Viabilidade miocárdica na prática clínica / Assessing myocardial viability in clinical practice

Embora a avaliação da viabilidade miocárdica seja comum na prática do cardiologista, muitos médicos têm dúvidas a respeito dos resultados dos métodos diagnósticos. A medicina nuclear tem papel importante nos estudos de viabilidade, mas os laudos precisam ser interpretados num contexto clínico e fisiopatológico. Este artigo teve o objetivo de revisar a origem e a evolução do conceito da viabilidade miocárdica. São expostos os métodos diagnósticos com ênfase na medicina nuclear com uma explicação funcional sobre cada tipo de exame. A partir disso, são mostradas imagens como exemplos e é proposta uma maneira de atuar nesses casos baseada na clínica, na porcentagem de miocárdio acometido e na topografia das lesões coronarianas (proximais ou distais). (AU)

Although assessing myocardial viability is a common cardiology practice, many physicians question the results of diagnostic methods. Nuclear medicine plays an important role in viability studies, but the reports require interpretation in a clinical and pathophysiological context. this article was aimed at reviewing the origin and evolution of myocardial viability. Here we present diagnostic methods by emphasizing nuclear medicine and provide a functional explanation of each test type using example images. We also propose how to act in these cases based on clinic examination findings, the percentage of affected myocardium, and coronary lesion topography (proximal or distal).(AU)

Dobutamine in paediatric population: a systematic review in juvenile animal models.

OBJECTIVE: Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/paediatric population. METHODS: Studies were identified by searching MEDLINE (1946-2012) and EMBASE (1974-2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included. RESULTS: Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions. CONCLUSION: There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.

New cardiomechanic pacing lead sensor based on high frequency parameters: experimental studies in sheep.

UNLABELLED: Pacing Lead as a High Frequency Cardiomechanic Sensor. INTRODUCTION: The purpose of this study was to investigate the possibility of detecting and quantifying ventricular contraction in sheep utilizing the cardiomechanic sensor based upon the high frequency (HF) parameters measurements on bipolar cardiac pacing leads. Measurement of the HF reflection coefficient yields the lead-bending signal (LBS) caused by myocardial contraction. The correlation between the lead-bending acceleration (LBA) expressed as the rate of rise of LBS and LV dP/dt should reveal that LBS may be utilized as a cardiomechanic sensor in implantable cardiac electrotherapy devices. METHODS AND RESULTS: We implanted 3 different pacing leads and tested the measurement system in 9 sheep (42 ± 6 kg) at baseline and during acute hemodynamic intervention with dobutamine infusion and tachycardia induced by VVI pacing at 200 bpm. A stable, consistent, and reproducible LBS was obtained in all sheep during the implantation procedure and 4 months after the implantation during different experimental conditions that included hemodynamic interventions. The dependence between LBAmax and LV dP/dtmax was found to be statistically significant and with high Pearson's correlation coefficient (r = 0.855, P <0.001). We could also observe the hemodynamic deterioration caused by fast ventricular pacing with the decrease of LV dp/dt and LBA compared with sinus rhythm. CONCLUSION: This study confirms the feasibility and efficacy of the hemodynamic sensor based upon HF lead parameters. Moreover, it was demonstrated that LBAmax is highly correlated to the ventricular contractility and, therefore, can be efficiently used as a hemodynamic and cardiomechanic sensor. (J Cardiovasc Electrophysiol, Vol. 24, pp. 338-346, March 2013).

[A reinforcement of acupuncture on the cardiac effect of dobatamine: exhibition of acupoint's functional specificity].

