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Biomedical subjects

K M Moser

Publications and source records attributed to K M Moser.

At least 19 recordsLinked to original sources
PubMed1992

Presence of active and latent type 1 plasminogen activator inhibitor associated with porcine platelets.

Data from a number of laboratories indicate that human platelets contain type I plasminogen activator inhibitor (PAI-1) primarily in a latent form; however, one report (Biochemistry 28:5773, 1989) indicated that it is predominantly the active form of PAI-1 that is present in and can be purified from an ammonium sulfate precipitate of porcine platelets. To clarify this situation, we investigated and compared the status of PAI-1 in porcine and human platelets. Immunologic analysis of the ability of PAI-1 to form complexes with immobilized t-PA indicated that porcine and human platelets contained 3.7 +/- 0.4 and 1.7 +/- 0.3 U of PAI activity per 10(8) platelets (n = 6; +/- SD), respectively; sodium dodecyl sulfate (SDS)-activation of the lysates increased PAI-1 activity to 10.8 +/- 3.0 and 3.8 +/- 0.5 U per 10(8) platelets. Platelet lysates were also treated with an excess of soluble t-PA, which formed complexes with active PAI-1, whereas the latent form was detected by SDS-polyacrylamide gel electrophoresis and reverse fibrin autography. Furthermore, immobilized t-PA was able to deplete active PAI-1 from the platelet extracts, and the latent form remaining in the absorbed extract could be quantitated by activation with 4 mol/L guanidine. To investigate the differences between our observations and the published data, porcine platelets were extracted, and PAI-1 was partially purified as described in the literature. For quantitative analysis, porcine platelet PAI-1 was also purified to homogeneity using standard chromatographic procedures optimized in our laboratory for endothelial PAI-1, and the purified protein was used to develop an enzyme-linked immunoabsorbent assay for porcine PAI-1 antigen. Our results indicate that: (1) latent PAI-1 in concentrated ammonium sulfate precipitates of porcine platelet lysates cannot be detected unless the precipitates are diluted before treatment with denaturants; and (2) active and latent porcine platelet PAI-1 can be separated by gel filtration over molecular sieving columns. In summary, this report documents that PAI-1 in porcine platelets is present in both an active and a latent form.

Animals↗
PubMed1992

Chronic major-vessel thromboembolic pulmonary artery obstruction: appearance at angiography.

The pulmonary angiograms of 250 patients evaluated for chronic thromboembolic pulmonary hypertension were reviewed. Pulmonary thromboendarterectomy was performed in each of these individuals, and the surgical findings were correlated with abnormal angiographic patterns. The pulmonary angiographic findings suggestive of chronic thromboembolic disease included "pouching" defects, webs or bands, intimal irregularities, abrupt vascular narrowing, and complete vascular obstruction. Pouching is reported by the authors to be a previously undescribed angiographic feature of this disease. Carefully obtained and properly interpreted pulmonary angiograms are necessary to confirm the diagnosis of operable chronic thromboembolic disease. Differential diagnostic possibilities should be considered prior to a decision to perform surgical correction.

Adolescent↗
PubMed1992

Endogenous fibrinolytic system in chronic large-vessel thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a disorder characterized by pulmonary arterial hypertension as a consequence of organized thrombotic material in the central pulmonary arteries. Incomplete resolution of acute pulmonary emboli is believed to be pathogenically important; however, the mechanism for poor thrombus dissolution remains to be explained. We undertook this study to assess the major determinants of plasma fibrinolysis in patients with CTEPH (n = 32). METHODS AND RESULTS: Immunological and functional levels of tissue-type plasminogen activator (t-PA) and type 1 plasminogen activator inhibitor (PAI-1) were quantified in platelet-poor plasma (PPP) from patients with CTEPH as well as age-matched controls. Although basal PPP t-PA antigen levels (CTEPH mean, 29.5 ng/ml; control mean, 2.7 ng/ml) and PAI-1 antigen levels (CTEPH mean, 55.8 ng/ml; control mean, 21.0 ng/ml) were higher in the CTEPH group, no between-group differences were detected in the enzymatic activities of these two molecules. The CTEPH group demonstrated a greater rise in t-PA antigen (CTEPH mean rise, 53.0 ng/ml; control mean rise, 5.6 ng/ml) and PA activity (CTEPH mean rise, 10.5 IU/ml; control mean rise, 1.2 IU/ml) than controls in response to an experimentally induced venous occlusion. Immunoprecipitation and fibrin autography of PPP from two patients with markedly elevated basal t-PA antigen levels demonstrate that the t-PA antigen was present in PPP primarily in complex with PAI-1. CONCLUSIONS: Although abnormalities of the fibrinolytic system were detected, neither a high resting plasma PAI-1 activity nor a blunted response of t-PA to venous occlusion can be invoked as an etiology for CTEPH:

Adolescent↗
PubMed1992

Lack of utility of bronchial brush biopsy in patients infected with the human immunodeficiency virus.

