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Biomedical subjects

L J Olson

Publications and source records attributed to L J Olson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Selective guanylyl cyclase inhibitor reverses nitric oxide-induced vasorelaxation.

Effects of a novel soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), were characterized on guanylyl cyclase activity in cytosolic fraction of COS-7 cells overexpressing the alpha 1 and beta 1 subunits of the rat soluble enzyme. ODQ was a noncompetitive inhibitor of soluble guanylyl cyclase with respect to Mn2+ or Mn(2+)-GTP and was a mixed competitive/noncompetitive inhibitor with respect to nitric oxide (NO) donation. ODQ (10 mumol/L) reduced deta nonoate-stimulated cGMP production in COS-7 cells overexpressing soluble guanylyl cyclase and in rat aortic vascular smooth muscle cells. ODQ did not inhibit particulate forms of the enzyme rat guanylyl cyclase-A, -B, or -C, did not block NO synthase, and did not auto-oxidize deta nonoate-donated NO in the presence of cells at physiological pH. Therefore, ODQ is a selective inhibitor of soluble guanylyl cyclase. Using ODQ in isolated aortic ring preparations, we tested the hypothesis that soluble guanylyl cyclase mediates vasorelaxant activity associated with NO. Phenylephrine (100 nmol/L)-precontracted, isolated rat aortas were relaxed in a concentration-dependent manner by deta nonoate (0.01 to 100 mumol/L) and nitroglycerin (0.01 to 300 mumol/L). ODQ (10 mumol/L) attenuated deta nonoate- and nitroglycerin-mediated relaxation of contracted aortas. ODQ had no effect on natriuretic peptide-, 8-bromo-cGMP-, isoproterenol-, or bimakalim-mediated aortic relaxation. These results support the hypothesis that soluble guanylyl cyclase mediates vasorelaxant activity associated with nitric oxide.

Animals↗
PubMed1997

Combined orthotopic heart and liver transplantation for genetic hemochromatosis.

A 47-year-old man with cirrhotic liver disease complicated by encephalopathy and class IV congestive heart failure caused by genetic hemochromatosis underwent combined orthotopic heart and liver transplantation. The patient remains well, working full time, 4 years after operation. Combined heart and liver transplantation is an effective therapy for selected patients with concurrent heart and liver failure caused by systemic iron overload.

Heart Failure↗
PubMed1996

Predictors of reversibility of pulmonary hypertension in cardiac transplant recipients in the first postoperative year.

BACKGROUND: Pulmonary hypertension remains a risk factor for early postoperative mortality in heart transplantation and may reduce the long-term benefits of the procedure. This study was undertaken to assess the value of baseline hemodynamic studies with nitroprusside used to predict the degree of postoperative reversibility of pulmonary hypertension in cardiac transplant recipients and to identify clinical risk factors for fixed pulmonary hypertension. METHODS AND RESULTS: Hemodynamic data from 55 consecutive patients who underwent orthotopic cardiac transplantation from June 1988 through September 1993 were analyzed. The effects of nitroprusside and transplantation on pulmonary artery pressure, cardiac output, and pulmonary vascular resistance were compared. Multiple regression analysis was used to identify the predictors of reversibility of pulmonary hypertension. Nitroprusside reduced pulmonary vascular resistance by increasing cardiac output and, to a lesser extent, by reducing the transpulmonary gradient. Pulmonary hypertension was less reversible in patients with ischemic heart disease (versus dilated cardiomyopathy) and in former smokers (versus nonsmokers). Patients with nonischemic heart failure and no smoking history had significantly lower posttransplant pulmonary vascular resistance (1.24 +/- 0.45 Wood units) than ischemic patients (who were all former smokers; 2.20 +/- 1.01 wood units) or nonischemic former smokers (1.72 +/- 0.70 Wood units). The correlation of pulmonary vascular resistance during nitroprusside challenge with posttransplant pulmonary vascular resistance was better than that of baseline pulmonary vascular resistance with posttransplant pulmonary vascular resistance. CONCLUSIONS: Nitroprusside testing improves the prediction of late posttransplant pulmonary vascular resistance; hence, it provides data that may be relevant to both early operative risk and later long-term effectiveness of cardiac transplantation. The finding of increased risk of fixed pulmonary hypertension associated with ischemic heart disease and smoking suggests that underlying atherosclerotic vascular disease may contribute to the irreversibility of pulmonary vascular resistance.

