scholarly journals NADH changes during hypoxia, ischemia, and increased work differ between isolated heart preparations

2014 ◽  
Vol 306 (4) ◽  
pp. H529-H537 ◽  
Author(s):  
Anastasia M. Wengrowski ◽  
Sarah Kuzmiak-Glancy ◽  
Rafael Jaimes ◽  
Matthew W. Kay
Keyword(s):  
Energy Supply ◽  
Oxygen Supply ◽  
Heart Function ◽  
Isolated Heart ◽  
Supply And Demand ◽  
Half Maximum ◽  
Low Oxygen ◽  
Heart Preparation ◽  
Perfused Hearts

Langendorff-perfused hearts and working hearts are established isolated heart preparation techniques that are advantageous for studying cardiac physiology and function, especially when fluorescence imaging is a key component. However, oxygen and energy requirements vary widely between isolated heart preparations. When energy supply and demand are not in harmony, such as when oxygen is not adequately available, the imbalance is reflected in NADH fluctuations. As such, NADH imaging can provide insight into the metabolic state of tissue. Hearts from New Zealand white rabbits were prepared as mechanically silenced Langendorff-perfused hearts, Langendorff-perfused hearts, or biventricular working hearts and subjected to sudden changes in workload, instantaneous global ischemia, and gradual hypoxia while heart rate, aortic pressure, and epicardial NADH fluorescence were monitored. Fast pacing resulted in a dip in NADH upon initiation and a spike in NADH when pacing was terminated in biventricular working hearts only, with the magnitude of the changes greatest at the fastest pacing rate. Working hearts were also most susceptible to changes in oxygen supply; NADH was at half-maximum value when perfusate oxygen was at 67.8 ± 13.7%. Langendorff-perfused and mechanically arrested hearts were the least affected by low oxygen supply, with half-maximum NADH occurring at 42.5 ± 5.0% and 23.7 ± 4.6% perfusate oxygen, respectively. Although the biventricular working heart preparation can provide a useful representation of mechanical in vivo heart function, it is not without limitations. Understanding the limitations of isolated heart preparations is crucial when studying cardiac function in the context of energy supply and demand.

Abstract 401: Shortening of Action Potential Duration With Increased Work in Contracting Rabbit Heart

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Kara E Garrott ◽  
Anastasia Wengrowski ◽  
Hanyu Zhang ◽  
Jack Rogers ◽  
Matthew Kay
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Energy Supply ◽  
Optical Mapping ◽  
Heart Function ◽  
Supply And Demand ◽  
High Stress ◽  
Aortic Pressure ◽  
Novel Method

Studying heart function in contracting hearts at higher workloads provides crucial knowledge of cardiac performance in high-stress situations. Ratiometric optical mapping of fully loaded hearts is a novel method to study electrical activity while replicating in vivo energy consumption. We predict that an imbalance between energy supply and demand during increased work and hypoxia will manifest in shortened action potential duration (APD), especially in the more physiologically-relevant bi-ventricular (BiV) working heart. Rabbit hearts were perfused with oxygenated Krebs-Henseleit solution in unloaded Langendorff and fully-loaded BiV mode. Epicardial action potentials (APs) were measured using optical mapping of Di-4-ANEPPS. Excitation ratiometry using 450 and 505 nm illumination on alternate camera frames together with motion tracking removed motion artifact. Aortic pressure, left atrial preload, and LVDP was measured. A range of workloads were studied by pacing at 330, 220, and 170 ms cycle length (CL). Gradual hypoxia was induced by bubbling with N2 gas. In Langendorff mode, the APD was 137.67±4.29 ms, 113.44±7.89 ms, and 106.44±0.44 ms at CL of 330ms, 220ms, and 170ms, respectively, while in BiV mode, the APD was 106.56±13.03 ms, 78.00±2.33 ms, and 69.33±0.77 ms. Aortic pressure dropped from NSR in BiV hearts by 1.26% at 330ms, 4.11% at 220ms, and 11.65% at 170ms CL. Shortening of APD, independent of restitution, with increasing HR indicates an imbalance of energy supply and demand with greater workload. KATP channels are implicated. This novel method of optical mapping reveals important implications of electrophysiological changes during high-stress situations.

