Effects of nitric oxide inhalation on pulmonary serial vascular resistances in ARDS

The pulmonary vasculature site of action of nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS) is still unknown. Seven patients were studied during the early stage of ARDS. The bedside pulmonary artery single-occlusion technique, which allows estimation of the pulmonary capillary pressure (Pcap) and segmental pulmonary vascular resistance, was used without NO or with increasing inhaled NO concentrations (15 and 25 parts per million [ppm]). Systemic circulatory parameters remained unaltered during 15 ppm NO inhalation, whereas 25 ppm NO inhalation slightly decreased mean systemic arterial pressure from 76.7 +/- 5.1 (mean +/- SEM) to 69 +/- 5.2 mm Hg (p < 0.01). Mean pulmonary arterial pressure (Ppam) and mean pulmonary capillary pressure (Pcapm) fell during 25 ppm NO inhalation from 27.4 +/- 3.5 to 21 +/- 2.2 mm Hg (p < 0.001) and from 14.8 +/- 1.5 to 10.7 +/- 1.4 mm Hg (p < 0.001) respectively, the total pulmonary resistance decreased by 28% (p < 0.01). The resistance of the capillary-venous compartment fell during 25 ppm NO inhalation from 100 +/- 16 to 47 +/- 16 dyn x s x m(2) x cm(-5) (p < 0.01), whereas the pulmonary arterial resistance was unchanged. In these patients NO inhalation during the early stage of ARDS reduces selectively Ppam and Pcapm by decreasing the pulmonary capillary-venous resistance. This latter effect may reduce the filtration through the capillary bed and hence alveolar edema during ARDS.     

Comparison of the effects of potential parenteral vehicles for poorly water soluble anticancer drugs (organic cosolvents and cyclodextrin solutions) on cultured endothelial cells (HUV-EC)

Left atrial (LA) adaptation during the development of left ventricular (LV) dysfunction is not fully understood. We performed echocardiographic assessment of LA volumes simultaneously with recordings of pulmonary wedge pressures in 60 patients. Twenty patients had no structural or functional LV abnormalities, 20 had a recent myocardial infarction with LV dysfunction, and 20 suffered from congestive heart failure (CHF). Pressure-volume loops were obtained at baseline and during increases in LA pressure produced by normal saline infusion. LA afterload was estimated by the effective LV elastance (E(LV)). Atrioventricular coupling was calculated by the E(LV)/E(es) ratio (where E(es) is the end-systolic elastance). E(es) increased in patients with myocardial infarction (0.80 +/- 0.09 mm Hg/ml, p <0.001), whereas it decreased in patients with CHF (0.22 +/- 0.05 mm Hg/ml, p <0.001) compared with controls (0.61 +/- 0.07 mm Hg/ml). Similarly, stroke workload increased in patients with myocardial infarction (60.7 +/- 7.3 mm Hg x ml, p <0.001), whereas it decreased in patients with CHF (25.4 +/- 2.2 mm Hg x ml, p <0.001) compared with controls (44.8 +/- 5.5 mm Hg x ml). In all patients LA stiffness (slope of the relation of the filling portion of the pressure-volume loop) was increased compared with controls (controls: 0.13 +/- 0.04, patients with myocardial infarction: 0.22 +/- 0.05, and patients with CHF: 0.27 +/- 0.05 mm Hg/ml, p <0.001 for both comparisons). Moreover, the E(LV)/E(es) ratio increased gradually as LV function deteriorated (controls: 1.06 +/- 0.10, patients with myocardial infarction: 1.35 +/- 0.16, and patients with CHF: 6.90 +/- 0.84, p <0.001). Thus, early in heart failure, LA pump function is augmented but LA stiffness increases and work mismatch occurs. With further progression of LV dysfunction, LA pump function decreases as a result of increased afterload imposed on the LA myocardium.     

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.     

Effects of continuous positive airway pressure on obstructive sleep apnea and left ventricular afterload in patients with heart failure

