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Biomedical subjects

B D Hoit

Publications and source records attributed to B D Hoit.

At least 73 records · Page 4Linked to original sources

Effects of a novel inotropic agent (OPC-18790) on systolic and diastolic function in patients with severe heart failure.

A double-blind placebo-controlled study to determine the acute hemodynamic and cardiac mechanical effects of the quinolinone derivative OPC-18790 was performed in 12 patients with New York Heart Association class III or IV congestive heart failure. Simultaneous echocardiographic, Doppler, and invasive hemodynamic studies were performed before and after a 6-hour intravenous infusion of drug at 2.5, 5.0, or 10.0 micrograms/kg/min or of placebo. OPC-18790 (mean dose 5.9 +/- 3.5 mg) caused significant increases in left ventricular (LV) ejection fraction (15% +/- 4% vs 23% +/- 5%; p < 0.05) and cardiac index (1.7 +/- 0.4 vs 2.5 +/- 0.6 L/min/m2; p < 0.05) and a rightward and upward shift in the stress-shortening relation. LV end-diastolic volume and heart rate were unchanged. LV filling and posterior LV wall thinning rates from digitized M-mode echocardiographic studies (0.49 +/- 0.16 vs 0.75 +/- 0.21 cm/sec and 2.0 +/- 0.9 vs 3.0 +/- 1.4 cm/sec, respectively; both p < 0.05), transmitral deceleration time (67 +/- 24 vs 81 +/- 19 msec, p < 0.05), and atrial filling fraction (31.0% +/- 11.2% vs 38.9% +/- 13.9%, p < 0.05) increased with OPC-18790 infusion. Despite a significant decrease in pulmonary capillary wedge pressure (28 +/- 9 vs 18 +/- 10 mm Hg) there was no change in the velocity-time integral of early diastolic filling (53 +/- 12 vs 59 +/- 22 cm), suggesting improved LV relaxation. Hemodynamics and parameters of LV function were unchanged in the 3 patients receiving placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of acutely altered loading conditions on left atrial appendage flow velocities.

OBJECTIVES: The purpose of this study was to identify the effects of altered loading conditions on left atrial appendage flow velocities. BACKGROUND: Although studies have suggested that Doppler analysis of left atrial appendage blood flow may have clinical utility, the hemodynamic and cardiac mechanical determinants of left atrial appendage flow are poorly understood. METHODS: Transesophageal Doppler echocardiography was performed in eight atrially paced anesthetized dogs instrumented with sonomicrometers on the left atrial appendage and the left ventricular minor axis and with left atrial and left ventricular micromanometers. Left atrial appendage emptying and filling velocities corresponding to early and late ventricular diastole, respectively, were measured using volume expansion and phenylephrine infusion. RESULTS: Volume infusion caused a significant decrease in the early to late emptying and filling ratios (mean +/- SD 0.85 +/- 0.24 vs. 0.46 +/- 0.17 and 0.80 +/- 0.50 vs. 0.40 +/- 0.20, both p < 0.05). By contrast, phenylephrine infusion did not significantly alter either filling or emptying ratio. The independent determinants of each flow wave were identified with multiple regression analysis: early emptying velocity--time constant of left ventricular relaxation, left ventricular end-systolic dimension and aortic pressure (r = 0.75, p < 0.001); late emptying velocity--left ventricular peak positive time derivative of left ventricular pressure (dP/dt) and fractional shortening (r = 0.74, p < 0.001); early filling velocity--left atrial appendage shortening fraction (r = 0.45, p = 0.01) and late filling velocity--left atrial appendage lengthening rate and left ventricular fractional shortening (r = 0.56, p < 0.01). CONCLUSIONS: These results indicate that 1) both the magnitude and the pattern of left atrial appendage emptying and filling velocities are dependent on loading conditions, and 2) left atrial appendage velocities are influenced to a greater extent by changes in left ventricular than in left atrial appendage function. These findings may have implications for the pathogenesis of left atrial appendage thrombi.

