HMGB1 and inflammatory cytokines in experimental acute lung injury induced in rabbits / [HMGB1 e citocinas inflamatórias em lesão pulmonar aguda experimental induzida em coelhos]

The aim of this work was to measure HMGB1, TNF-alpha, and IL-8 in bronchoalveolar lavage (BAL), serum and TLR2 and TLR4mRNA expression in lung tissue of rabbits with two grades of acute lung injury (ALI). The animals were randomly assigned to groups with severe (S) and mild/moderate (MM) ALI, induced with warm saline, and a control group. HMGB1, TNF-alpha, IL-8, TLR2mRNA and TLR4mRNA were measured after ALI induction. The results showed increased levels of IL-8, TNF-alpha, HMGB1 and TLR4mRNA in the ALI groups. HMGB1, IL-8 and TNF-alpha concentrations in BAL were higher in S compared MM. Increased TLR4mRNA was observed in S and MM versus control. The results suggest an early participation of HMGB1 in ALI together with IL-8 and TNF-alpha and association with severity. TLR4 has early expression and role in ALI pathophysiology but is not associated with severity.(AU)

O objetivo deste trabalho é determinar os níveis de HMGB1, TNF-alfa e IL-8 no lavado broncoalveolar (BAL), bem como quantificar a expressão sérica de TLR2 e TLR4 mRNA em tecido pulmonar de coelhos com dois graus de lesão pulmonar aguda (LPA). Os animais foram distribuídos aleatoriamente em grupos com LPA grave (S) e leve / moderada (MM), induzidas com solução salina morna, e um grupo controle. HMGB1, TNF-alfa, IL-8, TLR2mRNA e TLR4mRNA foram medidos após a indução de LPA e quatro horas de ventilação mecânica. Os resultados mostraram níveis aumentados de IL-8, TNF-alfa, HMGB1 e TLR4mRNA nos grupos com LPA. As concentrações de HMGB1, IL-8 e TNF-alfa no LBA foram maiores no S comparado ao MM. Aumento de TLR4mRNA foi observado em S e MM versus controle. Os resultados sugerem uma participação precoce da HMGB1 na LPA em conjunto com IL-8 e TNF-alfa e associação com a gravidade da LPA. O TLR4 foi expresso na ALI e possivelmente possui papel precoce na fisiopatologia da LPA, mas sem associação com a gravidade.(AU)

Food restriction induces in vivo ventricular dysfunction in spontaneously hypertensive rats without impairment of in vitro myocardial contractility.

Cardiac structures, function, and myocardial contractility are affected by food restriction (FR). There are few experiments associating undernutrition with hypertension. The aim of the present study was to analyze the effects of FR on the cardiac response to hypertension in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Five-month-old SHR were fed a control or a calorie-restricted diet for 90 days. Global left ventricle (LV) systolic function was evaluated in vivo by transthoracic echocardiogram and myocardial contractility and diastolic function were assessed in vitro in an isovolumetrically beating isolated heart (Langendorff preparation). FR reduced LV systolic function (control (mean +/- SD): 58.9 +/- 8.2; FR: 50.8 +/- 4.8%, N = 14, P < 0.05). Myocardial contractility was preserved when assessed by the +dP/dt (control: 3493 +/- 379; FR: 3555 +/- 211 mmHg/s, P > 0.05), and developed pressure (in vitro) at diastolic pressure of zero (control: 152 +/- 16; FR: 149 +/- 15 mmHg, N = 9, P > 0.05) and 25 mmHg (control: 155 +/- 9; FR: 150 +/- 10 mmHg, N = 9, P > 0.05). FR also induced eccentric ventricular remodeling, and reduced myocardial elasticity (control: 10.9 +/- 1.6; FR: 9.2 +/- 0.9%, N = 9, P < 0.05) and LV compliance (control: 82.6 +/- 16.5; FR: 68.2 +/- 9.1%, N = 9, P < 0.05). We conclude that FR causes systolic ventricular dysfunction without in vitro change in myocardial contractility and diastolic dysfunction probably due to a reduction in myocardial elasticity.

