Individual free fatty acids and lactate uptake in the human heart during severe sepsis.

Coronary haemodynamics and myocardial metabolism of nonesterified fatty acids (NEFA) and lactate were studied in 11 patients with severe sepsis, and compared to 10 control subjects. Coronary sinus blood flow was evaluated by thermodilution. Arterial and coronary sinus blood samples were collected for the measurement of lactate and total and individual NEFA concentrations both in septic and control patients. There was an increase in lactate and total NEFA arterial concentrations with a marked increase in palmitic and linolenic acids. The uptake of the main NEFA (C14:0 to C18:2) was significantly decreased. In the control group, individual NEFA uptake was proportional to their arterial concentrations. This relationship was not observed in patients with sepsis: there was no preferential extraction of any particular NEFA. Furthermore, in patients with sepsis, myocardial oxygen consumption did not correlate with NEFA, but only with lactate uptake. Alterations in NEFA uptake were found to be constant during severe sepsis and are consistent with major disturbances in myocardial metabolism.

Right ventricular performance in patients with acute respiratory failure.

To examine the right ventricular response to acute respiratory failure, serial studies of biventricular performance were analysed in 34 such patients, specifically detailing the role of associated underlying disease. During the initial study, the 34 patients with acute respiratory failure had a higher right ventricular end-diastolic volume than the control group (+21%), associated with a decrease in right ventricular ejection fraction, abnormalities which tended to return to normal values in the 15 survivors. In the 9 patients who died of refractory hypoxemia with severe pulmonary hypertension, the right ventricular dilation allowed to maintain stroke volume. In contrast, in 8 patients who died of septic shock, biventricular function was progressively altered (right and left ventricular ejection fraction = -37% and -35%). In 4 patients who died of cardiogenic shock (viral myocarditis), the cardiac function was the lowest (right and left ventricular ejection fraction = -59% and -60%). Only patients with acute respiratory failure associated with septic shock or viral myocarditis are unable to maintain their stroke volume.

Right ventricular dysfunction in patients with septic shock.

Using a rapid computerized thermodilution method, we examined the evolution of right ventricular performance in 23 patients with septic shock. Nine survived the episode of septic shock. The other 14 patients died of refractory circulatory shock. Significant right ventricular systolic dysfunction, defined as decreased ejection fraction (-39%) and right ventricular dilation (+38%) was observed in all patients with septic shock. However, in the survivors, increased right ventricular preload may prevent hemodynamic evidence of right ventricular pump failure by utilizing the Frank-Starling mechanism to maintain stroke volume. Conversely, in the nonsurvivors, right ventricular dysfunction was more prononced two days after the onset of septic shock, leading to a fall in stroke. In the last patients, a decrease in contractility appears to be the major factor accounting for decreased right ventricular performance, as evidenced by the marked increase in end-systolic volume (+27%) without significant change in pulmonary artery pressure, during the later stage of septic shock. The observed right ventricular pump failure then appears associated with an alteration in diastolic mechanical properties of this ventricle, as suggested by a leftward displacement of the individual pressure-volume curves.

Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.

To investigate disturbances in the coronary circulation and myocardial metabolism during septic shock, we examined coronary sinus blood flow and myocardial substrate extraction in 40 patients with septic shock and 13 control patients. Patients with coronary artery disease were excluded from this study. The global hemodynamic pattern of the septic patients was characterized by a lower stroke volume, despite an elevated cardiac index. Coronary sinus blood flow was high (187 +/- 47 vs 130 +/- 21 ml/min in the control group, p less than .001) due to marked coronary vasodilation, especially in the subgroup of nonsurvivors. In contrast to the control group, myocardial lactate uptake was elevated, while that of free fatty acids, glucose, and ketone bodies was diminished in patients with septic shock. These findings were especially prominent in the nonsurvivors. Expressed as oxygen equivalents, the contribution of free fatty acids as an energy source of the myocardium was markedly diminished in septic patients (12% vs 54% in the control group, p less than .005), while that of lactate was increased (36% vs 12%, p less than .01). The observed shift in myocardial substrate extraction was associated with a discrepancy between measured myocardial oxygen consumption and that calculated chemically from commonly available exogenous substrates: 41% of myocardial oxygen consumption was not explained by the utilization of commonly available substrates extracted from coronary circulation in all patients with septic shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Bedside evaluation of right ventricular performance using a rapid computerized thermodilution method.

