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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.

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 (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.

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.

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.

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.

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.

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.

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.

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)

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.

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)

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.

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.

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.

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.

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.

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 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.

Right ventricular diastolic collapse has been demonstrated to be a sensitive and specific sign of cardiac tamponade. Because the shape and position of the right ventricular wall are related to the relative pressures within the pericardial space and the right ventricular chamber, the usefulness of right ventricular diastolic collapse as a marker of cardiac tamponade may be influenced by intravascular volume and right heart filling pressures. This study was undertaken to determine the effects of volume loading and hemorrhage on the point within the hemodynamic progression of cardiac tamponade at which right ventricular diastolic collapse first appears. Five unanesthetized, chronically instrumented dogs were studied with two-dimensional echocardiography during 41 episodes of cardiac tamponade induced by the intrapericardial infusion of warm saline solution. Intravascular volume was adjusted before cardiac tamponade to a hypovolemic, euvolemic or hypervolemic state using saline solution and dextran infusion or hemorrhaging to achieve the prescribed mean right atrial blood pressure. The measurements recorded during each episode of cardiac tamponade were right atrial blood pressure, aortic blood pressure, cardiac output (by electromagnetic flow meter), heart rate and intrapericardial pressure. When compared with the euvolemic state, the onset of right ventricular diastolic collapse in volume contraction occurred at a lower intrapericardial pressure (with a lower aortic blood pressure and cardiac output), whereas in volume expansion it occurred at a higher intrapericardial pressure (with a higher aortic blood pressure and cardiac output). Volume expansion delayed the decrease in hemodynamic variables during cardiac tamponade in this canine model.

The onset of right ventricular diastolic collapse has been shown to be a very sensitive and specific sign of cardiac tamponade in both clinical and conscious canine studies, and is associated with a decline in cardiac output of about 20%. To determine if blood flow to critical regions was affected at the time of onset of right ventricular diastolic collapse, seven unanesthetized, chronically instrumented dogs were studied during cardiac tamponade induced by the intrapericardial infusion of warm saline solution. Aortic blood pressure, heart rate, and cardiac output (electromagnetic flowprobe) were recorded at baseline (drained pericardial space) and at the onset of right ventricular diastolic collapse as seen on two-dimensional echocardiography. Regional blood flow was measured with radionuclide-labeled microspheres. Despite the expected decline in cardiac output, there was no significant change in cardiac, renal, or cerebral cortical blood flow at the onset of right ventricular diastolic collapse. Therefore, this noninvasive marker of early cardiac tamponade begins before vital organ perfusion is compromised, thus strengthening its clinical value.

Clinical reports indicate that right ventricular diastolic collapse (RVDC) is associated with cardiac tamponade. To assess the hemodynamic abnormalities associated with RVDC, we studied six chronically instrumented conscious dogs (group A) with two-dimensional echocardiography during cardiac tamponade induced by continuous saline infusion into the pericardial space. We recorded cardiac output (electromagnetic flowmeter), heart rate, respiration, and aortic, intrapericardial, and right atrial pressures. In four additional animals (group B), we recorded right ventricular pressure and placed a hydraulic occluder around the pulmonary artery so that short-term reversible obstruction to right ventricular outflow could be produced. None of the dogs had RVDC when the pericardial space was empty, but all dogs showed RVDC during cardiac tamponade. The appearance of RVDC in group A was associated with a 21% reduction in cardiac output (p less than .01) and no change in mean aortic pressure. Short-term partial pulmonary artery obstruction led to increased right ventricular pressures and a striking reduction in RVDC in early tamponade, suggesting that RVDC is caused by pericardial pressure exceeding right ventricular pressure in early diastole. An additional animal had right ventricular hypertrophy caused by a severe "heart worm" infestation and did not show RVDC during cardiac tamponade. These observations suggest that in the absence of increased resistance to right ventricular outflow or right ventricular hypertrophy, RVDC occurs early in the course of cardiac tamponade and is associated with a hemodynamically important decrease in cardiac output.

