Silent--asymptomatic--ischaemia is one of the forms of ischaemic heart disease. Present possibili... more Silent--asymptomatic--ischaemia is one of the forms of ischaemic heart disease. Present possibilities of non-invasive diagnostics are based primarily on long-term ECG monitoring. With regards to the hypothesis that the raised algesic threshold at high level of analgetically reacting beta endorphins seems to be the pathophysiologic basis of this particular syndrome, we tried to verify the presumption by administering a beta-endorphin antagonist-naloxon. In 13 patients with a silent form of ischaemic heart disease (absence of stenocardia in objectively proved ischaemia in loading test) we made the loading test in a standard form and after administering of 2 mgs of naloxan intravenously. Owing to the fact that stenocardia developed only in one patient after endogenous opiate effect blockage we presume that pathophysiologic basis of this syndrome must be discovered elsewhere.
In hardly any other field of treatment of a chronic disease more evident progress can be seen tha... more In hardly any other field of treatment of a chronic disease more evident progress can be seen than in the therapy of hearth failure. Till the end of eighties of the previous century we were not able to influence the adverse development of the disease. With the critical prognosis, chronic heart disease represents more serious case than majority of tumours. In the meantime the only approach to decrease mortality has been modulation of the maladaptively activated regulatory mechanisms--the rennin, angiotensin, aldosteron axis and the sympatoadrenal system. During the previous decades we became witnesses of the development of new pharmacologic approaches aimed at the heart failure: New inotropics (e.g. lavosimendan and pomobendan) have been introduced, effects of anti-arrhythmiatics (amiodaron, dronedaron and others) and metabolically active drugs (trimetazidine, ranolazine and others) has been tested as well as methods decreasing fluid retention (aquaarretics) has been used. It is too early to conclude that such ethiopathogenetical approach can decrease mortality or morbidity. Along with the advance of new possibilities to interfere directly with the pathogenesis of the heart failure, approaches aimed at the treatment of deteriorating processes have been developing: prothrombotic state, atherogenesis or complications of anaemia.
Mountaineering brings many health risks, one of which is mountain sickness. Its mildest form - ac... more Mountaineering brings many health risks, one of which is mountain sickness. Its mildest form - acute mountain sickness - is mainly characterized by subjective symptoms (headache, loss of appetite, insomnia, weakness, nausea and rarely also vomiting). Advanced and life-threatening forms are characterized by tissue edema - cerebral or pulmonary high altitude edema. The common denominator of these acute forms is the low oxygen tension leading to hypoxemia and tissue ischemia. Sum of maladaptive or adaptive processes can modify the clinical picture. Underlying mechanisms of the chronic forms of pulmonary disease are the adaptation processes - pulmonary hypertension and polycythemia leading to heart failure.The only causal therapeutic intervention is to restore adequate oxygen tension, descend to lower altitudes or oxygen therapy. Pharmacotherapy has only a supportive effect. The prophylaxis includes stimulation of the respiratory center by carbonic anhydrase inhibitors (acetazolamide) antiedematous treatment with glucocorticoids (dexamethasone), increase lymphatic drainage of the lungs and brain by β2-agonists (salmeterol) or mitigation of pulmonary hypertension by calcium channel blockers or phosphodiesterase-5 inhibitors (sildenafil or tadalafil).
Lecba hypertenze neni vždy jednoduchou zaležitosti, optimalni lecebnou strategii ovlivňuje řada f... more Lecba hypertenze neni vždy jednoduchou zaležitosti, optimalni lecebnou strategii ovlivňuje řada faktorů: věk, přidružene choroby, výse krevniho tlaku, soucasně podavane leky, spoluprace nemocneho a řada dalsich proměnných. Výběr nejvhodnějsiho leku, který na jedne straně nejlepe přispěje ke zlepseni prognozy nemocneho a na druhe bude dobře tolerovan, pak zavisi na odhaleni a respektovani těchto zakonitosti. Předložený souhrn ukazuje, jake jsou soucasne nazory na lecbu hypertenze u diabetiků, u nemocných s onemocněnim ledvin, se srdecnim selhanim, s chlopennimi vadami ci u seniorů.
Prognosis of patients with coronary artery disease (CAD) is limited by two main factors: left ven... more Prognosis of patients with coronary artery disease (CAD) is limited by two main factors: left ventricular dysfunction and the extent of CAD. Detection of impaired left ventricular function in early stage of acute myocardial infarction (AMI) could be important for establishing of rational secondary prevention of CAD. Therefore, the main aim of study was to detect latent left ventricular dysfunction in patients after AMI. To discover AMI patients with high risk in the later course of their CAD a stress test was used. The second part of the study was aimed to the effect of isosorbide dinitrate (ISDN) on pulomonary artery wedge pressure (PAWP) at rest and during a stress test.
