Modification of the centerline method for assessment of echocardiographic wall thickening and motion: a comparison with areas of risk.

The ability of the centerline method to discern regional myocardial risk area was evaluated using two-dimensional echocardiographic measurements and coronary artery occlusion in 16 open chest, anesthetized dogs. The centerline method was modified to allow determination of both wall thickening and wall motion at control and during coronary artery occlusion. End-systolic and end-diastolic echocardiographic images were analyzed at 100 equally spaced points around the centerline of the short-axis view of the left ventricle to determine shortening and thickening abnormalities. In vivo risk regions were assessed by microsphere injection during occlusion, and autoradiographic analysis revealed a mean (+/- SD) circumferential risk area of 37.5 +/- 7.7%. Abnormal function was established by three criteria on the basis of the control values for both fractional shortening and wall thickening: 1) less than 2 SD, 2) less than 95% tolerance limits, and 3) dyskinesia. The criterion of less than 2 SD estimated a risk area of 45.9 +/- 16.7% for fractional shortening and 37.2 +/- 16.8% for wall thickening. Although neither value was significantly different from the actual mean value for the risk region, the results for fractional shortening were greater than for wall thickening (p less than 0.01). The less than 95% tolerance limit method significantly underestimated risk area for both shortening (25.6 +/- 15.1%, p less than 0.05) and thickening (19.1 +/- 12.7%, p less than 0.001), as did analysis by dyskinesia (13.1 +/- 12.1% for shortening, p less than 0.001; 20.6 +/- 12.1% for thickening, p less than 0.01). Thus, modification of the centerline method allowed determination of both fractional shortening and wall thickening from echocardiographic images.(ABSTRACT TRUNCATED AT 250 WORDS)

Tachycardia, contractility and volume loading alter conventional indexes of coronary flow reserve, but not the instantaneous hyperemic flow versus pressure slope index.

OBJECTIVES AND BACKGROUND: Because measurements of flow reserve are often made in the setting of fluctuating hemodynamic variables that cause alterations in basal or hyperemic coronary blood flow, traditional flow reserve indexes may be difficult to interpret. Prior work in this laboratory has suggested that the instantaneous hyperemic flow versus pressure slope index is a more hemodynamically stable alternative to measures of flow reserve. Although this index has no hemodynamic dependence on changes in aortic pressure, the extent to which it is affected by other factors that alter myocardial work is unknown. Therefore, the purpose of this investigation was to analyze the effects of tachycardia (induced by atrial pacing at 10 beats/min above the basal heart rate), dobutamine infusion (10 micrograms/kg per min) and saline solution volume loading (500 ml) on measurements of traditional coronary flow reserve, the resistance reserve ratio and the instantaneous hyperemic flow versus pressure slope index. METHODS: Twenty-nine open chest anesthetized dogs were studied in four sequential stages: baseline, tachycardia, dobutamine infusion and saline solution volume loading. Traditional coronary flow reserve was defined as the ratio of hyperemic coronary blood flow to basal coronary blood flow, the resistance reserve ratio as the ratio of basal coronary resistance to hyperemic coronary resistance and the instantaneous hyperemic flow versus pressure slope index as the slope of the instantaneous relation between diastolic hyperemic coronary blood flow and diastolic aortic pressure normalized by perfusion bed weight. Hyperemia was induced by intravenous adenosine infusion (1 mg/kg per min). Mean aortic pressure was kept nearly constant during the interventions by manipulation of an aortic clamp or a vena caval snare. RESULTS: The final study group comprised 18 open chest dogs. Coronary flow reserve was significantly decreased by tachycardia (3.7 +/- 1.2 to 3.0 +/- 1.2, p < 0.0001), decreased by saline solution volume loading (3.2 +/- 1.3 vs. 2.7 +/- 0.8, p = 0.06) and significantly increased by dobutamine infusion (3.2 +/- 1.3 to 4.3 +/- 1.5, p < 0.0005). In contrast, the instantaneous hyperemic flow versus pressure slope index was not affected by the three interventions (7.4 +/- 3.1 vs. 7.3 +/- 3.3, 7.4 +/- 3.2 vs. 7.4 +/- 3.4 and 7.5 +/- 3.1 vs. 7.3 +/- 3.4, respectively, all p = NS). The changes observed in the resistance reserve ratio were of similar or greater magnitude and significance to the changes in coronary flow reserve. CONCLUSIONS: The instantaneous hyperemic flow versus pressure slope index offers a hemodynamically stable alternative to measures of vascular reserve because it is independent of moderate changes in heart rate, contractility and volume loading that may occur commonly in clinical situations.

