Ryanodine and left ventricular function in intact dogs: dissociation of force-based and velocity-based indexes

1997 ◽  
Vol 273 (3) ◽  
pp. H1561-H1568 ◽  
Author(s):  
S. D. Prabhu ◽  
M. M. Rozek ◽  
D. R. Murray ◽  
G. L. Freeman
Keyword(s):  
Heart Rate ◽  
Sarcoplasmic Reticulum ◽  
Systolic Pressure ◽  
Specific Inhibitor ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Lv Function ◽  
Stroke Work ◽  
Mean Velocity ◽  
Release Channel

After anesthesia and autonomic blockade, nine dogs chronically instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied before and after the intravenous administration of 4 micrograms/kg ryanodine, a specific inhibitor of the sarcoplasmic reticulum Ca2+ release channel. Ryanodine prolonged LV contraction and relaxation (P < 0.001) without changing heart rate, end-diastolic volume (EDV), or end-systolic pressure. Velocity-dependent mechanical parameters were significantly depressed, including the maximal rate of LV pressure rise (dP/dtmax; P < 0.002), the mean velocity of circumferential fiber shortening (P < 0.002), the slope of the dP/dtmax-EDV relation (P < 0.05), and the time constant of LV relaxation (P < 0.01). In contrast, the slopes of the end-systolic pressure-volume (PES-VES) and stroke work (SW)-EDV relations, both force-based parameters, were increased (P < 0.05) or maintained, respectively. Ryanodine reduced overall LV contractile performance, evidenced by significant rightward shifts of the PES-VES, dP/dtmax-EDV, and SW-EDV relations and reduced SW at constant preload (P < 0.02). Thus, in the closed-chest dog, low-dose ryanodine resulted in 1) generalized slowing of LV mechanical events without changes in heart rate or load, 2) dissociation of velocity-based and force-based measures of LV function, with depression of the former but enhancement or maintenance of the latter, and 3) reduced overall LV inotropic performance. These effects are consistent with ryanodine-induced alterations of the Ca2+ transient and altered sarcoplasmic reticulum Ca2+ availability.

Positive Inotropic and Lusitropic Effects of Triiodothyronine in Conscious Dogs with Pacing-induced Cardiomyopathy 

1997 ◽  
Vol 87 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Iyad N. Jamali ◽  
Paul S. Pagel ◽  
Douglas A. Hettrick ◽  
Dermot Lowe ◽  
Judy R. Kersten ◽  
...  
Keyword(s):  
Heart Rate ◽  
Myocardial Contractility ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Segment Length ◽  
Lv Function ◽  
Baseline Heart Rate ◽  
Stroke Work ◽  
Lv Dysfunction

Background The effects of triiodothyronine (T3) on systemic hemodynamics, myocardial contractility (preload recruitable stroke work slope; Mw), and left ventricular (LV) isovolumic relaxation (time constant; tau) were examined before and after the development of pacing-induced cardiomyopathy in conscious dogs. Methods Dogs (n = 8) were chronically instrumented for measurement of aortic and LV pressure, dP/dtmax, subendocardial segment length, and cardiac output. Dogs received escalating doses (0.2, 2.0, and 20.0 mg/kg, intravenous) of T3 over 5 min at 1-h intervals, and peak hemodynamic effects were recorded 10 min after each dose and 24 h after the final dose. Dogs were then continuously paced at 220-240 beats/min for 21 +/- 2 days. Pacing was temporarily discontinued after the development of severe LV dysfunction, and administration of T3 was repeated. Results T3 produced immediate and sustained (24 h) increases (P &lt; 0.05) in Mw and dP/dtmax in dogs before the initiation of pacing, consistent with a positive inotropic effect. No changes in tau occurred. Rapid ventricular pacing over 3 weeks increased baseline heart rate (sinus rhythm) and LV end-diastolic pressure, decreased mean arterial and LV systolic pressures, and caused LV systolic (decreases in Mw and dP/dtmax) and diastolic (increases in tau) dysfunction. T3 caused immediate and sustained increases in Mw (63 +/- 7 during control to 82 +/- 7 mmHg after the 2 mg/kg dose) and decreases in tau (65 +/- 8 during control to 57 +/- 6 ms after the 20 mg/kg dose), indicating that this hormone enhanced myocardial contractility and shortened LV relaxation, respectively, in the presence of chronic LV dysfunction. In contrast to the findings in dogs with normal LV function, T3 did not affect heart rate and calculated indices of myocardial oxygen consumption and reduced LV end-diastolic pressure (27 +/- 3 during control to 20 +/- 2 mmHg after the 2 mg/kg dose) in cardiomyopathic dogs. Conclusions The findings indicate that T3 produces favorable alterations in hemodynamics and modest positive inotropic and lusitropic effects in conscious dogs with LV dysfunction produced by rapid LV pacing.

