Inotropic Agents In Patients Research Articles

Comparison of Bretschneider HTK cardioplegia solution and blood cardioplegia in terms of postoperative results in patients who underwent isolated supracoronary ascending aortic replacement.

Cardiac arrest with cardioplegia is the most common and reliable method of myocardial protection in cardiac surgery, but there is no definite consensus on the use of different types of cardioplegia. Two of the commonly used types of cardioplegia are Bretschneider histidine-tryptophan-ketoglutarate solution (Custodiol) and conventional blood cardioplegia. In this study, Custodiol solution and conventional blood cardioplegia used in patients with type A aortic dissection who underwent supracoronary ascending aortic replacement were aimed to be compared in terms of postoperative results. 70 patients with type A aortic dissection who underwent supracoronary ascending aortic replacement in our clinic between January 2011 - October 2020 were included. Patients were divided into two groups, blood cardioplegia group (n = 48) and Custodiol group (n = 22) and they were compared regarding preoperative, perioperative and postoperative variables. There was no significant difference between cardiopulmonary bypass time and cross-clamp time (p = 0.17 and p = 0.16, respectively). Mechanical ventilator weaning time, intensive care unit stay and hospital stay were shorter in Custodiol group (p = 0.04,p = 0.03 and p = 0.05, respectively). While inotropic support need was higher in the blood cardioplegia group (p = 0.001), there was no significant difference in terms of mortality, arrhythmia, neurological complications and renal complications. Our results show that Custodiol cardioplegia solution may be superior to blood cardioplegia in reducing mechanical ventilation weaning period, intensive care and hospital stay, and reducing the use of inotropic agents in patients with type A aortic dissection undergoing supracoronary ascending aorta replacement.

The role of levosimendan as inotropic agents in patients with LV dysfunction admitted to ICU post cardiac surgery

BACKGROUND: Coronary artery bypass graft (CABG) surgery is the standard of care for the management of patients with three-vessel and left main coronary artery disease (CAD) with viable myocardium. Positive inotropic agents are the treatment of choice in patients with LV dysfunction post CABG. Levosimendan is an inotropic drug that has three major mechanisms of action: positive inotropy, vasodilation, and cardiac cytoprotection. Levosimendan is a calcium sensitizer, it improves myocardial contractility by sensitising troponin C to calcium without increasing myocardial oxygen consumption and without impairing relaxation and diastolic function. AIM: The aim of this study was to determine the effect of levosimendan compared to the conventional inotropic agents on the outcomes of patients with LV dysfunction undergoing CABG. METHODS: It is a prospective observational study that patients were divided into 2 groups of 50 patients each. Group A received intravenous levosimendan (at a dose of 0.2μg per kilogram of body weight per minute for 1 hour, followed by a dose of 0.1μg per kilogram per minute for 23 hours), with the infusion started at the induction of anesthesia while Group B which included patients who received conventional drugs. Clinical examination, Hemodynamic data and Laboratory investigations pre-operative and post-operative were collected.

Inotropic agents use in patients hospitalized with acute decompensated heart failure: a retrospective analysis from a 22-year registry in a Middle-Eastern Country (1991-2013).

BackgroundData about the use of positive inotropic agents in patients hospitalized with acute decompensated heart failure (ADHF) is limited.MethodsThe records of 8066 patients with ADHF who were hospitalized at Hamad Medical Corporation, Qatar from 1991 to 2013 were analyzed to explore demographics and clinical characteristics of the patients according to inotropic agents use.ResultsEight hundred fifty eight patients [10.6 %, 95 % CI (10 to 11.3 %)] received intravenous inotropic support. Patients receiving inotropes were more likely to be female and have preserved ejection fraction when compared to those not receiving inotropic agents. Comorbidities associated with higher likelihood of receiving inotropic treatment included acute myocardial infarction, chronic renal impairment, dyslipidemia, hypertension, obesity and hyperglycemia. Patient on inotropes were more likely to undergone percutaneous coronary intervention (PCI), intra-aortic balloon pump support and intubation. There were no differences in the mean plasma BNP and CK-MB levels between the 2 groups. Heart failure patients receiving inotropes also were more likely to have complications including ventricular tachycardia (2.0 % vs. 0.9 %, p = 0.003), prolonged hospital stay (8.0 vs. 5.0 days, p = 0.001), cardiac arrest (14.6 % vs. 3.2 %, p = 0.001) and in-hospital mortality (30.8 % vs. 9.1 %, p = 0.001). Over the study period there was an increase use of inotropic agents and decreased mortality rates.ConclusionInotropic use increased over the period whereas; female gender and conventional cardiac risk factors were predictors of inotropic agents use in the study.