Adult↗
PubMed1996

The premortem recognition of systemic senile amyloidosis with cardiac involvement.

PURPOSE: To recognize systemic senile amyloidosis involving the heart and to determine outcome. PATIENTS AND METHODS: All patients with the diagnosis of amyloidosis at the Mayo Clinic from January 1, 1984 through May 1, 1992, were reviewed. Amyloid was confirmed histologically by sulfated alcian blue and alkaline Congo red staining. The labeled streptavidin-biotin immunoperoxidase method was used with antisera against A kappa, A lambda, AA, transthyretin, and beta 2-microglobulin. Anti-P-component and antisera to albumin were used as controls. Chest radiographs, electrocardiograms, transthoracic echocardiograms, and cardiac catheterization data of all patients were reviewed. Serum and urine were examined with immunoelectrophoresis and immunofixation for the presence of a monoclonal protein. Lymphocyte DNA was examined for transthyretin mutations associated with familial amyloidosis. RESULTS: We identified 18 patients with myocardial tissue that stained positive for amyloid with sulfated alcian blue and Congo red and with transthyretin antisera. Congestive heart failure was present at diagnosis in 17 of the 18 patients. Atrial fibrillation was found in 11 patients. No monoclonal protein was found in the serum or urine. The echocardiographic findings were consistent with infiltrative cardiomyopathy due to amyloidosis in 16 patients. Right heart pressures were elevated in all 7 patients who had right-side heart catheterization. No transthyretin mutations were found in the leukocyte DNA from 12 patients. The actuarial median survival was 5 years; in contrast, the median survival was 5.4 months in 147 patients with primary amyloidosis (AL) who presented with congestive heart failure. CONCLUSION: Patients with cardiac amyloid and no monoclonal protein in the serum or urine must have immunohistochemical staining for kappa and lambda light chains and transthyretin to distinguish between systemic senile amyloidosis, familial amyloidosis, and AL. Patients with systemic senile amyloidosis should not be treated with alkylating agents. Their survival is much longer than that of patients with AL (60 versus 5.4 months).

Age Factors↗
PubMed1996

Novel natriuretic peptide receptor/guanylyl cyclase A-selective agonist inhibits angiotensin II- and forskolin-evoked aldosterone synthesis in a human zona glomerulosa cell line.

We report the production of a novel human natriuretic peptide receptor/guanylyl cyclase A (hNPR-A)-selective agonist ANP [G9T, R11S, G16R] (sANP). This agonist has similar affinity to ANP for hNPR-A and 1,000-10,000-fold reduced affinity for the human natriuretic peptide clearance receptor (hNPR-C). sANP was used to directly test the hypothesis that hNPR-A mediates the inhibitory effect of natriuretic peptides on aldosterone generation in a human zona glomerulosa cell line, H295R. Human type A natriuretic peptide and sANP (10(-11) to 10(-6) M) resulted in concentration-dependent increases in cGMP levels and decreases in forskolin (100 nM)- and angiotensin II (5 nM)-induced aldosterone and pregnenolone production. These results revealed an inhibitory effect of both peptides on the agonist-stimulated conversion of cholesterol to pregnenolone (i.e., cytochrome P-450 cholesterol monooxygenase side-chain cleaving enzyme, EC 1.14.15.6). H295R cells also exhibited angiotensin II- and forskolin-evoked conversion of [3H]cortico-sterone to [3H]aldosterone (i.e., cytochrome P-450 steroid 11 beta-monooxygenase/aldosterone synthase, EC 1.14.15.4). Human type A natriuretic peptide and sANP (10(-7) M) inhibited the angiotensin II-stimulated late pathway but did not affect forskolin-facilitated conversion of corticosterone to aldosterone. Our results directly demonstrate inhibitory effects of hNPR-A-mediated signal transduction on cytochrome P-450 cholesterol monooxygenase side-chain cleaving enzyme and steroid 11 beta-monooxygenase/aldosterone synthase complex depending on the steroidogenic agonist used.

Aldosterone↗
PubMed1995

Increase in total plasma homocysteine concentration after cardiac transplantation.