BACKGROUND: The objectives of this study were to determine the effects of continuous positive airway pressure (CPAP) on blood pressure (BP) and systolic left ventricular transmural pressure (LVPtm) during sleep in congestive heart failure (CHF) patients with obstructive sleep apnea (OSA). In CHF patients with OSA, chronic nightly CPAP treatment abolishes OSA and improves left ventricular (LV) ejection fraction. We hypothesized that one mechanism whereby CPAP improves cardiac function in CHF patients with OSA is by lowering LV afterload during sleep. METHODS AND RESULTS: Eight pharmacologically treated CHF patients with OSA were studied during overnight polysomnography. BP and esophageal pressure (Pes) (ie, intrathoracic pressure) were recorded before the onset of sleep and during stage 2 non-rapid eye movement sleep before, during, and after CPAP application. OSA was associated with an increase in systolic BP (from 120.4+/-7.8 to 131.8+/-10.6 mm Hg, P<0.05) and systolic LVPtm (from 124.4+/-7.7 to 137.2+/-10.8 mm Hg, P<0.05) from wakefulness to stage 2 sleep. CPAP alleviated OSA, improved oxyhemoglobin saturation, and reduced systolic BP in stage 2 sleep to 115.4+/-8.5 mm Hg (P<0.01), systolic LVPtm to 117.4+/-8.5 mm Hg (P<0.01), heart rate, Pes amplitude, and respiratory rate. CONCLUSIONS: In CHF patients with OSA, LV afterload increases from wakefulness to stage 2 sleep. By alleviating OSA, CPAP reduces LV afterload and heart rate, unloads inspiratory muscles, and improves arterial oxygenation during stage 2 sleep. CPAP is a nonpharmacological means of further reducing afterload and heart rate during sleep in pharmacologically treated CHF patients with OSA.     

Airway occlusion pressure at 0.1 s (P0.1) after extubation: an early indicator of postextubation hypercapnic respiratory insufficiency

OBJECTIVE: To examine variables associated with postextubation respiratory distress in chronic obstructive pulmonary disease (COPD) patients. DESIGN: Prospective, clinical investigation. SETTING: Intensive care unit of a university hospital. PATIENTS: Forty COPD patients, considered ready for extubation. MEASUREMENTS AND MAIN RESULTS: We recorded, from the digital display of a standard ventilator, breathing frequency (f), tidal volume (VT) and f/VT for the respiratory pattern, airway occlusion pressure at 0.1 s (P0.1) for the respiratory drive and measured blood gases: i) before extubation, following 30 min of a 6 cm H2O pressure support (PS) ventilation trial, ii) 1 h after extubation, at the 30th min of a face mask 4 cm H2O PS ventilation trial. According to the weaning outcome, the patients were divided into two groups: respiratory distress, and non-respiratory distress within 72 h of the discontinuation of mechanical ventilation. The respiratory distress was defined as the combination of f more than 25 breaths/min, an increase in PaCO2 of at least 20% compared with the value measured after extubation, and pH lower than 7.35. We determined whether those patients who developed respiratory distress after extubation differed from those who did not. Respiratory pattern data and arterial blood gases recorded, either before or after extubation, and P0.1 recorded before extubation, were inadequate to differentiate the two groups. Only P0.1 recorded 1 h after the discontinuation of mechanical ventilation differentiated the patients who developed respiratory distress from those who did not (4.2+/-0.9 vs 1.8+/-0.8, p < 0.01). CONCLUSIONS: P0.1 recorded after extubation may be a good indicator of postextubation respiratory distress. Measuring P0.1 and/or the analysis of the evolution of this parameter could facilitate decisions during the period following extubation.     

Effects of felodipine on left ventricular systolic and diastolic performance in congestive heart failure

We studied the effects of a dihydropyridine calcium blocker, felodipine, on left ventricular (LV) contractile performance and diastolic filling dynamics in conscious dogs with pacing-induced congestive heart failure (CHF) before and after autonomic blockade. Eleven conscious dogs were instrumented to measure micromanometer LV and left atrial (LA) pressure (P) and to determine LV volume (V) from three dimensions. CHF was induced by 4 to 5 weeks of right ventricular pacing. After CHF, the mean LV end-diastolic (ED) P increased (9.7 +/- 2.9 vs. 27.9 +/- 6.8 mm Hg, P < .05), LVEDV and end-systolic (ES) V increased and stroke volume (SV) decreased (15.3 +/- 2.4 vs. 9.6 +/- 3.0 ml, P < .05). The time constant of LV relaxation (T) (25.9 +/- 2.9 vs. 37.9 +/- 5.1 msec, P < .05) and LVES wall stress (WS) (63.4 +/- 21.0 vs. 74.6 +/- 23.7 g/cm2, P < .05) also increased. After CHF, felodipine (25 nmol/kg i.v., plasma concentrations 17.4 +/- 3.2 nmol/L) produced significant decreases in LVESP (119 +/- 12 vs. 96 +/- 11 mm Hg, P < .05), arterial elastance, total systolic resistance (TSR) (0.11 +/- 0.04 vs. 0.07 +/- 0.03 mm Hg/ml/min, P < .05) and LVESWS (74.6 +/- 23.7 vs. 60.2 +/- 17.3 g/cm2, P < .05). Felodipine increased the slopes of the ESP-V relation (5.6 +/- 1.5 vs. 7.8 +/- 0.7 mm Hg/ml, P < .05), the dP/dtmax-EDV relation (51.4 +/- 6.1 vs. 85.3 +/- 10.1 mm Hg/ml sec, P < .05) and the stroke work-EDV relation (69.8 +/- 7.1 vs. 78.9 +/- 7.1 mm Hg, P < .05) and shifted all three relations to the left, indicating enhanced contractile performance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of ganglioside (GM1) on memory in senescent rats