In 34 patients, we assessed the reproducibility and accuracy of a new, computerized, thermodilution method that determines right ventricular ejection fraction (RVEF). We compared the results from this new algorithm with simultaneous results from the conventional plateau thermodilution method and from both first-pass and gated nuclear techniques. Using this new method improved the reproducibility of thermal determinations of RVEF. Although the thermal values were lower, the correlations between thermal and nuclear measurements were close [r = .92 (first-pass technique), r = .81 (gated technique)]. This new method seems particularly appropriate for serial monitoring of RV performance.

Mechanisms of decreased left ventricular preload during continuous positive pressure ventilation in ARDS.

Continuous positive pressure ventilation is associated with a reduction in left ventricular preload and cardiac output, but the mechanisms responsible are controversial. The decrease in left ventricular preload may result exclusively from a decreased systemic venous return due to increased pleural pressure, or from an additional effect such as decreased left ventricular compliance. To determine the mechanisms responsible, we studied the changes in cardiac output induced by continuous positive pressure ventilation in eight patients with the adult respiratory distress syndrome. We measured cardiac output by thermodilution, and biventricular ejection fraction by equilibrium gated blood pool scintigraphy. Biventricular end-diastolic volumes were then calculated by dividing stroke volume by ejection fraction. As positive end-expiratory pressure increased from 0 to 20 cm H2O, stroke volume and biventricular end-diastolic volumes fell about 25 percent, and biventricular ejection fraction remained unchanged. At 20 cm H2O positive end-expiratory pressure, volume expansion for normalizing cardiac output restored biventricular end-diastolic volumes without markedly changing biventricular end-diastolic transmural pressures. The primary cause of the reduction in left ventricular preload with continuous positive pressure ventilation appears to be a fall in venous return and hence in right ventricular stroke volume, without evidence of change in left ventricular diastolic compliance.

Bicarbonate hemodialysis of patients with acute renal failure and severe sepsis.

During hemodialysis (HD), septic patients with acute renal failure (ARF) often exhibit severe hemodynamic instability, with a fall in BP that requires a large-volume infusion or even cessation of dialysis. To investigate the hypothesis that acetate transfer plays a role in the BP decrease, we compared acetate (Ac) and bicarbonate (Bi) HD in ten septic ARF patients. Patients were dialyzed daily for 4 h with a single-pass system and 1.1 m2 cuprophan dialyzers, alternately using Ac and Bi as the dialysate buffer. Heart rate and systemic arterial resistance did not change significantly during use of either buffer, and changes in pulmonary wedge pressure were similar. However, decreases in cardiac output and mean arterial pressure were more pronounced during Ac-HD than during Bi-HD. Rapid correction of metabolic acidosis and a larger decrease of plasma potassium concentration occurred during Bi-HD. These results suggest that Bi-HD was better tolerated than Ac-HD because of changes in myocardial contractility that may be related to different effects on acid-base status and plasma potassium concentrations.

Alterations in contrast medium-induced coronary reactive hyperemia after bepridil in patients with coronary artery disease.

The acute effects of an intravenous infusion of bepridil (BEP) (4 mg . kg-1) on left ventricular (LV) hemodynamics, coronary sinus blood flow (CSBF), and myocardial metabolism were studied in eight patients with coronary artery disease. In contrast with data previously reported with calcium channel blockers, BEP induced an elevation in LV end-diastolic pressure from 12.0 +/- 7.1 to 20.1 +/- 7.2 mm Hg (mean +/- SD, p less than 0.001) and a fall in LV dp/dt max from 1339 +/- 302 to 1177 +/- 251 mm Hg . sec-1 (p less than 0.01). This significant alteration in LV function is likely to be explained by the lack of effect on heart rate and aortic pressure observed after an acute intravenous infusion of BEP. Myocardial oxygen consumption (MVO2) increased from 448 +/- 272 to 498 +/- 273 mumol . min-1/100 g LV (p less than 0.05) as did CSBF from 79.5 +/- 42.7 to 92.1 +/- 45.1 ml X min-1/100 g LV (p less than 0.01). Lactate extraction fell from 0.33 +/- 0.17 to 0.15 +/- 0.17 (p less than 0.05). A contrast medium-induced coronary reactive hyperemia (HPR) evidenced an increased hyperemic volume from 9.5 +/- 3.6 to 12.1 +/- 4.5 ml/100 g LV (p less than 0.01) and HPR duration from 23.3 +/- 6.9 to 32.3 +/- 15.4 sec (p less than 0.05) after BEP. However, the peak/resting CSBF ratio was blunted after BEP from 1.74 +/- 0.18 to 1.61 +/- 0.12 (p less than 0.05), evidencing a net effect of BEP on HPR.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen consumption during septic shock. Effects of inotropic drugs.