High-resolution visualization of oxygen distribution in the liver in vivo

2004 ◽  
Vol 286 (1) ◽  
pp. G37-G44 ◽  
Author(s):  
Markus Paxian ◽  
Steve A. Keller ◽  
Brian Cross ◽  
Toan T. Huynh ◽  
Mark G. Clemens
Keyword(s):  
Redox State ◽  
Oxygen Supply ◽  
Supply And Demand ◽  
Hepatic Tissue ◽  
Oxygen Distribution ◽  
Sprague Dawley ◽  
Additional Information ◽  
Nadh Fluorescence ◽  
Oxygen Sensitive

Microcirculatory failure after stress events results in mismatch in oxygen supply and demand. Determination of tissue oxygen distribution in vivo may help elucidate mechanisms of injury, but present methods have limited resolution. Male Sprague-Dawley rats were anesthetized, prepared for intravital microscopy, and received intravenously the oxygen-sensitive fluorescent dye Tris(1,10-phenanthroline)ruthenium(II) chloride hydrate [[Formula: see text]]. An impaired hepatic oxygen distribution was induced by either phenylephrine or hemorrhage. Intensity of [Formula: see text] fluorescence was compared with NADH autofluorescence indicating changes in the mitochondrial redox potential. Ethanol was injected to affect the NADH-to-NAD+ ratio without altering the Po2. Infusion of [Formula: see text] resulted in a heterogeneous fluorescence under baseline conditions reflecting the physiological acinar Po2 distribution. A decrease in oxygen supply due to phenylephrine or hemorrhage was paralleled by an increase in [Formula: see text] and NADH fluorescence reflecting an impaired mitochondrial redox state. Ethanol did not alter [Formula: see text] fluorescence but increased NADH fluorescence indicating independence of Po2 and redox state imaging. Intravenous administration of [Formula: see text] for intravital videomicroscopy represents a new method to visualize the hepatic tissue Po2. Combined with NADH autofluorescence, it provides additional information regarding the tissue redox state.

The low oxygen-carrying capacity of Krebs buffer causes a doubling in ventricular wall thickness in the isolated heart

2005 ◽  
Vol 83 (2) ◽  
pp. 174-182 ◽  
Author(s):  
R Southworth ◽  
S C Blackburn ◽  
K A.B Davey ◽  
G K Sharland ◽  
P B Garlick
Keyword(s):  
Wall Thickness ◽  
Carrying Capacity ◽  
Coronary Flow ◽  
Left Ventricular ◽  
Ventricular Wall ◽  
Low Oxygen ◽  
Ventricular Wall Thickness ◽  
Oxygen Carrying Capacity ◽  
Perfused Hearts

The buffer-perfused Langendorff heart is significantly vasodilated compared with the in vivo heart. In this study, we employed ultrasound to determine if this vasodilation translated into changes in left ventricular wall thickness (LVWT), and if this effect persisted when these hearts were switched to the "working" mode. To investigate the effects of perfusion pressure, vascular tone, and oxygen availability on cardiac dimensions, we perfused hearts (from male Wistar rats) in the Langendorff mode at 80, 60, and 40 cm H2O pressure, and infused further groups of hearts with either the vasoconstrictor endothelin-1 (ET-1) or the blood substitute FC-43. Buffer perfusion induced a doubling in diastolic LVWT compared with the same hearts in vivo (5.4 ± 0.2 mm vs. 2.6 ± 0.2 mm, p < 0.05) that was not reversed by switching hearts to "working" mode. Perfusion pressures of 60 and 40 cm H2O resulted in an increase in diastolic LVWT. ET-1 infusion caused a dose-dependent decrease in diastolic LVWT (6.6 ± 0.4 to 4.8 ± 0.4 mm at a concentration of 10–9 mol/L, p < 0.05), with a concurrent decrease in coronary flow. FC-43 decreased diastolic LVWT from 6.7 ± 0.5 to 3.8 ± 0.7 mm (p < 0.05), with coronary flow falling from 16.1 ± 0.4 to 8.1 ± 0.4 mL/min (p < 0.05). We conclude that the increased diastolic LVWT observed in buffer-perfused hearts is due to vasodilation induced by the low oxygen-carrying capacity of buffer compared with blood in vivo, and that the inotropic effect of ET-1 in the Langendorff heart may be the result of a reversal of this wall thickening. The implications of these findings are discussed.Key words: ultrasound, endothelin, ventricular wall thickness, vasodilation.

