Serotonin can induce pulmonary hypertension, hypoxia and bronchoconstriction, and ketanserin has been shown to reverse these effects on various experimental models of acute respiratory failure. In the present study, the hemodynamic and gasometric effects of ketanserin were studied during acute respiratory failure induced by an air infusion at a rate of 10 ml/min in dogs. During a 60-min air infusion, 10 dogs received 4 mg of ketanserin i.v. and 10 dogs served as control. Ketanserin-treated dogs had similar pulmonary hypertension even though more significant decreases in arterial pressure and systemic vascular resistance characterized the systemic effects of ketanserin. Similarly, a marked increase in hematocrit observed in control dogs (from 36.9 to 43.8%, p less than 0.01) was totally prevented by ketanserin (from 40.3 to 40.4%, NS). Hypoxia was similar, although the increase in pulmonary shunt was attenuated (259 instead of 468%). Therefore, the influence of serotonin is very limited in acute respiratory failure secondary to air embolization. Serotonin might have a more important influence on the systemic than on the pulmonary vasculature in these conditions.

This study explored the hemodynamic effects of amrinone, a phosphodiesterase inhibitor, in association with intravenous fluids, in the treatment of endotoxin shock. Mongrel dogs were anesthetized with pentobarbital and mechanically ventilated with room air. Treatment was started 30 min after slow intravenous administration of 3 mg/kg of E. coli endotoxin. In the first part of the study, ten dogs were resuscitated for 30 min with intravenous saline alone (10 ml/kg) and for the next 3 h by saline (10 ml/kg/h) and amrinone 40 micrograms/kg/min. During this latter period, arterial pressure remained stable while cardiac output significantly increased from 3.1 +/- 0.5 to 5.2 +/- 0.7 l/min (P less than 0.01), and oxygen delivery increased from 616 +/- 92 to 983 +/- 156 ml/min (P less than 0.01). Comparison with control animals revealed that amrinone infusion prevented the decrease in left ventricular stroke work and markedly increased oxygen delivery. In the second part of the study, 18 dogs were treated by saline infusion titrated to maintain pulmonary artery balloon-occluded pressure at baseline level. In ten dogs, amrinone was added 60 min after endotoxin administration at a dose of 40 micrograms/kg/min. Total amount of fluids infused averaged 87 +/- 14 ml in the amrinone-treated dogs and 64 +/- 15 ml in the control dogs (differences nonsignificant). Oxygen delivery and oxygen consumption increased significantly in the amrinone-treated dogs (from 541 +/- 36 to 1063 +/- 176 ml/min, P less than 0.01, and from 145 +/- 23 to 202 +/- 38 ml/min, P less than 0.01, respectively) but not in the control dogs. The amrinone-treated dogs had lower PaO2 and higher venous admixture than the control dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

The hemodynamic effects of dopamine and dobutamine (at doses of 6 micrograms X kg-1 X min-1) were compared during fluid resuscitation from septic shock induced by endotoxin (3 mg/kg) in the dog. In the first part of the study, when a standard amount of saline solution was infused (in 24 dogs), dopamine infusion resulted in higher cardiac filling pressures than did dobutamine infusion, whereas dobutamine infusion resulted in higher cardiac output. In the second part of the study, when fluid infusion was titrated to maintain pulmonary artery balloon-occluded pressure at constant level (in 24 dogs), the total amount of fluids was significantly greater with dobutamine than when dopamine was used (109 +/- 13 vs 71 +/- 10 ml/kg). The combination of dobutamine with fluids resulted in significantly greater stroke volume (39.6 +/- 3.8 vs 21.0 +/- 4.0 ml, P less than 0.05) and oxygen consumption (194 +/- 18 vs 144 +/- 8 ml/min, P less than 0.05). The different effects of dopamine and dobutamine on cardiac filling pressures can be due to differences in effects on myocardial contractility, ventricular afterload, and cardiac compliance. This experimental study indicates that when fluid therapy is combined with adrenergic agents in resuscitation from septic shock, dobutamine can be associated with higher cardiac output and oxygen transport and can result in higher tissue oxygen consumption than dopamine.

While calcium administration has been recommended in CPR, its beneficial effects have been challenged. The effectiveness of calcium chloride was evaluated and compared with epinephrine during successive episodes of electromechanical dissociation (EMD) after ventricular fibrillation in closed-chest dogs. Each of three successive episodes of CPR was randomly and blindly treated by repeated (every 2 min) injections of 5 ml H2O plus either 500 mg of calcium chloride (CaCl2), 1 mg of epinephrine (Epi), or 5% dextrose (D5W). Of 42 CPR attempts performed on 16 dogs, 16 were reversed by only chest compression and artificial ventilation. For the 26 CPR with pharmacologic intervention, recovery was obtained after one injection in 5 of 6 Epi but only in 4 of 11 CaCl2 and 4 of 9 D5W. Only four CPR attempts were ultimately unsuccessful, all in CaCl2 group. During recovery, the Epi group showed significantly higher arterial pressures and heart rates but less severe acidemia. In this model, calcium chloride alone is ineffective during EMD.

