Isolated heart
Dotaz
Zobrazit nápovědu
BACKGROUND: Detailed quantitative analysis of the effect of left ventricle (LV) hypertrophy on myocardial ischemia manifestation in ECG is still missing. The associations between both phenomena can be studied in animal models. In this study, rabbit isolated hearts with spontaneously increased LV mass were used to evaluate the effect of such LV alteration on ischemia detection criteria and performance. METHODS: Electrophysiological effects of increased LV mass were evaluated on sixteen New Zealand rabbit isolated hearts under non-ischemic and ischemic conditions by analysis of various electrogram (EG) parameters. To reveal hearts with increased LV mass, LV weight/heart weight ratio was proposed. Standard paired and unpaired statistical tests and receiver operating characteristics analysis were used to compare data derived from different groups of animals, monitor EG parameters during global ischemia and evaluate their ability to discriminate between unchanged and increased LV as well as non-ischemic and ischemic state. RESULTS: Successful evaluation of both increased LV mass and ischemia is lead-dependent. Particularly, maximal deviation of QRS and area under QRS associated with anterolateral heart wall respond significantly to even early phase (the 1st-3rd min) of ischemia. Besides ischemia, these parameters reflect increased LV mass as well (with sensitivity reaching approx. 80%). However, the sensitivity of the parameters to both phenomena may lead to misinterpretations, when inappropriate criteria for ischemia detection are selected. Particularly, use of cut-off-based criteria defined from control group for ischemia detection in hearts with increased LV mass may result in dramatic reduction (approx. 15%) of detection specificity due to increased number of false positives. Nevertheless, criteria adjusted to particular experimental group allow achieving ischemia detection sensitivity of 89-100% and specificity of 94-100%, respectively. CONCLUSIONS: It was shown that response of the heart to myocardial ischemia can be successfully evaluated only when taking into account heart-related factors (such as LV mass) and other methodological aspects (such as recording electrodes position, selected EG parameters, cut-off criteria, etc.). Results of this study might be helpful for developing new clinical diagnostic strategies in order to improve myocardial ischemia detection in patients with LV hypertrophy.
- Klíčová slova
- Electrogram, Increased left ventricular mass, Isolated heart, Myocardial ischemia detection, ROC analysis, Rabbit,
- MeSH
- elektrofyziologické techniky kardiologické * MeSH
- elektrokardiografie * MeSH
- funkce levé komory srdeční * MeSH
- hypertrofie levé komory srdeční komplikace diagnóza patofyziologie MeSH
- ischemická choroba srdeční komplikace diagnóza patofyziologie MeSH
- králíci MeSH
- modely nemocí na zvířatech MeSH
- plocha pod křivkou MeSH
- počítačové zpracování signálu MeSH
- prediktivní hodnota testů MeSH
- preparace izolovaného srdce MeSH
- remodelace komor * MeSH
- rizikové faktory MeSH
- ROC křivka MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Prolonged QT interval is an independent risk factor for development of ventricular arrhythmias. Haloperidol is one of the drugs inducing QT prolongation. Previous studies showed that haloperidol affects not only QT duration but also heart rate (RR interval). The present work focused on relationship between QT and RR and its changes under acute and chronic haloperidol administration. The study included 14 male guinea pigs divided into control and haloperidol-treated group. After 21-days administration of haloperidol or vehiculum, electrograms in isolated hearts were recorded. QT/RR and dQT/dRR coupling were calculated. Chronic haloperidol administration significantly decreases the coupling between QT and RR. Acute haloperidol exposure significantly decreases the dQT/dRR coupling in both treated and untreated guinea pig hearts. Flatter QT/RR relationship reveals a lack of QT adaptation to increased heart rate. It should be emphasized that in such situation ECG recording will not show significant QT prolongation evaluated according to clinical rules. However, if QT interval does not adapt to increased heart rate sufficiently, the risk of ventricular arrhythmias may be increased despite practically normal QT interval length. The results are supported by findings in biochemical analyses, which proved eligibility of the used model.