The efficacy of truncated exponential waveform shocks using a cardioverter-defibrillator catheter with and without a 13.9 cm2 subcutaneous thoracic patch electrode was examined in 10 pentobarbital-anesthetized dogs. The cardioverter-defibrillator catheter was positioned through the external jugular vein with the distal 4 cm2 shocking electrode located in the right ventricular apex and the 8 cm2 proximal electrode located in the superior vena cava. Four electrode configurations were tested: 1) distal electrode (cathode) to proximal electrode and chest wall patch (common anodes), 2) distal electrode (cathode) to chest wall patch (anode), 3) distal electrode (cathode) to proximal electrode (anode), and 4) chest wall patch (cathode) to proximal electrode (anode). The lowest randomized energy resulting in termination of alternating current-induced ventricular fibrillation on four trials at that energy was 20.2, 21.3, 27.4 and greater than 40 J, respectively, for configurations 1 through 4. The energy requirements for configurations 1, 2 and 3 were significantly lower than for configuration 4 (p less than 0.001). Additionally, configurations incorporating the distal electrode and the patch electrode (configurations 1 and 2) were significantly better than the catheter alone (configuration 3; p less than 0.05). There was no significant difference between configurations 1 and 2. In conclusion, the addition of a subcutaneous chest wall electrode to the cardioverter-defibrillator catheter significantly lowered energy requirements for defibrillation, suggesting that a nonthoracotomy approach for the automatic implantable cardioverter-defibrillator is feasible.

The myocardial damage and arrhythmogenicity of percutaneous transcatheter shocks utilizing two different defibrillator waveforms (truncated exponential and damped sinusoidal) were compared. Ten dogs (33.7 +/- 3.6 kg) were studied. Five received left ventricular damped sinusoidal R-synchronous shocks during sinus rhythm and the other five received truncated exponential waveform shocks. Each dog received four energies (60, 120, 180, and 240 joules) randomly assigned to four left ventricular sites. The immediate postshock rhythms were recorded. Ventricular tachycardia occurred after 90% of the damped sinusoidal shocks compared to only 25% of the truncated exponential shocks (p less than 0.005). The animals were sacrificed 14 days later. Infarct size as determined by planimetry was not significantly different for the two waveforms. Thus intracavitary shocks utilizing a truncated exponential waveform are less arrhythmogenic than damped sinusoidal waveform shocks but produce similar morphologic changes and therefore may offer a significant safety advantage for catheter ablation procedures.

We evaluated the ability of Doppler echocardiography to assess left ventricular performance in six open-chest dogs studied under various conditions. Intravenous infusions of nitroglycerin were used to vary preload, atrial pacing was used to control heart rate, and changes in inotropic state were induced by two different doses of dobutamine (5 and 10 micrograms/kg/min iv) and by administration of propranolol (1 mg/kg iv). Left ventricular anterior wall myocardial segment length was used as an index of preload. Maximum aortic blood flow, peak acceleration of aortic blood flow, and dP/dt were measured with an electromagnetic flow probe around the ascending aorta and a high-fidelity pressure transducer in the left ventricle. A continuous-wave Doppler transducer applied to the aortic arch was used to measure peak aortic blood velocity, mean acceleration, time to peak velocity, and the systolic velocity integral. The differences between mean values obtained under different inotropic conditions were significant at the p less than .01 level for peak velocity and at the p less than .05 level for mean acceleration. Within a given animal, Doppler measurements of peak velocity correlated very closely with maximum aortic flow (r = .96), maximum acceleration of aortic flow (r = .95), and with maximum dP/dt (r = .92). Mean acceleration measured by Doppler echocardiography also correlated very closely with conventional indexes, but was subject to greater interobserver variability. Doppler measurements of time to peak and the systolic velocity integral correlated less well with conventional hemodynamic indexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac tamponade is a spectrum ranging from pericardial effusions with minimal hemodynamic impairment to effusions causing circulatory collapse. In this study, we examined the roles played by the sympathetic nervous system and the renin-angiotensin system in controlling the distribution of blood flow in chronically instrumented conscious dogs during progressive cardiac tamponade. Fifty-one episodes of acute cardiac tamponade were induced to decompensation (decline in mean aortic blood pressure to 70% of the level present when the pericardium was free of fluid) in 6 dogs by intrapericardial infusion of warmed saline solution. Cardiac output (electromagnetic flow probe), intrapericardial pressure, aortic and right atrial blood pressures, and renal, coronary, and mesenteric artery blood flows (Doppler flow probes) were recorded during tamponade in the absence of blockade (control), during alpha-adrenergic blockade (phenoxybenzamine), beta-adrenergic blockade (propranolol), or angiotensin-converting enzyme blockade (captopril). Aortic and mesenteric artery blood flow decreased progressively during cardiac tamponade regardless of the presence or absence of blockade. Coronary artery blood flow did not significantly change during alpha-adrenergic blockade, suggesting that the continuous decline observed during cardiac tamponade in the absence of blockade was at least in part mediated by alpha-adrenergic mechanisms. Renal artery blood flow, in contrast, was well maintained in all situations, confirming the importance of autoregulation in this vascular bed during cardiac tamponade.