In the submitted review the author deals with specific features of the coronary circulation, coro... more In the submitted review the author deals with specific features of the coronary circulation, coronary reserve and importance of regulation of the tonus of the coronary arteries at their epicardiac course and the tonus at the arteriolar level. In the subsequent part the author deals systematically first with the nervous regulation incl. the basic importance of the alpha-adrenergic (vasoconstrictor) and beta-adrenergic (vaso-dilating) sympathomimetic component. He mentions also the importance of neuropeptides (neuropeptide Y and substance P). Attention is devoted to the importance of the endothelium and endothelial vasoactive substances in the control of circulation. The main representatives of substances with a vasodilatating action are the endothelial relaxation factor and prostacycline, as to vasoconstrictor substances it is endothelin, thromboxan A2 and some growth factors. The authors discuss also the mechanical component, i. e. the influence of the blood flow and viscosity on the tonus of the coronary arteries. Finally the author draws attention to the clinical importance of disorders of regulatory mechanism in atherosclerosis and some clinical entities.
Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, meta... more Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, metabolic and humoral abnormalities in experimental animals already during the prehypertensive period. With regard to the obvious ratio of hereditary factors in the pathogenesis of human essential hypertension (EH), the objective of the present study was to test whether also in healthy normotensive subjects with a positive family history of EH some metabolic and humoral deviations can be detected, as compared with offspring from normotensive families. The authors compared therefore selected biochemical and humoral parameters in 20 sons of hypertensive parents (SH) with the findings in 20 sons from normotensive pa families (SN). SH had, as compared with SN, a significantly higher systolic BP (119 +/- 2.59 > 111.0 +/- +/- 2.04 mmHg). The trend of higher basal blood sugar levels 5.03 +/- 0.15 > 4.70 +/- 0.41 mmol/l) and the higher concentration of immunoreactive insulin (81.4 +/- 9.54 > 70.4 +/- after a glucose load +/- 7.78 microU/l) did not reach statistical significance. In SH plasma concentrations of adrenaline, noradrenaline and dopamine were significantly higher as well as the atrial natriuretic factor (11.7 +/- 0.77 > 8.4 +/- 0.40 fmol/ml) and of endothelin (18.2 +/- 1.70 > 12.7 +/- 0.87 fmol/ml). A load of 75 g glucose raised, as expected, the blood sugar level, IRI and C-peptide, but reduced unexpectedly the endothelin concentration in both groups. As to other biochemical parameters (fibrinogen, sodium, potassium, urea, creatinine, uric acid, cholesterol, HDL- and LDL-fractions, triacylglycerols), no significant differences were found between SH and SN. The finding of a raised mass of the left ventricle and certain differences in the diastolic and systolic left ventricular function are discussed in another paper. The results indicate that in young men with a positive family-history of EH already certain haemodynamic, metabolic and humoral deviations exist before clinical manifestation of hypertension which could contribute to later development of EH and its organ complications.
Rate responsive cardiac pacemakers adapting their pacing frequency according to physical effort a... more Rate responsive cardiac pacemakers adapting their pacing frequency according to physical effort are able to solve not only a bradycardia, but a chronotropic incompetence too. 23 rate responsive pulse generators, implanted in 1987-1991 in our center, simulated the physiological conditions and in this way they significantly improved both working capacity in bicycle stress test (p < 0.0001) and well-being in comparison with ordinary demand pacers. The incidence of complications did not exceed that in simple common pacemakers, but the rate adaptive ones were expensive and their programming was time consuming. In all three rate adaptive principles used their non-specific response revealed some imperfection of sensor driven devices. In addition, both in QT and in respiratory dependent systems their pretty proportional frequency response was delayed, while the irregular pacing rate in body activity sensor was not very proportionate to the physical exercise. The non-specific sensor response may be reduced by a combination of biologic sensors.
