Slovakia
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Volume 97 / No. 10 / 1996
ACE-INHIBITORS IN THE TREATMENT OF CHRONIC HEART FAILURE: PATHOPHYSIOLOGICAL BACKGROUND OF PROTECTIVE EFFECT
SIMKO F., RIECANSKY I.
The aim of modern therapy of heart failure is not a pure removal
of symptomes but an improvement of survival. The angiotensin-converting
enzyme (ACE)-inhibitors reduced morbidity and mortality in several large
clinical trials in patients with dysfunctional left ventricle or manifestant
heart failure. Thus, ACE inhibitors are recommended for heart failure treatment
as a drug of primary option, unless contraindications are present,
and if tolerated by patient.
The mechanism of action of ACE inhibitors in heart failure is hypothetical.
Participation of three factors is supposed: improvement in the pumping
function of the failing heart, reduction on the risk of sudden death and
reduction in myocardial infarction incidence. Reduction of hemodynamic
load, antiischemic action and reduction of fibrotic tissue proliferation
in failing myocardium are responsible for heart function improvement. These
mechanisms together with potential antiatherosclerotic, antiaggregative,
fibrinolytic and protective effect on endothelial function are supposed
to participate in reduction of acute myocardial infarction and sudden death
origin. The mentioned effects are determined by interaction with both circulating
and local renin-angiotensin systems. The negative hemodynamic effects and
undesirable restructuralisation of the affected ventricle are thus influenced
on sytematic and local-tissue level.
Similarly as any other therapy also the treatment of heart failure
with ACE inhibitors needs experience and a rational well tailored
individual approach. (Fig. 1, Ref. 32.)
Key words: ACE-inhibitors, heart failure, mortality reduction.
Bratisl Lek Listy 1996; 97: 583586
CYTOPROTECTIVE EFFECT OF MAGNESIUM UNDER CONDITIONS OF GLOBAL ISCHAEMIA OF MYOCARDIUM
BADA V., KUCHARSKA J., GVOZDJAKOVA A., HERICHOVA I., GVOZDJAK J.
Background: Administration of magnesium in the therapy of ischaemic
heart diseases does not belong to the standard procedures. The results
of clinical trials with application of this cation are mutually contradictive,
mechanisms of its effect are not solved yet. Many physicians consider magnesium
to represent a classical placebo, or an uncertain light sedative.
Main Purpose and Objectives: The study is aimed at proving the
direct effect of magnesium on the heart muscle under ischaemic conditions
which exclude the placebo effects. These conditions are mostly fulfilled
by the model of isolated heart.
Material and Methods: The authors used isolated rabbit hearts
according to Langedorff with Krebs-Henseleit (KH) perfusion solution, the
only variable of which is represented by concentration of magnesium. The
following groups of patients were formed: 1. Control group 30-minute
perfusion with normal Mg concentration (0.5 mmol/l) in KH solution. 2.
Hypomagnesemia 30-minute perfusion with KH solution Mg-free. 3. Normomagnesemia
+ ischaemia 30-minute perfusion with normal concentration succeeded by
a 60-minute global ischaemia. 4. Hypomagnesiaemia + ischaemia 30-minute
perfusion with KH solution magnesium-free succeeded by a 60-minute
global ischaemia. 5. Hypermagnesiemia + ischaemia 30-minute perfusion
with increased Mg concentration in KH solution to 2.0 mmol/l succeeded
by a 60-minute global ischaemia. The investigated parameters: after
completion of perfusion the authors isolated mitochondria and evaluated
individual parameters of oxidative phosphorylation by means of oxygraph/Gilson/
with Clark's oxygen electrode. The calcium uptake by mitochondria was observed
by means of calcium-sensitive electrode Orion (oxygraph Gilson). The formation
of free oxygen radicals was observed indirectly by spectrophotometric assessment
of malondialdehyde production. Concentration of mitochondrial nucleotides
(AMP, ADP, ATP) was assessed by using HPLC.
