Effects of nitric oxide synthase inhibition on the cardiovascular response to low output shock.

OBJECTIVE: To study the role of nitric oxide in the cardiovascular response to a model of a low output syndrome. DESIGN: Prospective animal study. SETTING: Animal research laboratory. SUBJECTS: Sheep anesthetized with pentobarbital, mechanically ventilated, and monitored with pulmonary arterial and peripheral arterial catheters. INTERVENTIONS: A low output state was induced by inflating a balloon-tip catheter placed in the right atrium. Cardiac index was maintained at 1 L/min/m2 throughout the experiment in three groups of sheep: a) control (n=6) b)LNNA group (pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine [LNNA, 100 mg/kg, iv bolus, n=6); and c) dexamethasone group (pretreated with dexamethasone (6 mg/kg, intravenous bolus, n=6). Dexamethasone is an inhibitor of the induction of nitric oxide synthase. LNNA or dexamethasone were administered 15 mins before inducing the low output state. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport variables, and plasma lactate and pyruvate concentrations, were measured at baseline and during the next 3 hrs. For a comparable decrease in cardiac index and oxygen delivery in all groups, the LNNA group had less hypotension and a more marked increase in systemic vascular resistance as compared with the control group. Oxygen consumption and oxygen extraction were higher in the LNNA group as compared with the control group at 30 and 60 mins. Plasma lactate concentration increased significantly less in the LNNA group than in the control and the dexamethasone groups during the observation period. CONCLUSIONS: Inhibition of nitric oxide synthesis during a severe low output state in sheep is associated with a better hemodynamic response, as evidenced by a greater vasoconstriction, and signs of less marked tissue hypoxia. It is likely that inhibition of nitric oxide synthesis in this model leads to an imbalance between the tonic relaxing action of nitric oxide and the influences of vasoconstrictor agents.

Inhibition of nitric oxide synthesis improves the vasoconstrictive effect of noradrenaline in sepsis.

BACKGROUND: Septic shock is characterized by systemic vasodilation and an impaired reactivity to vasoconstrictor agents. It has been suggested that an excessive release of nitric oxide has a role in this hemodynamic derangement. OBJECTIVE: To investigate whether inhibition of nitric oxide synthesis by the administration of N omega-nitro-L-arginine (LNNA), improves the vasoconstrictor effects of catecholamines in sepsis. MATERIAL AND METHODS: Mechanically ventilated and pentobarbital-anesthetized sheep received either no treatment (n = 6) or LNNA (100 mg/kg IV bolus, n = 4). Other sheep (septic group) received live Escherichia coli (E coli) (1,5* 10(9) micro-organisms/kg over 30 min) followed 1 hour later by either no treatment (n = 5) or LNNA (100 mg/kg IV bolus, n = 7). After those interventions, all sheep were given noradrenaline in a continuous IV infusion at three different doses (0.5, 1.5, and 4.5 micrograms, kg-1, min-1). Cardiovascular parameters were recorded at maximal blood pressure response achieved with each dose. RESULTS: The administration of live E coli to the septic group resulted in systemic hypotension, high cardiac output, and hyperlactatemia. The LNNA caused a significant systemic and pulmonary vasoconstriction in both septic and nonseptic sheep. In nonseptic sheep, noradrenaline induced a significant increase in systemic vascular resistance (from 2,973 +/- 637 to 4,561 +/- 1,287 dyn/s/cm-5/m-2), whereas the increase caused in those that received LNNA was nonsignificant (5,562 +/- 3,489 to 6,693 +/- 2,871 dyn, s, cm-5, m-2). Septic sheep showed a nonsignificant vasoconstriction during the infusion of noradrenaline (from 1,438 +/- 1,132 to 2,244 +/- 1,391 dyn/s/cm-5/m-2). However, treatment with LNNA markedly improved the vasoconstrictor effect of noradrenaline (from 2,804 +/- 2,317 to 4,894 +/- 3,435 dyn/s/cm-5/m-2). The dose-response curve of systemic vascular resistance in these LNNA-pretreated septic sheep became very similar to the corresponding curve obtained in nonseptic animals. CONCLUSIONS: Inhibition of nitric oxide synthesis by the administration of LNNA significantly improves the vasoconstrictor effect of noradrenaline in septic sheep, allowing an increase in systemic vasomotor tone similar to that observed in nonseptic sheep. It is concluded that increased synthesis of nitric oxide contributes to the depressed vascular reactivity to vasoconstrictor agents characteristic of sepsis.

L-arginine pathway in the sepsis syndrome.

