Persistence of hapten-antibody complexes in the circulation of immunized animals after a single intravenous injection of hapten.

To study the fate of a low molecular weight antigen (hapten) in the circulation of animals whose sera contain antibodies specific for that low molecular weight antigen, a single injection of digoxin-(3)H (0.4 mg/kg) was administered intravenously to 18 rabbits. Thirteen animals (nine nonimmunized and four immunized with bovine serum albumin) served as control animals. In five rabbits which had been immunized with a digoxin-bovine serum albumin conjugate and whose sera contained digoxin-specific antibodies, the mean 12-h serum digoxin concentration was 8,300 ng/ml (control: 92 ng/ml) and the mean serum concentration 12 mo after the single injection of digoxin-(3)H was 85 ng/ml. In digoxin-immunized rabbits, less than 10% of the digoxin-(3)H was excreted in the first 10 days (control: 77% recovered in urine and feces) and the mean biological half-life of digoxin, as calculated from serum digoxin-(3)H disappearance curves, was 72 days (control: 3.4 days). In sera of digoxin-immunized rabbits, more than 90% of the circulating digoxin-(3)H was immunoglobulin bound, as determined by the double-antibody and dextran-coated charcoal methods. The serum disappearance rate of (125)I-antidigoxin antibodies was similar in nonimmunized and in immunized animals and in the presence or absence of digoxin. It is concluded that the biological half-life of a hapten may be markedly prolonged when the hapten is bound to specific antibody. The persistence of antibody-hapten complexes in the circulation suggests that these complexes may not be deposited in tissues and raises the possibility that low molecular weight determinants may be capable of preventing or reversing the deposition of immune complexes, containing macromolecular antigens, in the tissues of experimental animals and man.

Role of retrograde His Purkinje block in the initiation of supraventricular tachycardia by ventricular premature stimulation in the Wolff-Parkinson-White syndrome.

The precise mechanisms for paroxysmal reentrant supraventricular tachycardia (PSVT) initiation during right ventricular premature stimulation (V(2) method) were analyzed in 14 consecutive patients with Wolff-Parkinson-White Syndrome in whom the PSVT was inducible during retrograde refractory period studies. 9 patients had left-sided and the remaining 5 of 14 had right-sided ventriculo-atrial (VA) accessory pathway (AP). At the basic cycle lengths (V(1)V(1)) ranging from 550 to 900 ms (mean, 657.1+/-139.5), closely coupled V(2) (mean V(1)V(2), 357.3+/-59.2 ms, range 320-500) produced retrograde His bundle (H(2)) activation via the bundle branches and retrograde atrial (A(2)) activation via the AP. As the V(1)V(2) were further shortened, the V(2) showed a retrograde block in the His Purkinje system (HPS) and conducted to the atria via AP in 9 of 14 cases. Subsequently, the A(2) impulse conducted anterograde over the atrioventricular node-HPS to initiate a PSVT or an atrial echo response in all nine cases. In none of the patients was a PSVT induced by V(2) when the latter produced retrograde H(2) activation via the bundle branches. In 10 of 14 cases, however, the retrograde H(2) was followed by a V(3), due to macroreentry in the HPS. The V(3) in turn blocked retrogradely in the HPS while producing A(3) via the AP to initiate a PSVT or an atrial echo response in 9 of 10 cases. Retrograde block of V(2) and/or V(3) in the HPS resulted in PSVT initiation in 13 of 14 cases, whereas in the remaining 1 case the exact mechanism was not clear. In none of the patients in this series was the PSVT initiated with a retrograde block of V(2) in the atrioventricular node with or without concomitant retrograde A(2) activation via the AP. We conclude that within the ranges of cycle lengths tested, a retrograde block of V(2) and/or V(3) in the HPS is the most common mechanism for initiation of PSVT during ventricular premature stimulation in patients with the Wolff-Parkinson-White Syndrome.

Reversal of digoxin toxicity with specific antibodies.