Results: Hypomagnesemia lasting 30 minutes had a negative
effect on the index of oxidative phophorylation (ADP:O p<0.005)
the uptake of calcium (p<0.002), ATP concemtration in mitochondrial
ATP (p<0.05) and the production of free redicals significantly increased
(p<0.001). Normomagnesemia indicated practically no cytoprotective effect
before global ischaemia of myocardium lasting for 60 minutes. Hypermagnesemia
indicated a direct cytoprotective effect before global ischaemia affecting
respiration of isolated heart mitochondria in state of S3 (p<0.001),
respiration control index RCI (p<0.001), the rate of oxidative phosphorylation
OPR (p<0.001) and on the index of oxidative phosphorylation ADP:O (p<0.05)
on the uptake of calcium by mitochondria (p<0.002) and on concentration
of mitochondrial nucleotides ATP (p<0.002). It was remarkable that also
under conditions of moderate hypomagnesemia the production of malondialdehyde
increased.
Conclusions: Under our experimental conditions it was confirmed
that magnesium yields direct cytoprotective effect on the subcellular level
of the myocardium prior to global ischaemia, providing the process takes
place under the condition of hypermagnesemia. (Tab. 1, Fig. 12, Ref.
45.)
Key words: hypomagnesemia, normomagnesemia, hypermagnesemia, Langendorff's
global ischaemia, mitochondrial metabolism, cytoprotective effect.
Bratisl Lek Listy 1996; 97: 587595
THE DISTURBANCES OF HEPATIC CIRCULATION AND THE POSSIBILITIES OF THEIR IMAGING BY COLOUR DOPPLER ULTRASONOGRAPHY
SZANTOVA M., KUPCOVA V., VALKO L.
The authors analyse disturbances of hepatic circulation and the possibilities
of their imaging by colour Doppler ultrasonography (CDU) in combination
with standard B two-dimensional imaging. The predominance of arterial perfusion
in liver cirrhosis, portal vein thrombosis, malign diseases of the liver,
or extraluminal obstruction of portal vein are changes which can be imaged
by means of high-quality colour Doppler imaging. CDU is a non-invasive
method of evaluation of portal hypertension, namely of prehepatic, hepatic
and posthepatic type. It is a method of investigation of the viability
of the hepatic artery after transplantation of the liver, including that
of surgical portocaval anastomoses and transjugular intrahepatic portosystemic
shunts. (Fig. 6, Ref. 33.)
Key words: colour Doppler ultrasonography, hepatic circulation.
Bratisl Lek Listy 1996; 97:596602
COENZYME Q[_10] AND ALPHA-TOCOPHEROL IN PATIENTS AFTER TRANSPLANTATION OF THE HEART
KUCHARSKA J., GVOZDJAKOVA A., MIZERA S., MARGITFALVI P., SCHREINEROVA Z., SCHRAMEKOVA E., SOLCANSKA K., NOTOVA P., PECHAN I., FABIAN J.
Pathobiochemical mechanisms which participate in the rejection of transplanted
heart are not fully clarified. A signinficant role in this process
can be played by endogenous antioxidants, especially coenzyme Q[_10] which
aside from its antixidative properties is inevitable for cellular bioenergy.
The authors investigated the concentration of Q[_10] alpha-tocopherol in
endomyocardial biopsies in the blood in 11 patients from 1 to 9 years of
age after transplantation of the heart (HTx-pat) examined in ΪKVCH in Bratislava
who were compared with the group of 13 patients with cardiopathies of unclear
origin (KPNP-pat) as possible candidates for transplantation. They detected
a decreased concentration of coenzyme Q[_10] in the myocardium and
blood of HTx-patients. Levels of alpha-tocopherol in the myocardium were
identical in both groups, in plasma they were higher in patients after
HTx.
