QUANTIFICATION OF FIBROSIS IN THE LUNGS OF RATS USING A MORPHOMETRIC METHOD

The Wagner grading system is a qualitative histopathologic method designed to describe the severity of nonmalignant respiratory disease (NMRD) as it pertains to the pathology induced by fibrous particulates in humans and later in rats. However, once the method had been used in several rodent fiber studies it was found that it did not adequately differentiate the magnitude of early fibrosis. This article describes a modification of the Wagner scoring system that incorporates a semiquantitative yet simple approach to assuage this problem.     

CHRONIC INHALATION STUDIES OF TWO TYPES OF STONE WOOL FIBERS IN RATS

A summary is given of the pathology results after long-term inhalation in rats of insulation wool representing the new biosoluble types. The pathology results are compared with previously conducted long-term inhalation study with MMVF21 (traditional stone wool). The biosoluble fiber MMVF34/HT (HT) is characterized by a relatively high content of aluminum and a relatively low content of silica compared to the older MMVF21. HT has a high in vitro dissolution rate at pH 4.5, and a relatively low dissolution rate at pH 7.5. Male Fischer 344 rats were exposed at one exposure level of 30 mg/m³ by nose-only inhalation of a well-characterized fiber test atmosphere. The fibers had been size selected to be largely rat respirable. The negative control group was exposed to filtered air. The exposure duration was 6 h/day, 5 days/wk for 104 wk, with a subsequent nonexposure period lasting until approximately 20% survival in the air control group. Interim sacrifices were performed at wk 13, 26, 52, 78, and 104 to monitor the progression of pulmonary change and fiber numbers. Effectively the main protocol for the previously conducted chronic study with MMVF21 was the same, except that there were three concentration levels (3, 16, and 30 mg/m³). In addition to the endpoints measured in the previous study, slides from both studies were evaluated for collagen deposition using a quantitative morphometric method. The results of the comparative study clearly showed a marked difference in the pulmonary pathogenicity of the MMVF21 and HT in terms of their fibrogenic potential. MMVF21 caused pulmonary fibrosis, but the HT fiber did not. The incidence of tumors for both the HT and the MMVF21 fiber was comparable to the control groups.     

Custom extracellular matrix cylinder mitral valve in a pediatric patient

Mitral valve construction using extracellular matrix (ECM) is a relatively new procedure. In this case, a 15‐month‐old boy with a history of severe mitral valve regurgitation secondary to endocarditis underwent mitral valve surgery. Mitral valve repair was not possible, and thus, a 17 mm extracellular matrix cylinder valve (ECM‐CV) was constructed for valve replacement. The ECM‐CV is clearly imaged using echocardiography, especially three‐dimensional imaging, that helped define valve function. As the use of ECM for valve construction increases, echocardiography will play an essential role in evaluating the function and mechanics of these novel valves.     

Expression of fibrinogen receptors during activation and subsequent desensitization of human platelets by epinephrine

Epinephrine causes platelet aggregation and secretion by interacting with alpha 2-adrenergic receptors on the platelet surface. Platelet aggregation requires the binding of fibrinogen to a specific receptor on the membrane glycoprotein IIb-IIIa complex. Although the IIb-IIIa complex is identifiable on the surface of resting platelets, the fibrinogen receptor is expressed only after platelet activation. The current studies were designed to examine the effect of occupancy of platelet alpha 2-adrenergic receptors by epinephrine on the expression of fibrinogen receptors and on the aggregation of platelets. The ability of epinephrine to induce the expression of fibrinogen receptors was studied under two different conditions: acute stimulation (less than 1 min) and prolonged stimulation (50 to 90 min), the latter of which is associated with a reduction or "desensitization" of the platelet aggregation response. Expression of the fibrinogen receptor was monitored with 125I-fibrinogen as well as with 125I-PAC-1 (PAC-1), a monoclonal antibody that binds to the glycoprotein IIb-IIIa complex only after platelets are activated. Epinephrine caused an immediate increase in PAC-1 and fibrinogen binding that was dependent on occupancy of the alpha 2-receptor by epinephrine and on the presence of extracellular free Ca (KCa = 30 mumol/L). By itself, 1 mmol/L Mg was unable to support induction of the fibrinogen receptor by epinephrine. However, it did decrease the Ca requirement by about two orders of magnitude. Prolonged stimulation of unstirred platelets by epinephrine led to a 70% decrease in the aggregation response when the platelets were subsequently stirred. Despite their decreased aggregation response, desensitized platelets bound PAC-1 and fibrinogen normally, indicating that the loss of aggregation was not due simply to a decrease in fibrinogen receptor expression. Although desensitization was not affected by pretreatment of the platelets with aspirin, it was partially prevented when extracellular Ca was chelated by EDTA during the long incubation with epinephrine. These studies demonstrate that once platelet alpha 2-adrenergic receptors are occupied by epinephrine, extracellular Ca is involved in initiating the aggregation response by supporting the induction of the fibrinogen receptor and the binding of fibrinogen. Furthermore. Ca-dependent reactions subsequent to fibrinogen binding may be necessary for maximal platelet aggregation and are impaired when platelets become desensitized to epinephrine.     

B-type natriuretic peptide levels in adults with congenital heart disease and right ventricular failure

Right ventricular (RV) failure is a common problem for adults with systemic right ventricles or volume-overloaded right ventricles. The utility of B-type natriuretic peptide (BNP) levels for diagnosis and prognosis is now well documented in adults with acquired left ventricular (LV) systolic dysfunction, but not in the setting of RV failure. BNP levels were evaluated in adults with RV failure due to congenital heart disease and compared with levels in adults with acquired LV dysfunction and adults without structural heart disease.