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Biomedical subjects

W C Little

Publications and source records attributed to W C Little.

At least 19 recordsLinked to original sources
PubMed1992

Potential precipitating factors of the onset of myocardial infarction.

Myocardial infarction (MI) usually results from thrombotic coronary artery occlusion at the site of a ruptured atherosclerotic plaque. The factors responsible for triggering MI are not known but conditions that increase serum catecholamines may be involved. Accordingly, the authors prospectively evaluated the presence of factors that may increase catecholamines immediately prior to MI in 186 patients. Myocardial infarction was documented by a rise in serum CK-MB. There were 149 men and 37 women, aged 57 +/- 12 (mean +/- SD) years. All patients were interviewed within 72 hours of admission concerning strenuous physical activity, emotional stress, and assumption of the upright posture immediately prior to the onset of symptoms. Seventy-five (40%) patients had one or more of these factors immediately prior to the onset of MI chest pain. Fourteen (8%) experienced acute emotional upset; 28 (15%) were involved in strenuous physical activity; and 39 (21%) had suddenly changed position. In the latter group, 18 changed from being supine for more than 1 hour to standing; three rose from supine to sitting; and 18 changed from prolonged sitting (greater than 60 minutes) to standing. The conclusion is that a potential triggering factor is present in many patients immediately prior to the onset of MI. A sudden change in position is the most frequent potential trigger, typically occurring the morning after awakening from sleep.

Circadian Rhythm↗
PubMed1992

Restraining effect of intact pericardium during acute volume loading.

To determine the effect of the intact pericardium on ventricular end-diastolic pressures (EDP) during acute volume loading, we measured left ventricular (LV) and right ventricular (RV) micromanometer pressure and LV volume using a conductance catheter in eight open-chest, anesthetized dogs. A range of LV pressure and volume was obtained by intravascular volume expansion with the pericardium intact and then over a similar range after removal of the pericardium. Pericardial pressure (Pper) was calculated using static equilibrium analysis as the difference between LVEDP with the pericardium present and absent at a constant LV volume. At the beginning of the fluid infusion (LVEDP 7.3 +/- 1.7 mmHg and RVEDP 4.4 +/- 2.6 mmHg, mean +/- SD), Pper was not different from zero (-1.0 +/- 2.3 mmHg, P not significant). The onset of pericardial restraint (Pper greater than or equal to 0 mmHg) occurred when LVEDP was 9.1 +/- 2.9 mmHg and RVEDP was 4.1 +/- 2.9 mmHg. At low cardiac volumes before fluid infusion, RV transmural pressure was positive and significantly greater than the near zero Pper. After the onset of pericardial restraint, however, RVEDP and Pper increased similarly and were related according to Pper = 1.1 (+/- 0.34) RVEDP - 4.2 (+/- 2.6) mmHg, standard deviation 0.6 +/- 0.8 mmHg, r = 0.98 +/- 0.10. These data indicate that the intact pericardium behaves in two functionally distinct ways. At low cardiac volumes, Pper is zero and the pericardium does not affect LV filling. RV transmural pressure is positive and greater than Pper.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Mechanism of augmented rate of left ventricular filling during exercise.

