Cardiac contractility modulation by electric currents applied during the refractory period

2002 ◽  
Vol 282 (5) ◽  
pp. H1642-H1647 ◽  
Author(s):  
Satoshi Mohri ◽  
Kun-Lun He ◽  
Marc Dickstein ◽  
Yuval Mika ◽  
Juichiro Shimizu ◽  
...  
Keyword(s):  
Refractory Period ◽  
Cardiac Contractility ◽  
Total Duration ◽  
Peripheral Resistance ◽  
Systolic Pressure ◽  
Segment Length ◽  
Electric Currents ◽  
Inotropic Effects

Inotropic effects of electric currents applied during the refractory period have been reported in cardiac muscle in vitro using voltage-clamp techniques. We investigated how electric currents modulate cardiac contractility in normal canine hearts in vivo. Six dogs were instrumented to measure regional segment length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac contractility modulating (CCM) electric currents (biphasic square pulses, amplitude ±20 mA, total duration 30 ms) were delivered during the refractory period between pairs of electrodes placed on anterior and posterior walls. CCM significantly increased index of global contractility ( E es) from 5.9 ± 2.9 to 8.3 ± 4.6 mmHg/ml with anterior CCM, from 5.3 ± 1.8 to 8.9 ± 4.0 mmHg/ml with posterior CCM, and from 6.1 ± 2.6 to 11.0 ± 7.0 mmHg/ml with combined CCM ( P < 0.01, no significant change in volume axis intercept). End-systolic pressure-segment length relations showed contractility enhancement near CCM delivery sites, but not remotely. Relaxation was not influenced. CCM increased mean aortic pressure, but did not change peripheral resistance. Locally applied electrical currents enhanced global cardiac contractility via regional changes in myocardial contractility without impairing relaxation in situ.

Abstract P224: β-arrestin2 Stimulates SERCA2a SUMOylation and Activity in Cardiac Myocytes to Promote Contractility

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Katie A McCrink ◽  
Jennifer Maning ◽  
Ava Brill ◽  
Angela Vu ◽  
Walter J Koch ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Cardiac Contractility ◽  
Adapter Proteins ◽  
Inotropic Effects ◽  
Signal Transducers ◽  
Adenoviral Gene Transfer ◽  
Plasmic Reticulum ◽  
New Treatments

Background: Heart failure (HF) is the most lethal disease worldwide and new treatments are needed. The β 1 -adrenergic receptor (AR) mediates the positive inotropy of catecholamines, partly via Sarco(Endo)plasmic Reticulum Ca 2+ -ATPase (SERCA)-2a activation. Agonist-activated β 1 ARs, however, are desensitized/downregulated in human HF due to the actions of the βarrestins (βarrestin1 and 2). βarrestins are GPCR adapter proteins and signal transducers. βarrestin1 is by far the predominant isoform in the heart and reduces contractility by desensitizing the β 1 AR, whereas βarrestin2 is expressed at negligible levels and is beneficial post-myocardial infarction (MI), as it combats inflammation and apoptosis. Herein, we sought to investigate whether cardiac βarrestin2 exerts any inotropic effects. Methods: We used βarrestin knockout (KO) mouse hearts and also performed intra-cardiac adenoviral gene transfer of βarrestin2 (Adβarrestin2) in post-MI mice in vivo. For mechanistic signaling studies we used the cardiomyocyte cell line H9c2. Results: SERCA2a SUMO (small ubiquitin-like modifier)ylation and activity and, consequently, cardiac contractility were increased in βarrestin1 KO`s vs. WT`s post-MI. The opposite was true for βarrestin2 KO`s post-MI. Additionally, βarrestin2, but not βarrestin1, was found to directly bind SERCA2a and induce its SUMOylation and activation in mouse hearts in vivo, as well as in cardiomyocytes in vitro acutely in response to β 1 AR stimulation. Interestingly, βarrestin2 did not affect the classic β 1 AR cAMP-dependent pro-contractile signaling pathway in cardiomyocytes, again contrary to βarrestin1. Importantly, and consistent with these findings, Adβarrestin2 gene transfer in post-MI mouse hearts in vivo resulted in enhanced cardiac function (post-MI ejection fraction of Adβarrestin2 vs. control (AdGFP) mice: 40.3 + 1.3% vs. 23.1 + 1.2%, respectively, p<0.05, n=5). Conclusions: Cardiac β 1 AR-activated βarrestin2, but not βarrestin1, promotes SERCA2a SUMOylation and activity, increasing cardiac contractility. Given also its anti-inflammatory and anti-apoptotic effects post-MI, cardiac-specific βarrestin2 gene transfer may be a novel and safe inotropic therapy for both acute and chronic HF.

