[The pharmacodynamics of theophylline (euphylline)]. / Farmakodinamika teofillina (éufillina).

A single intravenous administration of 2.4%-10.0 euphylline to 35 patients with obstructive affections of the lungs entailed a broncholytic effect in large airways in patients with reversible obstruction under sub-therapeutical theophylline concentrations in the serum. In patients with mixed type of the obstruction and restrictive disturbances ineffective ventilation got worse, ventilation-perfusion relations disagreed, hemoglobin affinity to oxygen grew, pulmonary artery pressure dropped against the signs of pulmonary hypertension, EEG changed according to asynchronism pattern corresponding to brain hyperactivity. There was also elevation of both norepinephrine and epinephrine serum levels due to slow parenchymatous hepatic circulation which inhibited clearance of the substances. There was no relationship between changes in the indices and theophylline concentrations in the range 3.8-8.8 micrograms/ml.

Cardiac microdialysis measurement of extracellular adenine nucleotide breakdown products during regional ischemia and reperfusion in canine heart: protective effect of propranolol against reperfusion injury.

Using cardiac microdialysis, we studied release of the adenine nucleotide breakdown products (ANBP) adenosine (ADS), inosine (INS), and hypoxanthine (HYP) into the interstitium of canine myocardium during 20- and 40-min occlusion of the anterior descending coronary artery and reperfusion. Dialysate ANBP concentrations reached maximum values not at the end of ischemia but in the first 10 min of reperfusion. The effect was more pronounced after 20-min ischemia. Further reperfusion led to an ANBP decrease that was more prolonged after 40-min ischemia. Pretreatment with DL-propranolol (0.5 mg/kg, intravenously, i.v.) given 40 min before coronary occlusion had no effect on adenine nucleotide catabolism rate during 20- and 40-min ischemia, but it facilitated washout of ANBP from ischemic zone immediately after the start of reperfusion. A similar effect was elicited by a D-stereoisomer of propranolol with no beta-adrenoceptor blocking activity. Results suggest that the reperfusion injury and probably the no-reflow phenomenon were the cause of enhanced adenine nucleotide catabolism at the beginning of reperfusion and prolonged ANBP washout from the ischemic zone. Reduction of reperfusion injury by propranolol could be related to the membrane stabilizing and antioxidant activity of this agent. Examination of DL-propranolol kinetics in arterial and coronary venous blood plasma showed that drug accumulation in the myocardium was almost maximum at the start of ischemia; therefore, the efficiency of cardio-protection with DL-propranolol was not limited by pharmacokinetic causes. Insertion of an additional microdialysis probe in the myocardium allowed monitoring of extracellular propranolol concentrations.

[Microdialysis study of release of adenine nucleotide breakdown products into the intercellular space of the myocardium in ischemia and reperfusion]. / Mikrodializnoe issledovanie vysvobozhdeniia v mezhkletochnoe prostranstvo miokarda produktov raspada adeninnukleotidov pri ishemii i reperfuzii.

Interstitial concentrations of adenine nucleotide breakdown products (ANBP)--adenosine (ADS), inosine (INS), hypoxanthine (HYP), in perfused rat hearts were measured during total ischemia and reperfusion by microdialysis technique. Progressive accumulation of ANBP in the interstitial space was observed during ischemia, but unlike INS and HYP, maximal ADS concentration was reached not by the end of ischemia but after the beginning of reperfusion. During reperfusion the qualitative accordance between changes in ANBP levels in the interstitial space and venous effluent was observed, but interstitial concentrations were several times greater.

[Features of myocardial metabolism of adenylic nucleotides in patients with paroxysmal tachycardias]. / Osobennosti obmena adenilovykh nukleotidov miokarda u bol'nykh s paroksizmal'nymi takhikardiiami.

The authors revealed that concentrations of inosin, hypoxanthine and their total levels in the arterial blood and the blood of the coronary sinus in patients with paroxysmal tachycardias are higher than the corresponding levels in patients with chronic forms of coronary heart disease and neurocirculatory dystonia. In the absence of tachycardia, there was an accelerated metabolism of adenyl nucleotides of the myocardium: the myocardium produced inosin and extracted hypoxanthine. It is suggested that this type of metabolism of adenyl nucleotides requires additional energy expenditures as compared with the energy supply of the nucleotide metabolism of the healthy myocardium and may be one of the reasons underlying the development of tachycardiac paroxysm, with the place of the localization of the re-entry and/or the presence of coronary heart disease having no significant effect on the metabolism of adenyl nucleotides of the myocardium in such patients. The emergence of tachycardia leads to a decreased extraction of hypoxanthine by the myocardium as compared to the baseline and to insignificant elevation in the production of inosin which causes an increase in the levels of these metabolites in the arterial blood and the blood of the coronary sinus.

[Effect of myocardial ischemia on adenine nucleotide metabolism]. / Vliianie ishemii miokarda na obmen adenilovykh nukleotidov.

Patients with coronary heart disease (CHD), neurocirculatory dystonia and acute myocardial infarction showed statistically significant, positive linear correlations between the levels of inosine and hypoxanthine as well as the total concentration in the arterial blood and the blood from the coronary sinus. The correlation analysis ascertained that CHD patients in the initial state exhibited a considerable extraction of inosine by the myocardium as compared to patients with neurocirculatory dystonia and that in electrically stimulated ischemia it was sharply reduced. Electrostimulation in the group of patients with neurocirculatory dystonia had no effect on the rate of inosine extraction. Acute myocardial infarction was related to a higher rate of inosine extraction and to inosine production in the myocardium, the latter being explained by the degradation of adenyl nucleotides in conditions of acute ischemia. It is outlined that the total level of inosine and hypoxanthine in the arterial blood of patients with acute myocardial infarction may indicate the severity of infarction while its variations over time may be prognostically valuable.