We investigated the effects of aerosolized prostacyclin (PGI2) administration on hemodynamics and pulmonary gas exchange in 8 patients with severe respiratory failure and acute pulmonary hypertension. Nebulization of epoprostenol (5 ng/kg body weight for 15 min) decreased mean pulmonary blood pressure from 41.2 +/- 6.7 mm Hg (mean +/- SD, before administration) to 36.1 +/- 6 mm Hg < or = 15 min (p < 0.05). The effect was reversed 10 min after discontinuation of PGI2 (40.9 +/- 6.3 mm Hg). Pulmonary vascular resistance index (339 +/- 138 dynes.s.cm-5.m2, before administration) was significantly (p < 0.05) reduced < or = 15 min (260 +/- 89 dynes.s.cm-5.m2) and increased again after discontinuation of PGI2 (341 +/- 142 dynes.s.cm-5.m2). The ratio of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) increased from 119 +/- 34 mm Hg (before administration) to 163 +/- 76 mm Hg (15 min after initiation of administration p < 0.05) and was reduced after PGI2 discontinuation (116 +/- 35 mm Hg). Heart rate, mean blood pressure, central venous pressure, and pulmonary arterial wedge pressure remained unchanged, whereas cardiac index was slightly reduced. We assume that PGI2 aerosolization is a beneficial technique, applied with a ventilator nebulization system. The beneficial effect might be caused by selective pulmonary vasodilatation in well-ventilated areas of the lung.     

Treatment of subclinical fluid retention in patients with symptomatic heart failure: effect on exercise performance

BACKGROUND: Patients with heart failure frequently have elevated intracardiac diastolic pressures but no clinical evidence of excess fluid retention. We speculated that such pressure elevations may indicate subclinical fluid retention and that removal of this fluid could improve exercise intolerance. METHODS: To test this hypothesis, we studied 10 patients with right atrial pressure > or = 8 mm Hg but without rales, edema, or apparent jugular venous distension. Right-sided heart catheterization was performed, after which patients underwent maximal treadmill cardiopulmonary testing. Patients were then hospitalized and underwent maximal diuresis, after which exercise was repeated. RESULTS: Before diuresis, right atrial pressure averaged 16 +/- 5 mm Hg (+/-standard deviation), pulmonary capillary wedge pressure 30 +/- 6 mm Hg, and peak exercise Vo2 11.2 +/- 2.3 ml/min/ kg. Patients underwent diuresis of 4.5 +/- 2.2 kg over 4 +/- 2 days to a resting right atrial pressure of 6 +/- 4 and wedge pressure of 19 +/- 7 mm Hg. After diuresis, all patients reported overall symptomatic improvement. Maximal exercise duration increased significantly from 9.2 +/- 4.2 to 12.5 +/- 4.7 minutes. At matched peak workloads, significant improvements were also seen in minute ventilation (45 +/- 12 to 35 +/- 9 L/min), lactate levels (42 +/- 16 to 29 +/- 9 mg/dl), and Borg dyspnea scores (15 +/- 3 to 12 +/- 4) (all p < 0.05). CONCLUSIONS: Invasive hemodynamic monitoring allows the identification of excess fluid retention in patients with heart failure when there are no clinical signs of fluid overload. Removal of this subclinical excess fluid improves exercise performance and exertional dyspnea.     

The effects of long-term prone positioning in patients with trauma-induced adult respiratory distress syndrome

