High-fidelity Micromanometer Research Articles

Validation of pressure-volume data obtained in patients by initial transit radionuclide angiocardiography

In order to validate the measurement of pressure-volume loops and stroke work in humans, simultaneous digital subtraction ventriculography (DSA) and first-pass radionuclide angiocardiography (RNA) coupled with high-fidelity micromanometer left ventricular pressure measurements were undertaken in 34 patients, mean age 75 ± 9 years, with aortic stenosis. Twenty-nine patients had a repeat study after balloon valvuloplasty, for a total of 63 DSA and RNA pressure-volume loops. All data were analyzed in a systematic fashion in order to minimize intra- and interobserver error. Linear regression analysis was used to calculate the degree of agreement between the two technologies. Left ventricular ejection fraction (RNA: 0.47 ± 0.17, DSA: 0.49 ± 0.18) had a correlation coefficient of 0.96; left ventricular end-diastolic volume (RNA: 171 ± 42 ml, DSA: 168 ± 52 ml) and end-systolic volume (RNA: 95 ± 50 ml, DSA: 89 ± 50 ml) had correlation coefficients of 0.89 and 0.95, respectively. Left ventricular stroke volume (RNA: 75 ± 26 ml, DSA: 75 ± 27 ml) had a correlation coefficient of 0.92, while integrated pressure-volume loop or stroke work (RNA: 15.6 ± 6.6 ergs 10 6, DSA: 15.9 ± 6.3 ergs 10 6) had a correlation coefficient of 0.89. These data demonstrate that RNA measurements of left ventricular chamber dynamics concur with that obtained with DSA. With semiautomated data analysis, the portable first-pass RNA pressure-volume data are also less labor-intensive. Moreover, multiple measurements of ventricular performance during hemodynamic manipulations in the catheterization laboratory or operating room would allow for a more precise estimation of left ventricular performance.

Analysis of the early rise in aortic transvalvular gradient after aortic valvuloplasty

The relationship between dynamic changes in aortic valve gradient and left ventricular ejection performance in the early period after successful percutaneous aortic valvuloplasty has not been described in detail. Accordingly 20 adult patients with severe symptomatic calcific aortic stenosis underwent first-pass radionuclide angiography and Doppler echocardiography before, immediately after, and 2 to 4 days after the valvuloplasty procedure. A significant ( p < 0.001) reduction in peak-to-peak (72 ± 24 mm Hg to 36 ± 11 mmHg) and mean (60 ± 20 mm Hg to 34 ± 9 mm Hg) transaortic gradient and an increase in aortic valve area (0.5 ± 0.2 cm 2 to 0.8 ± 0.2 cm 2) were measured by high-fidelity micromanometer catheters immediately after aortic valvuloplasty. Results of Doppler echocardiography showed a significant ( p < 0.001) immediate decrease in peak instantaneous (81 ± 22 mm Hg to 53 ± 15 mm Hg) and mean (48 ± 14 mm Hg to 31 ± 9 mm Hg) aortic gradients. However, 2 to 4 days later a significant ( p < 0.001) return of peak (56 ± 15 mm Hg to 65 ± 20 mm Hg) and mean (31 ± 9 mm Hg to 39 ± 12 mm Hg) transvalvular gradient occurred. Aortic valve area as determined by the continuity equation also increased from 0.4 ± 0.2 cm 2 to 0.6 ± 0.2 cm 2 immediately after the procedure ( p < 0.001), then partially returned to baseline (0.5 ± 0.2 cm 2; p < 0.005) at 2 to 4 days. Results of serial first-pass radionuclide angiography performed at the same time as the Doppler evaluations showed a continued decrement in left ventricular end-diastolic volume (184 ± 42 ml to 158 ± 35 ml to 151 ± 35 ml) and a trend toward an increase in stroke volume. Additionally the mean ejection fraction continued to improve during this period (42 ± 18% to 49 ± 19% to 52 ± 19%). These data indicate that the early rise in aortic valve gradient seen after percutaneous aortic valvuloplasty is likely due to both remodeling of the aortic valve architecture and a small increase in stroke volume.