At rest, most of left ventricular (LV) filling occurs early in diastole. This LV filling occurs in response to the pressure gradient produced as LV pressure falls below left atrial (LA) pressure. Because mitral valve flow occurs in response to an LA to LV pressure gradient, augmented diastolic mitral valve flow during exercise may be due to an increased mitral valve pressure gradient resulting from a rise in LA pressure and/or a fall in LV early diastolic pressure. Accordingly, we studied 13 conscious dogs, instrumented to measure micromanometer LV and LA pressures, and determined LV volume from three ultrasonic dimensions during exercise. The animals ran on a treadmill for 8-15 minutes at 5-8 miles/hr. With reflexes intact, during exercise, the heart rate increased from 116 +/- 20 to 189 +/- 24 beats per minute (mean +/- SD, p less than 0.01), the maximum rate of change of LV volume (dV/dtmax) increased from 185 +/- 44 to 282 +/- 76 ml/sec (p less than 0.01), the ejection fraction and cardiac output increased, and the duration of diastole decreased from 296 +/- 83 to 162 +/- 71 msec (p less than 0.01). Mitral valve opening pressure, mean LA pressure (10.9 +/- 4.4 versus 10.2 +/- 3.9 mm Hg, p = NS), and LV end-diastolic pressure (12.8 +/- 4.8 versus 13.1 +/- 3.3 mm Hg, p = NS) were all relatively unchanged. The time constant of the fall of isovolumic LV pressure decreased from 28 +/- 3.3 to 21 +/- 4.4 msec (p less than 0.05). The early diastolic portion of the LV pressure-volume loop was shifted downward during exercise, with the minimum LV pressure decreasing from 3.3 +/- 2.8 to -2.8 +/- 3.4 mm Hg (p less than 0.05) and the maximum mitral valve pressure gradient increasing from 5.5 +/- 1.7 to 11.8 +/- 3.5 mm Hg (p less than 0.01). A similar downward shift of the early diastolic portion of the LV pressure-volume loop was produced by infusion of dobutamine (6 micrograms/kg/min i.v.) at rest, as well as by exercise when the heart rate was held constant by right ventricular pacing at 190-210 beats per minute. The downward shift during exercise was prevented by beta-blockade (metoprolol, 0.5 mg/kg i.v.). We conclude that during exercise, sympathetic stimulation and tachycardia produce a downward shift of the early diastolic portion of the LV pressure-volume loop.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗
PubMed1991

The underlying coronary lesion in myocardial infarction: implications for coronary angiography.

Myocardial infarction is usually caused by sudden thrombotic occlusion of a coronary artery at the site of a fissured atherosclerotic plaque. Recent evidence suggests that coronary angiography may be insensitive in detecting and quantitating atherosclerosis. Serial angiographic studies demonstrate that the majority of myocardial infarctions occur due to occlusion of arteries that previously did not contain angiographically significant (greater than 50%) stenoses. Similarly, quantitative angiography performed after thrombolytic therapy indicates that the coronary lesion underlying the clot is frequently not severely stenotic. Thus, an angiographically apparent stenosis is not necessary for the development of a thrombotic occlusion resulting in an MI. These observations suggest that coronary angiography does not accurately predict the site of a subsequent occlusion that will produce a myocardial infarction.

Autopsy↗
PubMed1991

ULFS-49 causes bradycardia without decreasing right ventricular systolic and diastolic performance.

The effects of ULFS-49, a new calcium channel blocker, on right ventricular (RV) systolic and diastolic performance were evaluated in nine anesthetized, closed-chest dogs by load-insensitive indexes. ULFS-49 (0.3 mg/kg) decreased heart rate (HR) from 76 +/- 25 to 47 +/- 11 beats/min (p less than 0.01) and cardiac output (CO) from 1.89 +/- 0.62 to 1.42 +/- 0.72 L/min (p less than 0.01), as RV free wall end-diastolic area increased from 486 +/- 126 to 581 +/- 45 mm2 (p less than 0.01) and RV end-diastolic volume increased from 66.6 +/- 26.4 to 85.3 +/- 28.5 ml (p less than 0.05). Pacing at 100 beats/min ablated these hemodynamic and dimensional changes. RV free wall contractility was assessed by the slope and midrange intercept values of the relation between RV end-systolic pressure (Pes) and end-systolic free wall area (Aes) and between RV free wall segmental work (SW) and end-diastolic area (Aed). RV free wall stiffness was measured by exponential fit of the RV end-diastolic pressure (Ped)-Aed points during caval occlusion. With pacing at 100 beats/min, the slope of the Pes-Aes relationship was unchanged by ULFS-49 (0.52 +/- 0.29 vs. 0.60 +/- 0.35 mm Hg/mm2) as was the midrange intercept (382.3 +/- 114.7 vs. 387.1 +/- 121.5 mm2). After administration of ULFS-49, the slope of the SW-Aed relation increased from 31.8 +/- 14.4 to 37.3 +/- 17.7 mm Hg.mm2 (p less than 0.05) without changing the midrange intercept (410.5 +/- 108.1 mm2 vs. 413.0 +/- 107.0 mm2). Similarly, neither the position nor curvature of the Ped-Aed relation was changed by ULFS-49. These data demonstrate that ULFS-49 causes significant bradycardia and increases the size of the right ventricle without directly depressing RV free wall systolic or diastolic performance.