To determine whether digoxin-specific antibodies can reverse established digoxin toxicity in the dog, digoxin intoxication was produced by the intramuscular administration of digoxin, 0.09 mg/kg, on each of 3 consecutive days. All animals developed toxic arrhythmias (atrioventricular block, ventricular premature contractions and/or ventricular tachycardia). In control animals not receiving antidigoxin antibodies, the arrhythmias persisted throughout a 6 hr study period. Seven of the nine control dogs were dead within 24 hr and one moribund animal was sacrificed at that time; the last animal died within 48 hr.In contrast, in six of eight dogs given digoxin-specific antibodies in canine plasma and/or rabbit serum, the arrhythmias reverted to a sinus mechanism within 30-90 min after the start of the infusion. At the end of a 6 hr period of study, these six dogs were in normal sinus rhythm and all eight were alive and in normal sinus rhythm at the end of 72 hr. This study provides evidence that digoxin-specific antibodies can reverse severe established digoxin toxicity in the dog.

Immunological protecion against dixin toxicity.

The lethal dose of digoxin was determined by administering 10 ml of a digoxin-saline solution to 26 nonimmunized rabbits through an ear vein over a 10 min period. Rabbits receiving less than 0.45 mg/kg digoxin showed no toxic effect, whereas all 15 rabbits that received 0.5 mg/kg developed an early arrhythmia and died within 1 hr. Moreover, eight rabbits which had been immunized with antigens unrelated to digoxin or injected with Freund's adjuvant mixture all died after receiving 0.6 mg/kg digoxin. Thus, it was concluded that 0.6 mg/kg digoxin was uniformly lethal in rabbits that had not been immunized or had received antigens unrelated to digoxin. By way of contrast, 17 rabbits immunized with a digoxin-albumin conjugate in complete Freund's adjuvant formed digoxin-specific antibodies and survived doses of digoxin varying between 0.6 and 0.9 mg/kg. In 10 rabbits immunized with digoxin-albumin conjugates, digoxin-specific antibody titers were determined following the administration of digoxin. There was a significant fall in antibody titer. This study indicates that rabbits protected by digoxin-specific antibodies suffer no acute adverse effects from an amount of digoxin which is uniformly lethal in nonimmunized rabbits and in rabbits immunized with other antigens.

Effects of sheep digoxin-specific antibodies and their Fab fragments on digoxin pharmacokinetics in dogs.

Intact sheep antidigoxin antibodies and their Fab fragments have both been found to exert profound effects on digoxin pharmacokinetics in [3H] digoxin-treated dogs. Both classes of molecule remove digoxin from the extravascular space and sequester it in the circulation in protein-bound form, a form in which the digoxin is presumably inactive. These two classes of molecule differ, however, in that the intact antibody molecules interfere with digoxin excretion, thereby promoting the retention of the glycoside; this retained digoxin is eventually released in free, active form when the administered antibody is metabolically degraded. In contrast, urinary excretion of digoxin continues in Fab-treated dogs, with significant quantities of digoxin being excreted promptly in the urine in complex with Fab fragments. These differences in urinary excretion, together with the probable decreased immunogenicity of sheep antidigoxin Fab fragments, suggest that such fragments possess potential advantages over intact antibody molecules for use in the therapy of life-threatening digoxin intoxication in man.

The relationship between regional myocardial perfusion at rest and arteriographic lesions in patients with coronary atherosclerosis.

