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Objective: We sought to correlate cervical and endometrial neoplasias with Papanicolaou (Pap) smears of atypical glandular cells of undetermined significance (AGUS) and to suggest management.Materials and Methods: One hundred seventy-one patients with AGUS Pap smears were followed prospectively with colposcopy, biopsies, endocervical curettage, and endometrial biopsies.Results: One hundred twelve patients (65%) with AGUS Pap smears favoring reactive changes were found to harbor 13 preinvasive and invasive cervical squamous neoplasias and 1 ovarian sarcoma (total, 12.5% of patients with smears). Fifty-nine patients (35%) with AGUS Pap smears favoring neoplastic changes harbored 25 preinvasive and invasive squamous and glandular cervical and endometrial neoplasias (42.3%).Conclusion: In the presence of an AGUS Pap smear favoring reactive changes, colposcopy, biopsies, and endocervical curettage should be performed. Endometrial biopsy should be added when AGUS Pap smear favors neoplasia. [ABSTRACT FROM AUTHOR]

Objective: To explore the possibility of using histologic microvessel count of sections from the tumor to predict recurrence of stage Ib squamous cell carcinoma of the cervix., Methods: Tumor sections from 22 patients (11 patients free of disease after 3 years and 11 patients with recurrence) were stained histoimmunochemically for factor VIII-related antigens. Vessel counting in the most active area of angiogenesis was performed by two pathologists on a x 200 microscopic field (0.739 mm2) without knowledge of the patient's' outcome. To predict recurrence, vessel count was compared with age, tumor size, tumor grade, lymph-vascular invasion, duration of follow-up, and type of therapy., Results: Only high microvessel count (mean 19.9, range 7-43, versus mean 30.1, range 17-78; P < .05) and tumor size (mean 2.84 cm, range 1-4.2, versus mean 4.11 cm, range 2.2-6; P < .05) were independent factors predicting recurrence., Conclusion: High microvessel count in tumors may be used to predict recurrence in stage Ib squamous cell carcinoma of the cervix.

Background: Regional disparities of ventricular primary-repolarization properties contribute to an electrophysiological substrate for arrhythmias. Such disparities can be assessed from body-surface distributions of ECG QRST areas. Our objective was to isolate and test those features of QRST-area distributions that would be suitable for identifying patients at risk for life-threatening ventricular arrhythmias., Methods and Results: We recorded ECGs simultaneously from 120 leads during sinus rhythm for 204 patients taking no antiarrhythmic drugs: half had had sustained ventricular tachycardia (VT); the other half, a myocardial infarction but no history of VT. For each patient, we calculated the QRST area in each lead and, using Karhunen-Loeve (K-L) expansion, reduced these data to 16 coefficients (each relating to one spatial feature, an eigenvector, derived from the total set of 204 QRST-area maps). Using stepwise discriminant analysis, we selected feature subsets that best discriminated between the two groups, and we estimated by a bootstrap procedure using 1000 trials how these subsets would perform on a prospective patient population. The mean diagnostic performance of the classifier for 1000 randomly selected training sets (n = 102 in each, with both groups equally represented) increased monotonically with the number of features used for classification. The initial trend for the corresponding test sets (n = 102 in each) was the same but reversed when the number of features exceeded eight. For an optimal set of eight spatial features, the sensitivity and specificity of the classifier for detecting patients with VT in 1000 test sets were (mean +/- SD) 90.3 +/- 4.3% and 78.0 +/- 6.1%, and its positive and negative predictive accuracies were 80.7 +/- 4.2% and 89.2 +/- 4.2%, respectively. Use of QRS duration as a supplementary feature to eight K-L coefficients can, in the test sets, increase specificity to 80.9 +/- 5.4% and positive predictive accuracy to 82.8 +/- 3.9% compared with the results for the optimal number of eight K-L features alone., Conclusions: Multiple body-surface ECGs contain valuable spatial features that can identify the presence of an arrhythmogenic substrate in the myocardium of patients at risk for ventricular arrhythmias. Our results compare very favorably with those achieved by any other known test, invasive or noninvasive, for arrhythmogenicity.

