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Acute decompensated heart failure (ADHF) is a common clinical problem associated with a high mortality rate. Because ADHF has various aetiologies, there are a range of therapeutic options, among others, positive inotropes (inotropic drugs). As an inotropic agent whose mechanism is different than that of “classical” medicines, levosimendan (LSM) is one of the most common therapeutic options. Despite many publications on LSM, some issues related to its application remain unclear. The authors of this paper have attempted to summarise expert recommendations and reports available in the literature.

Background: Levosimendan (LEVO), is an inotropic agent which has been shown to be associated with better myocardial performance, and higher survival rate in cardiac surgical patients. However, preliminary clinical evidence suggested that LEVO increased the risk of post-operative bleeding in patients undergoing valve surgery. Currently, there has been no randomized controlled trials (RCTs) designed specifically on this issue. Therefore, we performed present systemic review and meta-analysis. Methods: Electronic databases were searched to identify all RCTs comparing LEVO with Control (placebo, blank, dobutamine, milrinone, etc). Primary outcomes include post-operative blood loss and re-operation for bleeding. Secondary outcomes included post-operative transfusion of red blood cells (RBC), fresh frozen plasma (FFP) and platelet concentrates (PC). For continuous variables, treatment effects were calculated as weighted mean difference (WMD) and 95% confidential interval (CI). For dichotomous data, treatment effects were calculated as odds ratio (OR) and 95% CI. Results: Search yielded 15 studies including 1,528 patients. Meta-analysis suggested that, LEVO administration was not associated with increased risk of reoperation for bleeding post-operatively (OR = 1.01; 95%CI: 0.57 to 1.79; p = 0.97) and more blood loss volume (WMD = 28.25; 95%CI: –19.21 to 75.72; p = 0.24). Meta-analysis also demonstrated that, LEVO administration did not increase post-operative transfusion requirement for RBC (rate: OR = 0.97; 95%CI: 0.72 to 1.30; p = 0.83 and volume: WMD = 0.34; 95%CI: –0.55 to 1.22; p = 0.46), FFP (volume: WMD = 0.00; 95%CI: –0.10 to 0.10; p = 1.00) and PC (rate: OR = 1.01; 95%CI: 0.41 to 2.50; p = 0.98 and volume: WMD = 0.00; 95%CI: –0.05 to 0.04; p = 0.95). Conclusion: This meta-analysis suggested that, peri-operative administration of LEVO was not associated with increased risks of post-operative bleeding and blood transfusion requirement in cardiac surgical patients.

Backgrounds/aims Pancreatic leak and fistula formation following pancreatic resection is a dreaded complication associated with significant morbidity and mortality. The perioperative use of inotropes has been implicated in anastomotic dehiscence in other types of gastrointestinal surgery but their impact in pancreatic surgery remains unclear and a potentially modifiable risk factor for pancreatic leak. This study aims to assess the impact of perioperative inotrope infusion on the incidence of pancreatic leak following pancreaticoduodenectomy. Methods Retrospective data analysis of all patients undergoing pancreaticoduodenectomy at a tertiary HPB institute. Multivariate analysis and regression models assessed the impact of inotrope use against other known risk factors such as pancreatic duct size and gland texture. Pancreatic fistulae were graded as per ISGPF as Grade A (biochemical leak), Grade B and Grade C fistula. Results One-hundred and twenty-three (123) patients were included. A total of 52 patients (42%) developed a leak (29 grade A, 15 grade B, and 8 Grade C). In the fistula group, 28 patients (55%) received perioperative inotropes compared to 26 (35%) in the no fistula group. On univariate analysis, patients receiving inotropes (p=0.04) and patients with a soft pancreatic texture (p=0.003) had a statistically higher incidence of developing a pancreatic fistula of any grade. On multivariate analysis, only inotrope use was associated with an increased risk of developing a pancreatic fistula of any grade (OR 2.46, p=0.026), independent of pancreatic texture and pancreatic duct size. Conclusions Perioperative inotrope use is associated with an increase incidence of pancreatic leak following pancreaticoduodenectomy and should therefore be used judiciously.

Background Heart failure with preserved ejection fraction ( HF p EF ) is an increasingly prevalent form of heart failure, representing half of the total burden of heart failure. We hypothesised that modulation of the phosphodiesterase type 3/cyclic AMP using a novel oral formulation of milrinone might exert favorable effects HF p EF via pulmonary and systemic vasodilation and enhancement of ventricular relaxation. We assessed the safety and efficacy of oral milrinone on quality of life and functional outcomes in patients with HF p EF . Methods and Results The Mil HFPEF (Extended Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction) study was a randomized, double‐blind, placebo‐controlled pilot study in 23 patients with symptomatic HF p EF . Efficacy end points included changes from baseline in Kansas City Cardiomyopathy Questionnaire summary score and 6‐minute walk distance. The primary safety end point was the development of clinically significant arrhythmia. The Kansas City Cardiomyopathy Questionnaire score improved significantly in milrinone‐treated patients compared with placebo (+10±13 versus −3±15; P =0.046). Six‐minute walk distance also tended to improve in the treatment group compared with placebo (+22 [−8 to 49] versus −47 [−97 to 12]; P =0.092). Heart rate (−1±5 versus −2±9 bpm; P =0.9) and systolic blood pressure (−3±18 versus +1±12 mm Hg; P =0.57) were unchanged. Early filling velocity/early mitral annular velocity (−0.3±3.0 versus −1.9±4.8; P =0.38) was unchanged. One patient in the placebo arm was hospitalized for heart failure. Holter monitoring did not demonstrate evidence of a proarrhythmic effect of milrinone. Conclusions In this novel pilot study, extended release oral milrinone was well tolerated and associated with improved quality of life in patients with HF p EF . Further longer‐term studies are warranted to establish the role of this therapeutic approach in HF p EF . Registration URL : https://www.anzctr.org.au/ ; Unique identifier: ACTRN 12616000619448.

