Measuring standards of care for early breast cancer in an insured population.

PURPOSE: To demonstrate the use of a combined data base to evaluate the care for local/regional invasive breast cancer in a large insured population of women aged less than 64 years. PATIENTS AND METHODS: We linked the procedural and hospital claims from Blue Cross Blue Shield (BCBS) of Virginia with clinical stage data from the Virginia Cancer Registry (VCR) from 1989 to 1991. A total of 918 women were assessed with a median age of 50 years; 68% had tumors less than 2 cm, 30% had positive axillary nodes, and 68% were assessed as having local summary stage. A quality-of-care "report card" was used based on standards of care from international Consensus Conferences. RESULTS: Eight percent had a mastectomy as the initial biopsy procedure. Sixty-nine percent of women ultimately underwent mastectomy. Of those women who underwent lumpectomy, 86% had subsequent radiation. Within 3 months of diagnosis, 43% had a bone scan and 20% a computed tomography (CT) scan. Of women with positive axillary lymph nodes, 83% aged less than 51 years and 52% aged 51 to 64 years received chemotherapy. Fifty-six percent of all women had claims from a medical oncologist. Of women having a total mastectomy, 27% had claims from a plastic surgeon. Sixty-six percent to 76% of women had a mammogram, 24% a bone scan, and 14% a CT scan in the 0-18 and 18-36 month intervals following primary treatment. CONCLUSION: This study confirms the feasibility of linking sources of data that provide complementary information needed to develop measurements regarding standards of quality and efficiency of oncologic care. This report should serve as an initial benchmark while we await reports from other populations to define the best practice.

Trends in temporomandibular joint surgery.

We examined a large population of patients undergoing temporomandibular joint (TMJ) surgery and provide a documentation of the average patient population, frequency of procedures, frequency of repeat procedures, and trends in open (arthrotomy) versus closed (arthroscopy) TMJ surgery. Data on 194 TMJ surgical procedures was extracted from line item claims information collected by Trigon Blue Cross/Blue Shield of Virginia. The frequency of arthroscopy increased during the study, while the incidence of arthrotomies remained relatively low. Approximately half of the hospitals statewide did not perform either procedure. There was a low frequency (3%) of repeat procedures. In the Commonwealth of Virginia, since the advent of TMJ arthroscopy, it has become the preferred surgical technique for treatment of internal derangement. There is a low incidence of repeat procedures for both types of treatment. Analysis of insurance carrier computer records is a valid technique for evaluating trends in surgical care.

Mechanism of mitral leaflet excursion.

The factors that influence the extent of mitral leaflet opening (MLO) and closure (MLC) have not been defined. We hypothesized that left ventricular (LV) systolic function determines the rate of increase of the early diastolic left atrial (LA)-LV pressure gradient, which is responsible for the extent of MLO, and also the rate of change of the early systolic LV-LA pressure gradient, which determines the degree of MLC. Accordingly, global LV function was changed by altering left main coronary artery flow with LA pressure held relatively constant. LV end-systolic dimension and peak positive LV rate of pressure development (dP/dt) correlated best with the degrees of MLO and MLC, with average correlation coefficients of 0.88 and 0.68, and 0.86 and 0.72, respectively. Although transsecting the submitral apparatus resulted in flailing of the mitral leaflets during normal LV systolic function, the extents of MLO and MLC during LV systolic dysfunction were still influenced by LV systolic function. It is concluded that LV systolic function determines the extent (both opening and closure) of mitral leaflet excursion.

Impact of physician awareness on hospital charges for radical retropubic prostatectomy.

PURPOSE: We determine if physician awareness of hospital costs for radical retropubic prostatectomy affects physician practice patterns. MATERIALS AND METHODS: We reviewed 256 consecutive radical retropubic prostatectomies performed by 14 urologists during 4 years at a community hospital. After 2 years the physicians were provided information on factors that may decrease charges. RESULTS: Charges decreased significantly following intervention, from +f417,134 within the initial 2 years to +f413,826 within the last 2 years (p < 0.005). Significant decreases were noted for length of stay, need for intensive care, operating time and blood loss. CONCLUSIONS: Traditional methods of physician education can impact practice patterns to decrease hospital charges for radical retropubic prostatectomy.