Animals↗

The paradoxical pulse in tamponade: mechanisms and echocardiographic correlates.

Pulsus paradoxus is an exaggerated fall in systolic blood pressure with inspiration (usually greater than 10 mm). Understanding the accuracy of pulsus paradoxus for a diagnosis of cardiac tamponade requires a consideration of the mechanisms underlying its genesis, and a knowledge of its presence in other conditions and its variable absence in cardiac tamponade with associated disease states. Echocardiography (M-mode, 2-D, and Doppler) has aided considerably our understanding of pulsus paradoxus. Inspiratory increases in right heart filling and output are widely accepted as necessary for pulsus paradoxus to occur; inspiration causes increases in right ventricular dimensions and pulmonic and tricuspid velocities, and decreases in left ventricular (LV) dimensions and aortic and mitral velocities and LV diastolic compliance. Doppler studies of pulmonary venous inflow confirm that an inspiratory fall in left atrial filling is necessary for pulsus paradoxus. Pulsus paradoxus is complex and multifactorial in origin; it may be absent in cardiac tamponade when certain conditions (e.g., LV dysfunction) coexist and may accompany disease states other than cardiac tamponade (e.g., obstructive airway disease). Thus, the significance of pulsus paradoxus (and its Doppler echo correlates) must be considered in the clinical context.

Animals↗

In vivo assessment of left atrial contractile performance in normal and pathological conditions using a time-varying elastance model.

BACKGROUND: Contractile function of the ex vivo, isolated left atrium (LA) has been described by a time-varying elastance, but this atrial chamber property has not been shown in vivo. METHODS AND RESULTS: Instantaneous LA pressure-volume (P-V) relations were studied in 12 anesthetized, autonomically blocked, atrially paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a cast-validated formula. Data were collected during increases in LA pressure produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V points from 5 beats, representing a wide range of atrial pressures, were fitted by linear regression analysis (range of R2, .92 to .99). There were significant time-dependent increases in the slopes [E(t)] and small but statistically insignificant decreases in the volume axis intercepts [VO(t)] of the instantaneous LA P-V relations during atrial contraction; maximal elastance (Emax) occurred 29 +/- 16 milliseconds before atrial end systole (minimal LA volume). Emax was not significantly different than the slopes of either the nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V relation (EmaxPV): 5.5 +/- 2.8, 4.3 +/- 1.5, and 5.4 +/- 4.2 mm Hg/mL, respectively. In 7 dogs, data were collected both before and after a rapid infusion of calcium gluconate (1 to 2 g IV). Emax increased significantly with a calcium-induced increase in inotropic state (4.5 +/- 1.6 to 5.7 +/- 1.8 mm Hg/mL, P < .01), but the volume axis intercept was unchanged (3.6 +/- 0.7 versus 3.4 +/- 1.9, P = NS). In 4 additional dogs with heart failure (mean LA pressure, 26 +/- 6 mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume was significantly greater than and elastance determinations were similar to those of normal dogs. However, the effects of calcium infusion on LA function were attenuated in these animals. CONCLUSIONS: We conclude that (1) in the intact heart, LA contraction may be approximated by time-varying elastance with time-dependent changes in E(t) and that (2) LA systolic P-V relations using either the nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of Emax, are highly linear and sensitive to calcium-induced changes in inotropic state, and may be useful in identifying LA chamber adaptation to chronic hemodynamic loads.

Animals↗

Comparative assessment of regional left atrial perfusion by laser Doppler and radionuclide microsphere techniques.