Background Heart failure with preserved ejection fraction (HFpEF) is an increasingly prevalent form of heart failure, representing half of the total burden of heart failure. We hypothesised that modulation of the phosphodiesterase type 3/cyclic AMP using a novel oral formulation of milrinone might exert favorable effects HFpEF via pulmonary and systemic vasodilation and enhancement of ventricular relaxation. We assessed the safety and efficacy of oral milrinone on quality of life and functional outcomes in patients with HFpEF. Methods and Results The MilHFPEF (Extended Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction) study was a randomized, double‐blind, placebo‐controlled pilot study in 23 patients with symptomatic HFpEF. Efficacy end points included changes from baseline in Kansas City Cardiomyopathy Questionnaire summary score and 6‐minute walk distance. The primary safety end point was the development of clinically significant arrhythmia. The Kansas City Cardiomyopathy Questionnaire score improved significantly in milrinone‐treated patients compared with placebo (+10±13 versus −3±15; P=0.046). Six‐minute walk distance also tended to improve in the treatment group compared with placebo (+22 [−8 to 49] versus −47 [−97 to 12]; P=0.092). Heart rate (−1±5 versus −2±9 bpm; P=0.9) and systolic blood pressure (−3±18 versus +1±12 mm Hg; P=0.57) were unchanged. Early filling velocity/early mitral annular velocity (−0.3±3.0 versus −1.9±4.8; P=0.38) was unchanged. One patient in the placebo arm was hospitalized for heart failure. Holter monitoring did not demonstrate evidence of a proarrhythmic effect of milrinone. Conclusions In this novel pilot study, extended release oral milrinone was well tolerated and associated with improved quality of life in patients with HFpEF. Further longer‐term studies are warranted to establish the role of this therapeutic approach in HFpEF. Registration URL: https://www.anzctr.org.au/; Unique identifier: ACTRN12616000619448.

Background: Intra-aortic balloon pump (IABP) had a pivotal role in the therapy of cardiogenic shock (CS), but recent studies have questioned its effects on patients' outcome. Aim of this study is the description of a "real world" series of patients in which IABP was used as a primary mechanical circulatory support (MCS). Methods: All patients who received IABP in our institution during 1 year were prospectively enrolled in our study. The outcomes were: ICU mortality, length of ICU stay, factors associated with mortality and complications of IABP. A logistic regression model was developed to estimate the effect of several risk factors on mortality. Results: A total of 119 patients were enrolled, 54 patients underwent IABP placement for CS unrelated to cardiac surgery (medical CS) and 65 after open-heart surgery. There was no significant difference for mortality between medical CS [12/54 (22.2%)] and cardiac surgery [7/65 (10.8%)] (P=0.09). The morbidity rate related to IABP was 11.3%. Multivariable analysis identified AKI (OR =9.3; 95% CI, 2.0-40.0; P=0.004), inotropic score at the time of IABP implantation (OR =1.06; 95% CI, 1.01-1.11; P=0.009) and history of myocardial revascularization (OR =4.7; 95% CI, 1.1-20.2; P=0.036) as independent predictors for early death (P < 0.05). A ROC curve analysis for inotropic score at time of implantation and mortality was performed in the overall population [AUC=0.78 (95% CI, 0.66-0.90)]. A cutoff of 20 has a specificity =72% and sensitivity=74% in this population. Conclusions: Mortality is similar in medical and postcardiotomy CS. The benefits of IABP are limited if the amount of inotropes and the severity of shock are too high.

1 Department of Pathophysiology, Harbin Medical University, Harbin 150086, China; 2 Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; 3 Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA * Correspondence author. E-mail: wgao3@jhmi.edu ※ http://www.medscape.com/viewarticle/843901 ※※ http://www.cardioxyl.com

Prospective observational study was conducted in a tertiary care hospital of India over 8 months to measure blood pressure (BP) in healthy term and preterm neonates using oscillometric method and explore the associations with gestational age and birth weight. Consecutive BP measurements were taken by standard oscillometric method on 1617 neonates on day 4, 7 and 14 of life. Mean birth weight was 2.7 ± 0.46 kg, and mean gestational age was 38.2 ± 2.12 weeks. The mean arterial pressure (MAP) on day 4, 7 and 14 were 59.3 ± 7.33, 63.2 ± 6.55 and 66.4 ± 6.13 mmHg, respectively. Larger and mature newborns had significantly higher BP than those who were smaller and premature. Birth weight more strongly correlated with MAP than gestational age. Predictive equations linking MAP with gestational age and birth weight were deduced, which can be used for judicious fluid inotrope management.