Doppler echocardiographic indexes of ascending aortic blood flow velocity have been found to be an effective method of assessing changes in left ventricular performance induced by myocardial ischemia in both experimental animal preparations and in patients. In eight opened-chest anesthetized dogs, we investigated the influence of heart rate, aortic blood pressure, and size of the ischemic zone on Doppler indexes during regional myocardial ischemia. With control of mean aortic blood pressure and heart rate, transient coronary artery occlusion resulted in a statistically significant decline in peak velocity and mean velocity when as little as 24% of left ventricular myocardium was rendered ischemic. However, when heart rate and mean aortic blood pressure were not controlled, significant declines in peak velocity and mean velocity occurred only with simultaneous two-vessel occlusions involving greater than 47% of left ventricular myocardium. Although transient coronary artery occlusions generally produced no significant change in heart rate in the absence of atrial pacing, significant declines in aortic blood pressure were observed. We conclude that Doppler indexes of left ventricular performance obtained during myocardial ischemia are influenced not only by the extent of myocardium rendered ischemic, but also by changes in mean aortic blood pressure.

To investigate the influence of changes in afterload on Doppler echocardiographic determination of peak aortic blood velocity, mean acceleration, and systolic velocity integral, eight dogs with their chests opened were studied in four inotropic states at varying levels of heart rate and mean aortic blood pressure. Data were collected in the control state, at two different levels of dobutamine administration (5 and 10 micrograms/kg/min intravenously), and after administration of propranolol (0.5 mg/kg intravenously). In each inotropic state, phenylephrine was infused intravenously to produce at least two successive steady state increases of 10 mm Hg or more in mean aortic blood pressure. Within a given animal, peak velocity emerged as the Doppler index most closely correlated with changes in Qmax, dQ/dt, and dP/dt (r = 0.94, 0.91, and 0.89, respectively). Mean acceleration also correlated closely with the invasive indexes (r = 0.87, 0.89, and 0.89). The effect of changes in mean aortic blood pressure on Doppler index measurements was not statistically significant in any of the inotropic states and did not affect the closeness of their correlation with the invasive indexes. We conclude that Doppler echocardiographic measurements of aortic blood peak velocity and mean acceleration remained as sensitive to changes in the inotropic state under conditions of varying increases in afterload as did the conventional invasive indexes tested.