OBJECTIVE: To investigate the functional specificity of acupoint by means of acupoint injection of Dobutamine Hydrochloride (DH). METHODS: Male SD rats were randomized into normal control (NC), EA-Neiguan (PC6) + acupoint injection (AI, EA-PC 6 + AI), EA-Zusanli (ST 36) + AI (EA-ST 36 + AI), and EA-intramuscular injection site (IMIS) + intramuscular injection (EA-IMIS+ IMI) groups,with 8 rats being in each group. EA (2 Hz/15 Hz, 3 mA) was applied to bilateral "Neiguan" (PC 6), "Zusanli "(ST 36) and muscular-injection site for 10 min. DH (a beta1-adrenoceptor agonist) solution (100 microg/kg) was injected intramuscularly into the gluteus maximus after termination of EA intervention. The left ventricular systolic pressure (LVSP), heart rate (HR) and + dp/dt max were recorded before and 2, 5, 15 and 30 min after injection of DH. RESULTS: The values of LVSP, HR and + dp/dt max in EA-PC 6 + AI group were significantly higher than those in NC, EA-ST 36 + AI, and EA-IMIS + IMI groups (P < 0.01) 2 and 5 minutes after EA plus acupoint injection of DH. No significant differences were found between EA-ST 36 + AI and EA-IMIS+ IMI groups in LVSP, HR and +dp/dt max (P > 0.05). After injection of DH for 30 minutes, the values of LVSP, HR and + dp/dt max in EA-PC 6 + AI group were still significantly higher than those in NC group (P < 0.01). CONCLUSION: EA-PC 6+ AI DH is significantly superior to EA-ST 36 + AI DH and EA-IMIS+ IMI DH in producing a stronger cardiac excitatory effect and a longer post-effect, showing a relative specificity of the acupoint in upregulating cardiac functional activities.

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.

Magnesium supplementation significantly reduces serum S100beta concentrations in patients who have undergone coronary artery bypass surgery.

UNLABELLED: Magnesium (Mg) plays an important role in the prevention and treatment of central nervous system (CNS) damage. This pathology is a serious problem in patients undergoing coronary artery bypass graft surgery (CABG) with extracorporeal circulation (ECC). Its biochemical diagnosis is mainly based on S100beta protein observations. This study aims to analyse different forms of Mg supplementation on serum S100beta concentrations in patients who have undergone CABG. PATIENTS AND METHODS: One hundred and twenty adult patients, who underwent CABG with extracorporeal circulation (ECC) with normovolemic haemodilution (NH) under general anaesthesia, were examined. According to the dose of Mg supplementation, patients were divided into six groups: A) patients receiving 3.33 mg of MgSO4 per min intravenously (i.v.), during surgery and the early postoperative period (18 hours); B) patients receiving oral Mg supplementation (OPS-Mg) and 3.33 mg of MgSO4 per min i.v., preoperatively; C) patients receiving 6.66 mg of MgSO4 per min i.v.; D) patients receiving OPS-Mg and 6.66 mg of MgSO4 per min i.v.; E) patients receiving 10 mg of MgSO4 per min i.v.; F) patients receiving OPS-Mg and 10 mg of MgSO4 per min i.v. Additionally, all patients were divided into three groups: O) patients, who did not receive dopamine or dobutamine infusion, DOP) those receiving dopamine infusion, and DOB) those receiving dobutamine infusion in doses dependent on their clinical state. Total serum Mg concentrations (Mg(t)) were measured at five time-points: 1) just before anaesthesia; 2) 10 min after ECC; 3) just after surgery, 4) in the morning of the first postoperative day, 5) in the morning of the second postoperative day. RESULTS: ECC resulted in S100beta elevation in all patients. In groups A, B and C, S100beta increased from the second to the fourth time-points; in groups D and F, S100beta increased at the second and third time-points; and in group E, S100beta increased only at the third time-point. The highest serum S100beta concentrations were noted in groups A and B, and the lowest concentrations were noted in groups E and F. There were significant correlations between serum S100beta and Mg(t) concentrations at time-point 3 in groups A, B, C and F. Moreover, there were significant overall correlations between S100beta and Mg in groups A and B. CONCLUSIONS: 1) ECC resulted in S100beta elevation, 2) infusion of 10 mg of MgSO4 per min reduced serum S100beta concentrations, and 3) dopamine infusion resulted in the highest serum S100beta concentrations.

