Di-4-ANEPPS Modulates Electrical Activity and Progress of Myocardial Ischemia in Rabbit Isolated Heart

Frontiers in Physiology ◽

10.3389/fphys.2021.667065 ◽

2021 ◽

Vol 12 ◽

Author(s):

Marina Ronzhina ◽

Tibor Stracina ◽

Lubica Lacinova ◽

Katarina Ondacova ◽

Michaela Pavlovicova ◽

...

Keyword(s):

Heart Rate ◽

Myocardial Ischemia ◽

Electrical Activity ◽

Isolated Heart ◽

Sodium Current ◽

Statistical Tests ◽

Significant Inhibition ◽

Operating Characteristics ◽

Impulse Conduction ◽

Isolated Hearts

AimsAlthough 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 ResultsStudy 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.ConclusionOur 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.

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Cardiac nicotinic receptors show β-subunit dependent compensatory changes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00995.2020 ◽

2021 ◽

Author(s):

Katarina Targosova ◽

Matej Kucera ◽

Zuzana Kilianova ◽

Lubica Slobodova ◽

Kristina Szmicsekova ◽

...

Keyword(s):

Heart Rate ◽

Muscarinic Receptors ◽

Nicotinic Receptors ◽

Isolated Heart ◽

High Dose ◽

Β Subunit ◽

Adrenergic Stimulation ◽

Relative Expression ◽

Isolated Hearts ◽

Heart Functions

Nicotinic receptors (NR) play an important role in the cholinergic regulation of heart functions, and converging evidence suggests a diverse repertoire of NR subunits in the heart. A recent hypothesis about the plasticity of β NR subunits suggests that β2 and β4 subunits may substitute for each other. In our study, we assessed the hypothetical β subunit interchangeability in the heart at the level of mRNA. Using two mutant mice strains lacking β2 or β4 NR subunits, we examined the relative expression of NR subunits and other key cholinergic molecules. We investigated the physiology of isolated hearts perfused by Langendorff's method at basal conditions and after cholinergic and/or adrenergic stimulation. Lack of β2 NR subunit was accompanied with decreased relative expression of β4 and α3 subunits. No other cholinergic changes were observed at the level of mRNA, except for increased M3 and decreased M4 muscarinic receptors. Isolated hearts lacking β2 NR subunit showed different dynamics in heart rate response to indirect cholinergic stimulation. In hearts lacking β4 NR subunit, increased levels of β2 subunits were observed together with decreased mRNA for acetylcholine-synthetizing enzyme and M1 and M4 muscarinic receptors. Changes in the expression levels in β4-/- hearts were associated with increased basal heart rate and impaired response to a high dose of acetylcholine upon adrenergic stimulation. In support of the proposed plasticity of cardiac NRs, our results confirmed subunit-dependent compensatory changes to missing cardiac NRs subunits with consequences on isolated heart physiology.

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RE-EVALUATION OF THE STRETCH SENSITIVITY HYPOTHESIS OF CRUSTACEAN HEARTS: HYPOXIA, NOT LACK OF STRETCH, CAUSES REDUCTION IN HEART RATE OF ISOLATED HEARTS

Journal of Experimental Biology ◽

10.1242/jeb.176.1.223 ◽

1993 ◽

Vol 176 (1) ◽

pp. 223-232

Author(s):

J. L. Wilkens

Keyword(s):

Heart Rate ◽

Isolated Heart ◽

Carcinus Maenas ◽

Three Dimensional ◽

Decapod Crustacean ◽

Diastolic Filling ◽

Elastic Recoil ◽

Isolated Hearts

Decapod crustacean hearts are suspended by a three-dimensional array of alary ligaments. These ligaments are stretched during systole; diastolic filling via the ostia occurs as the ventricle is stretched by ligamental elastic recoil. There is no direct venous return to the hearts in these animals. In the present study, an isolated heart preparation with intact ligaments, hereafter called in situ, was used to evaluate the effects of artificially induced stretch on heart rate. Strongly beating in situ neurogenic hearts of the crab Carcinus maenas responded to direct perfusion of the ventricle with oxygenated saline and the attendant augmentation of natural stretch with a small increase in heart rate (fh); however, fh was well maintained for up to 15 min after eliminating stretch by cutting the alary ligaments. In contrast to crabs, high rates of artificial perfusion usually depressed fh in crayfish hearts. Crab heart rate falls during hypoxia and this is readily reversed by even low rates of perfusion with oxygenated saline. It is concluded that the gradual decline in fh of totally isolated in vitro hearts arises from the deepening intraventricular hypoxia experienced by the cardiac ganglion.

