Local renal medullary L-NAME infusion enhances the effect of long-term angiotensin II treatment.

We hypothesized that the relatively high doses of angiotensin (Ang) II required to produce hypertension in rats were related to stimulation of renal medullary nitric oxide production, which in turn blunted reductions in medullary blood flow and the development of hypertension. Ang II was infused (5 days at 3 ng. kg-1. min-1 IV) to uninephrectomized Sprague-Dawley rats in the presence and absence of a continuous medullary interstitial NG-nitro-L-arginine methyl ester (L-NAME) infusion. Renal cortical and medullary blood flows were determined with the use of implanted optical fibers and laser-Doppler flowmetry. Ang II in the absence of medullary nitric oxide synthase inhibition did not change cortical or medullary blood flow or mean arterial pressure. A threshold dose of L-NAME was determined (75 microg. kg-1. h-1) that did not produce significant short- or long-term changes in medullary blood flow and mean arterial pressure. In rats with blunted medullary nitric oxide synthase activity, Ang II infused intravenously resulted in a 30% reduction in medullary blood flow (from 1.3 to 0.9+/-0.2V) and approximately 20 mm Hg increase in mean arterial pressure with Ang II infusion over 5 days. During 70 minutes after the start of intravenous Ang II, there was an immediate reduction in medullary blood flow, with no changes in cortical blood flow or mean arterial pressure. We conclude that the relative insensitivity of rats to long-term elevations of circulating Ang II is due to the potent counterregulatory actions of the nitric oxide system, specifically within the renal medulla. The results provide novel insights of how the organism attempts to protect itself from the hypertensive effects of Ang II.

Increase in renal medullary nitric oxide synthase activity protects from norepinephrine-induced hypertension.

Studies were performed in conscious Sprague-Dawley rats to determine the role of the alpha(2)-adrenergic receptor-mediated increase in the renal medullary nitric oxide synthase (NOS) activity as a counterregulatory mechanism of blood pressure control in response to increased renal adrenergic stimulation. A subpressor dose of norepinephrine (NE, 8 microg. kg(-1). h(-1)) was infused intravenously, and NOS activity was determined with arginine-citrulline conversion by high-performance liquid chromatography in renal cortical and outer and inner medullary tissues. It was found that after 7 days of intravenous NE infusion, NOS activity was significantly higher in both the outer and inner medullary tissues (158+/-45 versus 30+/-24 pmol. mg(-1). h(-1) [outer medulla] and 5.1+/-0.7 versus 2.0+/-0.5 nmol. mg(-1). h(-1) [inner medulla] for NE-treated versus control rats, respectively). To determine whether the increase of NOS activity was mediated through renal medullary alpha(2)-receptors, the receptor antagonist rauwolscine (RAU, 1 microg. kg(-1). min(-1)) was infused via an implanted renal medullary interstitial catheter, and the consequences of intravenous NE administration were evaluated. NOS activity was significantly lower in the RAU-infused animals and did not increase with infusion of NE. To determine the systemic effects of the renal medullary alpha(2)-receptors, studies were performed to determine the consequences of chronic intravenous infusion of subpressor amounts of NE in the presence and absence of renal medullary alpha(2)-receptor inhibition. Under conditions in which RAU was continuously infused into the renal medulla, the same subpressor dose of NE caused sustained and reversible hypertension (mean arterial pressure increased from 120+/-3 to 131+/-3 mm Hg). Chronic blunting of the renal medullary NOS activity with N(G)-nitro-L-arginine methyl ester (75 microg. kg(-1). h(-1)) also enabled NE to produce a significant rise in mean arterial pressure (from 117+/-2 to 134+/-4 mm Hg). We conclude that the hypertensive effects of moderate elevations of renal adrenergic activity were chronically buffered by the alpha(2)-receptor-mediated increase in NOS activity within the renal medulla.

Effects of combined sex hormone replacement therapy on small artery biomechanics in pharmacologically ovariectomized rats.

