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Biomedical subjects

Z Vered

Publications and source records attributed to Z Vered.

At least 19 recordsLinked to original sources
PubMed2003

Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial.

BACKGROUND: The improvement in left-ventricular ejection fraction (LVEF) in response to beta blockers is heterogeneous in patients with heart failure due to ischaemic heart disease, possibly indicating variations in the myocardial substrate underlying left-ventricular dysfunction. We investigated whether improvement in LVEF was associated with the volume of hibernating myocardium (viable myocardium with contractile failure). METHODS: We did a double-blind, randomised trial to compare placebo and carvedilol for 6 months in individuals with stable, chronic heart failure due to ischaemic left-ventricular systolic dysfunction. We enrolled 489 patients, of whom 387 were randomised. Patients were designated hibernators or non-hibernators according to the volume of hibernating myocardium. The primary endpoint was change in LVEF, measured by radionuclide ventriculography, in hibernators versus non-hibernators, on carvedilol compared with placebo. Analysis was by intention to treat. RESULTS: 82 patients dropped out of the study because of adverse events, withdrawal of consent, or failure to complete the investigation. Thus, 305 (79%) were analysed. LVEF was unchanged with placebo (mean change -0.4 [SE 0.9] and -0.4 [0.8] for non-hibernators and hibernators, respectively) but increased with carvedilol (2.5 [0.9] and 3.2 [0.8], respectively; p<0.0001 compared with baseline). Mean placebo-subtracted change in LVEF was 3.2% (95% CI 1.8-4.7; p=0.0001) overall, and 2.9% (0.7-5.1; p=0.011) and 3.6% (1.7-5.4; p=0.0002) in non-hibernators and hibernators, respectively. Effect of hibernator status on response of LVEF to carvedilol was not significant (0.7 [-2.2 to 3.5]; p=0.644). However, patients with more myocardium affected by hibernation or by hibernation and ischaemia had a greater increase in LVEF on carvedilol (p=0.0002 and p=0.009, respectively). INTERPRETATION: Some of the effect of carvedilol on LVEF might be mediated by improved function of hibernating or ischaemic myocardium, or both. Medical treatment might be an important adjunct or alternative to revascularisation for patients with hibernating myocardium.

Adrenergic beta-Antagonists↗
PubMed2002

Left ventricular preload and function during graded haemorrhage and retranfusion in pigs: analysis of arterial pressure waveform and correlation with echocardiography.

BACKGROUND: Arterial pressure waveform analysis is a new method for assessment of cardiac preload. Despite the close correlation of parameters derived by its use with the degree of blood loss, their relationship with more precise estimates of cardiac preload remains controversial. METHODS: Systolic pressure variation (SPV), delta up (dUp), and delta down (dDown), which are the changes in the arterial blood pressure (BP) during mechanical ventilation, were measured during graded haemorrhage and retransfusion in seven pigs under light halothane anaesthesia, and compared with changes in cardiac filling pressures and left ventricular end-diastolic volume (LVEDV), measured by echocardiography. RESULTS: Significant changes in preload parameters and stroke volume (SV) but not in BP and heart rate occurred. SPV, dDown, and cardiac filling pressures correlated significantly with LVEDV. Following retransfusion, LVEDV returned to baseline values but the SV and left ventricular ejection fraction were significantly low. This deterioration in myocardial performance was associated with elevated dUp. CONCLUSIONS: During mechanical ventilation, dDown and the SPV may serve as minimally invasive indicators of preload. The retransfusion stage that follows significant blood loss may be associated with deterioration in LV function.

Animals↗
PubMed2001

Tezosentan (an intravenous endothelin receptor A/B antagonist) reduces peripheral resistance and increases cardiac power therefore preventing a steep decrease in blood pressure in patients with congestive heart failure.