Human model simulating right ventricular outflow tract tachycardia by high-frequency stimulation in the left pulmonary artery: autonomics and idiopathic ventricular arrhythmias.

INTRODUCTION: Frequent monomorphic premature ventricular contractions (PVC) and/or ventricular tachycardia (VT) in patients with structurally normal heart usually arise from the right ventricular outflow tract (RVOT). An animal model simulating RVOT tachycardia by high-frequency stimulation (HFS) of the sympathetic input to the proximal pulmonary artery (PA) has been previously described. The aim of this study was to similarly induce RVOT tachycardia in humans. METHODS: In 9 patients with no history of ventricular arrhythmias, a circumferential catheter was placed in the left, main, and proximal PA to contact the endovascular circumference of the PA. A 50-ms train of HFS (200 Hz/0.3 ms pulse duration), coupled to atrial pacing, was applied at each bipolar pair of the circumferential catheter. The coupling interval was adjusted so that the 50-ms train occurred during the ventricular refractory period. RESULTS: In 6 out of 9 patients, HFS in the left PA during dobutamine infusion induced monomorphic PVCs and/or VT with left bundle branch block (LBBB) morphology and inferior axis at an average stimulation level of 12.5 +/- 2.7 V. HFS in the main PA and in the proximal PA did not induce any ventricular arrhythmias with the highest energy of 15 V in baseline state and during dobutamine infusion. HFS in the left PA was associated with hiccough in all patients. CONCLUSION: Stimulation of the sympathetic input to the left PA during dobutamine infusion induces PVCs and/or VT exhibiting LBBB-morphology and inferior axis, closely simulating clinical RVOT tachycardia in humans.

Evoked changes in cardiovascular function in rats by infusion of levosimendan, OR-1896 [(R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide], OR-1855 [(R)-6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one], dobutamine, and milrinone: comparative effects on peripheral resistance, cardiac output, dP/dt, pulse rate, and blood pressure.

Levosimendan enhances cardiac contractility primarily via Ca(2+) sensitization, and it induces vasodilation through the activation of ATP-sensitive potassium channels and large conductance Ca(2+)-activated K(+) channels. However, the concentration-dependent hemodynamic effects of levosimendan and its metabolites (R)-N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide (OR-1896) and (R)-6-(4-aminophenyl)-5-methyl-4,5-dihydropyridazin-3(2H)-one (OR-1855) have not been well defined. Thus, levosimendan (0.03, 0.10, 0.30, and 1.0 mumol/kg/30 min; n = 6) was infused as four escalating 30-min i.v. doses targeting therapeutic to supratherapeutic concentrations of levosimendan (C(max), approximately 62.6 ng/ml); metabolites were infused at one-half log-unit lower doses and responses compared to dobutamine (beta(1)-agonist) and milrinone (phosphodiesterase 3 inhibitor). Peak concentrations of levosimendan, OR-1896, and OR-1855 at the end of the high dose were 323 +/- 14, 83 +/- 2, and 6 +/- 2 ng/ml, respectively (OR-1855 rapidly metabolized to OR-1896; peak = 82 +/- 3 ng/ml). Levosimendan and OR-1896 produced dose-dependent reductions in blood pressure and peripheral resistance with a rank potency, based on ED(15) values, of OR-1896 (0.03 mumol/kg) > OR-1855 > levosimendan > milrinone (0.24 mumol/kg); an ED(15) for dobutamine could not be defined. Only dobutamine produced increases in pulse pressure (30 +/- 5%) and rate-pressure product (34 +/- 4%). All of the compounds, with the exception of OR-1855, elicited dose-dependent increases in dP/dt with a rank potency, based on ED(50) values, of dobutamine (0.03 mumol/kg) > levosimendan > OR-1896 > milrinone (0.09 mumol/kg), although only levosimendan produced sustained increases in cardiac output (9 +/- 4%). Thus, levosimendan and OR-1896 are hemodynamically active at sub- to supratherapeutic concentrations (whereas the effects of OR-1855 in the rat are thought to be predominantly mediated by conversion to OR-1896) and produce direct inotropic effects and also direct relaxation of the peripheral vasculature, which clearly differentiates them from dobutamine, which does not elicit K(+) channel activation, suggesting a more balanced effect on the cardiac-contractile state and K(+) channel-mediated changes in vascular resistance.

