and hyperlipidemia. Additionally, STZ administered rats exhibited various histological changes in the cardiac muscles and significantly enhanced CK-MB and LDH. The significant enhancement of oxidative stress, inflammation, and apoptotic markers, and the capacity to curb oxidative stress was significantly abridged in the STZ induced diabetic heart. Chronic treatment with SA (20-40 mg/kg) ameliorated the increased level of glucose, lipid, and cardiac function markers and curtailed histological changes in the cardiac muscles. Chronic treatment also repressed inflammation, oxidative stress and apoptosis thereby and restoring antioxidant defenses in the myocardium of STZ induced diabetic rats. STZ induced cardiac dysfunction and cardiomyopathy by promoting inflammation and oxidative stress. Sinapic acid ameliorates cardiac dysfunction and cardiomyopathy via improvement of hyperglycemia, hyperlipidemia, inflammation, oxidative stress, and apoptosis. Thus, SA possesses possible therapeutic value for the prevention of diabetic cardiac dysfunction and cardiomyopathy via the NRF2/HO-1 and NF-κB pathways.

Aqueous extract of Solanum nigrum attenuates Angiotensin-II induced cardiac hypertrophy and improves cardiac function by repressing protein kinase C-ζ to restore HSF2 deSUMOlyation and Mel-18-IGF-IIR signaling suppression.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum nigrum, commonly known as Makoi or black shade has been traditionally used in Asian countries and other regions of world to treat liver disorders, diarrhoea, inflammatory conditions, chronic skin ailments (psoriasis and ringworm), fever, hydrophobia, painful periods, eye diseases, etc. It has been observed that S. nigrum contains substances, like steroidal saponins, total alkaloid, steroid alkaloid, and glycoprotein, which show anti-tumor activity. However; there is no scientific evidence of the efficacy of S. nigrum in the treatment of cardiac hypertrophy. AIM: To investigate the ability of S. nigrum to attenuate Angiotensin II - induced cardiac hypertrophy and improve cardiac function through the suppression of protein kinase PKC-ζ and Mel-18-IGF-IIR signaling leading to the restoration of HSF2 desumolyation. MATERIALS AND METHODS: Cardiomyoblast cells (H9c2) were challenged with 100 nM Angiotensin-II (AngII) for 24 h and were then treated with different concentration of S.nigrum or Calphostin C for 24 h. The hypertrophic effect in cardiomyoblast cells were determined by immunofluorescence staining and the modulations in hypertrophic protein marker along with Protein Kinase C-ζ, MEL18, HSF2, and Insulin like growth factor II (IGFIIR), markers were analyzed by western blotting. In vivo experiments were performed using 12 week old male Wistar Kyoto rats (WKY) and Spontaneously hypertensive rats (SHR) separated into five groups. [1]Control WKY, [2] WKY -100 mg/kg of S.nigrum treatment, [3] SHR, [4] SHR-100 mg/kg of S.nigrum treatment, [5] SHR-300 mg/kg of S.nigrum treatment. S. nigrum was administered intraperitoneally for 8 week time interval. RESULTS: Western blotting results indicate that S. nigrum significantly attenuates AngII induced cardiac hypertrophy. Furthermore, actin staining confirmed the ability of S. nigrum to ameliorate AngII induced cardiac hypertrophy. Moreover, S. nigrum administration suppressed the hypertrophic signaling mediators like Protein Kinase C-ζ, Mel-18, and IGFIIR in a dose-dependent manner and HSF2 activation (restore deSUMOlyation) that leads to downregulation of IGF-IIR expression. Additionally in vivo experiments demonstrate the reduced heart sizes of S. nigrum treated SHRs rats when compared to control WKY rats. CONCLUSION: Collectively, the data reveals the cardioprotective effect of S. nigrum inhibiting PKC-ζ with alleviated IGF IIR level in the heart that profoundly remits cardiac hypertrophy for hypertension-induced heart failure.