A Meta-Analysis of the Effects of Levosimendan on Cardiac Function and Outcomes in Patients with Sepsis.

Objective: To systematically evaluate the effect of levosimendan on cardiac function and outcomes in patients with sepsis. Method: We searched multiple databases including CNKI, VIP, WanFang Data, WOS, PubMed, EMbase, and The Cochrane Library up to February 2023. We targeted RCTs comparing levosimendan with dobutamine as a control for treating sepsis. After a rigorous screening and quality evaluation, 18 studies were selected for meta-analysis using Review Manager 5.4. Results: Out of 18 studies involving 980 sepsis patients, the meta-analysis revealed the following for the levosimendan group compared to dobutamine: (1) A significant reduction in mortality rate (OR = 0.63, 95% CI (0.42,0.95), P = .03). (2) Shortened ICU stay (MD = -2.55, 95% CI (-3.12, -1.98), P < .00001). (3) Increased left ventricular ejection fraction (LVEF) (MD = 6.05, 95%CI (5.28, 6.81), P < .00001) and cardiac index (CI) (MD = 0.47, 95%CI (0.35, 0.59), P < .00001). (4) Decreased blood lactate (Lac) (MD = -1.31, 95%CI (-1.73, -0.90), P < .00001) and troponin I (TnI) levels (MD = -0.43, 95%CI (-0.66, -0.21), P = .0002). (5) Reduced incidence of adverse events (OR = 0.43, 95% CI (0.23,0.81), P = .008). Conclusions: Compared to dobutamine, levosimendan substantially enhances cardiac function in sepsis patients, leading to improved outcomes and fewer adverse events.

Comparison of norepinephrine, dopamine and dobutamine combined with enteral nutrition in the treatment of elderly patients harboring sepsis.

The present study was performed in order to investigate the safety and efficacy of different vasoactive drugs combined with enteral nutrition in terms of treating elderly patients with sepsis. A total of 75 elderly patients with sepsis treated with enteral nutrition in our hospital were randomly divided into three groups: group A (n = 25), group B (n = 25) and group C (n = 25). The three groups were treated with dopamine, dobutamine and norepinephrine respectively. One week after treatment, the therapeutic effects of the three groups were compared, the vascular elastic indexes, hemodynamic indexes and levels of inflammatory factors of the three groups were measured. After treatment, the clinical effective rate of group C was evidently higher than that of group A and group B. The vascular elasticity coefficient and stiffness coefficient in group C were significantly lower than those in group A and group B, and the arterial compliance in group C was significantly higher than that in group A and group B (P < 0.05). The levels of MAP and PVRI in group C were significantly higher than those in group A and B, and the levels of CI, CVP and HR in group C were significantly lower than those in group A and group B (P < 0.05). Norepinephrine elicited greater effects in terms of improving hemodynamic indexes, vascular elasticity and reducing the level of inflammatory factors compared with dopamine and dobutamine in elderly patients harboring sepsis.

Dobutamine Versus Vasopressin After Mesenteric Ischemia.

BACKGROUND: Gastrointestinal blood flow may be compromised during and after vasopressor support. Endothelin expression may lead to microcirculatory dysfunction. The aim of this study was to analyze the effect of vasopressin and dobutamine after mesenteric ischemia on the gastrointestinal mucosal microcirculation, endothelin expression, and morphologic injury. MATERIALS AND METHODS: Pigs were studied in four groups (six pigs in each group): 1, sham; 2-4 ischemia (1 h superior mesenteric artery occlusion with 30 min reperfusion and 30 min of vehicle [2], dobutamine [3], or vasopressin [4] administration, followed by 30-min break and thiopental-induced hypotension [3, 4]). Blood flow of the gastric, jejunal, and rectosigmoidal mucosa was measured. At the end of the experiment, the mucosal expression of endothelin-1 (ET-1) and its receptor subtypes A (ETA) and B were determined by polymerase chain reaction. Mucosal injury, apoptotic cell death, and leukocytic infiltration were determined by histology and immunohistochemical analysis of cleaved caspase-3 and myeloperoxidase. RESULTS: Mesenteric ischemia increased jejunal mucosal ET-1 gene expression, arterial ET-1, intestinal fatty acid binding protein, and jejunal mucosal injury compared with sham. Dobutamine increased arteriovenous shunting at the cost of the jejunal mucosal blood perfusion. This was associated with an increased expression of ET-1 and ETA and mucosal leukocytic infiltration. In contrast, vasopressin increased postischemic capillary density and tissue blood flow. This was associated with a lower ET-1 gene expression. Vasopressin did not induce jejunal mucosal leukocytic infiltration. CONCLUSIONS: Vasopressin reduces mesenteric ischemia-associated alterations of the microcirculation and tissue integrity, whereas dobutamine does not.