Effect of human urotensin-II infusion on hemodynamics and cardiac function

2003 ◽  
Vol 81 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Ghada S Hassan ◽  
Fazila Chouiali ◽  
Takayuki Saito ◽  
Fu Hu ◽  
Stephen A Douglas ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Urotensin Ii ◽  
Ventricular Systolic Pressure ◽  
Wide Range ◽  
Dose Dependent Decrease

Recent studies have shown that the vasoactive peptide urotensin-II (U-II) exerts a wide range of action on the cardiovascular system of various species. In the present study, we determined the in vivo effects of U-II on basal hemodynamics and cardiac function in the anesthetized intact rat. Intravenous bolus injection of human U-II resulted in a dose-dependent decrease in mean arterial pressure and left ventricular systolic pressure. Cardiac contractility represented by ±dP/dt was decreased after injection of U-II. However, there was no significant change in heart rate or diastolic pressure. The present study suggests that upregulation of myocardial U-II may contribute to impaired myocardial function in disease conditions such as congestive heart failure.Key words: urotensin-II, rat, infusion, heart.

Inotropic effects of ejection are myocardial properties

1994 ◽  
Vol 266 (3) ◽  
pp. H1202-H1213 ◽  
Author(s):  
P. P. De Tombe ◽  
W. C. Little
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular ◽  
Negative Effects ◽  
Inotropic Effects ◽  
Contraction Duration ◽  
Loading System ◽  
Positive Effect ◽  
Isolated Rat

Recent studies in isolated and in vivo canine hearts have suggested that the left ventricular end-systolic pressure (LVPes) of ejecting beats is the net result of a balance between positive and negative effects of ejection. At present, it is unknown whether these ejection effects are merely a ventricular chamber property or represent a fundamental myocardial property. Accordingly, we examined the effects of ejection in eight isolated rat cardiac trabeculae at the sarcomere level. We approximated in situ sarcomere shortening patterns using an iterative computer loading system. Six isovolumic contractions were compared with four ejecting contractions. The superfusing solution contained either 0.7 mM Ca2+ or 0.65 mM Sr2+ plus 0.15 mM Ca2+. With Ca2+, simulated LVPes ("LVP"es) of ejecting contractions was significantly lower than isovolumic "LVP"es (-5.3 +/- 5.6%), whereas with Sr2+, ejecting "LVP"es was significantly higher than isovolumic "LVP"es (+4.5 +/- 7.5%). Contraction duration and time to end systole were markedly prolonged in ejecting vs. isovolumic contractions with either Ca2+ or Sr2+. As a consequence, comparison of simulated LVP between ejecting and isovolumic beats throughout the contraction, i.e., at the same simulated LVV and time, revealed only a positive effect of ejection with either Ca2+ (+18.8 +/- 5.5%) or Sr2+ (+23.4 +/-9.3%). We conclude that both positive and negative effects of ejection are basic myocardial properties.

In vivo characterization of vasocontractile activities in erythrocytes

1983 ◽  
Vol 58 (3) ◽  
pp. 356-361 ◽  
Author(s):  
Michael P. McIlhany ◽  
Lydia M. Johns ◽  
Thomas Leipzig ◽  
Nicholas J. Patronas ◽  
Frederick D. Brown ◽  
...  
Keyword(s):  
Vascular Resistance ◽  
Peripheral Resistance ◽  
Content Type ◽  
Control Value ◽  
Arterial Blood ◽  
Anesthetized Dogs ◽  
Chronic Cerebral Vasospasm ◽  
In Vivo Characterization

✓ Partially purified protein from washed and artificially hemolyzed erythrocytes, known to cause significant contractions of isolated canine cerebral vessels in vitro, was injected into the cisterna magna of intact anesthetized dogs. Cerebral blood flow, measured by the xenon-133 washout technique, decreased from a control value of 49.5 ± 1.17 ml/100 gm/min to an experimental value of 34.1 ± 1.65 ml/100 gm/min at 2 hours. Cerebral vascular resistance rose from a control value of 2.05 ± 0.17 PRU (peripheral resistance units) to an experimental value of 2.91 ± 0.25 PRU at 2 hours. Mean arterial blood pressure, heart rate, intracranial pressure, and cerebral perfusion pressure remained stable. Cardiac output also fell significantly (in 2-hour control animals it was 2.89 ± 0.37 liter/min, and in 2-hour experimental animals 1.43 ± 0.13 liter/min) and peripheral vascular resistance rose. These changes were evident by 10 minutes after the cisternal injection of the hemolysate protein, and remained for the duration of the 2-hour monitoring period. Serial vertebrobasilar angiograms demonstrated marked narrowing of the intracranial basilar artery when compared to control values. The narrowing persisted for several days in most animals, and tended to increase with time. Relaxation occurred by the 10th through the 14th day. The authors conclude that this experimental preparation may be a useful model for both in vitro and in vivo investigation of chronic cerebral vasospasm.