Food restriction induces in vivo ventricular dysfunction in spontaneously hypertensive rats without impairment of in vitro myocardial contractility

Cardiac structures, function, and myocardial contractility are affected by food restriction (FR). There are few experiments associating undernutrition with hypertension. The aim of the present study was to analyze the effects of FR on the cardiac response to hypertension in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Five-month-old SHR were fed a control or a calorie-restricted diet for 90 days. Global left ventricle (LV) systolic function was evaluated in vivo by transthoracic echocardiogram and myocardial contractility and diastolic function were assessed in vitro in an isovolumetrically beating isolated heart (Langendorff preparation). FR reduced LV systolic function (control (mean ± SD): 58.9 ± 8.2; FR: 50.8 ± 4.8 percent, N = 14, P < 0.05). Myocardial contractility was preserved when assessed by the +dP/dt (control: 3493 ± 379; FR: 3555 ± 211 mmHg/s, P > 0.05), and developed pressure (in vitro) at diastolic pressure of zero (control: 152 ± 16; FR: 149 ± 15 mmHg, N = 9, P > 0.05) and 25 mmHg (control: 155 ± 9; FR: 150 ± 10 mmHg, N = 9, P > 0.05). FR also induced eccentric ventricular remodeling, and reduced myocardial elasticity (control: 10.9 ± 1.6; FR: 9.2 ± 0.9 percent, N = 9, P < 0.05) and LV compliance (control: 82.6 ± 16.5; FR: 68.2 ± 9.1 percent, N = 9, P < 0.05). We conclude that FR causes systolic ventricular dysfunction without in vitro change in myocardial contractility and diastolic dysfunction probably due to a reduction in myocardial elasticity.

Early administration of inhaled nitric oxide to children with acute respiratory distress syndrome and its effects on oxygenation and ventilator settings: prospective preliminary report of ten patients.

AIM: To establish a protocol for the early introduction of inhaled nitric oxide (iNO) therapy in children with acute respiratory distress syndrome (ARDS) and to assess its acute and sustained effects on oxygenation and ventilator settings. PATIENTS AND METHODS: Ten children with ARDS, aged 1 to 132 months (median, 11 months), with arterial saturation of oxygen <88% while receiving a fraction of inspired oxygen (FiO2) >or=0.6 and a positive end-expiratory pressure of >or=10 cm H2O were included in the study. The acute response to iNO was assessed in a 4-hour dose-response test, and positive response was defined as an increase in the PaO2/FiO2 ratio of 10 mm Hg above baseline values. Conventional therapy was not changed during the test. In the following days, patients who had shown positive response continued to receive the lowest iNO dose. Hemodynamics, PaO2/FiO2, oxygenation index, gas exchange, and methemoglobin levels were obtained when needed. Inhaled nitric oxide withdrawal followed predetermined rules. RESULTS: At the end of the 4-hour test, all the children showed significant improvement in the PaO2/FiO2 ratio (63.6%) and the oxygenation index (44.9%) compared with the baseline values. Prolonged treatment was associated with improvement in oxygenation, so that FiO2 and peak inspiratory pressure could be quickly and significantly reduced. No toxicity from methemoglobin or nitrogen dioxide was observed. CONCLUSION: Administration of iNO to children is safe. iNO causes rapid and sustained improvement in oxygenation without adverse effects. Ventilator settings can safely be reduced during iNO treatment.

[Idiopathic pulmonary hemosiderosis: case report] / Hemossiderose pulmonar idiopática: relato de caso.

OBJECTIVE: To alert pediatricians about the possibillity of childhood Idiopathic Pulmonary Hemosiderosis, in cases of anemia associated with chronic lung disease. METHODS: This article documents a case of Idiopathic Pulmonary Hemosiderosis in a 6 year-old child, with histopathological documentation, and reviews it against published literature. RESULTS: A 6 year-old child with history of anemia and lung disease characterized by wheezing, recurrent pneumonia and digital clubbing was admitted to the hospital for investigation, where he suffered sudden respiratory failure and hemoptysis.He was submitted to a lung biopsy which showed a histopathological diagnosis compatible with pulmonary hemosiderosis. Therapy with high doses of corticosteroids was initiated with a good early response. After two and a half months of therapy he had a new bleeding episode, culminating in death. CONCLUSIONS: Idiopathic Pulmonary Hemosiderosis should be included as a possible diagnosis of children with anemia and chronic lung disease. This case is a good example.