To compare the sensitivity, specificity and predictive value of right ventricular (RV) diastolic collapse and pulsus paradoxus as signs of cardiac tamponade, 21 consecutive patients with pericardial effusion and suspected cardiac tamponade underwent prospective hemodynamic and echocardiographic evaluation. Simultaneous hemodynamic and echocardiographic data were obtained in all patients before and after pericardiocentesis. Cardiac tamponade was considered present when there was diastolic equilibration of the intrapericardial, right atrial and pulmonary capillary wedge pressures and elevation of these pressures to more than 10 mm Hg. RV diastolic collapse was 93% sensitive and 100% specific in diagnosing cardiac tamponade, whereas pulsus paradoxus was only 79% sensitive and 40% specific. The positive and negative predictive values of RV diastolic collapse (100% and 83%) were considerably better than pulsus paradoxus (81% and 40%) and demonstrate that RV diastolic collapse is more sensitive, specific and predictive of cardiac tamponade than is pulsus paradoxus. Serial simultaneous hemodynamic and echocardiographic observations at multiple points during pericardiocentesis in a smaller subgroup (5 patients) also suggest that the hemodynamic effects of RV diastolic collapse in cardiac tamponade are mediated by an increase in intrapericardial pressure.

Both pulsus paradoxus and right ventricular diastolic collapse detected by two-dimensional echocardiography are noninvasive markers of impaired cardiac function in cardiac tamponade, yet the reliability of each may vary with the patient's state of hydration. To examine the relative value of these noninvasive markers at various states of hydration, we studied five chronically prepared, conscious mongrel dogs during 37 episodes of cardiac tamponade at three different intravascular volumes. We continuously measured cardiac output (electromagnetic flowmeter), aortic blood pressure, right atrial blood pressure, intrapericardial pressure, and respirations. Intravascular volume was varied by adjusting the mean right atrial blood pressure to hypovolemic (-2 to -6 mm Hg), euvolemic (0 to 4 mm Hg), or hypervolemic (6 to 10 mm Hg) levels. The sensitivity and specificity of right ventricular diastolic collapse in predicting increases in intrapericardial pressure remained high at all levels of hydration. Pulsus paradoxus showed good sensitivity and specificity at low intravascular volumes, but both sensitivity and specificity declined at higher intravascular volumes. Thus right ventricular diastolic collapse was more sensitive and more specific than pulsus paradoxus in detecting increases in intrapericardial pressure during euvolemia and hypervolemia whereas the two tests were equally valuable in hypovolemic states.