Venom of Leiurus abdullahbayrami (Scorpiones: Buthidae) is an extremely toxic one and it stimulates voltage-gated sodium and potassium channels. In case of a stung by this scorpion; excessive catecholamine release occur and it impairs left ventricle contractility and consequently a heart failure occurs (scorpion sting-related cardiomyopathy). In addition to this cardiac-induced acute pulmonary, edema may occur in severe cases too. An 11-year-old male child who was stung by a scorpion (species: Leiurus abdullahbayrami) consulted to the Emergency Room. Even after 7 h of scorpion envenomation he was confused and having hallucinations. Besides he was dyspneic, tachycardic, hypotensive and got worse in overall situation due to cardiogenic pulmonary edema. These clinical findings are concordant with the Level III scorpion envenomation (major systemic manifestations). Positive inotropic agents, diuretics and antiagregant agents used on supportive therapy in his treatment. After 2 weeks he get recovered and discharged from the pediatric intensive care unit. This research is conducted by thinking emergency physicians should learn that Leiurus abdullahbayrami envenomation can cause scorpion-related cardiomyopathy and acute pulmonary edema especially in children. Keywords: Leiurus, Scorpionism, Cardiomyopathy, Pulmonary edema

Levosimendan is a pyridazinone-dinitrile derivative with positive inotropic and vasodilatory effects that has beneficial effects on myocardial performance.In previous randomized studies levosimendan improved hemodynamics and clinical course, but its effect on prognosis is still unclear. This important issue has limited its use. Although primarily used in the management of acute heart failure syndromes, this new inotropic agent may play a role in other clinical conditions.This review aims to summarize current knowledge on levosimendan and to present future prospects for the use of this drug. Resumo: O levosimendan é um derivado da piridazinona-dinitrilo que induz um efeito inotrópico positivo e vasodilatador, exercendo efeitos benéficos sobre o desempenho do miocárdio.Em estudos aleatorizados prévios o levosimendan melhorou a hemodinâmica e a evolução clínica dos doentes, com um significado ainda pouco definido no prognóstico. Esta questão importante tem condicionado o seu uso. Embora seja utilizado principalmente no tratamento da insuficiência cardíaca aguda, este novo agente poderá desempenhar um papel importante em outras condições clínicas.Esta revisão pretende resumir o conhecimento atual sobre o levosimendan e mostrar perspetivas futuras no uso deste fármaco. Keywords: Levosimendan, Heart failure, Inotropes, Palavras-chave: Levosimendan, Insuficiência cardíaca, Inotrópicos

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Is it possible to predict the risk of ischaemic bowel after cardiac surgery?' Altogether 80 papers were found as a result of the reported search, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. This best evidence topic presents 68 214 cardiac surgical patients from seven major cardiothoracic centres dated from 1980 to 2011. The incidence and mortality rates of bowel ischaemia after cardiac surgery range from 0.07-0.5 and 59-64%, respectively. Advanced age and peripheral vascular disease are the common preoperative risk factors, which were reported by 3 papers each. The most common intraoperative risk factors were prolonged cross-clamp and cardiopulmonary bypass time, which were reported by 3 papers each. Five of 7 papers reported that the use of intra-aortic balloon pump was a significant risk factor. The use of inotropes, postoperative blood loss and postoperative renal failure were reported by 3 of 7 papers, each to be a significant risk factor for postoperative bowel ischaemia in cardiac surgery patients. We, therefore, conclude that these are probably the most significant and useful predictive risk factors for bowel ischaemia after cardiac surgery. Thus, careful intraoperative management to minimize cardiopulmonary bypass and cross-clamp time and optimal care of patients' postoperative haemodynamic status, particularly in elderly patients with severe atherosclerotic disease, are useful in preventing this rare but lethal postoperative complication. Besides that, a heightened clinical suspicion in patients with these risk factors may lead to prompt diagnosis of bowel ischaemia, allowing intervention to prevent mortality. The variability of the study design and risk factors studied in each paper impose limitation to summarize the predicting risk factors.

Positive inotropic agents should be used judiciously when managing surgical patients with acute myocardial ischemia–reperfusion injury, as use of these inotropes is not without potential adverse effects.

