Effects of isosorbide dinitrate on exercise capacity in cardiac patients--relationship between oxygen uptake responses and hemodynamic effects

Acute effects of oral isosorbide dinitrate on exercise capacity were evaluated in 14 patients with chronic heart disease measuring the anaerobic threshold and left ventricular function during exercise. A symptom-limited exercise test was performed on a bicycle ergometer with work rates increased by 1W every 6 seconds. Left ventricular function was continuously monitored with a computerized cadmium telluride detector following the intravenous injection of technetium-labeled red blood cells. Thirty minutes after the control exercise test, patients were given isosorbide dinitrate, 5 mg orally. The second exercise test was performed 30 min later. Isosorbide dinitrate improved the anaerobic threshold from 715.4 +/- 172.9 to 774.9 +/- 173.5 ml/min (p less than 0.01) and ejection fraction at peak exercise from 36.7 +/- 11.6 to 39.9 +/- 12.3% (p less than 0.05). However, there was no significant change in maximum work rate or peak oxygen uptake. Those patients for whom isosorbide dinitrate resulted in a 10% or greater improvement in the anaerobic threshold had both higher pre-treatment ejection fractions and greater increases in peak exercise ejection fraction following isosorbide dinitrate. Measurements of the anaerobic threshold and left ventricular function during exercise may be useful in the evaluation of the efficacy of vasodilators in cardiac patients.     

Acute changes in global and regional rest left ventricular function after successful coronary angioplasty: comparative results in stable and unstable angina

The immediate effects of successful percutaneous transluminal coronary angioplasty on global and regional left ventricular function were assessed by comparing 30 degrees right anterior oblique left ventricular angiograms performed immediately before and after angioplasty on 39 patients undergoing 42 successful procedures. Mean (+/- SD) lesion stenosis decreased from 88 +/- 10% to 35 +/- 11% (p less than or equal to 0.001), whereas left ventricular ejection fraction increased from 57 +/- 11% to 64 +/- 10% (p less than or equal to 0.001) for the entire group. Left ventricular functional changes were further subgrouped according to stability of angina. Eighteen procedures were performed on 17 patients with stable angina: 24 procedures were performed on 22 patients with unstable angina defined as angina at rest or on minimal activity or recently accelerated angina. There were no significant subgroup differences in mean age, gender ratio, vessel anatomy, drug therapy or extent of coronary stenosis before or after angioplasty. Global ejection fraction increased significantly for the unstable group (from 54 +/- 11% to 66 +/- 9%, p less than or equal to 0.001) but was unchanged for the stable group (from 61 +/- 9% to 61 +/- 11%, p = NS). In unstable angina, regional ejection fraction (segmental area method) increased for both jeopardized (from 37 +/- 11% to 52 +/- 9%, p less than or equal to 0.001) and nonjeopardized myocardial segments (from 43 +/- 13% to 51 +/- 13%, p less than or equal to 0.001), but improvement was significantly (p less than or equal to 0.02) greater in jeopardized segments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Silent myocardial ischemia: hemodynamic changes during dynamic exercise in patients with proven coronary artery disease despite absence of angina pectoris

The hemodynamic changes during exercise occurring in 36 patients with proven coronary artery disease (10 without and 26 with previous myocardial infarction) who tolerated the stress test without angina were analyzed and compared with changes observed in a control group of 36 carefully matched patients whose exercise was limited by angina. All patients were exercised to the same extent, reaching a similar rate-pressure product at the end of the stress test (19,508 +/- 4,828 [SD] versus 19,247 +/- 4,117 beats/min X mm Hg [NS] in the study and control groups without prior infarction, and 19,665 +/- 3,950 versus 17,701 +/- 4,600 beats/min X mm Hg [NS] in the respective groups with infarction). In all groups left ventricular end-diastolic pressure increased from rest to exercise (from 18 +/- 4 to 36 +/- 11 and from 13 +/- 5 to 29 +/- 9 mm Hg, respectively, in the study and control groups without prior infarction and from 17 +/- 7 to 32 +/- 13 and from 19 +/- 7 to 36 +/- 9 mm Hg in the respective groups with prior infarction). Left ventricular ejection fraction decreased (from 59 +/- 7 to 50 +/- 15 and from 60 +/- 4 to 52 +/- 9% in the study and control groups without prior infarction and from 54 +/- 9 to 47 +/- 10 and 55 +/- 9 to 50 +/- 4% in the respective groups with prior infarction). Whereas the changes from rest to exercise were highly significant within each group, no significant differences were noted between the corresponding groups. Regional de novo hypokinesia appeared in all patients without prior infarction and in 25 and 22 patients, respectively, of the groups with prior infarction. Thus, under similar physical stress conditions, comparable hemodynamic changes indicative of ischemia are observed in patients with significant coronary artery lesions with or without previous myocardial infarction irrespective of the occurrence of angina. Therefore, angina pectoris cannot be considered a prerequisite for hemodynamically significant ischemia during exertion.     

