Quantitation of global and regional left ventricular function by cine magnetic resonance imaging during dobutamine stress in normal human subjects

Magnetic resonance imaging (MRI) provides high-resolution images of the heart. However, physical exercise during MRI is difficult due to space restriction and motion artefacts. To evaluate the feasibility of MRI during stress conditions, dobutamine was used as an alternative to exercise. Haemodynamics, ventricular volumes and wall thickening were measured at rest and during peak dobutamine infusion (15 micrograms.kg-1 x min-1) in 23 normal human subjects. To calculate left ventricular volumes, eight short-axis views were obtained encompassing the left ventricle from base to apex. At six levels, percent systolic wall thickening (%WTh) was measured in 18 segments (20 degrees intervals). Heart rate, systolic and diastolic blood pressures, stroke index, cardiac output and left ventricular ejection fraction increased significantly during dobutamine infusion (all P values < 0.001). In addition, %WTh increased significantly (P < 0.001) during dobutamine compared to the control state at all levels except in the apical and low-left ventricular levels. Both in control conditions and during dobutamine, segmental wall motion analysis showed the highest %WTh at the posterolateral area and the lowest %WTh at the septal region (P < 0.05). MRI clearly identifies wall motion dynamics and provides calculations of segmental wall thickening and haemodynamic parameters. Dobutamine is a useful stress agent by virtue of its safety, operator control and its effects which resemble physical exercise.     

Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses

BACKGROUND: Dobutamine stress echocardiography has been proposed as a diagnostic tool to identify viable myocardium. How regional wall thickening responds to dobutamine in the ischemic or short-term hibernating myocardium has not been adequately defined. We hypothesized that regional wall thickening would improve initially and subsequently deteriorate with incremental doses of dobutamine in viable myocardial regions supplied by a stenotic coronary artery. This study was undertaken to determine whether this biphasic pattern of regional function characterizes the response of ischemic or hibernating myocardium to dobutamine and to explore the factors and mechanisms that determine this response. METHODS AND RESULTS: Twenty-six pigs in four groups were studied: a control group (n = 5) to assess the response of myocardium perfused by nonstenotic coronary artery to incremental doses of dobutamine, and three experimental groups with a left anterior descending coronary artery stenosis producing acute myocardial ischemia (n = 7), short-term myocardial hibernation for 90 minutes (n = 7), and short-term hibernation for 24 hours (n = 7) to determine the functional and metabolic response to dobutamine under these conditions. Regional coronary flow was reduced to 40% to 60% of baseline, with significant reductions of regional wall thickening as measured by two-dimensional echocardiography and sonomicrometers. An incremental dobutamine infusion from 2.5 to 25 micrograms.kg-1.min-1 increased wall thickening and coronary flow without lactate production in the control group. In the other three groups, during the incremental dobutamine infusion, regional wall thickening improved initially, from 11.4 +/- 7.5% to 19.8 +/- 11.4%, P < .01, at dobutamine doses of 2.5 to 10 (4.5 +/- 2.2) micrograms.min-1.kg-1 but deteriorated subsequently to 5.0 +/- 5.8% at the maximal dose of dobutamine of 12.6 +/- 4.1 micrograms.min-1.kg-1. The initial improvement of regional wall thickening was associated with a small increase in regional coronary flow (from 0.53 +/- 0.18 to 0.68 +/- 0.25 mL.min-1.g-1 myocardium, P < .05) and with regional lactate production. High doses of dobutamine did not further increase regional coronary flow but markedly increased lactate production and induced regional myocardial acidosis (pH 7.26 +/- 0.07). The biphasic pattern of response to dobutamine was observed in each of the three experimental groups. Both peak improvement and peak deterioration occurred earlier and at lower dobutamine dose levels in the group with acute ischemia compared with the group with short-term hibernation for 24 hours (P < .05). CONCLUSIONS: A biphasic response of wall thickening to incremental dobutamine with initial improvement and subsequent deterioration is characteristic of ischemic or short-term hibernating myocardium. The initial low-dose dobutamine infusion improved wall thickening in the ischemic or hibernating myocardial region to a modest level. This initial modest improvement was transient and at the expense of metabolic deterioration of myocardial ischemia, so that at higher doses during prolonged dobutamine infusion, wall thickening deteriorated, lactate accumulated, and myocardial acidosis developed.     