YILMAZ, MEHMET BIRHAN/0000-0002-8169-8628; YILMAZ, MEHMET BIRHAN B/0000-0002-8169-8628; Demirbag, Recep/0000-0001-7831-2715; Guvenc, Tolga Sinan/0000-0002-6738-266X; YILMAZ, Mehmet Birhan/0000-0002-8169-8628; Basarici, Ibrahim/0000-0003-4435-337X; Celebi, Aksuyek savas/0000-0002-3637-0711 WOS: 000392634300003 PubMed: 28045409 Objective: The goal of this study was to develop a national database of patients hospitalized in Turkey with acute heart failure (AHF) using evaluations of diagnostic and therapeutic approaches. Methods: Patient data were collected using an Internet-based survey. A total of 588 patients were enrolled from 36 participating medical centers across the country. Results: Mean age was 62 +/- 13 years and 38% of the patients were female. Ratio of de novo AHF to study cohort was 24%. Coronary heart disease and hypertension were found in 61% and 53% of the patients, respectively. Valvular heart disease was the underlying cause in 46% of heart failure patients. The most frequent factor associated with decompensation was noncompliance with treatment, observed in 34% of patients. Systolic blood pressure was 125 +/- 28 mmHg and heart rate was 93 +/- 22 beats/minute in the cohort. The most common findings on physical examination were inspiratory fine crackles (84%), peripheral edema (64%), and cold extremities in 34%. Mean ejection fraction (EF) measured at admission was 33 +/- 13%. Preserved EF (>=%40) was present in 20% of patients. On admission, 60%, 46%, and 40% of patients were using angiotens-in-converting enzyme inhibitor/angiotensin receptor blocker, beta-blocker, or aldosterone antagonist, respectively. In-hospital events were reported as 3.4% death, 1.6% stroke and 2% myocardial infarction. Conclusion: Compared to previous data collected around the world, AHF patients in Turkey were younger, had more frequently valvular heart disease as the underlying cause, and were more noncompliant with medical treatment, but overall mortality was lower. Drugs shown to reduce mortality, and which also form the basis of guideline-directed medical therapy, are still used inadequately. Turkish Society of Cardiology Turkish Society of Cardiology

Shock is a common presentation to the ED, with the incidence of septic shock increasing in Australasia over the last decade. The choice of inotropic agent is likely dependent on previous experience and local practices of the emergency and other critical care departments. The relatively short duration of stay in the ED before transfer leaves little room for evaluating the appropriateness of and response to the agent chosen. Delays in transfer to inpatient facilities means that patients receive advanced critical care within the ED for longer, requiring initiation and titration of vasoactive agents in the ED. This article discusses the general concepts of shock and the indicators for inotrope and vasopressor use, revises the various agents available and reviews the current evidence for their use.

Possible arrhythmogenic side-effects of the positive inotropic agent prenalterol were studied in conscious dogs, three to four days after coronary artery ligation. Prenalterol showed a propensity to cause arrhythmias in one out of eight dogs, thereby confirming published data from clinical studies.

Purpose of review To critically examine the mortality rates of septic shock over the last 25 years to determine if significant improvements have been accomplished. Recent findings A gradual and progressive improvement in mortality rates associated with septic shock has been realized over the few decades. These improvements in outcome are quantitatively small but significant and they primarily represent improvements in supportive care, and the recognition that well meaning and seemingly logical treatments have been overused and probably contributed to excess mortality rates in the past. Summary Survival rates for patients in septic shock have gradually improved in critical care units worldwide over the last 25 years. Further improvement will be predicated on the discovery of new therapies to disrupt the underlying pathophysiology of sepsis and the development of improved rapid, diagnostic testing and immune monitoring of individual patients.

Leptospirosis is a re-emerging spirochetal zoonosis with a worldwide distribution affecting both animals and humans. The clinical syndromes may vary from a subclinical infection to a severe illness. Although it may potentially have a fulminant and fatal course, leptospirosis usually remains as an underdiagnosed cause of multiorgan failure. In this study, we report a patient with leptospirosis who presented with a fulminant course of diffuse alveolar haemorrhage and hepatorenal failure. His clinical condition deteriorated, despite appropriate antibiotic therapy and haemodialysis. However, he showed prompt clinical improvement when corticosteroids and plasma exchange were instituted in addition to the original therapy. We conclude that leptospirosis should be considered in any case presenting with pulmonary haemorrhage and hepatorenal failure. Plasma exchange and corticosteroids may be a choice of treatment in selected patients unresponsive to conventional therapy. Potential benefits of plasma exchange and corticosteroids may be based on a toxin- and/or cytokine-mediated pathogenesis of the disease. © 2007 The Authors Journal compilation 2007 Blackwell Publishing Ltd.

Dopamine is a commonly used positive inotropic agent for the treatment of hypotension in small animals. Two dogs that had undergone surgery, under isoflurane anaesthesia, developed a sudden and profound bradycardia when a dopamine infusion was administered. Bradycardia was attributed to the activation of the Bezold-Jarisch reflex, an inhibitory reflex, characterised by bradycardia and hypotension.

In the present study of mitral valve replacement, we investigated whether complete preservation of both leaflets (that is, the subvalvular apparatus) is superior to preservation of the posterior leaflet alone. Seventy patients who underwent mitral valve replacement in our clinic were divided into 2 groups: MVR-B (n=16), in whom both leaflets were preserved, and MVR-P (n=54), in whom only the posterior leaflet was preserved. The preoperative and postoperative clinical and echocardiographic findings were evaluated retrospectively. No signs of left ventricular outflow tract obstruction were observed in either group. In the MVR-B group, no decrease was observed in left ventricular ejection fraction during the postoperative period, whereas a significant reduction was observed in the MVR-P group (P=0.003). No differences were found between the 2 groups in their need for inotropic agents or intra-aortic balloon pump support, or in cross-clamp time, duration of intensive care unit or hospital stays, postoperative development of new atrial fibrillation, or mortality rates. Bileaflet preservation prevented the decrease in left ventricular ejection fraction that usually followed preservation of the posterior leaflet alone. However, posterior leaflet preservation alone yielded excellent results in terms of decreased left ventricular diameter. Bileaflet preservation should be the method of choice to prevent further decreases in ejection fraction and to avoid death in patients who present with substantially impaired left ventricular function.

