Relationship between the inhibition of receptor-induced increase in cytosolic free calcium concentration and the vasodilator effects of nitrates in patients with congestive heart failure.

Nitroglycerin, isosorbide dinitrate and sodium nitroprusside, like nifedipine, were found to inhibit the receptor-provoked increase of cytosolic free calcium concentration in human platelets loaded with 2-[(2-amino-5-methylphenoxy)methyl]-6-methoxy-8-aminoquinoline-N,N,N',N' - tetraacetate. Sodium nitroprusside and nitroglycerin induced elevation of cyclic guanosine 3',5'-monophosphate content in platelets which correlated with their calcium-blocking activity. Methylene blue and epinephrine decreased the calcium-blocking effect and the influence of nitroglycerin on cyclic guanosine 3'-5'-monophosphate content, but failed to suppress the inhibitory effect of sodium nitroprusside. Ascorbic acid increased the calcium blocking effect of sodium nitroprusside and its influence on cyclic guanosine 3'-5'-monophosphate content, but did not alter the inhibitory effect of nitroglycerin. In order to evaluate the relationship between the mode of action of nitrates at cellular level and their vasodilatory effectiveness, we studied the circulatory response of the forearm to isosorbide dinitrate and the influence of nitroglycerin on free calcium concentration in the platelets in 10 patients with chronic heart failure. We established a significant positive correlation between the basal values for venous tone and its peak decrease after administration of the 10-mg dose of isosorbide dinitrate. A correlation was also found between the deviation of maximal decrease of venous tone by this dose of isosorbide dinitrate from the regression line (the relationship between the basal venous tone and its lowering by the drug) and mean inhibitory concentration values for nitroglycerin in blocking that proportion of the rise of calcium ion concentration in platelets due to blocking of the platelet-activating factor. Thus, nitrates, like calcium antagonists, inhibit the receptor-provoked calcium supply to the contractile system of the cells so neutralizing the effects of increased concentrations of vasoconstrictors. This suggests that the effectiveness of nitrates appears to be positively related to the contribution of receptor-induced increase of cytosolic free calcium concentration in vasoconstriction together with their capacity to raise cyclic guanosine 3',5'-monophosphate.

[Effect of the calcium antagonist nifedipine on central and peripheral hemodynamics in patients with primary pulmonary hypertension]. / Vliianie kal'tsevogo antagonista nifedipina na tsentral'nuiu i perifericheskuiu gemodinamiku u bol'nykh pervichnoi legochnoi gipertoniei.

15 patients with primary pulmonary hypertension (PPH) were studied. An acute test with 20 mg nifedipine (N) sublingually was performed and the pulmonary artery pressure (PAP) was measured. N had manifest arterolodilating effect in the systemic and especially pulmonary circulation, induced decrease in the total peripheral and total pulmonary vascular resistance (TPerVR and TPulVR) by 21.7 and 25.3%, correspondingly. N had principal effect on pulmonary arterioles (TPerVR/TPulVR ratio increased by 16.9%). Systolic and diastolic PAP decreased in this case by 15.2 and 18.4%, correspondingly. All the patients demonstrated increase in cardiac output (on the average by 17.0%) and insignificant increase in heart rate (7.4%).

[New approaches to the study of the mechanism of action of nitrates]. / Novye podkhody k izucheniiu mekhanizma deistviia nitratov.

The effects of nitrates on a Ca+2 increase and the content of cyclic nucleotides in human platelets were studied. Nitroglycerin (GTN), isosorbide dinitrate (ISDN) and sodium nitroprusside (NP) were found to inhibit dose-dependently the intracellular Ca+2 increase induced by the platelet activating factor (PAF). The inhibiting effect of NP was at lower concentrations than those of GTN and ISDN. GTN calcium blocking action did not change significantly regardless of vasopressin, serotonin or PAF used as inducers of the intracellular Ca+2 increase. GTN suppressed the PAF provoked Mn+2 entering into the cells. NP and GTN induced increase of the cGMP content correlated with their calcium blocking activity. They did not augment the level of cAMP. Methylene blue (MB), a guanylate cyclase and glutathione reductase inhibitor, decreased the calcium blocking effect of GTN and its influence on the cGMP content but failed to suppress the inhibitory effect of NP. Ascorbic acid increased the calcium blocking effect of NP but did not influence the inhibitory effect of GTN. An increase in Ca+2 content induced by PAF in platelets from patients with chronic congestive heart failure was significantly higher in the group with dilatation cardiomyopathy. The effect of 10 mg of ISDN sublingually on forearm venous tone was higher in patients with initially elevated venous tone. There was a direct statistical correlation between the IC50 of GTN calcium blocking effects in platelets and the elevation of a forearm venous tone reaction from a statistic mean reaction to ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in regional hemodynamics and tissue oxygenation in heart failure patients as affected by nifedipine (corinfar)]. / Izmenenie regionarnoi gemodinamiki i oksigenatsii tkani u bol'nykh s serdechnoi nedostatochnost'iu pod vliianiem nifedipina (korinfara).

Regional hemodynamics using plethysmography and tissue oxygen tension at the basal level and during corinfar administration were investigated in 38 patients with heart failure against a background of rheumatic heart valvular diseases, dilatation cardiomyopathy and coronary heart disease. A considerable decrease in regional vascular resistance (RVR) and improvement of tissue oxygenation were noted in persons with a raised basal RVR level. A value of an acute test with corinfar for administration of regular therapy was determined.

[Use of peripheral vasodilators with different mechanisms of action in treating heart failure patients]. / Primenenie perifericheskikh vazodilatatorov s razlichnym mekhanizmom deistviia v lechenii bol'nykh s serdechnoi nedostatochnost'iu.

