Separation of large mammalian ventricular myosin differing in ATPase activityThis paper is one of a selection of papers published in this Special Issue, entitled The Cellular and Molecular Basis of Cardiovascular Dysfunction, Dhalla 70th Birthday Tribute.

2007 ◽  
Vol 85 (3-4) ◽  
pp. 326-331 ◽  
Author(s):  
Heinz Rupp ◽  
Bernhard Maisch

To investigate a possible heterogeneity of human ventricular myosin, papillary muscles of patients with valvular dysfunction were examined using a modified native gel electrophoresis. Myosin was separated into 2 components termed VA and VB, whereby the VA to VB proportion appeared to depend on the ventricular load. The proportion of the faster migrating band VA was correlated (P < 0.05) with end-diastolic pressure and the aortic pressure-cardiac index product. The regression based on these variables accounted for 67% of the variation in VA (R2 = 0.67). The VA proportion was, however, not significantly correlated with cardiac norepinephrine concentration. The ATPase activity of the 2 components of myosin was assessed from the Ca3(PO4)2 precipitation by incubating the gel in the presence of ATP and CaCl2. The ATPase activity of VA was 60% of that of VB. The VA and VB forms were observed also in the cat (31.4% VA), dog (32.1% VA), pig (28.5% VA), wild pig (33.7% VA), and roe deer (30.5% VA). VA and VB were not detected in the rat exhibiting the 3 isoforms V1, V2, and V3, rabbit (100% V3), and hare (86% V1). The data demonstrate a heterogeneity of large mammalian ventricular myosin, whereby an increased cardiac load appeared to be associated with a higher myosin VA proportion that exhibited a reduced ATPase activity.

PEDIATRICS ◽  
1966 ◽  
Vol 38 (3) ◽  
pp. 457-464
Author(s):  
Norman S. Talner ◽  
Thomas H. Gardner ◽  
S. Evans Downing

The performance of the left ventricle in 20 newborn lambs was examined in a preparation which allowed precise control of aortic pressure, cardiac output, heart rate, and temperature. Reduction of arterial pH from a normal range (7.35 to 7.5) to severe acidemia (6.8 to 7.0) by hydrochloric or lactic acid infusion resulted in no significant impairment of left ventricular function. Prolonged acidemia (over 2 hours) failed to produce a reduction in left ventricular stroke volume or mean ejection rate for a given left ventricular end-diastolic pressure. Responsiveness of the left ventricle of the lamb to catecholamine stimulation was not diminished over the pH range 7.5 to 6.8. Under conditions of these investigations the apparent resistance of the myocardium of the newborn lamb, as well as the adult cat, to wide variations in pH may reflect a buffering capacity of cardiac muscle which would allow minimal change in intracellular pH, even though extracellular pH may indicate the presence of severe metabolic acidosis.


1976 ◽  
Vol 230 (4) ◽  
pp. 893-900 ◽  
Author(s):  
ER Powers ◽  
Foster ◽  
Powell WJ

The modification by aortic pressure and stroke volume of the response in cardiac performance to increases in heart rate (interval-force relationship) has not been previously studied. To investigate this interaction, 30 adrenergically blocked anesthetized dogs on right heart bypass were studied. At constant low aortic pressure and stroke volume, increasing heart rate (over the entire range 60-180) is associated with a continuously increasing stroke power, decreasing systolic ejection period, and an unchanging left ventricular end-diastolic pressure and circumference. At increased aortic pressure or stroke volume at low rates (60-120), increases in heart rate were associated with an increased performance. However, at increased aortic pressure or stroke volume at high rates (120-180), increases in heart rate were associated with a leveling or decrease in performance. Thus, an increase in aortic pressure or stroke volume results in an accentuation of the improvement in cardiac performance observed with increases in heart rate, but this response is limited to a low heart rate range. Therefore, the hemodynamic response to given increases in heart rate is critically dependent on aortic pressure and stroke volume.


1999 ◽  
Vol 276 (2) ◽  
pp. H424-H428 ◽  
Author(s):  
N. Stergiopulos ◽  
P. Segers ◽  
N. Westerhof

We determined total arterial compliance from pressure and flow in the ascending aorta of seven anesthetized dogs using the pulse pressure method (PPM) and the decay time method (DTM). Compliance was determined under control and during occlusion of the aorta at four different locations (iliac, renal, diaphragm, and proximal descending thoracic aorta). Compliance of PPM gave consistently lower values (0.893 ± 0.015) compared with the compliance of DTM (means ± SE; r = 0.989). The lower compliance estimates by the PPM can be attributed to the difference in mean pressures at which compliance is determined (mean pressure, 81.0 ± 3.6 mmHg; mean diastolic pressure, over which the DTM applies, 67.0 ± 3.6 mmHg). Total arterial compliance under control conditions was 0.169 ± 0.007 ml/mmHg. Compliance of the proximal aorta, obtained during occlusion of the proximal descending aorta, was 0.100 ± 0.007 ml/mmHg. Mean aortic pressure was 80.4 ± 3.6 mmHg during control and 102 ± 7.7 mmHg during proximal descending aortic occlusion. From these results and assuming that upper limbs and the head contribute as little as the lower limbs, we conclude that 60% of total arterial compliance resides in the proximal aorta. When we take into account the inverse relationship between pressure and compliance, the contribution of the proximal aorta to the total arterial compliance is even more significant.