Prone positioning improves gas exchange in some patients with adult respiratory distress syndrome (ARDS), but the effects of repeated, long-term prone positioning (20 h duration) have never been evaluated systemically. We therefore investigated 20 patients with ARDS after multiple trauma (Injury Severity Score [ISS] 27.3 +/- 10, ARDS score 2.84 +/- 0.42). Patients who fulfilled the entry criteria (bilateral diffuse infiltrates, severe hypoxemia, pulmonary artery occlusion pressure [PAOP] < 18 mm Hg, and PaO2/fraction of inspired oxygen [FIO2] < 200 mm Hg at inverse ratio ventilation with positive end-expiratory pressure [PEEP] > 8 mm Hg for more than 24 h) were turned to the prone position at noon and were turned back to the supine position at 8:00 AM on the next day. Thus only two turns per day were necessary, and the risk of disconnecting airways or medical lines was minimized. Prone positioning was repeated for another 20 h if the patients fulfilled the entry criteria. Except for FIO2, the ventilator settings remained unchanged during the study period. All patients were sedated and, if needed paralyzed to minimize patient discomfort. One hour before and after each position change, ventilator settings and pulmonary and systemic hemodynamics were recorded and blood was obtained for blood gas analysis. Derived cardiopulmonary and ventilatory variables were calculated using standard formulas. Overall mortality was 10%. Oxygenation variables improved significantly each time the patients were placed prone. Immediately after the first turn from the supine to the prone position the following changes were observed: PaO2 increased from 97 +/- 4 to 152 +/- 15 mm Hg, intrapulmonary shunt (Qva/Qt) decreased from 30.3 +/- 2.3 to 25.5 +/- 1.8, and the alveolar-arterial oxygen difference decreased from 424 +/- 24 to 339 +/- 25 mm Hg. All these changes were statistically significant. Most of these improvements were lost when the patients were turned supine, but could be reproduced when prone positioning was repeated after a short period (4 h) in the supine position. Short periods in the supine position were necessary to allow for nursing care, medical evaluation, and interventions such as placement of central lines. No position-dependent changes of systemic hemodynamic variables were observed. We conclude that, in trauma patients with ARDS undergoing long-term positioning treatment, lung function improves significantly during prone position compared to short phases of conventional supine position during which the beneficial effects are partly lost.     

Value of classical and new criteria of electrocardiography in diagnosis of hypoxic cor pulmonale evaluated by hemodynamics tests

Electrocardiogram is commonly used in the diagnosis of cor pulmonale in patients with chronic obstructive pulmonary disease (COPD). Pulmonary hemodynamics being the definite method for diagnosis the disease can be used to vary the ecg criteria for diagnosis cor pulmonale. After excluding patients with old myocardial infarction and with pulmonary wedge pressure > 12 mm Hg in 66 patients aged 65.2 with advanced COPD (FEV1 0.78 +/- 0.3 litre) pulmonary hemodynamics and ecg were performed at the same time. The signs of right ventricular hypertrophy were sought for using 3 sets of criteria: the World Health Organisation criteria, new compiled Lehtonen et al. Criteria and right ventricular precordial leads. WHO criteria had a specificity and sensitivity of 50% and 57.6%, the modified right precordial leads-53% and 64.5% and compiled Lehtonen's criteria -57% and 59% respectively. In 32 patients with mild pulmonary hypertension (20-29 mm Hg) sensitivity of WHO criteria was 46.8%, right precordial leads -51.6%, and Lethonen and co. Criteria -50%, in 10 patients with moderate pulmonary hypertension (30-39 mm Hg) 59%-62.5%-50%, in 9 patients with severe hypertension (> or = 40 mm Hg) 100%-100%-100% respectively. Our studies confirm the poor sensitivity and of ecg criteria for diagnosis of cor pulmonale (pulmonary hypertension) in COPD. However, in mild and moderate pulmonary hypertension, sensitivity of ecg diagnosis of cor pulmonale is improved if right modifieds precordial leads are used. New, compiled Lehtonen's criteria failed to improved diagnosis of diagnosis of cor pulmonale. All studied sets of criteria are highly sensitive in COPD patients with severe pulmonary hypertension.     

Subretinal neovascularization developing after prophylactic argon laser photocoagulation of atrophic macular scars

Twenty-eight anemic control dogs were subjected to isolated cerebral hypoxemic (PO2,35+/-5 mm Hg) perfusion for 2 hours. All were found to have functional pulmonary impairment. Two hours later, twenty were sacrificed and found to have the bilateral anatomic complex of the respiratory distress syndrome (RDS). All those not sacrificed expired within 20 hours with progressive respiratory distress and at autopsy had the bilateral anatomic complex. Twenty-three beagles with chronic denervation (autotransplantation) of the left lung also were subjected to the 2 hour isolated cerebral arterial hypoxemic perfusion. Minimal pulmonary functional impairment was measurable in all. Ten of sixteen were long-term survivors. The six that succumbed did not appear to suffer respiratory deaths. These six, as well as seven sacrificed 2 hours after perfusion, had the anatomic complex of RDS in the normally innervated right lungs. However, the denervated left lungs were anatomically normal. These findings are offered as additional evidence that RDS has a centrineurogenic etiology. We postulate the following sequence: "shock" causes cerebral (probably hypothalamic) cellular oxygen deprivation and dysfunction; there is autonomically mediated, increased resistance of the pulmonary venules ("postcapillary sphincters"); this leads to capillary hypertension, congestion, hemorrhage, edema, surfactant inactivation, and atelectasis. Pulmonary denervation blocks this sequence and protects the lung.     

