Cardiac electrophysiological variables in blood-perfused and buffer-perfused, isolated, working rabbit heart

Effects of crystalloid buffer and blood-buffer perfusates on cardiac electrophysiological parameters were compared in four groups of isolated, working rabbit hearts. Hearts were perfused with Krebs-Henseleit buffer or blood plus Krebs-Henseleit buffer (10% hematocrit) over a range of left ventricular afterload (30-100 cmH2O) and cardiac outputs (30-180 ml/min). Left ventricular monophasic action potential duration (APD) was significantly shorter at low afterload and high cardiac output in buffer-perfused (114 +/- 35 ms) compared with blood-perfused hearts (177 +/- 23 ms, P < 0.001). APD shortened in blood-perfused hearts after an increase in afterload to 100 cmH2O (P < 0.05), and APD was similar in blood-perfused (151 +/- 19 ms) compared with buffer-perfused hearts (142 +/- 24 ms, P = NS). Ventricular effective refractory period (VERP) was significantly shorter at low afterload in buffer-perfused (154 +/- 32 ms) compared with blood-perfused hearts (227 +/- 17 ms, P < 0.001). VERP shortened in blood-perfused hearts after an increase in afterload to 100 cmH2O (P < 0.05) and was similar in blood-perfused (166 +/- 26 ms) compared with buffer-perfused hearts (151 +/- 37 ms, P = NS). Determination of VERP was associated with induction of ventricular fibrillation in 10 of 15 buffer-perfused hearts, whereas ventricular fibrillation was not observed in blood-perfused hearts (P < 0.001). Thus significant differences in ventricular repolarization and cardiac hemodynamics are observed in working rabbit hearts perfused with a blood-buffer perfusate compared with a crystalloid buffer. Blood-perfused working hearts are electrophysiologically more stable.

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Mechanoelectrical feedback effects of altering preload, afterload, and ventricular shortening

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.264.2.h423 ◽

1993 ◽

Vol 264 (2) ◽

pp. H423-H432 ◽

Cited By ~ 4

Author(s):

D. E. Hansen

Keyword(s):

Stroke Volume ◽

Action Potential ◽

Left Ventricular ◽

Ventricular Ejection ◽

Monophasic Action Potential ◽

Canine Heart ◽

Windkessel Model ◽

Pump System ◽

Ventricular Ejection Fraction ◽

Ventricular Afterload

Electrophysiological consequences of altering ventricular load (mechanoelectrical feedback) were characterized in an isolated canine heart preparation. A computerized servo pump system controlled left ventricular volume and allowed ventricular ejection against a simulated arterial load (3-element Windkessel model). In 12 ventricles, end-diastolic volume (Ved) was held constant (end-diastolic pressure 6-12 mmHg) as arterial resistance (R) was varied (0.5-12 mmHg.s.ml-1), but afterload-dependent changes in the monophasic action potential (MAP) were not observed despite a large stroke volume effect. In contrast, when R was held constant in eight ventricles while Ved was increased from 20 to 40 ml, the plateau phase of the MAP was abbreviated, the terminal portion of phase 3 repolarization was delayed, and MAP duration measured at 20, 70, and 90% repolarization decreased (P < 0.05). In six ventricles, immediate transitions from isovolumic to ejecting mode at constant Ved did not alter MAP duration, but the magnitude of early afterdepolarizations (EADs), observed during isovolumic beats at high Ved, was reduced with resumption of ventricular ejection. As stroke volume of the initial ejecting contraction was increased by stepwise reductions of R, the magnitude of the EADs decreased progressively. Thus altering ventricular afterload does not modulate action potential duration in ventricles subjected to elevated, physiological, or even greatly reduced levels of afterload, whereas diastolic filling to high Ved does. Under conditions that lead to reduced stroke volume and high end-systolic volume, EADs are produced that are virtually abolished when ventricular ejection fraction is normalized.

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Crystalloid and perfluorochemical perfusates in an isolated working rabbit heart preparation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1985.249.2.h285 ◽

1985 ◽

Vol 249 (2) ◽

pp. H285-H292 ◽

Cited By ~ 5

Author(s):

J. M. Chemnitius ◽

W. Burger ◽

R. J. Bing

Keyword(s):