The authors suppose that the levels of coenzyme Q[_10] in patients
after HTx can be influenced by an increased production of free oxygen radicals
during rejection episodes, as well as immunosupressive therapy, and indicate
to the possible consequences of this decrease. The presented results provide
the first information on the levels of coenzyme Q[_10] and alpha-tocopherol
in patients after transplantation of the heart, registered and controlled
in the Slovak Republic. They can contribute to the clarification of some
pathobiochemical mechanisms of rejection, respectively to their therapeutic
effect. (Fig. 2, Ref. 16.)
Key words: transplatnation of the heart, endomyocardial biopsies,
coenzyme Q[_10], alpha-tocopherol.
Bratisl Lek Listy 1996; 97: 603606
IDENTIFICATION OF INHALED DUST BY NONINVASIVE MAGNETOMETRIC METHOD
KRUTY F., SIMACEK I., MANKA J.
The autors performed an examination of the degree of lung contamination
by magnetic compounds present in gases originating during welding in 33
persons divided into four groups. The measurement was performed by a noninvasive
magnetometric method using a high sensitive SQUID and second degree
gradiometric antenna with presumed maximum sensitivity of 60 microg of
magnetic compound/cm[^3]. In the selected three groups of welders working
for a long period of time under the conditions of exposure, the changes
of the magnetic field were particularly evident in the group working in
small confined spaces. It has become obvious that further improvement in
the accuracy of the detected results in the lung may be reached in the
subjects by changing the polarity of magnetization. (Fig. 4, Ref. 13.)
Key words: professional lung diseases, welders's pneumoconiosis,
magnetometry.
Bratisl Lek Listy 1996; 97: 607610
MORFOLOGICKE NALEZY PO INTRAKORONARNEJ APLIKACII ENDOTELINU-1 U PSA
SIDLO J., BERNADIC M., ZLATOS L., HOLZEROVA J., MAASOVA D., HULIN I.
Background: Endothelin-1 is a strong vasoconstrictor, high
doses of which can cause prolonged vasoconstriction.
Main Purpose: The aim of our study was to investigate as to
whether the endothelin-induced vasoconstriction causes irreversible morphological
changes in the myocardium in experimental animals and to verify the appliability
of this experimental model in the study of the impact of endothelin.
Methods: Fourteen anaesthetized dogs were administered with
400 pmol of endothelin. The substance was applied into the left anterior
descending coronary artery. The serum activities of AST, CK and LD enzymes,
and changes in electric activity of the myocardium were monitored. The
heart of one of the dogs was analyzed morphologically.
Results: Following the application of endothelin, vasoconstriction
supervened, lasting from 25 to 27 minutes. Five dogs developed fibrillation
of ventricles and died. The dogs which survived yielded changes in the
activities of the investigated enzymes and changes in electric activity
which were typical of focal impairment of the myocardium in sense of necrosis.
Morphologically the changes represented disseminated fibrosis or minor
scars in the myocardium.
Conclusions: Application of endothelin into the coronary artery
can cause irreversible structural changes in the myocardium. (Fig. 1,
Ref. 18.)
Key words: endothelin, fibrillation of ventricles, coronary artery
application, dog, myocardium, morphological changes.
Bratisl Lek Listy 1996; 97: 611613
BIOENERGY OF MITOCHONDRIA IN PATIENTS PRIOR TO AND AFTER TRANSPLATATION OF THE HEART
GVOZDJAKOVA A., KUCHARSKA J., MIZERA S., SOLCANSKA K., MARGITFALVI P., SCHREINEROVA Z., SCHRAMEKOVA E., NOTOVA P., PECHAN I., FABIAN J.
Background: The results of the study of biochemical and genetic
characteristics of mitochondria in human medicine become widely used in
practice. This is confirmed also by the Nobel Symposium which took place
in 1994, and was dedicated to the problem of mitochondrial diseases and
the effect of their therapy. Relatively rare is the information on the
pathobiochemistry of heart muscle mitochondria in patients with cardiomyopathies.
No information, so far, is available on oxidative phosphorylation in cases
of myocardium transplantation in patients.
