Takashi Nagura

Two-dimensional echocardiographic evaluation of inferior vena cava, right ventricle, and left ventricle during positive-pressure ventilation with varying levels of positive end-expiratory pressure

The effects of intermittent positive-pressure ventilation (IPPV) with 0, 10, and 15 cm H2O of PEEP on inferior vena cava (IVC), right and left ventricular length and septal-lateral dimensions, and cardiac output were examined in 19 patients with respiratory failure using two-dimensional echocardiography. In five patients, cardiac output was also obtained by the thermodilution technique. As PEEP was increased, IVC dimensions increased during both inspiration and expiration, and the IVC collapsibility index decreased. This indicated an increase in venous stasis and decrease in venous return to the right atrium. Increasing PEEP was associated with progressive decreases in cardiac output, and length and septal-lateral dimensions of both ventricles. The decreased cardiac output during IPPV with 10 and 15 cm H2O PEEP may be due to the decreased venous return and ventricular filling. Cardiac output determined by echocardiography was correlated closely to that by the thermodilution technique.

Improvement of renal dysfunction in dogs with endotoxemia by a nonselective endothelin receptor antagonist

OBJECTIVES During endotoxemia, there is a marked and intractable decrease in systemic blood pressure, as well as profound vasoconstriction of the renal artery, thereby leading to septic shock and acute renal failure. The purpose of this study was to elucidate the effect of endothelin-1, a potent endothelium-derived vasoconstrictor peptide, on the hemodynamic and renal vascular changes seen in endotoxemia. DESIGN Prospective, comparative, experimental study. SETTING Laboratory at a university hospital. SUBJECTS Thirty-two male mongrel dogs (12.1+/-0.4 kg) under pentobarbital anesthesia. INTERVENTIONS Four groups of animals were studied: a) the lipopolysaccharide (LPS) group (n = 10), which received LPS (250 ng/kg/min for 2 hrs); b) the TAK-044 (a nonselective endothelinA/ endothelinB receptor antagonist) plus LPS group (n = 12), which received a bolus of TAK-044 (5 mg/kg) 0.5 hr before the start of LPS infusion; c) the TAK-044 plus vehicle group (n = 5), which received the same dose of TAK-044 0.5 hr before the start of vehicle infusion; and d) the control group (n = 5), which received only vehicle infusion. MEASUREMENTS AND MAIN RESULTS Changes in systemic and renal hemodynamics, blood gas, and renal function were measured at baseline, and at 0.5, 1, 2, 3, and 4 hrs. Infusion of LPS resulted in significant decreases in mean arterial pressure, arterial pH, Pao2, base excess, urine volume, renal blood flow, creatinine clearance, and urine osmolality. The administration of TAK-044 before LPS infusion did not affect the LPS-induced hypotension. In contrast, the receptor antagonist prevented LPS-induced metabolic acidosis and hypoxemia, and improved LPS-induced decreases in urine volume, renal blood flow, creatinine clearance, and urine osmolality, whereas TAK-044 or vehicle administered alone resulted in no significant hemodynamic or blood gas changes. Plasma endothelin-1 concentrations significantly increased after LPS infusion, with or without TAK-044. CONCLUSIONS The present study suggests that endothelin-1 plays an important role in the impaired renal hemodynamics and renal function associated with endotoxemia, and that endothelin receptor antagonists may be useful as therapeutic agents for acute renal failure during endotoxemia.

