Interactions between vasodilator drugs and human hemoglobin

The in vitro effect of the vasodilators papaverine, dipyridamole, nifedipine, prenylamine and glyceryl di-tri- and tetranitranitrate on the oxygen saturation curve of human hemoglobin (Hb) was evaluated. The Hb dissociation curve was measured spectrophotometrically both for freshly obtained heparinized blood and for purified Hb A after incubation with the drugs. For both purified Hb and whole blood samples, incubation with papaverine, dipyridamole and nifedipine modified P50 (PO2 for half saturation of the Hb/oxygen sites) at pH 7.4: 30.9 mmHg for 0.72 mM papaverine vs 23.9 mmHg for control; 23.9 mmHg for 1.43 mM dipyridamole vs 20.8 mmHg for control; 1.09 mmHg for 2.73 mM nifedipine vs 1.14 mmHg for control stripped Hb. The effects of the three vasodilators on Hb were correlated with pH, methemoglobin formation, temperature and incubation time. P50 values were determined for Hb of the blood of angina patients treated with one of the vasodilators, and blood 2,3-diphosphoglycerate (2,3-DPG) levels were also measured. In contrast to the in vitro data, neither P50 nor 2,3-DPG levels were significantly modified in the blood of patients treated with one of the vasodilators. These in vitro studies demonstrated that the vasodilators papaverine and dipyridamole decrease, and nifedipine increases the oxygen affinity of Hb in red blood cells or as a purified hemoglobin

correlation study between 2,3-diphosphoglycerate [2,3-DPG] and platelet aggregation on congenital heart diseases

This study was conducted upon 30 individuals, 20 patients having congenital heart diseases [CHD], 10 cyanotic and 10 acyanotic patients, and 10 healthy controls. All subjects were investigated for 2, 3-diphosphoglycerate [2, 3-DPG] in blood and ADP induced platelet aggregation to clarify any relationship between these two parameters. Also platelet aggregation to clarify any relationship between these two parameters. Also platelets count, hematocrit value, [HCT], O2 saturation, PO2 and blood pH were determined. The results revealed that platelet did not differ in patient groups compared to control group. In the cyanotic group ADP-induced platelet aggregation showed a marked impairment compared to control group. In addition 2, 3-DPG enzyme was significantly increased in both cyanotic and acyanotic groups, but this increase was much higher in the cyanotic group. Correlation study between 2, 3-DPG level in blood and platelet aggregation induced by revealed that there was an inverse relationship between 2, 3-DPG enzyme level in blood and ADP induced platelet aggregation in patients with cyanotic CHD. Thus, it could be concluded that the glycolytic pathway of red blood cells interact with the prostaglandin pathway of platelets in order to maintain blood flow homeostasis in hypoxic patients. If this is proved to be correct, then, there is another good reason apart from altering hemoglobin oxygen affinity, for elevated 2, 3-DPG concentration in erythrocytes in cyanotic patients. Such an enzyme could be of great clinical usefulness in the treatment of thromboembolic disease

Restoration of 2,3 diphosphoglycerate and adenosine trisphosphate concentrations in stored blood by using alanine and/or phosphoenol pyruvate

The effect of incubating dog red cells in citrate-phosphate dextrose adenine [CPDA] containing L-alanine [ALA] and/or phosphoenol pyravate [PEP], at 37°C for one hour was studied. All the additive mixtures increased 2, 3 diphosphoglycerate [2, 3 DPG] level as compared to CPDA control. CPDA-ALA-PED, CPDA-PEP and CPDA-ALA increased 2, 3 DPG level by 60%, 47% and 10% respectively. Also, CPDA-ALA-PEP and CPDA-PEP increased adenosine triphosphate level by 33% and 23% respectively. Storage of blood in the different additive showed that CPDA-ALA-PEP surpassed all other additives in maintaining 2, 3 DPG and ATP concentrations, and decreasing supernatant hemoglobin [Hb] and percent hemolysis, throughout 42 days at 4°C

Efecto de la adenosina sobre la P50 y su relación con el 2, 3-difosfoglicerato / The efect of adenosin on the P50 and its relationship with the 2, 3 diphosphoglyceric acid

En 17 perros anestesiados mantenidos en condiciones estables de ventilación, temperatura y equilibrio ácido base, estudiamos los efectos de dosis crecientes de adenosina administrada por infusión continua, sobre la posición de la curva de disociación de la hemoglobina (CDH) y su relación con los niveles intraeritrocíticos de 2,3 difosfo glicerato (2,3 DPG). en todos los perros la CDH (en sangre arterial y venosa) se desplazó a la izquierda en forma significativa, excepto a la dosis de 120 ug/kg/min, en que la CDH se desplazó a la derecha, y a partir de 240 ug/kg/minla CDH se estabilizó en un nivel inferior al control. Estos cambios fueron paralelos con los experimentos, la frecuencia cardiaca y la presión arterial disminuyeron significativamente. Concluimos que la adenosina modifica la CDH desplazándola en general hacia la izquierda, y que ésto parece estar en relación con un cambio en los niveles intraeritrocíticos de 2,3-DPG

Efecto de la transfusión sanguínea sobre los valores del 2,3-DPG del eritrocito y la P50 en lactantes sépticos / Effect of blood transfusion on values of 2,3-DPG of erythrocyte and the P50 in septic infants

Se compararon los valores previos y posteriores a transfusión de sangre, de 2,3-DPG, la P50, lactato sérico y diferencia arteriovenosa, en 12 pacientes lactantes sépticos, con anemia aguda que ameritaron transfusiones de sangre o paquete globular de urgencia. Además se tituló 2,3-DPG en la bolsa que se transfundió y se correlacionó con los días de almacenamiento. Treinta llactantes sanos formaron el grupo control. Se determinó el 2,3-DPG por el método enzimático en sangre total hemolizada, la P50 determinando la saturación medida en un cooxímetro y calculada con el nomograma de Shires, la PaO**2 en el gasómetro IL 513 y sangre arterial y venosa. Los 12 pacientes mostraron niveles bajos de 2,3-DPG (0.168 + ou - 0.18 micronmol/ml versus control 0.83 + ou - 0.18 micronmol/ml) comparados con el grupo control, con diferencia estadística significativa (p<0.005); la P50 estuvo baja (24.5 + ou - 3.4 mmHg versus 30.8 + ou - 4.05 mmHg, pNS); el lactato se encontró elevado (32.4 + ou - 19.8 mg/dl versus 15 + ou - 3 mg/dl). Los niveles de 2,3-DPG en las bolsas de sangre transfundidas estuvieron bajas en relación a los niveles séricos del grupo control (0.23 + ou - 0.17 micronmol/ml) con diferencia estadística (p<0.005). Se encontró correlación entre los días de almacenamiento y los niveles de 2,3-DPG en las bolsas (p<0.001); a los ocho días las bolsas estaban completamente depletadas 2,3-DPG. En nueve pacientes, los niveles de 2,3-DPG se elevaron después de la transfusión (0.31 + ou - 0.15 micronmol/ml); los que recibieron sangre menor de cinco días, todos sobrevivieron. La P50 en este grupo también se elevó (37.1 versus 23.5 + ou - 1.4 mmHg); el lactato disminuyó a niveles normales. De los tres pacientes que fallecieron, uno recibió sangre menor de cinco días y elevó la P50 y el 2,3-DPG; los otros dos disminuyeron el 2,3-DPG y la P50 y recibieron sangre mayor de 5 días