While bronchoalveolar lavage has been shown to be more sensitive than brush biopsy (BB) for the diagnosis of Pneumocystis carinii pneumonia in AIDS patients, some have reported that BB occasionally is positive in spite of a negative BAL. Many bronchoscopists, therefore, continue to perform routine BB when doing bronchoscopy on AIDS patients. We performed a retrospective study of all fiberoptic bronchoscopies done on human immunodeficiency virus-infected patients over a one-year period at our institution to determine if the use of BB added to the diagnostic yield of bronchoscopy over that of BAL alone. Of 84 bronchoscopies in which BB was performed in addition to BAL, BB yielded no diagnoses that were not obtained by BAL. Brush biopsy added approximately $400 to the cost of bronchoscopy. We conclude that BB should not be routinely done when performing bronchoscopy on HIV-infected patients.

Biopsy↗
PubMed1992

Chronic thromboembolic pulmonary hypertension: clinical picture and surgical treatment.

Chronic, major vessel thromboembolic pulmonary hypertension (CTEPH), is an uncommon condition which, in the past, was an autopsy curiosity. Advances in diagnostic approaches, surgical techniques and postoperative management have transformed this disorder into a potentially curable form of pulmonary hypertension. The predominant symptom is unexplained dyspnoea on exertion. In patients with this complaint, CTEPH should be considered. Numerous pitfalls exist along the diagnostic path. Perfusion lung scans point toward the diagnosis, but often underestimate the extent of central arterial obstruction. Pulmonary angiography is the key diagnostic procedure, but the many patterns of thrombus organization-recanalization require a base of experience for proper interpretation. Criteria for selection of patients for surgery are evolving, but assurance of thrombus accessibility to surgery is critical. Surgical thromboendarterectomy bears no resemblance to acute pulmonary embolectomy. Recognition of thrombus (versus normal intima), meticulous dissection and a bloodless surgical field are essential for adequate restoration of pulmonary vascular patency. Multiple complications may arise postoperatively, and detailed attention to these is required for patient survival. With a co-ordinated, multi-specialty team effort, however, haemodynamic and clinical outcomes have been rewarding and persist long-term. Surgical mortality should steadily decline with such a co-ordinated effort, as well as earlier diagnosis and advances in surgical and postoperative management techniques.

Angiography↗
PubMed1991

Catheter-based intravascular ultrasound imaging of chronic thromboembolic pulmonary disease.

Pulmonary thromboendarterectomy is now the treatment of choice for pulmonary hypertension due to chronic pulmonary thromboemboli. A precise assessment of location and extension of these thrombi is important because only proximal chronic pulmonary thromboemboli are accessible to surgery. Because intravascular ultrasound imaging can assess not only arterial luminal size, but also wall thickness, its value as a complement to angiography was assessed in 11 patients aged 35 to 64 years with severe pulmonary hypertension (systolic pulmonary artery pressure, mean +/- standard deviation 70 +/- 19 mm Hg; pulmonary artery resistance, 609 +/- 297 dynes.s.cm-5). Intravascular ultrasound was obtained in 10 of 11 patients and no complication occurred. Intravascular ultrasound identified 10 segments with suspected chronic pulmonary thromboemboli in 7 patients, all confirmed at operation. Nine segments were considered normal, all of which (except 1) were free of chronic pulmonary thromboemboli at operation. Image quality was highly dependent on pulmonary artery size and position of the catheter. Therefore, intravascular ultrasound of pulmonary arteries is feasible and safe in patients with pulmonary hypertension. It may help to assess the location and extension of the pathologic process involving pulmonary arteries.

Adult↗
PubMed1991

Epicardial activation and repolarization patterns in patients with right ventricular hypertrophy.