Measurements of mean left ventricular (LV) and regional myocardial blood flow rates were made at rest in 161 patients with 133Xe and a multiplecrystal scintillation camera. Myocardial perfusion rates were correlated with assessments of the degree of coronary artery disease made from the arteriograms obtained during the same studies. In patients with normal coronary arteries without heart failure, the presence of hypertension, aortic stenosis, or aortic insufficiency was not associated with changes in mean LV perfusion from the control value of 61+/-7 ml/100 g-min. However, mean LV perfusion was significantly reduced in patients with normal coronary arteries who had cariomyopathy and impaired ventricular performance. Mean LV perfusion was not significantly different from control values in patients with "mild" coronary artery disease (less than 50% obstruction) or in patients with significant isolated disease (greater than 50% obstruction) of the left anterior descending (lad) artery. Significant reductions in mean LV perfusion were found in patients with greater than 50% obstruction of two coronary arteries (LAD + right or LAD + circumflex) and in patients with triple-vessel disease. The average perfusion rate for regions distal to LAD obstructions in patients with isolated LAD disease was not lower than the LAD perfusion in control patients, but was significantly reduced in patients with LAD + right coronary artery disease (43+/-14 ml/100 g-min). In the latter group average perfusion distal to the LAD lesion was significantly lower than the average regional perfusion rate for the remainder of the LV. However, the mean blood flow rate for the remainder of the LV was also significantly lower than control values despite the lack of significant circumflex disease. The data demonstrate that the presence of radiographically "mild" or significant isolated LAD coronary disease is not associated with reductions in mean LV perfusion at rest, but that mean LV perfusion is reduced in the presence of significant disease of two or three coronary artieries. None of the patients experienced angina during the resting studies and most had clinical evidence of ventricular failure. The observation of depressed LV perfusion in this group, as in the patients with cardiomyopathy, raises the possibility that a lowered resting blood supply may be adequate for a reduced level of performance of a diseased ventricle. The lack of selective reductions of regional perfusion at rest in the majority of the patients with LAD lesions suggests that regional myocardial blood flow must be measured during an intervention which increases myocardial oxygen consumption in order to assess the physiological significance of lesions which are observed at coronary arteriography.

Effects of intraaortic balloon counterpulsation on myocardial blood flow in patients with severe coronary artery disease.

The purpose of this study was to test the hypothesis that myocardial blood flow distal to a critical stenosis would increase during intraaortic balloon counterpulsation. Accordingly, 13 patients with severe coronary artery disease were studied at the time of elective preoperative insertion of an intraaortic balloon catheter. Hemodynamic measurements and measurements of myocardial blood flow were made before and during counterpulsation. Myocardial blood flow was measured with a xenon-133 washout technique. Compared with control measurements, the heart rate decreased from 87.8 +/- 18.8 to 82.8 +/- 13.4 beats/min (p = 0.02) and systolic arterial pressure decreased from 112.1 +/- 17.9 to 97.8 +/- 14.8 mm Hg (p = 0.004) during counterpulsation. Diastolic arterial pressure increased from 72.2 +/- 10.1 to 120.2 +/- 21.4 mm Hg (p = 0.00002) during counterpulsation. Myocardial blood flow for the entire group decreased from 48.8 +/- 14.1 to 42.6 +/- 11.0 ml/100 g per min (p = 0.008). Regional flows in the left anterior descending and circumflex distributions also decreased. Left anterior descending artery blood flow decreased insignificantly from 51.5 +/- 14.4 to 47.4 +/- 11.7 ml/100 g per min (p = not significant), while circumflex flow decreased from 50.7 +/- 12.2 to 41.1 +/- 8.9 ml/100 g per min (p = 0.008). When normalized for the rate-pressure product, myocardial blood flow was 53 +/- 16 X 10(-4) at rest and 55 +/- 12 X 10(-4) (p = not significant) during counterpulsation.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of single vessel coronary artery disease: results of exercise electrocardiography, thallium-201 myocardial perfusion imaging and radionuclide angiography.

The sensitivity of the commonly used stress tests for the diagnosis of coronary artery disease was analyzed in 46 patients with significant occlusion (greater than or equal to 70% luminal diameter obstruction) of only one major coronary artery and no prior myocardial infarction. In all patients, thallium-201 perfusion imaging (both planar and seven-pinhole tomographic) and 12 lead electrocardiography were performed during the same graded treadmill exercise test and radionuclide angiography was performed during upright bicycle exercise. Exercise rate-pressure (double) product was 22,307 +/- 6,750 on the treadmill compared with 22,995 +/- 5,622 on the bicycle (p = NS). Exercise electrocardiograms were unequivocally abnormal in 24 patients (52%). Qualitative planar thallium images were abnormal in 42 patients (91%). Quantitative analysis of the tomographic thallium images were abnormal in 41 patients (89%). An exercise ejection fraction of less than 0.56 or a new wall motion abnormality was seen in 30 patients (65%). Results were similar for the right (n = 11) and left anterior descending (n = 28) coronary arteries while all tests but the planar thallium imaging showed a lower sensitivity for isolated circumflex artery disease (n = 7). The specificity of the tests was 72, 83, 89 and 72% for electrocardiography, planar thallium imaging, tomographic thallium imaging and radionuclide angiography, respectively. The results suggest that exercise thallium-201 perfusion imaging is the most sensitive noninvasive stress test for the diagnosis of single vessel coronary artery disease.