Mechanisms of platelet-induced angiospastic reactions: potentiation of calcium sensitivity

BACKGROUND: Zatebradine is a new specific bradycardiac agent that selectively slows the depolarization in the pacemaker cells of the sinoatrial node. The purpose of our investigation was to determine whether the tachycardia induced by dobutamine can be attenuated by the administration of zatebradine. The results were compared with those produced by propranolol, which is used in the treatment of sinus tachycardia. METHODS: Twelve pigs were anesthetized with sodium pentobarbital, intubated, and ventilated. After baseline hemodynamic measurements were obtained, dobutamine was administered until the heart rate reached 25% above baseline. Animals were randomized to one of two groups. Group I received zatebradine, 0.5 mg/kg i.v., and Group II received propranolol, 0.5 mg/kg i.v. RESULTS: Dobutamine 10 micrograms.kg-1.min-1 increased the heart rate (FIR) by 25%, and increased mean arterial blood pressure (MAP) left ventricular (LV) dp/dt, and cardiac output (CO) (P < 0.05). Zatebradine decreased the HR to baseline (P < 0.05) without affecting left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), LV dP/dt, or CO. Stroke volume (SV) increased significantly (P < 0.05). Propranolol also reduced HR to baseline, but decreased LV dP/dt, LVSP, CO, and SV (P < 0.05). CONCLUSION: Zatebradine effectively attenuates the tachycardia caused by dobutamine in anesthetized pigs, without reducing cardiac performance.     

Myocardial dysfunction after successful resuscitation from cardiac arrest

OBJECTIVE: To investigate the functional and metabolic changes in the myocardium after successful resuscitation from cardiac arrest. DESIGN: Prospective, randomized, sham-controlled study. SETTING: Animal laboratory at a university center. SUBJECTS: Domestic pigs. INTERVENTIONS: Electric induction of ventricular fibrillation by alternating current delivered to the right ventricular endocardium through a pacing electrode. Electric defibrillation was attempted after an interval of 12 mins of ventricular fibrillation, which included 4 mins of untreated ventricular fibrillation and 8 mins of precordial compression in 13 animals, seven of which were successfully resuscitated. Seven additional animals were randomized to serve as "sham" controls, in which cardiac arrest was not induced. MEASUREMENTS AND MAIN RESULTS: Left ventricular pressure-volume relationships utilizing the conductance method were obtained in conjunction with conventional hemodynamic and metabolic measurements at baseline and during a 6-hr interval after successful cardiac resuscitation. Progressive and striking increases in left ventricular volumes were observed after successful cardiac resuscitation. The end-diastolic volume increased from a prearrest level of 89 +/- 21 mL to a maximum of 154 +/- 53 mL (p<.05) at 360 mins after successful resuscitation. The time-coincident end-systolic volume increased from 54 +/- 21 to 126 +/- 54 mL (p<.05), such that the ejection fraction was reduced from 0.41 +/- 0.10 to 0.20 +/- 0.07 ( p<.05). Ventricular dilation was associated with marked reductions in stroke volume and ventricular work. However, compensatory increases in heart rate maintained cardiac output at levels that sustained adequate systemic oxygen delivery. The slope of the end-systolic pressure-volume relationships progressively decreased from 5.04 +/- 1.88 to 2.00 +/- 0.57 mm Hg/mL (p<.05) at 360 mins after successful resuscitation. The volume intercept at left ventricular pressure of 100 mm Hg increased from 43 +/- 19 to 94 +/- 51 mL (p=.03). Both the decrease in the slope and the increase in the volume intercept were characteristic of progressive impairment in contractile function. The rate of left ventricular pressure decrease was unchanged. Accordingly, no substantial changes in lusitropic properties were identified. Despite large increases in end-diastolic volume, the end-diastolic pressure remained unchanged. CONCLUSION: Postresuscitation myocardial dysfunction in this animal model was characterized by impaired contractile function, decreased work capability, and ventricular dilation.     

Pharmacokinetics of isosorbide dinitrate in healthy volunteers after 24-hour intravenous infusion

No studies have examined the pharmacokinetics of isosorbide dinitrate (ISDN) after infusion of long duration, even though such infusions are used in patients. We therefore measured ISDN and its active metabolites, isosorbide-5-mononitrate (IS5MN) and isosorbide-2-mononitrate (IS2MN), in plasma of 9 healthy volunteers who received a continuous intravenous infusion of ISDN for 24 hours at a dose rate that lowered diastolic blood pressure by 10% during the first 30 minutes of infusion. All subjects tolerated the infusion except one who experienced intolerable headache. Five subjects received 1 microgram.min-1.kg-1, one 2 micrograms.min-1.kg-1, and two 4 micrograms.min-1.kg-1 ISDN, whereas the full rate of 6 micrograms.min-1.kg-1 was used continuously in one subject. At all infusion rates the plasma concentrations of ISDN were higher at 24 hours than at earlier times, suggesting that a steady-state condition had not been reached at that time. The same was true for the mononitrate metabolites, which reached higher plasma concentrations and were cleared more slowly than the parent compound after the end of the infusion. Apparent elimination half-lives of ISDN, IS2MN, and IS5MN were 67 +/- 10 minutes, 115 +/- 13 minutes, and 272 +/- 38 minutes, respectively. Comparison of low-rate infusions (1 and 2 micrograms.min-1.kg-1) with high-rate infusions (4 and 6 micrograms.min-1.kg-1) showed that the plasma concentration ratios at 24 hours of mononitrate metabolites to parent drug and apparent plasma clearance of ISDN were almost halved at the higher infusion rates.     