Management of Neonatal Hypotension.

Hypotension is a common problem in neonates with complex underlying pathophysiology. Although treatment of low blood pressure is common, clinicians must use all available information to target neonates with compromised perfusion. Pharmacotherapy should be tailored to the specific physiologic perturbations of the individual neonate. Dopamine is the most commonly utilized agent and may be the most appropriate agent for septic shock with low diastolic blood pressure. However, alternative therapies should be considered for other etiologies of hypotension, including milrinone and vasopressin for persistent pulmonary hypertension of the newborn and dobutamine for patent ductus arteriosus. Additional studies are required to refine the approach to neonatal hypotension and document the long-term outcomes of treated neonates.

Eletroacupuntura para tratamento de hipotensão induzida por isofluorano em cavalos / Electroacupuncture treatment for isoflurane induced hypotension in horses

Objetivou-se avaliar a eficiência do tratamento da hipotensão arterial com eletroacupuntura comparativamente à dobutamina em equinos. Foram avaliados seis cavalos adultos, saudáveis, mantidos em anestesia inalatória, com isofluorano, em ventilação mecânica. Após a estabilização da anestesia, foi induzida hipotensão arterial, através do incremento da concentração do isofluorano, iniciando-se um dos tratamentos: DOB: dobutamina (1,5µg kg-1 min-1, infusão contínua intravenosa); EA: estímulo elétrico no acuponto pericárdio 6 (PC6), bilateralmente; SHAM: estímulo elétrico em ponto falso de acupuntura. Foram mensurados: frequência cardíaca (FC), pressão arterial média (PAM), temperatura retal (T), concentração final expirada de isofluorano (ETiso), variáveis hemogasométricas, concentração sérica de aspartato aminotransferase (AST) e creatina fosfoquinase (CK), tempo e qualidade da recuperação pós-anestésica. Houve incremento na PAM de 50%, 36,6% e 7,5% nos tratamentos DOB, EA e SHAM, respectivamente. Não houve diferença entre os grupos nas variáveis hemogasométricas, FC, T, ETiso, CK, AST, tempo e qualidade de recuperação pós-anestésica. Conclui-se que o tratamento com dobutamina foi mais efetivo para o tratamento da hipotensão em cavalos sob anestesia inalatória quando comparado ao estímulo elétrico do acuponto PC6 ou ponto falso de acupuntura...

This study aimed to evaluate the efficacy of electroacupuncture compared to the dobutamine treatment of hypotension in equines. Six adult horses were maintained in isoflurane anesthesia with mechanical ventilation. After anesthesia was established, the isoflurane concentration was raised until hypotension was achieved. After that the animals were treated with a constant rate of 1.5mg kg -1min-1 intravenous dobutamine (DOB), electroacupunture to pericardium 6 (PC-6) acupoint (EA) and false point treatment (SHAM). Heart rate (HH), median arterial blood pressure (MAP), rectal temperature (T), isoflurane end-tidal concentration, arterial blood gases, creatine kinase (CK), aspartate transaminase (AST), recovery time and quality of recovery were investigated. The MAP increased 50%, 36.5% and 7.5%% in DOB, EA and SHAM treatments, respectively. HH, T, arterial blood gases, CK, AST, recovery time and quality of recovery did not differ among treatments. It was concluded that the dobutamine treatment was more effective than EA and SHAM treatments for the reversion of isoflurane induced hypotension in horses...

Reserva contráctil negativa con bajas dosis de dobutamina en los pacientes con miocardiopatía isquémica estudiados mediante gated-SPECT de perfusión miocárdica / Negative contractile reserve with low-dose dobutamine in patients with ischemic cardiomyopathy investigated by gated myocardial perfusion SPECT