Myocardial injury due to acute carbon monoxide intoxication is often refractory to standard resuscitation methods. Levosimendan is a new inotropic agent that is used in the treatment of acute and chronic heart failure. We report a case of severe cardiopulmonary compromise after exposure to carbon monoxide in a 40-year-old woman who was monitored using transthoracic echocardiography and the arterial pulse contour analysis system (FloTrac) and successfully treated with levosimendan.

Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics. Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge. A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P

Intra-arterial catheterization is used for continuous pressure monitoring and blood gas analysis in intensive care units. Especially it is used routinely in patients that take inotropic agents. Radial artery is frequently preferred because of adequate collateral circulation and easy cannulation. During this procedure, risks of complication and failure are high. Catheterization may lead to complications such as peripheral neuropathy and cerebral embolization which can increase morbidity and mortality. Ultrasonography [USG]-guided arterial cannulation can prevent potential complications with an increased success. In this report, we aimed to present the USG-guided catheterization of radial artery in intensive care patients.

Background: There are currently many on-going clinical trials assessing therapies for the treatment of patients with heart failure. Aims: The purpose of this series of papers is to present concise summaries of current randomised trials in the field of heart failure and myocardial infarction (MI). Methods: Data from large double-blind, placebo-controlled trials, which are on-going or have only recently been published, are given in a format allowing easy comparison. Where appropriate, data from smaller studies are included. Results: Major studies which are examined in this issue include CIBIS II, MERIT-HF, RESOLVD, SPICE, VEST, MACH-1, ATLAS, RALES, CIDS and CASH. These trials assess the efficacy and safety of beta-blocker, angiotensin-II-receptor blocker, positive inotropic agent, calcium antagonist, angiotensin-converting enzyme (ACE) inhibitor, aldosterone receptor blocker, and antiarrhythmic interventions in the treatment of heart failure. Conclusions: The presentation of data from these on-going trials should allow an up-to-date assessment, by physicians, of the most appropriate and effective treatment for patients with heart failure. It is evident that some therapies may play no further role in the treatment of heart failure, due to the increased risk of mortality associated with their administration, whilst others may convey significant benefits.

The authors report a case where four novel strategies were successfully used in the management of advanced right ventricular failure with severe pulmonary hypertension and complex adult congenital heart disease. These included combination and optimisation of three advanced therapies for pulmonary hypertension, therapeutic abdominal paracentesis, correction of underlying metabolic/endocrine disturbance and a new inotropic agent.

Although international guidelines for hemodynamic support of pediatric septic shock suggest considering the potent calcium sensitizer inodilator levosimendan as a second-line inotropic agent to treat cold hypodynamic shock resistant to catecholamines, clinical experience in septic infants is lacking. We report the beneficial effects of levosimendan infusion in 2 infants (39 and 64 days old) with low cardiac output septic shock (ejection fraction, 29% and 33%; fractional shortening, 10% and 16% respectively) refractory to volume replacement and to the catecholamines dopamine and dobutamine. Levosimendan infusion (0.15 µg/kg/min) promptly increased both patients' myocardial contractility and improved tissue perfusion, thereby reducing lactate levels and increasing urine output. The only adverse effect was moderate hypotension in one infant, who reversed by adding norepinephrine to levosimendan. This clinical experience confirms the potential beneficial effects of levosimendan infusion to restore hemodynamics in infants with low cardiac output septic shock resistant to catecholamines.

In order to compare the acute hemodynamic effects of digoxin (0.01 mg/kg) and enoximone (1 mg/kg), a phosphodiesterase inhibitor inotropic agent, in severe chronic congestive heart failure, 8 patients (male, mean age 56.7 years, sinus rhythm) were investigated with a randomized cross-over study. Peak effect of enoximone (30 min) in comparison to that of digoxin (90 min) resulted in a similar reduction of left-ventricular filling pressure (-27 vs. -28%) and mean pulmonary artery pressure (-23 vs. -24%). Pulmonary (-39 vs. -16%; p0.01) and systemic vascular resistance (-27 vs. -4%; p0.001) were significantly lowered by enoximone. Cardiac index (+30 vs. +6%; p0.001) and heart rate (+11 vs. -3%; p0.05) were increased significantly more by enoximone than by digoxin. Since enoximone resulted in an enhancement of cardiac performance greater than that produced by digoxin, enoximone could be a useful and powerful substitute for digoxin in the acute therapy of severe chronic congestive heart failure with sinus rhythm.