Canadian Journal of Physiology and Pharmacology, Sep 1, 1991
Under an initial interval of immobilization stress in rats, reciprocal changes of plasma active a... more Under an initial interval of immobilization stress in rats, reciprocal changes of plasma active and inactive renin were observed, suggesting activation of circulating inactive renin. Molecular weight (MW) studies revealed that this activation might proceed via a MW shift from inactive renin with MW of 50 000 to active renin of MW 43 000. In a later interval of stress, under stimulated renin secretion, a lower MW form (38 000) of active renin was released into the circulation. This MW is close to that of active renin (39 000) found in rat kidney renin granules. In renin granules, equilibrated in fractions of 1.6 and 1.7 mol/L sucrose in discontinuous density gradient, trypsin-activatable renin activity formed 36 and 16% of total activity, respectively. In humans, under acute bicycle exercise, a lower MW form (39 000) of active renin was released into the circulation, while the content of inactive renin with MW in the range of 51 000–58 000 and at 47 000 did not substantially change. There was a slight decrease in circulating inactive renin passing through the kidney. The data suggest that, at least in rats, in vivo pathways for activation of inactive renin might exist, other than that proceeding before secretion from renin granules. Under the conditions of increased renin secretion, a lower MW form of active renin is mainly released into the circulation in both rats and humans.Key words: active renin, inactive renin, renal veins, renin granules, stress.
Our paper is discussing the presence and intensity of metabolic, humoral and haemodynamic abnorma... more Our paper is discussing the presence and intensity of metabolic, humoral and haemodynamic abnormalities in mild middle-aged essential hypertensives (EH) and in hereditary predisposed still normotensive offspring from hypertensive families and their possible association with candidate genes changes. Four groups of subjects were compared (middle-aged normotensive controls (n = 21), corresponding patients with EH (n = 21), normotensive offspring from hypertensive (SH) (n = 56) and normotensive families (SN) (n = 56). Our results demonstrate that middle-aged patients with EH in our country have the same indices of hyperinsulinemia, impared glucose tolerance and insulin-sensitivity as previously described for other populations. They are accompanied by higher plasma concentrations of vasopressor substance like catecholamines, endothelin and lower levels of vasodepressor substances as ANP and kallikrein. The finding of similar, but quantitatively less expressed metabolic and humoral changes in SH but not in SN support the evidence for hereditary background of these abnormalities. The humoral and metabolic abnormalities may participate in BP elevation and in morphological and functional changes of left ventricle seen in SH (higher LV mass index, impaired diastolic filling). We did not prove an association between BP and polymorphism of ACE and angiotensinogen genes, however, our findings of association of DD genotype for ACE and M235 for angiotensinogen with higher insulinemia, plasma catecholamines and plasma renin activity evoke the hypothesis, whether the bearers of these genotypes, exposed for long-time to the higher concentrations of vascoactive substances, are not the subset of hereditary threatened subjects in whom clinically evident EH will manifest during their life.
Silent--asymptomatic--ischaemia is one of the forms of ischaemic heart disease. Present possibili... more Silent--asymptomatic--ischaemia is one of the forms of ischaemic heart disease. Present possibilities of non-invasive diagnostics are based primarily on long-term ECG monitoring. With regards to the hypothesis that the raised algesic threshold at high level of analgetically reacting beta endorphins seems to be the pathophysiologic basis of this particular syndrome, we tried to verify the presumption by administering a beta-endorphin antagonist-naloxon. In 13 patients with a silent form of ischaemic heart disease (absence of stenocardia in objectively proved ischaemia in loading test) we made the loading test in a standard form and after administering of 2 mgs of naloxan intravenously. Owing to the fact that stenocardia developed only in one patient after endogenous opiate effect blockage we presume that pathophysiologic basis of this syndrome must be discovered elsewhere.
In hardly any other field of treatment of a chronic disease more evident progress can be seen tha... more In hardly any other field of treatment of a chronic disease more evident progress can be seen than in the therapy of hearth failure. Till the end of eighties of the previous century we were not able to influence the adverse development of the disease. With the critical prognosis, chronic heart disease represents more serious case than majority of tumours. In the meantime the only approach to decrease mortality has been modulation of the maladaptively activated regulatory mechanisms--the rennin, angiotensin, aldosteron axis and the sympatoadrenal system. During the previous decades we became witnesses of the development of new pharmacologic approaches aimed at the heart failure: New inotropics (e.g. lavosimendan and pomobendan) have been introduced, effects of anti-arrhythmiatics (amiodaron, dronedaron and others) and metabolically active drugs (trimetazidine, ranolazine and others) has been tested as well as methods decreasing fluid retention (aquaarretics) has been used. It is too early to conclude that such ethiopathogenetical approach can decrease mortality or morbidity. Along with the advance of new possibilities to interfere directly with the pathogenesis of the heart failure, approaches aimed at the treatment of deteriorating processes have been developing: prothrombotic state, atherogenesis or complications of anaemia.
