The effect of pentaerithrityl-tetranitrate on parameters of the microcirculation.
OBJECTIVE
The effect of organic nitrates on microcirculation was first studied in 1964 and with regard to glyceroltrinitrate (GTN) an "internal hemodilution" (i.e. a fluid shift from the extravascular fluid to the intravascular compartment) was observed. Therefore, we found it of interest to study the effects of the long-acting PETN on parameters of hemorrheology.


METHODS
The effects of single doses of 25, 50, and 80 mg PETN, 0.4 mg GTN, and of placebo were investigated on the capillary erythrocyte velocity (CEV; Capiflow), the tissue oxygen tension (tcpO2), the deformability of red blood cells, the plasma viscosity and of the fibrin content of the plasma in a single-blind, randomized study over 12 h in 12 healthy female and male volunteers. The CEV and the tcpO2 were measured in the nailfold of the fourth finger and on the skin of its end phalanx, respectively. Statistical analysis was performed by analysis of variance, the calculation of epsilon (Greenhouse-Geisser), and the multiple t test.


RESULTS
After administration of 50 or 80 mg PETN the CEV decreased by 30% over a period of 2 or 4 h (p = 0.02 or 0.002). A decrease by 11% was measured 1 and 2 h after administration of GTN (p = 0.034). Under the same PETN doses tcpO2 increased from 1.41 to 1.78 mm mercury (p = 0.002). The deformability of red blood cells was slightly increased after 50 and 80 mg PETN under share rates of 60 Pa from 55.5 to 58.0% 8 and 12 h after intake. The plasma viscosity was decreased after intake of 50 mg PETN 4 to 8 h (1.36 vs. 1.34 Pa x s, p = 0.023) and after intake of 80 mg 2 to 12 h post dose (1.36 vs. 1.33 Pa x s, p = 0.015). The systolic or diastolic blood pressure decreased, but was not significant.


CONCLUSIONS
The PETN-induced decrease in CEV can be explained with the pre- and afterload decreasing properties of the nitrates. The increase in tcpO2 and erythrocyte deformability and the decrease in viscosity are additional advantageous effects on the microcirculation. If the results are transferred from the nailfold of the finger to the myocardium, the benefit of nitrates could not only be seen in the decrease in preload due to their vasodilating properties, but also in improving the parameters of microcirculation. The internal hemodilution and the slightly enhanced deformability might provide an additional supply of myocardial capillaries in case of myocardial ischemia.
Clinical Pharmacology Erfurt, Friedrich-Schiller-Universität Jena, Germany.
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Böhm
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Haustein
D000284:Administration, Oral; D000328:Adult; D001785:Blood Gas Monitoring, Transcutaneous; D001794:Blood Pressure / Q000187:drug effects; D001809:Blood Viscosity / Q000187:drug effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D018056:Hemorheology / Q000187:drug effects*; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D005996:Nitroglycerin / Q000494:pharmacology*; D010417:Pentaerythritol Tetranitrate / Q000008:administration & dosage / Q000494:pharmacology*; D016037:Single-Blind Method; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate; D005996:Nitroglycerin