OBJECTIVE: The aim was to study the relation between left atrial microcirculatory flux, using laser Doppler flowmetry (LDF), and blood flow, using radiolabelled microspheres (MS). METHODS: Studies were done in five anaesthetised dogs. LDF probes were sewn to the appendage and body of the left atrium. Radionuclide spheres (15 microns) were used to quantitate blood flow at baseline, and during atrial pacing at 3.5 Hz, atrial fibrillation, and intravenous adenosine infusion (1 mg.kg-1 x min-1). RESULTS: In the left atrial body, both MS and LDF perfusion increased significantly during pacing and adenosine infusion; only LDF registered significant increases during atrial fibrillation. In the left atrial appendage, MS flow failed to increase significantly with any intervention and LDF perfusion increased significantly only during atrial fibrillation. There was a significant but weak correlation (r = 0.36, p < 0.05) between LDF and MS when data from all sample sites (n = 40) were compared, but good correlation when only baseline and pacing data were compared (r = 0.72, p = 0.0004, n = 20). In four additional dogs with heart failure [mean left atrial pressure 25.3(SD 7.4) mm Hg] produced by three weeks of rapid right ventricular pacing, flux values at baseline were increased significantly compared to control dogs and the responses registered by LDF to pacing, atrial fibrillation, and adenosine infusion were attenuated markedly. CONCLUSIONS: (1) Microcirculatory flux detected by LDF can identify the direction, and to a lesser extent, the magnitude of changes in regional atrial perfusion; and (2) LDF may be useful in identifying abnormalities of vasodilator reserve that accompany chronic left atrial myocardial dysfunction.

Animals↗

Determination of left atrial volume using sonomicrometry: a cast validation study.

We developed a technique for left atrial (LA) volume estimation using two pairs of sonomicrometers sewn to the anteroposterior (LAX) and mediolateral (SAX) LA diameters and validated the method against water displacement of LA casts in 15 dogs. LA pressure was adjusted to a preselected level (5, 10, or 15 mmHg) by dextran infusion and was matched by postmortem infusion of casting resin (Conthane DPEN-18402). LA volume was modeled empirically as an ellipsoid of revolution without regression constants [(SAX)2(LAX)]. There was a strong correlation between the calculated LA volume and water displacement of the LA body [r = 0.87, standard error of estimate (SEE) = 3.3 ml, P = 0.0001] but a weaker correlation against water displacement of the entire LA (body+appendage, r = 0.81, SEE = 3.9 ml, P = 0.0003). The appendage volume fraction (appendage volume/total LA volume), as determined by water displacement of the casts, increased with increasing LA size (r = 0.78, P = 0.001). These data indicate that, in the normal canine heart, LA volume can be estimated accurately with high temporal and spatial resolution sonomicrometry using two atrial dimensions, and the contribution of appendage to total LA volume may become significant as the atrium enlarges.

Animals↗

Influence of pericardium on left atrial compliance and pulmonary venous flow.

We studied seven open-chest anesthetized dogs to test the hypothesis that left atrial (LA) compliance is increased after pericardiectomy and to determine the effect of pericardiectomy on left atrial reservoir and conduit function. Two orthogonal sonomicrometer crystal pairs were used to estimate LA volume, and LA filling was assessed with a pulmonary vein (PV) flow probe. The left ventricular (LV) systolic (JFTI) and diastolic (KFTI) PV flow integrals were used as indexes of LA reservoir and conduit function, respectively. Diastolic LV transmitral flow was assessed with transesophageal Doppler echocardiography. Data were acquired over a wide range of intracardiac pressures and volumes obtained by intravenous hetastarch infusion both before and after pericardiectomy. The mean dynamic stiffness constant of the LA diastolic pressure-volume relation was significantly greater before pericardiectomy than afterwards (0.15 +/- 0.04 vs. 0.08 +/- 0.03 ml-1, P < 0.05). Data were analyzed before and after pericardiectomy at three matched levels of left atrial pressure (LAP; 7, 13, and 20 mmHg). The J-to-KFTI ratio increased significantly with volume infusion and was significantly less after pericardiectomy than before (1.2 +/- 0.7 vs. 1.2 +/- 0.6, 1.8 +/- 0.6 vs. 2.2 +/- 0.9, and 2.0 +/- 0.8 vs. 2.6 +/- 0.9 at low, mid, and high levels of LAP, respectively; P < 0.05 at mid and high levels of LAP). Peak early transmitral velocity increased with both volume infusion and pericardiectomy. We conclude that pericardiectomy increases LA compliance and early LV filling rate and is accompanied by a relatively greater augmentation in conduit than reservoir function of the left atrium.