The role of the physician in effecting change in hospital charge for radical prostatectomy.

BACKGROUND: Continuing effort is being made to provide the best medical care in a cost-effective manner, requiring an evaluation of factors that control charges. The number of cases of carcinoma of the prostate gland and the number of radical retropubic prostatectomies performed have increased in recent years, with an estimate of several hundred million dollars being spent annually on this procedure in the United States of America. Because physicians are reported to effect the majority of charges for a hospitalization, this study examines the influence of notification of the physician of hospital charges on the overall hospital charges for radical retropubic prostatectomy. STUDY DESIGN: Total hospital charge and duration per hospitalization were determined for all patients having radical prostatectomies performed at five community hospitals in Richmond, VA, between January 1991 and December 1993. Patients included 625 males diagnosed with carcinoma of the prostate gland undergoing radical prostatectomy by one of 20 urologists from several different private practice groups. Halfway into the time period studied, physicians were notified of data collection and of factors that seemed to have a role in hospital charges. Total hospital charges before and after physician notification were measured to determine whether or not physicians could effect hospital charges. RESULTS: Overall, hospital charges decreased significantly after notification of physicians in the study. The decline in total charges continued throughout the follow-up period. Duration of hospitalization decreased throughout the entire study period, while total charge per hospital day increased. CONCLUSIONS: Physician awareness of hospital charges for operative procedures and accompanying hospitalizations may influence the overall decrease in charges.

A retrospective analysis of 6,387 cholecystectomies.

This is the largest retrospective analysis of biliary tract surgery ever reported involving 6,378 patients operated on during a three year period, 1990-1992. During this time interval, the frequency of laparoscopic procedures has increased dramatically. The use of laparoscopic procedures was associated with a significant decrease in the total length of hospital stay and total charges as compared to the open procedures. Because of laparoscopic surgery's increased acceptance, we propose that the frequency of laparoscopic surgery of the biliary tract should be used as a quality control measure.

New insights into the physiology of retrograde cardioplegia delivery.

Although retrograde cardioplegia (RC) is being increasingly used in clinical practice, its physiology is unclear. Because the microvascular architecture of the coronary venous system is different from that of the arterial system, we hypothesized that myocardial perfusion would be different during RC compared with anterograde cardioplegia (AC) delivery. To better understand these differences, three groups of dogs were studied during similar RC and AC flow rates. Radiolabeled microsphere-derived microvascular flow underestimated total cardioplegia flow by 66% during RC. For the same flows, the first-pass extraction fractions of 201Tl and 99mTc were significantly less during RC compared with AC despite adjusting for microsphere loss. Myocardial contrast echocardiography (MCE), however, provided an accurate estimation of AC and RC flow rates. In addition, the rate of myocardial cooling for most of the left ventricular myocardium was similar for AC and RC at the same flow rates, as long as the flow rates were brisk. It is concluded that microvascular and nutrient flows are significantly lower at the same flow rates during RC compared with AC due to loss of RC at different microvascular sites. Unlike microspheres and diffusible radioisotopes, MCE can provide a reliable measure of myocardial flow during RC delivery. Furthermore, myocardial cooling is similar in most of the myocardium during high-flow RC and AC, which suggests that the clinical benefits of RC are probably related to myocardial cooling and that substrate replenishment may be better achieved at the same flow rates and myocardial temperatures with AC rather than RC.

The evolution of functional endoscopic sinus surgery in the Commonwealth of Virginia.