The present study was designed to evaluate the significance of echocardiography versus cardiac troponin I levels in early detection of anthracycline dependent cardiotoxicity in acute lymphoblastic leukemia (ALL) patients. A total of 276 pediatric ALL patients were included in the study prospectively along 3 phases of data collection lasted from 2002 to 2009; including phase I (March 2002 to February 2003; n = 25; 53.3% females), phase II (September 2003 to April 2004; n = 35; 57.1% females), and phase III (January 2005 to June 2009; n = 216; 52.7% females) with respect to cumulative anthracycline doses applied. Anthracycline was administered in accordance with berlin-Franfurt-Munich (BFM)-2000 protocol in doses of 30 to 350 mg/m(2) (in the first phase) and 30 to 240 mg/m(2) (in the following phases). Evaluation of cardiotoxicity was performed via echocardiography and measurement of cardiac troponin I levels. Patients in each phase were homogenous in terms of gender and age. Diastolic dysfunction determined via reduction E/A ratio below the cutoff value was demonstrated to deteriorate earlier than systolic functions and alteration in cardiac enzymes. Being similar between dose groups, cTnI levels were shown to rise in the presence of congestive heart failure. In conclusion, anthracycline cardiotoxicity appears to be detected in an earlier stage by using diastolic parameters compared to systolic parameters and cardiac enzymes.

Putative 5-HT 4 receptors were investigated in isolated piglet left atria and papillary muscles. In atrial tissues, 5-hydroxytryptamine (5-HT) was a potent positive inotropic agent with a pD 2 of 6.7. Its effects were antagonised in a selective and competitive manner by the 5-HT 4 receptor antagonist, SDZ 205-557, with a pA 2 of 7.3. In contrast to atrial tissues, piglet papillary muscles were virtually unresponsive to 5-HT 10 −8 −10 −3 M, suggesting that functional cardiac 5-HT 4 receptors are not present in ventricular tissue.

The influence of temperature on the myocardial inotropic response to norepinephrine was studied in rats of different ages. Right papillary muscles isolated from 3-, 12-, and 24-month-old rats were superfused at two temperatures (29 degrees C and 37 degrees C) with progressively larger doses of norepinephrine. At 29 degrees C, the contraction duration was longer and the inotropic effect of norepinephrine was significantly smaller in 24-month muscles than in 3- and 12-month preparations. In muscles superfused at 37 degrees C, these age-related differences in the contraction duration and in the response to norepinephrine disappeared. Analysis of variance and covariance showed that temperature, but not age, is responsible for the differences in the inotropic response to norepinephrine observed. These results show that experimental conditions, among which temperature may play a major role, deeply affect the responsiveness of cardiac preparations to beta-adrenergic agonists.

Triiodothyronine is an important regulator of cellular metabolism and may have potential use as an inotropic agent The aim of this study was to determine the effects of cardiopulmonary bypass on thyroid function in infants weighing less than 5 kg. Serial measurements of triiodothyronine, thyroxine, and thyroid-stimulating hormone were made in 10 infants and corrected for the effects of hemodilution. We demonstrated a fall in triiodothyronine and thyroxine levels, with some recovery after 3 to 6 hours. An additional decrease then occurred, reaching a trough at 48 hours (representing a fall of 78% for triiodothyronine and 57% for thyroxine) before hormone levels returned to normal at 5 to 7 days. Thyroid-stimulating hormone concentrations increased and decreased, predating and complementing exactly the changes in triiodothyronine and thyroxine. These results are quantitatively and, for thyroid-stimulating hormone, qualitatively different from those previously reported in adults. In two patients who died, however, and in one who had a particularly difficult postoperative course, no increase in triiodothyronine, thyroxine, or thyroid-stimulating hormone concentrations was found after a trough had been reached at 48 to 72 hours, which suggests abnormal function at the hypothalamopituitary level. (J T horac C ardiovasc S urg 1992;103:800-5)

The effects of DPI 201-106 (a novel, cyclic AMP-independent positive inotropic agent with Ca(2+)-sensitizing and Na(+)-channel agonistic mechanisms) on myocardial mechanics and energetics were assessed in the excised cross-circulated dog left ventricle. In the first protocol, the relation between left ventricular oxygen consumption (VO2) and systolic pressure-volume area (PVA) was analyzed before and during administration of DPI 201-106. The reciprocal of the slope of the VO2-PVA relation has been shown to reflect the contractile efficiency, and the VO2-intercept consists of the oxygen cost of contractility-dependent excitation-contraction coupling and basal metabolism. DPI 201-106 increased Emax (contractility index) and elevated the VO2-PVA relation in a parallel manner, i.e., the VO2-intercept increased without a change in the slope. In the second protocol, the increase in the VO2-intercept of the VO2-PVA relation for a unit increase in Emax (i.e., oxygen cost of enhanced contractility) was compared between DPI 201-106 and epinephrine in a paired manner in each heart. Epinephrine significantly abbreviated the time to end systole, whereas DPI 201-106 did not, suggesting that the mechanism of inotropic action differed between the two drugs. However, the oxygen cost of enhanced contractility was the same between the two drugs in each heart. Therefore, DPI 201-106 did not alter the contractile efficiency nor spare the oxygen cost of enhanced contractility as compared to epinephrine under the present experimental conditions. This suggests that the Ca(2+)-sensitizing effect of DPI 201-106, if any, is too small to spare the oxygen cost of contractility in the blood-perfused, non-failing dog heart.