Introducción y objetivos. Analizar la respuesta contráctil negativa (RCN) del ventrículo izquierdo (VI) en la gated-SPECT con bajas dosis de dobutamina (BDD) en pacientes con miocardiopatía isquémica (MI). Métodos. Se estudió prospectivamente a 68 pacientes (media de edad, 60 ± 11 años; 7 mujeres) con MI mediante gated-SPECT en reposo y durante la infusión de BDD. Se relacionó la RCN (aumento de la puntuación del engrosamiento ≥ 1 unidad) con los criterios gammagráficos de viabilidad y los resultados de la coronariografía. Resultados. El 42,6% (29/68) de los pacientes presentó uno o más segmentos con RCN. En el 14,7% (n = 10) de los pacientes se observó una disminución de la fracción de eyección ≥ 4% con las BDD. Estos pacientes se caracterizaron por tener un mayor número de segmentos con RCN (2,8 ± 2,5 frente a 0,87 ± 0,4; p = 0,042), con un valor de corte en el análisis de curva ROC ≥ 2 segmentos con RCN (sensibilidad, 70%; especificidad, 74%; +LR, 2,71; -LR, 0,40). El 94% (74/79) de los segmentos con RCN correspondía a miocardio vivo (normal o viable gammagráficamente). De los 17 segmentos con acinesia o hipocinesia severa y RCN, 12 (71%) tenían criterios gammagráficos de viabilidad y en su mayoría (10/12) correspondían a territorios con arteria coronaria abierta. Conclusiones. La RCN no es un fenómeno infrecuente en los pacientes con MI y se relaciona con una disminución de la función sistólica general del VI. Mayoritariamente se observa en segmentos con criterios gammagráficos de viabilidad y dependientes de una arteria coronaria abierta (AU)

Introduction and objectives. To investigate negative contractile responses in the left ventricle during low-dose dobutamine (LDD) gated single-photon emission computed tomography (SPECT) in patients with ischemic cardiomyopathy. Methods. Sixty-eight consecutive patients (mean age, 60±11 years; 7 male) with ischemic cardiomyopathy (i.e., left ventricular ejection fraction [LVEF] ≤40%) were evaluated using gated-SPECT at rest and during LDD infusion. Associations between a negative contractile reserve (i.e., a ≥1-grade improvement in wall thickening score with LDD infusion) and scintigraphic viability criteria and coronary angiography findings were analyzed. Results. Some 42.6% (29/68) of patients had a negative contractile reserve in one or more segments. In 14.7% (n=10), the LVEF decreased by ≥4% with LDD. These patients had more segments with a negative contractile reserve (2.8±2.5 vs. 0.87±0.40; P=.042), and the cut-off value on receiver operating characteristic curve analysis was ≥2 segments with a negative contractile reserve (sensitivity 70%, specificity 74%, positive likelihood ratio 2.71, negative likelihood ratio 0.40). Some 94% (74/79) of segments with a negative contractile reserve were in viable myocardium (i.e. normal or viable on scintigraphy). Twelve of 17 segments with akinesia or severe hypokinesia and a negative contractile reserve satisfied scintigraphic viability criteria, with the majority (10/12) lying in territories supplied by a patent coronary artery. Conclusions. A negative contractile reserve was not uncommon in patients with ischemic cardiomyopathy and was associated with a general decrease in left ventricular systolic function. It was observed mainly in myocardial segments that appeared viable on scintigraphy and were supplied by a patent coronary artery (AU)

[Treatment of heart failure patients with inotropic drugs: beyond traditional agents]. / La terapia con inotropi del paziente con insufficienza cardiaca: oltre i farmaci tradizionali.

Hospitalizations for acute heart failure are associated with high mortality and readmission rates. Ten to 20% of the patients have signs of low cardiac output and fluid overload. The administration of inotropic agents to correct these hemodynamic abnormalities may be indicated in these patients. However, the risk to benefit ratio of inotropic agents is high and an increase of untoward effects and mortality has been suggested by many retrospective analyses and meta-analyses. Limitations of inotropic therapy seem mainly related to their mechanisms of action based, in the case of the traditional agents, on an increase in intracellular cyclic AMP and calcium concentrations. Concomitant peripheral vasodilation, such as in the case of the novel agent levosimendan is another important limitation, above when patients are hypotensive and/or treated with vasodilators and high doses of diuretics. Myosin activators, histaroxime, sarcoplasmic reticulum ATPase activators and metabolic agents seem promising as active through different mechanisms than traditional agents and, in many cases, not associated with tachycardia or hypotension. Further studies are, however, needed.

Reassessment of dobutamine, dopamine, and milrinone in the management of acute heart failure syndromes.