This is the largest retrospective analysis of sinus surgery ever reported involving 5,860 surgical as well as 6,769 diagnostic sinus procedures during a six year period, 1988-1993. During this time interval, the frequency of endoscopic procedures has increased dramatically. Because of the increased frequency of this procedure, we see the need for strict definition of the clinical indications for surgery for patients with chronic or acute sinusitis. In addition, the number of open procedures, namely the Caldwell-Luc procedure, as a treatment for sinusitis remained relatively constant despite the frequent use of endoscopic technique. Because of the endoscopic surgery's increased acceptance and advantages over the open surgical technique, we emphasize the need for continuing educational programs to train surgeons to perform the endoscopic procedure or referral of the patient to an otolaryngologist experienced in this technique.

First metatarsophalangeal joint arthroplasties in the Commonwealth of Virginia.

This retrospective analysis of arthroplasty of the first metatarsophalangeal joint documents the incidence of surgery as well as the selection of the commercially available implants. During a 1-year period, 1994, arthroplasties were performed in 47 of the 1.7 million subscribers to Trigon Blue Cross Blue Shield of Virginia. Women received the majority of the arthroplasties (83%). Of the 47 cases, the silicone implant was predominantly used (83%). The most common indications for arthroplasty were hallux valgus (30%) and hallux rigidus (28%). Podiatrists performed 79% of the procedures, while orthopedic surgeons performed the remaining 21% of the cases. A prospective study is needed that will assess the long-term performance of the different implants.

Dobutamine echocardiography for determining the extent of myocardial salvage after reperfusion. An experimental evaluation.

BACKGROUND: Although dobutamine echocardiography is being increasingly used to determine the presence of viable myocardium in patients who have undergone successful reperfusion therapy, the physiological basis for such a use has not been clearly defined. Because postischemic myocardium has contractile reserve, we hypothesized that the absolute degree of wall thickening induced by dobutamine during reflow would be directly related to the amount of myocardium that has escaped necrosis. METHODS AND RESULTS: Three groups of 12 dogs each were studied at baseline and during 2 to 6 hours of coronary artery occlusion and 15 minutes of reperfusion. In group 1 dogs, which did not receive dobutamine during any of these stages, percent wall thickening at these stages was 32 +/- 6%, -2 +/- 6%, and 5 +/- 6%, respectively, and there was no relation between infarct size and percent wall thickening during reflow (r = .20, P = .51). In group 2 dogs, which received 15 micrograms/kg per minute of dobutamine at all stages, wall thickening at these stages was 40 +/- 8%, 0 +/- 8%, and 19 +/- 10%, respectively, and a good inverse correlation was noted between infarct size and percent wall thickening during reflow (r = -.81, P = .001). In group 3 dogs, in which wall thickening during reflow was measured both before and during infusion of 15 micrograms/kg per minute of dobutamine, it was 5 +/- 8% and 18 +/- 14%, respectively, at these stages. Although the correlation between infarct size and percent wall thickening was poor in the absence of dobutamine (r = .36, P = .26), an excellent inverse correlation was noted between the two in the presence of dobutamine (r = -.93, P < .001). A fair inverse correlation was also noted between infarct size and the absolute change in wall thickening induced by dobutamine (r = -.72, P < .01). Maximal wall thickening was noted at a dobutamine dose of 15 micrograms/kg per minute, and lower doses did not elicit thickening in the presence of larger infarcts despite the presence of viable myocardium. CONCLUSIONS: When myocardial necrosis coexists with post-ischemic myocardial dysfunction and no residual coronary stenosis, the absolute degree of wall thickening during dobutamine can be used to determine the extent of myocardium that has escaped necrosis. The dose of dobutamine needed to elicit maximal thickening of the postischemic myocardium is related to the amount of myocardial necrosis.

In vivo myocardial kinetics of air-filled albumin microbubbles during myocardial contrast echocardiography. Comparison with radiolabeled red blood cells.