Postoperative junctional ectopic tachycardia

PURPOSE: To report the management of junctional ectopic tachycardia after cardiac surgery in an infant. Postoperatively, the patient suffered profound cardiac decompensation secondary to the accelerated rhythm and required extracorporeal membrane oxygenation (ECMO) for haemodynamic support. CLINICAL FEATURES: A 14-day-old, 3.5 kg boy exhibited junctional ectopic tachycardia after cardiopulmonary bypass. Left atrial pressure was 25-28 mmHg. No impact on the tachycardia was seen after rapid overdrive atrial pacing or after 20 micrograms fentanyl i.v., 45 micrograms digitalis, 100 mg magnesium or procainamide (loading dose 15 mg, then 30 mg.kg-1.min-1). Active cooling decreased the nasopharyngeal temperature to 35.2 degrees C, when the heart rate decreased below 180 bpm with a left atrial pressure of 8-10 mmHg. Dopamine (2 micrograms.kg-1.min-1) and dobutamine (5 micrograms.kg-1.min-1) were added to improve the cardiac output. Sodium nitroprusside (0.25 to 1 microgram.kg-1.min) maintained the systolic pressure < 100 mmHg. On arrival in ICU, heart rate increased to 200 bpm. The patient received cardiac massage for severe hypotension 75 min after surgery. Emergency ECMO was instituted for circulatory support. Procainamide, digoxin, dopamine, dobutamine, sodium nitroprusside and hypothermia were continued. Sinus rhythm resumed on the first postoperative day, but procainamide and induced hypothermia at 34 degrees C were maintained for 36 hr after normalization of the rhythm to prevent recurrence of the tachycardia. Total duration of ECMO was three and a half days. Recovery was uneventful. CONCLUSION: The use of ECMO, as a first line of defence, is suitable for the emergency support of patients with JET because of the ease of support of circulation and precise control of hypothermia.     

Deliberate hypotensive epidural anesthesia for patients with normal and low cardiac output

The use of hypotensive anesthesia is contraindicated in patients with ventricular dysfunction, even though afterload reduction often improves ventricular performance. The purpose of this study was to prospectively assess systemic hemodynamic responses to deliberate hypotension with epidural anesthesia in patients with chronic left ventricular dysfunction. Hemodynamic measurements were performed in 29 patients undergoing total hip arthroplasty under deliberate hypotensive epidural anesthesia using low-dose intravenous epinephrine infusion to maintain mean arterial pressure (MAP) at 50-60 mm Hg. Intraoperative MAP decreased from 100 +/- 16 to 56 +/- 9 mm Hg by 30 min after epidural injection (P < 0.0005). Concurrently, cardiac index (CI) increased from a preanesthetic baseline value of 2.9 +/- 0.5 to 3.3 +/- 0.9 L.min-1.m-2 at 30 min (P < 0.005) after epidural injection and stroke volume index (SVI) increased from 41 +/- 8 to 50 +/- 14 mL.beat-1.m-2 30 min after epidural injection (P < 0.005). Heart rate and central venous and pulmonary artery diastolic pressures were maintained under hypotension with epidural anesthesia in all patients. During deliberate hypotension with epidural anesthesia, patients with a history of congestive heart failure or low preanesthetic CI (< or = 2.5 L.kg-1.m-2) increased their CI and SVI into the normal range. There were no significant perioperative complications in either of these groups. Hypotensive epidural anesthesia can be used successfully in patients with low cardiac output from ventricular dysfunction undergoing total hip arthroplasty.     

