M-mode echocardiographic predictors of six- to seven-year incidence of coronary heart disease, stroke, congestive heart failure, and mortality in an elderly cohort (the Cardiovascular Health Study).

Previous studies have identified a number of echocardiographic variables that predict cardiovascular disease (CVD) events and mortality, but have not focused on a large elderly cohort. The purpose of this study was to determine whether M-mode echocardiographic variables predicted all-cause mortality, incident coronary heart disease (CHD), congestive heart failure (CHF), and stroke in a large prospective, multicenter, population-based study. In the Cardiovascular Health Study, a biracial cohort of 5,888 men and women (mean age 73 years) underwent 2-dimensional M-mode echocardiographic measurements of left ventricular (LV) internal dimensions, wall thickness, mass and geometry, as well as measurement of left atrial dimension and assessment for mitral annular calcium. Participants were followed for 6 to 7 years for incident events; analyses excluded subjects with prevalent disease. One or more echocardiographic measurements were independent predictors of all-cause mortality and incident CHD, CHF, and stroke. After adjustment for anthropometric and traditional CVD risk factors, LV mass was significantly related to incident CHD, CHF, and stroke. The highest quartile of LV mass conferred a hazards ratio of 3.36, compared with the lowest quartile, for incident CHF. Furthermore, incident CHF-free survival was significantly lower for participants with LV mass in the highest versus the 2 lowest quartiles (86% vs 97%, respectively, at 2,500 days). Eccentric and concentric LV hypertrophy, respectively, conferred adjusted hazards ratios, compared with normal LV geometry, of 2.05 and 1.61 for incident CHD, and 2.95 and 3.32 for incident CHF. Thus, in an elderly biracial population, selected 2-dimensional M-mode echocardiographic measurements were important markers of subclinical disease and conferred independent prognostic information for incident CVD events, especially CHF and CHD.

Left ventricular diastolic filling in the elderly: the cardiovascular health study.

Changes in left ventricular (LV) diastolic function (e.g., as measured by transmitral flow velocity) are known to occur with aging. In addition, impaired LV diastolic function plays an important role in such cardiovascular disorders common in the elderly as hypertension, ischemic heart disease, and congestive heart failure (CHF). Participants in the Cardiovascular Health Study, a multicenter study of community-dwelling men (n=2,239) and women (n=2,962) > or = 65 years of age, underwent an extensive baseline evaluation, including echocardiography. Early diastolic LV Doppler (transmitral) peak filling velocity decreased, and peak late diastolic (atrial) velocity increased with age in multivariate analyses (all p <0.001). Early and late diastolic peak filling velocities were both significantly higher in women than in men, even after adjustment for body surface area (or height and weight). In multivariate models in the entire cohort and a healthy subgroup (n=703), gender, age, heart rate, and blood pressure (BP) were most strongly related to early and late diastolic transmitral peak velocities. Early and late diastolic peak velocities both increased with increases in systolic BP and decreased with increases in diastolic BP (p <0.001). Doppler transmitral velocities were compared among health status subgroups. In multiple regression models adjusted for other covariates, and in analysis of variance models examining differences across subgroups adjusted only for age, the subgroup with CHF had the highest early diastolic peak velocities. All clinical disease subgroups had higher late diastolic peak velocities than the healthy subgroup, with the subgroups with either CHF or hypertension having the highest age-adjusted means. The subgroup with hypertension had the lowest ratio of early-to-late diastolic peak velocity, and men with CHF had the highest ratio. These findings are consistent with previous reports that hypertensive subjects exhibit an abnormal relaxation pattern, whereas patients with CHF develop a pattern suggestive of an increased early diastolic left atrial-LV pressure gradient.

Left ventricular mass in the elderly. The Cardiovascular Health Study.