OBJECTIVE: This study investigated the effect of tezosentan (an intravenous endothelin-1 receptor antagonist) on vascular resistance and cardiac function and determined the dose response in patients with stable congestive heart failure (CHF) due to left ventricular systolic dysfunction. METHODS: In a double-blind fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50, 100 mg h(-1)) to 38 CHF (NYHA class III) patients with ejection fraction or=15 mmHg. Systemic vascular resistance index (SVRi) was estimated as mean arterial blood pressure [(MAP-right atrial pressure)/cardiac index (CI)]. Cardiac function was assessed as cardiac power index (Cpi), calculated as pressure x flow (MAP x CI), where MAP represents pressure and CI represents cardiovascular flow. RESULTS AND DISCUSSION: Compared to the placebo, tezosentan induced a dose-dependent decrease in SVRi (-32%), an increase in Cpi (+20%) and a small decrease in MAP (-9%). By contrast, patients treated with nitrate vasodilators or nesiritide (a natriuretic peptide) showed a decrease in SVRi not accompanied by a significant increase in Cpi leading to a steep decrease in MAP. CONCLUSIONS: The use of Cpi in the assessment of the hemodynamic effects of tezosentan, provides a useful alternative characterization of the complex influences of vasodilators on cardiac function in patients with CHF.

Adult↗
PubMed2001

Shu 508 A (Levovist)-enhanced Doppler echocardiography improves the assessment of valvular heart disease.

OBJECTIVE: To investigate whether intravenous injection of SHU 508 A improves the diagnostic accuracy of Doppler echocardiography in the assessment of valvular pathologies. METHODS AND RESULTS: One hundred and twenty-five consecutive patients with valvular pathology (aortic stenosis, n = 48; aortic regurgitation, n = 20; mitral stenosis, n = 21; and mitral regurgitation, n = 36) and diagnostically insufficient Doppler signal were enrolled in this multicenter study. The severity of valvular pathology was graded on a four-point scale using unenhanced and contrast-enhanced Doppler echocardiography as well as cardiac catheterization. Agreement with cardiac catheterization findings increased from 63% using the unenhanced examination to 73% using the contrast-enhanced Doppler examination. Grading was possible in all patients using SHU 508 A, whereas the unenhanced Doppler examination remained inconclusive in six patients. The weighted kappa coefficient between contrast-enhanced Doppler and cardiac catheterization for all diagnoses was 0.76 as compared to 0.68 between unenhanced Doppler and cardiac catheterization. Agreement was especially improved in aortic stenosis (kappa 0.69 unenhanced vs 0.81 contrast-enhanced) and in aortic regurgitation (kappa 0.45 unenhanced vs 0.75 contrast-enhanced). Patients with mitral stenosis and mitral regurgitation experienced less improvement. CONCLUSIONS: In case of an inconclusive unenhanced Doppler echo study, the administration of a left heart contrast agent should be considered. SHU 508 A is especially useful in improving the severity grading of aortic stenosis and aortic regurgitation, while grading of mitral stenosis and mitral regurgitation is less improved.

Adult↗
PubMed2001

Retrograde embolism and atherosclerosis development in the human thoracic aorta: are the fluid dynamics explanations valid?

The mechanisms of atherosclerosis development in the thoracic aorta is miscellaneous and still only partially understood. The marked variability of the sites of deposition of atherosclerotic plaques in the aorta could not be clarified based solely on the risk-factors theory of atherosclerosis. The sites of deposition of atherosclerotic plaques are considered to be affected by blood-flow patterns that cause areas of altered shear stress on the aortic wall. Close relations between protruding aortic plaques (PAP), stroke and peripheral emboli were established. The analysis of PAP distribution and motion to characterize atherogenesis in the human thoracic aorta and the pathogeneses of embolic events was performed. We concluded that protruding aortic plaques and markers of relative aortic flow instability (occurrences of vortices) are predominantly noticed in the human arch and in the descending aorta, whereas the ascending aorta showed lesser prevalence of atheromatosis. Reversal and rotational blood-flow in the thoracic aorta most likely exist in all patients with systemic emboli and mobile protruding aortic atheromas. Therefore, retrograde cerebral embolism from distal aortic plaques is conceivable.