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Evidence that blood pressure controls heart rate in the chick embryo prior to neural control

Development ◽

10.1242/dev.36.3.685 ◽

1976 ◽

Vol 36 (3) ◽

pp. 685-695

Author(s):

G. M. Rajala ◽

J. H. Kalbfleisch ◽

S. Kaplan

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Chick Embryo ◽

Heart Muscle ◽

Neural Control ◽

Isolated Heart ◽

Fluid Pressure ◽

Chick Embryos ◽

Isolated Hearts ◽

Increased Pressure

Blood pressure increases will increase heart rate in intact chick embryos, prior to tne development of neural control. Similarly, in surgically isolated hearts, increases in intraventricular fluid pressure will increase the rate of beat. However, fluid pressure applied equally to both interior and exterior surfaces of the isolated heart does not result in increased heart rate. Therefore, we conclude that the increased pressure stretches the heart muscle and that this stretch stimulates the increased heart rate. While heart rate is clearly influenced by blood pressure, the reverse is not true. Propranolol reduces the heart rate to about half normal in intact embryos but does not significantly alter the blood pressure.

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348 Effect of propranolol on heart rate and arrhythmias in freely moving mice and isolated hearts of deltaKPQ-SCN5A LQT3 mice

EP Europace ◽

10.1016/s1099-5129(05)80208-9 ◽

2005 ◽

Vol 7 ◽

pp. 71-71

Keyword(s):

Heart Rate ◽

Isolated Hearts ◽

Freely Moving

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Heart rate variability, autonomic regulation and myocardial ischemia

International Journal of Cardiology ◽

10.1016/j.ijcard.2020.03.012 ◽

2020 ◽

Vol 312 ◽

pp. 22-23

Author(s):

Daniela Lucini ◽

Massimo Pagani

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Myocardial Ischemia ◽

Autonomic Regulation

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Relation between heart rate and QT interval in exercise-induced myocardial ischemia

The American Journal of Cardiology ◽

10.1016/0002-9149(85)90770-2 ◽

1985 ◽

Vol 56 (13) ◽

pp. 861-862 ◽

Cited By ~ 25

Author(s):

Massimo Romano ◽

Teresa Di Maro ◽

Giovanni Carella ◽

Maria Rosaria Cotecchia ◽

Giuseppe Ferro ◽

...

Keyword(s):

Heart Rate ◽

Myocardial Ischemia ◽

Qt Interval ◽

Exercise Induced

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Abstract 150: Impact of Epinephrine on ECG Changes During Resuscitation From Out-of-Hospital Cardiac Arrest With Initial Pulseless Electrical Activity

Circulation ◽

10.1161/circ.138.suppl_2.150 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Gunnar W Skjeflo ◽

Eirik Skogvoll ◽

Jan Pål Loennechen ◽

Theresa M Olasveengen ◽

Lars Wik ◽

...

Keyword(s):