Background: Acute right ventricular (RV) hypertension may result in hemodynamic collapse. The associated reduction in left ventricular (LV) end-diastolic volume is thought to result from reduced RV output (secondary to RV ischemia) and adverse direct ventricular interaction. Aortic constriction improves cardiac function in these circumstances; this has been attributed to a reversal of the RV ischemia caused by an increased coronary perfusion pressure. We hypothesized that altered ventricular interaction, potentially via altered septal mechanics, may also contribute to the beneficial effects of aortic constriction., Methods and Results: We instrumented nine dogs with ultrasonic dimension crystals to measure RV segment length, septum-to-RV free wall and septum-to-LV free wall diameters, and LV anterioposterior diameter. Catheter-tipped manometers were used to measure LV and RV pressures. Pericardial pressure was measured with flat, liquid-containing balloon transducers. Inflatable cuff constrictors were placed on the pulmonary artery (PA) and aorta, and a flow probe was placed on the PA. The right coronary artery (RCA) was perfused independently by a roller pump calibrated for flow. During moderate PA constriction, while RCA pressure was maintained at control level, RCA flow did not change significantly (15.8 +/- 6.2 to 16.9 +/- 11.5 mL/min) and was similar during severe PA constriction (18.6 +/- 9.8 mL/min). During severe PA constriction, RV stroke volume decreased from a control value of 10.3 +/- 4.9 to 2.3 +/- 1.4 mL/beat (P < .05). When aortic constriction was added while RCA pressure was maintained at control level, there was an increase in RV stroke volume to 4.5 +/- 2.0 mL/beat (P < .05) with no associated change in RCA flow (17.8 +/- 9.5 mL/min). However, pressure-dimension loops clearly demonstrated changes in diastolic and systolic ventricular interaction; with aortic constriction, there was a large increase in the transeptal pressure gradient associated with a rightward septal shift. During either isolated severe PA constriction or simultaneous severe PA and aortic constriction, RCA flow was increased until RCA pressure was approximately equal to that in the aorta. This produced an increase in RCA flow of 50% (P < .05); however, this increase in coronary flow was ineffective in improving any measure of RV function., Conclusions: In this model of acute RV hypertension, aortic constriction improves cardiac function, at least in part, by altering ventricular interaction independent of changes in RCA flow. Changes in RCA flow do not appear to have a significant impact on cardiac function in this model in which coronary artery pressure was maintained at normal or increased levels.

Background: Distortion of the left ventricular (LV) cavity in patients with right ventricular pressure overload (RVPO) is well known. However, no direct measurements of regional myocardial function in terms of myocardial shortening and wall thickening are available; therefore, exactly how RVPO disturbs LV regional performance remains unclear. By using three-dimensional (3D) tagged magnetic resonance imaging, we were able to measure regional systolic function directly. Our objective was to study the relation between the distortion of the LV circular shape and regional LV function., Methods and Results: In nine patients with RVPO and six healthy volunteers, four parallel short-axis images (with 12 radial tags) and two mutually orthogonal long-axis images (with four parallel tags) were generated, and endocardial and epicardial borders were manually traced. By integration of the short- and long-axis images, 3D reconstruction of the LV tracking points from end diastole to end systole was obtained. Data from the midventricular two short-axis image slices were analyzed. These were then divided into anterior, lateral, posterior, and septal regions. Circumferential and longitudinal shortening were then calculated from the endocardial and epicardial tag intersection points. Wall thickness and thickening were calculated by the 3D volume-element approach. An eccentricity index (EI), the ratio of septum-to-free-wall to anteroposterior diameters, was used to describe the shape of the LV cavity. The regional curvature was also measured. The RVPO group was characterized by flattening of the septum and LV lateral wall, decreased EI reflecting the distorted LV shape, altered distribution of endocardial circumferential shortening, and preserved ejection fraction. Changes in EI closely correlated with the septal curvature. The EI was smaller at end systole, reflecting further shape distortion relative to end diastole. Reduced myocardial performance, as measured by wall thickening and circumferential and longitudinal shortening fractions, was observed for the septum. A reduction in endocardial circumferential shortening of the septal and lateral walls was directly related to the end-systolic EI. In addition, whereas for healthy subjects a linear relation between area ejection fraction and endocardial circumferential shortening was observed, in RVPO patients a curvilinear (quadratic) relation was observed., Conclusions: In patients with RVPO, compared with healthy subjects, the septal function was reduced, as evidenced by reduced thickening and shortening fractions. The distortion in LV cavity at end systole due to the flattening of the septum contributes to preserved systolic ventricular function and nonuniform distribution in endocardial circumferential shortening.