Left ventricular (LV) mass, as estimated from M-mode echocardiography (echo), has previously been shown to be an independent predictor of incident cardiovascular disease morbidity and mortality. We evaluated the relationship at baseline of echo LV mass to relevant cardiovascular disease risk factors and other potential covariates in the Cardiovascular Health Study, multicenter study sponsored by the National Heart, Lung, and Blood Institute of 5201 men and women aged 65 years or older (mean, 73). Two-dimensionally directed M-mode echo LV mass measurements could be obtained in 1357 men and 2053 women (66% of this elderly cohort). Stepwise linear regression analyses of the relationship of echo LV mass to demographic and risk factor, physical activity, electrocardiographic, and prevalent disease variables resulted in a model that explained 37% of the variance for the entire cohort. In order of decreasing importance, factors positively associated with echo LV mass were body weight, male sex, systolic pressure, presence of congestive heart failure, present smoking, major and minor electrocardiographic abnormalities, treatment for hypertension, valvular heart disease, aortic regurgitation by color Doppler, and mitral regurgitation by color Doppler (in men) whereas diastolic pressure, bioresistance (a measure of adiposity), and high-density lipoprotein cholesterol were inversely related to echo LV mass. Although height and weight were both related to LV mass, height added nothing once weight was entered in multiple linear regression analyses. Furthermore, in the multiple regression models, diastolic pressure was inversely and systolic BP positively related to LV mass, with similar magnitudes for their coefficients. In consonance with these findings, pulse pressure was positively related to LV mass in bivariate analyses. Multiple linear regression analyses explained less of the variance for ventricular septal thickness (R2 = .13) and LV posterior wall thickness (R2 = .14) than for LV mass (R2 = .37) and LV diastolic dimension (R2 = .27). Intriguing findings in the elderly Cardiovascular Health Study cohort included the presence of pulse pressure as a positive correlate, and high-density lipoprotein cholesterol as an inverse correlate, of LV mass. Longitudinal studies in the Cardiovascular Health Study cohort will help to clarify the importance of demographic, risk factor, and other variables, and changes in these variables, in predicting changes in echo LV mass and its components as well as the prognostic significance of LV mass in the elderly.

Depression of cardiac function after deep hypothermic circulatory arrest in deeply anesthetized neonatal lambs.

Cardiac dysfunction is common after neonatal cardiac operations. Previous in vivo studies in neonatal animal models however, have failed to demonstrate decreased left ventricular function after ischemia and reperfusion. Cardiac dysfunction may have been masked in these studies by increased endogenous catecholamine levels associated with the use of light halothane anesthesia. Currently, neonatal cardiac operations are often performed with deep opiate anesthesia, which suppresses catecholamine surges and may affect functional recovery. We therefore examined the recovery of left ventricular function after ischemia and reperfusion in neonatal lambs anesthetized with high-dose fentanyl citrate (450 micrograms/kg administered intravenously). Seven intact neonatal lambs with open-chest preparation were instrumented with left atrial and left ventricular pressure transducers, left ventricular dimension crystals, and a flow transducer. The lambs were cooled (< 18 degrees C) on cardiopulmonary bypass (22 +/- 6 minutes), exposed to deep hypothermic circulatory arrest (46 +/- 1 minutes), and rewarmed on cardiopulmonary bypass (30 +/- 10 minutes). Catecholamine levels and indexes of left ventricular function were determined before (baseline) and 30, 60, 120, 180, and 240 minutes after termination of cardiopulmonary bypass. Levels of epinephrine, norepinephrine, and dopamine were unchanged from baseline values. Left ventricular contractility (slope of end-systolic pressure-volume relationship) was depressed from baseline value (31.7 +/- 9.3 mm Hg/ml) at 30 minutes (15.7 +/- 6.4 mm Hg/ml) and 240 minutes (22.7 +/- 6.4 mm Hg/ml) but unchanged between 60 and 180 minutes. Left ventricular relaxation (time constant of isovolumic relaxation) was prolonged from baseline value (19.0 +/- 3.0 msec) at 30 minutes (31.4 +/- 10.0 msec) and 240 minutes (22.1 +/- 2.8 msec) but unchanged between 60 and 180 minutes. Afterload (left ventricular end-systolic meridional wall stress) was decreased at 30, 60, and 240 minutes. Indexes of global cardiac function (cardiac output, stroke volume), preload (end-diastolic volume), and left ventricular compliance (elastic constant of end-diastolic pressure-volume relationship) were unchanged from baseline values. In deeply anesthetized neonatal lambs exposed to ischemia and reperfusion, left ventricular contractility, relaxation, and afterload are markedly but transiently depressed early after reperfusion and mildly depressed late after reperfusion.