The appropriate role of intravenous inodilator therapy (inotropic agents with vasodilator properties) in the management of acute heart failure syndromes (AHFS) has long been a subject of controversy, mainly because of the lack of prospective, placebo-controlled trials and a lack of alternative therapies. The use of intravenous inodilator infusions, however, remains common, but highly variable. As new options emerge for the treatment of AHFS, the available information should be reviewed to determine which approaches are supported by evidence, which are used empirically without evidence, and which should be considered inappropriate. For these purposes, we reviewed data available from randomized controlled trials on short-term, intermittent, and long-term use of intravenous inodilator agents (dobutamine, dopamine, and milrinone) in AHFS. Randomized controlled trials failed to show benefits with current medications and suggested that acute, intermittent, or continuous use of inodilator infusions may increase morbidity and mortality in patients with AHFS. Their use should be restricted to patients who are hypotensive as a result of low cardiac output despite a high left ventricular filling pressure.

Enteral nutrition and cardiovascular medications in the pediatric intensive care unit.

BACKGROUND: Enteral nutrition has multiple benefits for critically ill patients. However, the administration of enteral nutrition to patients requiring medications for cardiovascular support is controversial secondary to concerns of altered splanchnic perfusion. The objective of this study is to evaluate the tolerance of enteral nutrition in pediatric patients receiving cardiovascular medications. METHODS: This was a retrospective chart review of patients admitted to the pediatric intensive care unit at Children's Healthcare of Atlanta at Egleston in a 1-year period. Patients were eligible for the study if they received enteral nutrition during or within 24 hours of requiring continuous infusion of dopamine, dobutamine, epinephrine, norepinephrine, or neosynephrine. RESULTS: Fifty-five admissions (52 patients) met study criteria. Patients ranged in age from 1 month to 20 years old. Although a large number (71%) of patients experienced at least 1 feeding interruption, the majority (70%) of reasons cited for stopping or slowing feedings were not related to gastrointestinal (GI) tolerance. Only 29% of patients had feedings held for perceived intolerance. Vomiting was the most often-cited reason for these interruptions. Constipation was reported in 36% of patients but cited only 4 times as a reason for feeding interruption. Four patients exhibited evidence of GI bleeding. This bleeding was considered clinically insignificant in 2 patients and appeared unrelated to enteral feedings in the others. CONCLUSIONS: This study suggests that many pediatric patients receiving cardiovascular medications tolerate enteral nutrition without adverse events. Further prospective studies are needed to determine whether enteral nutrition can consistently benefit these critically ill pediatric patients.

Reversible cardiomyopathy in paediatric Addison's disease--a cautionary tale.

A 13 year-old girl with clinical features of Addison's disease developed acute cardiac failure after initiation of treatment and after initial clinical improvement. Large doses of i.v. hydrocortisone and oral fludrocortisone, in addition to inotropic and ventilatory support, were required to achieve cardiovascular stability. The cardiomyopathy improved over one week and her condition then remained stable on oral glucocorticoid and mineralocorticoid replacement therapy. Reversible cardiomyopathy is a rare and potentially life-threatening complication of Addison's disease. The second reported paediatric patient is presented, the only one reported to require ventilatory support.

Implantable cardioverter-defibrillator placement in patients with mild-to- moderate left ventricular dysfunction: hemodynamics and recovery profile with two different anesthetics used during deep sedation.

OBJECTIVE: To compare the effects of thiopental and propofol during defibrillation threshold testing (DFT) on hemodynamics and recovery profile in patients requiring automatic internal cardioverter-defibrilator placement. DESIGN: Prospective clinical investigation. SETTING: University hospital. PARTICIPANTS: Thirty-four adult patients. INTERVENTIONS: After administration of midazolam, 0.025 mg/kg, and fentanyl, 0.5 to 1 mug/kg, surgery was performed under topical infiltration with 1% lidocaine. In group I (GI) (n = 17), patients received thiopental by slow injection and patients in group II (GII) (n = 17) received propofol before induction of ventricular fibrillation (VF). MEASUREMENTS AND MAIN RESULTS: Patients received 4.1 +/- 1.4 mg of midazolam, 114 +/- 34 mug of fentanyl, and 280 +/- 78 mg of thiopental in GI; and 4.6 +/- 1.7 mg of midazolam, 119 +/- 62 mug of fentanyl, and 147 +/- 40 mg of propofol in GII (p > 0.05). Hemodynamics did not show significant differences between the groups at any recording time. Average time needed to regain the pretest sedation level was 16.4 +/- 8.8 minutes in GI and 10.9 +/- 5.5 minutes in GII (p = 0.03). Time required to achieve a score of 10 using a modified Aldrete score was 26.4 +/- 9.3 minutes in GI and 17.4 +/- 4.9 in GII (p = 0.001). Seven patients in GII (41%) and 1 patient in GI (6%) became hypotensive after DFT (p = 0.04). CONCLUSIONS: Deepening the sedation level by slow injection of thiopental or propofol before DFT provided satisfactory conditions during brief episodes of VF. Delay in recovery of arterial pressure after DFT with propofol and delay in arousal and discharge of patients with thiopental are major disadvantages of the regimens.