2018 ◽  
Vol 315 (3) ◽  
pp. H669-H680 ◽  
Author(s):  
Alessio Alogna ◽  
Michael Schwarzl ◽  
Martin Manninger ◽  
Nazha Hamdani ◽  
Birgit Zirngast ◽  
...  

Experimental data indicate that stimulation of the nitric oxide-soluble guanylate cyclase(sGC)-cGMP-PKG pathway can increase left ventricular (LV) capacitance via phosphorylation of the myofilamental protein titin. We aimed to test whether acute pharmacological sGC stimulation with BAY 41-8543 would increase LV capacitance via titin phosphorylation in healthy and deoxycorticosteroneacetate (DOCA)-induced hypertensive pigs. Nine healthy Landrace pigs and 7 pigs with DOCA-induced hypertension and LV concentric hypertrophy were acutely instrumented to measure LV end-diastolic pressure-volume relationships (EDPVRs) at baseline and during intravenous infusion of BAY 41-8543 (1 and 3 μg·kg−1·min−1 for 30 min, respectively). Separately, in seven healthy and six DOCA pigs, transmural LV biopsies were harvested from the beating heart to measure titin phosphorylation during BAY 41-8543 infusion. LV EDPVRs before and during BAY 41-8543 infusion were superimposable in both healthy and DOCA-treated pigs, whereas mean aortic pressure decreased by 20–30 mmHg in both groups. Myocardial titin phosphorylation was unchanged in healthy pigs, but total and site-specific (Pro-Glu-Val-Lys and N2-Bus domains) titin phosphorylation was increased in DOCA-treated pigs. Bicoronary nitroglycerin infusion in healthy pigs ( n = 5) induced a rightward shift of the LV EDPVR, demonstrating the responsiveness of the pathway in this model. Acute systemic sGC stimulation with the sGC stimulator BAY 41-8543 did not recruit an LV preload reserve in both healthy and hypertrophied LV porcine myocardium, although it increased titin phosphorylation in the latter group. Thus, increased titin phosphorylation is not indicative of increased in vivo LV capacitance. NEW & NOTEWORTHY We demonstrate that acute pharmacological stimulation of soluble guanylate cyclase does not increase left ventricular compliance in normal and hypertrophied porcine hearts. Effects of long-term soluble guanylate cyclase stimulation with oral compounds in disease conditions associated with lowered myocardial cGMP levels, i.e., heart failure with preserved ejection fraction, remain to be investigated.


2002 ◽  
Vol 103 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Denis CHEMLA ◽  
Jean-Louis HÉBERT ◽  
Eduardo APTECAR ◽  
Jean-Xavier MAZOIT ◽  
Karen ZAMANI ◽  
...  

Mean arterial pressure (MAP) is estimated at the brachial artery level by adding a fraction of pulse pressure (form factor; = 0.33) to diastolic pressure. We tested the hypothesis that a fixed form factor can also be used at the aortic root level. We recorded systolic aortic pressure (SAP) and diastolic aortic pressure (DAP), and we calculated aortic pulse pressure (PP) and the time-averaged MAP in the aorta of resting adults (n = 73; age 43±14 years). Wave reflection was quantified using the augmentation index. The aortic form factor (range 0.35-0.53) decreased with age, MAP, PP and augmentation index (each P<0.001). The mean form factor value (0.45) gave a reasonable estimation of MAP (MAP = DAP+0.45PP; bias = 0±2mmHg), and the bias increased with MAP (P<0.001). An alternative formula (MAP = DAP+PP/3+5mmHg) gave a more precise estimation (bias = 0±1mmHg), and the bias was not related to MAP. This latter formula was consistent with the previously reported mean pulse wave amplification of 15mmHg, and with unchanged MAP and diastolic pressure from aorta to periphery. Multiple linear regression showed that 99% of the variability of MAP was explained by the combined influence of DAP and SAP, thus confirming major pressure redundancy. Results were obtained irrespective of whether the marked differences in heart period and extent of wave reflection between subjects were taken into account. In conclusion, the aortic form factor was strongly influenced by age, aortic pressure and wave reflection. An empirical formula (MAP = DAP+PP/3+5mmHg) that is consistent with mechanical principles in the arterial system gave a more precise estimate of MAP in the aorta of resting humans. Only two distinct pressure-powered functions were carried out in the (SAP, DAP, MAP, PP) four-pressure set.