Filling characteristics of left ventricle in newborn lambs.

An integral component of increased cardiac performance during the immediate newborn period is an increased rate of left ventricular (LV) filling. To determine the factors that facilitate increased LV filling in newborns, we compared filling characteristics in chronically instrumented awake newborn (7 +/- 2 days old) and older lambs (55 +/- 5 days old). The studies were performed 4 +/- 2 days after surgery, during which pressure transducers, dimension crystals, a flow transducer, and vascular occluders were placed. Newborn lambs had an increased cardiac index (247 +/- 40 vs. 127 +/- 48 ml.kg-1.min-1; P < 0.01) due to an increased heart rate (223 +/- 24 vs. 120 +/- 9 beats/min; P < 0.01) despite a similar stroke volume index (1.1 +/- 0.1 vs. 1.1 +/- 0.5 ml/kg; not significant). In newborn lambs, indexed mean LV filling rates were more than twofold higher (10.5 +/- 2.5 vs. 4.6 +/- 1.7 ml.kg-1.s-1; P < 0.01), and a much greater percentage of filling occurred in the first 35 ms after mitral valve opening (52 +/- 7 vs. 23 +/- 8%; P < 0.01). In newborn lambs, early diastolic filling was facilitated by more rapid LV relaxation (tau: 17.2 +/- 2.2 vs. 23.3 +/- 1.2 ms; P < 0.01) and a higher left atrial (LA) pressure at the time of mitral valve opening (11.6 +/- 2.4 vs. 7.2 +/- 3.2 mmHg; P < 0.05). LV filling in newborn lambs also occurred at the expense of a higher mean LA pressure (8.4 +/- 2.4 vs. 5.1 +/- 2.6 mmHg; P < 0.05). These findings improve our understanding of LV diastolic function in newborns.

Sex, age, and disease affect echocardiographic left ventricular mass and systolic function in the free-living elderly. The Cardiovascular Health Study.

BACKGROUND: Left ventricular (LV) hypertrophy, as measured by M-mode echocardiography, is an independent predictor of mortality and/or morbidity from coronary heart disease (CHD). LV global and segmental systolic dysfunction also have been associated with myocardial ischemia and cardiovascular morbidity and mortality. Echocardiographic data, especially two-dimensional, have not been available previously from multicenter-based studies of the elderly. This report describes the distribution and relation at baseline of echocardiographic LV mass and global and segmental LV wall motion to age, sex, and clinical disease category in the Cardiovascular Health Study (CHS), a cohort of 5201 men and women (4850 white) 65 years of age and older. METHODS AND RESULTS: M-mode LV mass adjusted for body weight increased modestly with age (P < .0001), increasing less than one gram per year increase in age for both men and women. After adjustment for weight, LV mass was significantly greater in men than in women and in participants with clinical CHD compared with participants with neither clinical heart disease nor hypertension (both P < .001). Across all CHS age subgroups, the difference in weight-adjusted LV mass by sex was greater in magnitude than the difference related to clinical CHD. M-mode measurements of LV mass could not be made in 34% of CHS participants, and this was highly related to age (29% in the 65 to 69 year versus 50% in the 85+ year age group, P < .001) and other risk factors. In participants with clinical CHD and with neither clinical heart disease nor hypertension, LV ejection fraction and segmental wall motion abnormalities were more prevalent in men than women (all P < .001). Of interest, 0.5% of men and 0.4% of women with neither clinical heart disease nor hypertension had LV segmental wall motion abnormalities, suggesting silent disease, compared with 26% of men and 10% of women in the clinical CHD group (P < .0001). Multivariate analyses revealed male sex and presence of clinical CHD (both P < .001) to be independent predictors of LV akinesis or dyskinesis. CONCLUSIONS: Significant baseline relations were detected between differences in sex, prevalent disease status, and echocardiographic measurements of LV mass and systolic function in the CHS cohort. Age was weakly associated with LV mass measurements and LV ejection fraction abnormalities. These relations should be considered in evaluating the preclinical and clinical effects of CHD risk factors in the elderly.

