Alterations In Contractile State Research Articles

Pattern of substrate utilization in vascular smooth muscle using 13C isotopomer analysis of glutamate.

Although vascular smooth muscle (VSM) derives the majority of its energy from oxidative phosphorylation, controversy exists concerning which substrates are utilized by the tricarboxylic acid (TCA) cycle. We used 13C isotopomer analysis of glutamate to directly measure the entry of exogenous [13C]glucose and acetate and unlabeled endogenous sources into the TCA cycle via acetyl-CoA. Hog carotid artery segments denuded of endothelium were superfused with 5 mM [1-13C]glucose and 0-5 mM [1,2-13C]acetate at 37 degreesC for 3-12 h. We found that both resting and contracting VSM preferentially utilize [1,2-13C]acetate compared with [1-13C]glucose and unlabeled substrates. The entry of glucose into the TCA cycle (30-60% of total entry via acetyl-CoA) exhibited little change despite alterations in contractile state or acetate concentrations ranging from 0 to 5 mM. We conclude that glucose and nonglucose substrates are important oxidative substrates for resting and contracting VSM. These are the first direct measurements of relative substrate entry into the TCA cycle of VSM during activation and may provide a useful method to measure alterations in VSM metabolism under physiological and pathophysiological conditions.

Interval-Dependent Changes in Left Ventricular Contractile State in Lone Atrial Fibrillation and in Atrial Fibrillation Associated With Coronary Artery Disease

In atrial fibrillation (AF), beat-to-beat changes in left ventricular (LV) systolic performance are caused by variations in filling (preload), aortic pressure (afterload), and ventricular inotropic or contractile state. These factors are known to be influenced by the preceding diastolic or RR interval (RR1), but the independent impact of variations in the pre-preceding RR interval (RR2) on contractile state is not well defined. This aspect was studied in 10 patients with lone AF and 8 with coronary artery disease by measuring LV peak ejection velocity (Vpe, Doppler echocardiography) in 80 to 100 consecutive cardiac cycles. Vpe was plotted against RR1 for beats with a short RR2 and for beats with a long RR2. Such function-interval plots indicate a direct relation between Vpe and RR1 (for RR1 = 500 to 1,000 ms). In lone AF, the slope (linear fit) of Vpe versus RR1 was similar for short and long RR2 (slopes = 46 and 50 s−1). Vpe, calculated from best linear fit and a common RR1, was consistently higher when RR2 was short than when it was long. At an RR1 = 750 ms, Vpe (% of max) was 87 ± 6% when RR2 was short versus 76 ± 6% when RR2 was long, p <0.05. Results were similar in patients with coronary artery disease and the observed interval-dependent potentiation of contractile state was preserved in patients with a low ejection fraction. By comparing Vpe at a common RR1, the effects of time-dependent changes in LV preload and afterload are minimized if not abolished. Thus, differences in Vpe reflect differences in contractile state caused by variations in RR2. Data confirm interval-dependent alterations in contractile state that are likely an expression of the force-frequency relation. Studies of LV function in AF should incorporate a consideration of cycle length-dependent changes in LV contractile state.

Altered left ventricular mechanics in patients with valvular aortic stenosis and coarction of the aorta: effects on systolic performance and late outcome.

Despite similar degrees of left ventricular systolic hypertension shortening characteristics are usually greater in patients with congenital valvular aortic stenosis (VAS) than in patients with coarctation of the aorta (CoA). We hypothesized that these dissimilarities were caused by differences in myocardial mechanics rather than by alterations in contractile state. Eleven patients with VAS (ages 6 to 41 years) and 11 with CoA were matched for age, body surface area, and peak systolic ejection gradient. Results were compared with data from 22 normal subjects matched for age and body surface area. Echocardiographic tracings of the left ventricle were recorded in conjunction with left ventricular pressure measurements (VAS) or calibrated carotid pulse tracings (CoA and normal subjects). Peak and end-systolic wall stresses as well as left ventricular shortening fraction (% delta D) and rate-corrected velocity of fiber shortening (Vcfc) were calculated. No differences for left ventricular dimensions, heart rate or peak wall stress were present. Ventricular peak systolic pressures and wall mass were higher for the patients with VAS or CoA than for the normal subjects (p less than .001). These parameters did not differ between the VAS and CoA groups. The patients with VAS had higher % delta D and Vcfc than either the CoA or normal groups (p less than .01). Afterload, as quantified by end-systolic stress, was 41% lower than normal for the patients with VAS (p less than .001) and 13% higher than normal for those with CoA (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic assessment of left ventricular structure and function in hypertension: Methodology

