Endotoxin and myocardial failure: role of the myofibril and venous return

1978 ◽  
Vol 235 (2) ◽  
pp. H150-H156 ◽  
Author(s):  
F. D. Bruni ◽  
P. Komwatana ◽  
M. E. Soulsby ◽  
M. L. Hess
Keyword(s):  
Atpase Activity ◽  
Venous Return ◽  
Normal Activity ◽  
Left Ventricular ◽  
Myofibrillar Atpase ◽  
Myocardial Failure ◽  
Myofibrillar Atpase Activity ◽  
Myofibril Preparation

The effects of gramnegative endotoxin-induced myocardial failure in the pentobarbital-anesthetized dog were examined by monitoring its influence on cardiac myofibrillar ATPase activity. Myofibrils were isolated from endo- and epicardial portions of the left ventricular wall. ATPase activities were determined in animals treated with 4 mg/kg endotoxin and monitored 5 h, in animals monitored for 5 h without endotoxin (controls), and in animals implanted with a unilateral femoral shunt and given endotoxin. No differences were seen in the activities between the endo- and epicardial portions of any preparation. Activity was significantly depressed in endotoxemic animals. Increasing venous return by 313 +/- 71 ml/min significantly increased coronary flow by reducing coronary vascular resistance and prevented any observed depression of myofibrillar ATPase activity. In in vitro studies, adding endotoxin directly to a myofibril preparation did not modify normal activity. It appears that the mechanical and myofibrillar dysfunctions are due to the action of endotoxin at sites not associated with the actomyosin ATPase, but may be due to the production of an intermediary agent in concert with a decreased venous return.

Contractile function and myofibrillar ATPase activity in the exercise-trained dog heart

1977 ◽  
Vol 43 (6) ◽  
pp. 977-982 ◽  
Author(s):  
R. T. Dowell ◽  
H. L. Stone ◽  
L. A. Sordahl ◽  
G. K. Asimakis
Keyword(s):  
Heart Rate ◽  
Exercise Training ◽  
Atpase Activity ◽  
Contractile Function ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Submaximal Exercise ◽  
Treadmill Running ◽  
Myofibrillar Atpase ◽  
Myofibrillar Atpase Activity

Myocardial contractility and the enzymatic (ATPase) activity of cardiac contractile proteins were examined after exercise training using the chronically instrumented, unanesthetized dog as an experimental model. Before training, heart rate and the maximum rate of left ventricular pressure development (max dP/dt) were measured at rest and during submaximal exercise. Animals were then subjected to an 8- to 10-wk treadmill running program. Training was verified by the establishment of a 10- to 20-beat/min reduction in heart rate during submaximal exercise. After training max dP/dt was within normal limits at rest, but significantly elevated during submaximal exercise. When max dP/dt was plotted as a function of heart rate, either with the animal standing quietly on the treadmill or during submaximal exercise, a marked elevation in max dP/dt at any given heart rate was observed following training. Myofibrillar protein yield and ATPase activity values were nearly identical in left ventricles from exercise-trained and sedentary control dogs. Although exercise training by treadmill running improved contractile function in the unanesthetized dog myocardium, this response does not appear to involve alterations in myofibrillar ATPase activity.

Nutritional modification of rat heart postnatal development

1984 ◽  
Vol 246 (3) ◽  
pp. H332-H338 ◽  
Author(s):  
R. T. Dowell
Keyword(s):  
Atpase Activity ◽  
Postnatal Development ◽  
Contractile Function ◽  
Left Ventricular ◽  
Activity Level ◽  
Myofibrillar Atpase ◽  
Fast Growing ◽  
Growing Rats ◽  
Myofibrillar Atpase Activity ◽  
Slow Growing

Postnatal development of the mammalian myocardium encompasses increases in cellularity, energy producing and energy utilizing systems, and concurrent augmentation of heart contractile performance. The present study disrupted normal developmental sequences by adjusting the number of newborn rats per litter at 4 days postbirth. Fast-growing (4 rats/litter), normal (8 rats/litter), or slow-growing (16 rats/litter) animals were studied when 21 days old. Left ventricular cellularity (total DNA) increased as a function of the nutritionally modified growth of the heart, having values of 562 +/- 27, 625 +/- 33, and 791 +/- 20 (SE) micrograms in 16, 8, and 4 rats/litter groups, respectively. Low levels of systolic pressure (55 + 5 mmHg) and rate of pressure development (dP/dt, 2,670 +/- 130 mmHg/s) were noted in the slow-growing rats. Growth-related augmentation of pressure and dP/dt occurred such that adult levels (104 +/- 4 mmHg; 5,810 +/- 290 mmHg/s) were observed in 21-day-old, fast-growing rats. An enzymatic marker for aerobic metabolism (malate dehydrogenase) indicated mitochondrial accumulation in excess of ventricular tissue, thereby establishing progressive increases in aerobic capacity. Myofibrillar ATPase activity was not significantly different among all groups. Thus heart contractile function during nutritionally induced changes in postnatal development is augmented in proportion to increases in heart DNA content. A positive relationship also exists between dP/dt and number of mitochondria; however, enhanced contractile function is achieved independently of myofibrillar ATPase activity level.