Abstract 12717: If Channel Blocker Ivabradine Counteracts Underisable Tachycardia in Patients Supported With Inotropic Agents

Introduction: The utilization of inotropic agents is usually linked to development of unappropriated and undesirable sinus tachycardia. That use also increases the myocardial oxygen consumption, could develop ischemic events and also has pro arrhythmic effects in coronary patients with acute heart failure, existing limited therapeutic options to face that situation. Hypothesis: The If channels blocker Ivabradine could be useful and safe for counteract the sinus tachycardia induced by inotropic agents and its undesirable effects without affecting the positive inotropic effect. Methods: Patients with ischemic-necrotic cardiomyopathy and low ejection fraction (under 35%) admitted for acute decompensation of heart failure with requirement of inotropic agents were prospectively and consecutively included. Patients with a rhythm different than sinus rhythm, impossibility for place a Swan-Ganz catheter or unable to use the oral route were excluded. Hemodynamic measurements with Pulmonary Artery catheters were performed before and three hours after oral administration of 15mg of Ivabradine. Results: The study included 52 patients (32 males and 20 females) with an average age of 65.6 years and an ejection fraction of 31.5% whe were under treatment with an average dose of 15 mcg/kg of Dobutamine. Three hours after started Ivabradine, it was observed a reduction of the heart rate from 123 +/-6 to 96+/-7 beats per minute (P=0.00002) with an increment of the systolic volume from 37.9+/-5 ml to 47.3+/-8 ml (P=0.00002) and the cardiac output from 4597 +/-550 ml/minute to 4825+/-535 ml/minute (P=0.041). No differences were observed nor in the filling pressures neither in the systemic or pulmonary resistances. There was a good clinical tolerance without evidence of hypotension, bradycardia, atrioventricular block episodes or need for transitory pacemaker . Conclusions: Ivabradine was an useful and safe intervention for controlling the undesirable sinus tachycardia linked to inotropic agents in patients with ischemic-necrotic cardiomyopathy. The drug didn’t affects the positive effect over contractility.

New pharmacologic interventions to increase cardiac contractility: challenges and opportunities.

The most extensively studied inotropic agents in patients with heart failure are phosphodiesterase (PDE) 3 inhibitors, which increase contractility by raising intracellular cyclic adenosine monophosphate content. In clinical trials, the inotropic benefits of these agents have been outweighed by an increase in sudden cardiac death. Here, I review recent findings that help explain what are likely to be distinct mechanisms involved in the beneficial and adverse effects of PDE3 inhibition. The proapoptotic consequences of PDE3 inhibition are becoming more apparent. Moreover, it has also become clear that individual PDE3 isoforms in cardiac myocytes are selectively regulated to interact with different proteins in different intracellular compartments. The beneficial and adverse effects of PDE3 inhibition may thus be attributable to the inhibition of different isoforms in different intracellular domains. In particular, PDE3A1 has been shown to interact directly with sarcoplasmic/endoplasmic reticulum Ca ATPase (SERCA2) in the sarcoplasmic reticulum through a phosphorylation of a site in its unique N-terminal domain, making it possible that this isoform can be selectively targeted to increase intracellular Ca cycling. Conventional PDE3 inhibitors target several functionally distinct isoforms of these enzymes. Isoform-selective and/or compartment-selective targeting of PDE3, through its protein-protein interactions, may produce the inotropic benefits of PDE3 inhibition without the adverse consequences.

Efficacy and Limitations of Oral Inotropic Agents for the Treatment of Chronic Heart Failure: A Single Center Cross-sectional Observational Study

The heart failure guideline in Japan has stated the necessity of investigating the role of oral inotropic agents in patients with chronic heart failure (CHF), which are clinically available only in Japan.