Endothelin-1 and atrial natriuretic peptide in septic shock

utes are being utilized. 4 Although a recent randomized trial of s tandard and high-dose epinephrine for cardiac arrest outside the hospital failed to reveal a survival advantage for the higher dose protocol, there was a t rend toward improved survival when high-dose epinephrine was administered within 10 minutes after the onset of cardiac arrest, as can be achieved in the catheterizat ion laboratory. 5 There are obvious l imitat ions to this report. I t is not randomized and it is retrospective. The dose of intracoronary epinephrine adminis tered to these pat ients was arbi t rar i ly selected and may not have resulted in the opt imal hemodynamic response. Int racoronary epinephrine was generally selected as a t rea tment of last resort and may have been more effective given earlier during the episode of hypotension. Fur thermore , it was often adminis tered simultaneously with other therapies, and its precise benefit, or even potent ia l harm to pat ients 5 through 8, is impossible to define. However, based on our observations in most pat ients of a rapid increase in arterial blood pressure after the adminis t ra t ion of intracoronary epinephrine, it would seem reasonable to consider its use in cases of refractory hypotension occurring during PTCA when other measures prove ineffective.

Increased Plasma Concentrations of Brain Natriuretic Peptide in Patients With Acute Lung Injury

PURPOSE This study was performed to elucidate the pathophysiological role of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in acute lung injury. MATERIALS AND METHODS We sequentially measured plasma concentrations of immunoreactive BNP and ANP in 10 patients (mean age, 63 years (with acute lung injury and compared those with hemodynamic parameters and pulmonary functions. RESULTS Plasma concentrations of immunoreactive BNP and ANP were markedly elevated at entry into the study. Plasma BNP concentrations during the early course (3 days) showed significant (P < .01) positive correlations with systemic vascular resistance index (r = .708) and pulmonary vascular resistance index (r = .573), but a negative correlation with cardiac index (r = .608). Plasma ANP concentrations showed a significant (P < .05) positive correlation with pulmonary capillary wedge pressure (r = .398). Plasma BNP in 4 patients who died and 1 patient with acute renal failure remained elevated during the entire hospital length of stay (12 days). CONCLUSION These findings suggest that circulating BNP plays an important role in acute lung injury along with ANP as a compensatory mechanism for cardiac dysfunction accompanied by increased systemic vascular resistance index and pulmonary vascular resistance index. Circulating BNP may be a sensitive humoral marker for the degree of ventricular dysfunction associated with acute lung injury.

PLASMA ALPHA -ATRIAL NATRIURETIC PEPTIDE CONCENTRATIONS IN ACUTE RESPIRATORY FAILURE ASSOCIATED WITH SEPSIS : PRELIMINARY STUDY

Plasma alpha-atrial natriuretic peptide (alpha-ANP) concentrations were measured during mechanical ventilation in nine patients with acute respiratory failure (ARF) associated with sepsis. The relationships between alpha-ANP and pulmonary hemodynamic variables were examined. A total of 22 measurements of alpha-ANP and other variables were obtained. The mean plasma alpha-ANP concentration of 22 measurements was 120.1 +/- 79.8 pg/ml (normal 31.7 +/- 12.0, mean +/- SD). Plasma alpha-ANP concentrations correlated with mean pulmonary artery pressure (MPAP) (r = .703, p less than .01) and pulmonary vascular resistance (PVR) (r = .606, p less than .01), but not with other variables. These findings suggest that alpha-ANP elevation may be related to the increases in MPAP and PVR in ARF associated with sepsis.

Pathologic role of endothelin-1 in septic shock.

To elucidate the pathologic role of endothelin-1 (ET-1) in septic shock, we measured plasma ET-1 concentrations after bacterial lipopolysaccharide (LPS) administration in dogs and determined systemic, pulmonary, and renal hemodynamics and blood gas parameters with or without the nonselective ET receptor antagonist TAK-044. Plasma ET-1 concentrations increased significantly after LPS administration, which correlated positively with mean arterial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, and central venous pressure. LPS infusion induced hypotension, metabolic acidosis, hypoxemia, and renal dysfunction. TAK-044 prevented LPS-induced metabolic acidosis, hypoxemia, and renal dysfunction, but not hypotension. These findings suggest that increased circulating ET-1 plays a compensatory role in the reversal of systemic vasodilatation in septic shock, but exerts deleterious effects on renal and pulmonary circulation.