Effects of dobutamine and dopexamine on hepatic micro- and macrocirculation during experimental endotoxemia: an intravital microscopic study in the rat.

OBJECTIVE: To test the effects of dobutamine and dopexamine on hepatic portal and sinusoidal blood flow in a model of normodynamic endotoxemia. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats (250-350 g). INTERVENTIONS: A total of 40 male Wistar rats were randomized into four groups: a control group, which only received Ringer's solution; an endotoxin group, which received a continuous infusion of 2 mg/kg body weight (bw)/hr of endotoxin; a dobutamine group, which received endotoxin and a continuous infusion of dobutamine (3 microg/kg bw/min); and a dopexamine group, which received endotoxin and dopexamine (2 microg/kg bw/min). The experimental period was 120 min. MEASUREMENTS AND MAIN RESULTS: Mean arterial blood pressure (MAP), heart rate (HR), and cardiac output (CO) were detected. Portal blood flow was measured using an ultrasonic flow probe positioned around the portal vein, and sinusoidal blood flow was detected in the left liver lobe using intravital microscopy. All detected variables remained stable in the control group. In the endotoxin group, HR increased significantly and MAP decreased significantly from 111 +/- 10 mm Hg to 95 +/- 8 mm Hg at 120 mins, whereas CO remained unchanged. Both in the dobutamine and the dopexamine group HR increased and MAP decreased more than in the endotoxin group. CO increased in both groups significantly. Portal blood flow (23 +/- 4 mL/min to 16 +/- 3 mL/min) and sinusoidal blood flow (38.6 +/- 2.5 to 22.8 +/- 1.2 10(3) microm(3)/sec) decreased significantly in the endotoxin group. In the dobutamine and the dopexamine group portal and sinusoidal blood flow remained at baseline values. CONCLUSIONS: In our model of endotoxemia, dobutamine and dopexamine preserved systemic and hepatic blood flow. These preservations of hepatic blood flow during endotoxemia could portend beneficial effects but need to be studied further.

Effects of dobutamine on splanchnic tissue perfusion during partial superior mesenteric artery occlusion.

OBJECTIVE: To evaluate the effects of dobutamine and fluid treatment on splanchnic hemodynamics and tissue oxygenation during partial superior mesenteric artery occlusion. DESIGN: Prospective, open randomized, full-factorial design. SETTING: University research laboratory. SUBJECTS: Forty-eight female pigs. INTERVENTIONS: In 24 anesthetized pigs (ischemic group), superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 mins; 24 pigs (sham group) served as nonischemic controls. The animals were further assigned into four treatment arms. In the control arm, the animals were administered only basic fluid therapy. In the fluid therapy arm, pulmonary artery occlusion pressure was maintained at 10 mm Hg with fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arm, dobutamine at 10 microg/min/kg was administered and pulmonary artery occlusion pressure was maintained at 10 mm Hg with fluids. MEASUREMENTS AND MAIN RESULTS: Systemic and regional hemodynamics and oxygen transport, as well as jejunal intramucosal pH, intramucosal-arterial PCO2 gradient, and portal venous-arterial lactate gradient were measured. Ischemia did not modify the effects of fluids or dobutamine on systemic hemodynamics and oxygen transport. Dobutamine-treated animals had a higher cardiac index compared with control animals (218 +/- 22 vs. 135 +/- 13 mL/min/kg; p = .012), and the effect was enhanced when dobutamine was combined with fluid treatment (365 +/- 23 mL/ min/kg; p = .019). Fluid treatment alone did not influence cardiac index, whereas it increased SMA blood flow compared with control groups (15 +/- 2 vs. 12 +/- 2 mL/min/kg; p = .023). Dobutamine also decreased the proportion of SMA blood flow of cardiac output compared with control groups (6 +/- 1 vs. 9% +/- 1%; p = .024). Other treatments had no effect on SMA blood flow. Ischemia increased intramucosal-arterial Pco2 gradient to 54.8 +/- 10.7 torr (7.31 +/- 1.43 kPa) (p = .002 vs. sham control) and decreased intramucosal pH to 7.13 +/- 0.06 (p = .028 vs. sham control). In the ischemic animals, dobutamine without fluid therapy reduced intramucosal pH further to 7.00 +/- 0.09 (p = .023 vs. ischemic control) and increased portal venous-arterial lactate gradient (p = .033). CONCLUSIONS: Dobutamine alone worsened splanchnic tissue perfusion during partial superior mesenteric artery occlusion. As compared with fluid treatment alone, the combination of fluid and dobutamine therapy did not improve tissue perfusion.