Efficacy and Limitations of Oral Inotropic Agents for the Treatment of Chronic Heart Failure

The heart failure guideline in Japan has stated the necessity of investigating the role of oral inotropic agents in patients with chronic heart failure (CHF), which are clinically available only in Japan. A total of 1,846 consecutive patients with heart failure (mean: 69.5 years old, 1,279 males) treated at our institute from November 2009 to August 2010 were investigated retrospectively. Thirty-one patients (1.84%) who had taken oral inotropic agents (pimobendan 27, docarpamine 6, and denopamine 4) were extracted for this study, and the efficacy and limitations of the treatments were analyzed. Following the oral inotropic treatment, the NYHA functional class (P = 0.017), cardiothoracic ratio (P = 0.002) and B-type natriuretic peptide levels (P = 0.011) were significantly improved, and the number of emergency room (ER) visits (P < 0.001) and hospitalizations (P < 0.001) were significantly reduced. The nonsurviving patients (n = 7/31, 22.6%) were significantly older (P = 0.02) and tended to have a larger cardiothoracic ratio (P = 0.084) compared with the survivors. An absence of concomitant beta-blocker therapy was significantly associated with a worse prognosis (oneyear mortality 2/21 versus 5/10, log rank, P = 0.011). Oral inotropic agents brought about improvements in the clinical parameters of CHF and a reduction in ER visits and hospitalizations. However, concomitant beta-blocker therapy should be considered for patients receiving oral inotropic treatment.

Hospital Patterns of Use of Positive Inotropic Agents in Patients With Heart Failure

This study sought to determine hospital variation in the use of positive inotropic agents in patients with heart failure. Clinical guidelines recommend targeted use of positive inotropic agents in highly selected patients, but data are limited and the recommendations are not specific. We analyzed data from 376 hospitals including 189,948 hospitalizations for heart failure from 2009 through 2010. We used hierarchical logistic regression models to estimate hospital-level risk-standardized rates of inotrope use and risk-standardized in-hospital mortality rates. The risk-standardized rates of inotrope use ranged across hospitals from 0.9% to 44.6% (median: 6.3%, interquartile range: 4.3% to 9.2%). We identified various hospital patterns based on the type of agents: dobutamine-predominant (29% of hospitals), dopamine-predominant (25%), milrinone-predominant (1%), mixed dobutamine and dopamine pattern (32%), and mixed pattern including all 3 agents (13%). When studying the factors associated with interhospital variation, the best model performance was with the hierarchical generalized linear models that adjusted for patient case mix and an individual hospital effect (receiver operating characteristic curves from 0.77 to 0.88). The intraclass correlation coefficients of the hierarchical generalized linear models (0.113 for any inotrope) indicated that a noteworthy proportion of the observed variation was related to an individual institutional effect. Hospital rates or patterns of use were not associated with differences in length of stay or risk-standardized mortality rates. We found marked differences in the use of inotropic agents for heart failure patients among a diverse group of hospitals. This variability, occurring in the context of little clinical evidence, indicates an urgent need to define the appropriate use of these medications.

Use of Inotropic Agents in Patients with Advanced Heart Failure

Abnormalities of cardiac function, with high intraventricular filling pressure and low cardiac output, play a central role in patients with heart failure. Agents with inotropic properties are potentially useful to correct these abnormalities. However, with the exception of digoxin, no inotropic agent has been associated with favourable effects on outcomes. This is likely related to the mechanism of action of current agents, which is based on an increase in intracellular cyclic adenosine monophosphate and calcium concentrations. Novel agents acting through different mechanisms, such as sarcoplasmic reticulum calcium uptake, cardiac myosin and myocardial metabolism, have the potential to improve myocardial efficiency and lower myocardial oxygen consumption. These characteristics might allow a haemodynamic improvement in the absence of untoward effects on the clinical course and prognosis of the patients.

Work-related sickness absence negotiations: GPs' qualitative perspectives

GPs can find their role as issuers of sickness certification problematic, particularly in trying to maintain a balance between certifying absence and preserving the doctor-patient relationship. Little research has been published on consultations in which sickness absence has been certified. To explore negotiations between GPs and patients in sickness absence certification, including how occupational health training may affect this process. A qualitative study was undertaken with GPs trained in occupational health who also participate in a UK wide surveillance scheme studying work-related ill-health. Telephone interviews were conducted with 31 GPs who had reported cases with associated sickness absence. Work-related sickness absence and patients' requests for a 'sick note' vary by diagnosis. Some GPs felt their role as patient advocate was of utmost importance, and issue certificates on a patient's request, whereas others offer more resistance through a greater understanding of issues surrounding work and health acquired through occupational health training. GPs felt that their training helped them to challenge beliefs about absence from work being beneficial to patients experiencing ill-health; they felt better equipped to consider patients' fitness for work, and issued fewer certificates as a result of this. Complex issues surround GPs' role in the sickness-certification process, particularly when determining the patient's ability to work while maintaining a healthy doctor-patient relationship. This study demonstrates the potential impact of occupational health training for GPs, particularly in light of changes to the medical statement introduced in 2010.