Superior bioavailability of digoxin solution in capsules.

The bioavailability of various formulations of digoxin was assessed after single and multiple doses in a series of crossover studies in human volunteers. Digoxin tablets that were 97% dissolved in 1 hr in vitro were not significantly better absorbed than tablets with a dissolution rate of 78%. A solution given in capsule form had greater bioavailability than tablets of 97% dissolution rate; serum and urinary glycoside levels after 0.4 mg doses of the encapsulated solution were similar to those attained after 0.5 mg doses of tablets with dissolution rates of 78% and 97%. The bioavailability of the solution in capsule form exceeded that of equal doses of the same solution given as a liquid or that of a standard elixir. No increase in gastrointestinal or cardiac toxicity was detected. Inter- and intrasubject variation in bioavailability was not decreased. Above a certain level, dissolution rate is no longer the limiting factor in digoxin absorption. The mechanism of the enhanced bioavailability of concentrated liquid digoxin in capsule form remains to be determined. Such a preparation deserves further consideration as a possible replacement for digoxin tablets.

Right anterior oblique first-pass radionuclide ejection fractions: effects of temporal smoothing and various background corrections.

Thirty-seven patients undergoing contrast left ventriculography were studied by first-pass radionuclide angiography (FPRA) in the right anterior oblique view. Ejection fraction (LVEF) was calculated from FPRA using (a) a spatially and temporally varying background correction (BGC) based on a matrix of activity in lung and left atrium and (b) BGC with temporal fluctuation but with no allowance for spatial variations. The two methods were performed on both raw and temporally smoothed data. All four LVEFs correlated well with contrast LVEF (r = 0.90 - 0.94). Absolute values differed significantly from contrast values except for the method using the spatially and temporally varying BGC on smoothed data, which provided the closest overall agreement at all levels of LVEFs, despite occasional large individual variations. The same method on raw data overestimated low LVEFs and the method applying only temporal fluctuation in background underestimated high LVWFs. Allowance for spatial and temporal variations in background is therefore important when first-pass radionuclide angiography is performed in the RAO view.

Background correction in first-pass radionuclide angiography: comparison of several approaches.

This study was designed to test the comparative accuracy of several commonly used background correction techniques in first-pass radionuclide angiography (FPRNA). Thirty patients underwent FPRNA and single plane contrast angiography (CA) within 1 hr of each other. The left ventricular ejection fractions (LVEF) calculated from the different background subtraction approaches to FPRNA were compared to the CA LVEF. When applied to a representative cycle, a horseshoe-shaped background region of interest (BKROI) underestimated LVEF (p less than 0.005, r = 0.91, s.e.e. = 0.06) while a ring shaped BKROI adjusted at end-systole for aortic valve motion insignificantly overestimated LVEF (p = NS, r = 0.91, s.e.e. = 0.07). A lung background approach applied to a representative cycle gave the best correlation with CA (p = NS, r = 0.96, s.e.e. = 0.04). Without using a representative cycle, time-activity curves from a horseshoe-shaped BKROI and the LV ROI were created and the LV curve was normalized to the peak counts in the BKROI curve. LVEF calculated from the normalized curve correlated favorably with CA LVEF (p = NS, r = 0.91, s.e.e. = 0.08). The influence of some recently described improvements in representative cycle generation are also documented.

High count rate first-pass radionuclide angiography using a digital gamma camera.