Clinical response and effects on left ventricular function of isosorbide dinitrate added to propranolol or diltiazem monotherapy in patients with chronic stable angina

Twenty-four patients were randomized to a double-blind, triple placebo controlled, latin square protocol to examine the relative efficacy of propranolol or diltiazem given as monotherapy or in combination with isosorbide dinitrate. Treatment phases were preceded and followed by placebo control periods. At the end of each phase, symptom-limited treadmill exercise stress tests were performed, as well as rest and exercise radionuclide ventriculography. Both forms of monotherapy were effective in reducing episodes of angina and nitroglycerin use, and in improving exercise tolerance. Diltiazem monotherapy was associated with slightly higher treadmill times (509.9 +/- 123 s) compared to propranolol (462.7 +/- 131 s, P less than 0.05). The addition of isosorbide dinitrate to either form of monotherapy allowed no further improvement in any of the measured clinical responses. Radionuclide ventriculography showed no significant difference in resting left ventricular function. The addition of isosorbide dinitrate to propranolol showed a reduction in end diastolic volume in keeping with a reduction in preload. In response to exercise, stress-induced left ventricular dysfunction was equal in all groups except for the diltiazem-nitrate combination, which was associated with a higher ejection fraction (56.2 +/- 8.6%) compared to monotherapy (52.6 +/- 10.9%, P less than 0.01). A higher cardiac output could be achieved in the groups treated with diltiazem; this was related to increased heart rate and maintenance of stroke volume. It was concluded that diltiazem is equally effective as propranolol for the treatment of chronic stable angina and, in terms of exercise capacity and cardiac output, superior to beta-blockade. The addition of isosorbide dinitrate appears to impart no overt benefits, but some evidence suggests a reduction in left ventricular decompensation in the face of stress.     

Left ventricular wall motion at rest in patients with organic coronary artery disease vs coronary spasm

Left ventricular ejection fractions and regional ejection changes obtained from left ventriculograms at rest were analyzed in 15 normal subjects, in 17 patients with isolated, organic left anterior descending coronary artery disease, and in 11 patients with isolated left anterior descending coronary artery spasm. Patients with coronary artery spasm did not have significant organic lesions at the site of spasm. All patients with organic coronary artery disease and coronary artery spasm had a history of angina pectoris without myocardial infarction. No significant differences in ejection fraction were observed among the three groups. The regional ejection change of the anterolateral and apical wall supplied by the left anterior descending coronary artery was significantly decreased in patients with organic coronary artery disease compared with those in normal subjects (anterolateral 39.5 +/- 10.3% vs 48.4 +/- 7.7%, p less than 0.05; apical 48.4 +/- 8.8% vs 55.6 +/- 7.8%, p less than 0.05). However, the anterolateral and apical wall motion was not impaired in patients with coronary artery spasm. Thus, patients with organic coronary artery disease had impairment of left ventricular wall motion, while those with coronary artery spasm did not, although both groups of patients had symptoms of angina. These results suggest that patients with organic coronary artery disease may have had coronary blood flow disturbances through stenosed vessels and chronic active ischemia that produced left ventricular impairment.     