M-mode and two-dimensional echocardiography now provide an armamentarium of noninvasive techniques that permit assessment of left ventricular pump function, quantitation of afterload, a load-independent assessment of contractile state, and quantitation of pressure overload hypertrophy. Combined application of these methods to problems in the assessment of hypertensive heart disease can clarify both disease mechanisms and therapeutic effects by identifying the contributions of changes in myocardial mass, alterations in contractile state and variations in afterload to a given phenomenon.

Sensitivity of end-systolic pressure-dimension and pressure-volume relations to the inotropic state in humans.

The value for the slope of the left ventricular (LV) end-systolic pressure-dimension and pressure-volume relations has been proposed as a quantitative measure of the LV inotropic state. This measure of LV inotropic state is attractive because it is independent of preload and incorporates afterload. To investigate the sensitivity of the slope of these relations to alterations in contractile state, 10 normal subjects were studied using M-mode echocardiographic, phonocardiographic and indirect carotid pulse recordings during infusion of methoxamine to alter end-systolic pressure and during infusion of dobutamine (5 micrograms/kg/min) to increase LV inotropic state. Heart rate was maintained within a narrow range for each subject. End-systolic volume was calculated from end-systolic echocardiographic dimension by standard methods. End-systolic pressure was estimated from the dicrotic notch pressure determined from a calibrated carotid pulse recording; peak systolic pressure was also measured. Regardless of the method of approximating end-systolic pressure, the positive inotropic intervention caused a leftward shift in the end-systolic pressure-dimension and pressure-volume lines. With the dobutamine infusion, the value for the slope of the end-systolic pressure-dimension relation increased by 25% (range 16-46%, p less than 0.001), while the slope of the end-systolic pressure-volume relation increased by 55% (range 37-85%, p less than 0.001). In all cases, the curves were linear and became steeper with the positive inotropic intervention. In contrast, the value of the slope of the peak systolic pressure-end-systolic dimension relation showed a variable response to the dobutamine infusion (mean change 13%, range -77% to 73%; NS). Although the position of the peak systolic pressure-end-systolic dimension curve is consistently shifted with an alteration in inotropic state, the values of the slope of these curves are not reliable indicators of change in LV contractility. The values for the slope of the line relating end-systolic pressure (estimated by dicrotic notch pressure) to end-systolic dimension or volume, however, are highly sensitive to a change in inotropic state in human subjects.

Comparative evaluation of the specificity and sensitivity of isometric indices of contractility.

It is generally held that a useful mechanical index of contractility is one that is unchanged by changes in initial muscle length, but that changes in appropriate direction and magnitude with a change in contractile state. A number of isometric indices were measured in vitro in isolated cat papillary muscles to quantitate their relative dependence on initial muscle length and contractile state. Results indicate that no one isometric index completely fulfills the definition of an ideal index of contractile state. In particular, indices that change considerably with alterations in contractile state (e.g., maximum dF/dt) are also moderately dependent on preload. Conversely, indices that are moderately insensitive to changes in contractile state (e.g., time-to-peak force) are also insensitive to changes in contractile state. Changes in extrapolated maximum velocity and peak VCE were similar and were less sensitive to changes in contractile state than maximum dF/dt. The most sensitive in vitro index of contractility appears to be maximum dF/dt at a constant preload.

Beat to beat alterations in contractile state as the mechanism of spontaneous pulsus alternans in man

Beat to beat alterations in contractile state as the mechanism of spontaneous pulsus alternans in man