Study of the use of noninvasive ventilation of the lungs in acute respiratory insufficiency due exacerbation of chronic obstructive pulmonary disease

Noninvasive positive pressure ventilation (NPPV) is a life-saving procedure in acute respiratory failure (ARF), but its technique is not yet in routine use in many respiratory centers. We carried out a prospective randomized study comparing the combination of NPPV with conventional therapy (oxygen, bronchodilators, steroids, and theophylline) with conventional therapy alone in patients with acute respiratory failure caused by exacerbation of chronic obstructive pulmonary disease (COPD). A total of 58 patients were recruited from a large group of patients admitted to our hospital between September 1995 and March 1997. Twenty-nine patients were randomly assigned to the NPPV group and 29 to the conventional (non-NPPV) group. The patients were matched for demographic and physiological norm values (mean age 63.4 +/- 5.5 vs. 66.2 +/- 7.1 years, mean FEV1 0.68 +/- 0.15 vs. 0.74 +/- 0.16 L, PaO2 51.4 +/- 6.8 vs. 52.3 +/- 6.5 mm Hg, PaCO2 63.4 +/- 10.9 vs. 64.9 +/- 9.7 mm Hg, and pH 7.28 +/- 0.07 vs. 7.26 +/- 0.06). The outcome end points were needed for endotracheal intubation, length of hospital stay, and incidence of complications. NPPV was administered using BiPAP ventilatory device (Respironics, Inc.) by spontaneous and spontaneous/timed modes via nasal and facial masks. The mean time of NPPV was 29 +/- 25 h. Three patients refused from NPPV because of intolerance of mask or ventilation procedure. Two of them were eventually intubated and one of them died. In patients administered NPPV, we observed a significant rise of pH and fall of PaCO2 after 1 h of ventilation, in contrast to the non-NPPV group (7.34 +/ 0.09 vs. 7.21 +/- 0.08, p < 0.05; 53.2 +/- 10.7 vs. 71.4 +/- 10.2 mm Hg, p < 0.01, respectively). The need in intubation was lower in the NPPV group as compared to the reference group (12 vs. 28%, p = 0.18), mortality rate was higher in the non-NPPV group (31 vs. 8%, p = 0.03), and hospital stay was shorter in NPPV patients (26 +/- 7 vs. 34 +/- 10 days). The incidence of complications was lower in the NPPV group, they were less significant, and did not involve discontinuation of ventilation. Hence, NPPV is a first-line therapy in patients with ARF caused by COPD exacerbation, due to obvious advantages over conventional methods of treatment.     

DNA reactions, mutagenic action and stealth properties of polycyclic aromatic hydrocarbon carcinogens (review)

OBJECTIVE: To present a critical review and meta-analysis of studies evaluating the long-term effects of pulmonary rehabilitation in patients with asthma and chronic obstructive pulmonary disease (COPD). DATA SOURCES: A database of articles published over the last 45 years, compiled by using medical subject heading key words pulmonary, obstructive, rehabilitation, and exercise. Articles not written in English, Dutch, or German and abstracts were excluded. STUDY SELECTION: Selected studies (1) evaluated the effects of pulmonary rehabilitation, (2) included patients with asthma or COPD older than 18 years, (3) evaluated outcome measures of exercise capacity or health related quality of life (HRQL), and (4) included a control condition lacking exercise training. DATA EXTRACTION: Independent extraction by two reviewers. DATA SYNTHESIS: For each outcome, summary effects were computed by pooling standardized mean differences as well as raw mean differences. Significant improvements were found for all outcomes (p < .001). Sensitivity analyses for methodological quality of the selected studies did not change summary effect sizes. Effect sizes were significantly heterogeneous for the outcome endurance time (p < .0001). Pooling raw mean differences revealed overall effects in 6-minute walking distance (49+/-26 m) and all 4 dimensions of the chronic respiratory questionnaire (range, 0.5+/-0.3 to 0.8+/-0.3 points), indicating substantial improvements in these outcomes. Significant summary effect sizes were found up to 9 months after finishing rehabilitation for maximal exercise capacity (p < .003) and 6-minute walking distance (p < .005). CONCLUSIONS: Patients with asthma and COPD benefit from pulmonary rehabilitation.     