The contractile response to Endothelin-1 (ET-1) has been investigated in electrically stimulated single cardiac myocytes isolated from hearts of young and senescent rats. ET-1 (0.1-10 nM) exhibited a marked negative inotropic effect in both age groups. ET-1 (1.0 nM) also reduced the occurrence of spontaneous contractile oscillations in young myocytes, suggesting depletion of sarcoplasmic reticulum-Ca(2+) stores. The possibility that ET-1 may have opposite effects on myocardial contractility is discussed.

The hyperadrenergic condition following surgical stress and inotropic drugs have been identified as leading causes for postoperative atrial fibrillation (AF). Smokers are characterized by higher catecholamine levels and tolerance. We tested the hypothesis that smoking patients are less prone to develop postoperative AF.A total of 3,245 coronary artery bypass and valvular procedures were reviewed. Predictors of AF and interaction between variables were explored by multivariable logistic regression. AF-predictive scores were created and validated for goodness of fit, and receiver operating characteristic curves were created.Postoperative AF occurred in 26% of patients. Smokers accounted for 15% of the study population and demonstrated a reduced incidence of postoperative AF compared with nonsmoking individuals (20% vs. 27%, p.001). Multivariate analysis revealed a significant interaction between smoking status and inotropic support requirement. The AF-protective effect of smoking was confounded by inotropic drugs. However, when we excluded from analysis the patients with inotropic support, smoking conferred a 46% risk reduction of AF (odds ratio [OR] = 0.54, 95% CI = 0.34-0.87, p = .011). In addition, age, valvular surgery, and hypertension were independently associated with AF. Postoperative AF increased the length of hospitalization, without affecting hospital mortality. AF was associated with an increased 1-year mortality (p = .002).Current smokers are less prone to develop AF after cardiac surgery. Our data support the hypothesis that hyperadrenergic state and catecholamines are key mechanisms in the pathophysiology of postoperative AF.

Shock is a situation of circulatory failure characterized by a generalized and severe decrease of tissue oxygen and nutrient delivery. Shock, whatever the etiology, induces reversible and later irreversible cell lesions.

Diuretics and angiotensin-converting enzyme inhibitors currently are the mainstay of both acute and chronic heart failure management. They have earned their place by bringing measurable and reliable clinical benefit to patients with all grades and types of heart failure. Other treatments--digoxin, vasodilators and inotropes--offer less secure efficacy and their clinical role is at times controversial. The need for new remedies is inescapable. Despite current therapy, heart failure causes a distressing reduction in both quality and quantity of life. As knowledge of the pathophysiology of heart failure is gained, more selective treatment options may become available offering hitherto unknown specificity but demanding remarkable levels of diagnostic accuracy.

Looking back reveals how the direction of therapy for heart failure has changed since the inception of the first large clinical trial of vesnarinone, an inotropic agent, in April 1990. At that time...

The aim of this study was to compare the positive inotropic effects of 3 different agents with 3 different mechanisms of actions-levosimendan, rolipram, and dobutamine-on human atrial trabecular muscles. Samples of right atrial appendage (1 cm, 500-1000 mg) were removed and immersed in preoxygenated and modified Tyrode solution. In oxygenated Tyrode solution, preparations were used to investigate the concentration-effect relationship of levosimendan, dobutamine, and rolipram on percentage developed tension (DT), from 10 to 10 M, each concentration for 15 minutes. All 3 agents produced concentration-dependent increments in DT. We found that levosimendan was the most efficacious positive inotropic agent on isolated human atrial trabeculae. Both the sensitivity (pD2) and maximum response (Emax) of human atrial trabeculae to levosimendan (6.711 +/- 0.26 and 23.2 +/- 2.2 mN, respectively) were significantly greater than those of dobutamine (6.663 +/- 0.19 and 17.6 +/- 2.8 mN) and rolipram (6.497 +/- 0.18 and 15.0 +/- 1.0 mN). pD2 and Emax values for dobutamine were significantly higher than those for rolipram. It was suggested that because of its potential to enhance cardiac performance without predisposition to calcium-induced arrhythmias, levosimendan might be more useful as a positive inotropic agent in clinical practice.