Effect of dynamic exercise on left atrial function in conscious dogs.

1. Dynamic changes in left atrial (LA) function during treadmill exercise were studied in ten conscious dogs instrumented to measure left ventricular (LV) pressure and diameter, LA pressure and diameter, and pulmonary venous blood flow (PVF, transit time flowmeter). 2. Systolic PVF volume (reservoir volume; a measure of LA reservoir function) increased from 38 +/- 4% of total PVF volume at baseline to 52 +/- 8% of total PVF volume during exercise, and diastolic PVF volume (conduit volume; a measure of LA conduit function) decreased from 62 +/- 5% at baseline to 48 +/- 8% during exercise (P < 0.005). 3. The increases in reservoir volume and the decrease in conduit volume were due not only to a greater decrease in diastolic interval than systolic interval but were also caused by a significantly greater increase (P < 0.05) in the mean systolic filling rate (93%) than in the mean diastolic filling rate (51%). 4. During exercise the pattern of LV filling derived from changes in LV diameter showed that a greater percentage of LV filling occurred during the second half of diastole at the time of atrial contraction (P < 0.05), suggesting that LA booster function was enhanced. 5. Changes in LA dimension revealed that during exercise more blood volume was reserved in the LA during systole and that this change was associated with an increase in the LA dimension at the beginning of LA contraction (r = 0.61, P < 0.05). 6. We conclude that LA reservoir and booster functions were augmented during exercise, whereas conduit function was not. Increased reservoir function may play an important role in accelerating LV filling by helping to maintain an enhanced atrioventricular pressure gradient during diastole and also by increasing LA booster function through an increase in LA preload.

Can pleural effusions cause tamponade-like effects?

Experimental studies have confirmed the clinical impression that large bilateral pleural effusions are able to raise the pressure in an otherwise hemodynamically insignificant pericardial effusion to a level sufficient to produce right ventricular diastolic collapse (RVDC). The hemodynamic consequences of this syndrome are not as severe as when the intrapericardial pressure is raised to the same level by excess intrapericardial fluid in the absence of pleural effusions. RVDC caused by excess pleural fluid with a minor pericardial effusion is a false positive indication for pericardial fluid drainage. Thoracentesis is more appropriate.

Accelerated myocardial relaxation in conscious dogs during acute cardiac tamponade.

Eight chronically instrumented conscious dogs were used to test the hypothesis that left ventricular (LV) relaxation is accelerated during cardiac tamponade. The time constant of LV transmural pressure fall was measured before and during intrapericardial (IP) saline infusion (baseline) with and without beta-adrenergic blockade (propranolol 1 mg/kg iv). Heart rate was controlled by atrial pacing. Increasing IP pressure caused a progressive linear decrease in stroke volume before and during beta-blockade in each animal. The time constant of LV transmural pressure fall also decreased continuously with an increase in IP pressure from 26 +/- 7 ms during baseline to 18 +/- 5 ms during severe cardiac tamponade (P < 0.01) before beta-blockade. However, after beta-blockade, the time constant of LV transmural pressure fall was constant over a wide range of IP pressures despite a continuous decrease in LV end-diastolic volume. The time constant of LV transmural pressure fall was not altered by vena caval occlusions that caused the same decrease in LV preload observed during cardiac tamponade. We concluded that despite decreased pump function, LV relaxation was accelerated progressively during graded cardiac tamponade, and this change was dependent not on changes in loading conditions but on an intact beta-adrenergic influence.