Effects of low-dose oral enoximone administration on mortality, morbidity, and exercise capacity in patients with advanced heart failure: the randomized, double-blind, placebo-controlled, parallel group ESSENTIAL trials

AimsUse of inotropic agents in patients with heart failure (HF) has been limited by adverse effects on outcomes. However, administration of positive inotropes at lower doses and concomitant treatment with beta-blockers might increase benefit–risk ratio. We investigated the effects of low doses of the positive inotrope enoximone on symptoms, exercise capacity, and major clinical outcomes in patients with advanced HF who were also treated with beta-blockers and other guideline-recommended background therapy.Methods and resultsThe Studies of Oral Enoximone Therapy in Advanced HF (ESSENTIAL) programme consisted of two identical, randomized, double-blind, placebo-controlled trials that differed only by geographic location (North and South America: ESSENTIAL-I; Europe: ESSENTIAL-II). Patients with New York Heart Association class III–IV HF symptoms, left ventricular ejection fraction ≤30%, and one hospitalization or two ambulatory visits for worsening HF in the previous year were eligible for participation in the trials. The trials had three co-primary endpoints: (i) the composite of time to all-cause mortality or cardiovascular hospitalization, analysed in the two ESSENTIAL trials combined; (ii) the 6 month change from baseline in the 6 min walk test distance (6MWTD); and (iii) the Patient Global Assessment (PGA) at 6 months, both analysed in each trial separately. ESSENTIAL-I and -II randomized 1854 subjects at 211 sites in 16 countries. In the combined trials, all-cause mortality and the composite, first co-primary endpoint did not differ between the two treatment groups [hazard ratio (HR) 0.97; 95% confidence interval (CI) 0.80–1.17; and HR 0.98; 95% CI 0.86–1.12, respectively, for enoximone vs. placebo]. The two other co-primary endpoints were analysed separately in the two ESSENTIAL trials, as prospectively designed in the protocol. The 6MWTD increased with enoximone, compared with placebo, in ESSENTIAL-I (P = 0.025, not reaching, however, the pre-specified criterion for statistical significance of P < 0.020), but not in ESSENTIAL-II. No difference in PGA was observed in either trial.ConclusionAlthough low-dose enoximone appears to be safe in patients with advanced HF, major clinical outcomes are not improved.

Relationship Between the Pharmacokinetics of Levosimendan and Its Effects on Cardiovascular System

Levosimendan, a Ca(2+) sensitizer, has emerged as an alternative option of pharmacologic inotropic support in patients with decompensated heart failure. In contrast to classic inotropes, rather than interfering with intracellular Ca(2+) levels in myocytes, levosimendan improves cardiac performance via Ca(2+) sensitization and K(+) channel-mediated peripheral vasodilatation. A two compartment pharmacokinetic model with zero-order input and first-order elimination has been found to describe best the pharmacokinetics of levosimendan. Although oral levosimendan has high bioavailability (approximately equal to 85%), in clinical practice it has been hitherto administered intravenously. Levosimendan has total clearance 175-250 mL/h/kg and most importantly a short half-life (about 1.5 hours). Therefore, this drug has a special pharmacokinetic interest: It is one of the few drugs used in cardiovascular medicine, whose prolonged action is not due to the drug itself but it is mainly due to its active metabolite OR-1896 (approximately 80 hours half life). Other metabolites with possible pharmacologic effect are N-conjugated OR-1855 (M7), N-hydroxylated OR-1855 (M8), N-hydroxylated OR-1896 (M10), O-glucuronide OR-1896 (M9) and O-sulfate (M11) of N-hydroxylated OR-1896. Initial reports on levosimendan's use in severe heart failure were positive and levosimendan has already been routinely used for the treatment of patients with decompensated heart failure, while it has been included to the European Society of Cardiology guidelines for the treatment of acute heart failure (class of recommendation IIb, level of evidence B). However, recent clinical trials have failed to demonstrate a clear benefit of levosimendan on survival, compared to other classic inotropic agents in patients requiring inotropic support. In this review article we provide a pharmacokinetic approach for the use of levosimendan in cardiovascular system by discussing its metabolism and mainly the pharmacology of its active metabolites in humans.