Septic shock may be defined as a clinical entity wherein a patient has an inadequate peripheral metabolism in the presence of circulating bacteria. The demands for metabolic requirements of the tissues and hence for oxygen transport to these tissues are then markedly high. The average response to increased metabolism in such patients is a percentage increase in cardiac output that is comparable to the percentage increase in oxygen consumption while oxygen extraction rate does not change or even decreases in severe or/and advanced septic shock. This emphasizes the high priority placed by the body on the ability to increase blood flow from the heart in the presence of increased metabolic demands due to sepsis. Concerning the myocardium, oxygen consumption is low in hyper- and hypodynamic states of septic shock, probably and partially due to marked arterial vasodilatation. However, in hypodynamic states, the lower value of perfusion pressure may account for a decrease in myocardial oxygen supply, especially in subendocardial areas and may be responsible for myocardial ischaemia, more especially as myocardial oxygen extraction as well as systemic oxygen extraction is impaired. The goal of therapeutics is to improve oxygen availability through: (1) maintenance of haemoglobin levels and (2) increases in stroke volume using inotropic drugs since these drugs may produce a rise in myocardial oxygen supply higher than their drug-induced increase in oxygen requirements in hypodynamic states of septic shock.

Analysis of increased myocardial contractility during sodium acetate infusion in humans.

To analyze the reported effects of acetate on left ventricular (LV) contractility during dialysis, LV function was studied before and after a 20-min sodium acetate (Na Ac) infusion (0.06 mmoles X kg-1 X min-1) in seven patients with heart rate (HR) controlled by atrial pacing. Angiographically determined LV volumes and LV pressures were used to calculate the LV function indices. A plasma acetate concentration of 3.13 +/- 1.05 (SD) mmoles X liter-1 induced an increase in cardiac index from 3.8 +/- 0.6 to 4.4 +/- 0.6 (SD) liter X min-1 X m-2 (P less than 0.01) and a rise in total body O2 consumption from 7.47 +/- 1.28 to 8.67 +/- 1.66 mmoles X min-1 X m-2 (P less than 0.05); there was no alteration of the volume elastic constant, of the end diastolic stress, and of the end systolic stress. There was an increase of the ejection fraction from 0.44 +/- 0.10 to 0.51 +/- 0.09 (P less than 0.01), the maximum velocity of shortening (Vmax, sec-1) from 1.37 +/- 0.25 to 1.55 +/- 0.28 (P less than 0.05), and of the end systolic stress-end systolic volume ratio (g X cm-2 X ml-1) from 2.99 +/- 0.76 to 3.40 +/- 0.98 (P less than 0.01). Hence, the enhancement of these indices was not the consequence of any alteration of HR, preload, or afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

[Improvement of dialysis tolerance in patients with severe infections using a bicarbonate dialysate]. / Amélioration de la tolérance dialytique des patients atteints d'infection grave par l'utilisation d'un dialysat au bicarbonate.

Severe septic patients, with high cardiac output (CO) and low systemic arterial resistances (SAR), often develop an uncontrolled fall in blood pressure (BP) during acetate hemodialysis (AcHD), because they are especially unable to increase appropriately their SAR with fluid removal. To investigate the possibility that Ac transfer plays a part in this fall in BP, we studied and compared hemodynamic and biochemistry status of such 10 patients with acute renal failure by alternately using Ac and bicarbonate (Bi) dialysate. CO and mean systemic arterial pressure decrease more during AcHD than during BiHD, whereas the changes in pulmonary wedge pressure were similar; heart rate and SAR remained unchanged. Thus the better hemodynamic tolerance during BiHD seems to be due to a change in myocardial contractility that may be related to differences in acid-base status and plasmatic potassium concentrations.