Although the cardiac protective and negative inotropic effects of nicorandil via opening the sarcolemmal or mitochondrial K(ATP) channel and NO-like action are well known, positive inotropic effects of nicorandil in normal hearts have not been reported. The aim of the current study was to investigate how nicorandil affects left ventricular (LV) function of in situ adult rat hearts through the entire cardiovascular system.We performed simultaneous and continuous measurements of LV pressure (P) by a catheter-tip micromanometer and LV volume (V) using a conductance catheter. We obtained steady-state LV P-V loops and intermittent curvilinear LV end-systolic pressure-volume relations (ESPVRs), LV end-systolic pressure (ESP(mLVV)), and systolic pressure-volume area (PVA(mLVV)) at midrange LVV (mLVV). We evaluated the effects of nicorandil on LV function by these mechanical indexes sensitively reflecting changes in LV contractility and work capability, preload (end-diastolic volume, EDV), and afterload (effective arterial elastance, Ea).Nicorandil (10 and 20 microg.kg(-1).min(-1)) (blood concentration: 0.53 +/- 0.14 and 1.48 +/- 0.21 microg/ml) largely shifted ESPVR upward and thus significantly increased ESP(0.06), PVA(0.06), stroke volume due to increase in EDV, and ejection fraction without significant changes in Ea and heart rate. In contrast, an NO donor, nitroglycerin (1 microg.kg(-1) . min(-1)), significantly decreased Ea but did not change ESP(0.06), PVA(0.06), and EDV. Furthermore, either a nonselective K(ATP) channel blocker, glybenclamide, or a mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, abolished these nicorandil-induced positive inotropic actions.These results suggest that nicorandil exhibited positive inotropic actions on LV function of in situ hearts in adult rats with resultant increased preload (EDV).

The aim of this study was to investigate and determine whether patients with significant (greater than or equal to%50) left main coronary artery stenosis could undergo coronary bypass on the beating heart and compare the results to those obtained using the conventional method. Prospectively collected data of patients with significant left main coronary artery disease who had undergone coronary bypass on the beating heart (group A, n=100) or with the conventional method (group B, n=100) were evaluated retrospectively. EuroSCORE values, preoperative and operative details, postoperative morbidity and mortality, and early results were compared. Groups were similar in terms of EuroSCORE, demographics, and preoperative variables. Number of distal anastomoses per patient was 3.1+/-0.9 in the beating heart group while it was 3.3+/-0.9 in the conventional group (P=0.09). Patients operated on with the conventional method had higher levels of peak creatine kinase-myocardial band, blood and blood product transfusions, and inotropic requirements, while mechanical ventilation times and hospital stay were longer. The incidence of postoperative atrial fibrillation, mediastinitis, and intra-aortic balloon usage were comparable between the groups. There was no neurological complication in group A whereas five major neurological complications (three transient ischemic attacks, two strokes) occurred in group B (P=0.06). Thirty-day mortality occurred in one patient in the beating heart group whereas five early deaths were observed in the conventional group (P=0.21). In significant left main coronary artery stenosis coronary bypass on the beating heart is a safe and effective alternative to the conventional method with the same or better early results. The long-term results need to be evaluated.

The purpose of this study was to examine the inotropic effects of nitroprusside (NP), a direct nitric oxide (NO) donor, in isolated rat hearts. Langendorff-perfused hearts (n = 5), paced at 6 Hz, were subjected to 15 min of equilibration (EQ) followed by infusion of NP, producing a coronary artery concentration of 1 x 10(-5) M. Coronary flow, left ventricular developed pressure (DP), end-diastolic pressure, and contractility and compliance (+/- dP/dt) were monitored throughout the experiment by a computerized data acquisition system. Myocardial oxygen consumption (MVO2) was measured at the end of EQ and after 2 1/2 min of NP infusion. Myocardial efficiency was calculated as the quotient of DP divided by MVO2. Values are expressed as the mean +/- SEM. Paired t tests were used to calculate statistical significance. Values for parameters monitored at end EQ and at 2 1/2 min NP infusion showed that there was a 93% increase in coronary flow, 18, 17, and 16% increases in developed pressure, contractility, and compliance, respectively, no significant change in end-diastolic pressure, a 49% increase in myocardial oxygen consumption, and a 21% decline in myocardial efficiency (P < 0.05 for all differences). We conclude that in the isolated rat heart, NO behaves as a positive inotrope.

Background: This study was conducted to compare the effect of histidine-triptophanketoglutalate solution (HTK) with that of cold blood cardioplegic solution (CBC) in mitral valve surgery. Method: Forty-six patients who underwent mitral valve replacement between January 1994 and December 1996 were enrolled in this study. Twenty patients received HTK (HTK group), while 27 patients had CBC (CBC group) as myocardial protection. HTK was given as a single high dose, whereas CBC was used in the usual multidose format. Result: The doses of inotropic agent at the end of extracorporeal circulation did not differ between the HTK group and the CBC group. Creatine kinase values (units) on day 1 and day 2 were 1140 ± 412, 921 ± 436 for the HTK group and 904 ± 335,816 ± 420 for the CBC group, respectively (p = NS). Spontaneous defibrillation occurred in 26% of the CBC group and 90% of the HTK group (p < 0.05). Pacing was temporarily used in 20% of the HTK group and 44% of the CBC group after extracorporeal circulation (p < 0.05). Conclusions: These results suggest that HTK provided more adequate myocardial protection in mitral valve surgery. (J Card Surg 1998; 13:43–47)

Cardiovascular collapse is a devastating clinical entity frequently observed in both medical and surgical intensive care unit patients. Despite the gravity of this condition, advances in cardiovascular physiology, molecular biology, and pharmacology, now allow physicians to offer rational therapeutic interventions to such patients. This chapter will review the basic pathophysiology of cardiac failure, identify cellular targets for pharmacologic intervention, and discuss the actions and uses of some of the newer inotropic agents.