Background: Vasodilator drugs have variable effects on veins and arteries. However, direct measurements of their effects on the splanchnic veins, perhaps the most important volume reservoir, have not been reported. We assessed the effect of acute heart failure and the subsequent administration of hydralazine, enalaprilat, and nitroglycerin on the splanchnic venous pressure-volume relation in intact dogs., Methods and Results: Experimental acute ischemic heart failure was induced in 19 splenectomized dogs by microsphere embolization of the left main coronary artery. Embolization was repeated until left ventricular end-diastolic pressure (LVEDP) reached 20 mm Hg and cardiac output decreased by 50%. The splanchnic vascular pressure-volume relation was determined by radionuclide plethysmography during the control stage, after acute heart failure had been established, and after administration of a vasodilator (hydralazine, enalaprilat, or nitroglycerin) at a dose sufficient to reduce mean aortic pressure by approximately 20%. Induction of acute heart failure was associated with a decrease in the splanchnic vascular volume from 100% to 86 +/- 2% and an increase in LVEDP from 6 +/- 1 to 21 +/- 1 mm Hg (P < .001). There was a parallel leftward shift of the splanchnic vascular pressure-volume curve. After the administration of hydralazine, enalaprilat, and nitroglycerin, the splanchnic vascular volumes increased from 86% to 88 +/- 3%, 96 +/- 3%, and 113 +/- 3%, respectively (P = NS, P < .01, and P < .001, respectively, versus heart failure). After drug administration, the LVEDPs were 18 +/- 2, 16 +/- 1, and 13 +/- 1 mm Hg (P = NS, P < .05, and P < .001, respectively, versus heart failure)., Conclusions: Acute heart failure was associated with a parallel leftward shift of the splanchnic venous pressure-volume relation (venoconstriction). Splanchnic (systemic) venoconstriction may in part explain the increased LVEDP during acute heart failure by displacement of blood to the central compartment. Subsequently administered enalaprilat and, to a greater degree, nitroglycerin produced splanchnic venodilation, thereby lowering LVEDP. Hydralazine had no significant effect on the splanchnic veins and only a modest effect on LVEDP. In this model, splanchnic capacitance changes appear to modulate change in left ventricular preload.

Background: To determine the transmural pressure-dimension relations of the right atrium (RA) and right ventricle (RV) before and after pericardiectomy, six open-chest dogs were instrumented with pericardial balloons placed over the RA and RV free walls., Methods and Results: PA appendage dimensions and RV free-wall segment lengths were measured using sonomicrometry. Intact-pericardium RA and RV transmural pressures were calculated by subtracting the pericardial pressures (measured using balloons) from the cavitary pressures. Pooled data from six animals with pericardium intact indicate that at RA and RV cavitary pressures of 5, 10, and 15 mm Hg, RV pericardial pressure was 4.3 +/- 0.3, 8.6 +/- 1.0, and 13.3 +/- 1.5 mm Hg, respectively, and RA pericardial pressure was 4.8 +/- 0.3, 9.6 +/- 0.6, and 14.6 +/- 0.6 mm Hg, respectively (mean +/- SD). With calculated unstressed dimensions, the cavity dimension data were normalized to strain (in percent). We determined that in the dog, RV strain would increase by 14% and RA by 68% to maintain cavitary pressure at 10 mm Hg on pericardiectomy. To compare these results with clinical data, RV (n = 7) and RA (n = 6) transmural pressures were measured using balloons in patients (age, 19 to 76 years) undergoing cardiac surgery. RA transmural pressure of six patients was 1.0 +/- 1.5 mm Hg when central venous pressures (CVPs) ranged from 3 to 16 mm Hg. RV transmural pressure equaled 1.2 +/- 1.9, 2.3 +/- 1.9, and 3.4 +/- 2.0 mm Hg when CVP was 5, 10, and 15 mm Hg, respectively., Conclusions: Pericardial constraint (as evaluated by the ratio of pericardial to intracavitary pressures when CVP is 10 mm Hg) accounted for 96% of RA cavitary pressure in the dog and 89% in humans and at least 86% of RV cavitary pressure in the dog and 77% in humans.

