A detailed analysis was performed of the immunomodulatory and proteomic profiles of mesenchymal stromal cells (MSCs) administered to two patients with refractory acute respiratory distress syndrome (ARDS). The respiratory, hemodynamic, and multiorgan failure resolved and multiple pulmonary and systemic inflammation markers decreased. These observations highlight the mechanistic information that can be gained from clinical experience and the value of correlating in vitro potency assessments with clinical effects.

These findings show that the microcirculatory response to hyperoxemia, seen under other circumstances, persists during continuous-flow cardiopulmonary bypass, normothermic as well as hypothermic. If these adverse effects on tissue oxygenation by hyperoxemia can be further verified and shown to be valid for other organs than skeletal muscle, we would suggest that hyperoxemia should be avoided, especially during normothermic cardiopulmonary bypass.

Amino acids, particularly glutamate, have been proposed to play an important role in the recovery of cardiac oxidative metabolism after ischemia. In this investigation, the metabolic and hemodynamic effects of glutamate infusion after coronary operations were studied. From 220 to 240 ml 0.1 mol/L l-glutamic acid solution was infused in 10 patients during 1 hour starting 2 hours after operation. A control group of 10 patients received an infusion of 240 ml saline solution. During glutamate infusion, there were significant increases in the uptake of glutamate (from 0.7 +/- 0.2 micromol/min in the basal state to a peak of 5.7 +/- 1.2 micromol/min at 20 minutes) and lactate (from 4.9 +/- 2.0 micromol/min in the basal state to 14.1 +/- 4.4 micromol/min at 60 minutes; p < 0.01), whereas the uptake and release of other substrates remained essentially unaffected. Arterial glutamate levels (in whole blood) increased from 103 +/- 10 micromol/L to 394 +/- 20 micromol/L at 60 minutes. Thirty minutes after discontinuation of the glutamate infusion, arterial levels had decreased to 129 +/- 17 micromol/L. The markedly improved utilization of lactate and the unchanged release of alanine together suggest that the oxidative metabolism of the heart was stimulated by glutamate. The metabolic changes were associated with improved myocardial performance. Left ventricular stroke work index increased from 26.8 +/- 2.1 gm x beat(-1) x m(-2) body surface area to 31.3 +/- 3.1 gm x beat(-1) x m(-2) body surface area during glutamate infusion. Metabolic support with amino acids may provide a means to improve recovery of metabolic and hemodynamic function of the heart early after cardiac operations.

The influence of systemic blood flow (pump flow) and arterial blood pressure on renal function was studied during hypothermic cardiopulmonary bypass (CPB) in 14 male patients where the pump flow rate was varied between 1.45 and 2.20 l.min-1 m-2. Renal blood flow (RBF) was measured in the left renal vein with retrograde thermodilution technique and urinary flow and circulatory variables were measured with an on-line computer set-up. During CPB the RBF comprised 12-13% of the systemic blood flow and was positively related to systemic blood pressure (r = 0.71; P < 0.001) and pump flow rate (r = 0.69; P < 0.001). These findings indicate that the renal autoregulation was not operative during the hypothermic CPB period. According to multiple regression analysis, RBF was primarily determined by the pump flow rate and systemic blood pressure was of secondary importance. Urinary flow increased during hypothermic CPB and became closely related to blood pressure and pump flow. According to multiple regression analysis, urinary flow was primarily determined by systemic blood pressure.

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