OBJECTIVE: To investigate the role of nitric oxide in the regulation of vascular tone in patients with the sepsis syndrome. DESIGN: Prospective, intervention study. SETTING: Tertiary care hospital. PATIENTS: Fifteen patients admitted to our medical intensive care unit with the diagnosis of sepsis syndrome by defined criteria. INTERVENTIONS: Eight patients received N omega-nitro-L-arginine (20 mg/kg, iv bolus) followed by L-arginine (200 mg/kg, iv bolus). Seven patients received L-arginine alone (200 mg/kg). MEASUREMENTS AND MAIN RESULTS: In the first group, hemodynamic and oxygen transport variables were recorded at baseline, during 45 mins after the injection of N omega-nitro-L-arginine, and during 45 mins after the administration of L-arginine. In the second group, hemodynamic parameters were recorded at baseline and during 15 mins after the administration of L-arginine. Data are mean +/- SEM. The administration of N omega-nitro-L-arginine was followed by hypertension (mean blood pressure increased from 89 +/- 8 to a maximum of 140 +/- 12 mm Hg) accompanied by a decrease in cardiac index (from 3.51 +/- 0.39 to a minimum of 2.65 +/- 0.21 L/min/m2) and an increase in right atrial and pulmonary artery occlusion pressure. Systemic vascular resistance index increased from 1871.1 +/- 302.3 to 3825.6 +/- 244.4 dyne.sec/cm5.m2, and pulmonary vascular resistance increased from 533.2 +/- 125.8 to 816.0 +/- 117.3 dyne.sec/cm5.m2. These changes induced by N omega-nitro-L-arginine were reversed by the administration of L-arginine. The administration of L-arginine to another group of patients caused transient hypotension (from 103 +/- 6 to 81 +/- 10 mm Hg) and an increase in cardiac index (from 3.57 +/- 0.15 to 4.74 +/- 0.54 L/min/m2). Both systemic and pulmonary vascular resistance indices decreased (from 1987.6 +/- 163.9 to 1251.4 +/- 231.5 dyne.sec/cm5.m2, and from 486.1 +/- 65.2 to 380.5 +/- 70.3 dyne.sec/cm5.m2). Parallel to the increase in oxygen transport due to the increase in cardiac output, oxygen consumption index increased significantly 1 min after L-arginine (from 127.0 +/- 19.0 to 182.5 +/- 37.3 mL/min/m2). All mentioned changes were statistically significant (p < .05). CONCLUSIONS: A continuous basal release of nitric oxide plays a role in the regulation of systemic and pulmonary vascular tone in patients with sepsis syndrome. L-arginine has systemic and pulmonary vasodilatory actions.

Effects of blood transfusion on oxygen transport variables in severe sepsis.

OBJECTIVE: To investigate whether increasing oxygen delivery (DO2) by increasing hematocrit results in increases in oxygen uptake (VO2) in septic patients with an abnormal DO2/VO2 relationship. DESIGN: Prospective, randomized, interventional crossover study. SETTING: Tertiary care hospital. PATIENTS: A consecutive sample of 16 patients admitted to the intensive care unit, who were diagnosed as having severe sepsis by defined criteria and who had a hemoglobin concentration of < 10 g/dL. INTERVENTIONS: Patients received, in random order, an infusion of dobutamine (10 micrograms/kg/min) and a blood transfusion (800 mL of packed red blood cells in 90 mins). Hemodynamic and oxygen transport variables were determined before and after each treatment, allowing at least 20 mins during the infusion of dobutamine to achieve the steady state. MEASUREMENTS AND MAIN RESULTS: Changes in DO2 and VO2 induced by each intervention were measured. Dobutamine significantly increased DO2 (48.5 +/- 6.9%; p = .0001) and VO2 (21.7 +/- 3.3%; p = .0001). Blood transfusion increased DO2 (21.4 +/- 4.3%; p = .005) but VO2 did not change significantly (2.2 +/- 4.1%). Correlation coefficients for the percent changes of DO2 and VO2 (r2 = .67, p = .001 for dobutamine; and r2 = 21, p = .07 for blood transfusion) were significantly different for each treatment (p = .0001). CONCLUSIONS: In patients with an abnormal DO2-dependent VO2, as shown by increases in VO2 brought about by an infusion of dobutamine, blood transfusion does not significantly increase VO2, despite significant changes in DO2. The VO2, in some critically ill patients, depends more on blood flow than on global DO2.

Role of nitric oxide in the hemodynamic changes of sepsis.