OBJECTIVES: The purpose of this study was to determine the effects of long-term combined sexual hormone replacement therapy on the biomechanical properties of the small artery wall in castrated female rats. METHODS: 30 non-pregnant mature female Sprague-Dawley rats were pharmacologically ovariectomized with 750 microg/kg triptorelin im. every 4th week. Ten of them received combined hormone replacement in form of 15 mg/kg medroxyprogesterone acetate (MPA) im. every 2 weeks and 450 microg/kg estradiol propionate im. once a week. Ten castrated animals received MPA only. Ten control, castrated animals were given the vehicles of these steroids. Ten other animals were kept parallelly, receiving the vehicles of all drugs (control animals). After 12 weeks of treatment cylindrical segments of the saphenous artery were isolated and cannulated at both ends and subjected to in vitro microarteriographic test. Pressure diameter curves, in the range of 0-200 mmHg, were recorded from segments in normal Krebs-Ringer (nKR) solution, in contraction with norepinephrine (1.6 x 10(-5) M), and then in relaxation with papaverine (2.8 x 10(-5) M). Biomechanical parameters were calculated based on the pressure diameter curves. RESULTS: Combined hormone replacement therapy significantly increased the passive diameter of small arteries, as compared to those from ovariectomized animals without hormone replacement. MPA monotherapy did not alter the vessel diameter, the inner radii at 100 mmHg intraluminal pressure were, 300+/-9 microm in the control castrated, 340+/-7 microm in the estradiol + MPA replaced and 306+/-8 microm in the MPA treated groups (P < 0.05 between the control castrated and the combined treatment groups). The vascular reactivity to norepinephrine or papaverine was not changed significantly either by combined hormone replacement or by MPA monotherapy when compared with ovariectomized controls. No significant alterations were found in wall thickness and distensibility. CONCLUSIONS: These results suggest that chronic medroxyprogesterone pretreatment does not influence the geometric, elastic and contractile properties of small arteries in castrated female rats. The combination of MPA + estradiol increased the morphological lumen: the morphological vasodilatation induced by estrogen, described earlier, was not affected by the addition of this progestin to the regimen.

Regional differences in nitric oxide-dependent vascular responses to somatostatin.

The mechanisms of the vascular effects of somatostatin (ST) are not well known. This study compares the direct effect of ST in different vascular regions and species. Isolated perfused segments of the cat superior mesenteric artery in vitro did not exhibit a vascular response in the resting state, however, ST-induced vasodilatation was observed with norepinephrine preconstriction. In contrast, ST only slightly dilated superior mesenteric vein segments. In the artery, NG-nitro-L-arginine inhibited both ST and endothelium-dependent nitric oxide (NO) mediated response. No regular dose-response curves were found when ST was applied on the large mesenteric artery in the cat, but rings of small mesenteric artery from both cats and dogs exhibited dose-dependent relaxations. These effects were also NO-dependent. Local application of ST on the rat saphenous artery in situ elicited NO-mediated dose-dependent vasodilatation. However, ST constricted rat saphenous veins in the case of either adventitial or intraluminal application. It is concluded that ST exerts different actions on the arterial and the venous vessel wall. The major response in arteries is endothelium-mediated vasodilatation seen in various species and vascular beds. Large and small arteries respond differently to ST but these differences require further elucidation.

[Treatment of paroxysmal ventricular tachycardia]. / Moznosti liecby paroxyzmálnej komorovej tachykardie.

The authors present a retrospective evaluation of the risk stratification and therapy of 53 patients with ventricular tachycardia. They present the diagnostical algorithm used for the detection of risk of sudden death. The most frequently used drug in the set of patients was amiodarone in monotherapy or in combination with other drugs. Sotalol was used for both, its antiarrhythmic nature, and for its ability to reduce the defibrillation threshold in patients with an implanted automatic implantable cardiovertor-defibrillator (AICD). Antiarrhythmic drugs of class I in monotherapy were used in patients with non-coronary causes of ventricular tachycardia and with normal left ventricular function. The authors, on the basis of sudden death of three patients with low ejection fraction of the left ventricle which were recorded even despite Holter apparatus and electophysiologically confirmed supression of ventricular tachycardia, recommend to consider in this group of patients the primary AICD implantation. (Tab. 4, Fig. 2, Ref. 13.)

[Management of ventricular tachycardia after acute myocardial infarct]. / Manazment komorovej tachykardie po akútnom infarkte myokardu.