Vascular peripheral resistance and compliance in the lobster Homarus americanus

1997 ◽  
Vol 200 (3) ◽  
pp. 477-485 ◽  
Author(s):  
J Wilkens ◽  
G Davidson ◽  
M Cavey
Keyword(s):  
Striated Muscle ◽  
Peripheral Resistance ◽  
Systolic Pressure ◽  
Body Part ◽  
Homarus Americanus ◽  
Arterial System ◽  
Flow Rates ◽  
Flow Through ◽  
Lateral Walls

The peripheral resistance to flow through each arterial bed (in actuality, the entire pathway from the heart back to the pericardial sinus) and the mechanical properties of the seven arteries leaving the lobster heart are measured and compared. Resistance is inversely proportional to artery radius and, for each pathway, the resistance falls non-linearly as flow rate increases. The resistance of the hepatic arterial system is lower than that predicted on the basis of its radius. Body-part posture and movement may affect the resistance to perfusion of that region. The total vascular resistance placed on the heart when each artery is perfused at a rate typical of in vivo flow rates is approximately 1.93 kPa s ml-1. All vessels exhibit adluminal layers of fibrils and are relatively compliant at pressures at or below heart systolic pressure. Arteries become stiffer at pressures greater than peak systolic pressure and at radii greater than twice the unpressurized radius. The dorsal abdominal artery possesses striated muscle in the lateral walls. This artery remains compliant over the entire range of hemolymph pressures expected in lobsters. These trends are illustrated when the incremental modulus of elasticity is compared among arteries. All arteries should function as Windkessels to damp the pulsatile pressures and flows generated by the heart. The dorsal abdominal artery may also actively regulate its flow.

Distinction of NPY receptors in vitro and in vivo. II. Differential effects of NPY and NPY-(18-36)

1990 ◽  
Vol 259 (1) ◽  
pp. H174-H180 ◽  
Author(s):  
N. A. Scott ◽  
M. C. Michel ◽  
J. H. Boublik ◽  
J. E. Rivier ◽  
S. Motomura ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Receptor Subtypes ◽  
Base Line ◽  
Hemodynamic Effects ◽  
Vascular Effects ◽  
Inotropic Effects ◽  
Npy Receptor ◽  
Negative Inotropic Effects

We have studied the hemodynamic effects of neuropeptide Y (NPY) and its COOH-terminal fragment NPY-(18–36) in conscious rats. Intra-arterial injection of NPY rapidly elevated systemic vascular resistance (SVR), which remained high for greater than 30 min. Cardiac output (CO) decreased, and it remained low for greater than 30 min. Accordingly, blood pressure rose only transiently and returned to base-line values within 5 min. The reduction of CO could be attributed to a decreased stroke volume with an only marginal reduction of heart rate. Thus a direct cardiodepressive effect of NPY rather than baroreflex activation appears to be the major cause of the reduced CO. In vitro experiments excluded the possibility that NPY has direct negative inotropic effects and suggest that its cardiodepressive action is caused by coronary vasoconstriction or by presynaptic inhibition of norepinephrine release. Intra-arterial injections of NPY-(18-36) caused different hemodynamic effects. NPY-(18–36) decreased CO in a manner similar to that seen with NPY but initially did not elevate SVR, resulting overall in a reduced blood pressure. Only later, when blood pressure was reduced, was an elevation of SVR observed, which could be associated with increased plasma levels of catecholamines, angiotensin II, vasopressin, and NPY. Thus NPY-(18–36) mimics the cardiac effects of NPY but does not elicit its vascular effects. As NPY-(18–36) discriminates between NPY receptor subtypes in vitro, we conclude that the cardiac and vascular effects of NPY are mediated by distinct receptor subtypes.

Developmental changes in cardiac contractility in fetal and postnatal sheep: in vitro and in vivo

1984 ◽  
Vol 247 (3) ◽  
pp. H371-H379 ◽  
Author(s):  
P. A. Anderson ◽  
K. L. Glick ◽  
A. Manring ◽  
C. Crenshaw
Keyword(s):  
Maximum Rate ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Developmental Changes ◽  
Common Mechanism ◽  
Postextrasystolic Potentiation ◽  
Maximum Rate Of Rise