Diastolic properties of the normal left ventricle during supine exercise.

Diastolic function in response to dynamic exercise was studied by biplane left ventriculography and by measuring left ventricular pressure with a high fidelity micromanometer tipped catheter at rest and during supine bicycle exercise in nine normal subjects. During exercise there was a fall in end systolic volume, in the time constant of left ventricular isovolumic pressure decay, and in the lowest diastolic pressure. Stroke volume, peak filling rate, mean passive filling rate, and the volume at the lowest diastolic pressure increased. There was an increase in the number of time constants that had elapsed before the lowest diastolic pressure was reached and the slope of the pressure-volume curves during passive filling (delta P/delta V) increased without changes in end diastolic pressure and volume. These results show that during exercise elastic recoil is enhanced and left ventricular relaxation is faster and more complete. Both phenomena reduce the lowest diastolic filling pressure. The observed increase in chamber stiffness from rest to exercise is probably related to increased resistance of the left ventricular wall caused by higher passive filling rates. The enhanced early diastolic pressure decay during exercise allows stroke volume to increase despite an increase in diastolic viscoelastic resistance and chamber stiffness.

The effects of acute ischemia on the isovolumic index

The isovolumic index is the ratio of the duration of isovolumic contraction (IVC) and relaxation (IVR) divided by ejection time (ET), and has been proposed as a more sensitive descriptor of ventricular performance than the systolic time index, which ignores the period of isovolumic relaxation. To determine the effects of acute ischemia on these indices, IVC, IVR, and ET were measured in seven open-chest dogs instrumented with high-fidelity micromanometers and ultrasonic crystals and subjected to a 10-second period of coronary occlusion. Fractional shortening was significantly impaired (18.4 ± 6.9% vs 1.9 ± 7.3%, p < 0.001) during coronary occlusion. ET was unaffected by the brief ischemia, whereas IVC time showed directional shortening that attained statistical significance (55 ± 7 msec control vs 50 ± 6 msec, p < 0.01) at 8 to 10 seconds. IVR time was prolonged by occlusion, significantly so at 6 to 8 seconds (72 ± 26 msec control vs 88 ± 22 msec, p < 0.01) and at 8 to 10 seconds (81 ± 19 msec, p < 0.05). The systolic time index showed no deterioration during ischemia, whereas the isovolumic index did show directional prolongation. Assessment of IVC, IVR, and ET at the time of the maximal change in the isovolumic index revealed significant changes of IVC and IVR (each p < 0.05 cs control), though ET and the systolic time index were unchanged. Through incorporation of IVR, the isovolumic index was more sensitive to acute brief ischemia than the systolic time index.

The development of the entire end-systolic pressure-volume and ejection fraction-afterload relations: a new concept of systolic myocardial stiffness.

In this study we introduce a new concept of systolic myocardial stiffness that extends the Suga-Sagawa maximum ventricular elastance concept to the myocardium. End-systole is defined as the time of maximum systolic myocardial stiffness (max Eav), which we examined for its load independence and sensitivity to changes in the inotropic state and to heart rate. Seven adult mongrel dogs were instrumented with ultrasonic crystals for measurements of long and short axes and left ventricular wall thickness, and a high-fidelity micromanometer was inserted for measurement of left ventricular pressures. Preload and afterload were altered by inferior vena cava occlusion, nitroprusside, angiotensin II, atropine, propranolol, and various combinations with propranolol. End-systolic stress-strain relations (slope: max Eav) were linear in all seven dogs, implying that end-systolic myocardial stiffness is independent of end-systolic stress. Changes in max Eav (for constant preload and afterload) reflected changes in the ejection fraction; max Eav was also insensitive to propranolol and to changes in heart rate over the range from 120 to 180 beats/min. End-systolic pressure-volume relations (ESPVRs), derived analytically from these stress-strain relations, were nonlinear, and estimates of volume at zero stress (Vom) were always positive. On the other hand, ESPVRs obtained on the basis of the Suga-Sagawa maximum ventricular elastance concept, were linear, and volume at zero pressure (Vop) estimated by linear extrapolation was negative in one case. Based on the concept of systolic myocardial stiffness, the slope of the ESPVR varies with end-systolic volume and attains its maximum value (Emax) at zero end-systolic pressure. Normalization of Emax with Vom demonstrated a close relationship to max Eav. Thus both max Eav and Vom and Emax are ideal variables for assessing changes in myocardial contractility when preload and afterload are constant. Furthermore, Vom and max Eav permit development of the entire ejection fraction-afterload relationship for a given preload, thus providing a method for comparing myocardial contractile states between ventricles.