Global and regional left ventricular ejection fraction abnormalities during exercise in patients with silent myocardial ischemia

Sixteen asymptomatic patients with coronary artery disease and silent myocardial ischemia were studied with exercise radionuclide ventriculography. Radionuclide ventriculograms were analyzed for changes in ejection fraction globally and in three regions. Results were compared with radionuclide ventriculograms in 24 symptomatic patients. Both groups (silent myocardial ischemia and angina) were similar in prevalence of multivessel disease and previous myocardial infarction, as well as in age and sex. Global ejection fraction decreased by 0.06 in both groups during exercise; regional ejection fraction also decreased by similar amounts in the two groups. Furthermore, the percent of regions with normal ejection fraction at rest that demonstrated a decrease during exercise was identical: 19 (60%) of 33 versus 26 (60%) of 46. These exercise radionuclide ventriculographic results suggest that abnormalities in regional and global left ventricular wall motion are similar in patients with coronary artery disease with and without silent myocardial ischemia.     

Resistance to isosorbide dinitrate in patients with severe chronic heart failure: incidence and attempt at hemodynamic prediction

Oral isosorbide dinitrate has been widely used to lower elevated left ventricular filling pressure in patients with chronic heart failure. Although the recommended dose of this drug is 40 mg every 6 h, failure to respond to this dose has been observed in many patients with heart failure. In the present study the incidence of resistance to isosorbide dinitrate was evaluated and an attempt was made to identify baseline hemodynamic predictors for this phenomenon in 50 patients with severe chronic heart failure due to left ventricular systolic dysfunction (mean left ventricular ejection fraction 0.23 +/- 0.08). Twenty-seven (54%) of the 50 patients responded to 40 mg of isosorbide dinitrate (greater than 20% decrease in mean pulmonary artery wedge pressure sustained greater than or equal to 1 h) and 23 patients (46%) failed to respond. Nonresponders to 40 mg of isosorbide dinitrate had a significantly higher baseline right atrial pressure than did responders (14 +/- 5 versus 10 +/- 6 mm Hg, p less than 0.02). In addition, all 7 patients with a baseline right atrial pressure of less than 7 mm Hg and 12 of 14 patients with a baseline right atrial pressure less than 10 mm Hg responded to 40 mg. No significant differences were noted between responders and nonresponders in any other baseline hemodynamic or clinical variables, or in peak isosorbide dinitrate serum levels (32 +/- 19 ng/ml in nonresponders versus 44 +/- 36 ng/ml in responders). Of the 23 nonresponders to 40 mg, 22 received a higher dose (80 to 120 mg).(ABSTRACT TRUNCATED AT 250 WORDS)     

External,noninvasive cardiac assistance and nitrate administration for patients with unstable angina pectoris or acute coronary insufficiency

The influence of external, noninvasive counterpulsation, alone and in combination with sublingual nitroglycerin or isosorbide dinitrate, on left ventricular volumes and ejection fractions was investigated. Patients with unstable angina pectoris or acute coronary insufficiency were selected for this evaluation. Left ventricular volumes and ejection fractions were estimated using a gated blood pool scintigraphic technique. Twenty minutes of external counterpulsation did not significantly alter left ventricular end-diastolic volumes, end-systolic volumes, or ejection fractions in 13 patients. When sublingual isosorbide dinitrate (10 mg.) was combined with 20 minutes of external counterpulsation in eight patients, left ventricular end-diastolic volumes decreased 16 ± 7 per cent (p = .05), but neither left ventricular end-systolic volumes (12 ± 7 per cent) nor ejection fractions were significantly changed. When sublingual nitroglycerin (0.4 mg.) was combined with 15 minutes of external counterpulsation in three patients, left ventricular end-diastolic volumes decreased 21 ± 3 per cent (p < .01), end-systolic volumes decreased 25 ± 4 per cent (p < .02), and ejection fractions were not significantly changed. When left ventricular volumes and ejection fractions were measured 30 and 65 minutes after isosorbide dinitrate administration, 10 and 45 minutes after cessation of external counterpulsation, respectively, left ventricular end-diastolic volumes and end-systolic volumes were significantly decreased by approximately 20 per cent while ejection fractions were unchanged. When left ventricular volumes and ejection fractions were measured 25 minutes after nitroglycerin administration, 10 minutes after cessation of external counterpulsation, end-systolic volumes decreased 23 ± 2 per cent (p < .005) and end-diastolic volumes decreased 27 ± 3 per cent (p < .005). No significant changes in left ventricular end-diastolic or end-systolic volumes were seen 60 minutes after nitroglycerin administration. As in the other studies, left ventricular ejection fractions were unchanged. The results suggest that relatively short periods of external, noninvasive cardiac assistance do not alter left ventricular volumes or ejection fractions in patients with unstable angina pectoris or acute coronary insufficiency. Although external counterpulsation combined with a vasodilator such as isosorbide dinitrate or nitroglycerin decreases left ventricular volumes, it offers no advantage over vasodilator treatment alone.     

