Intravenous vitamin K1 prior to orthotopic heart transplantation: effects in vivo and in vitro.

BACKGROUND: Vitamin K1 is used to reverse warfarin's anticoagulant action. It is unclear whether intravenous vitamin K1 is safe or efficacious prior to urgent cardiac surgery. METHODS: We retrospectively and prospectively examined the effects of preoperative intravenous vitamin K1 in vivo (administered for warfarin reversal immediately before heart transplantation) on intraoperative blood product utilization, hemodynamics and coagulation parameters. We also determined the direct effects of vitamin K1 in vitro on rings of human saphenous vein and internal mammary artery. RESULTS: In the retrospective limb, 29 of 67 patients were administered vitamin K1 preoperatively via slow intravenous infusion. Vitamin K1 administration produced no adverse outcome but did not affect subsequent perioperative use of blood products. In the prospective limb (n = 10), vitamin K1 significantly (P < or = 0.01, Student t-test) altered mean arterial pressure (from 85 +/- 15 to 76 +/- 16 mmHg), systemic vascular resistance (from 1364 +/- 308 to 1078 +/- 252 dyn.s.cm-5), and cardiac index (from 2.3 +/- 0.3 to 2.7 +/- 0.3 L/min/m2) (mean +/- SD). Significant decreases in prothrombin time (19.8 +/- 2.7 to 17.7 +/- 1.8 s) and activated clotting time (164 +/- 26 to 137 +/- 24 s) were observed at 60 min. In vitro vitamin K1 (10(-7) to 10(-4) M) had no effect on the tone of noradrenaline-constricted rings. CONCLUSIONS: Vitamin K1, administered by intravenous infusion prior to heart transplantation, did not alter subsequent perioperative blood product administration. Vitamin K1 rapidly reversed the anticoagulant effect of warfarin and produced modest hemodynamic changes. The decrease in systemic vascular resistance is probably not due to a direct effect of vitamin K1 on vascular smooth muscle.

Porcine gastroepiploic artery as an in vitro experimental model to study vasodilators in microsurgery.

Arterial vasospasm is a common problem in microsurgery. This pharmacological study compares seven vasodilators-lidocaine, papaverine, nicardipine, verapamil, diltiazem, sodium nitroprusside, and hydralazine-for their efficacy and potency in an experimental model of vasospasm. Porcine gastroepiploic arteries were cut into rings to measure isometric tension development in vitro. The arteries were preconstricted with endothelin-1, a stable thromboxane A2 analogue, norepinephrine, or potassium, and then exposed to increasing concentrations of each vasodilator. Every vasodilator except hydralazine and sodium nitroprusside was efficacious in producing near-maximal relaxation of arteries preconstricted with any vasospastic substance. The five efficacious vasodilators differed markedly in potency, as reflected in the concentrations producing half-maximal relaxation. The order of potency was nicardipine < or = verapamil or diltiazem < papaverine < lidocaine. This study suggests that nicardipine would be the most potent vasodilator for systemic or direct intra-arterial administration. Papaverine and lidocaine, in concentrations employed clinically, were both efficacious as topical vasodilators.

Use of monoclonal antiacetylcholine receptor antibodies to investigate the macrophage inflammation of acute experimental myasthenia gravis: refractoriness to a second episode of acute disease.

The acute phase of experimental autoimmune myasthenia gravis (EAMG) is characterized by macrophage inflammation of muscle endplates and by muscle fiber necrosis. We induced acute EAMG by passive transfer of monoclonal antibodies (mAbs) directed against the acetylcholine receptor (AChR) to investigate this brief and self-limited disorder. After the initial acute phase, animals were refractory to induction of a second episode by subsequent injection of the same mAb, or another anti-AChR mAb of different idiotype and which binds to a separate epitope. Therefore, the refractory state was not caused by an anti-idiotypic response or epitopic modulation. Adoptive transfer of spleen cells from refractory animals had no effect, excluding a role of suppressor lymphocytes, and there was no evidence from experiments involving adoptive transfer of spleen cells from naive animals to refractory animals that refractory animals lacked effector cells.