Effect of vasopressin on left ventricular performance.

We assessed the effect of arginine vasopressin (AVP) on left ventricular (LV) performance in eight conscious dogs. Five minutes after AVP infusion (6 microns.kg-1 x min-1 for 2 min) the plasma AVP was elevated from 3.9 +/- 0.9 to 14.7 +/- 4.6 pg/ml (P < 0.05). With all reflexes intact, AVP caused significant increases in LV end-systolic pressure (P) (112 +/- 8 vs. 122 +/- 7 mmHg, P < 0.05) end-systolic volume (V) (30 +/- 5.8 vs. 38 +/- 7.7 ml, P < 0.05), total systemic resistance (6.2 +/- 1.8 vs. 10.6 +/- 4.0 mmHg.dl-1 x min, P < 0.01) and arterial elastance (Ea) (6.8 +/- 3.0 vs. 8.6 +/- 3.9 mmHg/ml, P < 0.05), while the heart rate (110 +/- 6 vs. 82 +/- 10 beats/min, P < 0.05) and stroke volume (16.5 +/- 4.3 vs. 14.2 +/- 3.9 ml, P < 0.05) were decreased. There was no significant change in the coronary sinus blood flow (82 +/- 19 vs. 78 +/- 22 ml/min, P = not significant). AVP decreased the slopes of LV end-systolic P-V relation (10.7 +/- 1.1 vs. 8.1 +/- 1.9 mmHg/ml, P < 0.05), the maximal first derivative of LV pressure (dP/dtmax)-end-diastolic volume (VED) relation (135.2 +/- 18.7 vs. 63.1 +/- 7.7 mmHg.s-1 x ml-1, P < 0.05), and the stroke work-VED relation (81.1 +/- 4.1 vs. 66.7 +/- 2.8 mmHg, P < 0.05) and shifted the relations to the right, indicating a depression of LV performance. A similar increase in Ea produced by methoxamine did not depress LV performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Pleural effusion as a cause of right ventricular diastolic collapse.

BACKGROUND: We hypothesized, after seeing several suggestive clinical examples, that a process leading to a large bilateral pleural effusion in the presence of an otherwise insignificant pericardial effusion could result in right ventricular diastolic collapse (RVDC) as seen by two-dimensional echocardiography. This noninvasive marker for hemodynamically significant cardiac tamponade occurs when pericardial fluid is under pressure. Therefore, RVDC resulting from a large pleural effusion would represent a false-positive indication of cardiac tamponade caused by excessive pericardial fluid. METHODS AND RESULTS: Seven spontaneously breathing dogs were chronically instrumented to measure ascending aortic, right atrial, intrapericardial, intrapleural, left atrial, and pulmonary artery pressures and cardiac output. Intravascular volume was adjusted before each experiment to the euvolemic range with saline solution. The onset of RVDC was observed in each animal by two-dimensional echocardiography during seven paired episodes of tamponade induced by infusions of warm saline into the pericardial space alone and, after drainage of the pericardial fluid and complete recovery, into the pleural space in the presence of a small pericardial effusion. The onset of RVDC occurred at the same intrapericardial (8.17 versus 9.47 mm Hg) and right atrial (7.41 versus 7.46 mm Hg) blood pressures regardless of whether it was produced by an intrapericardial or an intrapleural effusion but began in expiration during the former and in inspiration during the latter. Intrapericardial pressure increased in the same manner as intrapleural pressure during intrapleural saline infusion. Nevertheless, cardiac output and aortic blood pressure were better preserved, and at the onset of RVDC, the pulmonary artery systolic blood pressure was higher (p less than 0.0001) and the degree of pulsus paradoxus lower (p less than 0.01) with intrapleural infusion. CONCLUSIONS: These results indicate that a large bilateral pleural effusion can elevate intrapericardial pressure sufficiently to cause RVDC and, perhaps, lead to misdirected therapy of an otherwise insignificant pericardial effusion.

