Biventricular cardiac dysfunction after acute massive pulmonary embolism in the rat.

Cardiac dysfunction has been documented in vivo after acute massive pulmonary embolism (AMPE). The present study tests whether intrinsic ventricular dysfunction occurs in rat hearts isolated after AMPE. AMPE was induced in spontaneously breathing ketamine-xylazine-anesthetized rats by thrombus infusion until mean arterial blood pressure (MAP) was approximately 40% of basal measurement. A hypotensive control group underwent controlled blood withdrawal to produce MAP approximately 40% of basal levels. Shams underwent identical surgical and anesthesia preparation but without pulmonary embolization. Hearts were perfused in isovolumetric mode, and simultaneous right ventricular (RV) and left ventricular (LV) pressures were measured. AMPE caused arterial hypotension with hypoxemia (PO(2) = 50 +/- 14 Torr), acidemia (pH = 7.26 +/- 0.11), and high lactate concentration (6.9 +/- 1.7 mM). Starling curves from both ventricles demonstrated that AMPE significantly reduced ex vivo systolic contractile function in the RV (P = 0.031) and LV (P = 0.008) compared with both the hypotensive control and sham hearts. AMPE did not alter coronary flow or compliance in either ventricle. Soluble tumor necrosis factor-alpha decreased in the RV (P = 0.043) and LV (P = 0.005) tissue. These data support the hypothesis that AMPE produces intrinsic biventricular dysfunction and suggest that arterial hypotension is not the principal mechanism of this dysfunction.     

Inhibition of prostaglandin synthesis during polystyrene microsphere-induced pulmonary embolism in the rat

Our objective was to test the effect of inhibition of thromboxane synthase versus inhibition of cyclooxygenase (COX)-1/2 on pulmonary gas exchange and heart function during simulated pulmonary embolism (PE) in the rat. PE was induced in rats via intrajugular injection of polystyrene microspheres (25 micro m). Rats were randomized to one of three posttreatments: 1) placebo (saline), 2) thromboxane synthase inhibition (furegrelate sodium), or 3) COX-1/2 inhibition (ketorolac tromethamine). Control rats received no PE. Compared with controls, placebo rats had increased thromboxane B(2) (TxB(2)) in bronchoalveolar lavage fluid and increased urinary dinor TxB(2). Furegrelate and ketorolac treatments reduced TxB(2) and dinor TxB(2) to control levels or lower. Both treatments significantly decreased the alveolar dead space fraction, but neither treatment altered arterial oxygenation compared with placebo. Ketorolac increased in vivo mean arterial pressure and ex vivo left ventricular pressure (LVP) and right ventricular pressure (RVP). Furegrelate improved RVP but not LVP. Experimental PE increased lung and systemic production of TxB(2). Inhibition at the COX-1/2 enzyme was equally as effective as inhibition of thromboxane synthase at reducing alveolar dead space and improving heart function after PE.     

Comparative proteomic study of acute pulmonary embolism in a rat model

Pulmonary embolism (PE) is a common, potentially fatal disease, whose blood clots originate from the deep venous system of the lower extremities. PE is of clinical importance because of the considerable mortality and morbidity. In this study, at first we established a rat PE model by injecting 3-4 emboli into the left jugular vein. Before collecting the lung tissues, we perfused them with saline through the right jugular vein and at the same time cut off the right carotid to remove the blood. Then we separated and identified differentially expressed proteins in lung tissues at different time points using the techniques of 2-DE and MS. After image analysis of 2-DE gels, 46 protein spots of interest were excised from the gels and identified by MALDI-TOF-MS. Thirty-two protein spots of them found their corresponding protein candidates in the database. These proteins are associated with distinct aspects of PE such as the contractive function of smooth muscles, metabolism of energy, collagen and toxicant, cellular differentiation, apoptosis and injury, blood pressure adjustment, maintaining of acid-base balance, and so on. Ten of the identified proteins were validated by semiquantitative RT-PCR, and three of them were further validated by Western blot analysis. The differential expression patterns of these proteins suggest the distinct roles they may play in different stages of the rat PE model, and information from this study may be helpful to uncover the pathophysiologic molecular mechanisms involved in PE.     

Early Awelysin therapy in massive pulmonary embolism after hip alloarthroplasty]

The fibrinolytic therapy of massive frest pneumatic embolism represents an ensured progress today. Until now it was only possible to report on those cases where the patients had survived at least two hours from the beginning of the acute event. Two cases are reported here where the patients were successfully treated in spite of a standstill in the circulation. In a 60 years old female patient and 54 years old female hypertonic patient a successful reanimation could be performed in the early postoperative phase by applying a high dosage of awelysin. The progress indicated that the therapy has led to a lysis or partial lysis of embolus respectively and thus again to a perfusion of the lungs. At the same time the serious bleeding complications clearly indicate the limits of this aggressive form of intensive therapy.     

Activity of pulmonary surfactant after blocking the associated proteins SP-A and SP-B

To investigate the role of the pulmonary surfactant-associated proteins SP-A and SP-B, the respective monoclonal antibody (anti-A or anti-B) was added to porcine pulmonary surfactant at a weight ratio of 1:2, and the mixtures were tested on surfactant-deficient immature newborn rabbits (gestational age 26 days). Under pentobarbital sodium anesthesia and mechanical ventilation with a 25-cmH2O peak insufflation pressure, the tidal volumes of the animals given surfactant alone and of those given surfactant containing anti-A were 27.9 +/- 5.1 and 25.1 +/- 9.6 (SD) ml/kg, respectively, whereas that of those given surfactant with anti-B was 5.8 +/- 3.6 ml/kg (P less than 0.05). The surface adsorption times of surfactant alone and of anti-A-containing surfactant were less than 0.8 s compared with greater than 120 s (P less than 0.01) for anti-B-containing surfactant. The anti-B suppressed the surfactant activity until the weight ratio was decreased to 2:100. The role of SP-A could not be clarified, but it was concluded that SP-B is an essential factor for surfactant activity.