OBJECTIVE: To study the role of nitric oxide in the hemodynamic changes of sepsis. DESIGN: Prospective, randomized, controlled, intervention study. SUBJECTS: Twenty-five sheep randomized to four groups: Group A (n = 8, nonseptic sheep) received NG-nitro L-arginine (20 mg/kg i.v.) followed 15 mins later by L-arginine (200 mg/kg i.v.); group B (n = 4, nonseptic sheep) received L-arginine followed 15 mins later by NG-nitro L-arginine; group C (n = 7, septic sheep) received NG-nitro L-arginine (20 mg/kg i.v.) alone; group D (n = 6, septic sheep) received L-arginine (200 mg/kg i.v.) followed by NG-nitro L-arginine (20 mg/kg i.v.). INTERVENTIONS: Sheep were anesthetized with pentobarbital, mechanically ventilated and monitored with a pulmonary artery catheter, a peripheral artery catheter, and a Miller catheter in the left ventricle. Sepsis was induced by the intravenous administration of live Escherichia coli (1.5 x 10(9) microorganisms/kg over 30 mins), which resulted in systemic hypotension, pulmonary hypertension, high cardiac output, and hyperlactatemia. Acetylcholine was administered before and after each intervention. MEASUREMENTS AND MAIN RESULTS: In nonseptic sheep (groups A and B) NG-nitro L-arginine induced an increase in mean blood pressure (BP), pulmonary arterial pressure, and systemic and pulmonary vascular resistances, accompanied by a decrease in cardiac index and the first derivative of left ventricular pressure. L-arginine administered to normal sheep induced systemic vasodilation. In the sepsis groups (groups C and D), the increases in BP and systemic vascular resistances induced by NG-nitro L-arginine were significant but less marked than in nonseptic sheep. Pretreatment of septic sheep with L-arginine totally abolished the NG-nitro L-arginine induced increases in systemic and pulmonary vascular resistances in this group. The administration of L-arginine in these animals induced both systemic and pulmonary vasodilation. Acetylcholine-mediated vasodilation was severely impaired in sepsis. In this condition, pretreatment with L-arginine improved the response to acetylcholine. CONCLUSIONS: These data support the view that nitric oxide plays a significant role in modulating systemic and pulmonary vasomotor tone in normal and septic sheep. L-arginine produced systemic vasodilation in normal sheep, whereas both systemic and pulmonary vasodilation were observed in septic animals. The impaired response to an endothelium-dependent vasodilator in sepsis was improved by the previous administration of L-arginine.

Oxygen delivery-dependent oxygen consumption in acute respiratory failure.

OBJECTIVE: To investigate whether oxygen consumption (VO2) is dependent on oxygen delivery (DO2) in adult respiratory distress syndrome (ARDS) and non-ARDS acute respiratory failure. DESIGN: Intervention study of a consecutive sample of patients admitted to the ICU with the diagnosis of acute respiratory failure. SETTING: Tertiary care center. PATIENTS: Thirteen consecutive patients with a diagnosis of ARDS and 11 with a diagnosis of respiratory failure not due to ARDS. Patients were monitored with an oximetric pulmonary artery catheter and mechanically ventilated. INTERVENTIONS: DO2 was decreased by the application of positive end-expiratory pressure (PEEP) (20 cm H2O), and subsequently increased by an iv infusion of dobutamine (10 micrograms/kg.min). RESULTS: After the application of PEEP, DO2 decreased significantly in both groups. However, VO2 decreased significantly (p less than .01) only in the ARDS group. When dobutamine was infused, DO2 increased significantly (p less than .01) in both groups, but VO2 increased only in ARDS patients. DO2 correlated significantly with VO2 both in ARDS (r2 = .81, p less than .01) and in non-ARDS (r2 = .38, p less than .05) patients. The correlation coefficient was significantly higher for ARDS than for non-ARDS patients. Comparing the slopes of the regression lines, a stronger dependency of VO2 on DO2 was found in ARDS than in non-ARDS respiratory failure (p less than .001). The oxygen extraction ratio correlated with DO2 in non-ARDS patients (r2 = .49, p less than .05), but not in ARDS patients. CONCLUSIONS: VO2 is dependent on DO2 over a wide range of DO2 values in acute respiratory failure. This dependency phenomenon is much stronger in ARDS than in respiratory failure due to other causes. Due to the abnormal dependency of VO2 on DO2, changes in the oxygenation status may not be reflected by changes in mixed venous oxygen saturation in ARDS.

Hemodynamic changes during whole bronchoalveolar lavage in two cases of pulmonary alveolar proteinosis.

Five whole bronchoalveolar lavages were performed in 2 patients with pulmonary alveolar proteinosis with continuous monitoring of mixed venous and arterial oxygen saturation. Hemodynamic parameters and gas-exchange status were measured during the different phases of the lavage. In the phase of filled lung, a significant increase of arterial partial pressure (PaO2) and arterial saturation of oxygen were observed, secondary to a decrease in the intrapulmonary shunt. The mean pulmonary arterial pressure, pulmonary vascular resistances and cardiac index were higher during the filling of the lung as compared to the controls. During the empty lung phase, although PaO2 decreased (without reaching statistical significance), due to an increase in the intrapulmonary shunt, the increase in cardiac output during this phase left the oxygen delivery (DO2) unchanged.

[Pulmonary microvascular cytology in critical patients]. / Citología microvascular pulmonar en el enfermo crítico.

Cytology in blood drawn through a wedged Swan-Ganz catheter appears as a sensitive method for the diagnosis of carcinomatous lymphangitis in patients in whom transbronchial biopsy is considered dangerous or who refuse to undergo the latter procedure. However, its usefulness has not been assessed in critical patients with acute respiratory failure of unknown etiology in whom malignant disease is suspected. We report our experience in two patients admitted to the Intensive Care Unit with acute respiratory failure of unknown etiology: they were a female with breast carcinoma and a male with lymphoma in whom the cytological study of pulmonary capillary blood disclosed malignant cells. The clinical evaluation and the subsequent histological studies confirmed the pulmonary involvement by malignant disease in both cases.