The efficacy of peripheral vasodilators with various mechanisms of action was studied in 26 patents with congestive heart failure, left ventricular dilatation and valvular regurgitation. An acute pharmacological test using prazosin was used in all the patients, 20 of them were given a 15-day course of prazosin therapy, 19 patients received a prolonged course of prazosin therapy (over 3 mos.), 15 patients were given a 15-day course with a combination of isosorbide dinitrate and hydralazine. ECG monitoring, catheterization of the right cardiac chambers, thermodilution, and tetrapolar impedance plethysmography were employed. Heart rate, arterial pressure, parameters of cardiac pre- and afterload and pulmonary hemodynamics were studied. Prazosin and isosorbide dinitrate in combination with hydralazine showed a high clinical efficacy in the treatment of patients with congestive heart failure. The improvement of clinical symptomatology was accompanied by considerable positive shifts of the central and peripheral hemodynamics. No considerable differences in the efficacy of prazosin and the combination of isosorbide dinitrate with hydralazine were revealed.

[Changes in peripheral hemodynamics and platelet aggregation during captopril treatment of patients with chronic circulatory failure]. / Izmeneniia perifericheskoi gemodinamiki i agregatsii trombotsitov pod vliianiem kaptoprila u bol'nykh s khronicheskoi nedostatochnost'iu krovoobrashcheniia.

A total of 18 patients with chronic congestive heart failure were examined using an acute pharmacological test (25-50 mg of captopril) and during 2-week course treatment. A marked positive effect of the drug was noted in 15 (83.3%) patients. Captopril significantly decreased venous tone by 19.0 +/- 2.4% and by 40.4 +/- 4.1% and regional vascular resistance by 25.7 +/- 1.9% and by 39.4 +/- 2.9% in the acute test and in course treatment, respectively. Microcirculatory indices also improved: there was an increase in tissue oxygenation (PO2 by 38.8 +/- 2.7%), oxygen supply rate and small arteriolar function (more pronounced in course treatment). Platelet aggregation in the captopril acute test was slightly decreased but in course treatment it did not significantly differ from the initial one. A conclusion was made that captopril, mostly in course treatment, decreased venular and arteriolar tone and improved microcirculatory processes making an insignificant effect on platelet aggregation permitting its recommendation for prolonged treatment of patients with chronic congestive heart failure with minimum risk of complications.

[Effects of ethmozine and ethacizin on the central hemodynamics, peripheral vascular tonus and tissue oxygenation in patients with ventricular rhythm disorders and cardiac insufficiency]. / Vliianie etmozina i etazitsina na tsentral'nuiu gemodinamiku, tonus perifericheskikh sosudov i oksigenatsiiu tkanei u bol'nykh s zheludochkovymi narusheniiami ritma serdtsa i serdechnoi nedostatochnost'iu.

Daily monitoring of the ECG, catheterization of the pulmonary artery, tetrapolar chest rheography, occlusion plethysmography and polarography were employed to study the antiarrhythmic efficacy and the effects on the central and peripheral circulation of the new antiarrhythmic etmozine and etacyzine. Twenty-two patients with a frequent chronic ventricular premature heart beat (PHB) and clinically marked circulatory failure (CF) were entered into the study. Intake of etmozine (600 to 800 mg daily) and etacyzine (100 to 300 mg daily) over 5 to 6 days exerted a positive antiarrhythmic effect in 52.6 and 83.3% of the patients, respectively. Etmozine did not produce any adverse hemodynamic action, whereas etacyzine brought about an insignificant increase in the stroke and minute volumes of the heart (12.3 and 9.8%, respectively). However, the lack of an increase in the heart rate (HR), diastolic pressure in the pulmonary artery and regional vascular resistance (RVR), and no significant rise of the preload (systolic pressure in the right atrium) and afterload (elevation of the mean arterial blood pressure and RVR) attest to the fact that etacyzine has a negligible adverse hemodynamic action in CF patients. Intravenous injection of etmozine does not elicit any changes in the RVR or in the venous tone. Meanwhile intravenous injection of etacyzine leads to a significant reduction in the RVR (23.3%). The treatment with both etmozine and etacyzine given in courses promotes the improvement of the microcirculation and tissue oxygen metabolism in patients presenting with CF. More pronounced positive shifts in the microcirculation were achieved with etacyzine. Apparently, this bears on a more demonstrable arteriolodilatation effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical and hemodynamic effectiveness of isolated ultrafiltration in the treatment of patients with severe cardiac insufficiency]. / Klinicheskaia i gemodinamicheskaia effektivnost' izolirovannoi ul'trafil'tratsii pri lechenii bol'nykh s tiazheloi serdechnoi nedostatochnost'iu.

A study was made of the clinical and hemodynamic efficacy of a session or a course of isolated ultrafiltration (IUF) and a relationship of changes of the central and peripheral hemodynamics with the activity of the renin-aldosterone system in patients with severe cardiac insufficiency. Two groups of patients were singled out differing in their hemodynamic and hormonal response to the first IUF session that might be due to a different level of adaptation mechanisms acting in the interference in disturbed homeostasis.

[Possibilities and prospects of the assessment of regional hemodynamics under clinical conditions]. / Vozmozhnosti i perspektivy otsenki regionarnoi gemodinamiki v klinike.

The paper is concerned with the methods of rheography and different types of plethysmography, with the possibilities of using them clinically for the assessment of the peripheral hemodynamics. It is concluded that the best type of mechanical plethysmography is plethysmography with the use of a mercuric timer; in addition, mechanical plethysmography compares very favourably with impedance one.