We tested the hypothesis that coronary artery blood flow is sufficient to meet myocardial requirements throughout cardiac tamponade in a conscious euvolemic canine model recovered from surgery. Seven mongrel dogs were chronically instrumented to measure ascending aortic blood flow (electromagnetic flowmeter); intrapericardial, right atrial, and aortic blood pressures; regional myocardial blood flow (radionuclide labelled microspheres); and myocardial consumption of lactate, pyruvate, and oxygen. Data were collected during progressive cardiac tamponade induced by intrapericardial saline infusion to the point of hemodynamic 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 minutes. Cardiac tamponade caused a continuous decline in coronary artery blood flow from 1.26 +/- 0.35 (baseline, mean +/- SD) to 0.53 +/- 0.15 ml/min/g (DCT, p less than 0.01), which was associated with a decrease in myocardial oxygen consumption from 1.26 +/- 0.35 (baseline) to 0.74 +/- 0.27 ml/min/g (DCT, p less than 0.05) and a slight increase in myocardial oxygen extraction from 71 +/- 3 (baseline) to 81 +/- 4% (DCT, p less than 0.05). This change in oxygen extraction occurred because of both an increase in arterial and a decrease in coronary venous oxygen content. At all degrees of cardiac tamponade, the lactate-pyruvate ratio did not change significantly from baseline (7.56 +/- 2.31), there was no evidence of lactate production, and the normal endocardial to epicardial blood flow ratio present at baseline (1.41 +/- 0.23) was preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the hemodynamic derangement associated with right ventricular diastolic collapse and to assess the value of right ventricular and right atrial collapse in identifying cardiac tamponade, two-dimensional echocardiograms were recorded simultaneously with measurement of right atrial, pulmonary capillary wedge, intrapericardial, and systemic arterial pressures and cardiac output in 16 patients as they underwent pericardiocentesis. Twelve patients (group I) had evidence of right ventricular or right atrial collapse or both on their echocardiograms and hemodynamic evidence of cardiac tamponade before pericardiocentesis. All hemodynamic parameters improved after pericardiocentesis (p less than or equal to .05). Continuous monitoring during pericardiocentesis in three of these patients showed significant improvement in all parameters except heart rate (p less than or equal to .02) at the point of disappearance of right ventricular diastolic collapse, with further improvement in cardiac output as pericardiocentesis continued (p less than .01). Right atrial collapse persisted after right ventricular collapse disappeared but was no longer present when pericardiocentesis was completed. Three patients (group II) had no right ventricular or right atrial collapse, no hemodynamic evidence of cardiac tamponade, and no improvement in hemodynamic parameters after pericardiocentesis. A single patient (group III) was found to have elevated right heart pressures and right ventricular hypertrophy before pericardiocentesis. Although there was hemodynamic evidence of cardiac tamponade in this patient, there was no evidence of right ventricular or right atrial collapse. In this study, the sensitivity of right ventricular collapse as a marker for cardiac tamponade was 92%, its specificity 100%, its accuracy 94%, and its predictive value 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent reports using anesthetized ventilator-dependent animal models, have suggested that in certain shock states, a disparity exists between arterial and mixed venous blood gases with regard to acid-base status and oxygenation. In a chronically instrumented unanesthetized canine model of acute cardiac tamponade breathing room air, we studied the effect of a graded decline in cardiac output on arterial and mixed venous pH, PCO2, and PO2. Cardiac tamponade resulted in a profound arterial respiratory alkalosis, whereas mixed venous pH, PCO2, and calculated serum bicarbonate levels remained relatively unchanged. As intrapericardial pressure increased and cardiac output declined, the difference between arterial and mixed venous PCO2 progressively increased. Further, whereas arterial oxygenation improved as cardiac output declined, mixed venous oxygenation steadily worsened. This disparity began early in cardiac tamponade (reductions in cardiac output of 20-40%) long before arterial blood pressure began to fall and progressively worsened as hemodynamic deterioration and lactic acidosis developed. Our findings are consistent with the hypothesis that a reduction in blood flow, resulting in decreased CO2 delivery to the lungs, is the primary mechanism responsible for the difference in pH and PCO2 observed between arterial and mixed venous blood. In this conscious, spontaneously breathing animal model, mixed venous blood gases thus are superior to arterial blood gases in assessing acid-base status and oxygenation, even early in acute cardiac tamponade when the decline in cardiac output is in the range of 20 to 40% and arterial blood pressure has not changed significantly.

Catheter ablation of arrhythmias is a promising new technique. The consequence of high-energy discharges in the right ventricle were investigated in a canine model of inducible ventricular tachycardia. Seventeen dogs were studied. Four served as controls while 13 underwent thoracotomy with right coronary artery ligation. Three animals died suddenly postoperatively. Programmed stimulation was performed 4 days later using a pervenous right ventricular electrode catheter. No control dog had inducible ventricular tachycardia. Eight of the experimental animals had inducible ventricular tachycardia and underwent catheter mapping. The earliest endocardial site during tachycardia was located in four dogs with monomorphic ventricular tachycardia. These sites received one or more 300 J transcatheter stored charges from a defibrillator, and at least temporary ablation was accomplished in each case. Five animals had inducible polymorphic ventricular tachycardia which could not be mapped. The endocardial electrogram amplitude decreased 55 +/- 7% (p less than 0.001) and the pacing threshold increased from 0.7 +/- 0.1 mA to 7.9 +/- 1.7 mA (p less than 0.001) after the shocks. Five of the discharges caused ventricular tachycardia or fibrillation. Autopsy revealed discrete transmural wedge-shaped necrosis without perforation. Thus when monomorphic tachycardia was induced, mapping and ablation were feasible. Transcatheter 300 J discharges produced only localized damage but had a propensity to initiate ventricular arrhythmias.