Myoclonus associated with continuous dobutamine infusion in a patient with end-stage renal disease.

PURPOSE: The occurrence of myoclonus associated with continuous i.v. infusion of dobutamine in a patient with end-stage renal disease (ESRD) is described. SUMMARY: A 65-year-old Caucasian man was admitted to the hospital on January 26, 2006, for worsening congestive heart failure (CHF). He had been receiving dobutamine 3 mug/kg/min by intermittent i.v. infusion over four hours once weekly as an outpatient. His medical history included ischemic cardiomyopathy, pacemaker placement, ESRD, carotid artery disease, and type 2 diabetes mellitus. Along with receiving multiple other drugs, the patient was started on a continuous i.v. infusion of dobutamine 3 mug/kg/min. On January 29, the patient began having myoclonic muscle spasms. Clonazepam was given as needed, and the patient was discharged on February 1 with myoclonus that soon subsided. On March 13 the patient was again admitted for worsening CHF and was started on continuous dobutamine infusion. He was discharged on March 15; myoclonic muscle spasms began that afternoon. Myoclonic movements were noted when the patient arrived at the outpatient infusion center to begin his intermittent dobutamine infusion, and he was sent to the emergency department, where he was treated with calcium gluconate, regular insulin, and lorazepam and was instructed to stop his potassium supplements; he then received his dobutamine infusion. The myoclonic symptoms continued until March 18, when they subsided. CONCLUSION: A patient with CHF and ESRD developed myoclonic muscle spasms after receiving dobutamine by continuous i.v. infusion.

Evaluation of blood flow parameters in addition to blood pressure and electrocardiogram in the conscious telemetered beagle dog.

INTRODUCTION: The objective of this study was to evaluate a model for measuring blood flow parameters in addition to blood pressure, heart rate and electrocardiogram (ECG) in conscious telemetered restrained and unrestrained beagle dogs. METHODS: Male beagle dogs were instrumented with fully implantable ITS radio telemetry devices for the measurement of blood pressure and ECG. In addition, the dogs were instrumented with a probe around the pulmonary artery for the measurement of blood flow by ultrasound. Dobutamine at 5, 10 and 20 mug/kg/min, given intravenously to sling restrained animals (n=4), and minoxidil at 2 mg/kg, given orally to unrestrained animals (n=4), were selected as test compounds known to cause changes in the cardiovascular parameters of interest in this work. RESULTS: Dobutamine produced a small increase in mean (9%) and systolic blood pressure (5%), and an increase in pulse pressure (37%) and heart rate (30%). The additional blood flow parameters showed that dobutamine also increased stroke volume (21%) and cardiac output (58%) and reduced total peripheral resistance (52%). Minoxidil treatment resulted in a prolonged reduction in mean, systolic and diastolic blood pressure (up to 24%). Additionally, a prolonged increase in heart rate (169%) and cardiac output (120%) were observed along with a reduction in total peripheral resistance (62%). The effects of both compounds were consistent with their known pharmacology. DISCUSSION: The results show that measurement of blood flow parameters can be successfully added to the standard telemetered cardiovascular dog model to provide valuable additional information on the effects of compounds on the cardiovascular system.

Electrophysiologic effects of salbutamol, a beta2-selective agonist.

