A new model to assess tcpO2 changes during heat-dependent vasodilation: preliminary observations.

The transcutaneous pO2 (tcpO2) changes induced by the increase of temperature to 45 degrees C after electrode stabilization at 37 degrees C were continuously recorded. The mathematical analysis of the curve led us to identify three different parameters: the half-slope "b" time, the angular "mT" coefficient and the angular "mb" parameter, which are not simply the expression of the maximum vasodilation capacity but mainly of the dynamic response of the microcirculatory system to skin heating. These parameters derived from the computerized mathematical analysis of the curve can be also obtained by a graphical approach with a very good approximation. The angular "mb" coefficient was shown to possess the highest statistical power in discriminating the POAD patients from normal controls. The clinical relevance and the possible pathophysiological meaning of these preliminary observations have to be confirmed.

Increase in plasma levels of adenosine and adenine nucleotides after intravenous infusion of buflomedil in humans.

To clarify the mode of action of the vasoactive agent buflomedil, we evaluated plasma levels of adenosine and adenine nucleotides after intravenous (i.v.) infusion in humans of 50, 100, and 200 mg of the drug in 20 min. Buflomedil induced an increase of the same order of magnitude in plasma levels of adenosine and adenine nucleotides. Maximal adenosine increase (84%) was observed at the end of the infusion period, whereas peak plasma levels of ATP and ADP (69 and 55%, respectively) and of AMP (61%) were detected 10 and 5 min after discontinuation of infusion, respectively. Although the exact mode of action of buflomedil at the molecular level remains unclear, some indirect findings suggest that the increase in adenosine may be due to enhanced release rather than to inhibition of cell uptake. Because such activity of buflomedil consists of enhancement of physiologic mechanisms of vasodilation and tissue protection occurring in the course of ischemic events, new pharmacologic perspectives for the drug may arise.

[The infusion of calcium gluconate in coronary disease patients induces myocardial ischemia via a possible adenosine-mediated mechanism]. / L'infusione di calcio gluconato in pazienti coronaropatici induce ischemia miocardica attraverso un possibile meccanismo adenosino-mediato.

In the first part of the study 5 control subjects were submitted to iv infusion of 0.2 mM/kg of calcium gluconate in 20 min. Total calcium (atomic absorbtion method), ionized calcium (ion-selective electrode method) and adenosine (HPLC technique) were measured at the following times: 0 (baseline), 5, 10, 15, 20 (end of infusion), 25, 30, 35, and 50 min. The increase of total and ionized calcium serum levels was associated with a significant increase of adenosine plasma levels (from 207 +/- 41 to 362 +/- 63 nM, p < 0.001). Since the increase of adenosine plasma levels, obtained either with adenosine or dipyridamole (an adenosine reuptake inhibitor), has been used to test the coronary reserve in patients with coronary artery disease (CAD), in the second part of the study we compared the effects of calcium infusion with dipyridamole in 15 CAD subjects. Pharmacological stress tests were evaluated by monitoring two-dimensional echocardiography, ECG, heart rate, blood pressure and rate-pressure product. Ten patients were positive both to dipyridamole stress test and to calcium infusion, ad demonstrated by the onset of new areas of transient asynergy in the same myocardial regions. Dipyridamole infusion determined a significant increase in heart rate and rate pressure-product in all patients (both in positive and in negative), whereas calcium induced a slight, not significant decrease of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacodynamics of salmon calcitonin in humans: new markers of pharmacological activity.

In order to define the pharmacodynamic profile of salmon calcitonin (sCT) in humans, several markers of the biological activity of the drug have been studied, namely cAMP, adenosine and pO2 in venous blood, and the cytosolic free calcium level in circulating cells. Different dosages and routes of administration (1.5 IU.kg-1 and 0.75 IU kg-1 IM, and 1.5 IU.kg-1 via nasal spray) were compared. sCT caused an increase in cAMP, adenosine and pO2, and a decrease in cytosolic free calcium in neutrophils, lymphocytes and platelets. The peak times of all these parameters ranged between 109 and 182 min, and 101 and 168 min after IM and nasal spray administration respectively. There was greater variability in the values after IM than nasal spray of administration of sCT. It is concluded that adenosine and pO2 in venous blood, and cytosolic free calcium in circulating cells are valuable markers of the activity of sCT and that sCT decreases the cytosolic free calcium level in neutrophils, lymphocytes and platelets. Pharmacodynamic analysis of the biological effects of the drug is highly reliable and valuable in predicting its pharmacological profile. sCT administration via a nasal spray is able to produce significant biological effects, although they are less marked than after IM dosing.