Inotropic Agents Improve the Peripheral Microcirculation of Patients With End-Stage Chronic Heart Failure

Background Skeletal muscle microcirculation impairment in patients with chronic heart failure (CHF) seems to correlate with disease severity. We evaluated the microcirculation by near-infrared spectroscopy (NIRS) occlusion technique before and after inotropic infusion. Methods We evaluated 25 patients with stable CHF, 30 patients with end-stage CHF (ESCHF) receiving treatment with intermittent infusion of inotropic agents, and 12 healthy subjects. Thenar muscle tissue oxygen saturation (StO 2%) was measured noninvasively by NIRS before, during, and after 3-minute occlusion of the brachial artery (occlusion technique) in all subjects and in patients with ESCHF before and after 6 hours of inotropic infusion (dobutamine and/or levosimendan) or placebo (N = 5). Results Patients with ESCHF or CHF presented significantly lower StO 2% than healthy subjects (74.5% ± 7%, 78.6% ± 6%, and 85% ± 5%, respectively; P = .0001), lower oxygen consumption rate during occlusion (24.6% ± 8%/min, 28.6% ± 10%/min, and 38.1% ± 11.1%/min, respectively; P = .001), and lower reperfusion rate (327% ± 141%/min, 410% ± 106%/min, and 480% ± 133%/min, respectively; P = .002). After 6 hours of inotropic infusion, patients with ESCHF showed significantly increased StO 2% (74.5% ± 7% to 82% ± 9%, P = .001), oxygen consumption rate (24.6% ± 8%/min to 29.3% ± 8%/min, P = .009), and reperfusion rate (327% ± 141%/min to 467% ± 151%/min, P = .001). No statistical difference was noted in the placebo group. Conclusion Peripheral muscle microcirculation as assessed by NIRS is impaired in patients with CHF. This impairment is partially reversed by infusion of inotropic agents in patients with ESCHF.

Stem cells in acute myocardial infarction: the good, the bad, and the ugly

Any new form of treatment, when based on solid experimental observations, initially generates a lot of enthusiasm among researchers as well as among patients (when media get involved). If the initial positive results in observational studies are then confirmed in small randomized trials with surrogate endpoints and finally in large randomized trials with clinical endpoints, the new treatment gains momentum and becomes common practice when incorporated in guidelines (for instance, the use of ACE inhibitors in patients with heart failure). At the other extreme, if the initial positive results are not confirmed in controlled randomized trials, the new treatment is quickly forgotten (for instance, the use of positive inotropic agents in patients with heart failure). As clinicians, we know, however, that we have to accept the grey area where things can remain uncertain for years or even decades. A good example is offered by lipid-lowering drugs: in spite of compelling evidence in the sixties that hypercholesterolaemia is a key atherogenic stimulus, statins have entered guidelines in the nineties only. The simple reason for this prolonged hovering in the grey area is that lipid-lowering drugs used prior to statins were able to significantly reduce cholesterol levels, but this reduction was not large enough to translate into a significant reduction of clinical endpoints. More recently, growing attention has been paid to the issue of safety. For instance, non-steroidal anti-inflammatory drugs are under close scrutiny because of an increased risk of thrombotic complications which went unnoticed during the last few decades. The interpretation of the growing number of trials of cell-based therapy following acute myocardial infarction (AMI) has to be considered in this broad context. After the seminal observation in 2001 by Anversa et al .1 that the human heart is not a post-mytotic organ, several studies in experimental models have confirmed that … *Corresponding author. Tel: +39 630154187; fax: +39 63055535. E-mail address : filippo.crea{at}rm.unicatt.it

Nesiritide for secondary pulmonary hypertension in patients with end-stage heart failure

