Endothelin receptor subtype A blockade selectively reduces pulmonary pressure after cardiopulmonary bypass.

BACKGROUND: The bioactive peptide endothelin-1 is elevated during and after cardiopulmonary bypass and exerts cardiovascular effects through its 2 receptor subtypes, endothelin-1A and endothelin-1B. Increased endothelin-1A receptor stimulation after cardiopulmonary bypass can cause increased pulmonary vascular resistance and modulate myocardial contractility. However, whether and to what degree selective endothelin-1A blockade influences these parameters in the postbypass setting is not completely understood. OBJECTIVES: Our objective was to measure left ventricular function and hemodynamics in a porcine model of cardiopulmonary bypass after selective blockade of endothelin-1A. METHODS: Adult pigs (n = 23) underwent 90 minutes of cardiopulmonary bypass and were randomized 30 minutes after bypass to receive a selective endothelin-1A antagonist (TBC 11251, 10 mg/kg; n = 13) or saline vehicle (n = 10). RESULTS: After bypass and before randomization, pulmonary vascular resistance rose nearly 4-fold, and left ventricular preload recruitable stroke work fell to one third of baseline values (both P <.05). In the vehicle group pulmonary vascular resistance continued to rise, and preload recruitable stroke work remained reduced. However, after endothelin-1A blockade, the rise in pulmonary vascular resistance was significantly blunted compared with that in the vehicle group. Moreover, the reduction in pulmonary vascular resistance with endothelin-1A blockade was achieved without a significant change in systemic perfusion pressures. CONCLUSIONS: The present study demonstrated that increased activity of the endothelin-1A receptor likely contributes to alterations in pulmonary vascular resistance in the postbypass setting. Selective endothelin-1A blockade may provide a means to selectively decrease pulmonary vascular resistance without significant effects on systemic hemodynamics.

Temporal endothelin dynamics of the myocardial interstitium and systemic circulation in cardiopulmonary bypass.

OBJECTIVE: Increased systemic levels of the bioactive peptide endothelin 1 during and after cardioplegic arrest and cardiopulmonary bypass have been well documented. However, endothelin 1 is synthesized locally, and therefore myocardial endothelin 1 production during and after cardiopulmonary bypass remains unknown. METHODS: Pigs (n = 11) were instrumented for cardiopulmonary bypass, and cardioplegic arrest was initiated. Myocardial interstitial and systemic arterial levels of endothelin 1 were measured before cardiopulmonary bypass, throughout bypass and cardioplegic arrest (90 minutes), and up to 90 minutes after separation from bypass. Myocardial interstitial endothelin 1 was determined by microdialysis and radioimmunoassay. RESULTS: Baseline myocardial endothelin 1 levels were higher than systemic endothelin 1 levels (25.6 +/- 6.7 vs 8.3 +/- 1.1 fmol/mL, P <.05). With the onset of bypass, myocardial endothelin 1 increased by 327% +/- 92% from baseline (P <.05), which preceded the increase in systemic endothelin 1 levels. CONCLUSION: Myocardial compartmentalization of endothelin 1 exists in vivo. Cardiopulmonary bypass and cardioplegic arrest induce temporal differences in endothelin 1 levels within the myocardial interstitium and systemic circulation, which, in turn, may influence left ventricular function in the postbypass period.

An evaluation of two compact analyzers used for lipid analysis.

BACKGROUND: A number of relatively inexpensive compact analyzers are available for use in physician offices and outpatient clinics to measure total cholesterol and, more recently, high-density lipoprotein (HDL) cholesterol and triglycerides. This study was designed to document the analytical performance of two of them, the Abbott Vision and the Kodak Ektachem DT60, for assays of total cholesterol, HDL cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol. METHODS: Lipid profiles were measured from venous blood samples of 70 subjects with each test device, and results were compared with those from a laboratory standardized to the Centers for Disease Control. Coefficient of variation (CV) of multiple measurements from three pools of human serum (ie, precision), mean percent difference between device and standard laboratory results (ie, accuracy or bias), and 95% tolerance intervals (total error) were determined. The correct classification of patients into risk categories with device results was compared with the standardized laboratory results. RESULTS: The average CVs for total cholesterol, triglycerides, and HDL cholesterol with the Vision analyzer were 3.6%, 4.4%, and 10.5%, respectively, and with the DT60, 5.0%, 4.1%, and 6.8%, respectively. The average percent biases for the same analytes with the Vision analyzer were 0.2%, 4.0%, and -2.3%, respectively, and with the DT60, -2.1%, 12.1%, and 0.1%, respectively. Total error assessments indicated that total and HDL cholesterol measurements in individual patients met the guidelines of the National Cholesterol Education Program with both devices, but that triglycerides and LDL cholesterol measurements did not. Classification of subjects into risk groups based on total or LDL cholesterol gave clinically satisfactory results with either device. CONCLUSIONS: More precise measurement technology for LDL cholesterol is needed. Physicians and others who rely on compact analyzer results for diagnosis and treatment decisions should consider the degree of inaccuracy and imprecision in these values.

Latent disseminated blastomycosis with choroidal involvement.

A 36-year-old man developed blurred vision and a cough five months after traveling to an area from where a large outbreak of acute blastomycosis had been reported. Examination revealed a left choroidal lesion in the macular region, skin lesions on the right calf, and a left lung apical infiltrate. Histopathologic examination of the skin lesion demonstrated a granulomatous inflammation and broad based, budding yeast characteristic of Blastomyces dermatitidis. Amphotericin B therapy produced a rapid resolution of both choroidal and pulmonary lesions. During a six-month follow-up, there was no evidence of recurrence.