Effects of catecholamines on the pulmonary venous bed in sheep.

OBJECTIVE: To assess the effects of various catecholaminergic agents on pulmonary venous tone. DESIGN: Prospective, randomized, controlled, experimental study. SETTING: Physiology laboratory of a university hospital. SUBJECTS: Thirty anesthetized, mechanically ventilated adult sheep. INTERVENTIONS: Four groups of six animals received 1-hr infusions of norepinephrine (0.5 microg/kg/min), epinephrine (0.5 microg/kg/ min), dopamine (10 microg/kg/min), or dobutamine (10 microg/kg/min). MEASUREMENTS AND MAIN RESULTS: A 7-Fr pulmonary artery catheter was placed in a proximal location to measure cardiac output and pressure in a large pulmonary vein (Ppw) after balloon inflation. Another catheter wedged in a small pulmonary artery measured pressure in a small pulmonary vein (Pdw). A third catheter measured left atrial pressure (PLA ). This method was able to detect the pulmonary venoconstrictive effects of histamine in a separate group of six animals. Pdw-PLA increased from a mean of 2.0+/-1.7 to 3.0+/-1.5 (SD) cm H2O (p < .01), 2.3+/-1.6 to 4.4+/-1.3 cm H2O (p < .01), and 1.7+/-1.0 to 3.5+/-2.2 cm H2O (p < .05) with norepinephrine, epinephrine, and dopamine, respectively. All of these drugs increased Pdw-Ppw, but only norepinephrine and epinephrine increased Ppw-PLA . No change in either pressure difference was observed with dobutamine. Elevation of cardiac output alone could not account for these findings since the increase in cardiac output induced by fluid infusion did not change the pressure differences. CONCLUSION: Norepinephrine, epinephrine, and dopamine at doses commonly used in humans increase pulmonary venous tone in sheep.

Global energetic failure in brain-dead patients.

The objective of this prospective, clinical study of consecutive patients was to test the hypothesis of a global energetic failure in brain-dead patients by analyzing indices of peripheral oxygenation during brain-dead resuscitation. Subjects comprised 24 subjects with brain death criteria from a multidisciplinary intensive care unit. The causes of brain death were multiple: severe traumatic head injury, cerebrovascular event, cerebral anoxia, primary brain tumor, and gunshot wound to the head. Interventions used were radial and pulmonary artery catheterization. Hemodynamic and gasometric parameters and blood lactate levels were measured immediately after the diagnosis of brain death (T0) and 4 hr later (T4), while patients were receiving a therapeutic protocol (fluids, vasopressive drugs) adjusted to reach a mean arterial pressure of 75 mmHg. In 18 of our 24 patients, a blood lactate level > or = 2 mmol/L (mean +/- SD: 4 +/- 2 mmol/L) associated with an increased mean lactate to pyruvate ratio (14.4 +/- 3.2) was observed at T0, while oxygen delivery (DO2) was high (533 +/- 208 ml/min/m2) and mean arterial pressure was 76 +/- 21 mmHg. Patients were subdivided into two groups according to changes in DO2 from T0 to T4: group D comprised 14 patients (10 with hyperlactatemia and 4 with normal lactate) in whom DO2 and oxygen consumption (VO2) simultaneously decreased from T0 to T4 without significant change in lactate level; group I comprised 10 patients (8 with hyperlactatemia and 2 with normal lactate) in whom DO2 and VO2 simultaneously increased, while the blood lactate level decreased significantly from 3.5 +/- 2.5 mmol/L at T0 to 2.1 +/- 1.0 mmol/L at T4 (P < 0.05). Our results indicate that the brain-dead state was frequently associated with a global energetic failure probably due to a cellular oxygen deficit, despite blood pressure within the normal range. This energetic failure, because it is associated with high levels of DO2, could result from a defect in peripheral oxygen extraction. Aggressive therapy, achieved by producing a further increase in DO2, may reduce this global tissue oxygen deficit.

Regional hemodynamic effects of perindopril in congestive heart failure.

The onset of heart failure is associated with complex neurohumoral, cardiac, and vascular changes. These disorders partly explain that, in this situation, regional distribution of blood flows is hardly modified with stability or increase in heart and brain flows and impairement of limb, renal, and splanchnic blood flows. Using the bidimensional Doppler technique to measure brachial blood flow and diameter and standard clearance techniques to determine renal and hepatic blood flows, we studied the effects of perindopril, a long-lasting angiotensin-converting enzyme inhibitor, on regional hemodynamics. We demonstrated that perindopril produces a very marked increase in forearm and kidney flows but a very minor increase in the hepatosplanchnic territory, resulting in a regional distribution of cardiac output that favors the renal and musculocutaneous territories. This mechanism of action might be an important contribution to clinical improvement observed with perindopril.

Effects of cardiovascular drugs on oxygen consumption/oxygen delivery relationship in patients with congestive heart failure.

The oxygen consumption (VO2)/oxygen delivery (DO2) relationship was analyzed in ten patients with severe congestive heart failure (CHF) and normal blood lactate levels. First dobutamine and then enoximone, after a washout period, were administered to each patient to increase cardiac output by at least 15 percent. Similar increases in DO2 were obtained with both drugs: from 285 +/- 46 to 393 +/- 87 ml/min/m2 for dobutamine, and from 285 +/- 54 to 392 +/- 99 ml/min/m2 for enoximone. However, while VO2 did not change (132 +/- 24 vs 132 +/- 21 ml/min/m2) (VO2/DO2 independency) with a dobutamine infusion (mean dose of 10 +/- 2 micrograms/kg/min), a significant increase in VO2 from 134 +/- 22 to 157 +/- 21 ml/min/m2 was observed with a bolus infusion of enoximone (mean dose of 1.7 +/- 0.5 mg/kg). These results, observed in patients with CHF without patent oxygen debt, suggest that an artefactual VO2/DO2 dependency might be induced by the cardiovascular drug used to elevate DO2, probably because of a drug-induced oxygen demand increase.

[Demonstration of tissue hypoxia due to defective peripheral extraction of oxygen (O2) during brain death]. / Mise en évidence d'une hypoxie tissulaire par trouble de l'extraction périphérique de l'oxygène (O2) des sujets en état de mort cérébrale.

Adequate oxygenation of potentially transplantable tissues must be maintained in patients in a state of cerebral death. An analysis of the relationship between oxygen consumption and arterial oxygen supply shows that proven tissue hypoxia occurs associated with high lactate in almost all patients in a state of cerebral death, even before haemodynamic parameters (blood pressure, heart rate) reach alarming levels. This tissue hypoxia, which exists even though arterial supply remains high, would suggest that there is a defect in peripheral oxygen extraction during the state of cerebral death. Intensive units should take this into account when maintaining these patients.

[Harvesting multiple organs]. / Les prélèvements multiples.

The development of organ transplants is limited by the shortage of organs. The improvement of this situation depends on two factors: increased awareness by the general public that refraining from refusing the removal of organs from the body of a patient with brain death is the most modern form of solidarity; and increased awareness by the medical profession that removal of organs should be proposed for every patient with brain death and that adequate resuscitative techniques should be used to preserve the organs in these patients. When the decision to harvest organs is taken, the transplant specialists must decide whether an organ should be used or not. Advances have been made in preservation techniques but are still insufficient to allow a reduction in immunosuppression. The UW solution is a major advance for liver, kidney and pancreas transplants. During harvesting, the separation of the vascular pedicles requires a good knowledge of surgical anatomy. Furthermore, the needs of the other surgical groups should be taken into account and concessions made to allow the harvesting of the greatest possible number of organs and consequently the treatment of the largest number of patients awaiting organs.