1990 ◽  
Vol 258 (4) ◽  
pp. H1250-H1254 ◽  
Author(s):  
A. Chu ◽  
D. E. Chambers ◽  
C. C. Lin ◽  
W. D. Kuehl ◽  
F. R. Cobb

This study evaluates the role of endogenous nitric oxide in the modulation of basal coronary vasomotor tone by studying the effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide formation from L-arginine, on resting epicardial coronary diameter and coronary flow. L-NMMA (5 mg/kg) was infused in seven awake dogs chronically instrumented with coronary dimension crystals for measurement of epicardial coronary diameter, and Doppler flow probes for quantitation of phasic coronary flow (vasomotion of distal regulatory resistance coronary vessels). Epicardial coronary diameter decreased 5.5% from 3.47 +/- 0.17 to 3.28 +/- 0.15 mm (mean +/- SE). The diameter change was gradual, reaching a maximum at 13 +/- 2 min after infusion, and persistent, lasting greater than 90 min. Phasic coronary flow did not change. Mean aortic pressure significantly increased from 99 +/- 3 to 111 +/- 3 mmHg and heart rate decreased from 56 +/- 4 to 46 +/- 3 beats/min. Left ventricular end-diastolic pressure and contractility were not significantly altered. L-Arginine (66 mg/kg) but not D-arginine reversed all hemodynamic parameters. These data support an important role of nitric oxide in modulating basal epicardial coronary vasomotor tone and systemic vascular resistance.


1988 ◽  
Vol 254 (2) ◽  
pp. H361-H368 ◽  
Author(s):  
J. J. Smolich ◽  
P. L. Weissberg ◽  
A. Broughton ◽  
P. I. Korner

We studied the effect of graded aortic blood pressure reduction on left ventricular (LV) blood flow in anesthetized, autonomically blocked, open-chest dogs at constant heart rate and mean left atrial pressure. Aortic diastolic pressure (ADP) was lowered from rest (average 116 mmHg) to 90, 75, and 60 mmHg with an arteriovenous fistula. Global and regional LV blood flow was measured with radioactive microspheres. Mean LV blood flow fell stepwise from 145 ml.min-1.100 g-1 at rest to 116 ml.min-1.100 g-1 at ADP of 60 mmHg, whereas the endocardial-to-epicardial flow ratio decreased from 1.20 to 0.84. The transmural redistribution of LV blood flow was not accompanied by increases in LV oxygen extraction, depression of LV contractility, LV dilatation or LV electrical dysfunction and also occurred in the presence of considerable coronary vasodilator flow reserve. Electrical evidence of subendocardial ischemia appeared at ADP of 32 mmHg and an endocardial-to-epicardial flow ratio of 0.41 in a subgroup of animals. We conclude that the redistribution of LV flow during moderate aortic pressure reduction was an appropriate physiological adjustment to uneven transmural alterations in regional LV wall stress and that it preceded a more pronounced redistribution evident with myocardial ischemia.


1975 ◽  
Vol 229 (5) ◽  
pp. 1261-1270 ◽  
Author(s):  
W Enrlich ◽  
FV Schrijen ◽  
TA Solomon ◽  
E Rodriguez-Lopez ◽  
RL Riley

The transient circulatory changes following paced heart rate increase are reported from 133 trials with 6 unanesthetized dogs with chronically implanted monitoring devices for heart rate, cardiac output, aortic blood pressure, and mean right atrial pressure. In 62 trials with 2 of the dogs, pulmonary artery, and left ventricular end-diastolic pressure, as well as left ventricular dP/dt were also studied. The sequence of changes in pressures and flows is analyzed in terms of probable underlying mechanisms, particularly with respect to the nature of vascular resistances. The rise in aortic pressure and flow during the first 3 s of paced heart rate increase, before arterial stretch receptor reflexes become active, is more consistent with an effective downstream pressure of about 49 mmHg, presumably at the arteriolar level, than with an effective downstream pressure close to 0 mmHg at the right atrial level. In the pulmonary circulation where vascular reflex effects are less prominent, the pattern of pulmonary arterial pressure and flow for the entire 30 s of observation is consistent with an effective downstream pressure of 9 mmHg, presumably at the alveolar or pulmonary arteriolar level, rather than at the level of the left ventricular end-diastolic pressure.


2017 ◽  
Vol 574 ◽  
pp. 1164-1173 ◽  
Author(s):  
Matthew C. Brondum ◽  
Zachary A. Collier ◽  
Christopher S. Luke ◽  
Buddy L. Goatcher ◽  
Igor Linkov

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