BACKGROUND: Risk stratification of malignant ventricular tachyarrhythmias and sudden cardiac death after myocardial infarction is essentially important for high risk patients identification, who require specific therapeutic procedures. Non-invasive risk markers--LVEF, late potentials LP, Q-T dispersion, decreased heart rate variability (HRV) and baroreflex sensitivity (BRS)--and ventricular tachycardia inducibility have low positive predictive value. The appropriate combination and consecutiveness which will provide most precise identification of patients threatened by sudden arrhythmic death, applicable to all patients after myocardial infarction, is being analysed. METHODS: In a group of 87 patients after myocardial infarction suffering from ventricular tachycardia retrospective assessment of sudden cardiac death risk markers incidence was performed. RESULTS: 1. The most frequent risk marker was LVEF 0.40 (48.3%), abnormal LP (84.9%), DQT 80 ms and decreased HRV (73.1%) and their combinations. 2. Patients with inducible ventricular tachycardia (62.1%) had lower LVEF in comparison with non-inducible ventricular tachycardia patients (0.42 +/- 0.11 vs 0.51 +/- 0.01, p = 0.002), higher QT dispersion (85.0 +/- 30.5 ms versus 63.6 +/- 30.7 ms, p = 0.003). 3. In patients with recurrent malignant ventricular tachyarrhythmias and sudden cardiac death occurring during the follow-up is sustained inducible ventricular tachycardia with antiarrhythmic therapy and induction of ventricular tachycardia during native state significantly more frequent. LVEF is significantly reduced, FQRS on SAECG is significantly prolonged, DQT is significantly higher. CONCLUSION: On the basis of the results and data from literature the authors recommend LVEF assessment in all patients after myocardial infarction and further stratification in patients with left ventricular dysfunction.

[Dispersion of the Q-T interval after myocardial infarct]. / Disperzia intervalov Q-T po infarkte myokardu.

Non-homogenity of ventricular myocardial repolarization is a substrate for the reentry mechanism of ventricular arrhythmias. It is manifestant by dispersion of Q-T and Q-Tc intervals on the standard ECG curve. The authors studied the possibility of using the dispersity of Q-T and Q-Tc intervals in clinical practice. They evaluated the dispersion of these intervals within the set of 21 patients after myocardial infarction with sustained ventricular tachycardia, and compared it with the dispersion within the control set of 17 patients after myocardial infarction without an arrhythmic episode. By means of comparison, they have discovered that: 1) the dispersion of Q-T and Q-Tc intervals is significantly higher in patients with ventricular tachycardia: Q-T (mean +/- SE) 82.8 +/- 7.8 msec vs 42.2 +/- 4.8 msec, Q-Tc 93.0 +/- 10.2 msec vs 47.1 +/- 4.8 msec, p > 0.001, 2) the dispersion of Q-Tc when higher than 60 msec is an optimum discrimination value for the prognosis of sudden arrhythmic death after myocardial infarction (sensitivity 81%, specificity 76%) and 3) the dispersion of Q-T and Q-Tc intervals has no relation to the function of the left ventricle. Therefore the authors consider the dispersion of Q-T and Q-Tc intervals as being a useful marker of malignant ventricular arrhythmia which could be included into the algorithm of assessment of the risk of sudden arrhythmic death after myocardial infarction.

[Radiofrequency ablation of type I atrial flutter. Personal experience]. / Rádiofrekvencná ablácia atriálneho flutteru typ I. Nase skúsenosti.

The cause of Afl-I is macroentry in the right atrium. The critical site of reentry is the narrow anatomical space in the isthmic region between the posterior part of the annulus of the tricuspid valve and the vena cava inferior (isthmus TA-IVC). Radiofrequency ablation (RF) of the isthmus TA-IVC is successful on average in 90% of patients. The best criterium for evaluation of short-term and long-term effect of RF ablation is a two-way block of conduction in the TA-IVC insthmus, created by RF ablation. In case of a relapse it is possible to repeat ablation. Although a proarrhythmic effect of ablation is not assumed, the cause of the higher frequency of atrial fibrillation is not known. The authors present their own experience with the treatment of Afl-I by RF ablation of the TA-IVC isthmus in a group of 18 patients. RF ablation was successful in 83.3% patients of the group, no complications were recorded. Late relapses of Afl-1 in three patients were resolved by repeated RF ablation which was successful. The results are comparable with results in other departments. Based on their own experience the authors consider ablation treatment of Afl-1 a safe and effective therapeutic method in a selected group of patients.