Influence of the elevation of the left ventricular diastolic pressure on the values of the first temporal derivative of the ventricular pressure (dP/dt).

PURPOSE: To assess the effects of the elevation of the left-ventricular end-diastolic pressure (LVEDP) on the value of the 1st temporal derivative of the ventricular pressure (dP/dt). METHODS: Nineteen anesthetized dogs were studied. The dogs were mechanically ventilated and underwent thoracotomy with parasympathetic nervous system block. The LVEDP was controlled with the use of a perfusion circuit connected to the left atrium and adjusted to the height of a reservoir. The elevation of the LVEDP was achieved by a sudden increase in the height of a reservoir filled with blood. Continuous recordings of the electrocardiogram, the aortic and ventricular pressures and the dP/dt were performed. RESULTS: Elevation of the LVEDP did not result in any variation of the heart rate (167 +/- 16.0 bpm, before the procedure; 167 +/- 15.5 bpm, after the procedure). All the other variables assessed, including systolic blood pressure (128 +/- 18.3 mmHg and 150 +/- 21.5 mmHg), diastolic blood pressure (98 +/- 16.9 mmHg and 115 +/- 19.8 mmHg), LVEDP (5.5 +/- 2.49 and 9.3 +/- 3.60 mmHg), and dP/dt (4,855 +/- 1,082 mmHg/s and 5,149 +/- 1,242 mmHg/s) showed significant increases following the expansion of the ventricular cavity. Although the elevation of the dP/dt was statistically significant, 6 dogs curiously showed a decrease in the values of dP/dt. CONCLUSION: Sudden elevation of the LVEDP resulted in increased values of dP/dt; however, in some dogs, this response was not uniform.

The rate of force generation by the myocardium is not influenced by afterload

The influence of afterload on the rate of force generation by the myocardium was investigated using two types of preparations: the in situ dog heart (dP/dt) and isolated papillary muscle of rats (dT/dt). Thirteen anesthetized, mechanically ventilated and thoracotomized dogs were submitted to pharmacological autonomic blockade (3.0 mg/kg oxprenolol plus 0.5 mg/kg atropine). A reservoir connected to the left atrium permitted the control of left ventricular end-diastolic pressure (LVEDP). A mechanical constriction of the descending thoracic aorta allowed to increase the systolic pressure in two steps of 20 mmHg (conditions H1 and H2) above control values (condition C). After arterial pressure elevations (systolic pressure C: 119 + 8.1; H1: 142 + 7.9; H2: 166 + 7.7 mmHg; P<0.01), there were no significant differences in heart rate (C: 125 + 13.9; H1: 125 + 13.5; H2: 123 + 14.1 bpm; P>0.05) or LVEDP (C:6.2 + 2.48; H1: 6.3 + 2.43; H2: 6.1 + 2.51 mmHg; P>0.05). The values of dP/dt did not change after each elevation of arterial pressure (C:3,068 + 1,057; H1: 3,112 + 996; H2: 3,086 + 980 mmHg/s; P>0.05). In isolated rat papillary muscle, an afterload corresponding to 50 percent and 75 percent of the maximal developed tension did not alter the values of the maximum rate of tension development (100 percent: 78 + 13; 75 percent: 80 + 13; 50 percent: 79 + 11 g mm-2 s-1, P>0.05). The results show that the rise in afterload per se does not cause changes in dP/dt or dT/dt.