Heart Rate ◽

Cardiac Arrest ◽

Electrical Activity ◽

Multivariate Regression ◽

Life Support ◽

Controlled Trial ◽

Pulseless Electrical Activity ◽

Qrs Complex ◽

Epinephrine Administration ◽

Hospital Cardiac Arrest

Introduction: Presence of electrocardiographic rhythm, documented by the electrocardiogram (ECG), in the absence of palpable pulses defines pulseless electrical activity (PEA). Our aims were to examine the development of ECG characteristics during advanced life support (ALS) from Out-of-Hospital-Cardiac-Arrest (OHCA) with initial PEA, and to explore the effects of epinephrine on these characteristics. Methods: Patients with OHCA and initial PEA in a randomized controlled trial of ALS with or without intravenous access and medications were included. QRS widths and heart-rates were measured in recorded ECG signals during pauses in compressions. Statistical analysis was carried out by multivariate regression (MANOVA). Results: Defibrillator recordings from 170 episodes of cardiac arrest were analyzed, 4840 combined measurements of QRS complex width and heart rate were made. By the multivariate regression model both whether epinephrine was administered and whether return of spontaneous circulation (ROSC) was obtained were significantly associated with changes in QRS width and heart rate. For both control and epinephrine groups, ROSC was preceded by decreasing QRS width and increasing rate, but in the epinephrine group an increase in rate without a decrease in QRS width was associated with poor outcome (fig). Conclusion: The QRS complex characteristics are affected by epinephrine administration during ALS, but still yields valuable prognostic information.

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Effects of water ingestion on gastric electrical activity and heart-rate variability in healthy human subjects

Journal of the Autonomic Nervous System ◽

10.1016/0165-1838(95)00110-7 ◽

1996 ◽

Vol 58 (1-2) ◽

pp. 44-50 ◽

Cited By ~ 16

Author(s):

Michio Watanabe ◽

Yutaka Shimada ◽

Shinya Sakai ◽

Naotoshi Shibahara ◽

Harumi Matsuda ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Electrical Activity ◽

Human Subjects ◽

Gastric Electrical Activity ◽

Healthy Human ◽

Water Ingestion ◽

Healthy Human Subjects

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Small, Oral Dose of Clonidine Reduces the Incidence of Intraoperative Myocardial Ischemia in Patients Having Vascular Surgery

Anesthesiology ◽

10.1097/00000542-199610000-00004 ◽

1996 ◽

Vol 85 (4) ◽

pp. 706-712 ◽

Cited By ~ 124

Author(s):

Klaus-Dieter Stuhmeier ◽

Bernd Mainzer ◽

Jochen Cierpka ◽

Wilhelm Sandmann ◽

Jorg Tarnow

Keyword(s):

Myocardial Infarction ◽

Blood Pressure ◽

Coronary Artery Disease ◽

Heart Rate ◽

Coronary Artery ◽

Myocardial Ischemia ◽

Oral Dose ◽

Fluid Volume ◽

Arterial Blood ◽

Artery Disease

Background Most new perioperative myocardial ischemic episodes occur in the absence of hypertension or tachycardia. The ability of alpha 2-adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients with coronary artery disease by increasing the myocardial oxygen supply and -demand ratio. Methods A randomized double-blind study design was used in 297 patients scheduled to have elective vascular surgical procedures to evaluate the effects of 2 micrograms/kg-1 oral clonidine (n = 145) or placebo (n = 152) on the incidence of perioperative myocardial ischemic episodes, myocardial infarction, and cardiac death. Continuous real-time S-T segment trend analysis (lead II and V5) was performed during anesthesia and surgery and correlated with arterial blood pressure and heart rate before and during ischemic events. Dose requirements for vasoactive and antiischemic drugs to control blood pressure and heart rate as well as episodes of myocardial ischemia (i.e., catecholamines, beta-adrenoceptor antagonists, nitrates, and systemic vasodilators) and fluid volume load were recorded. Results Administration of clonidine reduced the incidence of perioperative myocardial ischemic episodes from 39% (59 of 152) to 24% (35 of 145) (P < 0.01). Hemodynamic patterns, percentage of ischemic time, and the number of ischemic episodes per patient did not differ. Nonfatal myocardial infarction developed after operation in four patients receiving placebo compared with none receiving clonidine (day 2 to 21; P = 0.07). The incidence of fatal cardiac events (1 vs. 2) was not different. Dose requirements for vasoactive and antiischemic drugs did not differ between the groups, but the amount of presurgical fluid volume was slightly greater in patients receiving clonidine (951 +/- 388 vs. 867 +/- 381 ml; P < 0.03). Conclusion A small oral dose of clonidine, given prophylactically, can reduce the incidence of perioperative myocardial ischemic episodes without affecting hemodynamic stability in patients with suspected or documented coronary artery disease.

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