Efficacy of aprotinin with various anticoagulant agents in cardiopulmonary bypass.

BACKGROUND: Aprotinin has recently been approved for clinical use in cardiopulmonary bypass. Although unfractionated heparin has been the only anticoagulant widely used for cardiopulmonary bypass, disadvantages involving heparin have led to ongoing investigations of alternative anticoagulant agents. METHODS: The objective of this study was to evaluate the efficacy of aprotinin in combination with other anticoagulant agents, specifically low molecular weight heparin and recombinant hirudin, using a dog model of cardiopulmonary bypass. RESULTS: The blood conservation resulting from the use of aprotinin was observed only with unfractionated heparin. Efficacy of anticoagulation as measured by protein deposits in the bypass circuit filter revealed an unexpected reduction in the quantity of deposits when aprotinin was used in combination with low molecular weight heparin. CONCLUSIONS: As alternative anticoagulant agents are sought, the potential benefits of aprotinin in the reduction of operative blood loss must be evaluated independently for each anticoagulant agent.

Effect of HeartMate left ventricular assist device on cardiac autonomic nervous activity.

BACKGROUND: Clinical performance of a left ventricular assist device is assessed via hemodynamic parameters and end-organ function. This study examined effect of a left ventricular assist device on human neurophysiology. METHODS: This study evaluated the time course change of cardiac autonomic activity of 3 patients during support with a left ventricular assist device before cardiac transplantation. Cardiac autonomic activity was determined by power spectral analysis of short-term heart rate variability. The heart rate variability before cardiac transplantation was compared with that on the day before left ventricular assist device implantation. RESULTS: The standard deviation of the mean of the R-R intervals of the electrocardiogram, an index of vagal activity, increased to 27 +/- 7 ms from 8 +/- 0.6 ms. The modulus of power spectral components increased. Low frequency (sympathetic activity) and high frequency power (vagal activity) increased by a mean of 9 and 22 times of each baseline value (low frequency power, 5.2 +/- 3.0 ms2; high frequency power, 2.1 +/- 0.7 ms2). The low over high frequency power ratio decreased substantially, indicating an improvement of cardiac sympatho-vagal balance. CONCLUSIONS: The study results suggest that left ventricular assist device support before cardiac transplantation may exert a favorable effect on cardiac autonomic control in patients with severe heart failure.

Evaluation of CGP 39393 as the anticoagulant in cardiopulmonary bypass operation in a dog model.

Recombinant desulphatohirudin HV1 (CGP 39393), a specific and potent peptidic inhibitor of thrombin, was evaluated as the sole anticoagulant in a dog model of cardiopulmonary bypass. CGP 39393 was administered as a bolus plus infusion for a 1-hour pump period at doses of 1.0 mg/kg + 0.75 mg.kg-1.h-1, 1.0 mg/kg + 1.50 mg.kg-1.h-1, 1.0 mg/kg + 2.25 mg.kg-1.h-1, or 1.0 mg/kg + 3.0 mg.kg-1.h-1 (n = 5 per group). The lowest dose was ineffective, as a high degree of clot formation (314 +/- 160 mg) occurred as determined by quantitation of protein deposits in the pump line filter. The three higher doses inhibited clot formation (35 to 44 mg) but did not reveal a dose-dependent effect (p = 0.308 between groups). All four doses produced the same amount of postoperative blood loss (6.5 to 10 g/kg over 2 hours; p = 0.215 between groups) and no oozing of blood from cut tissues (sternum, muscle, skin) during or after operation. No adverse hemodynamic or hematologic effects were observed. Animals were physiologically stable coming off pump, requiring minimal fluid replacement or other cardiovascular supportive measures. The chromogenic anti-IIa assay could be used to monitor CGP 39393. Some activated partial thromboplastin time and all activated clotting time values were off scale on pump, but they fell immediately after cardiopulmonary bypass, typically reaching near-normal levels within 30 to 60 minutes. No reversal of CGP 39393 was used, as blood levels declined rapidly after cessation of the infusion. This study in a dog model shows that CGP 39393 administered as a bolus plus infusion (minimum dose, 1.0 mg/kg + 1.50 mg.kg-1.h-1) can be used safely and effectively during cardiopulmonary bypass for cardiac operation.