Animals↗

Altered left atrial compliance after atrial appendectomy. Influence on left atrial and ventricular filling.

Previous studies have shown regional differences in atrial distensibility. We studied 12 open-chest dogs to test the hypothesis that left atrial compliance is decreased after removal of the left atrial appendage and to determine the effect of altered atrial compliance on atrial reservoir and conduit function. Sonomicrometer crystal pairs were used to measure the long- and short-axis diameters of the left atrium over a wide range of intracardiac pressures and volumes obtained by intravenous hetastarch infusion both before and after suture ligation of the left atrial appendage (appendectomy). Pulmonary venous flow was measured with an ultrasonic flowmeter, and transmitral flow velocities were measured with transesophageal Doppler echocardiography. After appendectomy, the diastolic pressure-volume relation was shifted upward and to the left in six of seven dogs. The mean dynamic stiffness constant of the left atrial diastolic pressure-volume relation was significantly greater after appendectomy than before (0.20 +/- 0.11 [mean +/- SD] versus 0.14 +/- 0.08 ml-1, p < 0.01); the mean y intercept was slightly, but significantly, less after appendectomy (0.6 +/- 0.3 versus 1.3 +/- 0.6 mm Hg, p < 0.05). The left atrial reservoir volume (maximum minus minimum left atrial volume) was significantly less after appendectomy at matched left atrial pressures. The systolic to diastolic flow integral ratio of pulmonary venous flow (JFTI/KFTI), an index of the relative reservoir to conduit functions of the left atrium, increased significantly with volume infusion only before appendectomy; at matched left atrial pressure, JFTI/KFTI was significantly less afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Load independence of early diastolic filling parameters in the anesthetized canine model.

To evaluate radionuclide diastolic filling indices during acute pharmacologic changes in ventricular loading, 11 atrially paced dogs underwent simultaneous micromanometer left atrial and left ventricular pressure measurements. During phenylephrine infusion, systolic blood pressure increased from 110 +/- 16 (s.d.) to 147 +/- 19 mmHg (p < 0.01), causing the atrioventricular gradient to increase from 5 +/- 2 to 8 +/- 5 mmHg (p < 0.03) with no change in the time constant of isovolumic relaxation (Tau). Absolute peak filling rate increased from 40 +/- 21 to 59 +/- 44 kcts/sec (p < 0.05), but there was no change in first-half filling fraction. During dobutamine infusion, Tau shortened from 43 +/- 13 msec to 33 +/- 5 msec (p < 0.01) and first-half filling fraction increased from 39% +/- 19% to 56% +/- 18% (p < 0.05), with no change in atrioventricular gradient or absolute peak filling rate. Absolute changes from baseline for the first-half filling fraction were inversely proportional to absolute changes in Tau (r = -0.76, p < 0.05). We conclude that the left ventricular absolute peak filling rate is a load dependent index of diastolic function. In contrast, the radionuclide first-half filling fraction is independent of loading conditions, but is sensitive to substantial alterations in the rate of left ventricular isovolumic myocardial relaxation.

Animals↗

Regional atrial distensibility.

We studied 12 open-chest dogs to determine whether there are regional differences in left atrial distensibility. Sonomicrometer crystal pairs were used to measure the anteroposterior diameters of the left atrial body and appendage simultaneously over a wide range of intracardiac pressures and volumes obtained by intravenous saline infusion. Left atrial pressure-natural strain data for the body and appendage were fitted to an exponential function. The mean coefficient of the left atrial monoexponential pressure-strain relationship was greater for the body than appendage (3.1 +/- 1.1 vs. 1.9 +/- 0.7 mmHg, P less than 0.01). The Y-intercepts were not significantly different (5.2 +/- 1.7 vs 4.9 +/- 1.8 mmHg). The maximum minus minimum left atrial dimension, an index of the reservoir function of the atrium, increased with volume infusion in both the body and appendage and was significantly greater in the appendage than body at each level of left atrial pressure. Similarly, atrial systolic shortening fraction increased with volume infusion, and regional shortening was greater in the appendage than the body at each level of left atrial pressure. We conclude that regional differences in atrial distensibility exist in vivo and may play an important role in modulating systolic and diastolic function of the left atrium.