Establishing comprehensive, quantitative criteria for detection of restenosis and remodeling after percutaneous transluminal coronary angioplasty.

To establish comprehensive criteria for detecting restenosis and remodeling, inter- and intraobserver reproducibility of quantitative arteriography in the analysis of 20 lesions immediately after and 6 months after percutaneous transluminal coronary angioplasty (PTCA) were assessed. Geometric single-plane (minimum, maximum, mean diameter and percent diameter stenosis), biplane (absolute and relative cross-sectional area stenosis), relative densitometric area stenosis and the average of densitometric area stenosis in orthogonal views were compared. A high intra- and interobserver reproducibility of all absolute measurements was found, with the highest correlations for minimum diameter and cross-sectional area (interobserver, r = 0.85 and 0.85; intraobserver, r = 0.93, and 0.95 for minimum diameter and cross-sectional area, respectively). Of the relative measurements, biplane geometric percent cross-sectional area stenosis was the most reliable and percent densitometric area stenosis was the most variable (interobserver, r = 0.67; intraobserver, r = 0.71). Only small differences were demonstrated for the absolute measurements between the analysis of lesions immediately after PTCA and after follow-up, whereas a greater variability was found for relative measurements, especially videodensitometry. In both circumstances, a poor correlation between relative densitometric cross-sectional area from orthogonal views was found, whereas geometric elliptical cross-sectional area correlated quite well with the average of densitometric percent cross-sectional area in orthogonal views (interobserver, r = 0.86; intraobserver, r = 0.84). Thus, data in this study support the suitability of geometric quantitative analysis for the assessment of PTCA results. Densitometry was the least reliable quantitative parameter.

Cardiac care unit admission criteria for suspected acute myocardial infarction in new-onset atrial fibrillation.

Management of new-onset atrial fibrillation (AF) varies between institutions and individual physicians. Because AF often occurs in elderly patients and is associated with coronary artery disease, patients presenting for the first time are often selected for admission to the coronary care unit to exclude the possibility of acute myocardial infarction (AMI). A review of 245 patients with AF admitted to an intensive care unit revealed 45 cases that were of new onset. AMI was diagnosed in 5 (11%) on the basis of elevated serum creatine kinase-MB levels. Evaluation of 56 clinical variables available during initial assessment indicated that infarction patients could be distinguished from others by the presence of left ventricular hypertrophy (p less than 0.01), electrocardiographic evidence of old myocardial infarction (p less than 0.01), typical cardiac chest pain (p less than 0.01), and duration of cardiac symptoms less than 4 hours (p less than 0.05). The presence of 2 or more of these features identified all AMI patients and 7 others at high risk for serious cardiac complications. The findings indicate that new-onset AF in the absence of clinical predictors suggesting myocardial ischemia or AMI does not warrant routine admission to the coronary care unit.

Comparison of automated quantitative coronary angiography with caliper measurements of percent diameter stenosis.

Measurement of coronary artery stenosis is an invaluable tool in the study of coronary artery disease. Clinical trials and even day-to-day decision making should ideally be based on accurate and reproducible quantitative methods. Quantitative coronary angiography (QCA) using digital angiographic techniques has been shown to fulfill these requirements. Yet many laboratories have abandoned visual analysis in favor of the intermediate quantitative approach involving hand-held calipers. Thus, the purpose of this study was to determine the relation between QCA and the commonly used caliper measurements. Percent stenosis was assessed in 155 lesions using 3 techniques: QCA, caliper measures from a 35-mm cine viewer (cine) and caliper measures from a video display (CRT). Good overall correlation was noted among the 3 different techniques (r greater than or equal to 0.72). Both of the caliper methods underestimated QCA for stenosis greater than or equal to 75% (p less than or equal to 0.001) and overestimated stenosis less than 75% (p less than 0.05). Reproducibility assessed in 52 lesions by independent observers showed QCA to be superior (r = 0.95) to either of the caliper measurements (cine: r = 0.63; CRT: r = 0.73). Therefore, the commonly used caliper method is not an adequate substitute for QCA because overestimation of noncritical stenoses and underestimation of severe stenoses may occur and the measurements have poor reproducibility. These factors definitely preclude its use in rigorous clinical trials. Moreover, since they do not appear to overcome known deficiencies of visual analysis, caliper measurements for day-to-day clinical use must also be seriously questioned.