The effect of coronary artery bypass grafting on left ventricular systolic function at rest: evidence for preoperative subclinical myocardial ischemia

Successful coronary artery bypass grafting (CABG) improves exercise-induced left ventricular (LV) dysfunction in patients with coronary artery disease (CAD), but its potential for improving resting LV function remains controversial. To assess the influence of CABG on LV function at rest, 31 CAD patients without previous myocardial infarction were studied before and 6 months after CABG by radionuclide angiography after all cardiac medicines were withdrawn. No patient had angina or ischemic electrocardiographic changes at rest. In 27 patients with patent bypass grafts, CABG significantly increased LV ejection fraction during exercise (47 +/- 11% before to 63 +/- 9% after operation, p less than 0.001), indicating reduction in exercise-induced LV ischemia. Moreover, LV ejection fraction at rest also increased (55 +/- 9 to 60 +/- 8%, p less than 0.001), with 20 of 27 patients manifesting an increase compared with preoperative values. Eleven of these 20 patients had apparently normal LV function at rest (ejection fraction and regional wall motion) before CABG. LV regional ejection fraction was computed by dividing the LV region of interest into 20 sectors. Regional analysis indicated that improved ejection fraction at rest after CABG occurred in regions developing ischemia during exercise before CABG. In 4 patients with occluded grafts, the ejection fraction at rest was unchanged by CABG globally (59 +/- 8 to 58 +/- 9%, difference not significant) and regionally. Thus, LV global and regional function at rest improved after successful CABG, even in patients with normal global LV ejection fraction and no visually detectable wall motion abnormality before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of nitroglycerin, nifedipine and metoprolol on regional left ventricular function in patients with one-vessel coronary disease

To compare acute effects of nitroglycerin (0.8 mg sublingually), nifedipine (5 ng/kg/min i.v.) and metoprolol (0.15 mg/kg i.v.) on normal, ischemic and scarred myocardial segments in man, we performed simultaneous hemodynamic and radionuclide measurements of left ventricular functions. Sixteen patients with isolated left anterior descending (LAD) disease were studied at rest and during exercise. Nine patients had angina and exercise-induced ischemia (LAD stenosis) and seven patients had previous transmural myocardial infarction and no ischemic changes during thallium imaging (LAD occlusion). The effects of the drugs on regional ejection fraction of the involved anteroseptal region and the normal posterolateral area were compared. Global ejection fraction at rest did not change after nitroglycerin, increased after nifedipine and decreased after metoprolol. In patients with ischemia, the exercise ejection fraction improved after all drugs due to increased regional ejection fraction in ischemic segments: i.e., a regional antiischemic effect evidenced by improved regional function could be demonstrated with all three agents. Regional ejection fraction increased from 35.8 +/- 19.5% to 66.2 +/- 15.2% (+/- SD) after nitroglycerin (p less than 0.001), to 61.7 +/- 8.7% after nifedipine (p less than 0.001), and to 48.4 +/- 7.0% after metoprolol (p less than 0.01). In regions of myocardial scar, regional ejection fraction was not changed after any drug. In normal areas, regional ejection fraction remained unchanged after nitroglycerin and nifedipine, but decreased after metoprolol. Despite similar antiischemic effects of all three drugs, underlying hemodynamic mechanisms were quite different and may provide a rationale for combined forms of treatment. These results may help to select optimal drug combinations to improve myocardial performance in patients with chronic ischemic heart disease.     

Vasodilator therapy in acute myocardial infarction. Use of sublingual isosorbide dinitrate.