DIFFERENTIAL EFFECTS OF HALOTHANE AND ISOFLURANE ON OXYGEN SUPPLY AND DEMAND IN ISOLATED PERFUSED HEARTS

1989 ◽  
Vol 71 (Supplement) ◽  
pp. A1155
Author(s):  
D F Stowe ◽  
J Marijic ◽  
S Monroe ◽  
Z J Bosnjak ◽  
J P Kampine
Keyword(s):  
Oxygen Supply ◽  
Supply And Demand ◽  
Differential Effects ◽  
Perfused Hearts

Arachidonic acid induced coronary reactions and their inhibition by docosahexaenoic acid

1986 ◽  
Vol 64 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Jaime Talesnik
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Docosahexaenoic Acid ◽  
Isolated Heart ◽  
Isolated Perfused Heart ◽  
Perfused Heart ◽  
Dependent Inhibition ◽  
Perfused Hearts ◽  
Vascular Compartment

The objective of the present study was to further investigate the influence exerted by docosahexaenoic acid (DHA) on the coronary reactions induced in isolated perfused hearts of rats and guinea pigs by bolus doses of arachidonic acid (AA). As in previous studies, we found that AA produced a coronary constriction followed by a longer lasting dilatation. The present data demonstrate that a 5-min infusion of DHA at 0.17–0.68 μM caused a concentration-dependent inhibition of the AA-induced constriction. The vasodilatation determined by AA was also depressed, but only after about 30 min of a sustained DHA infusion. The precursor of AA, linoleic acid (LA), was also infused for about 30 min, and like DHA it inhibited the coronary reactions induced by AA. LA is not converted into AA by the isolated heart, but like DHA, was probably incorporated into the cells of the coronary vascular compartment. It is known that LA, administered "in vivo" to mammals, is converted into AA and increases the production of eicosanoids, whereas DHA does not follow this metabolic pathway. The incorporation of these essential polyunsaturated fatty acids by the isolated perfused heart would inhibit the cyclooxygenase in the coronary vessel walls, interfering with the generation of vasomotor metabolites from AA. We postulate that the systemic administration of DHA, by inhibiting the synthesis of a constrictor metabolite, could be beneficial in reducing the damage due to microvascular constriction in myocardial ischaemia.

Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment

1991 ◽  
Vol 69 (3) ◽  
pp. 346-354 ◽  
Author(s):  
Robert L. Rodgers ◽  
Amy J. Davidoff ◽  
Mark J. Mariani
Keyword(s):  
Insulin Therapy ◽  
Diabetic Cardiomyopathy ◽  
Ex Vivo ◽  
Heart Function ◽  
Left Ventricular ◽  
Left Renal Artery ◽  
Hypertensive Rats ◽  
Heart Performance ◽  
Perfused Hearts

The influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left renal artery of Wistar–Kyoto (WKY) rats, and diabetes was induced 2 weeks later by streptozotocin (STZ; 55 mg/kg i.v.). The WKY strain was selected because it is relatively resistant to the cardiodepressant effects of diabetes, so that the influence of superimposed hypertension would be more apparent. Performance of working Krebs–Henseleit buffer perfused hearts was quantified by measuring left ventricular pressure and flow characteristics. The results showed that renovascular clipping caused a marked hypertension and left ventricular hypertrophy (LVH) but had no effect on perfused heart performance after 10 weeks. They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats. Treatment of diabetic RVH rats with T3 (10 μg∙kg−1∙day−1) in vivo was nearly as effective as insulin therapy (10 U∙kg−1∙day−1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline in serum T3 levels, even though it intensified the hyperglycemia and body weight loss. The results provide support for a synergistic effect of diabetes and hypertension on heart function. They also add support to the hypothesis that attendant hypothyroidism contributes significantly to diabetic cardiomyopathy in the hypertensive rat.Key words: heart performance, triiodothyronine, hypothyroidism, cardiomyopathy.

scholarly journals OXYGEN SUPPLY AND IN VITRO PERFORMANCE OF THE SYSTEMIC HEART OF OCTOPUS VULGARIS: EFFECTS OF HAEMOCYANIN

1991 ◽  
Vol 157 (1) ◽  
pp. 523-540 ◽  
Author(s):  
C. AGNISOLA ◽  
D. F. HOULIHAN
Keyword(s):  
Oxygen Consumption ◽  
Stroke Volume ◽  
Oxygen Supply ◽  
Sea Water ◽  
Isolated Heart ◽  
Carbon Dioxide Production ◽  
Octopus Vulgaris ◽  
Systemic Heart

The effect of increasing oxygen supply on the perfused systemic heart of Octopus vulgaris (Lam.) by using oxygenated or haemocyanin-containing perfusates was investigated. Providing aerated blood or seawater solutions of haemocyanin that were comparable with blood in oxygen-carrying capacity improved the performance of the isolated heart compared with that of hearts perfused with aerated sea water. Aortic outputs were similar to in vivo values (44ml min−1 g−1) at close to in vivo values of preload and afterload owing to an increase in both heart rate (from 24.0 to 38.4beatsmin−1) and stroke volume (from 0.69 to 1.10ml g−1). Coronary flow fell in these conditions, becoming 2.5% of the aortic output (against 24% with aerated sea water). A parallel increase in coronary resistance was found. Oxygenated sea water also improved the performance of the heart, mainly by improving the stroke volume. Both with haemocyanin solutions or blood and with oxygenated sea water, the isolated heart was able to do more work at lower preloads compared with the hearts perfused with aerated sea water. Power output was linearly related to total oxygen consumption and carbon dioxide production. The major site of oxygen consumption was the coronary bed. Haemocyanin released about 70% of the bound oxygen as it passed through the ventricular wall. Note: Present address: Department of Zoology, University of Aberdeen, Aberdeen AB9 2TN, Scotland, UK.

Computer modeling of the oxygen supply and demand of cells of the avian growth cartilage

1993 ◽  
Vol 265 (2) ◽  
pp. C497-C506 ◽  
Author(s):  
J. C. Haselgrove ◽  
I. M. Shapiro ◽  
S. F. Silverton
Keyword(s):  
Oxygen Consumption ◽  
Blood Vessels ◽  
Computer Modeling ◽  
Growth Plate ◽  
Oxygen Supply ◽  
Supply And Demand ◽  
Protective Mechanism ◽  
Low Oxygen ◽  
Growth Cartilage ◽  
Oxygen Tensions

We have used computer modeling studies to investigate the oxygen supply to the prehypertrophic and hypertrophic regions of avian growth plate. We measured experimentally the characteristics of the oxygen consumption of chondrocytes at different oxygen tensions. The oxygen consumption decreases at low oxygen tensions. This relation between oxygen tension and oxygen consumption serves as a protective mechanism that prevents the cells in the prehypertrophic zone from becoming anoxic in the regions farthest from the blood vessels. The results of the calculations, when combined with redox measurements of the cells in the growth plate, indicate that the metabolism of the chondrocytes is not controlled simply by the available oxygen supply.