Myocardial contrast echocardiography (MCE) is a new technique for assessing myocardial perfusion that uses intracoronary injections of microbubbles of air. Because these microbubbles have a mean diameter of 4.3 +/- 0.3 microns and an intravascular rheology similar to that of red blood cells (RBCs), we hypothesized that their mean myocardial transit rates recorded on echocardiography would provide an estimation of regional myocardial blood flow in the in vivo beating heart. Accordingly, blood flow to the left anterior descending coronary artery (LAD) of 12 open-chest anesthetized dogs (group I) was adjusted to 4 to 6 flows (total of 60 flows), and microbubbles and radiolabeled RBCs were injected into the LAD in a random order at each stage. The mean myocardial RBC transit rates were measured by fitting a gamma-variate function to time-activity plots generated by placing a miniature CsI2 probe over the anterior surface of the heart, and the mean myocardial microbubble transit rates were measured from time-intensity plots derived from off-line analysis of MCE images obtained during the injection of microbubbles. An excellent correlation was noted between flow (measured with an extracorporeal electromagnetic flow probe) and mean myocardial RBC transit rate (y = 2.83 x 10(-3)x + 0.01, r = .96, SEE = 0.02, P < .001). A close correlation was also noted between mean RBC and microbubble myocardial transit rates (y = 1.01x + 0.01, r = .89, SEE = 0.02, P < .001). Despite its theoretical advantages, a lagged normal density function did not provide a better fit to the MCE data than the gamma-variate function.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of spatial patterns of flow within the reperfused myocardium by myocardial contrast echocardiography. Implications in determining extent of myocardial salvage.

BACKGROUND: Since myocardial blood flow changes dynamically after reperfusion and since both hyperemia and impairment in microvascular function exist within the acutely reperfused bed, we sought to investigate the role of myocardial contrast echocardiography (MCE) in (1) defining the temporal variability in perfusion patterns after reflow and relating these to microsphere-derived blood flow; (2) differentiating viable from infarcted tissue during different periods of reflow; and (3) defining spatial perfusion patterns within the infarct bed in response to exogenously induced maximal vasodilation and relating these to infarct size and extent of myocardial salvage. METHODS AND RESULTS: Twenty-one dogs with 3 hours of left anterior descending coronary artery occlusion and 2 to 3 hours of reflow were studied. MCE was performed at 15 and 45 minutes and 2 and 3 hours after reflow. It was also performed at either 2 or 3 hours after reflow in the presence of 0.56 mg/kg of dipyridamole. Radiolabeled microsphere-derived blood flow was measured at 15 minutes and 2 and 3 hours after reflow and during dipyridamole effect. Infarct size was measured at the end of the experiment by use of triphenyl tetrazolium chloride. MCE data were processed with color-coding schemes that highlighted differences in myocardial videointensities in proportion to the concentration of microbubbles within the microvasculature. There was significant variability in MCE-defined perfusion patterns after reflow, with contrast defects noted mainly within the endocardium. There were fair and significant (P < .05) correlation (r = -.73 to r = -.55) between MCE defect size and normalized endocardial blood flow. Except at 15 minutes after reflow, there was poor correlation (r = .31 to r = .51) between MCE defect and infarct sizes. Even at 15 minutes after reflow, MCE defect size underestimated infarct size by 50%. In comparison, in the presence of dipyridamole, MCE defect size correlated strongly (r = .87, P < .001) with infarct size and reasonably well with normalized transmural blood flow (r = -.62, P = .04). Moreover, the topography of the MCE perfusion defect reflected the topography of the infarct. CONCLUSIONS: MCE revealed striking temporal heterogeneity in the spatial distribution of myocardial perfusion during postischemia reflow and either significantly underestimated or did not correlate with infarct size during reperfusion. Because of abnormalities in coronary vascular reserve specific to infarcted tissue, MCE in conjunction with intravenous dipyridamole depicted, in vivo, the actual topography of the infarct with remarkable accuracy.

Assessment of risk area during coronary occlusion and infarct size after reperfusion with myocardial contrast echocardiography using left and right atrial injections of contrast.