Animals↗
PubMed1991

Left ventricular ejection activation in the in situ heart.

We tested, in the in situ heart, the hypothesis that the end-systolic pressure (ESP) of small ejecting contraction (EC) is greater than that of an isovolumic contraction (IC) with a similar end-systolic volume. We produced ECs with varying amounts of ejection by partial aortic occlusion while measuring left ventricular pressure, one or two left ventricular dimensions (anteroposterior and septal-lateral), and aortic flow. In 11 dogs, we plotted ventricular pressure against the time integral of aortic flow of ECs and IC with the same end-diastolic anteroposterior dimension. The end-systolic pressure-volume line was drawn from the peak isovolumic pressure-volume point tangential to the left upper corner of the pressure-volume loop of ECs. The slope of the tangential line of the middle EC, whose stroke volume was 51 +/- 8% of that of the control EC, was decreased by 54 +/- 16% compared with that of the control EC. In eight dogs with two pairs of crystals, left ventricular volume was controlled by partial vena caval occlusion, and ICs were produced by total aortic occlusion. The end-systolic pressure of small ejections exceeded (11.3 +/- 7.7 mmHg, P less than 0.01) those of isovolumic contractions with the same end-systolic cross-sectional area, whereas the end-systolic pressure of beats with large ejections was similar (-9.4 +/- 14.4 mmHg, P = NS) to an IC with the same end-systolic cross-sectional area. We conclude that the end-systolic pressure-volume point of beats with a small ejection is located above the isovolumic end-systolic pressure-volume relation in the in situ dog left ventricle.

Animals↗
PubMed1991

Left ventricular-arterial coupling in conscious dogs.

We investigated the criteria for the coupling of the left ventricle (LV) and the arterial system to maximize LV stroke work (SW) and the transformation of LV pressure-volume area (PVA) to SW. We studied eight conscious dogs that were instrumented to measure LV pressure and determine LV volume from three ultrasonically determined dimensions. The LV end-systolic pressure (PES)-volume (VES) relation was determined by caval occlusion. Its slope (EES) was compared with the arterial elastance (EA) and determined as PES per stroke volume. At rest, with intact reflexes, EES/EA was 0.96 +/- 0.20 EES/EA was varied over a wide range (0.18-2.59) by the infusion of graded doses of phenylephrine and nitroprusside before and during administration of dobutamine. Maximum LV SW, at constant inotropic state and end-diastolic volume (VED), occurred when EES/EA equaled 0.99 +/- 0.15. At constant VED and contractile state, SW was within 20% of its maximum value when EES/EA was between 0.56 and 2.29. The conversion of LV PVA to SW increased as EES/EA increased. The shape of the observed relations of the SW to EES/EA and SW/PVA to EES/EA was similar to that predicted by the theoretical consideration of LV PES-VES and arterial PES-stroke volume relations. We conclude that the LV and arterial system produce maximum SW at constant VED when EES and EA are equal; however, the relation of SW to EES/EA has a broad plateau. Only when EA greatly exceeds EES does the SW fall substantially. However, the conversion of PVA to SW increases as EES/EA increases. These observations support the utility of analyzing LV-arterial coupling in the pressure-volume plane.

Animals↗
PubMed1991

Effect of felodipine on left ventricular performance in conscious dogs: assessment by left ventricular pressure-volume analysis.

We assessed the effect of felodipine on left ventricular (LV) performance in 10 healthy, conscious, chronically instrumented dogs, using load-independent measures derived from variably loaded pressure-volume relations. With all reflexes intact, felodipine (25 nmol/kg, intravenously) caused significant decreases in LV end-systolic pressure (132 +/- 13 vs. 109 +/- 14 mm Hg, P less than .05) and effective arterial elastance (11.1 +/- 1.6 vs. 8.7 +/- 1.1 mm Hg/ml, P less than .01), while the heart rate increased (109 +/- 15 vs. 118 +/- 16 min-1, P less than .05). There were no significant changes in LV end-systolic volume, stroke volume or the maximum time derivative of LV pressure. The plasma felodipine concentration was 16.1 +/- 1.4 nmol/l (mean +/- time S.D.). Three relations that provide load-insensitive measures of LV performance were determined from variably loaded pressure-volume loops produced by transient caval occlusions. Felodipine increased the slopes of the LV end-systolic pressure-volume relation (8.1 +/- 0.9 vs. 10.3 +/- 1.3 mm Hg/ml, mean +/- S.D., P less than .05), the maximal time-derivative of LV pressure-end-diastolic volume relation (103 +/- 28 vs. 127 +/- 34 mm Hg/sec ml, P less than .05) and the stroke work-end diastolic volume relation (82 +/- 4 vs. 93 +/- 6 mm Hg, P less than .05). All three relations were shifted toward the left after felodipine. Similar increases in slopes and leftward shifts with felodipine, indicating enhanced contractile effect, were also present after autonomic blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction.