Cardiac Output ◽

Coronary Flow ◽

Systolic Pressure ◽

Pressure Rise ◽

Rabbit Heart ◽

Left Ventricular ◽

Heart Weight ◽

Perfused Heart ◽

Heart Preparation ◽

Perfused Hearts

Krebs-Henseleit buffer (KH) and a perfluorochemical (FC-43) were compared as perfusates in an isolated working rabbit heart preparation. Both perfusates were oxygenated in an identical manner using an infant bubble oxygenator. After 60 min of perfusion, no difference could be detected in the ratio of wet to dry heart weight between KH- and FC-43-perfused hearts (KH, 6.25 +/- 0.3; FC-43, 5.99 +/- 0.20). Left ventricular systolic pressure, maximal rate of left ventricular pressure rise, mean aortic systolic pressure, cardiac output, aortic flow, left ventricular power, and myocardial O2 consumption (MVO2) were significantly higher in FC-43-perfused hearts throughout the time of perfusion. However, there were no differences in resistance to cardiac output and heart rate. In KH- and FC-43-perfused hearts, MVO2 and left ventricular power were closely correlated (KH, r = 0.793; FC-43, r = 0.831). Significantly higher coronary flow of KH-perfused hearts could be attributed to the lower viscosity of KH (1.05 Pa . s) compared with FC-43 (1.91 Pa . s). Increased O2 extraction during KH perfusion could not compensate for low O2-carrying capacity of KH buffer (345 compared with 705 nmol O2 X ml-1 in FC-43 emulsion). A postischemic increase of coronary flow was observed only in FC-43-perfused hearts (28%). These results demonstrate a different response of perfused heart preparations to FC-43 and KH buffer.

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Modulation of arrhythmias by isoproterenol in a rabbit heart model of d-sotalol-induced long Q-T intervals

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.1.h15 ◽

2000 ◽

Vol 279 (1) ◽

pp. H15-H25 ◽

Cited By ~ 6

Author(s):

Joseph F. Spear ◽

E. Neil Moore

Keyword(s):

Rabbit Heart ◽

Left Ventricular ◽

Monophasic Action Potential ◽

Adrenergic Stimulation ◽

Heart Model ◽

Recovery Interval ◽

Potential Map ◽

Recovery Times ◽

Mean Cycle ◽

Temporal Dispersion

Sympathetic influences have been implicated in arrhythmias associated with both congenital and acquired long Q-T intervals. We recorded epicardial electrograms, a left ventricular endocardial monophasic action potential (MAP), and a bipolar electrocardiogram in 23 isolated rabbit hearts. Spontaneous focal arrhythmias appeared within 8–18 min following 92 μM d-sotalol in 15 of 23 hearts. The epicardial activation-recovery interval was shorter at baseline and increased to a significantly greater degree after d-sotalol administration in the hearts that developed focal activity. The standard deviation of the activation-recovery interval of the epicardial sites also increased. With the addition of 0.01 μM isoproterenol, the incidence of focal activity increased, and its mean cycle length was shortened by 7%. Also, myocardial recovery time in the epicardium was shortened to a greater degree than the endocardial MAP duration. It did not alter local epicardial heterogeneity of recovery but did increase the regional dispersion between epicardial recovery times, and the endocardial MAP duration. Therefore, β-adrenergic stimulation in the presence of d-sotalol favors the appearance of arrhythmias by increasing the propensity for closely coupled focal activity and the temporal dispersion of recovery.

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Management of Ventricular Fibrillation during Acute Myocardial Infarction

Methods of Information in Medicine ◽

10.1055/s-0038-1635344 ◽

1984 ◽

Vol 23 (04) ◽

pp. 209-213

Author(s):

B. J. Northover

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Ventricular Fibrillation ◽

Coronary Care Unit ◽

Patient Survival ◽

Left Ventricular ◽

Ventricular Failure ◽

Before And After ◽

Coronary Care ◽

The Creation

SummaryAnalysis of electrocardiograms tape-recorded from patients admitted to hospital with acute myocardial infarction revealed that the pattern of ventricular extrasystolic activity was not significantly different among those who subsequently developed ventricular fibrillation and those who did not. Episodes of ventricular fibrillation occurred predominantly within 4 hours from the start of infarction. Patients were 3 times less likely to survive an episode of ventricular fibrillation if they also had left ventricular failure than if this feature was absent. Management of episodes of ventricular fibrillation was compared in patients before and after the creation of a specially staffed and equipped coronary care unit. The success of electric shock as a treatment for ventricular fibrillation was similar before and after the creation of the coronary care unit. An attempt was made to determine which features in the management of ventricular fibrillation in this and in previously published series were associated with patient survival.

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Effects of genetic background, sex, and age on murine atrial electrophysiology

EP Europace ◽

10.1093/europace/euaa369 ◽

2021 ◽

Author(s):

Julius Obergassel ◽

Molly O’Reilly ◽

Laura C Sommerfeld ◽

S Nashitha Kabir ◽

Christopher O’Shea ◽

...