BACKGROUND: Myocardial opacification during echocardiography has been demonstrated after left (LA) and right (RA) atrial injections of contrast, and microvascular damage with reduced blood flow and impaired flow reserve has been documented in necrotic myocardial tissue. Therefore, we hypothesized that because of its ability to depict capillary perfusion, myocardial contrast echocardiography (MCE) can be used to define risk area during coronary occlusion and infarct size after reperfusion with LA and RA injections of contrast in the presence of pharmacologically induced coronary hyperemia. METHODS AND RESULTS: Eighteen open-chest anesthetized dogs with 3 to 6 hours of left anterior descending artery occlusion and 15 minutes of reflow were studied in the presence of either dipyridamole (0.56 mg/kg over a period of 4 minutes) or dobutamine (15 micrograms.kg-1.min-1). Technetium autoradiography was performed for risk area assessment; infarct size was measured with triphenyl tetrazolium chloride; and in 11 dogs, myocardial blood flow was measured with radiolabeled microspheres. A close linear relation was noted between the MCE defect size and autoradiographic risk area during coronary occlusion both during LA (y = 0.95x-0.25, r = .97, P < .001) and RA (y = 0.90x+0.98, r = .86, P < .001) injections of contrast. During reperfusion, the contrast defect size on MCE was always less transmural than during occlusion and correlated closely with infarct size during both LA (y = 1.07x-2.37, r = .98, P < .001) and RA (y = 1.02x-0.61, r = .95, P < .001) injections of contrast. In the 11 dogs in whom radiolabeled microsphere-derived blood flow was measured during reperfusion, an inverse relation was noted between infarct size and transmural blood flow (y = -1.12x+121, r = -.95, P = .001), implying that MCE defects after reperfusion indicate necrotic regions with reduced blood flow or impaired microvascular flow reserve. A close linear relation (y = 0.79x-0.001, r = .98, P < .001) was also noted between endocardial/epicardial ratio of background-subtracted peak video intensity on MCE and endocardial/epicardial blood flow ratio in the eight dogs with infarction who underwent this measurement after reperfusion. CONCLUSIONS: MCE performed with LA and RA injections of contrast in the presence of pharmacologically induced coronary hyperemia can be used to determine, in vivo, the risk area during coronary occlusion and infarct size after reperfusion. These results could have important implications in this era of myocardial reperfusion.

Transpulmonary transit of microbubbles during contrast echocardiography: implications for estimating cardiac output and pulmonary blood volume.

We postulated that the pulmonary transit rate of sonicated albumin microbubbles, which have an intravascular rheology similar to that of red blood cells, would be directly proportional to cardiac output (CO) and inversely proportional to pulmonary blood volume (PBV). Accordingly, 4 ml of Albunex ultrasound contrast agent (0.5 billion/ml of 4.3 mu bubbles) was injected into the right atrium of six dogs (Group I) during simultaneously performed two-dimensional echocardiography, and the time between the initial appearance of the bubbles in the right and left ventricle, respectively, was measured. CO was either increased (by intravenous infusion of 15 micrograms/kg/min of dobutamine) or decreased (by producing left ventricular ischemia or by administering 2 mg of intravenous propranolol) in a random order and microbubbles were injected again. At each stage, thermodilution CO was measured. There was a close linear relation between CO and pulmonary transit rate of Albunex in each dog with the correlation coefficient ranging from 0.79 to 0.99, with a mean of 0.92. Pulmonary blood volume was derived in each dog from the reciprocal of the slope of the regression between CO and pulmonary transit rate and varied from 106 to 261 ml in the six dogs with a mean value of 178 +/- 64 ml. There was excellent interobserver and intraobserver correlation (r = 0.99 each) for determining the pulmonary transit rate of Albunex. The reproducibility of pulmonary transit rate estimation from repeated contrast injections at the same hemodynamic state in another group of six dogs (Group II) was also good (r = 0.99). It is concluded that the pulmonary transit rate of Albunex ultrasound contrast agent can be used to assess directional changes in CO and to measure pulmonary blood volume. This method may have clinical applications.

Myocardial contrast echocardiography and the transmural distribution of flow: a critical appraisal during myocardial ischemia not associated with infarction.