Selection of the optimal nonexercise stress for the evaluation of ischemic regional myocardial dysfunction and malperfusion. Comparison of dobutamine and adenosine using echocardiography and 99mTc-MIBI single photon emission computed tomography

BACKGROUND: The mechanisms of action of exercise-simulating and vasodilator stressors support their combination with imaging techniques that evaluate left ventricular function and perfusion, respectively. However, reported accuracies of either pharmacological stress together with two-dimensional echocardiography (2DE) or single photon emission computed tomography (SPECT) of myocardial perfusion are similar. The purpose of this study was to establish the optimal stress for each imaging technique by comparing the results of digitized 2DE and 99mTc-methoxyisobutyl isonitrile (MIBI) SPECT using both dobutamine and adenosine stresses in the same patients and conditions. METHODS AND RESULTS: Ninety-seven consecutive patients without evidence of previous infarction undergoing coronary angiography for clinical indications were studied prospectively. Dobutamine was infused during clinical, ECG, and echocardiographic monitoring in dose increments from 5 to 40 micrograms.kg-1.min-1. Adenosine was infused under the same conditions in doses of 0.10, 0.14, and 0.18 mg.kg-1.min-1. For each protocol, the end points were achievement of peak dose, development of severe ischemia, or intolerable side effects. At peak stress, 20 mCi of MIBI was injected, and SPECT imaging was performed 2 hours later; abnormal poststress images were compared with resting SPECT: Digitized 2DE images were compared qualitatively before, during, and after stress in a cine-loop display. Significant coronary disease (n = 59 patients) was defined by the quantification of > 50% stenosis in a major epicardial vessel. The sensitivity of adenosine 2DE was 58%, less than those of adenosine MIBI (86%, p = 0.001), dobutamine 2DE (85%, p = 0.001), and dobutamine MIBI (80%, p = 0.01). Their respective specificities were 87%, 71%, 82%, and 74% (p = NS). The accuracy of adenosine 2DE was 69%, compared with 80% for adenosine MIBI (p < 0.001), 84% for dobutamine 2DE (p = 0.001), and 77% for dobutamine MIBI (p = 0.005); the latter three did not differ significantly in either sensitivity or accuracy. CONCLUSIONS: This prospective, direct comparison of alternative pharmacological stresses in patients without myocardial infarction shows vasodilator stress scintigraphy and dobutamine stress echocardiography and scintigraphy to share equivalent levels of sensitivity. All three are significantly more sensitive than adenosine stress echocardiography. Dobutamine stress may be used for wall motion or perfusion imaging, but adenosine stress is best combined with perfusion scintigraphy.     

Complete unloading alone may not adequately protect the left ventricle

BACKGROUND: The benefit of left ventricular (LV) unloading for preserving LV function is commonly accepted, but its efficacy remains incompletely defined. METHODS: We studied the influence of complete LV unloading on LV systolic and diastolic mechanics using an in situ isovolumic preparation with two different coronary perfusion pressures (CPPs) in 12 dogs during prolonged normothermic cardiopulmonary bypass. RESULTS: Multivariate analysis of covariance with time as a covariate revealed that a high CPP (143 +/- 36 mm Hg; n = 6) was associated with better preservation of systolic LV function over time as assessed by LV end-systolic elastance (p < 0.001) and the end-systolic pressure-volume relation physiologic intercept (p < 0.001) compared with a moderate CPP (107 +/- 18 mm Hg; p < 0.005 versus a high CPP by t-test; n = 6). Dobutamine (2 micrograms.kg-1.min-1) improved LV end-systolic elastance (p < 0.005) and LV physiologic intercept (p < 0.01) only in the high-CPP group. Conversely, impaired LV diastolic function (as measured by LV stiffness) was observed (p < 0.001) with a high CPP, but did not change with a moderate CPP. CONCLUSIONS: These observations in canine hearts suggest that complete LV unloading may not preserve LV systolic function adequately over time when CPP is maintained in the accepted clinical range. A higher CPP is required to prevent deterioration over prolonged cardiopulmonary bypass times, but diastolic dysfunction still occurs.     