Relation between graded, subcritical impairments of coronary flow reserve and regional myocardial dysfunction induced by isoproterenol infusion in dogs

Isoproterenol has been used experimentally and clinically to elicit ischemia. The usefulness of this approach, however, in eliciting regional dysfunction in the presence of mild to moderate single-vessel coronary disease quantitated on the basis of coronary flow reserve measurements has not been previously defined. Open-chest, anesthetized dogs were instrumented with an electromagnetic flow probe, high-fidelity micromanometers, and subendocardial ultrasonic crystals. A rigid, screw occluder was used to produce five subcritical coronary stenoses in each dog associated with varying impairment of postocclusion reactive hyperemia at rest but no impairment of resting coronary blood flow. Regional function at rest and in response to the isoproterenol challenge (0.25 μg/kg/min) in nonstenotic and stenotic conditions was assessed. Relative regional function was maintained during the infusion until nearly total loss of coronary flow reserve. With this near-critical stenosis, function was lower than in the nonstenotic state but remained greater than resting control values. Moderate impairments of coronary flow reserve were not associated with isoproterenol-induced deterloration of regional function. In conclusion, detection of impaired coronary flow reserve at rest is a more sensitive index of the severity of a coronary stenosis than is detection of regional dysfunction during isoproterenol challenge. Fallure to maintain the expected isoproterenol-induced increase in regional function is manifested only when stenoses are associated with nearly total loss of resting coronary flow reserve. This suggests that the clinical use of isoproterenol challenge is not effective in eliciting regional dysfunction when mild coronary disease is present.

The hemodynamic determinants of the isovolumic index

The isovolumic index is a recently described echocardiographic parameter of left ventricular function that is calculated as the ratio between the sum of the time of isovolumic contraction and relaxation divided by the ejection time. Although the individual components of this index may be altered by heart rate and loading conditions, an analysis of the net effect of such alterations on the isovolumic index has not been undertaken. Thus, dogs were instrumented with high-fidelity micromanometers in the left ventricle, ascending aorta, and left atrium to allow determination of the individual comoonents of the isovolumic index and calculation of the index itself. Four sets of experiments were undertaken in random order. Left atrial pacing was used to increase heart rate by approximately 10 bpm in five steps. Preload was elevated in five stages by saline infusions which caused successive increases of 1 to 2 mm Hg in the left ventricular end-diastolic pressure. Systolic blood pressure was lowered or raised by approximately 10 mm Hg per stage by three progressive, steady-state infusions of nitroprusside and phenylephrine, respectively. These experiments demonstrated little change in the isovolumic index over a broad range of heart rate. Increased left ventricular end-diastolic pressure and decreased systemic pressure caused shortening of the index. Multiple regression analysis of all experiments yielded the following: isovolumic index = 0.41 − 0.015 (left ventricular end-diastolic pressure) + 0.004 (systolic blood pressure); r = 0.57, standard error = 0.13, p < 0.0001. Therefore, this investigation establishes the hemodynamic determinants of the isovolumic index and provides the basis for interpretation of directional changes in response to cardiac diseases and cardioactive drugs that can alter loading conditions.