Acute hemodynamic effects of biventricular DDD pacing in patients with end-stage heart failure

OBJECTIVES: The aim of this study was to assess the potential acute benefit of multisite cardiac pacing with optimized atrioventricular synchrony and simultaneous biventricular pacing in patients with drug-refractory congestive heart failure (CHF). BACKGROUND: Prognosis and quality of life in severe CHF are poor. Various nonpharmacological therapies have been evaluated but are restricted in their effectiveness and applications. In the early 1990s, dual chamber pacing (DDD) pacing was proposed as primary treatment of refractory CHF but results were controversial. Recently, tests to evaluate the effect of simultaneous pacing of both ventricles have elicited a significant improvement of cardiac performance. METHODS: Acute hemodynamic study was conducted in 18 patients with severe CHF (New York Heart Association class III and IV) and major intraventricular conduction block (IVCB) (QRS duration = 170+/-37 ms). Using a Swan-Ganz catheter, pulmonary artery pressure, pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured in different pacing configurations: atrial pacing (AAI) mode, used as reference, single-site right ventricular DDD pacing and biventricular pacing with the right ventricular lead placed either at the apex or at the outflow tract. RESULTS: The CI was significantly increased by biventricular pacing in comparison with AAI or right ventricular (RV). DDD pacing (2.7+/-0.7 vs. 2+/-0.5 and 2.4+/-0.6 l/min/m2, p < 0.001). The PCWP also decreased significantly during biventricular pacing, compared with AAI (22+/-8 vs. 27+/-9 mm Hg; p < 0.001). CONCLUSIONS: This acute hemodynamic study demonstrated that biventricular DDD pacing may significantly improve cardiac performance in patients with IVCB and with severe heart failure, in comparison with intrinsic conduction and single-site RV DDD pacing.     

Serologic test for syphilis as a surrogate marker for human immunodeficiency virus infection among United States blood donors

OBJECTIVE: To determine the presence of tricuspid regurgitation (TR) in patients affected by acute lung injury (ALI) and the adult respiratory distress syndrome (ARDS) during mechanical ventilation with positive end-expiratory pressure (PEEP). DESIGN: A prospective clinical study. SETTING: 10-bed general intensive care unit in a University Hospital. PATIENTS: 7 consecutive patients an age 44.7 +/- 8.6 years with a diagnosis of ALI or ARDS were studied. All were on mechanical ventilation with PEEP. INTERVENTIONS: PEEP was increased in steps of 5 cm H2O until the appearance of TR or up to a limit of 20 cm H2O. MEASUREMENTS AND RESULTS: Right atrial pressure, pulmonary artery pressure, and wedge pressure were measured and cardiac output was determined by thermodilution. TR was graded from 0 to 3. Standard 2D echocardiographic and pulsed-wave images were obtained at each level of PEEP. PEEP was increased from 4 +/- 3 to 17 +/- 2 cm H2O. Mean PAP increased from 27.7 +/- 2.9 to 36.7 +/- 3.5 mm Hg (p < 0.02) when PEEP was increased. Five patients had competent valves and two had mild TR at baseline. In six out of the seven, TR either developed or increased when PEEP was increased. CONCLUSIONS: Our study demonstrated the development of TR after the use of PEEP in patients with ALI and ARDS as a consequence of pulmonary hypertension and right ventricular overloading. Since TR may randomly affect cardiac output values and derived parameters, the assessment of cardiac performance by some techniques such as thermodilution should be used with caution.     

Pressure support ventilation in adult respiratory distress syndrome: short-term effects of a servocontrolled mode

PURPOSE: To assess the short-term effects of pressure support ventilation in adult respiratory distress syndrome (ARDS), we studied 17 patients with moderate to severe ARDS using mandatory rate ventilation (MRV), a servocontrolled mode of PSV having respiratory rate as the targeted parameter. MATERIALS AND METHODS: Based on the duration of ARDS, the patients were divided into two groups: Group 1, early ARDS (duration up to 1 week), 10 patients; Group 2, intermediate ARDS (duration between 1 and 2 weeks). The patients were initially ventilated with assisted mechanical ventilation then with MRV, and finally with controlled mechanical ventilation. After a 20-minute period allowed for stabilization in each mode, ventilatory variables, gas exchange, hemodynamics, and patient's inspiratory effort were evaluated. RESULTS: During MRV blood gases, airway pressures and hemodynamic variables remained within acceptable limits in all patients. Compared with assisted mechanical ventilation, during MRV, patients of group 1 decreased their VT and V (from 0.64 +/- 0.04 to 0.42 +/- 0.03 L/sec) and increased their TI/TT (from 0.39 +/- 0.03 to 0.52 +/- 0.03). f did not change. PAO2 - PaO2 and QS/QT decreased (from 306 +/- 16 to 269 +/- 15 mm Hg, and from 20.2 +/- 1.4 to 17.5 +/- 1.1, respectively), while PaCO2 increased (from 44 +/- 3 to 50 +/- 3 mm Hg). On the contrary, patients of group 2 increased their VT (from 0.69 +/- 0.02 to 0.92 +/- 0.09 L), decreased their f (from 22.3 +/- 0.5 to 19.3 +/- 0.3 b/min), although they did not change their V and TI/TT. PAO2 - PaO2 and QS/QT remained stable. PaCO2 diminished (from 39 +/- 3 to 34 +/- 3 mm Hg). Pressure support level was higher in group 2 than in group 1 (29.4 +/- 3.0 v 19.8 +/- 2.9 cm H2O). CONCLUSIONS: We conclude that (1) PSV delivered by MRV may adequately ventilate patients with moderate to severe ARDS, preserving gas exchange and hemodynamics, at least for the short period tested; (2) early and intermediate ARDS respond in a different manner to MRV in terms of breathing pattern, gas exchange, and level of pressure assistance; and (3) patients with early ARDS are those who have an improvement in intrapulmonary oxygenation probably due, at least in part, to alveolar recruitment augmented by active diaphragmatic contraction.     

