Search

OBJECTIVE This study was undertaken to test the hypothesis that hemodialysis with a large-pore membrane would improve heart function during acute endotoxin shock. SETTING Large animal laboratory. DESIGN Eighteen mongrel dogs were instrumented to measure left ventricular maximum end-systolic elastance (left ventricular maximum elastance at end systole), cardiac output, circumflex artery blood flow, and myocardial mechanical efficiency (CO x MAP/MVO2, where CO is cardiac output, MAP is mean arterial pressure, and MVO2 is myocardial oxygen consumption). Plasma catecholamine concentrations were determined by high-performance liquid chromatography. Endotoxin shock was induced by infusing 5.0 microg/kg/min of Escherichia col 0127:B8 endotoxin in the portal vein for 60 mins, followed by 2.0 microg/kg/min of constant infusion. Control dogs (n = 6) received 4.0 mL/kg/min of saline; hemodialysis dogs (n = 6) underwent venovenous hemodialysis in 50-min intervals using a polysulfone filter (1.2 m2; mean pore size, 0.50 nm; blood flow rate, 400 mL/min; ultrafiltrate, "zero-balanced"); shams (n = 5) were treated identically to hemodialysis dogs, except that no convective dialysis was performed. A fourth group (n = 6) was treated with dopamine (5.0-7.0 microg/kg/min, optimal dose for contractile increase based on dose-response studies). MEASUREMENTS AND MAIN RESULTS After 2 hrs of treatment, left ventricular maximum elastance at end systole increased and was unchanged in controls (30 +/- 5 mm Hg/mm) and shams (24 +/- 6 mm Hg/mm) compared with basal control. Hemodialysis treatment increased contractility (53 +/- 4 mm Hg/mm), as did dopamine treatment (54 +/- 7 mm Hg/mm). Endotoxin shock reduced mechanical efficiency to 45% of basal control; with hemodialysis treatment, left ventricular efficiency returned to 64% of basal control measurement, compared with 49% with dopamine treatment. During treatment, myocardial glucose uptake was increased with hemodialysis compared with other groups. No difference was observed among groups for left ventricular end-diastolic pressures or dimensions, or catecholamine concentrations. CONCLUSIONS Large-pore hemodialysis increased left ventricular contractility to a similar degree as dopamine and provided a marginal improvement in myocardial glucose uptake and mechanical efficiency.

Currently, there are no practical means of prospectively determining cardiopulmonary resuscitation (CPR) adequacy in the field. Airway CO2 excretion can be noninvasively and stably measured under changing environmental conditions. We investigated the relationships between the volume of airway CO2 excreted (CO2EX) during CPR to regional blood flow (RBF) and survival. A total of 21 dogs were randomly divided into four CO2EX groups (5, 5-6,6-7 and7 ml CO2/min per kg), anesthetized, instrumented and ventilated with an in-line infrared airway CO2 sensor. Anesthesia was reduced and baseline measurements made. Ventricular fibrillation (VF) was initiated and resuscitation withheld for 3 min, followed by 17 min of CPR. Compression force alone was adjusted to maintain predetermined CO2EX. Animals were resuscitated, monitored for 2 h and observed for an additional 22 h. RBF was determined at baseline, 16 min post-VF and 60 min post-resuscitation. Mean CO2EX during CPR was significantly higher in survivors than nonsurvivors. The probability of survival increased as CO2EX increased. The highest CO2EX group had the highest rate of survival (86%), but did not always have significantly higher cardiac output (CO), myocardial or cerebral blood flows (MBF, CBF) than the lowest CO2EX group with a 0% survival rate. These data suggest survival is tracked better by CO2EX than by CO, MBF or CBF. Therefore, CO2EX appears to provide a practical reliable noninvasive method of determining CPR efficacy in the field.

There is currently no practical method for determining cardiopulmonary resuscitation (CPR) efficacy in the field. We investigated the relationship between the volume of carbon dioxide (CO2) excreted in the airway (CO2EX) when tidal volume and respiratory rate are controlled, and cardiac output (CO), an indicator of CPR efficacy, to determine the potential of CO2EX as a practical noninvasive field monitor of CPR efficacy. Thirteen mongrel dogs were anesthetized, instrumented and ventilated 13 times/min at a fixed tidal volume with an infrared airway CO2 sensor. CO2EX = (PCO2/bar. press) x (tidal vol) x (breaths/min), and expressed in ml/min per kg. Sequences of control, CPR with 3-4 different compression forces, and recovery measurements were recorded 10-15 times/animal. CO2EX and CO fell simultaneously with ventricular fibrillation. CPR immediately increased CO2EX and CO. Both changed consistently and in the same direction as compression force. Return of spontaneous circulation immediately increased CO2EX and CO above controls, with a gradual return to control levels. CO2EX was always below 8 ml-CO2/min/kg during CPR and above this during spontaneous circulation. With alveolar ventilation controlled, CO2 movement is regulated by CO, CO distribution and CO2 stores shifts. Normally, CO accounts for 15% of CO2EX variability. In this study CO accounted for > or = 65% of CO2EX variability during CPR, indicating CO2EX changes were primarily due to CO changes. When ventilation is controlled, CO2EX during CPR reliably tracks changes in CO. Therefore, CO2EX may provide a practical noninvasive method of determining CPR efficacy as the CPR is being performed.

A large animal model of fulminant hepatic necrosis is necessary to test the efficacy of artificial liver support systems. A recent model was developed using D-galactosamine in anesthetized dogs. Because of the difficulties encountered with prolonged anesthesia, a similar protocol was used in 10 unanesthetized dogs. Intravenous infusions of D-galactosamine (1.0 to 1.5 gm/kg) did not result in uniform death of all animals at 72 hours or development of hypoglycemia. Severe hepatic necrosis was observed in all animals, but residual hepatocyte viability was evident in some. All animals developed severe consumption coagulopathy with histological evidence of disseminated intravascular coagulation (DIC) in four. A clinical picture characteristic of endotoxic shock was observed in most animals as a terminal event. The presence of endotoxin was confirmed in all dogs tested after 12 hours (7/10). The differences observed between this model and the anesthetized model are probably because of the toxic synergism between halothane and D-galactosamine. Neither model seems satisfactory for the testing of artificial liver support systems. The halothane model requires extremely long periods of anesthesia and mechanical ventilation. The present model does not cause uniform or universal death of the animals within 3 days. Foremost, both models result in DIC and endotoxic shock, neither of which is likely to respond to bioartificial liver support or treatment with conventional dialysis membranes.