INTRODUCTION: A positive chronotropic effect of beta2 stimulation is well known. Case reports of ventricular arrhythmias during beta2-inhalation therapy have been published. The aim of this study was to asses the overall electrophysiologic effects of the beta2-agonist salbutamol. METHODS AND RESULTS: Electrophysiologic and hemodynamic variables were measured in 10 healthy volunteers during atrial pacing at baseline and during infusion of salbutamol at two different rates (0.1 and 0.2 microg/kg/min). To characterize beta2-agonist effects, a comparison was made with the beta1-selective agonist dobutamine. Salbutamol infusion produced significant changes in electrophysiologic properties in both myocardial and nodal tissues, with significantly greater effects on nodal properties. The proportional decreases in AV nodal parameters were more pronounced than in the sinus node (P < 0.001). An interesting result was a significant increase in the duration of the QS interval, which in the presence of an unchanged His-Purkinje conduction (HV) represents slower depolarization of the ventricle. QT dispersion also increased. CONCLUSION: Infusion of salbutamol results in significant electrophysiologic effects on most heart structures, proportionally most pronounced in the AV node. Discordant effects on ventricular conduction, which slowed, and the refractoriness of the ventricular myocardium, which shortened, were seen. QT dispersion was increased.

The pharmacologic treatment of vasospasm after subarachnoid hemorrhage: a case study.

The patient with a diagnosis of SAH and subsequent vasospasm presents many nursing challenges and requires complex pharmacologic management. By paying careful attention to the therapeutic and potential side effects of the medications prescribed, the nurse can be instrumental in the patient's recovery.

Myocardial high-energy phosphate metabolism in patients with stable chronic dilated cardiomyopathy under a dobutamine-induced prolonged mild workload.

BACKGROUND: The myocardial phosphocreatine (PCr) to beta-adenosine triphosphate ratio measured by phosphorus 31 nuclear magnetic resonance spectroscopy, which is analogous to energy reserve, is one of the important clinical predictors in patients with dilated cardiomyopathy (DCM). However, it may vary with the cardiac workload. METHOD: The myocardial PCr to beta-adenosine triphosphate ratio was measured before and during a 5 and 10 microgram/kg/min infusion of dobutamine in 7 patients with DCM and in 8 normal patients. Dobutamine infusion was kept constant for 50 minutes in each stage. Myocardial contractility and ventricular size were determined by echocardiography with the same protocol. RESULTS: This ratio was unchanged from 1.5 +/- 0.4 to 1.8 +/- 0.6 in the low-dose stage and stable (1.7 +/- 0.3) in the high-dose stage in patients with DCM. The heart rate and the mean rate of circumferential fiber shortening increased dose dependently both in patients with DCM and in patients without. CONCLUSION: These results demonstrate that constant loading of dobutamine for hours is tolerated without deterioration of myocardial metabolic function by patients with nonischemic DCM. We concluded that the high-energy phosphate metabolism of stable patients with cardiomyopathy is stable if the workload is temporary and weak. This implies the possibility that mild exercise can be tolerated in patients with heart failure.

Neither dopamine nor dobutamine corrects mesenteric blood flow depression caused by positive end-expiratory pressure in a rat model of acute lung injury.