To map global epicardial repolarization patterns and test the "SI" model of T wave generation, the patterns of epicardial activation and repolarization in patients with chronic pulmonary thromboembolism and right ventricular hypertrophy were studied by computerized mapping techniques and monophasic action potential (MAP) recording. The ventricular activation patterns were characterized by delayed right ventricular activation and the absence of normal early epicardial ventricular breakthrough in some cases. The repolarization patterns were characterized by nonuniform distribution of T wave morphologies. The T waves were predominantly positive over the left ventricular epicardium and negative or biphasic over the right ventricular epicardium. The activation-recovery (A-R) intervals were measured from the local activation to the maximal dV/dt of the upstroke of the T waves (Wyatt method). The difference between the A-R intervals and the MAP from onset of activation to 90% repolarization (MAP90) varies according to T wave morphology and could be as high as 96 msec with positive T waves, despite significant correlations (r = 0.56-0.90) between MAP90 and A-R intervals for each morphology. Better overall correlations were found if the minimal dV/dt on the downslope of the positive T waves was chosen to estimate the time of local repolarization (alternative method). Using this method, the mean A-R intervals were the same over the right and left ventricles. Cardiopulmonary bypass significantly prolonged the action potential duration equally at all parts of the epicardium. We conclude that in patients with right ventricular hypertrophy, the time of local repolarization can be estimated by our alternative method; the right ventricle completes activation and repolarization later than the left ventricle, and the distribution of T wave morphologies is nonuniform, with predominantly positive T waves observed over the left ventricle and negative or biphasic T waves observed over the right ventricle. These findings are compatible with the SI model of the generation of T waves.

Action Potentials↗
PubMed1991

Chronic pulmonary thromboembolism in dogs treated with tranexamic acid.

BACKGROUND: Many questions remain regarding the pathogenesis, natural history, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension in patients. To answer such questions, we developed an animal model of this disorder. The brisk thrombolytic response of canines to acute embolism has, previously, prevented the establishment of such a model. METHODS AND RESULTS: The fibrinolytic inhibitor tranexamic acid was given orally to canines before, and for intervals after, pulmonary emboli were released from venous thrombi formed in vivo in femoral veins or the inferior vena cava. Preliminary studies disclosed that embolic residuals from femoral vein thrombi were not sufficient to cause significant, persistent pulmonary hypertension. With repetitive, larger thrombi embolized from the inferior vena cava, however, persistent pulmonary hypertension was achieved in most animals. CONCLUSIONS: Resolution of emboli in the canine can be inhibited by tranexamic acid. As in humans, a spectrum of embolic residuals is encountered, and the perfusion lung scan consistently underestimates the extent of embolic residuals. Studies of this animal model continue.

Animals↗
PubMed1990

Current early results of pulmonary thromboendarterectomy for chronic pulmonary embolism.

Some patients with chronic pulmonary embolism causing severely symptomatic pulmonary hypertension have been managed by heart-lung transplantation with an associated hospital mortality of 24%. To allow comparison with pulmonary thromboendarterectomy (PTE), we have reviewed the hospital morbidity and mortality in 149 consecutive patients. From 1 October 1984 to 18 September 1989, these patients underwent PTE utilizing a standardized procedure consisting of median sternotomy, cardiopulmonary bypass, deep hypothermia and circulatory arrest for bilateral PTE in 91% (136/149) of the procedures with 7.4% (11/149) and 1.3% (2/149) undergoing right or left PTE, respectively. Ventilator dependency (greater than or equal to 5 days on respirator) occurred in 28.3% (41/146). Hospital mortality (death within 30 days or in hospital) was 11.4% (17/149). The most common causes of death were respiratory and multiorgan failure, 10 (59% of deaths) and acute pulmonary hemorrhage, 3 (17% of deaths). We conclude that PTE with an operative mortality of half that of heart-lung transplantation (11.4% vs. 24%) should be the procedure of choice for significantly symptomatic chronic pulmonary embolism. Furthermore, the hazards of immunosuppression and chronic graft rejection are avoided.

Adult↗
PubMed1990

Gas exchange in chronic thromboembolism after pulmonary thromboendarterectomy.

Thromboendarterectomy is the treatment of choice for chronic large vessel thromboembolic pulmonary hypertension. To identify the mechanisms responsible for the improvement in gas exchange following thromboendarterectomy, we studied nine patients with chronic thromboembolic pulmonary hypertension before and eight to 18 months after surgery using the multiple inert gas elimination technique. Preoperatively, all subjects had pulmonary hypertension and were hypoxemic or had an elevated P(A-a)O2. The VA/Q distribution was widened with an elevated VD/VT and a low cardiac index. After thromboendarterectomy, significant improvement had occurred. The VA/Q distribution had narrowed to near normal, and the cardiac index increased. It was concluded that thromboendarterectomy improved gas exchange both by improving VA/Q relationships and by increasing cardiac output.

Adult↗
PubMed1990

Pulmonary vascular steal in chronic thromboembolic pulmonary hypertension.