Adolescent↗
PubMed2001

Caseous calcification of the mitral annulus: a neglected, unrecognized diagnosis.

BACKGROUND: Mitral annular calcification is a common echocardiographic finding. Caseous calcification is a rare variant seen as a large mass with echolucencies that resembles a tumor, occasionally resulting in exploratory cardiotomy. The aim of this study was to assess the prevalence of caseous calcification of the mitral annulus, to evaluate patient characteristics and the echocardiographic variables for diagnosing this entity, and to describe the clinical outcome on follow-up of such patients. METHODS: Caseous calcification was defined as a large, round, echo-dense mass with smooth borders situated in the periannular region, with no acoustic shadowing artifacts and containing central areas of echolucencies resembling liquefaction. Eighteen patients were diagnosed by 2-dimensional echocardiography as having caseous calcification of the mitral annulus. One had calcification of the tricuspid annulus. Nine patients underwent transesophageal echocardiographic studies. RESULTS: A typical finding of a round, sometimes semilunar, large, echo-dense, soft mass with central echolucencies seen on both transthoracic and in particular transesophageal echocardiography, resembling a periannular mass, was demonstrated. The mass was posteriorly located in all mitral patients. Transesophageal echocardiography added limited information. Three patients underwent mitral valve replacement. The operative findings were a solid mass adherent to the posterior portion of the mitral valve. Sectioning revealed a toothpaste-like, white, caseous material. Sixteen (84%) patients were treated conservatively. On follow-up of 3.8 +/- 2.4 years, 4 patients died of unrelated causes. CONCLUSION: The characteristic appearance of a large, soft, echo-dense mass containing central areas of echolucencies resembling liquefaction at the posterior periannular region of the mitral valve on 2D echocardiography is compatible with the diagnosis of caseous abscess. Such a finding should not be confused with a tumor. Transesophageal echocardiography does not appear to contribute to the diagnosis. This rather impressive lesion appears to carry a benign prognosis.

Aged↗
PubMed2001

Pulmonary edema: new insight on pathogenesis and treatment.

Pulmonary edema is one of the most serious and life-threatening situations in emergency medicine. Lately it has become apparent that in most cases pulmonary edema is not caused by fluid accumulation but rather fluid redistribution that is directed into the lungs because of heart failure. Based on a series of recently published studies, we propose that often the pathogenesis of pulmonary edema is related to a combination of marked increase in systemic vascular resistance superimposed on insufficient systolic and diastolic myocardial functional reserve. This resistance results in increased left ventricular diastolic pressure causing increased pulmonary venous pressure, which yields a fluid shift from the intravascular compartment into the pulmonary interstitium and alveoli, inducing the syndrome of pulmonary edema. Therefore, the emphasis in treating pulmonary edema has shifted from diuretics (ie, furosemide) to vasodilators (ie, high-dose nitrates) combined with noninvasive positive airway pressure ventilation and rarely inotropes. New classes of drugs that are currently being investigated for treating decompensated heart failure such as natriuretic peptides, calcium promoters, and endothelin antagonist are also being assessed for treating pulmonary edema. This review will explore this new hypothesis put forward to explain the pathogenesis of pulmonary edema and the evolving management strategies.

Humans↗
PubMed2001

Insulin-like growth factor I and II preserve myocardial structure in postinfarct swine.