Ways of knowing

BACKGROUND: Although it has become clear that habitual exercise in older individuals can partially offset age-associated cardiovascular declines, it is not known whether the beneficial effects of exercise training in older individuals depend on their prior fitness level. METHODS AND RESULTS: Ten sedentary men (S), age 60.0 +/- 1.6 years (mean +/- SEM), who were carefully screened to exclude cardiac disease underwent exercise training for 24 to 32 weeks, and eight age-matched endurance-trained men (ET) stopped their exercise training for 12 weeks. All underwent treadmill exercise and rest and maximal cycle exercise upright gated blood pool scans at baseline and after the lifestyle intervention. Before the intervention, the treadmill maximum rate of oxygen consumption (Vo2max) was 49.9 +/- 1.9 and 32.1 +/- 1.4 mL.kg-1.min-1 in ET and S, respectively. During upright cycle exercise at exhaustion, although heart rate did not differ between groups, cardiac index, stroke volume index, ejection fraction, and left ventricular contractility index (systolic blood pressure/end-systolic volume index) all were significantly higher, and end-systolic volume index, diastolic blood pressure, and total systemic vascular resistance all were significantly lower in ET versus S. After the partial deconditioning of ET men, Vo2max fell to 42 +/- 2.2 mL.kg-1.min-1, and training of S increased Vo2max to 36.2 +/- 1.6 mL.kg-1.min-1. Training of S had effects on cardiovascular function that were similar in magnitude but directionally opposite those of detraining ET. All initial differences in cardiovascular performance at peak work rate between S and ET were abolished with the intervention. Across the broad range of fitness levels encountered before and after change in training status (Vo2max of 26 to 58 mL.kg-1.min-1), cardiac index, stroke volume index, end-systolic volume index, ejection fraction, and the left ventricular contractility index were all linearly correlated with Vo2max. CONCLUSIONS: Exercise training or detraining of older men results in changes in left ventricular performance that are qualitatively and quantitatively similar, regardless of the initial level of fitness before the intervention.     

Fenoldopam improves renal hemodynamics impaired by positive end-expiratory pressure

BACKGROUND: Mechanical ventilation with positive end-expiratory pressure (PEEP) can impair renal hemodynamics. Fenoldopam, a dopamine receptor agonist, has been shown, in animal experiments, to improve renal perfusion. The purpose of the current study was to examine the effects of this agent on altered renal hemodynamics secondary to positive pressure ventilation. METHODS: Twelve patients requiring mechanical ventilation of their lungs and PEEP for the treatment of hypoxemia after multiple trauma or visceral surgery were studied. Hemodynamic variables, renal vascular resistance, urine flow, creatinine, inulin and PAH clearance, and excretion of sodium and potassium (NaE and KE) were measured before and after introduction of a level of PEEP high enough to decrease urine flow rate by 25% or more, and after administration of intravenous fenoldopam. RESULTS: No hemodynamic effect resulted from 0.1 microgram.kg-1.min-1, but 0.2 micrograms.kg-1.min-1 fenoldopam decreased both diastolic and mean arterial blood pressure from 66 +/- 37 (mean +/- SEM) to 57 +/- 21 mmHg, and from 83 +/- 3 to 74 +/- 4 mmHg, respectively. Renal vascular resistance was reduced from 54 +/- 12 to 19 +/- 5 dynes.s.cm-5 at 0.2 micrograms.kg-1.min-1. Fenoldopam produced a dose-related increase in renal blood flow and PAH clearance. With 0.2 micrograms.kg-1.min-1 fenoldopam, urine flow increased from 81 +/- 25 to 116 +/- 29 ml/h, NaE from 28 +/- 7 to 85 +/- 70 microM/min, and KE from 65 +/- 12 to 109 +/- 16 microM/min. CONCLUSIONS: The results of the current study indicate that intravenous fenoldopam at a dose of 0.2 micrograms.kg-1.min-1 improves renal hemodynamics and increases Na and K excretion in patients requiring mechanical ventilation of their lungs and PEEP. These effects are probably caused by an increased kidney perfusion secondary to renal artery vasodilation.     

Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography

Transfusion-dependent (TD) patients develop cardiac iron overload that will eventually lead to cardiac pump failure. Low-dose dobutamine stress echocardiography may complement resting echocardiography and identify preclinical myocardial dysfunction caused by early cardiac hemosiderosis. Twenty-six iron-overloaded TD patients had stress echocardiography with 5 microg/kg per minute of dobutamine. Indexed left ventricular (LV) mass, LV dimensions, meridional wall stress, and cardiac index were significantly increased. TD patients had similar LV shortening fraction by M-mode (40.5% +/- 5.6% vs 39.4% +/- 4.5%) but had a lower mean LV ejection fraction (53.3% +/- 3.9% vs 46.8% +/- 6.9%, P < .002) and a subnormal increase in cardiac index during dobutamine stress (35% +/- 20% vs 11% +/- 16%, P < .0001). Impairment in LV relaxation was demonstrated by a prolonged isovolumetric relaxation time (0.060 +/- 0.005 vs 0.088 +/- 0.019 seconds, P < .0001), increased peak mitral E wave, and abnormal E/A ratio. Asymptomatic TD patients demonstrate decreased systolic functional reserve and abnormal left ventricular relaxation that may be caused by cardiac hemosiderosis. Low-dose dobutamine stress echocardiography may be useful for detecting and following cardiac dysfunction in patients at risk for cardiac hemosiderosis.     