- Klíčová slova
- Drug-induced QT prolongation, Guinea pig, Haloperidol, Isolated heart, QT/RR coupling,
- MeSH
- antipsychotika farmakologie MeSH
- haloperidol farmakologie MeSH
- morčata MeSH
- srdce účinky léků fyziologie MeSH
- srdeční frekvence účinky léků MeSH
- syndrom dlouhého QT MeSH
- zvířata MeSH
- Check Tag
- morčata MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antipsychotika MeSH
- haloperidol MeSH
AIMS: Although voltage-sensitive dye di-4-ANEPPS is a common tool for mapping cardiac electrical activity, reported effects on electrophysiological parameters are rather. The main goals of the study were to reveal effects of the dye on rabbit isolated heart and to verify, whether rabbit isolated heart stained with di-4-ANEPPS is a suitable tool for myocardial ischemia investigation. METHODS AND RESULTS: Study involved experiments on stained (n = 9) and non-stained (n = 11) Langendorff perfused rabbit isolated hearts. Electrophysiological effects of the dye were evaluated by analysis of various electrogram (EG) parameters using common paired and unpaired statistical tests. It was shown that staining the hearts with di-4-ANEPPS leads to only short-term sporadic prolongation of impulse conduction through atria and atrioventricular node. On the other hand, significant irreversible slowing of heart rate and ventricular conduction were found in stained hearts as compared to controls. In patch clamp experiments, significant inhibition of sodium current density was observed in differentiated NG108-15 cells stained by the dye. Although no significant differences in mean number of ventricular premature beats were found between the stained and the non-stained hearts in ischemia as well as in reperfusion, all abovementioned results indicate increased arrhythmogenicity. In isolated hearts during ischemia, prominent ischemic patterns appeared in the stained hearts with 3-4 min delay as compared to the non-stained ones. Moreover, the ischemic changes did not achieve the same magnitude as in controls even after 10 min of ischemia. It resulted in poor performance of ischemia detection by proposed EG parameters, as was quantified by receiver operating characteristics analysis. CONCLUSION: Our results demonstrate significant direct irreversible effect of di-4-ANEPPS on spontaneous heart rate and ventricular impulse conduction in rabbit isolated heart model. Particularly, this should be considered when di-4-ANEPPS is used in ischemia studies in rabbit. Delayed attenuated response of such hearts to ischemia might lead to misinterpretation of obtained results.
- Klíčová slova
- di-4-ANEPPS, electrogram analysis, myocardial ischemia, patch-clamp, rabbit isolated heart, voltage-sensitive dye,
- Publikační typ
- časopisecké články MeSH
Isolated rat heart cells permeabilized by digitonin were examined as an experimental model to study heart bioenergetics. The cells displayed good parameters of oxidative phosphorylation (acceptor control ratio ca. 8 with pyruvate + malate). High ATPase activity detected in the cells was characterized. The ATPase activity was Ca-dependent (optimum [free Ca] ca. 400 nM), and Mg was necessary for its full activity. Double reciprocal plot l/v vs. 1/[free Ca] at physiological [free Ca] was linear, thus showing free Ca to be a substrate for the ATPase (Km for Ca ca. 149 nM). Double reciprocal plot 1/v vs. 1/[ATP] was also liner, thus showing the ATPase activity could be ascribed to a single enzyme. The ATPase is supposed to represent Ca, Mg-ATPase of sarcoplasmic reticulum. The ATPase activity appeared to be functionally coupled to oxidative phosphorylation of the cells by apparently preferring ATP supplied by mitochondria (KmATP = 74 microM) to external ATP (KmATP = 169 microM; P less than 0.05). Apparent preference by oxidative phosphorylation for ADP supplied by the ATPase (KmATP = 45 microM) to external ADP (KmATP = 152 microM) was also manifested by significant difference (P less than 0.02) in Km.
1. Definition. The isolated perfused heart according to Langendorff is a preparation which is easily obtained from all warm-blooded animals. The heart is usually perfused at constant pressure, but frequently at constant flow, mostly with oxygenated saline solutions. The ventricles do not fill with the perfusate and therefore do not perform pressure-volume work. If, however, an intraventricular balloon is inserted, the ventricle can contract isovolumetrically. 2. Measuring parameters. Mechanical parameters of the working myocardium (contractile force, volume, ventricular diameter), mean coronary flow, bioelectrical parameters (EKG, monophasic injury potentials), and cardiac rhythm can be measured and recorded. 3. Function tests. The intact function of the working myocardium and the coronary vessels should be examined using various simple tests regarding the myocardium, the smooth musculature, and the endothelium of coronary vessels. 4. Possible applications. In the Langendorff-heart of normal or pretreated animals, inotropic, chronotropic, antiarrhythmic or vasoactive substances can be investigated in the steady state or by means of specific stress tests. In addition, the preparation is particularly suitable for biochemical studies of myocardial metabolism. 6. Advantages. Due to the technical ease with which a variety of parameters can be measured, a single heart can provide maximum information about the condition of the myocardium and the coronary vessels. Thus, it is not surprising to find that 90 years after its first description, the isolated perfused heart according to Langendorff continues to be utilized.
Hypertrophied hearts are known for increased risk of arrhythmias and are linked with reduced ischemic tolerance. However, still little is known about state characterized only by increased left ventricle (LV) mass fraction. Seventeen isolated rabbit hearts with various LV mass were divided into two groups according to LV weight/heart weight ratio (LVW/HW ratio), namely group H and L (with higher and lower LVW/HW ratio, respectively) and underwent three short cycles of global ischemia and reperfusion. The differences in electrogram (heart rate, QRS(max), mean number, onset and dominant form of ventricular premature beats) and in biochemical markers of myocardial injury (creatine kinase, lactate dehydrogenase - LDH) and lipid peroxidation (4-hydroxy-2-nonenal - 4-HNE) were studied. As compared to group L, hearts in group H exhibited lower tolerance to ischemia expressed as higher incidence and severity of arrhythmias in the first ischemic period as well as increase of LDH and 4-HNE after the first reperfusion. In the third cycle of ischemia-reperfusion, the preconditioning effect was observed in both electrophysiological parameters and LDH release in group H. Our results showed consistent trends when comparing changes in electrograms and biochemical markers. Moreover, 4-HNE seems to be good potential parameter of moderate membrane alteration following ischemia-reperfusion injury.