BACKGROUND: Insulin-like growth factors (IGF) I and II improve myocardial function after coronary occlusion in different animal models. OBJECTIVES: To investigate the mechanism of improved myocardial function after administration of IGF-I or IGF-II in acute myocardial infarction. METHODS: Female pigs (mean (SD) weight 25 (5) kg) were subjected to acute myocardial infarction by microembolisation with 75-150 micrometer affigel blue beads. The beads contained and slowly released 150 microgram/pig of IGF-I (n = 6), IGF-II (n = 6), or pig albumin (n = 6). Echocardiography, perfusion imaging, and haemodynamic measurements were performed before infarction and during four weeks after infarction. Regional wall motion of different left ventricular segments was scored semiquantitatively on the basis of a three point scoring system, from normal = 0 to dyskinesia = 3. Serum cardiac troponin I concentration was measured before, immediately after, and three hours after the infarct. Excised hearts were analysed for actin, desmin, blood vessel density, and DNA laddering within the infarct, border, and normal myocardial areas. RESULTS: Myocardial function of the infarct related area improved significantly during the four weeks of follow up in both the IGF groups (p = 0.01). Myocardial perfusion, heart rate, and blood pressure were similar in all the animals during the study. Treated animals had lower serum cardiac troponin I concentration (p = 0.001), more actin in the border area (p = 0.01) and infarct area (p = 0.0001), and reduced DNA laddering in the infarct area compared with the controls (p < 0.05). IGF groups had more blood vessels in the border area (p = 0.04) and the infarct area (p = 0.003). CONCLUSIONS: Both types of IGF improved myocardial function and the improvement was associated with preservation of myocardial structure. IGF-I was more effective than IGF-II.

Actins↗
PubMed2001

Dobutamine echocardiography in patients with aortic stenosis and left ventricular dysfunction: predicting outcome as a function of management strategy.

STUDY OBJECTIVE: To prospectively address the question whether the assessment of valvular hemodynamics and myocardial function during low-dose dobutamine infusion can guide decision making in patients with aortic stenosis and left ventricular (LV) dysfunction. PATIENTS AND MEASUREMENTS: Twenty-four patients with aortic stenosis and LV dysfunction (mean ejection fraction, 28%; New York Heart Association class, II to IV) were studied by dobutamine echocardiography assessing mean pressure gradient, aortic valve area, and aortic valve resistance. Patients were prospectively divided into severe and nonsevere aortic stenosis groups according to the response of the valve area to the augmentation of systolic flow. The clinical decision was considered to be concordant with the results of dobutamine echocardiography, when patients with severe aortic stenosis and preserved contractile function were referred by a specialist for aortic valve replacement and when patients with nonsevere aortic stenosis were not. Patients were observed for up to 3 years. RESULTS: All eight patients with severe aortic stenosis who were referred for surgery survived and had good cardiovascular outcomes, and six of eight patients who were not initially referred for surgery had poor outcomes, including heart failure and sudden cardiac death. The eight patients with nonsevere aortic stenosis did comparatively well without valve replacement. Cardiac death or pulmonary edema occurred in 4 of 16 patients (25%) when the clinical decision was concordant with the results of the dobutamine echocardiogram and occurred in 6 of 8 patients (75%) when the clinical decision was discordant (p = 0.019 [chi(2) test]). CONCLUSION: Patients with aortic stenosis, LV dysfunction, and relatively low gradients have better outcomes when management decisions are based on the results of dobutamine echocardiograms. Those patients identified as having severe aortic stenosis and preserved contractile reserve by dobutamine echocardiography should undergo surgery, while patients identified as having nonsevere aortic stenosis can be managed conservatively.

Aged↗
PubMed2000

Impact of atrioventricular compliance on pulmonary artery pressure in mitral stenosis: an exercise echocardiographic study.

BACKGROUND: The decay of the pressure gradient across a stenotic mitral valve is determined by the size of the orifice and net AV compliance (C(n)). We have observed a group of symptomatic patients, usually in sinus rhythm, characterized by pulmonary hypertension (particularly during exercise) despite a relatively large mitral valve area by pressure half-time. We speculated that this discrepancy was due to low atrial compliance causing both pulmonary hypertension and a steep decay of the transmitral pressure gradient despite significant stenosis. We therefore tested the hypothesis that C(n) is an important physiological determinant of pulmonary artery pressure at rest and during exercise in mitral stenosis. METHODS AND RESULTS: Twenty patients with mitral stenosis were examined by Doppler echocardiography. C(n), calculated from the ratio of effective mitral valve area (continuity equation) and the E-wave downslope, ranged from 1.7 to 8.1 mL/mm Hg. Systolic pulmonary artery pressure (PAP) increased from 43+/-12 mm Hg at rest to 71+/-23 mm Hg (range, 40 to 110 mm Hg) during exercise. There was a particularly close correlation between C(n) and exercise PAP (r=-0.85). Patients with a low compliance were more symptomatic (P<0.025). Catheter- and Doppler-derived values for C(n), determined in 10 cases, correlated well (r=0.79). CONCLUSIONS: C(n), which can be noninvasively assessed, is an important physiological determinant of PAP in mitral stenosis. Patients with low C(n) represent an important clinical entity, with symptoms corresponding to severe increases in PAP during stress echocardiography.