OBJECTIVE: To determine if either dopamine or dobutamine would counteract the deleterious effect that positive end-expiratory pressure (PEEP) has on cardiac output and mesenteric blood flow in a rat model of acute lung injury. DESIGN: Prospective, randomized, controlled trial in a clinically relevant model of acute lung injury. SETTING: Microcirculation research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The animals were anesthetized with pentobarbital (30 mg/kg) by intraperitoneal injection. They underwent tracheostomy, jugular and femoral vein cannulation, femoral artery cannulation, carotid artery thermistor placement, and bowel preparation for in vivo video microscopy. Acute lung injury was created by administering 0.1 N hydrochloric acid (1 mL/kg) via the tracheostomy. Dopamine or dobutamine (2.5 or 12.5 microg/kg/min), followed by two intravenous fluid boluses, was administered to rats ventilated with 5, 10, 15, and 20 cm H2O of PEEP. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, thermodilution cardiac output, mesenteric arteriolar diameter, and red blood cell velocity were measured and mesenteric blood flow was calculated. Cardiac output was depressed in rats exposed to 20 cm H2O of PEEP by 32+/-2%. The corresponding values for cardiac output depression at 20 cm H2O of PEEP in rats receiving 2.5 and 12.5 microg/kg/min of dopamine and 2.5 and 12.5 microg/kg/min of dobutamine were 31+/-1%, 21+/-1%, 29+/-0%, and 24+/-2%, respectively. Mesenteric blood flow was depressed in rats ventilated with 20 cm H2O of PEEP by 74+/-3%, while the corresponding values in rats exposed to 20 cm H2O of PEEP and receiving 2.5 or 12.5 microg/kg/min of dopamine or 2.5 or 12.5 microg/kg/min of dobutamine were 86+/-3%, 77+/-3%, 73+/-3%, and 66+/-3%, respectively. Fluid boluses did not correct the deficits in cardiac output or mesenteric blood flow caused by the combination of acute lung injury and PEEP. CONCLUSIONS: The higher doses of dopamine and dobutamine partially, but insignificantly, corrected the cardiac output depression caused by PEEP in a model of acute lung injury. Neither dose of dopamine nor dobutamine was able to improve PEEP-induced mesenteric blood flow depression.

Effects of antianginal therapy with a calcium antagonist and nitrates on dobutamine-atropine stress echocardiography. Comparison with exercise electrocardiography.

BACKGROUND: Anti-ischaemic therapy with nitrates and/or calcium channel blockers profoundly affects the results of pharmacological stress echocardiography with coronary vasodilators but the influence on catecholamine stress testing remains unsettled. AIMS: The present study aimed to assess the effects of non-beta-blocker antianginal therapy on dobutamine (up to 40 micrograms.kg-1.min-1)-atropine (up to 1 mg) stress. echo-cardiography and to evaluate whether drug-induced changes in the dobutamine atropine stress echocardiography response may predict variations in exercise tolerance. METHODS: Twenty six patients with angiographically assessed coronary artery disease (seven patients with single-, 10 with double-, and nine with triple-vessel disease) performed a dobutamine atropine stress echocardiography and an exercise electrocardiography test in random order both off and on antianginal drugs (nitrates and calcium antagonists). In doubtamine-atropine stress echocardiography, we evaluated: dobutamine time (i.e. the time from initiation of the dobutamine infusion to obvious dyssynergy), wall motion score index (in a 16-segment model of the left ventricle, each segment ranging from 1 = normal, to 4 = dyskinetic), and rate-pressure product at peak stress. RESULTS: Dobutamine-atropine stress echocardiography positivity occurred in 26 out of 26 patients off and in 23 patients on therapy (100 vs 88%, P = ns). Atropine coadministration was needed to evoke echo positivity in no patient off and in five out of 26 on therapy (0 vs 19% P < 0.01). The achieved rate pressure product during dobutamine-atropine stress echocardiography was comparable on and off therapy (17 +/- 4 vs 19 +/- 5 x 10(3) mmHg x heart rate. min-1, P = ns). Therapy induced an increase in dobutamine time (on = 16 +/- 3 vs of = 13 +/- 3 min, P < 0.01) and a decrease in peak wall motion score index (on = 1.3 +/- 0.2 vs off = 1.5 +/- 0.3, P < 0.01). The therapy induced changes in exercise time during the exercise electrocardiography test were not significantly correlated to dobutamine-atropine stress echocardiography variations in either dobutamine time (r = 0.07, P = ns), or peak rate pressure product (r = 0.24, P = ns), or peak wall motion score index (r = 0.02, P = ns). CONCLUSIONS: (1) non-beta-blocker antianginal therapy only modestly reduces dobutamine-atropine stress echocardiography sensitivity, although atropine coadministration is more often required to reach stress echo positivity under therapy; (2) therapy reduces the severity of dobutamine atropine stress echocardiography ischaemia stratified in the time and space domain, but these changes are only poorly correlated to variations in exercise tolerance.