Electrophysiological effects of transient aortic occlusion in intact canine heart

1985 ◽  
Vol 249 (5) ◽  
pp. H1017-H1023 ◽  
Author(s):  
D. G. Benditt ◽  
J. M. Kriett ◽  
H. G. Tobler ◽  
C. C. Gornick ◽  
B. L. Detloff ◽  
...  
Keyword(s):  
Systolic Pressure ◽  
Left Ventricular ◽  
Drive Train ◽  
Aortic Occlusion ◽  
Canine Heart ◽  
Stroke Work ◽  
Shortening Velocity ◽  
Mean Velocity ◽  
Transient Aortic Occlusion ◽  
Premature Beats

This study utilized sonomicrometers transmural multipolar electrodes and cardiac electrical stimulation techniques to examine the effect on myocardial electrophysiological characteristics of altering ventricular systolic mechanical properties by transient aortic occlusion. Nine anesthetized open-chest dogs were atrially paced, and timed extrastimuli were inserted during alternate drive-train sequences at right or left ventricular (RV, LV) epicardial sites to measure ventricular effective refractory period (ERP). Sonomicrometer measurements of LV systolic mechanical parameters and both RV and LV electrophysiological findings were determined prior to and during periods of transient aortic occlusion. Aortic occlusion was applied just prior to the last beat of each eight-beat atrial drive train and released immediately following the programmed ventricular extrastimulus. Aortic occlusion increased LV systolic pressure (+42 +/- 26.6 mmHg, P less than 0.01) and diminished segmental stroke shortening (0.100 +/- 0.059 mm, P less than 0.02), shortening fraction (0.086 +/- 0.048, P less than 0.001), mean velocity of stroke shortening (0.444 +/- 0.186 mm/s, P less than 0.001), and stroke work (P less than 0.001). LV epicardial and endocardial ERP were prolonged as a result of aortic occlusion (5 +/- 7.2 and 6 +/- 6.5 ms, respectively, P less than 0.05), whereas RV ERP was unchanged. Latency of premature beats at equivalent coupling intervals was unaltered. ERP prolongation correlated most strongly with reductions of segmental stroke shortening (r = 0.928, P less than 0.001), shortening fraction (r = 0.901, P less than 0.001), and mean shortening velocity (r = 0.819, P less than 0.01). Thus transient aortic occlusion prolonged LV refractoriness, and electrophysiological changes closely paralleled the severity of systolic mechanical disturbance.

scholarly journals Endotoxin impairs cardiac hemodynamics by affecting loading conditions but not by reducing cardiac inotropism

2010 ◽  
Vol 299 (2) ◽  
pp. H492-H501 ◽  
Author(s):  
Li Jianhui ◽  
Nathalie Rosenblatt-Velin ◽  
Noureddine Loukili ◽  
Pal Pacher ◽  
François Feihl ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Laboratory Animals ◽  
Lv Function ◽  
Stroke Work ◽  
Loading Conditions ◽  
Arterial Elastance ◽  
End Diastolic Volume

Acute myocardial dysfunction is a typical manifestation of septic shock. Experimentally, the administration of endotoxin [lipopolysacharride (LPS)] to laboratory animals is frequently used to study such dysfunction. However, a majority of studies used load-dependent indexes of cardiac function [including ejection fraction (EF) and maximal systolic pressure increment (dP/d tmax)], which do not directly explore cardiac inotropism. Therefore, we evaluated the direct effects of LPS on myocardial contractility, using left ventricular (LV) pressure-volume catheters in mice. Male BALB/c mice received an intraperitoneal injection of E. coli LPS (1, 5, 10, or 20 mg/kg). After 2, 6, or 20 h, cardiac function was analyzed in anesthetized, mechanically ventilated mice. All doses of LPS induced a significant drop in LV stroke volume and a trend toward reduced cardiac output after 6 h. Concomitantly, there was a significant decrease of LV preload (LV end-diastolic volume), with no apparent change in LV afterload (evaluated by effective arterial elastance and systemic vascular resistance). Load-dependent indexes of LV function were markedly reduced at 6 h, including EF, stroke work, and dP/d tmax. In contrast, there was no reduction of load-independent indexes of LV contractility, including end-systolic elastance (ejection phase measure of contractility) and the ratio dP/d tmax/end-diastolic volume (isovolumic phase measure of contractility), the latter showing instead a significant increase after 6 h. All changes were transient, returning to baseline values after 20 h. Therefore, the alterations of cardiac function induced by LPS are entirely due to altered loading conditions, but not to reduced contractility, which may instead be slightly increased.