The impact of adding nesiritide to standard therapy and positive inotropic agents in patients with end-stage heart failure and secondary pulmonary hypertension (PH) was studied. Patients included in this retrospective study were 18 years of age or older, admitted to the hospital with PH secondary to end-stage heart failure (New York Heart Association functional class IV), had received a pulmonary artery catheter, had been treated with nesiritide because of inadequate hemodynamic response to previous therapy (pulmonary capillary wedge pressure [PCWP], >18 mm Hg), and had shown minimal symptomatic benefit from standard heart-failure therapy, continuous infusions of loop diuretics, and positive inotropic agents (milrinone or dobutamine or both). The primary endpoint was change in PCWP. Secondary endpoints included change in mean pulmonary artery pressure (MPAP), change in cardiac index (CI), change in mean arterial pressure (MAP), change in serum creatinine (SCr) concentration, and occurrence of symptomatic hypotension. The study included 33 patients. Mean PCWP was reduced by 31.1% with the addition of nesiritide to previous therapy (p < 0.0001). Significant improvements in other hemodynamic variables, including MPAP (15.6% reduction) and CI (13.0% increase), were also observed. MAP was reduced significantly (by 15.2%), but SCr concentration did not change. There were five episodes of symptomatic hypotension. All patients exhibited relief of dyspnea symptoms. The addition of nesiritide to standard therapy and positive inotropic agents improved hemodynamic measures and clinical symptoms in patients with end-stage heart failure and secondary pulmonary hypertension.

Apelin has in vivo inotropic effects on normal and failing hearts.

Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat hearts using a novel combination of a perivascular flow probe and a conductance catheter. Native rats (n =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 microg/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 mm Hg for native animals). The present study is the first to show that apelin has positive inotropic effects in vivo in both normal rat hearts and rat hearts in failure after myocardial infarction. Apelin may have use as an acute inotropic agent in patients with ischemic heart failure.

Beta-blocker therapy influences the hemodynamic response to inotropic agents in patients with heart failure: A randomized comparison of dobutamine and enoximone before and after chronic treatment with metoprolol or carvedilol

ObjectivesWe compared the hemodynamic effects of dobutamine and enoximone administration before and after long-term beta-blocker therapy with metoprolol or carvedilol in patients with chronic heart failure (HF). BackgroundPatients with HF on beta-blocker therapy may need hemodynamic support with inotropic agents, and the hemodynamic response may be influenced by both the inotropic agent and the beta-blocker used. MethodsThe hemodynamic effects of dobutamine (5 to 20 μg/kg/min intravenously) and enoximone (0.5 to 2 mg/kg intravenously) were assessed by pulmonary artery catheterization in 29 patients with chronic HF before and after 9 to 12 months of treatment with metoprolol or carvedilol at standard target maintenance oral doses. Hemodynamic studies were performed after ≥12 h of wash-out from all cardiovascular medications, except the beta-blockers that were administered 3 h before the second study. ResultsCompared with before beta-blocker therapy, metoprolol treatment decreased the magnitude of mean pulmonary artery pressure (PAP) and pulmonary wedge pressure (PWP) decline during dobutamine infusion and increased the cardiac index (CI) and stroke volume index (SVI) response to enoximone administration, without any effect on other hemodynamic parameters. Carvedilol treatment abolished the increase in heart rate, SVI, and CI and caused a rise, rather than a decline, in PAP, PWP, systemic vascular resistance, and pulmonary vascular resistance during dobutamine infusion. The hemodynamic response to enoximone, however, was maintained or enhanced in the presence of carvedilol. ConclusionsIn contrast with its effects on enoximone, carvedilol and, to a lesser extent, metoprolol treatment may significantly inhibit the favorable hemodynamic response to dobutamine. No such beta-blocker–related attenuation of hemodynamic effects occurs with enoximone.

Cardiovascular Effects of Intravenous Triiodothyronine in Patients Undergoing Coronary Artery Bypass Graft Surgery

Objective. —To test the hypothesis that triiodothyronine (T 3 ) administration improves hemodynamic variables and decreases inotropic drug requirements in cardiac surgery patients. Design. —Prospective, randomized, double-blind, placebo-controlled trial. Setting. —Tertiary care medical center. Patients. —A total of 211 patients undergoing coronary artery surgery at high risk for requiring inotropic drug support. Intervention. —At release of aortic cross-clamp, patients were randomized to an intravenous infusion of T 3 (0.8 μg/kg followed by 0.12 μg·kg -1 ·h -1 for 6 hours), dopamine (positive control, 5 μg·kg -1 ·min -1 for 6 hours), or placebo. Main Outcome Measures. —Perioperative hemodynamic variables, inotropic support requirements, and serum T 3 concentrations. Results. —Mean±SEM free T 3 serum concentrations decreased significantly during cardiopulmonary bypass in all groups (from 0.0035±0.0001 nmol/L [0.23±0.01 ng/dL] to 0.001±0.0001 nmol/L [0.07±0.00 ng/dL]; P =001) and increased to 0.0133±0.0004 nmol/L [0.87±0.03 ng/dL] (twice normal range; P 3 . Intravenous T 3 did not change hemodynamic variables or inotropic drug requirements; however, heart rate increased ( P Conclusions. —Triiodothyronine administration prevents decreases in serum thyroid hormone concentrations associated with cardiopulmonary bypass. Intravenous T 3 does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T 3 as an inotropic agent in patients undergoing coronary artery bypass graft surgery. ( JAMA . 1996;275:687-692)