Mountaineering brings many health risks, one of which is mountain sickness. Its mildest form - ac... more Mountaineering brings many health risks, one of which is mountain sickness. Its mildest form - acute mountain sickness - is mainly characterized by subjective symptoms (headache, loss of appetite, insomnia, weakness, nausea and rarely also vomiting). Advanced and life-threatening forms are characterized by tissue edema - cerebral or pulmonary high altitude edema. The common denominator of these acute forms is the low oxygen tension leading to hypoxemia and tissue ischemia. Sum of maladaptive or adaptive processes can modify the clinical picture. Underlying mechanisms of the chronic forms of pulmonary disease are the adaptation processes - pulmonary hypertension and polycythemia leading to heart failure.The only causal therapeutic intervention is to restore adequate oxygen tension, descend to lower altitudes or oxygen therapy. Pharmacotherapy has only a supportive effect. The prophylaxis includes stimulation of the respiratory center by carbonic anhydrase inhibitors (acetazolamide) antiedematous treatment with glucocorticoids (dexamethasone), increase lymphatic drainage of the lungs and brain by β2-agonists (salmeterol) or mitigation of pulmonary hypertension by calcium channel blockers or phosphodiesterase-5 inhibitors (sildenafil or tadalafil).
Lecba hypertenze neni vždy jednoduchou zaležitosti, optimalni lecebnou strategii ovlivňuje řada f... more Lecba hypertenze neni vždy jednoduchou zaležitosti, optimalni lecebnou strategii ovlivňuje řada faktorů: věk, přidružene choroby, výse krevniho tlaku, soucasně podavane leky, spoluprace nemocneho a řada dalsich proměnných. Výběr nejvhodnějsiho leku, který na jedne straně nejlepe přispěje ke zlepseni prognozy nemocneho a na druhe bude dobře tolerovan, pak zavisi na odhaleni a respektovani těchto zakonitosti. Předložený souhrn ukazuje, jake jsou soucasne nazory na lecbu hypertenze u diabetiků, u nemocných s onemocněnim ledvin, se srdecnim selhanim, s chlopennimi vadami ci u seniorů.
Prognosis of patients with coronary artery disease (CAD) is limited by two main factors: left ven... more Prognosis of patients with coronary artery disease (CAD) is limited by two main factors: left ventricular dysfunction and the extent of CAD. Detection of impaired left ventricular function in early stage of acute myocardial infarction (AMI) could be important for establishing of rational secondary prevention of CAD. Therefore, the main aim of study was to detect latent left ventricular dysfunction in patients after AMI. To discover AMI patients with high risk in the later course of their CAD a stress test was used. The second part of the study was aimed to the effect of isosorbide dinitrate (ISDN) on pulomonary artery wedge pressure (PAWP) at rest and during a stress test.
In the submitted review the author deals with specific features of the coronary circulation, coro... more In the submitted review the author deals with specific features of the coronary circulation, coronary reserve and importance of regulation of the tonus of the coronary arteries at their epicardiac course and the tonus at the arteriolar level. In the subsequent part the author deals systematically first with the nervous regulation incl. the basic importance of the alpha-adrenergic (vasoconstrictor) and beta-adrenergic (vaso-dilating) sympathomimetic component. He mentions also the importance of neuropeptides (neuropeptide Y and substance P). Attention is devoted to the importance of the endothelium and endothelial vasoactive substances in the control of circulation. The main representatives of substances with a vasodilatating action are the endothelial relaxation factor and prostacycline, as to vasoconstrictor substances it is endothelin, thromboxan A2 and some growth factors. The authors discuss also the mechanical component, i. e. the influence of the blood flow and viscosity on the tonus of the coronary arteries. Finally the author draws attention to the clinical importance of disorders of regulatory mechanism in atherosclerosis and some clinical entities.
Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, meta... more Investigations in genetic forms of experimental hypertensions revealed certain haemodynamic, metabolic and humoral abnormalities in experimental animals already during the prehypertensive period. With regard to the obvious ratio of hereditary factors in the pathogenesis of human essential hypertension (EH), the objective of the present study was to test whether also in healthy normotensive subjects with a positive family history of EH some metabolic and humoral deviations can be detected, as compared with offspring from normotensive families. The authors compared therefore selected biochemical and humoral parameters in 20 sons of hypertensive parents (SH) with the findings in 20 sons from normotensive pa families (SN). SH had, as compared with SN, a significantly higher systolic BP (119 +/- 2.59 > 111.0 +/- +/- 2.04 mmHg). The trend of higher basal blood sugar levels 5.03 +/- 0.15 > 4.70 +/- 0.41 mmol/l) and the higher concentration of immunoreactive insulin (81.4 +/- 9.54 > 70.4 +/- after a glucose load +/- 7.78 microU/l) did not reach statistical significance. In SH plasma concentrations of adrenaline, noradrenaline and dopamine were significantly higher as well as the atrial natriuretic factor (11.7 +/- 0.77 > 8.4 +/- 0.40 fmol/ml) and of endothelin (18.2 +/- 1.70 > 12.7 +/- 0.87 fmol/ml). A load of 75 g glucose raised, as expected, the blood sugar level, IRI and C-peptide, but reduced unexpectedly the endothelin concentration in both groups. As to other biochemical parameters (fibrinogen, sodium, potassium, urea, creatinine, uric acid, cholesterol, HDL- and LDL-fractions, triacylglycerols), no significant differences were found between SH and SN. The finding of a raised mass of the left ventricle and certain differences in the diastolic and systolic left ventricular function are discussed in another paper. The results indicate that in young men with a positive family-history of EH already certain haemodynamic, metabolic and humoral deviations exist before clinical manifestation of hypertension which could contribute to later development of EH and its organ complications.