Prognostic importance of quantitative analysis of coronary cineangiograms.

Many studies have shown the prognostic value of angiographic data, but few have examined quantitative parameters of wall motion and shape or coronary stenosis severity. To determine whether these parameters have prognostic importance, baseline angiograms of 283 patients with up to 11.2 years (mean 8.3) of follow-up were quantitated. Event-free survival curves were constructed using log-rank testing. These indexes were also considered in 2 predictive models (Cox regression models): 1 with ("clinical") and 1 without ("quantitative") subjective angiographic analysis and clinical information. Regional shape (anterior and inferior walls) and motion (anterior wall only) indexes were predictive of event-free survival when considered singly. But these parameters were not of independent prognostic importance in the regression models. The most important independent parameters in the quantitative model for predicting overall cardiac mortality or an initial lethal cardiac event were the ejection fraction and the percent diameter narrowing of each major coronary artery. Myocardial infarction was predicted by the percent diameter stenosis of the left main and left anterior descending arteries but not the ejection fraction. In the clinical model, the factors of overriding prognostic importance were the ejection fraction and the subjective determination of the number of vessels involved with "significant" stenoses. Quantitative coronary arteriography still contributed independent prognostic value. Thus, quantification of the ejection fraction and severity of coronary lesions were of independent, prognostic importance, whereas indexes of regional function and shape were not.

Immediate effects of graded ionic and nonionic contrast injections on coronary blood flow and myocardial function. Implications for digital coronary angiography.

The comparative immediate effects of ionic and nonionic contrast agents on coronary blood flow and regional function have not been studied. Therefore, subselective intracoronary injections of iohexol and sodium meglumine diatrizoate (Renografin 76) were compared at different rates (1, 3, and 4 mL/sec) and volumes (2 and 4 mL). Open chest dogs were instrumented with electromagnetic flow probes, subendocardial ultrasonic crystals, and a subselective intracoronary catheter. The 2- and 4-mL volumes of Renografin infused at 3 mL/sec, caused reductions in coronary blood flow that were maximal at 2 to 3 seconds after injection. These changes were significant for the 4-mL dose (61 +/- 19 at control vs. 23 +/- 12 mL/min, mean +/- SD, P less than .01) but not for the 2-mL dose. Iohexol produced identical flow responses but regional function was not significantly altered, whereas Renografin caused significant depression at both dose levels. Injections of 4 mL of Renografin at 1 and 4 mL/sec caused maximal flow decrements at 4.5 and 2 seconds after injection, respectively. Again, iohexol caused identical responses. At these doses, the effects of iohexol on regional function were also identical to those of Renografin. Thus, despite differences in physical properties, no significant differences in early blood flow changes were detected between these two agents.

Early reocclusion after successful thrombolysis is related to lesion length and roughness.

BACKGROUND: Reocclusion is a significant problem after thrombolysis. Results of previous studies conflict regarding the association of various features of postlytic lesions that might predict reocclusion. METHODS: A computer-assisted algorithm was therefore used to quantitatively measure edge roughness in the 90-minute postlysis angiogram of 84 patients receiving recombinant tissue plasminogen activator within 6 hours of chest pain. RESULTS: Twenty-five patients had reocclusion, and 59 did not. The baseline angiogram showed no differences between these two groups with respect to minimal dimensions or relative percentage of stenosis. Length was greater in the reocclusion group (12.2 +/- 5.0 vs 10.0 +/- 4.2 mm, P < 0.05). Three of four roughness indices based on curvature analysis indicated greater roughness in those patients with reocclusion. These differences were largely due to the increased length of these lesions. The scaled edge-length ratio, an index of roughness that is independent of length, was, however, significantly greater in the reocclusion group (1.15 +/- 0.10 vs 1.09 +/- 0.08, P < 0.006). Multiple regression analysis showed that lesion length, the scaled edge-length ratio, and the number of features (invaginations and evaginations) per cm correlated independently with the risk for reocclusion. CONCLUSIONS: The length and roughness of postlytic residual lesions are determinants of reocclusion.

Pharmacologic alterations of the isovolumic index: a study of the effects of isoproterenol, propranolol and verapamil.