Adult↗
PubMed2000

Prognostic significance of mild mitral regurgitation by color Doppler echocardiography in acute myocardial infarction.

Mitral regurgitation (MR) complicating acute myocardial infarction (AMI) is associated with increased mortality. The prognostic significance of only mild MR detected by echocardiography in patients with AMI is unknown. This study assessed the long-term risk associated with mild MR detected by color Doppler echocardiography within the first 48 hours of admission in 417 consecutive patients with AMI. No MR was detected in 271 patients (65%), mild MR was seen in 121 patients (29%), and moderate or severe MR was noted in 25 patients (6%). One-year mortality rates were 4.8%, 12.4%, and 24%, respectively (p<0.001). Multivariate analysis revealed that mild MR was independently associated with increased 1-year mortality (p<0.05) after adjustment for age, gender, previous myocardial infarction, diabetes mellitus, systemic hypertension, Killip grade > or =2 on admission, and left ventricular ejection fraction < or =40%. The hazard ratio for 1-year mortality was 2.31 (95% confidence interval 1.03 to 5.20) for mild MR and 2.85 (95% confidence interval 0.95 to 8.51) for moderate or severe MR. Thus, mild MR detected by color Doppler echocardiography within the first 2 days of admission in patients with AMI is a significant independent risk predictor for 1-year all-cause mortality.

Adult↗
PubMed2000

Minimal heparinization in coronary angioplasty--how much heparin is really warranted?

The purpose of the study was to assess the results of percutaneous transluminal coronary angioplasty (PTCA), performed with a single intravenous bolus of 2,500 U of heparin, in a nonemergency PTCA cohort. Three hundred of 341 consecutive patients (87.9%) undergoing PTCA were prospectively enrolled in the study. They received heparin, 2,500-U intravenous bolus, before PTCA, with intention of no additional heparin administration. Patient and lesion characteristics as well as PTCA results were evaluated independently by 2 physicians. Patients were followed up by structured telephone questionnaires at 1 and 6 months after PTCA. Mean activated clotting time obtained 5 minutes after heparin administration was 185+/-19 seconds (range 157 to 238). There were 3 (1%) in-hospital major adverse cardiovascular events: 2 deaths (0.66%), 1 (0.33%) Q-wave myocardial infarction. Emergency coronary surgery and stroke were not reported. Six patients (2%) experienced abrupt coronary occlusion within 14 days after PTCA, warranting repeat target vessel revascularization. Angiographic and clinical success were achieved in 96% and 93.3%, respectively. No bleeding or vascular complications were recorded. Six-month follow-up (184 patients) revealed 3 cardiac deaths (1 arrhythmic, 2 after cardiac surgery), 1 Q-wave myocardial infarction, and 9.7% repeat target vessel revascularization. This study suggests that very low doses of heparin and reduced activated clotting time target values are safe in non-emergency PTCA, and can reduce bleeding complications, hospital stay, and costs. Larger, randomized, double-blind heparin dose optimization studies need to confirm this notion.

Angioplasty, Balloon, Coronary↗
PubMed2000

L-NMMA (a nitric oxide synthase inhibitor) is effective in the treatment of cardiogenic shock.