Background: Regional performance of the hypertrophied left ventricle (LV) in hypertrophic cardiomyopathy (HCM) is still incompletely characterized with studies variably reporting that the hypertrophied myocardium is hypokinetic, akinetic, or has normal function. Different imaging modalities (M-mode or two-dimensional echocardiography) and methods of analysis (fixed or floating frame of reference for wall motion analysis) yield different results. We assessed regional function in terms of systolic wall thickening and shortening and related these parameters to end-diastolic thickness using tagged magnetic resonance imaging and the three-dimensional volume-element approach., Methods and Results: In 17 patients with HCM and 6 healthy volunteers, four parallel short-axis images with 12 radial tags and two mutually orthogonal long-axis images with four parallel tags were obtained at end diastole and end systole. After the LV endocardial and epicardial borders were traced, three-dimensional volume elements were constructed by connecting two matched planar segments in two adjacent short-axis image planes, accounting for translation, twist, and long-axis shortening. A total of 72 such volume elements encompassed the entire LV. From each of these elements, end-diastolic thickness and systolic function (fractional thickening and circumferential shortening) were calculated. The average end-diastolic thickness was 15.8 +/- 4.2 mm in patients with HCM, which was significantly greater than that in healthy subjects (8.6 +/- 2.1 mm, P < .001). Fractional thickening was significantly less in patients with HCM than in healthy subjects (0.31 +/- 0.22 versus 0.56 +/- 0.23, P < .001). There was a highly significant inverse correlation between fractional thickening and end-diastolic thickness that was independent of the type of hypertrophy or age group. Similar inverse relations were observed between circumferential shortening and end-diastolic wall thickness., Conclusions: The myocardium in patients with HCM is heterogeneously thickened and the fractional thickening and circumferential shortening of the abnormally thickened myocardium are reduced compared with healthy subjects. The decrease in fractional thickening and shortening is inversely related to the local thickness.

Adult patients who had arthroscopic surgery under general anesthesia and requested postoperative pain relief were randomized to receive treatment in a double-blind protocol with 5 mg of intravenous dezocine (20 patients), morphine (22 patients), nalbuphine (18 patients), or saline (24 patients). At 10-min intervals, starting with the first dose of analgesic, patients could choose up to three additional doses of the primary treatment, or choose an alternative analgesic if the primary drug was unsatisfactory. One to four doses of morphine were given as the alternate treatment if the initial treatment was dezocine or nalbuphine, and one to four doses of dezocine were given if the initial treatment was saline or morphine. The proportion of patients treated successfully by the initial treatments (i.e., not requesting alternate treatment), with P value for difference from placebo treatment, were saline 25%, nalbuphine 33% (P = 0.048), morphine 54% (P = 0.04), and dezocine 75% (P = 0.003). Dezocine and morphine are more efficacious than nalbuphine in the management of early postoperative pain. As an alternate analgesic in this study, dezocine required fewer doses to achieve patient satisfaction and was thus more efficacious than morphine. The incidence of treatment-related, adverse effects was different from that of saline or other treatments only for nalbuphine-related pain or burning on injection and dezocine-related facial itching. With respect to analgesic actions and side effects, dezocine seems more like morphine than nalbuphine.

Background: At end diastole, the position and shape of the ventricular septum depend on the transseptal pressure gradient. It is not clear, however, how the septal radius of curvature changes in response to the gradual change in transseptal pressure gradient during progressive pulmonary arterial constriction (PAC) and aortic constriction (AC)., Methods and Results: In 11 anesthetized open-chest dogs, the septal radius of curvature was measured from the short-axis two-dimensional echocardiogram, and the transseptal pressure gradient (left ventricular [LV] pressure minus right ventricular [RV] pressure) was calculated from ventricular pressures measured with micromanometers. Seven dogs were studied with both PAC and AC (group 1) and four dogs only with PAC, which was initiated before and after volume loading (group 2). The transseptal pressure gradient decreased during PAC. As the transseptal pressure gradient decreased, the septum shifted continuously leftward with decreases in the LV septum-free wall diameter and in LV cross-sectional area. The septal radius of curvature (Rs) increased until the septum became flat. The flat septum (i.e., Rs = infinity) occurred at a relatively constant value of transseptal pressure gradient (-4.6 +/- 1.4 mm Hg) independently of the absolute values of LV pressures when between 2 and 9 mm Hg, although necessarily a greater RV pressure was needed to make the septum flat when LV pressure was higher. After inversion, the septum again became curved, with a decrease in the absolute value of septal radius of curvature as the transseptal pressure gradient became increasingly negative. The septum was still concave to the LV cavity at zero transseptal pressure gradient, and its curvature decreased (i.e., its radius of curvature increased) with increases in ventricular pressures. During AC, the septal radius of curvature also increased, but with an increase in transseptal pressure gradient accompanied by increases in LV septum-free wall diameter and in LV area. In group 2 animals, at zero transseptal pressure gradient, the normalized septal radius of curvature was greater (p less than 0.005) at high LV pressure than at low LV pressure. The transseptal pressure gradient required to make the septum flat was not significantly different between low and high LV pressure, which confirmed the results of group 1., Conclusions: The results of the present study show that the shape and position of the ventricular septum are determined by the transseptal pressure gradient but that the shape of the septum is also affected by the ventricular pressures. The septum was not flat but rather still concave to the LV cavity at zero transseptal pressure gradient. Approximately 5 mm Hg of negative transseptal pressure gradient was required to displace the septum farther leftward and make it flat. The septal radius of curvature increased during both PAC (which decreased transseptal pressure gradient) and AC (which increased transseptal pressure gradient), indicating that the mechanisms involved in changing septal radius of curvature are different during PAC and AC.