In this study, first-pass radionuclide angiography (FPRNA) was performed using a digital single-crystal gamma camera. Twenty-nine men and six women (ages 43-80, mean 61 yr) underwent FPRNA in the supine position immediately prior to cardiac catheterization. Total counts/sec in the whole field-of-view in the right ventricular phase were 150,352 +/- 26,006. Background uncorrected counts in the representative cycle were 7,651 +/- 2,527 at end-diastolie and 4,904 +/- 2,314 at end-systolie. A linear correlation between FPRNA left ventricular (LV) ejection fraction and contrast LV ejection fraction gave an r = 0.95 with an s.e.e. of 0.05. Analyses of intra- and interobserver variability gave r = 0.99 and 0.98 and an s.e.e. of 0.02 and 0.03, respectively. Spearman-Rank correlation coefficients between FPRNA and contrast angiographic wall-motion scores were greater than 0.8 for all walls, while sensitivity/specificity were 0.86/0.90, 0.76/1.00, 0.76/1.00 for anterior, apical, and inferior wall-motion abnormalities, respectively. We conclude that satisfactory counting statistics for FPRNA can be obtained with a digital gamma camera, and that accurate and reproducible measurements of global and regional left ventricular function can be obtained with this technique.

Left ventricular volume calculation using a count-based ratio method applied to first-pass radionuclide angiography.

Most count-based radionuclide methods for calculating left ventricular volume rely on measurement of radioactivity in a peripheral blood sample and a measurement of ventricle to collimator distance. We have developed a method which requires neither a blood sample nor a distance measurement and which is applicable to first-pass radionuclide angiography. The parameters used to calculate volume are the area of pixel, the total counts in the left ventricle and the maximum pixel count. The equation was used to calculate the volumes in 50 patients who had both resting first-pass radionuclide angiography (25 patients with a single crystal and 25 patients with a multicrystal camera) and contrast ventriculography on the same day. Correlation coefficients for end-diastolic and end-systolic volumes showed r ranging 0.93-0.98 and standard error of estimate ranging 23-35 ml for end-diastolic volume (14%-17% of mean end-diastolic volume) and 16-23 ml for end-systolic volume (18%-21% of mean end-systolic volume). Image processing software for extracting the needed values is generally available on most commercial nuclear medicine imaging systems and the additional time for the calculations is short. Although the theory is based on multiple assumptions, the volume calculation appears to be reasonably accurate and clinically applicable.

Left ventricular volume calculation using a count-based ratio method applied to multigated radionuclide angiography.

The purpose of this study was to investigate the accuracy of a new count-proportional method for the measurement of left ventricular volume when applied to gated equilibrium blood-pool imaging. An equation is developed that relates total chamber volume, Vt, to the area of a pixel (M) and the ratio (R) of total counts within the chamber to the counts within the hottest pixel in the chamber such that Vt = 1.38 M3R3/2. The value of M is a constant for the particular scintillation camera-collimator system and R is obtained from observed count rates. All calculated volumes were compared to volumes measured using biplane contrast ventriculography. In 25 patients, the method for ventricular volumes gave an r of 0.95 and an s.e.e. of 23 ml [Volume (nuclear) = 0.94 Volume (cath) + 1.3]. Endsystolic volume was best calculated from end-diastolic volume and ejection fraction. Manual regions of interest were more accurate than automated regions of interest. This method appears to be as accurate as more complex approaches and has the advantage of not requiring attenuation correction or blood sampling.

Evaluation of transient mitral regurgitation in coronary artery disease.