Experiments on five chronically instrumented dogs were performed to study the effects of changes in circulating blood volume on the aortic smooth muscle activity in awake animals. The external diameter of the proximal descending aorta was measured with a sonomicrometer. Aortic pressure was measured in the same cross-sectional area with a catheter-tip transducer. Acute hemorrhage of 15% of the estimated blood volume was performed 17 times by quickly withdrawing blood through a jugular cannula. At any given arterial pressure within the range of overlap the aortic diameter (D) was always decreased after hemorrhage compared with control, and the pressure-strain elastic modulus (Ep) and the characteristic impedance (Zc) were always increased. For example at 140 kdyn X cm-2 (104.5 mmHg) delta D = -0.61 +/- 0.12 mm or delta D = -3.44 +/- 0.68% of control, delta Ep = 31.0 +/- 8.6%, and delta Zc = 22.6 +/- 4.5%. Each of these changes was significant with P less than 0.01. Volume expansion of 30% was performed eight times by infusing warm saline. At any given arterial pressure D was always increased and Ep and Zc were always decreased. At 140 kdyn X cm-2 delta D = 0.55 +/- 0.15 mm or delta D = 3.12 +/- 0.95% of control, delta Ep = -12.4 +/- 3.2%, and delta Zc = -12.0 +/- 2.1%. Each of these changes was significant with P less than 0.01. Since in these awake animals the changes in circulatory blood volume modified the arterial pressure only slightly, the contribution of viscoelasticity and myogenicity to the observed responses was minimal.

The purpose of this study was to determine the relative magnitudes of the reflex effects mediated by sensory endings in the left ventricle activated by intracoronary injection of nicotine or veratridine into left anterior descending (LAD) or circumflex (Cx) coronary arteries in the dog. Injection of nicotine or veratridine into the Cx consistently resulted in larger decreases in heart rate, arterial pressure, and in gracilis perfusion pressure than were observed following injection of the same dose into the LAD. Vagotomy abolished the cardioinhibitory and vasodepressor responses to intracoronary nicotine or veratridine. The weight of left ventricle perfused by LAD or Cx was not different (43.5 +/- 1.65 and 44.5 +/- 2.2 g, respectively. These data indicate that chemical activation of sensory endings with vagal afferents in the inferoposterior left ventricle of the dog results in larger cardionhibitor and vasodepressor responses than result from activation of respects in the anterior left ventricle. Further, these data provide strong evidence that these sensory endings which are chemically activated are preferentially distributed to the inferoposterior left ventricle.

The purpose of this study was to determine the relative magnitudes of the reflex effects mediated by cardiac receptors during anterior as opposed to inferoposterior ischemia of the left ventricle of the dog. Cessation of perfusion (coronary "occlusion") of the circumflex coronary artery (Cx) in 29 chloralose-anesthetized dogs with common carotids ligated (group I) resulted in significant bradycardia and hypotension, but in no significant change in perfusion pressure in the gracilis muscle perfused at constant flow. Occlusion of the left anterior descending coronary artery (LAD) produced less hypotension, no change in heart rate, and vasoconstriction in the gracilis. After vagotomy and aortic nerve section, no significant change in heart rate or gracilis perfusion pressure was observed during lad or Cx occlusion, and the blood pressure responses to LAD and Cx occlusion were not different. In nine dogs with sinoaortic denervation (group II), brief Cx occlusion resulted in bradycardia, hypotension, and vasodilation in the gracilis muscle. LAD occlusion in group II dogs caused less hypotension and no change in heart rate or gracilis perfusion pressure. After vagotomy, the bradycardia and vasodilation resulting from Cx occlusion were abolished and the blood pressure responses to LAD and Cx occlusion were not different. The weights of left ventricle perfused by each occluded vessel were not different. These data show that left ventricular receptors with vagal afferents which are activated during coronary occlusion and which mediate cardioinhibitory and vasodepressor responses are located mainly in the inferoposterior left ventricle of the dog heart.