Background: Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined., Methods and Results: Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/- 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03)., Conclusions: QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia.

The purpose of this study was to investigate the dependence of tau, the time constant of left ventricular (LV) isovolumic relaxation, on pericardial pressure and to compare values of tau as determined by the methods of previous investigators and by a standard exponential curve fit. All of the more recent methods involve an additional parameter--the pressure to which the exponential relaxation finally declines (PB, the pressure intercept in the method of Craig and Murgo and the asymptote in the exponential fits). An additional purpose of the study was to determine the relation of these parameters to pericardial pressure. In eight closed-chest anesthetized dogs, tau was calculated from intracavitary (Plv) and transmural LV pressure (Plv = Plv-Pper) by each method as pericardial (Pper) and LV end-diastolic pressure were changed by pericardial infusion and intravenous volume loading. The time constant determined by the method of Weiss et al was dependent on pericardial pressure; the time constants determined by the other methods were not. PB and the asymptotes were found to be similar and to increase almost equally with pericardial pressure. When pericardial pressure was zero, these values were approximately -20 mm Hg. Thus, both these parameters seem to indicate the same baseline pressure, a pressure that increases pari passu with pericardial pressure. Reported changes in the value of tau calculated from intracavitary LV pressure by the method of Weiss et al may reflect factors other than changes in LV diastolic function.

To determine the better method of measuring pericardial constraint, pericardial pressure was recorded by a liquid-filled open-ended catheter and a liquid-containing flat balloon in six open-chest anesthetized dogs. Left ventricular pressure was measured by a micromanometer-tipped catheter and left ventricular anteroposterior diameter was measured by sonomicrometry. Left ventricular end-diastolic pressure was raised to 20 +/- 1.7 (mean +/- SD) mm Hg by intravenous saline. Left ventricular diastolic pressure-diameter loops were constructed (1) with incremental amounts of saline (0 to 50 ml) in the resealed pericardium, (2) with several small holes in the pericardium, and (3) with the pericardium widely open. Measured pericardial pressures were compared with what was assumed to be the correct pericardial pressure, i.e., the calculated difference between left ventricular diastolic pressure (at a given left ventricular diameter) before and after opening the pericardium. Pressure recorded by the flat balloon was similar to the calculated pericardial pressure at all pericardial liquid volumes. Pressure recorded by the open-ended catheter, however, was significantly lower (p less than .05) than the calculated pressure unless there was at least 30 ml of liquid in the pericardium. After several holes had been made in the pericardium it still exerted a constraining effect, as shown by a marked rightward or downward shift of the left ventricular diastolic pressure-diameter relationships after completely opening the pericardium. After holes were made in the pericardium pressure recorded by the flat balloon was still similar to the calculated pericardial pressure. However, pressure recorded by the open-ended catheter was significantly (p less than .02) lower than the calculated pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Previously, we have shown that pericardial constraint cannot be measured by true (hydrostatic) pressure except when an excess of pericardial fluid is present and that a device such as a balloon (which reflects radial contact stress as well as hydrostatic pressure) must be used. Since radial contact stress is the major component of the constraint exerted by the pericardium when little pericardial liquid is present, it follows that the pressure measured by the balloon might be different over different parts of the heart. In an attempt to test this hypothesis, in 11 anesthetized dogs we placed pericardial balloons over the right and left ventricular free walls, instrumented the animals to measure ventricular dimensions (sonomicrometry) and pressure, mounted pneumatic constrictors on the aortic and pulmonary artery, reapproximated the pericardium, and closed the chest under suction. We studied the transient effects of constrictions of the ascending aorta and pulmonary artery and of angiotensin infusion before and after intravenous saline infusion. Aortic constriction and, to a lesser degree, angiotensin increased pericardial pressure over the left ventricle more than over the right ventricle. Pulmonary artery occlusion increased pericardial pressure over the right ventricle but significantly decreased pericardial pressure over the left ventricle. We conclude that there are significant local differences in pericardial pressure (recorded by balloon) over the lateral ventricular surfaces during acute changes in afterload. These observations may be explained in part by decreased venous return to the contralateral ventricle, the tendency of the heart to resist lateral displacement, and the limited mobility of the pericardium.

Acute paraplegia followed a vertebral infection with Mycobacterium fortuitum. There was a satisfactory response to surgery and antibiotics. No predisposing factors for this primary bone infection could be found.