OBJECTIVES: This study was undertaken to determine whether myocardial contrast echocardiography can be used to estimate the transmural distribution of flow. BACKGROUND: Myocardial contrast echocardiography has been shown to reliably measure average transmural blood flow during myocardial ischemia. However, there is controversy regarding its ability to determine the transmural distribution of flow. METHODS: The transmural distribution of flow was measured in 21 open chest anesthetized dogs with use of radiolabeled microspheres and sonicated albumin microbubbles (mean size 4.5 microns). In the 11 Group I dogs, myocardial contrast echocardiography was performed at baseline and during left anterior descending artery stenosis. In five of these dogs, it was also performed during left circumflex artery stenosis. In these dogs large (mean 12 microns) hand-agitated bubbles were also used. In the five Group II dogs, myocardial contrast echocardiography was performed before and 45 s after intracoronary injection of 6 mg of papaverine in the presence of a critical left circumflex artery stenosis. The five Group III dogs were studied during cardiopulmonary bypass at baseline and during left anterior descending artery stenosis. Off-line image analysis of the echocardiographic images was performed and time-intensity curves obtained from these images were correlated with radiolabeled microsphere-derived flows. RESULTS: The ratios of the parameters derived from the endocardium and epicardium during myocardial contrast echocardiography were found to correlate poorly (ranging from R2 = 0 to R2 = 0.35) with radiolabeled microsphere-derived endocardial/epicardial flow ratios over a wide range of flow ratios (0.01 to 2.58). These results were not influenced either by the location of the regions of interest (left anterior descending vs. left circumflex artery bed) or by the size of the bubbles (4.5 vs. 12 microns). CONCLUSIONS: Myocardial contrast echocardiography cannot be used to assess the transmural distribution of flow during myocardial ischemia not associated with infarction.

Effects of antifibrinolytic agents on the life span of fibrin sealant.

Fibrin sealant, a biologic glue consisting of fibrinogen and thrombin, has been used in a variety of surgical procedures. The usefulness of fibrin sealant may be prolonged by the addition of antifibrinolytic agents. This study compared the efficacy of transexamic acid (30 mg/ml), epsilon-aminocaproic acid (25 mg/ml), and aprotinin (3000 KIU/ml) to provide data on the choice of an appropriate antifibrinolytic agent for use with fibrin sealant. By use of a modified in vitro plasma euglobulin lysis time (hours), all agents were found to be superior (n = 10 for each agent, P < 0.05, analysis of variance for completely randomized design followed by Dunnett's test for multiple comparisons) to control. Lysis times (mean +/- SE) were (control) 50.9 +/- 0.5, (tranexamic acid) 402.6 +/- 25.4, (epsilon-aminocaproic acid) 433.5 +/- 21.2, and (aprotinin) 393.9 +/- 26.0. Using the in vivo implantation of fibrin sealant supplemented with 125I-fibrinogen in the rat peritoneum significant improvement in percentage clot (mean +/- SE) remaining was found (P < 0.05, analysis for repeated measures followed by tests for multiple comparisons) under the following conditions: at 3 hr by weight (n = 15), tranexamic acid (70.13 +/- 2.02%) was superior to aprotinin (61.22 +/- 2.21%) and control (61.28 +/- 2.36%); at 3 hr by radioactivity counts (n = 19), tranexamic acid (76.29 +/- 0.75%) was superior to epsilon-aminocaproic acid (72.52 +/- 1.28%) and aprotinin (73.84 +/- 0.78%); at 72 hr by radioactivity counts (n = 10), aprotinin (27.30 +/- 2.45%) was superior to epsilon-aminocaproic acid 19.76 +/- 3.09% and control (20.38 +/- 3.01%). These data suggest the early (3-hr) superiority of tranexamic acid as an inhibitor of plasminogen activation and the late (72-hr) effectiveness of aprotinin as an inhibitor of plasmin. The possibility of a synergistic effect of tranexamic acid and aprotinin is suggested.

A mathematical model for the quantification of mitral regurgitation. Experimental validation in the canine model using contrast echocardiography.