Cardiovascular effects of intravenous triiodothyronine in patients undergoing coronary artery bypass graft surgery. A randomized, double-blind, placebo- controlled trial. Duke T3 study group

To test the hypothesis that triiodothyronine (T(3)) administration improves hemodynamic variables and decreases inotropic drug requirements in cardiac surgery patients. Prospective, randomized, double-blind, placebo-controlled trial. Tertiary care medical center. A total of 211 patients undergoing coronary artery surgery at high risk for requiring inotropic drug support. At release of aortic cross-clamp, patients were randomized to an intravenous infusion of T(3) (0.8 microg/kg followed by 0.12 microg.kg(-1).h(-1) for 6 hours), dopamine (positive control, 5 microg.kg(-1).min(-1) for 6 hours) or placebo. Perioperative hemodynamic variables, inotropic support requirements, and serum T(3) concentrations. Mean+/-SEM free T(3) serum concentrations decreased significantly during cardiopulmonary bypass in all groups (from 0.0035+/-0.0001 nmol/L [0.23+/-0.01 ng/dL] to 0.001+/-0.0001 nmol/L [0.7+/- 0.00 ng/dL]; P=.001) and increased to 0.0133+/-0.0004 nmol/L [0.87+/-0.03 ng/dL] (twice normal range; P<.001) following initiation of intravenous T(3). Intravenous T(3) did not change hemodynamic variables or inotropic drug requirements; however, heart rate increased (P<.001), and a trend toward decreased use of inotropic agents was demonstrated in the dopamine group. Triiodothyronine administration prevents decreases in serum thyroid hormone concentrations associated with cardiopulmonary bypass. Intravenous T(3) does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery.

Inotropic effects of alpha 1-adrenergic agonists in myocardium from rats with postinfarction heart failure.

In clinical and experimental heart failure, the inotropic response to beta-adrenergic receptor stimulation is depressed. Therefore, non-beta-adrenergic mechanisms may assume increasing importance for summoning inotropic reserve in the failing heart. To test the integrity of the inotropic pathway mediated by alpha 1-adrenergic receptor stimulation in a model of chronic ischemic heart failure, we administered phenylephrine to noninfarcted left ventricular papillary muscles isolated from sham-operated rats (n = 10) and rats with large (> 40% left ventricular circumference) anterior myocardial infarctions (n = 9). Isometric force was monitored, and intracellular Ca2+ (Cai2+) transients were recorded with the bioluminescent protein aequorin. Compared with muscles from sham-operated rats, contractility of muscles from rats with postinfarction heart failure was depressed at extracellular Ca2+ concentrations between 0.5 and 3.0 mM. Phenylephrine produced comparable dose-dependent increases in developed tension (126 +/- 4 vs. 125 +/- 7% of baseline) and peak rate of tension rise (125 +/- 4 vs. 140 +/- 9% of baseline) in muscles from sham and infarcted rats, respectively. There was no significant change in the time course of the isometric twitch or in the time course or amplitude of the Cai2+ transient after phenylephrine administration in muscles from either group. No evidence of Cai2+ overload, as defined by spontaneous Ca2+ release, was observed during phenylephrine administration in muscles from normal or failing hearts. The density of alpha 1-adrenoceptors measured with [3H]prazosin binding in crude membranes isolated from noninfarcted left ventricular tissue was not different in control and infarcted hearts (48 +/- 5 vs. 53 +/- 4 fmol/mg protein). These data indicate that the positive inotropic effect of alpha-agonists may be preserved in chronic ischemic heart failure. In both normal and failing myocardium, the inotropic effects of alpha 1-adrenergic stimulation occurred with little or no increase in Cai2+ availability and no apparent adverse effects on myocardial relaxation. Therefore, agents that act by similar mechanisms may have certain therapeutic advantages over traditional inotropic agents in patients with heart failure.