The pathoanatomy and factors associated with transient mitral regurgitation (MR) induced by myocardial ischemic stress are unknown. Changes in valvular and ventricular parameters during transient, stress-induced MR in patients with coronary artery disease were investigated, and the clinical characteristics of these patients were identified. Color flow Doppler echocardiography was used to quantify the MR color area, the coaptation point of the mitral leaflets, the mitral valve anulus diameter, and left ventricular volumes and wall motion in 42 patients before and immediately after exercise echocardiography (group 1, n = 27), or before and during percutaneous transluminal coronary angioplasty (PTCA) (group 2, n = 15). Of the 27 patients with exercise echocardiography, 4 developed new, transient MR (group 1B) and 9 had MR both at rest and during exercise (group 1C). Of the 15 patients with PTCA, 7 developed new MR (group 2B). New MR (groups 1B and 2B) was associated with more severe stress-induced ventricular dyskinesia (p less than 0.05) than was seen in patients with chronic MR (group 1C) or in patients without MR, and occurred predominantly in patients with left anterior descending or right coronary artery stenoses. Stress-induced MR was not associated with changes in blood pressure or in mitral valve anulus diameter, nor with the development of mitral valve prolapse. It was associated with apical displacement of the mitral leaflets in patients in group 1B and C (p less than 0.05). New MR flow areas were significantly smaller than those in patients with chronic MR (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of exercise protocol on the left ventricular response to exercise.

The purpose of this study was to determine whether the left ventricular response during exercise radionuclide angiography would be influenced by exercise protocol. One hundred twenty healthy volunteers (aged 18 to 40 years) performed upright bicycle exercise using 1 of 5 protocols. Ejection fraction was measured using first-pass radionuclide angiography. Exercise protocols were as follows: (1) graded exercise (25 W increase every 2 minutes) to fatigue, heart rate greater than 85% of age-predicted maximum, n = 53; (2) graded exercise to 85% of age-predicted maximal heart rate or to fatigue with heart rate less than 85% of age-predicted maximum, n = 26; (3) graded exercise to fatigue, with "exercise" imaging performed immediately after exercise, n = 15; (4) abrupt presentation of a supermaximal work load (400 W), n = 10; (5) graded exercise to a work load of 75 W preceding the abrupt presentation of a supermaximal work load (300 to 400 W), n = 16. Protocols 2 and 3, representing less than maximal stress, yield higher ejection fractions than Protocol 1 and may reduce the sensitivity of exercise radionuclide angiography. Protocols 4 and 5, representing supermaximal stress, yield lower ejection fractions than Protocol 1 and may reduce the specificity of exercise radionuclide angiography. Thus, exercise protocol has a significant influence on the left ventricular response during exercise radionuclide angiography.

Peak exercise and immediate postexercise imaging for the detection of left ventricular functional abnormalities in coronary artery disease.

Eleven patients without significant coronary artery disease (CAD) (group A), 22 patients with significant CAD and no prior myocardial infarction (MI) (group B), and 10 patients with CAD and a previous MI (group C) were imaged at rest, at peak exercise and immediately after exercise by first-pass radionuclide angiography. At peak exercise, mean left ventricular (LV) ejection fraction (EF) did not change significantly in group A or C and decreased significantly in group B. However, in all groups mean LVEF increased significantly immediately after exercise. Examination of potential criteria for an abnormal LVEF response showed that changes from rest to peak exercise were sensitive for detection of CAD but were not specific. Postexercise criteria were more specific but relatively insensitive: 15 of 32 patients (47%) with CAD showed a normal (greater than 5% increase over rest) response after exercise. Similarly, a regional abnormality at peak exercise was 100% sensitive, compared with a sensitivity of 78% after exercise for the whole group, and only 68% in patients without prior MI. Seven patients would have been misclassified as normal if postexercise imaging alone had been performed. The likelihood of an abnormal postexercise EF response was related to the extent of CAD: No patient with 1-vessel, 8 of 17 with 2-vessel and 9 of 12 with 3-vessel CAD showed such a response. Peak exercise imaging is necessary to achieve maximal sensitivity for the detection of CAD, and a high false-negative rate will be obtained if postexercise imaging only is used. The combination of peak exercise and postexercise imaging may be of value in assessing the severity of CAD.

Measurement of regional myocardial blood flow in man: description and critique of the method using xenon-133 and a scintillation camera.