Uso de escores preditivos na parada cardiorrespiratória em UTI pediátrica / Application of predictive score in cardiopulmonary arrest in pediatric ICU

Foram estudados prospectivamente em todos os 108 casos de parada cardiorrespiratoria (PCR) que ocorreram nas 501 internacoes na UTIP da Unesp em dois anos, a idade, estado nutricional, patologias envolvidas, escores prognosticos disfuncao de multiplos orgaos e evolucao. Os principais foram: Insuficiencia Respiratoria, Choque, Broncopneumonia. Houve grande incidencia de entroficos, porem a mortalidade foi crescente com a piora nutricional (eut. - 55,8 por cento; DPCI - 66,7 por cento; DPCII - 75 por cento; DPCIII - 75,9 por cento). O tempo de internacao foi prolongado (apneia/bradicardia - 11,5 + 6,6 d.; PCR sob. - 9,8 + 7,4 d.; PCR =b. - 6,2 + 10.3 d.). A mortalidade foi maior (88,6 por cento nas criancas maiores de um ano com maior instabilidade fisiologica (PRISM - 31.1 + 10,8) e maior intervencao terapeutica (TISS - 50,6 + 7). Com o aumento do numero de disfuncoes organicas aumentou a mortalidade devido a uma maior instabilidade fisiologica e maior necessidade de intervencao terapeutica (um sistema (d.s.) - 16,7 por cento mortalidade; tempo de internacao (t.i) - 2,7 + 2 d.; PRISM 15,5 + 5,7; TISS 27,5 + 6,4; 2 d.s. - 51, 7 por cento mort.; t.i. - 5,3 + 4,7 d.; PRISM 20,5 + 7,7,; TISS 44,1 + 7,3; 3 d.s. - 69 por cento mort., t.i. - 8,5 + 10,8 d.; PRISM 28,2 + 9,1; TISS 50,6 + 5,6; 4 ou + d.s. - 77,3 por cento mort.; t.i. - 9,2 + 11 d.; PRISM 34,7 + 9,1; TISS 53,8 + 4,6). Os sistemas que apresentaram maior incidencia de disfuncao foram o hemodinamico em 104 pacientes com mortalidade de 69 por cento e o respiratorio com mortalidade de 65,4 por cento, porem a disfuncao gastrointestinal, renal e neurologica apresentaram a maior mortalidade (respectivamente 100 por cento, 89,3 por cento e 85,1 por cento) com maior instabilidade fisiologica (PRISM 35,4 + 9,3; 37,5 + 7,7; e 34,7 + 9,6) e maior intervencao terapeutica (TISS 54,3 + 4,6; 55,9 + 5,5; e 52,2 + 6,5). Quando a mortalidade prevista pelo PRISM foi maior que 60 por cento, 81,8 por cento destes pacientes faleceram demonstrando a boa correlacao em prever o obito deste escore preditivo. A medida que a instabilidade fisiologica e a necessidade de intervencao terapeutica aumentou, diminuiu o tempo ate o obito. Concluimos entao ser freqnente a PCR em UTIP (21,6 por cento das internacoes); com mortalidade de 64,8 por cento semelhante a dados de literatura, sendo bem avaliados por dados de escores prognostico; a mortalidade aumenta com a piora nutricional, com o aumento na instabilidade fisiologica medida...

The rate of force generation by the myocardium is not influenced by afterload.

The influence of afterload on the rate of force generation by the myocardium was investigated using two types of preparations: the in situ dog heart (dP/dt) and isolated papillary muscle of rats (dT/dt). Thirteen anesthetized, mechanically ventilated and thoracotomized dogs were submitted to pharmacological autonomic blockade (3.0 mg/kg oxprenolol plus 0.5 mg/kg atropine). A reservoir connected to the left atrium permitted the control of left ventricular end-diastolic pressure (LVEDP). A mechanical constriction of the descending thoracic aorta allowed to increase the systolic pressure in two steps of 20 mmHg (conditions H1 and H2) above control values (condition C). After arterial pressure elevations (systolic pressure C: 119 +/- 8.1; H1: 142 +/- 7.9; H2: 166 +/- 7.7 mmHg; P < 0.01), there were no significant differences in heart rate (C: 125 +/- 13.9; H1: 125 +/- 13.5; H2: 123 +/- 14.1 bpm; P > 0.05) or LVEDP (C: 6.2 +/- 2.48; H1: 6.3 +/- 2.43; H2: 6.1 +/- 2.51 mmHg; P > 0.05). The values of dP/dt did not change after each elevation of arterial pressure (C: 3,068 +/- 1,057; H1: 3,112 +/- 996; H2: 3,086 +/- 980 mmHg/s; P > 0.05). In isolated rat papillary muscle, an afterload corresponding to 50% and 75% of the maximal developed tension did not alter the values of the maximum rate of tension development (100%: 78 +/- 13; 75%: 80 +/- 13; 50%: 79 +/- 11 g mm-2 s-1, P > 0.05). The results show that the rise in afterload per se does not cause changes in dP/dt or dT/dt.