OBJECTIVE: To determine whether plasma homocysteine concentrations are increased in patients after cardiac transplantation. DESIGN: Total plasma homocysteine concentration was measured in 44 consecutive patients before and at 3, 6, and 12 months after orthotopic heart transplantation between June 1, 1988, and Oct. 15, 1992, and the data were analyzed statistically. RESULTS: Mean homocysteine concentrations (normal range, 4 to 17 mumol/L) increased 70% from 12.5 mumol/L before cardiac transplantation to 21.2 mumol/L (P < 0.002) 3 months after transplantation, at which time the concentrations were above normal in 14 of 26 patients (54%). Homocysteine concentrations remained elevated 6 and 12 months after transplantation (20.4 and 22.6 mumol/L, respectively) but did not increase further. Mean concentrations of plasma folic acid and vitamin B12, cofactors in homocysteine metabolism, decreased 20% and 49%, respectively, within 3 months after transplantation (11.6 to 9.3 micrograms/L [P = 0.04] and 584 to 295 ng/L [P = 0.01]). The mean glomerular filtration rate decreased 25% during this same interval (81 to 61 mL/min; P = 0.0001). Linear regression analysis revealed an association between the increase in homocysteine concentration and the folic acid concentration that approached statistical significance (P = 0.07); we found no statistically significant correlates of the increase in homocysteine concentration. CONCLUSION: The homocysteine concentration increases in most patients within 3 months after cardiac transplantation to levels previously associated with premature atherosclerotic coronary artery disease, and it remains increased for at least 1 year. Further investigation into the mechanism for the increase in homocysteine concentration and the relationship between homocysteine and coronary artery disease after transplantation is warranted.

Adolescent↗
PubMed1993

Right ventricular assessment in patients presenting for lung transplantation.

Chronic pulmonary disease is associated with varying degrees of cardiac dysfunction. Because of the potentially predominant effect of severe lung disease on right ventricular (RV) size and function, a reliable method to assess RV mechanics before and after lung transplantation may provide information of long-term significance and/or prognosis. Conventional invasive and non-invasive imaging methods have a number of limitations in evaluating RV function. Ultrafast computed tomographic (ultrafast CT) scanning has been shown to provide quantitative assessment of RV and left ventricular (LV) function in individuals with and without cardiac disease. Twenty-two patients presenting during evaluation for possible lung transplantation with end-stage pulmonary disease formed the basis of this study. There were 14 patients with chronic obstructive pulmonary disease and 8 with pulmonary fibrosis. Conventional transthoracic echocardiography and ultrafast CT were used for the assessment of RV and LV function. All patients had invasive assessment of right-sided hemodynamics and pulmonary function studies performed within 7-10 days of cardiac imaging. A qualitative assessment of RV size or function was possible in all but two patients by echocardiogram, but in 45%, the echocardiographic examination was described as suboptimal. In contrast, a quantitative assessment of ventricular volumes and systolic function was obtained in all patients by ultrafast CT. Pulmonary function parameters or hemodynamic measurements obtained during cardiac catheterization did not correlate with any assessment of RV function. We concluded that (1) ultrafast CT provides measurement of the RV and LV cavity dimension and systolic function; (2) invasive right-sided hemodynamics or pulmonary function studies do not predict RV function; and (3) echocardiography does not uniformly provide assessment of RV function in patients with chronic pulmonary disease.

Adult↗
PubMed1992

Management of patients after cardiac transplantation.

During the past decade, the morbidity and mortality associated with cardiac transplantation have decreased dramatically. The current survival for patients who undergo orthotopic cardiac transplantation is 80 to 90% at 1 year and 70 to 80% at 5 years; these results are attributed chiefly to improved immunosuppression and the consequent decrease in infectious illnesses and rejection. Because surgical mortality and technique have not changed appreciably during the past 20 years, improved survival can be ascribed to advances in the medical management of recipients of cardiac transplants. Medical problems frequently encountered in such patients include allograft rejection, allograft vasculopathy, hypertension, renal dysfunction, hyperlipidemia, hyperglycemia, malignant disorders, general surgical disease, and osteopenic bone disease. Hence, the expertise needed for management of patients who undergo cardiac transplantation is not confined to a particular specialty--optimal care necessitates the integrated efforts of a team, including transplant physicians and personnel to provide broad subspecialty and laboratory support. Meticulous management with proactive intervention and minimal effective immunosuppression will prevent or ameliorate many problems and contribute to increased survivorship and improved quality of life. For additional substantive improvement in long-term survival and quality of life for recipients of cardiac allografts, multicenter, prospective, and placebo-controlled clinical investigations will be necessary.

Heart Transplantation↗
PubMed1989

Endomyocardial biopsy in hemochromatosis: clinicopathologic correlates in six cases.

