Immunogenetic studies of the platelet-specific antigen P1A1 (Zw(a))

The phenotype frequency of the platelet-specific antigens PI^A1/^A2 (= Zw(a,b)) in the German population (N = 711) is 97.75 % and 2.25 % respectively. The corresponding gene frequencies are PI^A2 0.85; PI^A2 0.15. The PI^A1 determinant is codominantly inherited (19 families; 151 family members). There is a strong gene dosage effect between PI^A1-homoand heterozygous individuals. No definite linkage of the locus PIAl versus the loci HLA-ABC, ABO, or Rh was found.     

CARDIOVASCULAR EFFECTS OF NICOTINE DURING PHYSICAL ACTIVITY AND FOLLOWING MEAL CONSUMPTION

1. In two separate studies using healthy male smokers as subjects, the acute cardiovascular effects of a measured dose of nicotine (15 micrograms/kg) were examined in conjunction with light physical activity and following consumption of a meal, conditions typical of nicotine intake via smoking. 2. Increases in heart rate and systolic blood pressure attributable to nicotine were similar during rest, physical activity, and following eating, demonstrating additivity with the cardiovascular effects of activity and a caloric load. Diastolic blood pressure was less affected by nicotine. 3. These results indicate that cardiovascular activity is acutely increased following nicotine (smoking) regardless of other influences on the cardiovascular system. Such effects may help explain increased risks of acute cardiac abnormalities due to smoking.     

Validity of CO2-rebreathing cardiac output during rest and exercise in young adults

To validate the CO2-rebreathing method ( Defare 's method) for estimating cardiac output in children and young adults, measurements were compared to thermodilution ( TDCO ) cardiac output in 16 subjects (age 7-19 yr) with congenital heart disease. Data were collected at rest (N = 11) and during 4-min stages of supine bicycle exercise (N = 13). Estimated arterial-venous (-v-a)CO2 content differences related linearly to the measured CO2 content difference (Y = 0. 29X + 2.47, r = 0.65, P less than 0.001). With this (v-a)CO2 difference correction for all patients (N = 16), the correlation between CO2-rebreathing cardiac output and the TDCO was r = 0.87 (SEE = +/- 1.8 l X min-1). The correlation was higher for exercise (r = 0.81) than for rest (r = 0.65). We conclude that the CO2-rebreathing method, with a (v-a)CO2 content difference adjustment, is a simple, noninvasive technique providing estimates of cardiac output in children and young adults with congenital heart disease. Individual estimates should be treated with caution, especially when used for clinical evaluations.     

Assay of glyceryl trinitrate, isosorbide dinitrate, and their metabolites in plasma by large-bore capillary column gas-liquid chromatography

Two large-bore capillary columns, one with dimethyl polysiloxane (HP-1) as the stationary phase and the other with phenyl (50 per cent) methyl (50 per cent) polysiloxane (DB-17), were used to develop gas-liquid chromatographic (GLC) assays for measuring isosorbide dinitrate (ISDN), glyceryl trinitrate (GTN), and their metabolites. ISDN, isosorbide-2-mononitrate (2-ISMN), and isosorbide-5-mononitrate (5-ISMN) in plasma, ranging in concentration from 1 to 300 nM, and GTN, glyceryl-1,2-dinitrate (1,2-GDN), and glyceryl-1,3-dinitrate (1,3-GDN), ranging in concentration from 3 to 60 nM in plasma, were analysed on both columns. GLC analysis yielded baseline resolution of the analytes. The method using the dimethyl polysiloxane column gave a lower limit of detectability for GTN of 0.75 nM (signal/noise (s/n) = 2), and the procedure using the phenyl-methyl column provided a lower limit of detectability for ISDN of 81 pM (s/n = 2). The large-bore column GLC procedures exhibited shorter retention times for both ISDN and GTN than those previously reported for capillary-column assays. The chromatographic resolution of analytes and column efficiency of the large-bore capillary columns were comparable to the results previously found using capillary-column GC. The assays for ISDN and GTN have been shown to be appropriate for pharmacokinetic studies in volunteers and patients. We determined that the HP-1 column is appropriate for the analysis of GTN and metabolites, and the DB-17 column is suitable for analysis of ISDN and its metabolites. We conclude that the use of large-bore capillary columns provides rapid and reliable GLC assays for organic nitrates.