Serial angiographic studies of patients with myocardial infarction and unstable angina suggest that the culprit plaque underlying a thrombus need not have produced severe luminal obstruction before onset of the event. An atherosclerotic coronary artery lesion can, therefore, have 2 important characteristics. First, it may be obstructive. Second, it may be "vulnerable" in that it has the potential to become thrombogenic if exposed to the appropriate triggering stimulus. A lesion need not be obstructive to become thrombogenic, nor do all obstructive lesions have thrombogenic potential. The cause of an infarction may thus be rupture of a nonobstructive plaque leading to occlusive thrombus formation. Because it may be difficult to predict the site of a subsequent occlusion from a coronary angiogram, coronary bypass surgery or angioplasty directed only at discernible stenotic lesions may not be effective for preventing subsequent myocardial infarctions. Appropriate therapy may need to be directed at the entire coronary tree. Such therapy might include cholesterol lowering, beta blockade and aspirin.

Angiography↗
PubMed1990

Effect of alteration in loading conditions on both normal and abnormal patterns of left ventricular filling in healthy individuals.

Doppler analysis of mitral flow provides a means of analyzing left ventricular (LV) diastolic function. While experimental studies have suggested that changes in left atrial pressure may affect the normal pattern of early diastolic filling, the effect of such changes on abnormal patterns of filling is unknown. Accordingly, the Doppler pattern of LV filling was analyzed in 20 subjects with LV hypertrophy (mean age 59 +/- 13 years, +/- standard deviation), in 25 healthy normal subjects (29 +/- 6 years) and in 11 elderly subjects (68 +/- 5 years). All underwent Doppler examination of LV inflow at rest and immediately after postural changes. In all 3 groups, head-down positioning increased early diastolic flow velocity (E) (p less than 0.001), and raised the E to late diastolic flow velocity (A) ratio (p less than 0.01). However, an abnormal E/A ratio never approached a normal resting value. Likewise, although E and the E/A ratio decreased significantly in normal subjects with head-up positioning, it did not become abnormal. The magnitude of change in E, A and E/A ratio did not differ among the 3 groups in response to postural changes. Thus, alterations of LV loading conditions alter the pattern of LV filling, whether normal or abnormal at baseline. The magnitude of change appears to be independent of the resting flow pattern. Although loading conditions may affect the Doppler pattern of filling, simple changes in venous return do not "normalize" an abnormal pattern, nor do they "abnormalize" a normal pattern.

Adult↗
PubMed1990

Effect of acute cardiac tamponade on left ventricular pressure-volume relations in anaesthetised dogs.

STUDY OBJECTIVE: The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN: Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation, the left ventricular dP/dtmax-end diastolic volume relation, and the left ventricular stroke work-end diastolic volume relation during acute cardiac tamponade in dogs. EXPERIMENTAL MATERIAL: In eight pentobarbitone anaesthetised dogs (15.7-24.8 kg), transducer tipped and volume impedance catheters were positioned in the left ventricle. Through a median sternotomy incision, a pericardial catheter was inserted to produce varying stages of cardiac tamponade. By the use of transient bicaval occlusions, variably loaded pressure-volume loops were recorded. MEASUREMENTS AND RESULTS: Incremental tamponade reduced mean arterial pressure from 105(SEM 3) to 89(2) mm Hg (mild tamponade), 75(2) mm Hg (moderate tamponade), and 59(10) mm Hg (severe tamponade). The slope of the end systolic pressure-volume relation was 6.3(1.2) mm Hg.ml-1 at baseline and increased slightly to 7.7(1.8), 8.5(1.3), and 9.2(1.5) mm Hg.ml-1 with the progressive levels of tamponade (NS). The role of autonomic reflexes was assessed by repeating the tamponade sequence after beta adrenergic blockade with 10 mg of metoprolol intravenously. The slope of the end systolic pressure-volume relation was reduced by metoprolol, at 4.9(1.0) mm Hg.ml-1 (p less than 0.01), but was not significantly altered by the sequence of tamponade following beta blockade [5.6(0.9), 6.0(1.0), and 5.5(7.0) mm Hg.ml-1, respectively (NS)]. Neither were changes found indicative of depressed contractile function with progressive tamponade in the slopes of the left ventricular dP/dtmax-end diastolic volume and stroke work-end diastolic volume relations. CONCLUSIONS: Left ventricular contractility was not altered during acute cardiac tamponade in an anaesthetised, closed chest canine model. Depressed left ventricular contractile function was not responsible for the observed haemodynamic deterioration.

