Cardiac nicotinic receptors show β-subunit dependent compensatory changes

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.

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

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.

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

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.

scholarly journals Beat-to-beat modulation of heart rate is coupled to coronary perfusion pressure in the isolated heart

1999 ◽  
Vol 86 (2) ◽  
pp. 694-700 ◽  
Author(s):  
David P. Slovut ◽  
John C. Wenstrom ◽  
Richard B. Moeckel ◽  
Christopher T. Salerno ◽  
Soon J. Park ◽  
...  
Keyword(s):  
Heart Rate ◽  
Perfusion Pressure ◽  
Isolated Heart ◽  
Sinus Node ◽  
Coronary Perfusion Pressure ◽  
High Dose ◽  
Coronary Perfusion ◽  
Perfused Heart ◽  
Langendorff Preparation ◽  
Heart Preparation

A goal of clinicians caring for heart transplant recipients has been to use heart rate variability as a noninvasive means of diagnosing graft rejection. The determinants of beat-to-beat variability in the surgically denervated heart have yet to be elucidated. We used an isolated, blood buffer-perfused porcine heart preparation to quantitatively assess the relationship between coronary perfusion and sinus node automaticity. Hearts ( n = 9) were suspended in a Langendorff preparation, and heart rate (HR) fluctuations were quantified while perfusion pressure was modulated between 70/50, 80/60, 90/70, and 100/80 mmHg at 0.067 Hz. In 32 of 32 recordings, the cross spectrum of perfusion pressure vs. HR showed the largest peak centered at 0.067 Hz. In eight of nine experiments during nonpulsatile perfusion, HR accelerated as perfusion pressure was increased from 40 to 110 mmHg (mean increase 24.2 ± 3.0 beats/min). HR increased 0.34 beats/min per mmHg increase in perfusion pressure (least squares linear regression y = −25.8 mmHg + 0.34 x; r = 0.88, P < 0.0001). Administration of low- and high-dose nitroglycerin (Ntg) resulted in a modest increase in flow but produced a significant decrease in HR and blunted the response of HR to changes in perfusion pressure (HR increase 0.26 beats ⋅ min−1 ⋅ mmHg−1, r = 0.87, P < 0.0001 after low-dose Ntg; 0.25 beats ⋅ min−1 ⋅ mmHg−1, r = 0.78, P < 0.0001 after high-dose Ntg). These experiments suggest that sinus node discharge in the isolated perfused heart is mechanically coupled to perfusion pressure on a beat-to-beat basis.

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

Development ◽  
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.

A Comparison of Two Exercise Training Programs on Cardiac Responsiveness to β-Stimulation in Obesity

2005 ◽  
Vol 230 (3) ◽  
pp. 180-188 ◽  
Author(s):  
Joan F. Carroll ◽  
Jeremy J. Thaden ◽  
Allison M. Wright
Keyword(s):  
Exercise Training ◽  
Isolated Heart ◽  
Training Volume ◽  
Adrenergic Stimulation ◽  
Isolated Hearts ◽  
Response Data ◽  
New Zealand White Rabbits ◽  
Obese Control ◽  
Developed Pressure ◽  
Post Hoc

We demonstrated previously that exercise training did not restore normal cardiac β-adrenergic responsiveness in obese rabbits. This study tested the hypothesis that an increased training volume was required to attenuate obesity-related reductions in isolated heart responsiveness to isoproterenol. Female New Zealand White rabbits were divided into lean control, lean exercise-trained, obese control, and obese exercise-trained groups. For the exercise-trained groups, total treadmill work over 12 weeks was increased 27% when compared with lean and obese animals trained with lower total training volume. After 12 weeks, Langendorff isolated hearts were used to study developed pressure, +dP/dtmax, and –dP/dtmax responses to isoproterenol (10−9 – 3 × 10−7 M). Concentration-response data were fit to a sigmoidal function using a four-parameter logistic equation. Controls were compared with animals trained under the low– and high–training volume programs using one-way analysis of variance and Tukey's post-hoc test; separate analyses were conducted for lean and obese rabbits. In both lean and obese groups trained under the high–training volume program, EC50 values for +dP/daytmax and –dP/dtmax were higher compared with same-weight controls and animals trained under the low–training volume program, indicating that contractility and relaxation responsiveness to isoproterenol was reduced by the higher training volume. Therefore, these data indicate that increased training volume failed to attenuate obesity-related decrements in isolated heart responsiveness to β-adrenergic stimulation and caused reduced sensitivity to isoproterenol in both lean and obese animals.

Pre-emptive Analgesia for Postoperative Pain Relief in Children – Role of Paracetamol

2009 ◽  
pp. 9-16
Author(s):  
Rubina Yasmin ◽  
AKM Akhtaruzzaman ◽  
Paresh Chandra Sarker ◽  
Neaz Ahmed ◽  
Ranadhir Kumar Kundu ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Postoperative Pain ◽  
Diclofenac Sodium ◽  
Total Duration ◽  
Pain Scale ◽  
Prospective Clinical Study ◽  
High Dose ◽  
Induction Of Anaesthesia

This prospective clinical study was carried out in the Dept. of Anaesthesia, Analgesia and Intensive Care Medicine, BSMMU, Dhaka, during the period of May 2003 to July 2003. The study was done to emphasize the importance of giving analgesics preemptively instead of waiting for the child to complain of pain and to produce smooth recovery after surgery by decreasing immediate postoperative pain in children by a simple, safe acceptable drug. The children scheduled for tonsillectomy under general anaesthesia were recruited in this study. The analgesic efficiency of rectal paracetamol in two doses, 25 mg/kg bodywt.(Gr-P25) and 50 mg/kg. bodywt. (Gr-P50) were compared with Diclofenac Sodium suppository 1mg/ kg body weight (Gr-D) given half an hour before induction of anaesthesia. Pain scoring was done by TPPPS (Toddler Pre-schooler postoperative pain scale). Heart rate and blood pressure were stable in Gr-P50 and Gr-D. Time of first demand of analgesic was delayed in Gr-P50 and Gr-D. Total paracetamol consumption in 24 hours was less in Gr-P50(181±14.25) and Gr-D (212±25) than Gr-P25(318± 26.39). Total duration of analgesia in Gr- P50 (657±9.94) mins. and in Gr- D(502±10.63) mins. and in Gr-P25(288±23.17) mins. Pre-emptive high dose rectal paracetamol appears to be more effective than diclofenac sodium suppository for postoperative analgesia in children undergoing tonsillectomy. Journal of BSA, Vol. 18, No. 1 & 2, 2005 p.9-16

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