[Microvascular angina pectoris and insulin resistance]. / Mikrovaskulárna angina pectoris a inzulínová rezistencia.

The authors examined 29 patients with the syndrome of microvascular angina pectoris. In 12 patients (41.4%) they recorded hyperinsulinaemia as a manifestation of insulin resistance. The body weight, HDL cholesterol level, LDL cholesterol and triglycerides did not differ significantly in the two groups and were at the upper borderline of the range of reference values. The authors analyze mechanisms common to the pathophysiology of the syndrome of microvascular angina pectoris and the syndrome of insulin resistance.

[Risk factors and prevention of sudden cardiac death in patients with ventricular tachycardia after myocardial infarct]. / Markery rizika a prevencia náhlej srdcovej smrti u pacientov s komorovou tachykardiou po infarkte myokardu.

UNLABELLED: The optimal therapeutic procedure for prevention of sudden cardiac death (SCD) after myocardial infarction involves identification of the patients with a high risk of malignant ventricular arrhythmias using non-invasive risk markers, invasive electrophysiological evaluation of high risk patients, selection of treatment (ICD, RFTA, antiarrhythmics) and evaluation of the effectiveness of treatment. The objective of this work is retrospective evaluation of the incidence of risk markers of sudden cardiac death and the importance of programmed ventricular stimulation for the prognosis of patients with malignant ventricular arrhythmias after myocardial infarction. RESULTS: 1. Retrospective analysis of 87 patients with ventricular tachycardia (VT) after myocardial infarction confirmed a high incidence of non-invasive risk markers. 2. For the long-term course a combination of the left ventricular ejection fraction (LVEF) < 0.40 + reduced heart rate variability (HRV) and abnormal ventricular potentials are most important (or dispersion of QT > 80 ms). The absence of ventricular extrasystoles on the Holter monitor does not predict the course without malignant arrhythmical episodes. 3. There is a statistically significant relation to the inducibility of BP during programmed ventricular stimulation with LVEF, persisting BP, RMS voltage of the terminal 40 ms (RMS40) and QT dispersion. 4. The inducibility of BP and persistence of inducibility on antiarrhytmic drugs in patients with LVEF < 40 is associated with a 14.8% incidence of SCD within four months after the first arrhythmic episode. The authors recommend to examine LVEF as the basis of risk stratification of SCD along with values of coronary reserve after myocardial infarction. In patients with LVEF (they recommend to examine Holter s monitor (assessment of HRV and analysis of ventricular arrhythmias) and mean ECG. Abnormal late ventricular potentials, reduced HRV or BP indicate programmed ventricular stimulation.

[Prevention of polymorphous ventricular tachycardia in patients with congenital long QT interval syndrome]. / Moznosti prevencie polymorfnej komorovej tachykardie u pacientov s kongenitálnym syndrómom dlhého QT intervalu.

Patients with the Romano-Ward long QT interval syndrome run a high risk of sudden cardiac death. Beta-blockers of the sympathetic nerve are effective treatment. Some patients die suddenly despite this treatment. The treatment of choice is a combination of beta-blockers of the sympathetic nerve and cardiostimulation. The authors describe a group of their own five patients from three families with the Romano-Ward syndrome. The course was favourable. The stimulation rate needed for normalization of the QT interval and a favourable clinical development was 78 +/- 6 imp./min. Based on data in the literature and their own experience the authors recommended combined treatment with beta-blockers and cardiostimulation in patients with the Romano-Ward syndrome, if monotherapy with beta-blockers is not effective.

[Thallium scintigraphy of the myocardium in evaluation of patients with insulin resistance syndrome and microvascular angina pectoris]. / Táliová spect scintigrafia myokardu v hodnotení pacientov so syndrómom inzulínovej rezistencie a mikrovaskulárnou anginou pectoris.

Insulin resistance syndrom (IR) is often associated with the syndrome of microvascular angina pectoris (MVAP) or with coronary artery disease (CAD). The authors quantified distribution and washout of 201Tl in heart (C), lungs (L) and liver (H) to evaluate the results 201Tl stress (s) and redistribution SPECT in 50 patients. They compared 2 groups of patients with laboratory verified IR (MVAP and CAD) and control group (CG) of patients with normal coronarography without any symptoms of IR. In Patients with IR and MVAP were found significantly more frequent local perfusion abnormalities then in CG. The index sL/C calculated by ROI analysis is significantly lower in controls, then in CAD. The index sC/H is lower in patients with IR (MVAP significantly) then in CG. The washout of 201Tl in CAD myocardium decreased and in MVAP liver increased. 201thalium scintigraphy is useful for separation of patients with MVAP and local perfusion abnormalities. This findings had probably prognostic value in patients with IR.