BACKGROUND: Because the clearance of contrast from the left atrium (LA) relative to the left ventricle (LV) depends on the degree of mitral regurgitation (MR), we hypothesized that a mathematical model can be developed that would provide a quantitative estimation of MR from the washout of contrast from these chambers. METHODS AND RESULTS: After mathematically developing the model, we performed experiments in two groups of dogs with the use of contrast echocardiography. Group 1 consisted of nine dogs in which different degrees of MR were produced by creating ischemic LV dysfunction. Contrast was injected into the LV, and MR was graded visually on a scale of from 0 to 4+. Videointensity plots generated from the LA and LV were provided to the model. There was excellent correlation between visual assessment of MR and model-derived regurgitant fraction in the 33 stages: y = 0.16x + 0.002 (r = 0.97, p less than 0.001, SEE = 0.06). To obtain a more quantitative validation, we placed electromagnetic flow probes on the aorta and just cephalad to the mitral annulus in six dogs (group 2) during cardiopulmonary bypass. Different degrees of MR were produced by chordal traction and/or myocardial ischemia. Regurgitant fraction was calculated at each stage from the flow probe and videointensity data. There was excellent correlation between flow probe and model-derived regurgitant fraction (y = 0.90x + 0.03; r = 0.96, p less than 0.001, SEE = 0.06), and close interobserver and intraobserver correlations were noted using flow probe and contrast echocardiographic data. CONCLUSIONS: A mathematical model that uses the clearance of contrast from the LA relative to the LV can be used to accurately measure the severity of MR. These findings may have important practical implications for the quantification of MR.

Successful and reproducible myocardial opacification during two-dimensional echocardiography from right heart injection of contrast.

BACKGROUND: Myocardial contrast echocardiography currently involves intro-arterial injection of contrast. For this technique to have a broader application, it is necessary that myocardial opacification be achieved from a venous injection of contrast. METHODS AND RESULTS: To achieve myocardial opacification after right-side injection of contrast, two groups of open-chest anesthetized dogs were studied. Group 1 included nine dogs in whom microbubbles of various sizes, concentrations, and volumes were injected into the left atrium to determine microbubble characteristics that influence myocardial opacification. Group 2 included eight dogs in whom the effect of the combination of microbubble characteristics and myocardial blood flow on myocardial opacification was evaluated after right atrial injection of contrast. Background-subtracted time-intensity plots were generated from the myocardium to measure peak videointensity. In the group 2 dogs, digital subtraction and color coding were used to further highlight the contrast effect. The number, concentration, and size of the microbubbles all independently affected (p less than 0.01) peak myocardial videointensity after left atrial injection of contrast on multivariate analysis. Highly concentrated microbubbles (4.4 to 5.1 billion/ml) given during dipyridamole-induced coronary hyperemia was most frequently (88%) associated with myocardial opacification after right atrial injection of contrast and was the best predictor of this result on multivariate analysis (chi 2= 9.01, p = 0.003). No changes were noted in left atrial, left ventricular, and pulmonary artery pressures despite injection of large numbers of microbubbles into the right atrium. CONCLUSIONS: Successful and reproducible myocardial opacification can be achieved during myocardial contrast echocardiography after right atrial injection of contrast. These findings could have far-reaching implications in the use of myocardial contrast echocardiography in acute and chronic ischemic syndromes in humans.

Mechanism of ischemic mitral regurgitation. An experimental evaluation.