Progression from hypertrophic to dilated cardiomyopathy in mice that express a mutant myosin transgene

2001 ◽  
Vol 280 (1) ◽  
pp. H151-H159 ◽  
Author(s):  
Kalev Freeman ◽  
Cynthia Colon-Rivera ◽  
M. Charlotte Olsson ◽  
Russell L. Moore ◽  
Howard D. Weinberger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dilated Cardiomyopathy ◽  
Exercise Tolerance ◽  
Heart Function ◽  
Isolated Heart ◽  
Transgenic Animals ◽  
Actin Binding ◽  
Isolated Hearts ◽  
Cardiac Decompensation

A mouse model of hypertrophic cardiomyopathy (HCM) was created by expression of a cardiac α-myosin transgene including the R403Q mutation and a deletion of a segment of the actin-binding domain. HCM mice show early histopathology and hypertrophy, with progressive hypertrophy in females and ventricular dilation in older males. To test the hypothesis that dilated cardiomyopathy (DCM) is part of the pathological spectrum of HCM, we studied chamber morphology, exercise tolerance, hemodynamics, isolated heart function, adrenergic sensitivity, and embryonic gene expression in 8- to 11-mo-old male transgenic animals. Significantly impaired exercise tolerance and both systolic and diastolic dysfunction were seen in vivo. Contraction and relaxation parameters of isolated hearts were also decreased, and lusitropic responsiveness to the β-adrenergic agonist isoproterenol was modestly reduced. Myocardial levels of the G protein-coupled β-adrenergic receptor kinase 1 (β-ARK1) were increased by more than twofold over controls, and total β-ARK1 activity was also significantly elevated. Induction of fetal gene expression was also observed in transgenic hearts. We conclude that transgenic male animals have undergone cardiac decompensation resulting in a DCM phenotype. This supports the idea that HCM and DCM may be part of a pathological continuum rather than independent diseases.

scholarly journals The Insecticidal Activity of Rhinella schneideri (Werner, 1894) Paratoid Secretion in Nauphoeta cinerea Cocroaches

Toxins ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 630
Author(s):  
Allan Leal ◽  
Etiely Karnopp ◽  
Yuri Correia Barreto ◽  
Raquel Soares Oliveira ◽  
Maria Eduarda Rosa ◽  
...  
Keyword(s):  
Isolated Heart ◽  
Acetylcholinesterase Activity ◽  
Nauphoeta Cinerea ◽  
Rhinella Schneideri ◽  
Heart Preparation ◽  
Dose Dependent Decrease ◽  
Ld50 Value ◽  
Nerve Muscle ◽  
Dose Dependent

Rhinella schneideri is a common toad found in South America, whose paratoid toxic secretion has never been explored as an insecticide. In order to evaluate its insecticidal potential, Nauphoeta cinerea cockroaches were used as an experimental model in biochemical, physiological and behavioral procedures. Lethality assays with Rhinella schneideri paratoid secretion (RSPS) determined the LD50 value after 24 h (58.07µg/g) and 48 h exposure (44.07 µg/g) (R2 = 0.882 and 0.954, respectively). Acetylcholinesterase activity (AChE) after RSPS at its highest dose promoted an enzyme inhibition of 40%, a similar effect observed with neostigmine administration (p < 0.001, n= 5). Insect locomotion recordings revealed that RSPS decreased the distance traveled by up to 37% with a concomitant 85% increase in immobile episodes (p < 0.001, n = 36). RSPS added to in vivo cockroach semi-isolated heart preparation promoted an irreversible and dose dependent decrease in heart rate, showing a complete failure after 30 min recording (p < 0.001, n ≥ 6). In addition, RSPS into nerve-muscle preparations induced a dose-dependent neuromuscular blockade, reaching a total blockage at 70 min at the highest dose applied (p < 0.001, n ≥ 6). The effect of RSPS on spontaneous sensorial action potentials was characterized by an increase in the number of spikes 61% (p < 0.01). Meanwhile, there was 42% decrease in the mean area of those potentials (p < 0.05, n ≥ 6). The results obtained here highlight the potential insecticidal relevance of RSPS and its potential biotechnological application.

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