Animals↗

Influence of loading conditions and contractile state on pulmonary venous flow. Validation of Doppler velocimetry.

BACKGROUND: Although recent studies suggest that pulmonary venous flow velocities may be used to evaluate left ventricular diastolic function, the influence of loading conditions and contractile state on the magnitude and pattern of pulmonary venous flow are poorly understood. METHODS AND RESULTS: Fourteen anesthetized open-chest mongrel dogs were instrumented with pulmonary venous flow probes, atrial sonomicrometer crystal paris, and high-fidelity micromanometers; transesophageal Doppler echocardiography was used to obtain simultaneous pulmonary venous flow velocities. Measurements were made over a wide range of left atrial pressure obtained by either intravascular volume infusion and inferior vena caval balloon inflation (n = 8), halothane inhalation (n = 6), or phenylephrine infusion (n = 5). There was an excellent correlation for pulmonary venous systolic (J) to diastolic (K) time integral between the Doppler and flow probe signal (r = 0.94; SEE, 0.18). When left atrial pressure was increased by volume infusion, there was a significant linear relation between mean left atrial pressure and the Doppler J/K peak (r = 0.64; SEE, 3.4 mm Hg) and flow velocity-time integral ratio (r = 0.75; SEE, 2.9 mm Hg). By contrast, when left atrial pressure was elevated by halothane-induced cardiac depression, there was no correlation. The independent determinants of the pattern of pulmonary venous flow (stepwise multiple linear regression analysis) under all conditions were atrial systolic shortening, aortic systolic pressure, heart rate, and left ventricular end-systolic dimension (cumulative r = 0.80). CONCLUSIONS: The pattern of pulmonary venous flow can be measured accurately with Doppler velocities and is differentially influenced by loading conditions and myocardial contractile state; in the absence of myocardial contractile dysfunction, the pattern of pulmonary venous flow may provide an estimate of left atrial pressure; and pulmonary venous flow is determined largely by atrial systolic function.

Animals↗

Influence of acute right ventricular dysfunction on cardiac tamponade.

Echocardiographic and hemodynamic data were measured in nine closed chest dogs during graded cardiac tamponade (pericardial pressure 5, 10, 15 mm Hg) before and after production of diffuse acute ischemic right ventricular dysfunction. Right ventricular dysfunction was produced by intracoronary injection of nonradioactive microspheres (mean diameter +/- SD 54 +/- 4 microns) and caused a significant increase in right atrial pressure (7.6 +/- 1.4 vs. 1.6 +/- 1 mm Hg, p less than 0.001) and cross-sectional areas of both the right atrium (8.3 +/- 0.3 vs. 5.6 +/- 0.2 cm2, p less than 0.001) and right ventricle (8.8 +/- 0.4 vs. 5.7 +/- 0.4 cm2, p less than 0.001). Right atrial and ventricular collapse required a significantly larger pericardial effusion and pericardial pressure after right ventricular infarction than before. Mean aortic pressure had fallen 1.9 +/- 2% and 6.5 +/- 6.9% at the time of right atrial collapse (p = NS before vs. after right ventricular dysfunction) and 3 +/- 4.1% and 20.1 +/- 20.8% at the time of right ventricular collapse (p less than 0.03) before and after right ventricular dysfunction, respectively. In the presence of ischemic right ventricular dysfunction, echocardiographic signs of cardiac tamponade are less sensitive and occur later in the hemodynamic progression of cardiac tamponade. Pulsus paradoxus with cardiac tamponade was not prevented by coexisting ischemic right ventricular dysfunction.

Animals↗

Medical treatment of valvular heart disease.