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)

Echocardiographic design of a multicenter investigation of free-living elderly subjects: the Cardiovascular Health Study.

The Framingham study has shown by M-mode echocardiography that left ventricular hypertrophy is a powerful, independent predictor for the development of coronary heart disease and that increased left atrial dimension has been associated with an increased risk of stroke. No previous population-based study has evaluated the risk factor correlates and predictive value for coronary heart disease and stroke of two-dimensional and Doppler, as well as M-mode, echocardiography. The Cardiovascular Health Study is a multi-year prospective epidemiologic study of 5201 men and women older than 65 recruited from four geographic sites in the United States. The main objectives of incorporating echocardiography were to determine whether echocardiographic indices, or changes in these indices, are (1) correlated with traditional risk factors for coronary heart disease and stroke; and (2) independent predictors of morbidity and mortality for coronary heart disease and stroke. Echocardiographic measurements of interest include those related to global and segmental left ventricular systolic and diastolic structure and function and left atrial size. For each subject, a baseline echocardiogram was recorded in super-VHS tape using a standard protocol and equipment. All studies were sent to a reading center where images were digitized and measurements were made using customized computer algorithms. Calculated data and images were stored on optical disks to facilitate retrieval and future comparisons in longitudinal studies. A second echocardiogram is scheduled in year 7, with a goal of determining whether changes in cardiac anatomy or function over a 5-year period are important predictors of morbidity or mortality from coronary heart disease and stroke. Quality control measures included standardized training of echocardiography technicians and readers, technician observation by a trained echocardiographer, periodic blind duplicate readings with reader review sessions, phantom studies, and quality control adults.

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.

Influence of naloxone on response to acute cardiac tamponade in conscious dogs.

During progressive acute cardiac tamponade (CT) in conscious dogs, cardiac output (CO) falls continuously while arterial blood pressure (BP) is well maintained until an abruptly terminal decline. This response is primarily dependent on alpha-adrenergic mechanisms. During hemorrhagic shock, the opioid receptor blocker naloxone increases CO and BP and improves survival perhaps by reversing an opioid-induced cardiovascular depression. We produced 10 episodes of decompensated CT (DCT; 30% decline in BP) by intrapericardial saline infusion (20 ml/min) in five euvolemic conscious dogs. CT resulted in a decrease in CO and BP from base line (3.79 +/- 0.37 l/min and 89.6 +/- 5.2 mmHg, means +/- SE) to DCT (1.35 +/- 0.15 l/min and 57.5 +/- 3.1 mmHg; P less than 0.05). Naloxone (3 mg/kg iv) given at the onset of DCT resulted in a prompt sustained return of BP to base-line levels (P less than 0.05) with no change in CO. Four more animals were studied before and during naloxone (3 mg/kg iv then 0.3 mg.kg-1.min-1 iv). DCT occurred at a higher intrapericardial pressure (20.1 vs. 18.3 mmHg; P less than 0.025) if CT were induced during naloxone treatment than in its absence. Thus naloxone during DCT promptly reversed hypotension with no change in CO and, if present during induction of CT, naloxone allowed slightly higher levels of intrapericardial pressure to be tolerated. Further studies are needed to determine whether naloxone produced these effects solely by its actions on opioid receptors. This study suggests that the interaction between opioid and adrenergic influences plays a role in causing hypotension during CT.

Estrogen modulates responses of atherosclerotic coronary arteries.