Total intravenous anaesthesia with sufentanil-midazolam for major abdominal surgery

Haemodynamic and endocrine stress responses were compared during total intravenous anaesthesia with sufentanil and midazolam or fentanyl and midazolam in patients undergoing elective major abdominal surgery. Twenty-two ASA I and II patients were allocated randomly to receive sufentanil (induction 1.5 micrograms kg-1 plus infusion 1.5 micrograms kg-1 h-1) or fentanyl (induction 10 micrograms kg-1 plus infusion 10 micrograms kg-1 h-1) supplemented with 0.15 microgram kg-1 sufentanil or 1 microgram kg-1 fentanyl as necessary. Midazolam was infused to obtain plasma concentrations of 500-600 ng ml-1. Ventilation was with oxygen-enriched air. The opioid infusion was reduced post-operatively by half and benzodiazepine effects were reversed by titration with flumazenil. Mean arterial pressure, heart rate and cardiac index decreased in both groups after induction (cardiac index: sufentanil 4.94 +/- 0.45 to 2.99 +/- 0.18 litre min-1; fentanyl 4.97 +/- 0.45 to 3.71 +/- 0.36 litre min-1), but all returned to baseline during surgery. With sufentanil; mean arterial pressure was lower throughout the study period, and heart rate was lower intra-operatively. Oxygen uptake decreased in both groups after induction (sufentanil 289 +/- 29 to 184 +/- 21 ml min-1; fentanyl 318 +/- 32 to 216 +/- 32 ml min-1) and remained low with sufentanil until flumazenil was given. Adrenaline concentrations increased in both groups but there was no intergroup difference. The median noradrenaline concentration was lower intra-operatively with sufentanil (0.47 nmol litre-1 (range 0.06-6.77)) than with fentanyl (0.73 nmol litre-1 (0.07-4.58)). Cortisol, glucose and lactate concentrations increased in both groups. Bradycardia occurred in four patients with sufentanil and in three with fentanyl. There were two cases of marked thoracic rigidity with sufentanil and one with fentanyl.     

Effects of loprinone hydrochloride on hemodynamics and respiratory oxygenation in patients after cardiac surgery

Loprinone hydrochloride (Lop), a phosphodiesterase fraction III inhibitor and positive inotrope, was recently released in Japan. We evaluated its dose-related effects on hemodynamics and oxygenation as as well as on plasma levels of Lop in ten patients after cardiac surgery. Immediately after admission to the intensive care unit, baseline hemodynamics and arterial blood gas data were obtained; patients with inotropic support, were given 0.1, 0.2, 0.3 microgram.kg-1.min-1.lop over 1 hour incrementally, and additional data were obtained. CI increased significantly from baseline (2.1 +/- 0.3 l.min-1.m-2) to 3.2 +/- 0.8 at 0.3 microgram.kg-1.min-1. Systemic vascular resistance decreased significantly from baseline (2853 +/- 439 dynes.sec.cm-5.m-2) to 1554 +/- 440 at 0.3 micrograms. kg-1.min-1, and mean arterial pressure also decreased significantly from baseline. There were no significant changes in heart rate (HR), central venous pressure (CVP), pulmonary artery occlusion pressure (PAOP), or PaO2.FIO2(-1) in patients over the period evaluated. Plasma levels of Lop rapidly increased to 27.8 ng.ml-1 (effective level; 20 ng.ml-1) at 0.3 microgram.kg-1.min-1. In this study, Lop was shown to effectively increase CI in patients after cardiac surgery with no significant changes in HR, CVP, PAOP or PaO2/FIO2. Thus, Lop has a beneficial effect in the treatment of patients with low cardiac output immediately after cardiac surgery.     

Comparison of biological activity of high molecular weight and low molecular weight forms of immunoreactive prolactin from human serum in cultured lymphoma NB2 cells

The aim of this study was to determine the cardiac performance of conscious healthy dogs during stimulation with dobutamine. Eight healthy unsedated beagle dogs were used. Cardiac output was measured by the thermodilution technique and blood pressures by extravascular pressure transducers. Dobutamine challenge at a dosage ranging from 27.5 to 50 micrograms kg-1 min-1 induced a significant rise in cardiac power index (CPI), cardiac index (CI), stroke index (SI) and heart rate (HR) and a significant decrease in pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR). The highest CPI was 2.05 times greater than its basal resting value. The CI was primarily responsible for this increase in CPI. The SI and HR contributed approximately 55 per cent and 45 per cent respectively of the maximal increase in CI.     