Experimental hypothermia and rewarming: changes in mechanical function and metabolism of rat hearts

1996 ◽  
Vol 80 (1) ◽  
pp. 291-297 ◽  
Author(s):  
T. Tveita ◽  
M. Skandfer ◽  
H. Refsum ◽  
K. Ytrehus
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Stroke Volume ◽  
Maximum Rate ◽  
Energy Charge ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Mechanical Function ◽  
Control Value

Rewarming from accidental hypothermia is associated with fatal circulatory derangements. To investigate potential pathophysiological mechanisms involved, we examined heart function and metabolism in a rat model rewarmed after 4 h at 15-13 degrees C. Hypothermia resulted in a significant reduction of left ventricular (LV) systolic pressure, cardiac output, and heart rate, whereas stroke volume increased. The maximum rate of LV pressure rise decreased to 191 +/- 28 mmHg/s from a control value of 9,060 +/- 500 mmHg/s. Myocardial tissue content of ATP, ADP, and glycogen was significantly reduced, whereas lactate content remained unchanged. After rewarming, heart rate returned to control value, whereas LV systolic pressure, cardiac output, and stroke volume all remained significantly depressed. The posthypothermic maximum rate of LV pressure rise was 5,966 +/- 1.643 mmHg/s. The posthypothermic myocardial lactate content was significantly increased (to 13.3 +/- 3.2 nmol/mg from control value of 5.7 +/- 1.9 nmol/mg), and ATP and glycogen remained significantly lowered. Creatine phosphate or energy charge did not change significantly during the experiment. The finding of deteriorated myocardial mechanical function and a shift in energy metabolism shows that the heart could be an important target during hypothermia and rewarming in vivo, thus contributing to the development of a posthypothermic circulatory collapse.

scholarly journals Muscle metaboreflex-induced increases in effective arterial elastance: effect of heart failure

2020 ◽  
Vol 319 (1) ◽  
pp. R1-R10 ◽  
Author(s):  
Joseph Mannozzi ◽  
Jasdeep Kaur ◽  
Marty D. Spranger ◽  
Mohamed-Hussein Al-Hassan ◽  
Beruk Lessanework ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Cardiac Output ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Dynamic Exercise ◽  
Stroke Work ◽  
Arterial Elastance ◽  
Muscle Metaboreflex ◽  
Effective Arterial Elastance

Dynamic exercise elicits robust increases in sympathetic activity in part due to muscle metaboreflex activation (MMA), a pressor response triggered by activation of skeletal muscle afferents. MMA during dynamic exercise increases arterial pressure by increasing cardiac output via increases in heart rate, ventricular contractility, and central blood volume mobilization. In heart failure, ventricular function is compromised, and MMA elicits peripheral vasoconstriction. Ventricular-vascular coupling reflects the efficiency of energy transfer from the left ventricle to the systemic circulation and is calculated as the ratio of effective arterial elastance ( Ea) to left ventricular maximal elastance ( Emax). The effect of MMA on Ea in normal subjects is unknown. Furthermore, whether muscle metaboreflex control of Ea is altered in heart failure has not been investigated. We utilized two previously published methods of evaluating Ea [end-systolic pressure/stroke volume ( EaPV)] and [heart rate × vascular resistance ( EaZ)] during rest, mild treadmill exercise, and MMA (induced via partial reductions in hindlimb blood flow imposed during exercise) in chronically instrumented conscious canines before and after induction of heart failure via rapid ventricular pacing. In healthy animals, MMA elicits significant increases in effective arterial elastance and stroke work that likely maintains ventricular-vascular coupling. In heart failure, Ea is high, and MMA-induced increases are exaggerated, which further exacerbates the already uncoupled ventricular-vascular relationship, which likely contributes to the impaired ability to raise stroke work and cardiac output during exercise in heart failure.