[Relation between cytokines (TNF-alpha, IL-1 and 6) and homocysteine in android obesity and the phenomenon of insulin resistance syndromes]. / Vzt'ah cytokínov (TNF-alfa, IL-1 a 6) a homocysteínu k androidnej obezite a k fenoménom syndrómu inzulínovej rezistencie.

TNF-alpha (so-called cachectin), IL-1 and 6 are important regulating agents in the homeostasis of energy in the organism, as among others they control processes of apoptosis and thus also the volume of adipose and muscular tissues. They are produced not only in immunocompetent cells but also in adipocytes and muscle cells. The cytokine system is then activated not only in tumours and infections but elevated values were found also in obesity, NIDDM, in myocardial infarction and in advanced decompensated cardiac patients. By acting on phosphorylation of IRS-1 and PI-3 kinase TNF-alpha promotes significantly insulin resistance, causes deterioration of diabetes, as well as elevated body temperature, sleepiness and anorexia. In a group of 65 patients, mostly with android obesity, in hyperleptinaemic and insulin resistant probands with coronarographically confirmed microvascular angina pectoris (n = 22) or IHD, mostly after a myocardial infarction (n = 43) with one or more significant stenoses on the epicardial coronary arteries in half the patients positive or elevated TNF-alpha was found and in 28% also IL-6. This increase did not correlate however with BMI, the percentage of body fat, IRI and C peptide levels nor with cortisol and leptin levels. Insulin resistant subjects had more frequently elevated homocysteine and Lp(a) values which are further two independent risk factors of atherothrombogenesis. Hyperhomocysteinaemia can be favourably influenced by vitamin fortification of the diet or by administration of folate and pyridoxine (1 tablet per day) involving negligible financial costs.

Prevalence of metabolic syndrome, insulin resistance, and microvascular angina pectoris in 500 consecutive patients referred to coronarography.

OBJECTIVE: This work was aimed to evaluate the prevalence of insulin resistance (IR) and metabolic syndrome in a large cohort of 40-60 years old patients with cardiovascular symptoms. METHODS: A total of 500 consecutive males and females referred to coronarography and coronary catheterization, because of spontaneous or after load precordial pain plus denivelisation of ST segment by electrocardiography, were included. Besides standard clinical examinations, ergometry, echocardiography, fundamental laboratory tests, and several other laboratory examinations were also performed, including oral glucose toleration test (OGTT), total and high-density lipoprotein (HDL) cholesterol, triglycerides, apoprotein A1 and B, apolipoprotein (a), uric acid, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), cytokines (tumor necrosis factor α, TNFα, interleukin-1, IL-1, interleukin-6, IL-6), endothelin-1, as well as hormones (insulin, C peptide, leptin, growth hormone, cortisol). RESULTS: In 81.6% of patients, IR syndrome with compensatory hyperinsulinemia was found in a positive correlation with various symptoms of metabolic syndrome, including abdominal obesity, increased body mass index (BMI), dysglycemia, dyslipoproteinemia, coronary stenosis, decreased HDL level, and hypertension. Hirsutism with polycystic ovarian syndrome was found in 52% of examined women with IR. However, a normal coronary angiogram, called as a microvascular form of the angina pectoris (MIV-AP), was found in 14% of predominantly periclimacteric and benign hirsutic females with long-term disorders of menstrual cycle. Since these patients showed the same symptoms as their gender, age, BMI, and degree of coronary stenoses adjusted pairs with the macrovascular form (such as the same levels of several lipids, hormones and obesity measures), our data strongly support the view that MIV-AP might belong to the IR syndrome. CONCLUSIONS: Hyperinsulinemia and high prevalence of various symptoms of metabolic syndrome (MS) were found in high percentage of patients with after load precordial pain who were referred to coronarography. Similarly, in several women, MIV-AP was detected and its affiliation to MS suggested.