Intravenous almitrine combined with inhaled nitric oxide for acute respiratory distress syndrome. The NO Almitrine Study Group

Inhaled nitric oxide (iNO), a selective pulmonary vasodilator and intravenously administered almitrine, a selective pulmonary vasoconstrictor, have been shown to increase PaO2 in patients with acute respiratory distress syndrome (ARDS). This prospective study was undertaken to assess the cardiopulmonary effects of combining both drugs. In 48 consecutive patients with early ARDS, cardiorespiratory parameters were measured at control, after iNO 5 ppm, after almitrine 4 micrograms. kg-1. min-1, and after the combination of both drugs. In 30 patients, dose response to 2, 4, and 16 micrograms. kg-1. min-1 of almitrine with and without NO was determined. Almitrine and lactate plasma concentrations were measured in 17 patients. Using pure O2, PaO2 increased by 75 +/- 8 mm Hg after iNO, by 101 +/- 12 mm Hg after almitrine 4 micrograms. kg-1. min-1, and by 175 +/- 18 mm Hg after almitrine combined with iNO (p < 0.001). In 63% of the patients, PaO2 increased by more than 100% with the combination of both drugs. Mean pulmonary artery pressure (Ppa) increased by 1.4 +/- 0.2 mm Hg with almitrine 4 micrograms/kg/ min (p < 0.001) and decreased by 3.4 +/- 0.4 mm Hg with iNO and by 1.5 +/- 0.3 mm Hg with the combination (p < 0.001). The maximum increase in PaO2 was obtained at almitrine concentrations <= 4 micrograms. kg-1. min-1, whereas almitrine increased Ppa dose-dependently. Almitrine plasma concentrations also increased dose-dependently and returned to values close to zero after 12 h. In many patients with early ARDS, the combination of iNO 5 ppm and almitrine 4 micrograms. kg-1. min-1 dramatically increases PaO2 without apparent deleterious effect allowing a rapid reduction in inspired fraction of O2. The long-term consequences of this immediate beneficial effect remain to be determined.     

Pharmacokinetics of intravenous milrinone in patients undergoing cardiac surgery

BACKGROUND: Milrinone is a phosphodiesterase inhibitor with positive inotropic and vasodilator effects that are useful in the treatment of ventricular dysfunction after cardiac surgery. However, the pharmacokinetics of the drug have been investigated only in healthy volunteers and in patients with chronic congestive heart failure. This study investigates the pharmacokinetics of milrinone in adult cardiac surgical patients after cardiopulmonary bypass. METHODS: Milrinone was administered to 25 patients just before or immediately after separation from cardiopulmonary bypass. Arterial blood was sampled over the next 16 h and milrinone plasma concentrations were determined by high-performance liquid chromatography. Data were analyzed by extended nonlinear least-squares regression. The relation between milrinone plasma concentration and hemodynamic effect was examined in an additional 11 patients who had cardiac indices less than 2.5 l.min-1.m-2 immediately after separation from cardiopulmonary bypass. Milrinone was administered and plasma concentrations were related to changes in cardiac index during the next 10 min. RESULTS: A milrinone dose of 50 micrograms/kg in conjunction with an infusion of 0.5 micrograms.kg-1.min-1 consistently maintained plasma concentrations in excess of 100 ng/ml. A triexponential equation describing the plasma concentration as a function of time was used to describe the data. Central-compartment volume was 102 ml/kg, volume of distribution was 1,698 ml/kg, and elimination clearance was 1.88 ml.kg-1.min-1. Pharmacokinetic parameters were independent of dose. The relation between plasma concentration and percentage increase in cardiac index could be described by a sigmoidal curve with the plasma concentration associated with a 50% increase in cardiac index equal to 167 ng/ml. CONCLUSIONS: A milrinone dose of 50 micrograms/kg with an infusion at 0.5 micrograms.kg-1.min-1 maintains plasma concentrations at or above the threshold of therapeutic effects.     

Hematopoietic effects and clinical uses of granulocyte-macrophage colony-stimulating factor and PIXY321

We tested the influence of in vivo volume resuscitation on intrinsic contractile properties of left ventricular (LV) preparations of endotoxemic guinea pigs. Escherichia coli endotoxin (LPS)-injected animals were divided into nonresuscitated and resuscitated groups. Volume resuscitation improved cardiac output and stroke volume, increased arterial pH and body temperature, and decreased mortality. In isovolumetric LV preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) preparations isolated 4 h after LPS injection, LV systolic pressures (in mmHg) of LPS with (42 +/- 3) and without (42 +/- 2) fluid resuscitation were consistently less than control values (70 +/- 3). LV end-diastolic pressure-volume (compliance) decreased in LPS-nonresuscitated hearts, while LV compliance of LPS-resuscitated hearts was similar to control. Thus, intravascular volume expansion selectively improved LV diastolic compliance of LPS hearts without affecting LV systolic function. These findings suggest that LV systolic and diastolic dysfunctions associated with endotoxemia and Gram-negative sepsis may involve separate pathogenic mechanisms.     