A method has been devised to measure regional myocardial blood flow in man. The approach consists of selective injection of xenon-133 into a coronary artery and the external monitoring of radioisotope washout curves from multiple areas of the myocardium with a multiple crystal scintillation camera. Rate constants of isotope washout are calculated using a monoexponential model, and the capillary blood flow rates in multiple regions of the heart are calculated by the Kety formula. The pattern of perfusion rates is related to the coronary arteriogram obtained in the same study. Myocardial perfusion patterns obtained in patients with and without coronary artery disease and during atrial pacing are given, as well as examples of results obtained in myocardial aneurysms, in regions of ischemic myocardium supplied by collateral vessels and after tracer injection into an aortocoronary bypass graft. Advantages of the method are discussed along with limitations related to the tracer, the scintillation camera, the form of mathematical analysis and the three dimensional nature of the heart.

Sequential internal mammary artery grafts. Expanded utilization of an ideal conduit.

The internal mammary artery, when used as a conduit for coronary artery bypass, offers a better long-term patency rate and survival rate than the saphenous vein; however, its utility has been limited. Among other factors, the availability of only two internal mammary arteries for anastomosis has been a major limitation. In an attempt to overcome this limitation, we constructed sequential internal mammary artery grafts in 87 patients. In 49 patients (Group I), only one internal mammary artery was used for sequential anastomosis. In another 31 patients (Group II), one internal mammary artery was used for sequential anastomosis and the other was used for single end-to-side anastomosis. Both internal mammary arteries were used in seven patients (Group III) for the construction of sequential anastomoses. Postoperatively, 64 patients were evaluated by exercise stress tests. None of these patients had a positive stress test although seven patients (11%) had electrocardiographic changes that were considered equivocal. Coronary angiography was performed in 35 of the 87 patients, with 92 vein grafts and 90 internal mammary artery anastomotic sites evaluated within 1 year of operation. A total of 83 vein grafts and 84 internal mammary artery anastomotic sites evaluated within 1 year of operation. A total of 83 vein grafts and 84 internal mammary artery anastomoses were found to be patent. Thus the patency rate for vein grafts was 90% and for internal mammary artery grafts, 93%. During the follow-up period (8 to 52 months), three patients died and one was lost to follow-up. Among the remaining patients, 79 had complete relief from symptoms, three had minimal symptoms, and one patient obtained no relief from symptoms. Based on these results, we have concluded that the extended use of internal mammary artery, constructing sequential anastomoses, is technically feasible and provides adequate perfusion to the area of myocardium supplied by such grafts.

Improvement in left ventricular function after myocardial revascularization: assessment by first-pass rest and exercise nuclear angiography.

Thirty-six patients with coronary artery disease were studied by first-pass radionuclide angiography to assess the effects of myocardial revascularization on exercise-induced myocardial ischemia. The radionuclide studies were performed in the 30 degree right anterior ablique position, at rest and during exercise, 1 to 3 days preoperatively and 10 to 14 days postoperatively. The mean population age was 53 years; the mean number of grafts placed was 4.0 per patient. Fifteen normal male volunteers were tested by rest and exercise radionuclide angiography to serve as normal control subjects. In all exercise radionuclide studies, progressive upright bicycle exercise was performed to symptoms of fatigue, dyspnea, or chest pain. The parameters of ejection fraction (EF), end-diastolic volume (EDV), and regional wall motion (RWM) were determined. Twenty-nine of the 36 patients had postoperative coronary arteriography that was correlated with radionuclide determinations. The results showed that in the normal subjects with maximal exercise the mean EF rose, the mean EDV increased 19%, and there was no exercise-induced regional wall motion dysfunction (ERWMD). In the patients with coronary artery disease prior to operation, the mean EF fell significantly, the mean EDV rose 24%, and 26 of 36 patients had ERWMD. After operation, the mean EF of the group rose, the EDV increased only 15%, and only two of 36 patients continued to show ERWMD. Of the eight patients who demonstrated on abnormal response postoperatively, seven had what was considered to be inadequate revascularization, and in one there was no explanation. The data demonstrate that myocardial revascularization does improve ventricular function by abolishing exercise-induced evidence of ischemia (decreased EF, increased EDV, and ERWMD) as assessed by radionuclide angiography. Failure to abolish the exercise-induced functional instability suggests incomplete revascularization.