The isovolumic index has been proposed as a noninvasive index of left ventricular function which, unlike the traditional systolic time index, incorporates the period of isovolumic relaxation. The responses of the isovolumic index and the systolic time index to three cardioactive drugs (isoproterenol, propranolol and verapamil) were assessed by measurements of ejection time (ET), isovolumic contraction time (IVC) and isovolumic relaxation time (IVR) in 23 dogs instrumented with high fidelity micromanometers and ultrasonic crystals. Isoproterenol infusions resulted in improvements in both the isovolumic and systolic time indices as a result of significant shortening of ET, IVC and IVR. Propranolol infusions caused significant and parallel increases of IVC (P less than 0.01) and ET (P less than 0.05) but failed to cause prolongation of either the systolic time index, defined as (IVC/ET) or deterioration of regional function. A higher propranolol dose caused significant increases in ET, IVC (P less than 0.001) and IVR (P less than 0.05), yet neither the systolic time index or the isovolumic index (IVC + IVR/ET) were prolonged, and regional function remained normal. Verapamil infusion caused an upward, nonsignificant trend in the isovolumic index and no change in the systolic time index. Stepwise multiple linear regression analysis demonstrated a similar load dependency of both indices and a higher inverse correlation of the isovolumic index with fractional shortening. The systolic time index showed a higher dependency on peak positive dP/dt whereas only the isovolumic index showed dependency on the isovolumic relaxation time constant. When altered loading conditions are accounted for, the isovolumic index shows directional changes that reflect changes in peak positive dP/dt, the isovolumic relaxation time constant and regional shortening.

The effects of acute ischemia on the isovolumic index.

The isovolumic index is the ratio of the duration of isovolumic contraction (IVC) and relaxation (IVR) divided by ejection time (ET), and has been proposed as a more sensitive descriptor of ventricular performance than the systolic time index, which ignores the period of isovolumic relaxation. To determine the effects of acute ischemia on these indices, IVC, IVR, and ET were measured in seven open-chest dogs instrumented with high-fidelity micromanometers and ultrasonic crystals and subjected to a 10-second period of coronary occlusion. Fractional shortening was significantly impaired (18.4 +/- 6.9% vs 1.9 +/- 7.3%, p less than 0.001) during coronary occlusion. ET was unaffected by the brief ischemia, whereas IVC time showed directional shortening that attained statistical significance (55 +/- 7 msec control vs 50 +/- 6 msec, p less than 0.01) at 8 to 10 seconds. IVR time was prolonged by occlusion, significantly so at 6 to 8 seconds (72 +/- 26 msec control vs 88 +/- 22 msec, p less than 0.01) and at 8 to 10 seconds (81 +/- 19 msec, p less than 0.05). The systolic time index showed no deterioration during ischemia, whereas the isovolumic index did not show directional prolongation. Assessment of IVC, IVR, and ET at the time of the maximal change in the isovolumic index revealed significant changes of IVC and IVR (each p less than 0.05 vs control), though ET and the systolic time index were unchanged. Through incorporation of IVR, the isovolumic index was more sensitive to acute brief ischemia than the systolic time index.

The effects of dopamine and dobutamine on regional function in the presence of rigid coronary stenoses and subcritical impairments of reactive hyperemia.

Intraluminal stenosing cylinders were inserted in the coronary arteries of open-chest, anesthetized dogs to assess the sensitivity of sympathomimetic infusion for detection of subcritical impairment of reactive hyperemia. Observations were made at rest and during steady-state infusions of dopamine and dobutamine (each 10 micrograms/kg/min) before and after placement of the cylinder. Each stenosis was associated with subcritical impairment of postocclusion reactive hyperemia at rest. The degree of impairment was used to stratify experiments into mild (group A) and moderate (group B) cohorts. In group A, reactive hyperemia was 217 +/- 55 cc/min prior to cylinder placement and 82 +/- 17 cc/min (p less than 0.002) after insertion. In group B, reactive hyperemia was 235 +/- 54 cc/min and 63 +/- 7 cc/min (p less than 0.001) before and after insertion. Both drugs resulted in a significant increase in regional shortening (ultrasonic crystal technique) in the absence of a stenosis. After creation of the stenoses, dopamine continued to cause a significant increase in shortening in both groups, whereas this increase was impaired in group B during dobutamine infusion (14.8 +/- 5.9% at rest vs 21.4 +/- 10.3% during infusion, p = NS). Thus, with subcritical lesions in a single vessel, dobutamine infusion was associated with depressed regional function when reactive hyperemia was impaired by more than 80%.