MR guidance of laser disc decompression: preliminary in vivo experience

BACKGROUND: The mechanism of atrial natriuretic peptide (ANP) release has been difficult to demonstrate in patient studies because of inaccuracies in measuring atrial volumes using conventional techniques. METHODS: Magnetic resonance imaging was performed in 28 clinically stable patients (New York Heart Association class 3) with chronic heart failure to determine right atrial (RA), left atrial (LA), and ventricular volumes. In addition, right heart catheterization was serially performed and plasma ANP levels (in picograms per milliliter) were drawn from the right atrium. RESULTS: Five patients had to be excluded from data analysis for technical reasons. The remaining 23 patients had the following hemodynamic measurements (mean +/- SD): RA mean pressure 7+/-5 mm Hg, pulmonary artery mean pressure 28+/-10, pulmonary capillary wedge pressure 21+/-8 mm Hg, and cardiac index 2.9+/-1.4 (L/min/m2), respectively. Plasma ANP levels were significantly elevated at 162+/-117 (normal range 20 to 65 pg/ml, p < 0.05), as were LA and RA volumes compared with healthy controls (RA volume 128+/-64 ml vs 82+/-25 ml, p < 0.05; LA volume 157+/-54 ml vs 71+/-24 ml, p < 0.01, respectively). ANP showed a stronger relation with atrial volumes (RA volume, r = 0.91, p = 0.0001; LA volume, r = 0.80, p = 0.001) than with atrial pressures (RA mean pressure, r = 0.45, p = 0.03; pulmonary capillary wedge pressure, r = 0.67, p = 0.001). A subgroup analysis of patients with increased RA or LA volumes (>1 SD of mean of controls) revealed a stronger relation between ANP and RA volumes than between ANP and LA volumes. CONCLUSIONS: These data suggest that increased right heart volume with subsequent increased atrial stretch is the major determinant for ANP release in patients with stable CHF.     

Oncotic pressure and edema formation in hypoalbuminemic HIV-infected patients with proteinuria

Human immunodeficiency virus nephropathy (HIVN) continues to challenge nephrologic consultative services at major urban institutions. Although noted in the literature, the decreased incidence of peripheral edema in HIVN has been unexplained to date. In HIV patients, total proteins frequently are found to be elevated due to an elevated globulin fraction. The impact that plasma proteins, specifically globulins, have on the total oncotic pressure has not been reported in HIVN, but may play a role in the paucity of edema noted in this proteinuric population. To evaluate the contributions of serum globulin to the total oncotic pressure and the presence or absence of edema in HIVN, we randomly selected 27 patients with proteinuria greater than 2.5 g/24 hr and serum albumin less than 3.1 g/dL from patients presenting to the nephrology outpatient clinic at the University of Miami/Jackson Memorial Hospital. Seventeen of the patients (63%) had a known diagnosis of HIV infection (group 1). These patients were subdivided into two subgroups: those presenting with clinically evident edema on physical examination (n = 7 [41%]; group 1A) and those who had an absence of edema (n = 10 [59%]; group 1B). Conversely, group 2 comprised 10 patients without known HIV infection, of whom six (60%) had edema (group 2A) and four (40%) did not (group 2B). Blood pressures were noted, and mean arterial pressure was calculated using standard formulas. Serum albumin, serum total proteins, and urine total proteins were measured using standard laboratory methods. Oncotic pressures for albumin (alpha), globulin (beta), and total protein (c) were calculated using the following formula: COPpl = alpha(2.8c + 0.18c2 + 0.012c3) + beta(0.9c + 0.12c2 + 0.004c3). We used Student's t-test to analyze the data. There is no significant difference between the albumin concentrations of HIV patients without edema (group 1B) and non-HIV patients with edema (group 2A), with mean concentrations of 2.3 +/- 0.1 g/dL versus 2.3 +/- 0.15 g/dL, respectively (P = NS). Group 1B, however, has a total oncotic pressure of 17.1 +/- 1.5 mm Hg, whereas both groups with edema (groups 1A and 2A) have statistically significant lower total oncotic pressures (12.1 +/- 2.3 mm Hg and 12.9 +/- 1.1 mm Hg, respectively; P < 0.05). The globulin oncotic pressures may account for some of the differences in total oncotic pressures, being significantly higher for those patients without edema in group 1B compared with group 2A (7.1 +/- 0.9 mm Hg v 3.9 +/- 0.4 mm Hg, respectively; P < 0.05). In patients with HIV, however, the presence or absence of edema is mandated by albumin concentration because both groups have similar globulin concentrations (group 1A 3.1 +/- 0.1 g/dL v group 1B 3.8 +/- 0.3 g/dL; P = NS). Mean arterial pressure does not play a role in edema formation in this study because the HIV patients without edema had the higher blood pressures (group 1B 97.8 +/- 4.7 mm Hg v group 2A 84.7 +/- 5.5 mm Hg; P < 0.05). We conclude that globulins play an important role in maintaining oncotic pressure in low albumin states. HIVN patients with increased serum immune globulin may benefit from higher globulin oncotic pressure, delaying the onset of clinical edema in the setting of proteinuria.     