Although stroke volume may decrease markedly after acute pulmonary embolism, left ventricular end-diastolic pressure (LVEDP) usually changes very little, which suggests that compliance or contractility or both are reduced. To test the hypothesis that the altered LV function during pulmonary embolism is primarily due to reduced preload mediated by increased pericardial constraint, hemodynamics and chamber dimensions (measured by sonomicrometry) were assessed in seven anesthetized dogs during control volume loading, after pulmonary embolism (with autologous blood clot), and after repeated pulmonary embolism in the volume-loaded state. The correlation between LVEDP and an index of LVED volume (LVED area index) throughout a wide range of LVEDP before and after embolism was poor (mean r = 0.42; range, 0-0.82). However, the correlation between transmural LVEDP (LVEDP-directly measured pericardial pressure) and LVED area index (mean r = 0.78; range, 0.61-0.94) was significantly higher (p = 0.03). Similarly, an index of stroke work (LV area stroke work) correlated less well (p less than 0.01) with LVEDP (mean r = 0.43; range, 0.07-0.77) than with transmural LVEDP (mean r = 0.82; range, 0.68-0.92). LV area stroke work also correlated well with the LV area index (mean r = 0.84; range, 0.70-0.95). These data indicate that neither compliance nor contractility is substantially altered during acute pulmonary embolism. The altered LV performance is due to reduced LV preload as reflected by a decrease in transmural LVEDP. This study also demonstrates that LVEDP is a poor index of LV preload during pulmonary embolism, whereas transmural LVEDP accurately reflects LVED dimensions.

Racemic tocainide [R,S-T], which is used in the treatment of ventricular arrhythmias, consists of an R(-)-enantiomer [R-T] and an S(+)-enantiomer [S-T]. The present experiments examined these substances for pharmacodynamic differences. The ability of various doses of R-T, S-T, and R,S-T to both induce ataxia (A) and protect against chloroform-induced ventricular arrhythmias (P) in mice were compared at 20 min after subcutaneous treatment. For A effects, the ED50S (95% Fieller Limits) of R-T, S-T, and R,S-T were 125 (78-802), 125 (84-283), and 90 (61-149) mg/kg, respectively. For P effects, the ED50S were 40 (11-71), 116 (82-204), and 86 (55-187) mg/kg. The ratios of A/P, a measure of the margin of safety, were 3.1, 1.1, and 1.0. Effects upon intracardiac conduction in isolated rabbit hearts also exhibited, qualitatively, similar patterns of selectivity. At 1 X 10(-4) M intraatrial, His-Purkinje, intraventricular conduction times, and the QT interval were prolonged with the following order of potency: R-T greater than R,S-T greater than S-T; A-V nodal conduction was unchanged. R-T also evoked the greatest decrease in contractility. With respect to separation of antiarrhythmic action and the production of ataxia, R-T has a greater margin of safety than either S-T or R,S-T.

Despite the clinical prevalence of paradoxic interventricular septal (IVS) motion, its pathogenesis remains unclear. To assess the influence of the end-diastolic transseptal pressure gradient, we studied eight open-chest dogs during right ventricular (RV) volume loading (induced by opening a Dacron shunt between the pulmonary artery [PA] and right atrium), RV pressure loading (constriction of PA), and left bundle branch block (RV pacing). Ultrasonic crystals in the IVS and on the RV and left ventricular (LV) free walls (FW) allowed measurement of RV septal-to-free wall (S-FW) and LVS-FW diameters. Another set measured the anteroposterior (AP) diameter of the LV (LVAP). Two-dimensional and M mode echocardiograms confirmed IVS shape and motion pattern, respectively. RV volume load caused a reduction in mean transseptal end-diastolic pressure gradient from 2.1 to -2.6 mm Hg (p less than .001), with a concomitant increase in mean end-diastolic RVS-FW diameter of 2.5 mm (p less than .001) and a decrease in LVS-FW diameter of 2.8 mm (p less than .001). LVAP was unchanged. Echocardiograms confirmed a leftward IVS shift during diastole with paradoxic systolic motion. PA constriction and RV pacing caused similar directional changes in transseptal end-diastolic pressure gradients and diameters. Compared with control values, shunt opening and PA constriction also caused a small leftward shift of IVS at end-systole. Normalized data from all eight dogs revealed significant (p less than .001) correlations between reduction in LV-RV end-diastolic pressure gradients and increases in RVS-FW (r = .85) and decreases in LVS-FW (r = .80) diameters.(ABSTRACT TRUNCATED AT 250 WORDS)