A comparison of traditional wall motion assessment and quantitative shape analysis: a new method for characterizing left ventricular function in humans.

To forego the need to arbitrarily choose coordinate, reference, and indexing systems and to make other assumptions mandated by traditional methods of measuring wall motion, a technique of regional function analysis based on shape characteristics and pattern recognition was developed. The method is based on curvature analysis, a fundamental shape parameter, and is adaptive to the complex geometry of cineangiographic ventricular images. Quantitative shape parameters were compared to a standard method of regional function analysis (center-line method) in 130 patients. Quantitative shape and wall motion indexes showed a positive correlation over a broad range of normal and abnormal function (r = 0.748, p less than 0.001). Overall sensitivity and specificity for categorization of regional function were not statistically different for either technique. Within regions, however, shape criteria were more specific in categorizing inferior zones than anterior zones and were more often abnormal in the presence of mild regional abnormalities that were not located in the apical region. In conclusion, shape analysis and pattern recognition techniques can be used to forego dependence on the numerous assumptions and approximations required by traditional wall motion techniques, while providing performance characteristics that are similar to, and in some instances better than, traditional approaches. Incorporation of shape information in assessments of regional function provides a more comprehensive evaluation that includes the important visual cues used by experienced observers or "experts."

Quantitative regional curvature analysis: a prospective evaluation of ventricular shape and wall motion measurements.

To overcome the assumptions and approximations mandated by the use of traditional wall motion methodologies, a method was recently developed for measuring ventricular shape based on quantitative curvature analysis of ventricular outlines. This study was designed to assess prospectively the performance of this algorithm, to compare it to traditional wall motion measurements (centerline method), and to determine the comparative degree to which each method mimicked the interpretation of wall motion by clinical observers. Semiquantitative visual grading of regional function in 52 patients was performed by four independent observers on two occasions. Anterior, apical, or inferior segments were judged to be normal (0 points) or abnormal (1 point) based on viewing nonrealigned, end-diastolic and end-systolic ventricular silhouettes from cineventriculograms obtained in the 30-degree right anterior oblique projection. Each segment was assigned a collated score ranging from 0 (all observers felt the region was normal on both readings) to 8 (all observers felt the region was abnormal on both readings). Quantitative regional curvature analysis and wall motion analysis (centerline method) were performed. Quantitative shape and wall motion scores correlated equally well with the semiquantitative visual scores. When a visual score of greater than or equal to 4 was used to designate an abnormal segment, both quantitative approaches demonstrated comparable sensitivity, specificity, and concordance rates. Both methods achieved optimal performance when maximum and minimum deviations from normal were recorded. Under these circumstances, the shape analysis demonstrated a greater concordance with the clinical diagnosis than did wall motion analysis (99% vs-93%, p less than 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

The immediate effects of iohexol on coronary blood flow and myocardial function in vivo.

Radiographic techniques used to quantify coronary blood flow all require bolus injection of contrast material, which markedly alters the flow being measured. Newer nonionic contrast agents have been shown to have fewer adverse hemodynamic, inotropic, and rheologic effects compared with ionic media and it has been suggested that they might not substantially affect coronary blood flow. Six dogs were instrumented with electromagnetic flow probes and subendocardial ultrasonic crystals. Intracoronary injections of iohexol (300 mg/ml iodine) were administered to establish a relationship between the dose and rate of contrast injection and the effect on flow and regional myocardial function. Two and 4 ml volumes of iohexol were injected at 3 ml/sec; 4 ml volumes were administered at 1 and 4 ml/sec. The 2 and 4 ml volumes decreased coronary flow by a mean of 31% (p less than .01) and 77% (p less than .001). The 4 ml injection at 1 and 4 ml/sec 77% (p less than .001) and 69% (p less than .001). The magnitude of the fall in flow was directly related to the dose, and the rate at which the flow nadir was attained was directly related to the rate of injection. Decrements in fractional shortening were temporally delayed by several beats compared with the flow changes and showed mean decrements of 19% to 29%. The effects on regional myocardial function were independent of contrast volume. However, the degree of dysfunction was more profound with slower infusion rates, suggesting that prolongation of contrast-induced ischemia was a major modulating factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensitivity and reproducibility of the instantaneous hyperemic flow versus pressure slope index compared to coronary flow reserve for the assessment of stenosis severity.