Effects of pulsed external augmentation of diastolic pressure on coronary and systemic hemodynamics in patients with coronary artery disease

The purpose of this study was to define the effects of pulsed external diastolic pressure augmentation on coronary and systemic hemodynamics in 14 men with coronary artery disease and normal left ventricular function. Coronary sinus and great vein blood flow (thermodilution) and systemic hemodynamics were measured before, during, and after timed lower extremity compression, augmenting peak diastolic pressure to within 5 mm Hg of systolic pressure. Systolic and diastolic pressure-time indices were calculated from the high-fidelity micromanometer left ventricular-aortic recordings. External counterpulsation increased mean arterial pressure (108 ± 11 [1 SD] to 114 ± 12 mm Hg, p < 0.01) and the diastolic pressure-time index (440 ± 51 to 498 ± 82 units, p < 0.01), with no change in the systolic pressure-time index, absolute coronary sinus, or great cardiac vein blood flow. External diastolic pressure augmentation did not affect heart rate, right heart hemodynamics, cardiac output, or calculated myocardial oxygen consumption. An unanticipated finding was a ≥ 10% reduction in peak systolic pressure during external diastolic pressure augmentation in 8 of 14 patients. Despite minimal changes in absolute myocardial blood flow and oxygen consumption, the increase in the diastolic pressure-time/systolic pressure-time index ratio suggests that subendocardial perfusion may be favorably influenced by diastolic pressure augmentation and may explain the previously reported clinical benefits of external counterpulsation in some patients with ischemic heart disease.

Different effects of two types of ischemia on myocardial systolic and diastolic function.

Acute increases in left ventricular (LV) diastolic pressure relative to volume occur during angina in humans and after pacing tachycardia in dogs with coronary stenoses. In this study we assessed myocardial function following pacing tachycardia in dogs with coronary stenoses and compared it with function of the same myocardial segment during coronary occlusion. Also we calculated regional wall stiffness following pacing tachycardia in dogs with coronary stenoses. In anesthetized dogs with two-vessel critical (90%) coronary stenoses, ultrasonic crystals were implanted subendocardially to measure either anterior wall (AW) and lateral wall (LW) segment lengths (SL; n = 14) or LV wall thickness (h; n = 7). LV pressure was measured using a high-fidelity micromanometer catheter. After pacing tachycardia in dogs with two-vessel coronary stenoses, there was a substantial rise in LV end-diastolic pressure (from 6 +/- 1 to 15 +/- 1 mmHg; P less than 0.001), a slight increase in end-diastolic segment length (AWEDSL from 15.6 +/- 1.0 to 16.4 +/- 1.0 mm; p less than 0.01; and LWEDSL from 13.8 +/- 1.4 to 14.3 +/- 1.4 mm; P greater than 0.01) and a reduction of percent systolic shortening of the ischemic segments. An upward shift of the diastolic pressure-SL relation was observed in the postpacing period. During coronary occlusion the diastolic pressure-SL relation of the same segment shifted rightward, or rightward and downward, and systolic shortening became holosystolic bulging. Ischemia due to coronary stenoses plus increased O2 demand had substantially different effects on regional wall motion and segmental diastolic mechanics than did ischemia due to coronary occlusion. Over the same range of residual transmural LV diastolic pressure, the radial stiffness modulus was higher after pacing tachycardia in the presence of coronary stenoses.

Experimental coxsackie B3 virus myocarditis in golden hamsters. II. Evaluation of left ventricular function in intact in situ heart 14 months after inoculation.

The hemodynamic changes of the left ventricle (LV) of golden hamsters surviving for 14 months after acute coxsackie B3 virus myocarditis were assessed with the use of a high fidelity micromanometer pressure system. Of 25 infected hamsters, 10 survived to the 14th month, and 4 of these had cardiomegaly. Body weight (BW) was 150.0 +/- 20.7 g (mean +/- SD) (controls, 164.5 +/- 20.1 g, NS); heart weight (HW), 0.499 +/- 0.084 g (controls, 0.448 +/- 0.035 g, NS); and HW/BW, 3.39 +/- 0.79 X 10(-3) (controls, 2.74 +/- 0.23 X 10(-3), p less than 0.05). The hemodynamic data under anesthesia were: HR, 378 +/- 42 (controls, 414 +/- 43, NS); LVSP, 108 +/- 16 mmHg (controls, 126 +/- 16, NS); LVDP, 4.0 +/- 4.8 mmHg (controls, 0.6 +/- 0.7, NS); LVEDP, 9.7 +/- 7.5 mmHg (controls, 3.4 +/- 1.4, NS); peak positive dp/dt, 4960 +/- 1431 mmHg/sec (controls, 6714 +/- 1326, p less than 0.05); (dp/dt)/DP40, 56.8 +/- 9.8 sec-1 (controls, 73.1 +/- 7.0, p less than 0.01); peak negative dp/dt, 3876 +/- 1072 mmHg/sec (controls, 4971 +/- 599, p less than 0.05); and time constant T of LV pressure fall, 7.7 +/- 1.3 msec (controls, 5.9 +/- 0.7, p less than 0.01). Five hamsters had congestion of the lungs and liver with or without an elevation of LVEDP. One of them had an organizing thrombus in the left atrium, and one had an aneurysm in the LV free wall. Though markedly varied in extent, residual myocardial fibrosis was always evident in the hearts in which isovolumic contractility and early diastolic relaxation of the LV were significantly impaired. In a clinical extension of these findings, it may be that some cases of dilated cardiomyopathy in man develop in a way similar to the pathological processes noted in this experiment.