Main Purpose and Objectives: To bring early metabolic changes
in mitochondria within EMB (endomyocardial biopsy) under control in patients
after transplantation of the heart (Htx). These detected metabolic changes
can contribute to the clarification of the mechanisms participating in
the rejection of the transplanted myocardium.
Patients and methods: The investigated group of patients included:
a) patients with cardiopathies of unclear origin (NYHA II, NYHAIII)
b) patients after transplantation of the heart (NYHAI-II)
The authors assessed the properties of the respiratory chain and ATP
production in mitochondria of EMB.
Conclusions: The new methodical approach to the study of bioenergy
of mitochondria of the myocardium in patients allows an early recognition
of pathobiochemical changes in myocardium. Supplementing studies are going
to reveal wether the presented methodical approach bear diagnostic value.
(Fig. 3, Ref. 25.)
Key word: mitochondrial medicine, endomyocardial biopsy, patients
prior to and after transplantation of the heart.
Bratisl Lek Listy 1996; 97: 614618
BIOENERGY OF MITOCHONDRIA IN THE LIVER OF RATS WITH EXPERIMENTALLY INDUCED INSULIN-DEPENDENT DIABETES
ULICNA O., VOLKOVOVA K., ISTVANOVA B.
Oxidative stress in the course of diabetes mellitus can cause disturbance
of lipid membranes of cellular organelles. The study is aimed at the determination
of oxidative phosphorylation in mitochondria in rats with experimentally
induced acute and chronic insulin-dependent diabetes mellitus (IDDM). IDDM
was induced by single dose of streptozotocin (45 mg per kg[^-1]). Insulin
Interdep (6 U per kg[^-1]) was administered once a day subcutaneously.
The authors investigated glycaemia, cholesterol and triacylglycerol concentrations
in the blood and liver. Isolation of mitochondria was succeeded by measurement
of oxidative phosphorylation indicators after 8 days (acute IDDM) or after
8 weeks (chronic IDDM) from streptozotocin administration. The authors
found out that both acute and chronic IDDM were concommited by hyperglycaemia.
The group with acute IDDM yielded an increase in cholesterol and triacyglycerols
concentrations in the blood, as well as that of cholesterol in the liver.
The group with chronic IDDM yields an increase in cholesterol in the blood.
Trialcylglycerols in the liver increased in none of the investigated groups.
Liver steatosis did not occur. Indicators of oxidative phosphorylation
in the liver mitochondria of rats with acute and with chronic IDDM decreased
in contrast to healthy controls from NAD substrates glutamate and pyruvate
and also form FAD substrate of succinate. Significant decrease in consumption
of oxygen in the 3 state occurred, while in acute IDDM the decrease was
more significant than in chronic IDDM. Phosphorylation rate significantly
decreased in contrast to controls, but there was no difference between
IDDM groups. The investigation results imply that in both acute and chronic
IDDM there are decreased effectivity of energetic metabolism in liver mitochondria.
(Tab. 5, Ref. 29.)
Key words: liver, mitochondria, diabetes mellitus, oxidative phosphorylation.
Bratisl Lek Listy 1996; 97: 619624
EFFECT OF ESSENTIAL PHOSPHOLIPIDS ON PLASMA PROTEINS IN PATIENTS WITH LIVER STEATOSIS
TURECKY L., KUPCOVA V., SZANTOVA M., LAKTIS K., UHLIKOVA E.
Background: Steatosis of the liver is the most frequent diffuse
disturbance of liver parenchyma. Accumulation of fat droplets in hepatocytes
determine the damage of function of subcellular structures and energy metabolism
of liver cells. The damagables include functions also the synthesis of
phospholipids which are required for the correct function of membranes.
Essentiale forte is a mixture of choline phosphatides with high content
of polyenic carboxylic acids. In our study we were interested in the effect
of administration of the drug Essentiale forte to patients with liver steatosis.