The objective of this study was to compare the reproducibility and sensitivity of the instantaneous hyperemic flow versus pressure slope index (i-HFVP) and coronary flow reserve (CFR). The i-HFVP is the slope of the relationship between diastolic hyperemic coronary flow and diastolic aortic pressure, normalized for bed weight. In contrast to CFR (the ratio of hyperemic to basal coronary flow), the i-HFVP has been shown to be independent of changes in aortic pressure, heart rate, contractility, and preload. To compare reproducibility, i-HFVP and CFR were measured three times in eight dogs instrumented with high-fidelity micromanometers and flow probes, allowing for full hemodynamic recovery between phases (15 to 40 minutes). Maximum hyperemia was induced with intravenous adenosine. The sensitivity of i-HFVP and CFR was assessed in 16 instrumented dogs. Measurements were performed for one basal state and for five subcritical incremental stenoses created with a screw occluder during hyperemia. Intraclass variability correlation coefficients were 0.96 for i-HFVP but only 0.56 for CFR. Both i-HFVP and CFR showed significant decrements with each increasing stenosis. However, the percentage reductions at each level were significantly greater for the i-HFVP. The difference in percentage reduction favoring increased sensitivity of the i-HFVP ranged from 11% to 23%. It was concluded that the i-HFVP is more reproducible and more sensitive to the presence of stenoses than CFR.

Relation between graded, subcritical impairments of coronary flow reserve and regional myocardial dysfunction induced by isoproterenol infusion in dogs.

Isoproterenol has been used experimentally and clinically to elicit ischemia. The usefulness of this approach, however, in eliciting regional dysfunction in the presence of mild to moderate single-vessel coronary disease quantitated on the basis of coronary flow reserve measurements has not been previously defined. Open-chest, anesthetized dogs were instrumented with an electromagnetic flow probe, high-fidelity micromanometers, and subendocardial ultrasonic crystals. A rigid, screw occluder was used to produce five subcritical coronary stenoses in each dog associated with varying impairment of postocclusion reactive hyperemia at rest but no impairment of resting coronary blood flow. Regional function at rest and in response to the isoproterenol challenge (0.25 micrograms/kg/min) in nonstenotic and stenotic conditions was assessed. Relative regional function was maintained during the infusion until nearly total loss of coronary flow reserve. With this near-critical stenosis, function was lower than in the nonstenotic state but remained greater than resting control values. Moderate impairments of coronary flow reserve were not associated with isoproterenol-induced deterioration of regional function. In conclusion, detection of impaired coronary flow reserve at rest is a more sensitive index of the severity of a coronary stenosis than is detection of regional dysfunction during isoproterenol challenge. Failure to maintain the expected isoproterenol-induced increase in regional function is manifested only when stenoses are associated with nearly total loss of resting coronary flow reserve. This suggests that the clinical use of isoproterenol challenge is not effective in eliciting regional dysfunction when mild coronary disease is present.

The hemodynamic determinants of the isovolumic index.

The isovolumic index is a recently described echocardiographic parameter of left ventricular function that is calculated as the ratio between the sum of the time of isovolumic contraction and relaxation divided by the ejection time. Although the individual components of this index may be altered by heart rate and loading conditions, an analysis of the net effect of such alterations on the isovolumic index has not been undertaken. Thus, dogs were instrumented with high-fidelity micromanometers in the left ventricle, ascending aorta, and left atrium to allow determination of the individual components of the isovolumic index and calculation of the index itself. Four sets of experiments were undertaken in random order. Left atrial pacing was used to increase heart rate by approximately 10 bpm in five steps. Preload was elevated in five stages by saline infusions which caused successive increases of 1 to 2 mm Hg in the left ventricular end-diastolic pressure. Systolic blood pressure was lowered or raised by approximately 10 mm Hg per stage by three progressive, steady-state infusions of nitroprusside and phenylephrine, respectively. These experiments demonstrated little change in the isovolumic index over a broad range of heart rate. Increased left ventricular end-diastolic pressure and decreased systemic pressure caused shortening of the index. Multiple regression analysis of all experiments yielded the following: isovolumic index = 0.41 - 0.015 (left ventricular end-diastolic pressure) + 0.004 (systolic blood pressure); r = 0.57, standard error = 0.13, p less than 0.0001. Therefore, this investigation establishes the hemodynamic determinants of the isovolumic index and provides the basis for interpretation of directional changes in response to cardiac diseases and cardioactive drugs that can alter loading conditions.