Comparative effects of ionic and nonionic contrast materials on indexes of isovolumic contraction and relaxation in humans

The effects of contrast media on left ventricular (LV) relaxation as assessed by the time constant of iso-volumic relaxation have not previously been studied. A new nonionic contrast agent (iohexol) has been shown to have fewer deleterious effects than standard ionic agents. Nineteen patients received iohexol and sodium meglumine diatrizoate (Renografin-76 ®) in a double-blind, crossover study during left and right coronary arteriography and with simultaneous high-fidelity micromanometer measurements of LV pressure. Neither agent induced significant changes in LV end-diastolic pressure after right or left coronary arteriography. After right coronary arteriography, neither agent produced significant deterioration of peak positive dP dt or ( dP dt ) DP 40 ( dP dt at a developed pressure of 40 mm Hg). However, after right coronary arteriography both agents caused a transient deterioration in peak negative dP dt and the time constant of isovolumic relaxation (p < 0.05 at 20 seconds after arteriography). After left coronary arteriography, sodium meglumine diatrizoate induced deterioration of systemic blood pressure (p < 0.05), peak positive dP dt (p < 0.01), ( dP dt ) DP 40 (p < 0.05), peak negative dP dt (p < 0.01) and the relaxation time constant (p < 0.01). These effects were not induced by iohexol. Thus, nonionic contrast media exert negligible alterations on LV function when used for coronary arteriography. The findings are of potential clinical importance in view of the large number of patients with depressed LV function who undergo coronary arteriography.

Effect of the ouabain-quinidine interaction on left ventricular and left atrial function in conscious dogs.

The effect of the ouabain-quinidine interaction was examined in 10 conscious dogs. Left ventricular (LV) pressure, LV dP/dt, LV diameter and left atrial (LA) diameter were measured with high-fidelity micromanometers and sonomicrometer crystals. Ouabain, 0.025 mg/kg, significantly (p less than 0.05) increased LV dP/dt, LV and LA fractional shortening and LV and LA velocity of circumferential fiber shortening (Vcf). In a separate experiment, quinidine was administered as a bolus dose, 3.85 mg/kg, followed by an infusion, 0.28 mg/kg/min. This resulted in steady-state quinidine concentrations that produced no change in wall motion or hemodynamics. When ouabain was given 1 hour into the quinidine infusion, only LV dP/dt increased significantly (p less than 0.05). Ouabain alone increased LV dP/dt 26.4 +/- 3.5%, whereas ouabain during the quinidine infusion increased it by 9.5 +/- 2.3%. Similar differences were seen in the responses to ouabain in the absence and presence of quinidine: LV Vcf, 22.4 +/- 4.9% vs 6.0 +/- 2.1%, LV fractional shortening, 23.1 +/- 4.6% vs 5.8 +/- 2.1%, LA Vcf, 22.7 +/- 5.9 vs 4.6 +/- 2.0% and LA fractional shortening, 21.8 +/- 7% vs 7.8 +/- 3.3%. Thus, in the presence of quinidine the increase in intropy usually seen with ouabain was markedly attenuated. These data suggest that the quinidine-induced increase in digoxin serum concentrations is accompanied by a decrease in the contractile response of the heart to digoxin.