Dobutamine restores intestinal mucosal blood flow in a porcine model of intra-abdominal hyperpressure.

OBJECTIVE: To assess the effects of dopamine and dobutamine administration on the systemic and mesenteric (macro- and microvascular) circulatory disturbances induced by intra-abdominal hyperpressure. DESIGN: Prospective, randomized study. SETTING: Animal research laboratory in a university hospital. SUBJECTS: Twenty-five pigs of either gender, weighing 30-35 kg. INTERVENTIONS: Animals were anesthetized, and their lungs were mechanically ventilated. Pulmonary artery flotation and carotid artery catheters were inserted for hemodynamic monitoring and blood sampling. A perivascular flow probe was placed around the superior mesenteric artery, and a laser Doppler probe was positioned in the lumen of the ileum to measure arterial and intestinal mucosal blood flows, respectively. CO2 was insufflated into the peritoneal cavity to reach an intra-abdominal pressure of 15 mm Hg, and 60 mins later, animals received dopamine (5 microg/kg/min; n = 10), dobutamine (5 microg/kg/min; n = 10), or saline (n = 5) for 30 mins. MEASUREMENTS AND MAIN RESULTS: Peritoneal CO2 insufflation induced significant increases in heart rate, arterial pressure, and systemic vascular resistance with concomitant decreases in cardiac output and superior mesenteric arterial and intestinal mucosal blood flows. Although dobutamine infusion reversed the decrease in cardiac output, it failed to restore superior mesenteric artery blood flow; however, intestinal mucosal blood flow returned to baseline levels. Dopamine also attenuated the decrease in cardiac output, but it had no beneficial effect on splanchnic hemodynamic variables. CONCLUSIONS: Low-dose infusion of dobutamine, but not dopamine, corrects the intestinal mucosal perfusion impairment induced by moderate increases in intra-abdominal pressure.

Differential alteration of cardiotonic effects of EMD 57033 and beta-adrenoceptor agonists in volume-overload rabbit ventricular myocytes.

BACKGROUND: We investigated the effects of EMD 57033, a prototype Ca2+ sensitizer, and beta-adrenoceptor agonists in ventricular myocytes isolated from the volume-overload (V-O) heart failure model of the rabbit. METHODS AND RESULTS: V-O cardiac hypertrophy was induced in rabbits by the formation of an arterio-venous shunt between the carotid artery and jugular vein 12 to 15 weeks after the operation. Ventricular myocytes were enzymically isolated from normal and V-O rabbit hearts. The myocyte was loaded with a fluorescence Ca2+ dye, indo-1, and Ca2+ transients, and cell lengths were measured simultaneously. V-O myocytes were significantly larger than control myocytes. Duration of Ca2+ transients and cell shortening was significantly longer in the V-O myocytes than in control myocytes. Effects of cardiotonic interventions, including EMD 57033, isoproterenol, and dobutamine, on Ca2+ transients and cell shortening in V-O myocytes were compared with those in control rabbit myocytes. Isoproterenol and dobutamine increased the systolic cell shortening and peak Ca2+ transients and abbreviated the duration of cell shortening and Ca2+ transients. These responses were markedly attenuated in V-O myocytes. By contrast, the response of cell shortening to EMD 57033 was unaltered, and the Ca2+ sensitizing effect of EMD 57033 was rather enhanced in V-O myocytes. CONCLUSION: Our results indicate that the effectiveness of Ca2+ sensitizers is maintained in the V-O rabbit hypertrophy and heart failure model in contrast to the blunted response to beta-adrenoceptor agonists, which provides an insight on therapeutic strategy with Ca2+ sensitizers for the treatment of contractile dysfunction in congestive heart failure.

Gallopamil activity on asynergic viable myocardium in acute myocardial infarction: insights on stunned and hibernating myocardium.