The diastolic hyperemic flow versus pressure relation. A new index of coronary stenosis severity and flow reserve.

The measurement of coronary flow reserve, traditionally calculated as the ratio of maximal hyperemic blood flow divided by basal flow, is difficult to interpret in serial studies because fluctuating hemodynamic parameters may affect either basal or hyperemic flow measurements. To determine the magnitude of this problem and to develop alternative approaches for measuring vascular reserve, 10 anesthetized dogs were instrumented with aortic and inferior vena cava occluders, electromagnetic coronary flow probes, and high-fidelity micromanometers in the left ventricle and aortic root. Coronary flow was measured in the basal state and during maximal hyperemia induced by a steady-state adenosine infusion. Observations were made in the absence of a stenosis and in the presence of two incremental degrees of subcritical stenosis produced by a rigid, external screw occluder. Several parameters of vascular reserve were determined: 1) coronary flow reserve (defined above), 2) mean hyperemic flow divided by mean aortic pressure, 3) mean hyperemic flow divided by the difference between mean aortic pressure and left ventricular end-diastolic pressure, and 4) the slope of the instantaneous relation between diastolic hyperemic flow versus pressure. Each parameter was measured during five steady-state pressure levels achieved by partial occlusion of either the inferior vena cava or the aorta and the levels ranged from 82 +/- 8 mm Hg (mean +/- SD) to 127 +/- 9 mm Hg during hyperemia. All measures of vascular reserve were found to be dependent on hemodynamic parameters such as heart rate and mean aortic pressure. The slope of the instantaneous relation between diastolic hyperemic flow and pressure, however, showed only minimal dependence on heart rate and, in contrast to coronary flow reserve measurements, distinguished between the normal and the two stenotic states. Further, this optimal performance of the hyperemic flow versus pressure slope index was shown in a model in which coronary flow and myocardial work were not independently controlled. This index provides a sensitive and reliable indication of subcritical stenosis severity that may have clinical applications.

Determination of coronary flow reserve by parametric imaging.

Nine mongrel dogs were instrumented with electromagnetic flow probes (EMF) to measure coronary blood flow through the left anterior descending (LAD) and left circumflex (LCx) coronary arteries at rest and after maximal coronary vasodilation (1 mg/kg/min adenosine). Relative coronary blood flow was determined by parametric imaging in the left posterior oblique projection using digital subtraction angiography (DSA). Transmural myocardial perfusion of the LAD and LCx beds was determined with tracer-labeled microspheres. Coronary flow reserve (maximal coronary blood flow divided by resting blood flow) was calculated under control conditions and after constriction of the proximal LAD or LCx by a screw occluder. Heart rate decreased significantly from 140 beats/min at rest to 122 beats/min after adenosine (p less than 0.001) and from 134 (rest) to 120 beats/min (adenosine; p less than 0.05) after coronary constriction. Peak systolic pressure was kept constant with an aortic constrictor. Left ventricular end-diastolic pressure increased significantly from 18 mm Hg at rest to 23 mm Hg (p less than 0.05) after coronary constriction. At baseline, coronary flow reserve was 4.2 with DSA, 3.8 with EMF, and 3.7 with microspheres; after coronary constriction, it was 2.6 (DSA), 1.9 (EMF), and 1.5 (microspheres) (all p less than 0.001 versus baseline). Coronary blood flow showed a good correlation between EMF and microspheres (r = 0.87, p less than 0.001), with a standard error of estimate (SEE) of 0.78 ml/g/min. Coronary flow reserve also showed a good correlation between EMF and microspheres (r = 0.82, p less than 0.001), with an SEE of 0.93. There was a moderate correlation between EMF and DSA (r = 0.68, p less than 0.001), with an SEE of 1.35 (40% of mean coronary flow reserve). The correlation coefficient between microspheres and DSA was 0.54 (p less than 0.01), with an SEE of 1.46 (39% of mean coronary flow reserve). The mean difference (accuracy) and standard deviation of difference (precision) were 0.2 +/- 1.0 between EMF and microspheres, -0.1 +/- 1.4 between EMF and DSA, and -0.6 +/- 1.7 between microspheres and DSA. We conclude that determination of coronary flow reserve by parametric imaging is associated with large variations that are greater than variations also inherent in the two reference techniques. Parametric imaging allows relatively accurate assessment of coronary flow reserve (small mean difference), but precision is low (large standard deviation of mean differences).(ABSTRACT TRUNCATED AT 400 WORDS)