Effects of short-term administration of verapamil on left ventricular relaxation and filling dynamics measured by a combined hemodynamic-ultrasonic technique in patients with hypertrophic cardiomyopathy.

The effects of short-term administration of verapamil on left ventricular isovolumetric relaxation and early and late diastolic filling dynamics were studied in 10 patients with hypertrophic cardiomyopathy by a combined hemodynamic-ultrasonic technique. Left ventricular pressures (recorded with high-fidelity micromanometers) were determined simultaneously with M mode echocardiography. After 10 mg of verapamil was given intravenously (2 mg/min), left ventricular contractility and systolic pressure dropped significantly (p less than .05). Left ventricular dP/dt fell from 1947 +/- 544 to 1489 +/- 334 mm Hg/sec, maximal velocity of the contractile element at zero load fell from 50 +/- 17 to 42 +/- 15 1/sec, peak velocity contraction of the contractile element fell from 37 +/- 10 1/sec to 29 +/- 10 1/sec (p less than .05), and left ventricular systolic pressure fell from 149 +/- 30 to 127 +/- 22 mm Hg. Left ventricular negative dP/dt increased from 1770 +/- 479 to 1477 +/- 377 mm Hg/sec (p less than .05), and the time constant of isovolumetric pressure decay was prolonged from 48 +/- 9 to 64 +/- 15 msec (p less than .05). Left ventricular end-diastolic pressure rose from 21 +/- 7 to 23 +/- 6 mm Hg (p less than .05). The time constant of isovolumetric pressure decay was calculated in three different ways, but none of these measurements was influenced by verapamil. Time of isovolumetric relaxation, duration of rapid ventricular filling, and peak rate of left ventricular lengthening were not significantly influenced by verapamil and remained highly abnormal. In contrast, peak rate of left ventricular posterior wall thinning declined further after verapamil from 2.9 +/- 1.2 to 2.4 +/- 1.4 1/sec (p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ischemia on left ventricular regional function in the conscious dog.

Three-dimensional regional geometry of the left ventricle was assessed in seven conscious trained dogs chronically implanted with pulse-transit ultrasonic-dimension transducers. Minor and major axis segment lengths and wall thickness were measured in the distribution of the left anterior descending coronary artery; transmural pressure (TMP) was measured with high-fidelity micromanometers. Data were recorded during the control state and following 30 s and 30 min of ischemia. Dimensions were normalized as a fractional extension from the length at zero TMP (Lo). Dynamic cube mass was calculated and remained constant throughout the cardiac cycle in both control and ischemic states, although the calculated mass decreased by an average of 5% during ischemia. The slope constants of the exponential diastolic pressure-dimension relationship increased following acute coronary occlusion indicating increases in regional myocardial stiffness with increasing periods of ischemia. Coronary occlusion also was associated with an increase in the Lo measurements in the major and minor axis dimensions and a decrease in the wall thickness Lo. These findings are consistent with an ischemia-induced plastic deformation of the regional myocardium defined as creep. Thus, acute ischemia results in a decline of regional systolic function, induces myocardial creep, and causes an immediate and sustained increase in regional myocardial stiffness.

Left ventricular function in exercise-induced hypertrophy in dogs

Indexes of left ventricular function and diastolic compliance were studied in 10 awake exercise-trained greyhounds with left ventricular hypertrophy. Mean left ventricular to body weight ratio and mean myocardial cell diameter were significantly greater than in normal dogs (8.73 ± 2.7 [standard error of the mean]versus 4.63 ± 0.24 g/ kg, P <0.01; and 18.3 ± 0.67 versus 12.5 ± 0.71 μ, P <0.01, respectively). In awake resting animals, 7 to 50 days after implantation of a high fidelity micromanometer and sonomicrometer crystals, left ventricular contractility indexes were similar to those measured previously in normal dogs (maximal derivative of left ventricular pressure [dP/dt] 3,800 ± 250 versus 3,810 ± 330 mm Hg/ sec, difference not significant; and mean rate of circumferential fiber shortening 1.54 ± 0.12 versus 1.43 ± 0.12 sec −1, difference not significant). During volume loading sufficient to produce a left ventricular end-diastolic pressure of 20 mm Hg, changes in contractility Indexes were similar to those in normal dogs; however, heart rate increased significantly (74 percent, P <0.005) in the trained greyhounds but not in normal dogs. Left ventricular diastolic stiffness did not differ from normal (51.6 ± 3.0 versus 45.9 ± 5.9 mm Hg/ cm, P <0.01). These findings suggest that left ventricular function in exercise-induced left ventricular hypertrophy is substantially normal.