BACKGROUND: The objective was to assess the safety and efficacy of L-NMMA in the treatment of cardiogenic shock. METHODS: We enrolled 11 consecutive patients with cardiogenic shock that persisted after >24 hours from admission, despite coronary catheterization and primary percutaneous transluminal coronary revascularization, when feasible, and treatment with mechanical ventilation, intraaortic balloon pump (IABP), and high doses of catecholamines. L-NMMA was administered as an IV bolus of 1 mg/kg and continuous drip of 1 mg. kg(-1). h(-1) for 5 hours. Treatment with catecholamines, mechanical ventilation, and IABP was kept constant throughout the study. RESULTS: Within 10 minutes of L-NMMA administration, mean arterial blood pressure (MAP) increased from 76+/-9 to 109+/-22 mm Hg (+43%). Urine output increased within 5 hours from 63+/-25 to 156+/-63 cc/h (+148%). Cardiac index decreased during the steep increase in MAP from 2. 0+/-0.5 to 1.7+/-0.4 L/(min. m(2)) (-15%); however, it gradually increased to 1.85+/-0.4 L/(min. m(2)) after 5 hours. The heart rate and the wedge pressure remained stable. Twenty-four hours after L-NMMA discontinuation, MAP (+36%) and urine output (+189%) remained increased; however, cardiac index returned to pretreatment level. No adverse events were detected. Ten out of eleven patients could be weaned off mechanical ventilation and IABP. Eight patients were discharged from the coronary intensive care unit, and seven (64%) were alive at 1-month follow-up. CONCLUSIONS: L-NMMA administration in patients with cardiogenic shock is safe and has favorable clinical and hemodynamic effects.

Aged↗
PubMed2000

Feasibility of mitral flow assessment by echo-contrast ultrasound, part I: determination of the properties of echo-contrast agents.

Data on the ultrasonic properties of commercially available contrast agents are limited by being instrument-dependent, especially with regard to their backscattering properties. The present work describes methods of measurements that provide instrument-independent estimations of a contrast agent's attenuation coefficient and integrated backscatter index and provide them as functions of its concentration. The two studied commercially available contrast agents were Albunex and Levovist SHU 508-A, both representative of agents in common use for echocardiography. The attenuation coefficients and integrated backscatter indices of both agents were found to be a linear function of their concentrations. Proportionality coefficients +/- their standard deviations are provided. Actually, square root values of the averaged backscatter indices normalized with respect to the rms of the reference signal were determined. The coefficients of proportionality were found to be: C(A) = 3.11+/-0.1813 dB/mm; C(L) = 0.07+/-0.005 dB/mm for attenuation coefficients of the Albunex and Levovist contrast agents, respectively, and the corresponding values for backscattering were: D(A) = 0.07+/-0.0054; D(L) = 0.02+/-0.0012. Being apparatus-independent, the findings of the study are important prerequisites for the use of these echo-contrast agents as an indicator in research for a quantitative assessment of blood flow.

Albumins↗
PubMed2000

Feasibility of mitral flow assessment by echo-contrast ultrasound, part II: experimental study on a mechanical model of the left heart.

The feasibility of assessing mitral flow by means of ultrasonic monitoring of backscattered power from an echo-contrast agent in the left atrium and left ventricle was studied. A mechanical model of the left heart was built in which two thin rubber balloons connected to each other in a feedback loop via two artificial heart valves mimicked the left atrium and left ventricle. The model was driven by compressed air. Its input and output flows were measured as the functions of a pacing rate, driving pressure and artificially introduced mitral regurgitation. These were compared with the corresponding data derived from the ultrasonic measurements that are based on the correlation between echo-contrast agent concentration in the volume of interest and the flow through it. Algorithms for quantitative estimations of forward stroke volume (cardiac output) and mitral regurgitation are given. This study shows, for the first time, both analytically and experimentally, that the pulsating modulation of contrast agent concentration vs. time curves in the ventricle and atrium volumes is closely related to the pulsating nature of the flow in the system. It also shows that the amplitude of the atrium concentration modulation is directly proportional to the maximum value of the incoming (to atrium) flow.

Albumins↗
PubMed2000

High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema.

OBJECTIVE: To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy. BACKGROUND: Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities. METHODS: We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival. RESULTS: Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee. CONCLUSIONS: High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema.

Dose-Response Relationship, Drug↗