Alterations in Systemic Vascular Volume of the Dog in Response to Hexamethonium and Norepinephrine

1957 ◽  
Vol 191 (2) ◽  
pp. 283-286 ◽  
Author(s):  
John C. Rose ◽  
Edward D. Freis
Keyword(s):  
Cardiac Output ◽  
Venous Return ◽  
Cardiac Activity ◽  
Left Ventricular ◽  
Vascular Volume ◽  
Vasomotor Activity ◽  
Constant Output ◽  
Arteriolar Tone ◽  
Integrated Responses

A diaphragm pump of controlled constant output was substituted for the left ventricle in dogs. Left auricular blood was conducted to a reservoir, from which it was pumped into the thoracic aorta. Left ventricular by-pass was complete. Alterations in total vascular volume were continually monitored by observation of the pump reservoir level. Sympathetic blockade (hexamethonium) increased total vascular volume (mean 15%). This resulted in decreased venous return and decreased right ventricular output. Norepinephrine constricted the total vasculature and decreased vascular volume (mean 12%). This resulted in increased venous return and cardiac output. These experiments demonstrated the complex integrated responses of the total circulation to sympathetic vasomotor activity. The role of the sympathetic nervous system not only in the regulation of arteriolar tone and cardiac activity but also in adjusting total vascular volume and venous return was emphasized. Venous return, and hence cardiac output alterations accompanying systemic vasomotor activity can only be detected by continuous methods of flow measurement.

Role of sarcoplasmic reticulum in loss of load-sensitive relaxation in pressure overload cardiac hypertrophy

1994 ◽  
Vol 266 (1) ◽  
pp. H68-H78 ◽  
Author(s):  
C. R. Cory ◽  
R. W. Grange ◽  
M. E. Houston
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Cardiac Hypertrophy ◽  
Atpase Activity ◽  
Pressure Overload ◽  
Fold Increase ◽  
Left Ventricular ◽  
Isometric Tension ◽  
Tension Development ◽  
Sequestration Potential

The loss of load-sensitive relaxation observed in the pressure-overloaded heart may reflect a strategy of slowed cytosolic Ca2+ uptake to yield a prolongation of the active state of the muscle and a decrease in cellular energy expenditure. A decrease in the potential of the sarcoplasmic reticulum (SR) to resequester cytosolic Ca2+ during diastole could contribute to this attenuated load sensitivity. To test this hypothesis, both in vitro mechanical function of anterior papillary muscles and the SR Ca2+ sequestration potential of female guinea pig left ventricle were compared in cardiac hypertrophy (Hyp) and sham-operated (Sham) groups. Twenty-one days of pressure overload induced by coarctation of the suprarenal, subdiaphragmatic aorta resulted in a 36% increase in left ventricular mass in the Hyp. Peak isometric tension, the rate of isometric tension development, and the maximal rates of isometric and isotonic relaxation were significantly reduced in Hyp. Load-sensitive relaxation were significantly reduced in Hyp. Load-sensitive relaxation quantified by the ratio of a rapid loading to unloading force step in isotonically contracting papillary muscle was reduced 50% in Hyp muscles. Maximum activity of SR Ca(2+)-adenosinetriphosphatase (ATPase) measured under optimal conditions (37 degrees C; saturating Ca2+) was unaltered, but at low free Ca2+ concentrations (0.65 microM), it was decreased by 43% of the Sham response. Bivariate regression analysis revealed a significant (r = 0.84; P = 0.009) relationship between the decrease in SR Ca(2+)-ATPase activity and the loss of load-sensitive relaxation after aortic coarctation. Stimulation of the SR Ca(2+)-ATPase by the catalytic subunit of adenosine 3',5'-cyclic monophosphate-dependent protein kinase resulted in a 2.6-fold increase for Sham but only a 1.6-fold increase for Hyp. Semiquantitative Western blot radioimmunoassays revealed that the changes in SR Ca(2+)-ATPase activity were not due to decreases in the content of the Ca(2+)-ATPase protein or phospholamban. Our data directly implicate a role for decreased SR function in attenuated load sensitivity. A purposeful downregulation of SR Ca2+ uptake likely results from a qualitative rather than a quantitative change in the ATPase and possibly one of its key regulators, phospholamban.

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