Evaluation of long-term variance of left ventricular performance indexes in closed-chest dogs

1989 ◽  
Vol 257 (1) ◽  
pp. H70-H78
Author(s):  
G. L. Freeman ◽  
J. T. Colston
Keyword(s):  
Ejection Fraction ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Left Ventricular Performance ◽  
Mean Velocity ◽  
Ventricular Performance ◽  
End Diastolic Volume ◽  
Pressure Development

To assess the long-term variance of several parameters of left ventricular performance, we evaluated maximum rate of pressure development (dP/dtmax), ejection fraction, mean velocity of circumferential fiber shortening (VCF), the slope and volume-axis intercept of the end-systolic pressure-volume (PES-VES) relation, the stroke-work end-diastolic volume (SW-EDV) relation, and the dP/dtmax-EDV relation in six chronically instrumented dogs. Each dog was studied five times over a period of 3 wk in the conscious autonomically intact state, after autonomic blockade, and after administration of anesthesia. For each index under each set of testing conditions, a coefficient of variation was determined, defined as (SD/mean) x 100, and expressed as a percent. In conscious autonomically intact dogs, a low day-to-day variance was present in dP/dtmax (6.4%), ejection fraction (6.8%), mean VCF (6.5%), and the slope and volume intercept of the SW-EDV relation (7.2 and 6.2%), whereas higher variance was seen in the slope and intercept of the PES-VES relation (18.1 and 36.1%). The highest variance was present in parameters of the dP/dtmax-EDV relation. Thus dP/dtmax, ejection fraction, and the slope and volume intercept of the SW-EDV relation may be the most reliable indexes for long-term evaluation of left ventricular performance.

Prostaglandin E1 increases myocardial contractility in the conscious dog

1984 ◽  
Vol 62 (12) ◽  
pp. 1505-1510 ◽  
Author(s):  
S. Roux ◽  
J. G. Latour ◽  
P. Théroux ◽  
J. P. Clozel ◽  
M. G. Bourassa
Keyword(s):  
Heart Rate ◽  
Myocardial Contractility ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Lv Function ◽  
Initial Increase ◽  
Prostaglandin E ◽  
Inotropic Effects ◽  
Conscious Dog

The systemic and inotropic properties of prostaglandin E1 (PGE1) were investigated in 20 unanesthetized dogs. Pairs of ultrasonic dimension gauges and a micromanometer were implanted in the subendocardium and the apex of the left ventricle (LV), respectively. Seven to ten days later, increasing doses of PGE1 were infused into the left atrium. To appreciate the inotropic effects of the agent, the heart rate was maintained constant at 150 beats/min in a subgroup of dogs while preload was modified by bleeding or saline infusion over matched ranges of end-diastolic segmental length (EDL) during placebo and PGE1 infusions (0.25 μg∙kg−1∙min−1). LV function curves (ΔL: systolic segmental shortening versus EDL) were plotted. Increasing doses of PGE1 above 0.031 μg∙kg−1∙min−1 brought a progressive decrease of left ventricular end-diastolic pressure, EDL, ΔL, and peak left ventricular systolic pressure. The heart rate increased significantly at dosages from 0.063 to 0.125 μg∙kg−1∙min−1, and peak positive dP/dt after an initial increase fell at the dose of 0.5 μg∙kg−1∙min−1. The LV function curves invariably showed a shift to the left when PGE1 was administered; as the basal EDL was restored during PGE, infusion, ΔL reached a 33% increase (p < 0.001). Thus, in addition to its potent vasodilating properties that are more prominent on preload than afterload, PGE1 increases myocardial contractility in the conscious dog.

Age-related left ventricular function in the mouse: analysis based on in vivo pressure-volume relationships

1999 ◽  
Vol 277 (5) ◽  
pp. H1906-H1913 ◽  
Author(s):  
Bo Yang ◽  
Douglas F. Larson ◽  
Ronald Watson
Keyword(s):  
Contractile Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Volume Index ◽  
Lv Function ◽  
Mouse Heart ◽  
Stroke Work ◽  
Arterial Elastance ◽  
Systolic Volume ◽  
End Systolic Volume