An inspiratory decline in systolic arterial blood pressure exceeding 10 mm Hg has been used clinically to identify hemodynamically significant pericardial effusions. Recently, the echocardiographic sign of right ventricular diastolic collapse (RVDC) has been shown to occur early in the course of cardiac tamponade in association with a hemodynamically important decline in cardiac output. This study was undertaken to compare the relative merits of pulsus paradoxus and the onset of RVDC in the early detection of cardiac tamponade in an unanesthetized canine preparation. We studied six chronically instrumented, conscious dogs with two-dimensional echocardiography during cardiac tamponade induced by continuous infusion of saline into the pericardial space. We recorded intrapericardial pressure, cardiac output (electromagnetic flowmeter), aortic (catheter-tip transducer) and right atrial blood pressures, heart rate, and respiration. None of the dogs had RVDC when the pericardial space was empty, but all dogs showed RVDC during cardiac tamponade. We found that RVDC was strongly related to all of the cardiac parameters evaluated (intrapericardial pressure, cardiac output, aortic blood pressure, heart rate, and stroke volume) and provided information on each that was independent of that provided by pulsus paradoxus. Furthermore, RVDC appeared to be more strongly related to most cardiac parameters than was pulsus paradoxus and to be more sensitive and specific than pulsus paradoxus in detecting changes in intrapericardial pressure early in cardiac tamponade.

During progressive cardiac tamponade in conscious dogs, cardiac output falls continuously while arterial blood pressure is maintained until cardiovascular decompensation by increases in total peripheral resistance (TPR). Plasma renin activity (PRA) is known to increase at decompensation. We hypothesized that the increase in TPR during cardiac tamponade was mediated by alpha-adrenergic and renin-angiotensin mechanisms. Twelve adult dogs were instrumented to measure cardiac output (electromagnetic flow probe), aortic and right atrial blood pressures, and intrapericardial pressure (IPP). TPR was calculated as the conscious euvolemic animals underwent cardiac tamponade induced by intrapericardial saline infusion at 20 ml/min. Six dogs underwent cardiac tamponade in the control condition (no medications) and during independent alpha- and beta-adrenergic and angiotensin-converting enzyme (ACE) inhibition. PRA and angiotensin II (ANG II) were measured during control tamponade. We found that TPR increased continuously to levels of greater than 200% of base line as IPP rose during cardiac tamponade (P less than 0.01). This increase in TPR was unaffected by beta-adrenergic or ACE blockade but was blunted by alpha-adrenergic blockade. PRA and ANG II increased only at decompensated tamponade (P less than 0.05) when arterial blood pressure had fallen by 30%. These changes in PRA and ANG II during tamponade were not altered by beta-blockade in six separate animals. We conclude that cardiac tamponade stimulates renin release and ANG II generation by a non-beta-receptor-mediated mechanism. The increase in TPR during cardiac tamponade is primarily dependent on alpha-adrenergic mechanisms, with a limited late contribution from the renin-angiotensin system.

We hypothesized that a process leading to an acute increase in cardiac size would change the relationship between intrapericardial pressure and fluid volume during cardiac tamponade, resulting in a change in the time of onset of right ventricular diastolic collapse (RVDC) as seen on the two-dimensional echocardiogram. Five spontaneously breathing dogs were instrumented to measure ascending aortic and right atrial blood pressures and intrapericardial pressure (IPP). A hydraulic occluder was placed around the proximal descending thoracic aorta. Each animal underwent six consecutive episodes of cardiac tamponade, three in the presence alternating with three in the absence of aortic constriction. The onset of RVDC was recorded and the volume infused into the pericardial space was measured. In the presence of aortic constriction, the relationship between pericardial pressure and incremental pericardial fluid volume was shifted so that IPP was an average of 3.4 mm Hg higher at any given intrapericardial fluid volume (p less than .001). At the onset of RVDC, the mean IPP was higher and the intrapericardial fluid volume was lower during aortic constriction than under control conditions (p less than .001 for both comparisons). Thus, a rapid increase in left ventricular volume in the presence of an otherwise unimportant pericardial effusion may increase intrapericardial fluid pressure sufficiently to cause RVDC.