Clinical and pathologic features of cardiac hemochromatosis diagnosed by endomyocardial biopsy in six men, aged 32 to 75 years (mean 52), are described. Echocardiography demonstrated left ventricular enlargement and marked global systolic dysfunction in five. Cardiac catheterization demonstrated normal coronary arteries, increased left ventricular end-diastolic pressure and decreased left ventricular systolic function in all five so studied. Stainable iron was present in all endomyocardial biopsy specimens from the five patients with decreased left ventricular systolic function. Histologically, iron was detected only within the sarcoplasm, and its extent varied inversely with ventricular function. Thus, cardiac hemochromatosis represents a storage rather than an infiltrative disease. These results indicate that stainable iron is consistently observed in endomyocardial biopsy specimens from patients with impaired left ventricular systolic function. Iron staining is recommended for endomyocardial biopsy specimens from patients with idiopathic cardiac dysfunction.

Adult↗
PubMed1989

Surgical pathology of the pulmonary valve: a study of 116 cases spanning 15 years.

The gross surgical pathologic features of the pulmonary valve were reviewed in 116 patients (63 male and 53 female) who had undergone a cardiac operation with pulmonary valve excision at our institution during the period 1973 through 1987. Although the mean age was 12 years, subjects ranged in age from 3 months to 73 years, and 25 patients, including 19 with congenital heart disease, were older than 20 years of age. Among 105 patients who had pure pulmonary stenosis, 61 (58%) had tetralogy of Fallot, 18 had isolated pulmonary stenosis, 23 had other congenital cardiac anomalies, and 3 had carcinoid heart disease. Five patients had pure pulmonary regurgitation (four with tetralogy and one with infective endocarditis), and four had combined pulmonary stenosis and regurgitation (two with congenital cardiac anomalies and two with carcinoid heart disease). In two patients, the valve was neither stenotic nor regurgitant. Thus, congenital heart disease accounted for 110 of the 116 cases (95%), and tetralogy of Fallot was the most commonly observed form (65 cases). Bicuspid pulmonary valve was the most common anomaly and was present in 58% of patients with tetralogy but in only 17% of those with isolated pulmonary stenosis.

Adolescent↗
PubMed1987

Echocardiographic features of idiopathic hemochromatosis.

To characterize cardiac involvement in idiopathic hemochromatosis, clinical records and 2-dimensional (2-D) echocardiograms of 24 patients with idiopathic hemochromatosis were reviewed. The 17 men and 7 women were 24 to 80 years old (mean 48). Of 19 patients without valvular, ischemic, hypertensive or other known heart disease, 7 (37%) had structural and functional echocardiographic abnormalities attributed to idiopathic hemochromatosis (group 1) and 12 had normal echocardiographic findings (group 2). Age, gender and laboratory markers of iron overload did not differentiate patients with cardiac dysfunction (group 1) from those without cardiac dysfunction (group 2). In group 1, echocardiographic abnormalities included chamber dilatation and global systolic dysfunction. Increased wall thickness was not a feature of idiopathic hemochromatosis. All group 1 patients had abnormal electrocardiographic findings and cardiomegaly on radiography. Despite therapeutic phlebotomy, 4 patients in this group died, between 0.5 and 30 months after echocardiography, because of congestive heart failure. In conclusion, there is a spectrum of cardiac dysfunction in idiopathic hemochromatosis. In patients with idiopathic hemochromatosis and left ventricular dysfunction, absolute wall thickness is normal. Survival is poor in patients with idiopathic hemochromatosis and severe left ventricular dysfunction.

Adult↗
PubMed1987

Senile cardiac amyloidosis with myocardial dysfunction. Diagnosis by endomyocardial biopsy and immunohistochemistry.

Senile cardiac amyloid discovered at autopsy is usually regarded as an incidental finding. However, in immunohistochemical studies of autopsy material, three distinct forms of senile cardiovascular amyloid have been characterized, including a systemic form that diffusely infiltrates the cardiac ventricles. The systemic form can be identified immunohistochemically with use of antiserum to human prealbumin. We diagnosed senile systemic amyloidosis causing cardiac dysfunction in five men (57 to 72 years old) by using antiserum to prealbumin in myocardial biopsy tissue. Clinically, the five patients were indistinguishable from patients with nonsecretory immunoglobulin-derived primary amyloidosis with cardiac involvement; only immunohistochemical staining of myocardial tissue distinguished between the two entities. This distinction is important, because the treatment and prognosis of the two disorders are different. We recommend immunohistochemical staining of myocardial tissue for prealbumin in patients with biopsy-proved cardiac amyloid in whom no monoclonal immunoglobulin light chain is detectable in the serum or urine.