Our study compared left ventricular (LV) function between senescent and young adult mice through in situ pressure-volume loop analysis. Two groups of mice ( n = 9 each), 6-mo-old and 16-mo-old (senescent) mice, were anesthetized with urethan and α-chloralose, and their LV were instrumented with a Millar 1.4-Fr conductance micromanometer catheter for the acquisition of the pressure-volume loops. The senescent mice had a significantly decreased contractile function related to load-dependent parameters, including stroke volume index, ejection fraction, cardiac output index, stroke work index, and maximum derivative of change in systolic pressure over time. The load-independent parameters, preload recruitable stroke work and the slope (end-systolic volume elastance) of the end-systolic pressure-volume relationship, were significantly decreased in the senescent mice. Heart rate and arterial elastance were not different between the two groups; however, the ventricular-to-vascular coupling ratio (ratio of elastance of artery to end-systolic volume elastance) was increased by threefold in the senescent mice ( P < 0.001). Thus there were significant decreases in contractile function in the senescent mouse heart that appeared to be related to reduced mechanical efficiency but not related to arterial elastance.

scholarly journals Environmentally persistent free radicals compromise left ventricular function during ischemia/reperfusion injury

2015 ◽  
Vol 308 (9) ◽  
pp. H998-H1006 ◽  
Author(s):  
Brendan R. Burn ◽  
Kurt J. Varner
Keyword(s):  
Free Radicals ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Halogenated Hydrocarbons ◽  
Lv Function ◽  
Stroke Work

Increases in airborne particulate matter (PM) are linked to increased mortality from myocardial ischemia. PM contains environmentally persistent free radicals (EPFRs) that form as halogenated hydrocarbons chemisorb to transition metal oxide-coated particles, and are capable of sustained redox cycling. We hypothesized that exposure to the EPFR DCB230 would increase cardiac vulnerability to subsequent myocardial ischemia-reperfusion (MI/R) injury. Rats were exposed to DCB230 or vehicle via nose-only inhalation (230 μg max/day) over 30 min/day for 7 days. MI/R or sham MI/R (sham) was initiated 24 h after the final exposure. Following 1 or 7 days of reperfusion, left ventricular (LV) function was assessed and infarct size measured. In vehicle-exposed rats, MI/R injury did not significantly reduce cardiac output (CO), stroke volume (SV), stroke work (SW), end-diastolic volume (EDV), or end-systolic volume (ESV) after 1 day of reperfusion, despite significant reductions in end-systolic pressure (ESP). Preload-recruitable SW (PRSW; contractility) was elevated, presumably to maintain LV function. MI/R 1-day rats exposed to DCB230 also had similarly reduced ESP. Compared with vehicle controls, CO, SV, and SW were significantly reduced in DCB230-exposed MI/R 1-day rats; moreover, PRSW did not increase. DCB230’s effects on LV function dissipated within 8 days of exposure. These data show that inhalation of EPFRs can exacerbate the deficits in LV function produced by subsequent MI/R injury. Infarct size was not different between the MI/R groups. We conclude that inhalation of EPFRs can compromise cardiac function during MI/R injury and may help to explain the link between PM and MI/R-related mortality.

Intrinsic effects of heart rate on left ventricular performance

1963 ◽  
Vol 205 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Jere H. Mitchell ◽  
Andrew G. Wallace ◽  
N. Sheldon Skinner
Keyword(s):  
Heart Rate ◽  
Left Ventricle ◽  
Diastolic Pressure ◽  
Pressure Rise ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Left Ventricular Performance ◽  
Ventricular Performance ◽  
Wide Range

The effects of heart rate on left-ventricular performance were studied in an areflexic dog right-heart bypass preparation which allowed independent control of aortic pressure, cardiac output, and heart rate. When the heart rate was increased while stroke volume and mean aortic pressure were maintained constant the left-ventricular mean rate of pressure rise during isovolumic systole, the maximal rate of pressure rise during isovolumic systole, and the mean rate of ejection were all increased without any change in left-ventricular end-diastolic pressure. Further, it was shown that the left ventricle performed the same amount of stroke work over a wide range of heart rates without an increase in end-diastolic pressure in spite of the markedly shortened time available for performing this work. This was accomplished because of the increase in stroke power. These observations demonstrate that the performance of the left ventricle becomes intrinsically "faster" as the heart rate is increased. When the transient phenomena that occur when the heart rate is increased are considered, the fact that the same stroke work is produced over a wide range of heart rates without an increase in end-diastolic pressure indicates that the left ventricle has also become "stronger" than it would have been if the adaptive change had not occurred.

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