Air embolization has been shown to produce a reversible permeability-type of pulmonary oedema. The present study investigated the haemodynamic, gasometric and haematological changes associated with air infusion in the spontaneously breathing dog (weight 31 +/- 5 kg). Air was infused at a rate of 10 ml X min-1 for 60 min (10 dogs) or 180 min (5 dogs). During the air infusion, a dramatic increase in pulmonary artery pressure was associated with only a moderate increase in right atrial pressure and limited decreases in arterial pressure and in cardiac output. A marked decrease in end-tidal PCO2 reflected the increase in dead space. These changes were stable during air infusion, but rapidly reversed after the end of infusion. However, hypoxaemia, defined by a decreased PaO2/PAO2 ratio, deteriorated with time and was only partially reversible. At histological examination, interstitial pulmonary oedema was present around the pulmonary arterioles. Air infusion was associated with rapid decreases in circulating leukocytes and platelets and complement activation. Since leukotriene release might be associated with leukocyte activation in this model, seven additional dogs were pretreated by inhalation of 10 mg of the leukotriene inhibitor U-60,257. The increase in pulmonary vascular resistance and in pulmonary shunt were moderately reduced and the drop in circulating leukocytes and platelets was strikingly abolished in the treated animals. Air infusion in the spontaneously breathing dog represents a model of very stable and reversible pulmonary hypertension. It can reproduce important pathophysiological features implicated in the development of pulmonary oedema.(ABSTRACT TRUNCATED AT 250 WORDS)

Domb, Marc; der Linden, Philippe Van; Azimi, Grace; Motte, Serge; de Boelpaepe, Corinne; Vincent, Jean-Louis Author Information

Hypertonic saline has been used in the treatment of hypovolemic or burn shock for its rapid volemic effects. Hypertonic solutions could also improve cardiac performance and protect cellular metabolism in acute circulatory failure. We therefore studied the hemodynamic effects of continuous hypertonic saline infusion in the treatment of severe endotoxic shock in the dog. Thirty minutes after slow injection of 3 mg/kg of Escherichia coli endotoxin, fluid resuscitation with either hypertonic saline containing 1,200 mOsm of NaCl/liter (eight dogs) or normotonic saline solution (eight dogs) was started and titrated to maintain left-sided filling pressures at control level. For the next 210 min, the total amount of fluid administered was 64.5 +/- 7.8 ml/kg in the hypertonic group and 83.6 +/- 10.3 ml/kg in the normotonic group. These differences were not statistically significant. Intravascular pressures were similar in the two groups, but cardiac output, stroke volume, and oxygen consumption were significantly higher in the hypertonic group. These results therefore indicate that hypertonic saline can rapidly restore oxygen transport and tissue oxygen consumption in septic shock. The duration of these hemodynamic effects, however, remains to be determined.

Prostacyclin (PGI2) has been shown to present myocardial protective effects which could be beneficial during cardiac arrest. We tested this hypothesis in a closed-chest dog model in which electromechanical dissociation (EMD) can be predictably observed after 90 to 120 seconds of ventricular fibrillation whithout chest compression. Six dogs were pretreated with a PGI2 infusion at a rate of 1 mcg/kg/min and six other dogs served as control animals.

Blecic, Serge; Backer, Daniel De; Huynh, Chin Huy; Domb, Marc; Deleuze, Michel; Luypaert, Pascal; Vincent, Jean-Louis Author Information

Calcium-entry blockers were administered in an attempt to protect myocardium during cardiac arrest due to ventricular fibrillation in mechanically ventilated dogs. An intravenous injection of verapamil, nifedipine, or lidoflazine was administered prior to successively prolonged episodes of ventricular fibrillation, during which no thoracic compression was performed. It is of interest that ventricular defibrillation was more easily obtained after treatment with the three drugs. As previously observed in this model, nine control dogs developed electromechanical dissociation (EMD) after 120 seconds of ventricular fibrillation. In contrast, six of the 11 dogs treated with 0.3 mg/kg of verapamil recovered mechanical systole after 120 seconds of ventricular fibrillation (p less than 0.05). Nifedipine administration also postponed the onset of EMD in three of four dogs. However, lidoflazine postponed the onset of EMD in only one of the eight dogs. The later onset of EMD after administration of verapamil or nifedipine in this model was attributed to myocardial protection by calcium-entry blockers during ventricular fibrillation. Decreased energy utilization during cardiac arrest was considered to be the principal protective mechanism. These observations indicate calcium-entry blockers, and especially verapamil and nifedipine, can be valuable drugs during cardiac resuscitation for ventricular fibrillation.

Increased release of serotonin (5-hydroxytryptamine, 5-HT) can play a significant role in the development of acute respiratory failure. The hemodynamic effects of ketanserin, a selective inhibitor of 5-HT2 receptors, were studied in eight patients who developed acute respiratory insufficiency after an episode of circulatory shock. Administration of ketanserin was associated with reductions in systemic and pulmonary artery pressures, without significant change in heart rate or cardiac output. Concomitant decreases in hemoglobin and protein concentrations suggested an associated increase in plasma volume. These changes were attributed to an increased peripheral pooling of blood related to vasodilation. Arterial oxygenation and pulmonary shunt were unaffected. These results indicate ketanserin represents a promising vasoactive agent for treatment of acute respiratory failure in critically ill patients.