BACKGROUND: Papillary muscle dysfunction (PMD) has been implicated in the pathogenesis of ischemic mitral regurgitation (MR). We hypothesized that ischemic MR is not caused by PMD and/or dysfunction of the myocardial regions from where the papillary muscles arise but is related to reduction in global left ventricular (LV) function. To test this hypothesis, three groups of dogs were studied. METHODS AND RESULTS: In group 1 dogs (n = 8), varying degrees of regional and global LV dysfunction were produced. In group 2 dogs (n = 7), the circulation to the papillary muscles was isolated from that of the rest of the LV. Dysfunction of one or both papillary muscles was produced without producing global LV dysfunction. Global LV dysfunction was also produced while keeping papillary muscle function intact. The degree of MR (assessed using contrast echocardiography) was correlated in both groups of dogs with thickening of the papillary muscles and regional and global LV function. In the group 3 dogs (n = 6), the spatial distribution of blood flow within each papillary muscle was determined during ischemia by using radiolabeled microspheres. Thickening of the papillary muscles was assessed at three different levels along their lengths and was correlated with average blood flow at these levels. In group 1 dogs, MR was noted only when global LV function was affected and its severity correlated inversely with global LV function (r = -0.84 with peak positive LV dP/dt and r = -0.95 with global LV thickening, respectively). In comparison, there was poor correlation between MR and anterior and posterior papillary muscle thickening (r = -0.38 and r = -0.49, respectively). In group 2 dogs, MR did not occur in the presence of either PMD or akinesia of the immediately adjacent LV myocardium. MR occurred only when global LV dysfunction was produced (with the papillary muscle function intact), and its severity correlated inversely with global LV function (r = -0.92 with LV dP/dt and r = -0.86 with global LV thickening, respectively). There was poor correlation between the degree of MR and thickening of the anterior and posterior papillary muscles (r = -0.24 and r = -0.38, respectively). In both groups of dogs, MR was associated with incomplete mitral leaflet closure (IMLC), and the severity of MR correlated linearly with the degree of IMLC (r = 0.98). MR was never associated with mitral valve prolapse. In the group 3 dogs, despite more inhomogeneous flow during ischemia to the anterior compared with the posterior papillary muscle, mean thickening of these muscles was similar (3 +/- 10% and 3 +/- 4%, respectively). Furthermore, there was minimal variability in thickening between different parts of the muscles (3 +/- 2% and 5 +/- 3%, respectively). CONCLUSIONS: It is concluded that PMD and/or dysfunction of the immediately adjacent LV myocardium does not result in MR. MR occurs during ischemia only when global LV function is affected, even when thickening of the papillary muscles and the immediately adjacent LV remains intact. MR in this situation is related to IMLC; the greater the degree of IMLC, the greater the MR. These findings suggest that the mechanism of ischemic MR is not related to PMD. There may also be important therapeutic implications of these findings.

Relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies: experimental and clinical implications.

The relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies is not known. Accordingly, the left circumflex coronary artery was cannulated and perfused with arterial blood in 12 open chest mongrel dogs. In Group I dogs (n = 7), the goal was to correlate the size of the perfusion bed with the magnitude of anterogradely derived myocardial blood flow. The size of the perfusion bed was measured with use of two-dimensional myocardial contrast echocardiography, whereas anterograde myocardial blood flow was determined by injecting radiolabeled microspheres directly into the artery. In Group II dogs (n = 5), the goal was to study the effects of altering coronary blood flow on both anterogradely and collateral vessel-derived myocardial flow within the perfusion bed. In these dogs, microspheres were injected directly into both the coronary artery and the left atrium at each flow rate. In Group I dogs, the left circumflex perfusion bed size, as defined by myocardial contrast echocardiography, decreased at lower anterograde myocardial blood flow rates. The change in perfusion bed size occurred at the lateral zones. There was a linear relation between the normalized perfusion bed size and the normalized anterograde myocardial blood flow: y = 0.45x + 54.2 (p less than 0.001, r2 = 0.77). These results were substantiated in Group II dogs, in which the size of the perfusion bed was approximated with use of radiolabeled microspheres. The size of the perfusion bed was most affected when anterograde myocardial blood flow decreased to less than approximately 33% of normal. At the lowest flow rates, there was a linear relation between anterograde blood flow versus the fraction of the left circumflex flow derived anterogradely: y = 2.41x + 0.22 (p less than 0.001, r2 = 0.90). The lower the level of anterograde flow, the greater was the blood flow derived from remote vessels. It is concluded that the size of the area perfused by a coronary artery is significantly influenced by the magnitude of anterograde blood flow through that artery. These findings may have important implications in experimental and clinical models of myocardial ischemia.