The influence of the calcium antagonist gallopamil on the contractility of asynergic viable myocardium after acute myocardial infarction treated with thrombolysis was investigated by two-dimensional echocardiography. Sixteen patients with > or = 1 viable segment(s), identified during the low-dose phase (up to 10 micrograms/kg/min) of a dobutamine echocardiographic test (up to 40 micrograms/kg/min) performed 4-5 days after a first acute myocardial infarction, were given a gallopamil intravenous bolus (50 micrograms/kg) 12-24 hours later. Two-dimensional echocardiography was done before and 15 minutes after the bolus. A score index of 1 (normokinesis) to 4 (dyskinesis) and a 16-segment model were used. A segment was considered viable when a resting asynergy (score > or = 2) improvement of > or = 1 grade was seen during low-dose dobutamine. Follow-up echocardiograms were done 3-5 months later. A total of 30 viable segments were found; of these, 10 showed sustained improvement in contractility (group A) during high-dose dobutamine, while 20 exhibited a biphasic response returning to their basal contractile state (group B). After the gallopamil bolus, 9 of 10 group A segments improved their contractility, in comparison with 0 of 20 group B segments (P < .001). Infarct-related vessel significant (> or = 75%) coronary stenosis was present in the tributary vessel of 0 of 10 group A and of 20 of 20 group B segments (P < .001). At follow-up, 9 of 10 group A segments showed a spontaneous contractile improvement; of the 20 group B segments, 8 of 10 that underwent revascularization (7 angioplasty, 3 bypass graft) showed contractile improvement, in comparison with 0 of 10 segments not revascularized (P = .001). We conclude that gallopamil may reverse the contractile dysfunction of postischemic stunned myocardium in patients with acute myocardial infarction, whereas no effects are apparent on ischemic/hibernating myocardium.

Dobutamine improves gastrointestinal mucosal blood flow in a porcine model of endotoxic shock.

OBJECTIVE: To test the hypothesis that saline solution plus dobutamine increases gastrointestinal mucosal perfusion better than saline solution alone in a model of endotoxic shock. DESIGN: Prospective, randomized, unblinded study. SETTING: Animal research laboratory affiliated with a university teaching hospital. SUBJECTS: Twelve female pigs, weighing 30 to 32 kg. INTERVENTIONS: Animals were anesthetized, and their lungs were mechanically ventilated. Catheters were inserted into the right atrium, pulmonary artery, and carotid artery for blood sampling and blood pressure and cardiac output measurements. A tonometer and a laser Doppler probe were placed in the lumen of the stomach and the ileum for determination of mucosal acid-base status and measurement of mucosal blood flow. Group 1 animals (n = 6) received an infusion (T = 0 min) of 150 mcirog/kg Escherichia coli endotoxin and normal saline solution (0.3 mL/kg/min). Group 2 animals (n = 6) received an infusion of endotoxin and were resuscitated with the same method as used in group 1, but an infusion of dobutamine (5 microg/kg/min) was begun at T = 60 mins, and continued for the duration of the experiment. MEASUREMENTS AND MAIN RESULTS: Both experimental regimens produced shock, with decreased mean arterial pressure and systemic vascular resistance, without change in cardiac output and oxygen delivery. Endotoxin plus saline infusion decreased gastrointestinal mucosal blood flow to <60% of baseline and decreased gastrointestinal pH. In contrast, gastrointestinal mucosal blood flow returned to baseline values, and intramucosal pH tended to normalize by the end of the saline solution plus dobutamine resuscitative protocol. CONCLUSION: Compared with saline solution alone, saline solution plus dobutamine increased blood flow to the gastrointestinal mucosa, and may have partially improved oxygenation.

Dilated cardiomyopathy in an American cocker spaniel with taurine deficiency.

An American Cocker Spaniel with low plasma taurine concentration (< 2 nmol/mL) was presented with dyspnoea associated with pulmonary oedema and a left ventricular shortening fraction of 9%. Emergency therapy with furosemide, dobutamine, nitroglycerine and oxygen supplementation led to a good response. Chronic therapy was started with enalapril, furosemide, digoxin and taurine. Improvement in all echocardiographic indices were noted over a 22 week follow-up, most notably an increase in left ventricular shortening fraction to 20%, a decrease of E-point septal separation from 14 mm to 7 mm and marked left ventricular remodelling. This degree of improvement in myocardial function may represent a direct link between dilated cardiomyopathy in the American Cocker Spaniel and plasma taurine deficiency. Alternatively, this response may reflect a breed-related cardiomyopathy with a natural history and therapeutic response not commonly seen in the more common large breed cardiomyopathy presentations.