Aged↗
PubMed1987

Aortic valve stenosis: etiology, pathophysiology, evaluation, and management.

More patients with valvular aortic stenosis are being recognized, especially elderly patients with degenerative disease of the aortic valve. For nearly all patients with aortic valvular stenosis, 2-D and Doppler echocardiography have been found to be reliable for both the diagnosis and the establishment of severity (by gradient and valve area) of stenosis as well as for assessment of left ventricular function. Therefore, we project a lesser role for cardiac catheterization in the future, limited to definition of the coronary anatomy. Aortic valve replacement remains the proven therapy for patients with symptomatic aortic stenosis, although the decalcification/lithotripsy and balloon valvuloplasty techniques appear to be promising options in selected patients.

Aortic Valve↗
PubMed1987

Surgical pathology of the mitral valve: a study of 712 cases spanning 21 years.

The gross surgical pathologic features of the mitral valve were reviewed in 712 patients who had undergone mitral valve replacement at our institution during 1965, 1970, 1975, 1980, and 1985. Among the 452 cases of mitral stenosis, either with or without mitral insufficiency, 99% were attributable to postinflammatory disease and 1% were related to congenital mitral stenosis. Among the 260 cases of pure mitral regurgitation, the two most common causes were a floppy valve (38%) and postinflammatory disease (31%). Moreover, a floppy valve was observed in 73% of the 59 examples of chordal rupture and in 38% of the 16 cases of infective endocarditis. Women accounted for 73% of the 452 cases of mitral stenosis and for 72% of the 530 cases of postinflammatory disease. In contrast, men accounted for 58% of the 260 cases of pure mitral regurgitation, including 76% of the floppy valves and 69% of the infected valves. During the 21 years spanned by the study, the relative frequency of postinflammatory mitral insufficiency progressively decreased, whereas that of floppy mitral valves increased. It is unclear whether aging, heredity, environmental factors, changes in the frequency of acute rheumatic fever, or changes in patient referral practices may account for this observation.

Adolescent↗
PubMed1987

Cardiac iron deposition in idiopathic hemochromatosis: histologic and analytic assessment of 14 hearts from autopsy.

In each heart taken from autopsies of 14 men with idiopathic hemochromatosis, the conduction system, atria and 10 sites in the ventricles were histologically graded for stainable iron. Stainable iron was exclusively sarcoplasmic; none was observed in the interstitium. The histologic grade for the same anatomic site varied among hearts and among different anatomic sites in the same heart. Ten hearts had stainable iron in all ventricular sites; one of the three hearts from patients who had undergone therapeutic phlebotomy had no iron at any site. Seven hearts had iron in the atria but at a lesser grade than that found in the ventricles; six hearts had mild focal iron deposition in the atrioventricular conduction system. None of the 14 hearts had stainable iron in the sinus node. Elemental iron was quantitated by atomic absorption spectroscopy in ventricular specimens contiguous to those studied histologically and also in age-matched control hearts. Elemental iron content was markedly increased in hearts with idiopathic hemochromatosis compared with control hearts (p less than 0.01). The quantity of elemental iron varied greatly, similar to stainable iron, but was highest subepicardially. Among the hearts from the 11 patients without prior phlebotomy, three had no stainable iron in the right ventricular septal subendocardium, suggesting that sampling error may be a problem in the evaluation of hemochromatosis by endomyocardial biopsy. The sarcoplasmic location of the iron indicates that cardiac involvement in idiopathic hemochromatosis represents a storage disease and not an infiltrative process; this finding is consistent with the normal ventricular wall thicknesses observed.

Adult↗
PubMed1986

Cardiac involvement in Lyme disease: manifestations and management.

Cardiac involvement in Lyme disease may manifest as atrioventricular block, myopericarditis, and left ventricular dysfunction. Diagnosis depends on recognition of the systemic nature of Lyme disease, including cardiac involvement, and its natural history. Serologic tests that are both sensitive and specific may aid in diagnosis. Although current recommendations for the treatment of Lyme disease with carditis include antibiotics and salicylates or corticosteroids, these types of therapy have not been unequivocally demonstrated to alter the natural history of cardiac involvement. Supportive therapy may necessitate temporary transvenous cardiac pacing in symptomatic patients.

Adult↗