Delayed time response of the continuous cardiac output pulmonary artery catheter.

Previous studies of the accuracy of pulmonary artery catheters (PAC) which provide continuous cardiac output (CCO) monitoring have investigated the performance during steady-state conditions. We compared the response time to hemodynamic change using a CCO PAC and an ultrasonic flow probe (UFP). In five sheep, a CCO PAC was inserted, and an UFP for measurement of CCO was placed around the pulmonary artery via a left thoracotomy. Six interventions which rapidly alter cardiac output were studied: crystalloid bolus, balloon inflation in the inferior vena cava (IVC), IVC balloon deflation, dobutamine infusion, hemorrhage, and reinfusion of blood. Cardiac output measured before and after each intervention was used to calculate the total change caused by the intervention, and the time intervals from intervention to 20%, 50%, and 80% of that change were noted. For all interventions, the time response of CCO was significantly slower than UFP. The largest differences were seen with the rapid infusion of lactated Ringer's solution for which the time interval for 20% change was 7.3 +/- 2.3 min (mean +/- SD) for CCO versus 0.5 +/- 0.3 min for UFP. The time interval for 80% change was 14.5 +/- 4.1 min for CCO versus 1.8 +/- 0.9 min with UFP. The current study demonstrates clinically important time delays in the response of the CCO catheter. This delay must be considered when rapid alterations of the hemodynamic state may occur.

NG-methyl-L-arginine, an inhibitor of nitric oxide formation, acts synergistically with dobutamine to improve cardiovascular performance in endotoxemic dogs.

OBJECTIVE: To evaluate the hemodynamic effects of the nitric oxide inhibitor, NG-methyl-L-arginine, and dobutamine during experimental endotoxemia. DESIGN: Prospective, randomized, controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult, male mongrel dogs. INTERVENTIONS: After catheterization with a flow-directed, thermal-dilution pulmonary artery flotation catheter and arterial catheter, awake dogs received either NG-methyl-L-arginine or dobutamine alone or in combination (controls; n = 5). Other animals were administered endotoxin (50 micrograms/kg), then received either NG-methyl-L-arginine alone or in combination with dobutamine after the onset of hypotension (endotoxin-treated; n = 5). MEASUREMENTS AND MAIN RESULTS: Both dobutamine and NG-methyl-L-arginine alone had a small, but significant vasopressor effect on control animals. In contrast, administration of the combination of NG-methyl-L-arginine and dobutamine resulted in a 48.6% increase in mean arterial pressure, an effect which was dose-dependent with respect to NG-methyl-L-arginine. In dogs treated with 50 micrograms/kg of endotoxin, hypotension could be only partially reversed by NG-methyl-L-arginine, mainly due to a decline in cardiac output. Co-infusion of dobutamine reversed this depression of cardiac output and resulted in a complete restoration of blood pressure. CONCLUSIONS: Later stages of septic shock are characterized by hypotension and decreased myocardial performance. A major mediator of hypotension is nitric oxide, a vasodilatory agent derived from L-arginine. Administration of the arginine derivative, NG-methyl-L-arginine, improved systemic vascular resistance but not myocardial performance. The addition of an inotropic agent to NG-methyl-L-arginine, a nitric oxide synthase inhibitor, resulted in an enhancement of the antihypotensive action of NG-methyl-L-arginine through the restoration of cardiac output. The synergistic action between dobutamine and NG-methyl-L-arginine may be of therapeutic value in the treatment of septic shock.

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.