Acute Disease↗
PubMed1990

External pressure of undisturbed left ventricle.

We evaluated the contribution of the thorax and the undisturbed pericardium to the external pressure of the euvolemic left ventricle in thirteen anesthetized dogs. Left ventricular (LV) end-diastolic pressure (EDP) in the euvolemic state was 7 +/- 2 mmHg initially and increased to 10 +/- 2 mmHg after the chest and pericardium were opened. LV end-diastolic volume (conductance catheter) was 43 +/- 20 ml initially and did not change after the chest or the pericardium was opened. Intrathoracic (PIT) and pericardial (PPER) pressures were calculated as the difference in LV chamber pressure before and after opening these spaces. Thus for the LV, PIT was -3 +/- 1 mmHg, and PPER was 0 +/- 2 mmHg. Isovolumic relaxation, early diastolic filling, and total diastolic filling were not significantly altered after the chest or pericardium was opened. Thus under euvolemic conditions in this model pericardial pressure is negligible, and the external pressure of the undisturbed left ventricle is negative and equal to intrathoracic pressure.

Animals↗
PubMed1990

Simultaneous conductance catheter and dimension assessment of left ventricle volume in the intact animal.

We compared left ventricle (LV) volume (V) simultaneously measured using the conductance catheter (VM) with volume calculated from three LV dimensions (VD) determined ultrasonically from endocardial crystals. Seven adult mongrel dogs (20-30 kg) were anesthetized and instrumented to measure micromanometer LV pressure and V. Three pairs of crystals were placed orthogonally in subendocardial positions and a conductance catheter was placed in the LV retrograde across the aortic valve. Under steady-state conditions, over the range of a single cardiac cycle, the relation between VM and VD was well described by a straight line. There was an excellent correlation of conductance and dimension volumes with r equal to 0.97 +/- 0.04 and SEE 0.8 +/- 0.5 ml. The gain (1/alpha) and parallel conductance volume (alpha VC) were constant. At lower volumes obtained during bicaval occlusion, however, the relation between VM and VD was curvilinear. 1/alpha and alpha VC both decreased as LVV fell. Thus, determination of absolute volume using the conductance catheter depended on the conditions under which the data were obtained. Under steady-state conditions, alpha VC calculated by both the saline method (mean +/- SD, 50 +/- 15 ml) and by regression of VM and VD, (45 +/- 21 ml) were similar. Consequently, absolute LV end-diastolic volumes and end-systolic volumes by the conductance and dimension methods were similar (53 +/- 14 ml and 38 +/- 14 ml vs. 56 +/- 17 ml and 44 +/- 16 ml, respectively, p = NS). When volume decreased during bicaval occlusion, there was a progressively greater decrease in VM as compared with VD. The absolute slope (EES) of the end-systolic pressure-volume relation (ESPVR) was consistently higher by the dimension method, group average, 16.3 +/- 7.6, than by the catheter, 8.5 +/- 5.9, p less than 0.05. The direction and magnitude of the change in EES at different inotropic states (autonomic blockade; dobutamine), however, was similarly measured by both the conductance catheter and dimension method. We conclude that the gain and offset of the conductance catheter are relatively constant at steady state but vary when volume is reduced by caval occlusion. Thus, the conductance catheter accurately measures absolute volumes at steady state but can underestimate the slope and position of the ESPVR when it is determined by caval occlusion. The conductance catheter does, however, accurately measure the directions and magnitude of change in contractile state.

Animals↗