Despite recent advances in operative and percutaneous surgical techniques for valvular heart disease, medical management of complications of valvular disease, such as atrial fibrillation and infection, and prevention of thromboembolism remain important clinical problems. This review discusses recent data that address the role of vasodilator therapy in valvular regurgitation, the management of severe, asymptomatic aortic stenosis, and studies pertinent to the treatment of complications of valvular heart disease. Although vasodilators are promising agents, their efficacy in delaying the need for valve replacment remains unproven.

Anticoagulants↗

Influence of splenectomy on hemodynamics during cardiac tamponade.

The effect of prior splenectomy on the hemodynamics of cardiac tamponade was investigated in 15 closed-chest pentobarbital sodium-anesthetized dogs. Hemodynamics were compared at baseline and during staged cardiac tamponade (pericardial pressures of 5, 10, and 15 mmHg) at control (n = 15) and after splenectomy (n = 8) and sham operation (n = 7). The fall in mean arterial pressure with cardiac tamponade was significantly greater in splenectomized dogs than in either sham-operated or control dogs (P less than 0.001). Cardiac output was more depressed at the third level of cardiac tamponade in splenectomized than in sham-operated or control dogs (12.8 +/- 14.5 vs. 29.3 +/- 8.7 and 25.4 +/- 9.4 ml.min-1.kg-1, respectively; both P less than 0.05 vs. splenectomy). Hemodynamic failure, defined as an inability to maintain mean arterial pressure greater than 50 mmHg for 5 min, occurred at a lower pericardial pressure in splenectomized than in sham-operated dogs (13.1 +/- 3.8 vs. 18.1 +/- 3.5 mmHg, P less than 0.05). Hematocrit increased significantly with cardiac tamponade in controls and sham-operated but not splenectomized dogs. The percent increase in hematocrit from baseline to the third stage of cardiac tamponade was 19.6 +/- 9.8 and 22.3 +/- 5.6% in control and sham dogs, respectively. Thus the canine spleen plays an important role in cardiovascular compensation to cardiac tamponade. Parallel changes in hematocrit suggest that a part of this response is due to splenic autotransfusion.

Animals↗

Pericardial influences on right and left ventricular filling dynamics.

The influence of the pericardium on right and left ventricular filling was studied using two-dimensional and Doppler echocardiography in 14 open-chest dogs. Doppler echo parameters of filling included early (E) and late (A) velocities and their ratio (E/A) for the mitral and tricuspid valves. Right and left ventricular volumes were calculated from orthogonal two-dimensional echocardiographic images. Data were compared at three levels of left ventricular end-diastolic pressure (6 +/- 2, 13 +/- 3, and 21 +/- 4 mm Hg) at matched heart rates before and after pericardiectomy. The instantaneous diastolic pressure gradient was measured in 12 of the dogs. Pericardiectomy resulted in an increase in early mitral velocity, peak early diastolic pressure gradient, and E/A but not early mitral velocity normalized for end-diastolic volume. In contrast, for the tricuspid valve flow, pericardiectomy did not change E but caused a marked increase in A and a decrease in E/A. Right ventricular end-diastolic volumes at matched left ventricular end-diastolic volumes were similar before and after the pericardium was removed. However, removal of the pericardium caused a significant decrease of the slope for the right (86.0 +/- 27.0 x 10(-4) versus 50.0 +/- 19.5 x 10(-4) mm Hg/ml, p less than 0.01), but not left, ventricular ln end-diastolic pressure-volume relation (21.2 +/- 9.2 x 10(-3) versus 21.4 +/- 5.3 x 10(-3) mm Hg/ml, p = NS), and a decrease of the pressure intercept for the left (3.0 +/- 2.0 versus 1.6 +/- 0.9 mm Hg, p less than 0.05), but not right, ventricular ln end-diastolic pressure-volume relation (2.8 +/- 1.4 versus 1.4 +/- 0.8 mm Hg, p = NS). In conclusion, filling of the two ventricles is affected by the pericardium over a wide range of physiological ventricular volumes and pressures. At matched left ventricular end-diastolic volume, pericardiectomy causes a fundamental alteration in right, but not left, ventricular filling.

Animals↗