- MeSH
- extrasystoly patologie patofyziologie MeSH
- hypertrofie levé komory srdeční patologie patofyziologie MeSH
- ischemická choroba srdeční patologie patofyziologie MeSH
- králíci MeSH
- preparace izolovaného srdce metody MeSH
- reperfuzní poškození myokardu patologie patofyziologie MeSH
- srdce MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The authors describe, in a case report, an isolated defect of the ventricular septum developing due to a stab injury to the heart not requiring an emergency surgical intervention. Two months after the injury, the authors performed primary surgical correction of the defect.
- MeSH
- angiografie MeSH
- bodné rány komplikace diagnóza chirurgie MeSH
- defekty srdečního septa diagnóza etiologie chirurgie MeSH
- dospělí MeSH
- echokardiografie transezofageální MeSH
- kardiochirurgické výkony MeSH
- lidé MeSH
- následné studie MeSH
- poranění srdce komplikace diagnóza chirurgie MeSH
- srdeční septum diagnostické zobrazování zranění chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Cardiovascular diseases represent an economic burden for health systems accounting for substantial morbidity and mortality worldwide. Despite timely and costly efforts in drug development, the cardiovascular safety and efficacy of the drugs are not always fully achieved. These lead to the drugs' withdrawal with adverse cardiac effects from the market or in the late stages of drug development. There is a growing need for a cost-effective drug screening assay to rapidly detect potential acute drug cardiotoxicity. The Langendorff isolated heart perfusion technique, which provides cardiac hemodynamic parameters (e.g., contractile function and heart rate), has become a powerful approach in the early drug discovery phase to overcome drawbacks in the drug candidate's identification. However, traditional ex vivo retrograde heart perfusion methods consume a large volume of perfusate, which increases the cost and limits compound screening. An elegant and cost-effective alternative mode for ex vivo retrograde heart perfusion is the constant-flow with a recirculating circuit (CFCC), which allows assessment of cardiac function using a reduced perfusion volume while limiting adverse effects on the heart. Here, we provide evidence for cardiac parameters stability over time in this mode. Next, we demonstrate that our recycled ex vivo perfusion system and the traditional open one yield similar outputs on cardiac function under basal conditions and upon ?-adrenergic stimulation with isoproterenol. Subsequently, we validate the proof of concept of therapeutic agent screening using this efficient method. ?-blocker (i.e., propranolol) infusion in closed circulation countered the positive effects induced by isoproterenol stimulation on cardiac function. Keywords: Drug development, Drug screening, Cardiovascular safety, Langendorff method, Closed circulation.
- MeSH
- isoprenalin farmakologie MeSH
- krysa rodu Rattus MeSH
- perfuze * metody MeSH
- preklinické hodnocení léčiv metody MeSH
- preparace izolovaného srdce * metody MeSH
- srdce * účinky léků fyziologie MeSH
- srdeční frekvence účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- isoprenalin MeSH
- Klíčová slova
- ANTIHYPERTENSIVE AGENTS/pharmacology *, HEART/pharmacology *,
- MeSH
- antihypertenziva farmakologie MeSH
- savci * MeSH
- srdce farmakologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antihypertenziva MeSH
BACKGROUND: A significant proportion of patients with exertional dyspnea require exercise to diagnose heart failure with normal ejection fraction (HFNEF). METHODS AND RESULTS: In this review article, we evaluate current data on the prevalence, clinical significance and specifically the establishment of a diagnosis of isolated, exercise-induced HFNEF. Despite the unquestioned clinical importance and high prevalence of exercise-induced HFNEF, there are limited and conflicting data on making a diagnosis of exercise-induced HFNEF. This mostly relies on the evidence of exercise-induced elevation in left ventricular filling pressure (LVFP). At present, there is no agreement on the ability of exercise echocardiographic parameteres to predict exercise-induced LVFP elevation. In addition, even invasively measured exercise LVFP faces the problem of defining normal exercise LVFP values. More data and probably new diagnostic approaches are necessary to reliably diagnose exercise HFNEF. CONCLUSIONS: There are conflicting results and significant problems associated with the diagnosis of exercise HFNEF. This review hopefully will encourage further research in this difficult but clinically important area of heart failure.
- Klíčová slova
- exercise echocardiography, heart failure with normal ejection fraction, left ventricular filling pressure,
- MeSH
- barevná dopplerovská echokardiografie MeSH
- cvičení fyziologie MeSH
- dysfunkce levé srdeční komory diagnóza patofyziologie MeSH
- dyspnoe etiologie MeSH
- krevní tlak fyziologie MeSH
- lidé MeSH
- srdeční selhání diagnóza patofyziologie MeSH
- tepový objem fyziologie MeSH
- zátěžová echokardiografie MeSH
- zátěžový test MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