[Influence of sustained increases of arterial pressure on left ventricular dP/dt when the left ventricular diastolic pressure is kept constant]. / Influência da elevação sustentada da pressão arterial sobre a dP/dt do ventrículo esquerdo mantendo-se constante a pressão diastólica do ventriículo esquerdo.

PURPOSE: To evaluate the influence of sustained elevations of arterial pressure on dP/dt values, while the left ventricular end diastolic pressure was kept constant. METHODS: Thirteen anesthetized dogs, mechanically ventilated and submitted to thoracotomy and pharmacological autonomic block (atropine-0.5 mg/kg i.v. + oxprenolol-3 mg/kg i.v.) were studied. The arterial pressure elevation was obtained by mechanical constriction of the descending thoracic aorta. Analyses were made in control (C) situation and after two successive increments of arterial pressure, sustained for 10 min, called hypertension 1 (H1) and hypertension 2 (H2), respectively. The end diastolic left ventricular pressure was kept constant by utilization of a perfusion system connected to the left atria. RESULTS: Heart rate did not change (C: 125 +/- 13.9 bpm; H1: 125 +/- 13.5 bpm; H2: 123 +/- 14.1 bpm; p > 0.05); the LVSP increased (C: 119 +/- 8.1 mmHg; H1: 142 +/- 7.9 mmHg; H2: 166 +/- 7.7 mmHg; p < 0.01); the AoDP increased (C: 89 +/- 11.6 mmHg; H1: 99 +/- 9.5 mmHg; H2: 120 +/- 11.8 mmHg; p < 0.01); the LVEDP (C: 6.2 +/- 2.48 mmHg; H1: 6.3 +/- 2.43 mmHg; H2:6.1 +/- 2.51 mmHg; p > 0.05) and the dP/dt (C: 3068 +/- 1057.1 mmHg/s; H1: 3112 +/- 995.7 mmHg/s; H2: 3086 +/- 979.5 mmHg/s; p > 0.05) did not change. CONCLUSION: dP/dt values are not influenced by a sustained elevation of arterial pressure, when the end diastolic left ventricular pressure is kept constant.

Análise dos casos de choque séptico e coagulaçäo intravascular disseminada em UTI: pediatria / Septic shock and disseminated intravascular coagulation in the intensive care unit

Realizou-se uma análise retrospectiva de 44 internaçöes na UTI pediátrica da Universidade Estadual Paulista-Unesp por choque séptico e coagulaçäo intravascular disseminada (CIVD), diagnosticados de acordo com os critérios propostos por Sprung (1991) e história crônica e laboratorial compativel com CIVD, segundo os critérios descritos por Forbes (1990) e Montgomery e Hathaway (1980). No periodo estudado 27,5 por cento dos pacientes sépticos apresentaram choque séptico e CIVD, grupo de risco foram lactentes menores de 6 meses (mais ou menos 55 por cento), desnutridos de II e II grau (>60 por cento), associaçäo infecciosa e falência de múltiplos órgäos e sistemas de acordo com critérios propostos por Wilkinson (DMOS> 4 órgäos.=80 por cento mortalidade). Encontrou-se alteraçäo hematológica no grupo de óbitos e nos sobreviventes, porém com maior gravidade nos óbitos