Although evidence indicates that estrogen replacement therapy reduces risk of coronary heart disease, the mechanism remains unknown. Among the possibilities are that estrogen replacement therapy may 1) inhibit growth of atherosclerotic plaque and 2) decrease the prevalence of transient myocardial ischemia and myocardial infarction by modulating vasomotion in atherosclerotic coronary arteries. Using quantitative coronary angiography, we determined vasomotor responses of atherosclerotic coronary arteries in ovariectomized cynomolgus monkeys; six were given physiological estrogen "replacement" by subcutaneous implants, and six were not. Intracoronary infusion of the endothelium-dependent dilator acetylcholine (1 X 10(-6) M) caused paradoxical constriction of coronary arteries (from 1.2 +/- 0.2 to 0.6 +/- 0.1 mm, p less than 0.05) in the estrogen-deficient monkeys. However, acetylcholine tended to minimally dilate the left circumflex coronary artery in estrogen-treated monkeys (from 1.2 +/- 0.2 to 1.5 +/- 0.2 mm, p greater than 0.2). Although estrogen replacement therapy reduced plaque extent in coronary arteries, altered vasomotion was not related to plaque extent. We conclude that estrogen modulates vasomotion of atherosclerotic coronary arteries of monkeys and speculate that estrogen-modulated constrictor responses of atherosclerotic coronary arteries may reduce the incidence of coronary heart disease in postmenopausal women.

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.

Increasing atrial pressure during cardiac tamponade does not elevate plasma levels of the peptide ANP in conscious dogs.

1. Factors influencing the release of atrial natriuretic peptide (ANP) are not well understood. We chose a conscious euvolaemic canine model of cardiac tamponade to investigate the roles played by atrial blood pressure, transmural atrial pressure, atrial size, and arginine vasopressin (AVP) on ANP release since during cardiac tamponade the atrial transmural pressure and size decrease as atrial pressure increases. The haemodynamic response to acute cardiac tamponade in conscious dogs differs from that in anaesthetized or convalescent animals. 2. Eighteen mongrel dogs were prepared for the chronic measurement of: ascending aortic blood flow (electromagnetic flowmeter); intrapericardial, right atrial and aortic blood pressures, and the evaluation of right atrial size (two-dimensional echocardiography). After the animals had recovered from surgery, data were collected during progressive cardiac tamponade induced by intrapericardial infusion of warmed saline (20 ml/min) to the point of haemodynamic decompensation. Decompensated cardiac tamponade (DCT) was defined as a decline in mean aortic blood pressure to 70% of the level present when the pericardial space was drained of fluid (baseline) and was produced in all animals within 25 min. Plasma ANP and AVP levels were measured at selected intervals. 3. Cardiac output decreased progressively as intrapericardial pressure, right atrial blood pressure and heart rate increased. Mean aortic blood pressure was well maintained until late in tamponade when it declined rapidly, while atrial transmural pressure and atrial size decreased continuously. These haemodynamic changes were associated with stable ANP plasma levels. There was no significant change in AVP plasma levels from the baseline level of 2.5 +/- 0.4 pg/ml until the point of DCT when they abruptly increased to 117 +/- 36.4 pg/ml. 4. The ability to increase ANP plasma levels was confirmed in a subgroup of animals by noting the response to AVP injection. Although the animals were able to increase plasma ANP levels in response to AVP injection (when intrapericardial pressure was normal) and the plasma AVP level was markedly increased late in tamponade, the time course of plasma AVP elevation could not explain why plasma ANP levels did not decrease as atrial transmural pressure and atrial size declined. 5. Thus, although atrial distention and not simply atrial blood pressure must play a dominant role in stimulating ANP release from the atria, decreased atrial size does not result in lowering of plasma ANP levels below baseline levels in this conscious euvolaemic canine model.

The pathophysiology of pericardial disease--contributions derived from echocardiography/Doppler studies in animal models.

The use of acute and chronically prepared animal models of pericardial disease free of the confounding influences of other disease processes have greatly accelerated the development of echocardiographic and Doppler diagnostic methods and have allowed the correlation of these noninvasive findings with hemodynamic abnormalities.