Keyword(s):

Genetic Background ◽

Monophasic Action Potential ◽

Atrial Arrhythmias ◽

Activation Time ◽

Factors Influencing ◽

Normal Ranges ◽

Atrial Electrophysiology ◽

Cycle Lengths ◽

Perfused Hearts ◽

Atrial Effective Refractory Period

Abstract Aims Genetically altered mice are powerful models to investigate mechanisms of atrial arrhythmias, but normal ranges for murine atrial electrophysiology have not been robustly characterized. Methods and results We analyzed results from 221 electrophysiological (EP) studies in isolated, Langendorff-perfused hearts of wildtype mice (114 female, 107 male) from 2.5 to 17.7 months (mean 7 months) with different genetic backgrounds (C57BL/6, FVB/N, MF1, 129/Sv, Swiss agouti). Left atrial monophasic action potential duration (LA-APD), interatrial activation time (IA-AT), and atrial effective refractory period (ERP) were summarized at different pacing cycle lengths (PCLs). Factors influencing atrial electrophysiology including genetic background, sex, and age were determined. LA-APD70 was 18 ± 0.5 ms, atrial ERP was 27 ± 0.8 ms, and IA-AT was 17 ± 0.5 ms at 100 ms PCL. LA-APD was longer with longer PCL (+17% from 80 to 120 ms PCL for APD70), while IA-AT decreased (−7% from 80 to 120 ms PCL). Female sex was associated with longer ERP (+14% vs. males). Genetic background influenced atrial electrophysiology: LA-APD70 (−20% vs. average) and atrial ERP (−25% vs. average) were shorter in Swiss agouti background compared to others. LA-APD70 (+25% vs. average) and IA-AT (+44% vs. average) were longer in 129/Sv mice. Atrial ERP was longer in FVB/N (+34% vs. average) and in younger experimental groups below 6 months of age. Conclusion This work defines normal ranges for murine atrial EP parameters. Genetic background has a profound effect on these parameters, at least of the magnitude as those of sex and age. These results can inform the experimental design and interpretation of murine atrial electrophysiology.

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Acute effects of a mavacamten-like myosin-inhibitor (MYK-581 in a feline model of obstructed hypertrophic cardiomyopathy: evidence of improved ventricular filling (beyond obstruction reprieve)

European Heart Journal ◽

10.1093/ehjci/ehaa946.3713 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

B.S Ferguson ◽

J.A Stern ◽

M.S Oldach ◽

Y Ueda ◽

E.S Ontiveros ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Acute Treatment ◽

Left Ventricular ◽

Funding Source ◽

Private Company ◽

Cardiac Phenotype ◽

Diastolic Stiffness ◽

Cardiac Hemodynamics ◽

Feline Model ◽

Ventricular Filling

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is a progressive disease characterized by cardiac remodeling, hyperdynamic contraction, and impaired ventricular filling that can lead to dynamic left-ventricular outflow-track (LVOT) obstruction and exertional intolerance. Direct myosin-inhibition with mavacamten can normalize contractility and improve exercise capacity in patients with oHCM, providing sustained symptomatic relief. However, mavacamten can also improve ventricular filling by limiting residual cross-bridges during diastole, and therefore, may offer cardiac benefits beyond obstruction reprieve. This study leveraged a feline model of oHCM, cats with the A31P MYBPC3 variant, to study the acute in vivo effects of MYK-581, a mavacamten surrogate, on cardiac hemodynamics and filling. Methods A31P-homozygous cats with HCM (A31P, n=10) and wild-type healthy controls (CTRL, n=9) were anesthetized and instrumented for invasive pressure-volume (PV) measurements as well as trans-thoracic echocardiographic recording. A subset of cats were assigned to receive either vehicle (VEH, n=7) or MYK-581 (MYK, n=8) with a short IV infusion. Cardiac hemodynamics, function, and geometry were assessed at steady state before and during dobutamine challenges (2.5 μg/kg/min IV). Results A31P cats had thicker ventricular walls (6.4±0.1 vs. 5.2±0.2 mm, P<0.05) and hyperdynamic contraction (FS: 61±4 vs. 50±3%, P<0.05) relative to controls and presented with dynamic LVOT obstruction in 54% of cases. HCM cats had elevated end-diastolic pressures (17±1.4 vs. 9±1.0 mmHg, P<0.05), with prolonged time constants of relaxation (60±4.1 vs. 36±2.4 ms, P<0.05) and elevated end-diastolic stiffness (Eed: 0.44±0.06 vs. 0.25±0.01 mmHg/mL). Acute treatment with MYK-581 alleviated LVOT obstruction (0% vs. 38%), normalized contractility (FS: −7±2%), and increased systolic/diastolic chamber dimensions (e.g., LVIDd: +13±4%) (all P<0.05), while reducing EDP (15±2 to 13±2 mmHg, P<0.05), suggesting acute improvement in ventricular distensibility. Indeed, MYK-581 treatment reduced end-diastolic stiffness (Eed: 0.48±0.11 vs. 0.36±0. 10 mmHg/mL, P<0.05) and normalized trans-mitral motion patterns during filling. Conclusions Bred cats, homozygous for the A31P MYBPC3 variant, presented a cardiac phenotype that models multiple characteristics of the human oHCM phenotype including dynamic LVOT obstruction. Acute treatment with the mavacamten surrogate, MYK-581, not only alleviated hypercontractility and LVOT obstruction, but improved ventricular filling and end-diastolic pressures. Taken together, these pre-clinical observations show potential salutary effects beyond obstruction relief in patients with HCM. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): MyoKardia

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