Development of decompensated dilated cardiomyopathy is associated with decreased gene expression and activity of the milrinone-sensitive cAMP phosphodiesterase PDE3A

BACKGROUND: Phosphodiesterase III (PDE3) inhibitors are inotropic agents used to treat congestive heart failure (CHF) and are less effective in patients with severe CHF. Little is known about relative changes in PDE3 activity or gene expression during the evolution of cardiomyopathy. METHODS AND RESULTS: In the present study, we evaluated temporal changes in PDE3A gene expression before and after pacing-induced CHF in nine mongrel dogs. Three weeks of left ventricular (LV) pacing produced LV end-diastolic pressures of 15+/-1.7 mm Hg, whereas overt CHF at 4 to 5 weeks was associated with LV end-diastolic pressures of 24+/-1.7 mm Hg; prepacing values were 6.6+/-0.6 mm Hg. Total RNA isolated from LV tissues was analyzed on Northern blots; 10 unpaced normal hearts served as tissue controls. Signals for PDE3A mRNAs (7, 8, and 10 kb) or PDE4D (7.6 kb) were normalized against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or ribosomal 18S RNA. Before the onset of CHF, PDE3A/GAPDH ratios were not different between the control and 3-week paced groups. In contrast, all PDE3A/GAPDH ratios were selectively reduced by 52%, and PDE3A/18S was reduced by 70% (P<.05) in CHF; PDE4D/GAPDH (or 18S) was unchanged. LV tissues from four control and four CHF dogs were also processed to isolate cytosolic and microsomal membrane protein for cAMP PDE3 activity assays. CHF was associated with a significant 54% reduction (P<.05) in microsomal but not cytosolic PDE3 activity. CONCLUSIONS: Selective downregulation of PDE3A may account in part for the ineffectiveness of milrinone in the treatment of severe CHF.     

Prognostic value of hypercapnia in patients with chronic respiratory failure during long-term oxygen therapy

Hypercapnia observed in patients with chronic respiratory failure may not be an ominous sign for prognosis when they are receiving long-term oxygen therapy (LTOT). In this study, we selected 4,552 patients with chronic obstructive pulmonary disease (COPD) and 3,028 with sequelae of pulmonary tuberculosis (TBsq) receiving LTOT from 1985 to 1993 throughout Japan and prospectively analyzed their prognoses. The hypercapnic patients (PaCO2 >= 45 mm Hg) had a better prognosis than the normocapnic patients (35 <= PaCO2 < 45 mm Hg) for TBsq, but no difference was found between the two groups with COPD. Furthermore, Cox's proportional hazards model revealed that in TBsq hypercapnia was an independent factor for favorable prognosis, and that the relative risk for mortality was 0.76 in patients with 45 <= PaCO2 < 55 mm Hg, 0.64 for those with 55 <= PaCO2 < 65 mm Hg, and 0. 49 for patients with PaCO2 >= 65 mm Hg against normocapnic patients. This favorable effect of hypercapnia in TBsq was particularly apparent in the patients without severe airway obstruction. Even a rise of 5 mm Hg or more in PaCO2 over the initial 6- to 18-mo follow-up period was not associated with poor prognosis in TBsq, although it was in COPD. From these findings, we conclude that hypercapnia should not be generally considered an ominous sign for prognosis in those patients who receive LTOT.