Force-frequency characteristics of the left ventricle in the conscious dog.

SUMMARY The early and late alterations in left ventricular function which follow a change in contraction frequency were assessed in 10 conscious dogs. Chronically implanted pulse-transit ultrasonic dimension transducers were wed to measure the dynamic geometry of the left ventricle and a high-fidelity micromanometer was employed to measmre left ventricular pressure. The heart was paced from the atrium and, after every 20th regular beat, an extrasystole and a postextrasystole were introduced into the basic pacing rhythm. The ratio of the maximum derivative of left ventricular pressure (!*„,„) of the postextrasystolic beat to the P,, , of the control beat was used as a measure of the degree of postextrasystolic potentiation of ventricular function. This postextrasystolic ratio was found to be significantly influenced by the interval preceding the postextrasystolic beat; as this interval was increased, the end-diastolic volume and the Vnax of the postextrasystole also increased. When the end-diastolic geometry of the control and postextrasystolic beats were made identical, the postextrasystolic ratio reflected postextrasystolic potentiation of the inotropic state. The degree of postextrasystolic inotropic potentiation was found to be a direct linear function of the change in contraction frequency induced by the extrasystole (r 2= 0.97). Thus, end-diastolic geometry and the magnitude of the frequency perturbation must be carefully controlled when postextrasystolic potentiation is used to evaluate left ventricular function. In contrast to postextrasystolic potentiation, steady state changes in contraction frequency did not significantly alter VmMX (P > 0.20). However, significant decreases in end-diastolic volume were observed with increasing steady state heart rates (P < 0.0S). This decrease in end-diastolic volume may be partially responsible for the lack of potentiation of steady state Pmml after a sustained increase in contraction frequency. THE DEPENDENCE of the force of contraction on the frequency of preceding contractions is a fundamental property of myocardium first appreciated by Bowditch in his 1871 description of the treppe phenomenon. 1 Since

Hyperfunction with normal inotropic state of the hypertrophied left ventricle.

Conscious dogs were instrumented with an inflatable cuff around the ascending aorta, a high-fidelity micromanometer in the left ventricle (LV), and pairs of ultrasonic crystals for measurements of LV wall thickness and internal LV diameter. Wall stress (WSt) and mean velocity of wall shortening (VCF) were calculated. Mean force-velocity relations and WSt-diameter loops in single contractions were then analyzed over a range of matched systolic pressures during acute aortic constrictions both before and after induction of chronic hypertrophy by sustained aortic constriction. At normal LV systolic pressures and at each matched level of systolic LV pressure, wall shortening velocity was increased in the hypertrophied ventricle. However, force-velocity relations obtained by relating mean VCF to mean WSt at various stress levels fell on the same relation as during control. The linear relation between LV diameter and pressure at the end of ventricular ejection was shifted to the left in the hypertrophied ventricle, indicating enhanced shortening. However, linear WSt-diameter relations at end-ejection were not different in control and hypertrophied hearts. These findings indicate that the ventricle hypertrophied by pressure overload exhibited hyperfunction as a pump but that its myocardium had a normal level of inotropic state.

Evaluation of the force-frequency relationship as a descriptor of the inotropic state of canine left ventricular myocardium.