Patients: An open clinical trial was performed in 29 patients
(15 men and 14 women) suffering from liver steatosis. Two capsules of Essentiale
forte (Rhone-Poulenc Rorer) were administered 3 times daily for 3 months.
Individual biochemical parameters were determined each month.
Results: The therapeutic effect of the substance on the patient's
well-being and the clinical condition was assessed as being good in 23
patients (76 %). There was a significant improvement in parameters
of hepatocyte integrity (aminotransferases) and a decrease of activity
of gamma-glutamyltransferase in sera of patients after therapy. In the
group of acute-phase proteins there was a significant decrease in
the alpha-1-acid glycoprotein level. A similar tendency was also in
the level of haptoglobin. In the group of the parameters of proteosynthetic
function of the liver (albumin, transferrin, prealbumin) there was no change.
Statistically significant decreases were detected also in the levels of
immunoglobulins G and M.
Conclusion: The submitted findings confirm positive effect of
essential phospholipids on the treatment of liver steatosis. (Fig. 4,
Ref. 15.)
Key words: liver steatosis, plasma proteins, Essentiale forte,
essential phospholipids, fatty liver.
Bratisl Lek Listy 1996; 97: 625628
THE SITE OF VASCULAR RECONSTRUCTION SURGERY IN THE THERAPY OF CEREBROVASCULAR INSUFFICIENCY
SEFRANEK V., TOMKA J., MOLCAN T., DULKA T., BREZNA M., STANOVA L., LESNY P., MISTRIK A., LEDERER P.
Background: Management of cerebrovascular insufficiency (CVI)
is one of the greatest medical challenges in our country. Retardation in
this field has been causing serious medical and socioeconomic consequenses.
Main purpose and starting points (objectives): In spite of existing
unfavourable conditions the authors of this paper have managed to standardize
their own policy in diagnosis, surgical indications and techniques. This
caused substantial improvement of their results, as well as cooperation
with the neurologic clinics. In connection with the increasing numbers
of operations and improved results, the authors report their recent experience
in this field and compare them with the results from previous years.
Methods: The authors compare two series of patients. The first
series of 65 consecutive patients surgically treated from 1st Jan. 1987
to 31st Dec. 1990 (69 operations alltogether). The 2nd series of 169 consecutive
patients surgically treated from January 1st 1993 to December 31st 1994
(191 operations alltogether), 149 due of them were subjected to carotic
endarterectomy (CEA). Mean age of the first series was 55.3 (3573), 2nd
series 59.7 years (4286). The authors have studied participation of neurologically
and angiographically unstable patients. In the first series the ratio of
neurologically stable and unstable patients was 63.4:36.6 %, while in the
2nd series it was 75.4:24.6 %. The ratio of angiographically stable and
unstable patients was in the 1st series 60.2:39.8 %, while in the 2nd series
it was 50.3:49.7 %. In the 2nd series the authors observed also the percent
age of ulcerated lesions in the carotic bifurcation and found a surprisingly
high number 59.2 %.
Results: The combined mortality-morbidity index of the first
series was 11.6 %, of the 2nd series 3.1 %. In the first series there were
two deaths (2.9 %) and 6 brain infarctions. In the 2nd series four patients
died from acute myocardial infarction (2.1 %) and there were two cases
of a perioperative brain infarction, respectively. The necessity of
wound revision due to of bleeding was found in two patients (2.9 %) in
the first series, and in two cases (1 %) in the 2nd series.
Conclusions: The authors emphasize the complicated nature of
these problems, the necessity to recognize the surgical indications and
techniques, and protective measures to prevent serious complications. There
is, in their opinion, inevitable to increase bringing the patients in need
of surgical reconstruction under control. On the other hand, there is the
necessity to increase the accessibility of qualified surgery in the CVI.
That means in the first place to increase the number of centers able to
accomplish these operations with minimal combined mortality-morbidity index.
(Tab. 10, Ref. 37.)
Key words: cerebrovascular insufficiency, surgical management,
complications.
Bratisl Lek Listy 1996; 97: 629637