It is now well established that the vulnerability of the ventricular myocardium to repetitive dysrhythm increases in the presence of greater than normal disparity local recovery times. Local recovery is reflected in the electrocardiographic waveform as an area of the ventricular deflection (QRST time integral), and thus disparate ventricular recovery may be manifested in the body surface distribution of this quality. To assess this possibility, we obtained simultaneous 120-lead electrocardiograms from both the anterior and posterior torso in 140 subjects (ages 8 to 75) grouped as follows: group A, 97 normal subjects; group B, 16 patients resuscitated from ventricular fibrillation or sustained ventricular tachycardia; and group C, 27 patients 6 to 12 months after myocardial infarction but without clinically significant arrhythmia. In each subject, the QRST integral was evaluated for each lead and isointegral contour maps were plotted. A score was assigned to each map, based on the number of extrema; each maximum or minimum scored one point, with the exception of simultaneously occurring anterior and posterior minima on the right shoulder (frequently occurring in normal subjects), which scored together only one point. All but one group A subject had dipolar QRST integral maps (mean +/- SD score 2.11 +/- 0.2). Conversely, 10 of 16 (62.5%) group B patients had scores of 3 or more (mean 3.16 +/- 1.08; p less than .01 vs group A). Group C patients had intermediate values, with eight of 27 (29.6%) scoring 3 or more (mean 2.46 +/- 83); this was less than in group B (p less than .01), but more (p less than .05) than in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume loading is used to treat hemodynamically compromised patients with acute pulmonary embolism despite data to suggest that volume loading after embolism might cause a leftward shift of the ventricular septum with a subsequent decrease in left ventricular (LV) end-diastolic volume and stroke work. We studied 10 closed-chest, anesthetized, and ventilated dogs to assess the effects of volume loading after pulmonary embolism caused by autologous clot. LV, right ventricular, and right atrial pressures as well as LV anteroposterior, septum-to-right ventricular, and septum-to-LV free wall diameters (sonomicrometry) were measured. Pericardial pressure was measured with flat, liquid-containing balloons. The effects of volume loading were assessed before embolism, after one episode of embolization, and after repeated embolizations. The LV area index (as a reflection of LV volume) increased during volume loading before embolism (2,870 +/- 430 to 3,080 +/- 520 mm2; p less than 0.05), did not change significantly during infusion of fluid after one embolization (2,850 +/- 470 to 2,860 +/- 500 mm2; p = NS), and decreased significantly during volume expansion after repeated embolizations (2,760 +/- 440 to 2,660 +/- 420 mm2; p less than 0.01). An index of LV stroke work increased (188 +/- 85 to 260 +/- 101 mm Hg x mm2; p less than 0.05), did not change significantly (188 +/- 39 to 203 +/- 52 mm Hg x mm2; p = NS), and decreased markedly (133 +/- 64 to 45 +/- 27 mm Hg x mm2; p less than 0.001) before embolism, after one embolization, and after repeated embolizations, respectively. The decrease in LV area index during volume loading after repeated embolizations was associated with an increase in septum-to-right ventricular free wall diameter (31 +/- 8 to 34 +/- 8 mm; p = 0.001) and a decrease in the septum-to-LV free wall diameter (44 +/- 5 to 42 +/- 5 mm; p less than 0.001), whereas the LV anteroposterior diameter did not change (62 +/- 5 to 63 +/- 5 mm; p = NS). This is compatible with a leftward septal shift being partially responsible for the decrease in LV end-diastolic volume; such a shift would be expected with the observed decrease in transseptal end-diastolic pressure gradient (-3 +/- 2 to -5 +/- 2 mm Hg; p = 0.001). In addition, after repeated embolizations, LV transmural pressure decreased in response to the volume load reflecting a marked increase in pericardial pressure.(ABSTRACT TRUNCATED AT 400 WORDS)

Mental arithmetic stress is known to cause forearm arterial dilation, but the venous responses, including possible changes in the volume-pressure relation, have not been defined. Hence, 10 apparently normal subjects, eight men and two women, mean age 46 +/- 9 years, were studied before and during mental arithmetic stress. Changes in forearm venous volume were estimated with 99mTc blood pool scintigraphy. Group variability of this measurement technique was 1.8 +/- 2.3%. A brachial blood pressure cuff was used to obtain venous occluding pressures of 0, 10, 20, and 30 mm Hg. Mental arithmetic stress increased group systolic and diastolic blood pressure from 126 +/- 12 to 152 +/- 20 mm Hg and from 83 +/- 8 to 93 +/- 15 mm Hg, respectively (p less than 0.001). Heart rate increased from a mean of 75 +/- 15 to 85 +/- 17 beats/min (p less than 0.01). There was no evidence of interaction between or nonlinearity of the volume-pressure plots. Linear regression then yielded the equations V = 99.8 + 0.96P before and V = 86.3 + 0.96P during mental arithmetic stress, which represents a 13.5 +/- 1.6% decrease in forearm vascular volume (p less than 0.001). We conclude that 1) a linear relation exists between forearm venous volume and pressure at physiologic pressures before and during mental arithmetic stress; 2) mental arithmetic stress causes forearm venoconstriction; and 3) such venoconstriction takes place by a parallel shift in the volume-pressure relation (i.e., a shift in unstressed venous volume).