After pulmonary thromboendarterectomy, performed for relief of chronic thromboembolic pulmonary hypertension, perfusion lung scans have frequently disclosed new perfusion defects in segments served by undissected pulmonary arteries. Our hypotheses were that these new postoperative defects occurred with great frequency and did not represent postoperative vessel occlusion. We retrospectively reviewed the preoperative and postoperative perfusion scans of 33 consecutive patients undergoing pulmonary thromboendarterectomy. New postoperative perfusion defects were noted in 23 of 33 patients. The incidence of new defects was increased tenfold in segments that had (1) normal preoperative angiographic findings, (2) normal preoperative radionuclide perfusion, and (3) not been entered at the time of surgery. Postoperative angiograms, available in 15 of 33 patients, documented the nonembolic, nonocclusive nature of the new perfusion scan defects. The most plausible alternate explanation for this previously undescribed finding is a redistribution of pulmonary arterial resistance induced by the thromboendarterectomy, namely, a pulmonary vascular "steal."

Adult↗
PubMed1990

Risk factors for pulmonary thromboendarterectomy.

Pulmonary thromboendarterectomy is being performed with increasing frequency for incapacitating pulmonary hypertension caused by chronic large-vessel pulmonary embolism. However, patient-related risk factors and procedural complications associated with morbidity and mortality have not been fully defined. From Oct. 1, 1984, to April 10, 1989, we performed pulmonary thromboendarterectomy using deep hypothermia and circulatory arrest in 127 consecutive patients (62.2% male, mean age 50 +/- 16 [standard deviation], range 20 to 82 years) in whom the exposure and dissection of the pulmonary arteries and methods for myocardial protection have been standardized. End points for univariate and multivariate analyses of risk factors were reperfusion pulmonary edema leading to respiratory insufficiency as defined by ventilator dependency (greater than or equal to 5 days) (31.5%, 39/124) and hospital mortality (12.6%, 16/127). Multivariate analyses showed that ascites and need for 4 units of blood or more predicted ventilator dependency (p less than 0.03). Increased cardiopulmonary bypass times predicted both end points (p less than 0.03 to less than 0.0001), and failure to achieve at least a 50% reduction in pulmonary vascular resistance strongly predicted hospital death (p less than 0.0001). However, other factors that exhibited trends for association with one of the end points may prove important with a larger sample size. A hospital mortality rate of 12.6% for pulmonary thromboendarterectomy is acceptable when compared with approximately 25% for heart-lung transplantation, which is the only therapeutic alternative. Increased ventilator dependency and hospital mortality can be anticipated with longer cardiopulmonary bypass times and inadequate reduction of pulmonary vascular resistance.

Adult↗
PubMed1989

Mechanisms of hypoxemia in chronic thromboembolic pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension is characterized by widespread central obstruction of the pulmonary arteries with organized thrombus and thereby differs substantially from other forms of pulmonary hypertension. We studied 25 patients using the multiple inert gas elimination technique to identify and quantitate the physiologic mechanisms of hypoxemia in this disorder. All patients had chronic obstruction of the central pulmonary arteries, which was demonstrated angiographically and later surgically confirmed. All patients but one were hypoxemic (PaO2 = 65 +/- 11 mm Hg, PaCO2 = 32 +/- 4 mm Hg, AaPO2 = 45 +/- 14 mm Hg), and all patients had pulmonary hypertension (mean Ppa = 45 +/- 11 mm Hg) with an elevated pulmonary vascular resistance (mean PVR = 1,000 +/- 791 dyne/s/cm5, normal less than 300). The cardiac index was reduced (1.7 +/- 0.6 L/min/m2), as was the P-vO2 (31 +/- 5 mm Hg). Inert gas studies revealed widened unimodal Va/Q distributions in 20 of 25 subjects, with a log standard deviation of 1.01 +/- 0.32 (upper limit of normal, 0.6; ages 20 to 40), shunt = 0.03 +/- 0.05 of cardiac output, and dead space of 3.4 +/- 1.1 ml/kg (upper limit of normal, 2.9). The VD/VT ratio was 0.51 +/- 0.10. No low (VA/Q less than 0.1) or high (VA/Q greater than 10.0) regions were present, and no evidence for diffusion limitation of O2 transfer at rest was found. The low cardiac output and resulting low P-VO2 were responsible for approximately 33% of the increased AaPO2. The magnitude of the VA/Q abnormality correlated poorly with the PVR, the mean Ppa, or the magnitude of vascular obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Gas Analysis↗