Pharmacologic support with high-energy phosphate preservation in the postischemic neonatal heart.

Milrinone improves function in failing adult hearts. This study examined its effect on immature myocardium. Using an isolated working neonatal rabbit heart preparation, we measured myocardial function, high-energy compounds, and cyclic adenosine monophosphate. Hearts were subjected to 1 hour of normothermic ischemia, 10 minutes of reperfusion with Ringer's solution, and 30 minutes of reperfusion with either unaltered Ringer's, Ringer's with dobutamine (0.1 microgram/mL), or Ringer's with milrinone (1 microgram/mL). These hearts were compared with each other, with a control group continuously perfused for 70 minutes, and with a group of hearts that were made ischemic and reperfused for only 10 minutes. There was a progressive decline in adenosine triphosphate levels measured in hearts from the groups receiving 10 and 40 minutes of reperfusion with unaltered perfusate, and cardiac output fell to 82% +/- 4% of preischemic control in the latter group. When either dobutamine or milrinone was added to the reperfusion solution, postischemic myocardial function was restored completely, and the loss of adenosine triphosphate with reperfusion was halted. Cyclic adenosine monophosphate level was highest in ischemic/40-minute reperfused hearts, and there was no measurable increase in cyclic adenosine monophosphate level in the group of hearts receiving milrinone. The mechanism of preservation of high-energy stores with inotropic agents is not known but may involve potentiation of mitochondrial oxidative phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Improved hemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate.

OBJECTIVES: The purpose of this study was to determine whether sodium dichloroacetate improves hemodynamic performance and mechanical efficiency in congestive heart failure. BACKGROUND: Congestive heart failure is associated with impaired hemodynamic performance and reduced mechanical efficiency. Dichloroacetate stimulates pyruvate dehydrogenase activity by inhibition of pyruvate dehydrogenase kinase, which results in inhibition of free fatty acid metabolism and stimulation of high respiratory quotient glucose and lactate consumption by the heart. Facilitation of glucose and lactate consumption with dichloroacetate should improve mechanical efficiency of the failing ventricle. METHODS: Ten patients with New York Heart Association functional class III to IV congestive heart failure were studied. Dichloroacetate (50 mg/kg body weight) was administered intravenously for 30 min, with measurements of hemodynamic variables, coronary sinus blood flow and blood gas, glucose and lactate levels for 2 h. The same patients were also given dobutamine (5 to 12.5 micrograms/kg per min) for comparison. RESULTS: Therapeutic levels of dichloroacetate were achieved (100 to 160 micrograms/liter of plasma). Myocardial consumption of lactate was stimulated from 29% to 37.4%. Forward stroke volumes increased (+5.3 ml/beat, p < 0.02), as did left ventricular stroke work (+1.8 g-m/m2 per beat, p < 0.02) and left ventricular minute work (from 1.38 to 1.55 kg-m/m2 per min, p < 0.01). Myocardial oxygen consumption decreased (from 19.3 to 16.5 ml/min, p = 0.06) as left ventricular minute work increased. Left ventricular mechanical efficiency thus improved from 15.2% to 20.6% (p = 0.03). Dobutamine administration resulted in the opposite trend with respect to myocardial lactate extraction (from 34% to 15.3%, p < 0.02). Stroke volume increased (+7.4 ml/beat, p = NS vs. dichloroacetate), as did left ventricular minute work (from 1.29 to 1.59 g-m/m2 per min, p < 0.01 vs. dichloroacetate) and myocardial oxygen consumption (from 18.6 to 21.0 ml/min, p = 0.06 vs. dichloroacetate). Left ventricular mechanical efficiency did not change with dobutamine administration (from 16.4% to 15.8%, p = NS). CONCLUSIONS: Dichloroacetate administration stimulates myocardial lactate consumption and improves left ventricular mechanical efficiency. Forward stroke volume and left ventricular minute work increase significantly, with a simultaneous reduction in myocardial oxygen consumption. Dobutamine administration results in similar hemodynamic improvements but with no change in left ventricular mechanical efficiency and with opposite effects on lactate metabolism. The opposing metabolic actions, yet similar hemodynamic responses, of dichloroacetate and dobutamine suggest that these agents may be complementary in the treatment of congestive heart failure.