Rate responsive cardiac pacemakers adapting their pacing frequency according to physical effort a... more Rate responsive cardiac pacemakers adapting their pacing frequency according to physical effort are able to solve not only a bradycardia, but a chronotropic incompetence too. 23 rate responsive pulse generators, implanted in 1987-1991 in our center, simulated the physiological conditions and in this way they significantly improved both working capacity in bicycle stress test (p < 0.0001) and well-being in comparison with ordinary demand pacers. The incidence of complications did not exceed that in simple common pacemakers, but the rate adaptive ones were expensive and their programming was time consuming. In all three rate adaptive principles used their non-specific response revealed some imperfection of sensor driven devices. In addition, both in QT and in respiratory dependent systems their pretty proportional frequency response was delayed, while the irregular pacing rate in body activity sensor was not very proportionate to the physical exercise. The non-specific sensor response may be reduced by a combination of biologic sensors.
Canadian Journal of Physiology and Pharmacology, Sep 1, 1991
Under an initial interval of immobilization stress in rats, reciprocal changes of plasma active a... more Under an initial interval of immobilization stress in rats, reciprocal changes of plasma active and inactive renin were observed, suggesting activation of circulating inactive renin. Molecular weight (MW) studies revealed that this activation might proceed via a MW shift from inactive renin with MW of 50 000 to active renin of MW 43 000. In a later interval of stress, under stimulated renin secretion, a lower MW form (38 000) of active renin was released into the circulation. This MW is close to that of active renin (39 000) found in rat kidney renin granules. In renin granules, equilibrated in fractions of 1.6 and 1.7 mol/L sucrose in discontinuous density gradient, trypsin-activatable renin activity formed 36 and 16% of total activity, respectively. In humans, under acute bicycle exercise, a lower MW form (39 000) of active renin was released into the circulation, while the content of inactive renin with MW in the range of 51 000–58 000 and at 47 000 did not substantially change. There was a slight decrease in circulating inactive renin passing through the kidney. The data suggest that, at least in rats, in vivo pathways for activation of inactive renin might exist, other than that proceeding before secretion from renin granules. Under the conditions of increased renin secretion, a lower MW form of active renin is mainly released into the circulation in both rats and humans.Key words: active renin, inactive renin, renal veins, renin granules, stress.
Our paper is discussing the presence and intensity of metabolic, humoral and haemodynamic abnorma... more Our paper is discussing the presence and intensity of metabolic, humoral and haemodynamic abnormalities in mild middle-aged essential hypertensives (EH) and in hereditary predisposed still normotensive offspring from hypertensive families and their possible association with candidate genes changes. Four groups of subjects were compared (middle-aged normotensive controls (n = 21), corresponding patients with EH (n = 21), normotensive offspring from hypertensive (SH) (n = 56) and normotensive families (SN) (n = 56). Our results demonstrate that middle-aged patients with EH in our country have the same indices of hyperinsulinemia, impared glucose tolerance and insulin-sensitivity as previously described for other populations. They are accompanied by higher plasma concentrations of vasopressor substance like catecholamines, endothelin and lower levels of vasodepressor substances as ANP and kallikrein. The finding of similar, but quantitatively less expressed metabolic and humoral changes in SH but not in SN support the evidence for hereditary background of these abnormalities. The humoral and metabolic abnormalities may participate in BP elevation and in morphological and functional changes of left ventricle seen in SH (higher LV mass index, impaired diastolic filling). We did not prove an association between BP and polymorphism of ACE and angiotensinogen genes, however, our findings of association of DD genotype for ACE and M235 for angiotensinogen with higher insulinemia, plasma catecholamines and plasma renin activity evoke the hypothesis, whether the bearers of these genotypes, exposed for long-time to the higher concentrations of vascoactive substances, are not the subset of hereditary threatened subjects in whom clinically evident EH will manifest during their life.
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