Developmental changes in contractility were sought in the fetal and postnatal sheep heart by using postextrasystolic potentiation and force, pressure, and wall-motion measures. Two different preparations were used, isolated myocardium and the chronically instrumented lamb. In the isolated muscle, the following increased significantly with age: force of contraction, the maximum rate of rise of force, and postextrasystolic potentiation. In the intact heart prior to birth [period of study, 20 +/- 4 (SD) days] heart rate (HR) fell significantly, and the following increased significantly: postextrasystolic potentiation [measured with the maximum rate of rise of left ventricular (LV) pressure (Pmax)], LV peak systolic pressure (LVP), end-diastolic dimension (EDD), end-systolic dimension (ESD), and aortic diastolic pressure. After birth, LVP, Pmax, HR, LVEDP, EDD, and ESD increased and postextrasystolic potentiation fell. The latter fall was not found in vitro and probably demonstrates a transient change in contractility, related to hormonal or neural stimulation. Over the subsequent postnatal days (6-122 days), HR fell while potentiation, EDD, and ESD increased significantly. Both in vitro and in vivo, the overall increase in postextrasystolic potentiation demonstrates a similar long-term change in contractility. The similarity of this change to that induced by mild hypertrophy suggests that development and mild hypertrophy alter myocardial contractility through a common mechanism.

Ligustilide Reduces Phenylephrine Induced-Aortic Tension In Vitro but has No Effect on Systolic Pressure in Spontaneously Hypertensive Rats

2007 ◽  
Vol 35 (03) ◽  
pp. 487-496 ◽  
Author(s):  
Jun-Rong Du ◽  
Yan Yu ◽  
Yao Yao ◽  
Bo Bai ◽  
Xu Zong ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Essential Oil ◽  
Systolic Blood Pressure ◽  
Systolic Pressure ◽  
Reduce Blood Pressure ◽  
Shr Rats ◽  
Spontaneously Hypertensive ◽  
Long Time

Radix Angelica sinensis, known as Danggui in Chinese, has been used to treat cardiovascular diseases in traditional Chinese medicine for a long time. Experimental evidence showed that the essential oil of Danggui could reduce blood pressure in rabbits, cats or hypertensive dogs when given intravenously. In this study, we investigated the effects of Z-ligustilide, the main lipophilic component of the essential oil of Danggui on aortic tension induced by phenylephrine, an alpha-adrenergic agonist, in vitro and the systolic blood pressure in SHR rats. We demonstrated for the first time that ligustilide can significantly reduce the phenylephrine-induced aortic tension in vitro with IC50 about 64 μg/ml, but has no in vivo effect on systolic blood pressure in SHR rats when administrated orally. The data on transport of ligustilide across Caco-2 monolayer suggested an efficient intestinal absorption of ligustilide in vivo, implying that the non-effectiveness of ligustilide in vivo is not due to the poor absorption in the gastrointestinal tract. Further studies on whether ligustilide is one of the main anti-hypertensive components of the essential oil are needed.

Direct effects of acute hypoxia on the reactivity of peripheral arteries of the chicken embryo

2002 ◽  
Vol 283 (2) ◽  
pp. R331-R338 ◽  
Author(s):  
K. Ruijtenbeek ◽  
C. G. A. Kessels ◽  
E. Villamor ◽  
C. E. Blanco ◽  
J. G. R. De Mey
Keyword(s):  
Chicken Embryo ◽  
Acute Hypoxia ◽  
Peripheral Resistance ◽  
Cardiovascular Responses ◽  
Direct Effects ◽  
No Donor ◽  
Femoral Arteries ◽  
Contraction And Relaxation

In the chicken embryo, acute hypoxemia results in cardiovascular responses, including an increased peripheral resistance. We investigated whether local direct effects of decreased oxygen tension might participate in the arterial response to hypoxemia in the chicken embryo. Femoral arteries of chicken embryos were isolated at 0.9 of incubation time, and the effects of acute hypoxia on contraction and relaxation were determined in vitro. While hypoxia reduced contraction induced by high K+ to a small extent (−21.8 ± 5.7%), contractile responses to exogenous norepinephrine (NE) were markedly reduced (−51.1 ± 3.2%) in 80% of the arterial segments. This effect of hypoxia was not altered by removal of the endothelium, inhibition of NO synthase or cyclooxygenase, or by depolarization plus Ca2+ channel blockade. When arteries were simultaneously exposed to NE and ACh, hypoxia resulted in contraction (+49.8 ± 9.3%). Also, relaxing responses to ACh were abolished during acute hypoxia, while the vessels became more sensitive to the relaxing effect of the NO donor sodium nitroprusside (pD2: 5.81 ± 0.21 vs. 5.31 ± 0.27). Thus, in chicken embryo femoral arteries, acute hypoxia blunts agonist-induced contraction of the smooth muscle and inhibits stimulated endothelium-derived relaxation factor release. The consequences of this for in vivo fetal hemodynamics during acute hypoxemia depend on the balance between vasomotor influences of circulating catecholamines and those of the endothelium.

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