The objective of this study was to determine the constraining effect of the normal human pericardium. Accordingly, immediately after thoracotomy in nine patients undergoing elective cardiac surgery, we measured mean pericardial surface pressure over the lateral free wall of the left ventricle with a flat balloon as well as mean right atrial pressure while incrementally infusing up to 2.1 liters of Ringer's solution to increase right atrial pressure. In each case, the slope of the relationship between right atrial (range -4 to 20 mm Hg, overall) and pericardial pressures was near unity (1.16 +/- 0.20 mean +/- SD) and the intercept was approximately zero (0.71 +/- 2.48 mm Hg). Correlation coefficients ranged from .86 to .97. These observations suggest that right atrial pressure can be used as an estimate of pericardial surface pressure. If this is the case, true left ventricular preload (i.e., effective distending pressure or transmural diastolic pressure) might be estimated from the difference between left ventricular filling pressure and right atrial pressure, both conveniently measurable clinically by means of a triple-lumen, flow-directed catheter.

Previous studies from our laboratory have shown that the position of the ventricular septum relative to the two ventricles at end-diastole is determined by the instantaneous transseptal pressure gradient (TSG) defined as left ventricular minus simultaneous right ventricular pressure. Since patients with mitral stenosis often have exaggerated leftward (paradoxic) motion of the ventricular septum during early diastole, we studied seven patients with mitral stenosis undergoing cardiac catheterization to determine if position (and therefore motion) of the ventricular septum was determined by TSG throughout diastole. M Mode echocardiograms derived from a two-dimensional parasternal short-axis view were recorded with simultaneous micromanometer measurements of left ventricular and right ventricular pressures. Six of seven patients demonstrated abnormal early diastolic leftward motion of the ventricular septum in at least one cardiac cycle. TSG measured at intervals throughout diastole ranged from -2.5 to +20 mm Hg, with abnormal TSG observed in most of the 40 cardiac cycles selected for analysis. The intracardiac position of the ventricular septum, defined as the distance from the right ventricular epicardium (RVEpi) to the left surface of the ventricular septum normalized for total cardiac dimension (RVEpi-VS), was plotted against left ventricular pressure, right ventricular pressure, and TSG. Linear regression of pooled data from all patients (164 observations) demonstrated a highly significant correlation between the instantaneous TSG and the relative intracardiac position of the ventricular septum (RVEpi-VS = 1.52 TSG + 42.7; r = .79, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

The aim of the present study was to test the hypothesis that vasoactive drugs may modify left ventricular diastolic function by shifting blood between the systemic vascular bed and the heart, thereby changing pericardial and left ventricular pressure. The experiments were done in 10 open-chest, anesthetized, previously splenectomized dogs in which changes in pericardial surface pressure in response to intravenous sodium nitroprusside and angiotensin were related to changes in blood volume in the abdominal region. Blood volume was determined by blood pool scintigraphy (99mTc) and regions of interest were drawn in the liver and in the mesenteric area. Angiotensin was infused at rates that were adjusted to increase mean aortic pressure by 20 and 30 mm Hg, and nitroprusside was infused at rates to decrease mean aortic pressure by 30 and 50 mm Hg. Angiotensin increased pericardial pressure by 3 and 5 mm Hg at the respective doses and there were increments in left ventricular end-diastolic pressure (LVEDP) and left ventricular diameter (sonomicrometry). Angiotensin decreased blood volume in the mesenteric region by 14% and 17%, but did not significantly change blood volume in the liver region. Angiotensin increased portal venous pressure and decreased mesenteric blood volume, suggesting decreased mesenteric venous compliance. Nitroprusside had opposite effects: pericardial pressure was decreased by 5.5 and 6.5 mm Hg by the respective doses. The doses of nitroprusside increased blood volume in the mesenteric region by 14% and 20%, but did not significantly change blood volume in the liver region.(ABSTRACT TRUNCATED AT 250 WORDS)