Value of single oral loading dose of propafenone in converting recent-onset atrial fibrillation. Results of a randomized, double-blind, controlled study

OBJECTIVE: To assess the effects of dobutamine at a rate of 5 micrograms/kg/min on hemodynamics and gastric intramucosal acidosis in patients with hyperdynamic septic shock treated with epinephrine. DESIGN: A prospective, interventional, clinical trial. SETTING: An adult, 16-bed medical/surgical intensive care unit of a university hospital. PATIENTS: Twenty septic shock patients with a mean arterial pressure of > 75 mm Hg and a cardiac index of > 3.5 L/min/m2. INTERVENTIONS: After baseline measurements (H0), each patient received dobutamine at a rate of 5 micrograms/kg/min. Baseline measurements included: hemodynamic parameters, tonometric parameters, arterial and mixed venous gases, and arterial lactate concentrations. These measurements were repeated after 1 (H1), 2 (H2), and 3 (H3) hrs. After H2 measurements, dobutamine was stopped. The patients were separated into two groups according to their PCO2 gap (tonometer PCO2-PaCO2). The increased PCO2 gap group was defined by a PCO2 gap > 8 torr (> 1.1 kPa) (n = 13), and the normal PCO2 gap group by a PCO2 gap < or = 8 torr (< or = 1.1 kPa)(n = 7). MEASUREMENTS AND MAIN RESULTS: Dobutamine at 5 micrograms/kg/min had no significant effects on mean arterial pressure, heart rate, cardiac index, systemic vascular resistance, oxygen delivery, and oxygen consumption in epinephrine-treated septic shock. No patients developed arrhythmia or electrocardiographic signs of myocardial ischemia. During dobutamine infusion, arterial lactate concentration decreased from 5.1 +/- 0.4 in the increased PCO2 gap group and 4.2 +/- 0.4 in the normal PCO2 gap group to 3.9 +/- 0.3 and 3.5 +/- 0.3 mmol/L, respectively (p < .01). The PCO2 gap decreased and gastric intramucosal pH increased in the increased PCO2 gap group from 12 +/- 0.8 (1.6 +/- 0.1 kPa) to 3.5 +/- 0.8 torr (0.5 +/- 0.1 kPa) (p < .01) and from 7.11 +/- 0.03 to 7.18 +/- 0.02 (p < .01), respectively, and did not change in the normal PCO2 gap group. After stopping dobutamine infusion, the PCO2 gap and intramucosal pH returned to baseline values in the increased PCO2 gap group. CONCLUSION: The addition of 5 micrograms/kg/min of dobutamine added to epinephrine in hyperdynamic septic shock selectively improved the adequacy of gastric mucosal perfusion without modification in systemic hemodynamics.     

Left ventricular diastolic filling alterations in subjects with mitral valve prolapse: a Doppler echocardiographic study

To assess left ventricular diastolic filling in mitral valve prolapse (MVP), we studied 22 patients with idiopathic MVP and 22 healthy controls matched for sex, age, body surface area and heart rate. A two-dimensional, M-mode and Doppler echocardiographic examination was performed to exclude any cardiac abnormalities. The two groups had similar diastolic and systolic left ventricular volumes, left ventricle mass and ejection fraction. Doppler measurements of mitral inflow were: E and A areas (the components of the total flow velocity-time integral in the early passive period of ventricular filling, E; and the late active period of atrial emptying, A), the peak E and A velocities (cm.s-1), acceleration and deceleration half-times (ms) of early diastolic rapid inflow, acceleration time of early diastolic flow (AT), total diastolic filling time (DFT) (ms), and the deceleration of early diastolic flow (cm.s-2). From these measurements were calculate: peak A/E ratio (A/E), E area/A area, the early filling fraction, the atrial filling fraction, AT/DFT ratio. All the Doppler measurements reported are the average of three cardiac cycles selected at end expiration. The mean peak A velocity, A/E velocity ratio, deceleration half time and atrial filling fraction were each significantly higher for subjects presenting a MVP (60 +/- 12 cm.s-1 vs 49 +/- 14, P < 0.008; 98 +/- 13% vs 64 +/- 12%, P < 0.0001; 120 +/- 36 ms vs 92 +/- 11, P < 0.002; 0.45 +/- 0.14 vs 0.36 +/- 0.08, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)