The short-term force-frequency characteristics of canine left ventricular myocardium were examined in both isolated and intact preparations by briefly pertubing the frequency of contraction with early extrasystoles. The maximum rate of rise of isometric tension (Fmas) of the isolated trabeculae carneae was potentiated by the introduction of extrasystoles. The ratio of Fmas of potentiated to control beats (force-frequency ratio) was not altered significantly by a change in muscle length. However, exposure of the trabeculae to isoproterenol (10(-7)M) significantly changed the force-frequency ratio obtained in response to a constant frequency perturbation. Similar experiments were performed on chronically instrumented conscious dogs. Left ventricular minor axis diameter was measured with implanted pulse-transit ultrasonic dimension transducers, and intracavitary pressure was measured with a high fidelity micromanometer. Atrial pacing was performed so that the end-diastolic diameters of the beats preceding and following the extrasystole could be made identical. Large increases in the maximum rate of rise of pressure (Pmas) were seen in the contraction after the extrasystole. The ratio of Pmax of the potentiated beat to that of the control beat was not changed by a 9% increase in the end-diastolic diameter, produced by saline infusion. Conversely, isoproterenol significantly altered this relationship in the same manner as in the isolated muscle. Thus, either in vitro or in situ, left ventricular myocardium exhibits large functional changes in response to brief perturbations in rate. The isoproterenol and length data indicate that the force-frequency ratio reflects frequency-dependent changes in the inotropic state, independent of changes in length.

The three-dimensional dynamic geometry of the left ventricle in the conscious dog.

The dynamic geometry of the left ventricle was assessed with the use of chronically implanted pulse-transit ultrasonic dimension transducers. The orientation of the transducers allowed the measurement of left ventricular minor and major axis diameters and equatorial wall thickness in the conscious dog. The left ventricle was modeled as a three-dimensional, prolate ellipsoidal shell. Left ventricular and pleural pressures were measured with high fidelity micromanometers. Aortic blood flow was obtained with electromagnetic flow probes. To test the assumptions inherent in this technique, left ventricular mass, internal volume, stroke volume, and peak aortic flow were computed from the dimension data and compared to directly measured values. Correlation coefficients of 0.95 or greater were obtained for each of these comparisons. In addition, the calculated left ventricular mass was constant to within +/- 6% of the mean value throughout the cardiac cycle. We found that the dynamic contraction pattern of the left ventricle was dependent on the physiological state of the dog. Furthermore, in the conscious state, shortening of the minor axis diameter, lengthening of the major axis diameter, and slight thickening or thinning of the wall were noted during isovolumic contraction (isovolumic ellipticalization pattern). In the open-chested, anesthetized state, however, marked rearrangements in geometry were observed during isovolumic contraction manifested by lengthening of the minor axis diameter, and significant thickening of the wall (isovolumic sphericalization pattern). We also observed that left ventricular volume was significantly diminished in the open-chested state. The isovolumic contraction pattern in open-chested dogs could be changed from sphericalization to ellipticalization by increasing end-diastolic volume with the infusion of saline. During a vena caval occlusion in the conscious state, the contraction pattern changed from isovolumic ellipticalization to isovolumic sphericalization as the end-diastolic volume decreased. Thus, the exact pattern of left ventricular contraction was found to be a function of left ventricular volume.

Influence of poststimulation potentiation and heart rate on the fetal lamb heart.

Isolated cardiac muscle techniques and studies of the chronically instrumented fetal lamb heart were employed to evaluate the ability of fetal myocardium to exhibit poststimulation potentiation. Isometric tension development and the response to paired electrical stimulation were significantly reduced in isolated fetal ventricular myocardium when compared to the adult (P less than 0.001). As in the adult, increasing stimulation frequency raised fetal isometric tension via an increase in the rate of rise of tension development in the presence of reduction in time-to-peak tension. In seven fetal lambs the left ventricle was chronically instrumented with endocardial ultrasonic crystals and a high-fidelity micromanometer. After a 2-wk recovery period, heart rate was increased by atrial pacing from an average control level of 150 to 300 beats/min. Left ventricular dP/dt increased progressively and then fell beyond a heart rate of 270/min. When comparable pre- and immediate postpacing beats were analyzed, a step-wise increase in the velocity of left ventricular shortening and the mean rate of circumferential fiber shortening was observed in association with an increase in the extent of shortening. Thus, increases in the frequency of contraction exert a significant positive inotropic effect on the fetal heart.