The haemodynamic effect of a long-acting vasodilator isosorbide dinitrate has been studied in 10 patients after an acute myocardial infarct, all of whom had evidence of left ventricular failure. Left ventricular filling pressure measured as the mean pulmonary artery wedge pressure was raised in all patients and fell significantly from 20+/-6 to 13+/-5 mmHg (P less than 0-001) within 10 minutes of sublingual isosorbide dinitrate. This 35 per cent fall in left ventricular preload was accompanied by significant fall in mean pulmonary artery pressure from 30+/-7 to 20+/-4 mmHg (P +less than 0-001) and mean right atrial pressure from 11+/-3 to 6+/-2 mmHg but cardiac output measured by thermodilution was unchanged. Mean systemic blood pressure was also significantly reduced. This improvement in left ventricular performance resulting from a reduction in left ventricular filling pressure and systemic blood pressure indicates that there may be a place for long-acting vasodilator in the treatment of acute myocardial infarction.     

Left ventricular diastolic properties and filling characteristics during spontaneous angina pectoris at rest

Diastolic left ventricular (LV) properties were studied at rest and during spontaneous angina pectoris during cardiac catheterization in 10 patients with severe coronary artery disease. During spontaneous angina there was a significant increase in LV filling pressures through diastole. The right ventricular end-diastolic pressure was measured at rest and during spontaneous angina in 7 of 10 patients and showed an increase from 7 +/- 3 to 10 +/- 4 mm Hg (mean +/- SD) (p less than 0.02). The T index (a measure of LV isovolumic relaxation) at rest was 51 +/- 17 ms and increased during angina to 58 +/- 12 ms (p less than 0.01), indicating an early diastolic relaxation dysfunction. Frame-by-frame LV volumes and corresponding pressures were analyzed from 3 consecutive beats in 5 of 10 patients. In 4 of these 5, the pressure-volume loop shifted upward and slightly to the right during angina. There was a significant increase in the rate of filling during mid-diastole with angina. Left atrial stroke work index increased by 35% during angina, suggesting an increased work load on the left atrium to maintain late diastolic filling.     

Comparison of nifedipine and isosorbide dinitrate when added to maximal propranolol therapy in stable angina pectoris

A study was performed to compare isosorbide dinitrate and nifedipine as adjunctive therapy in 14 patients with coronary artery disease and stable angina pectoris taking maximal beta-blocking drugs. Drug titration phases ensured maximal therapy of propranolol, isosorbide or nifedipine. The combination of nifedipine and propranolol was more effective than the combination of isosorbide and propranolol in reducing angina and increasing exercise capacity (323 vs 416 seconds, p less than 0.005) during exercise treadmill testing. Nifedipine produced a greater reduction in systolic blood pressure at submaximal exercise than isosorbide. Global and regional ejection fraction at rest and exercise was assessed with radionuclide ventriculography. The substitution of nifedipine for isosorbide depressed the global ejection fraction at rest (0.61 to 0.56 p less than 0.05) and produced a slight improvement in exercise ejection fraction (0.47 to 0.51, difference not significant). The decrease in ejection fraction from rest to exercise was 0.14 to 0.04 with nifedipine (p less than 0.005). The benefit of nifedipine compared with isosorbide occurred in regions with marked exercise-induced ischemia. In patients treated with maximal beta-blocking therapy, nifedipine is an effective alternative to isosorbide as a combination agent with propranolol. The salutary effects of nifedipine included afterload reduction with exercise and possible improvements in coronary blood supply.     

Effects of isosorbide dinitrate on the response to atrial pacing in coronary heart disease.

To study the efficacy of isosorbide dinitrate in prevention of myocardial ischemia, 20 patients with angiographically proved coronary artery disease underwent atrial pacing (mean rate 138/min) before (P1), 10 minutes after (P2) and 65 minutes after (P3) sublingual administration of 5 mg of isosorbide dinitrate. The symptomatic, hemodynamic and metabolic responses were evaluated at rest and during each pacing period. Angina occurred in all subjects during P1. Angina did not recur or was less severe in 17 of 19 patients during P2 and in 19 of 20 patients during P3. Resting left ventricular end-diastolic pressure for the group was normal at 11 plus or minus 4 mm Hg (mean plus or minus standard deviation). On interruption of pacing at 4.5 minutes during P1, average end-diastolic pressure during sinus rhythm was abnormal (18 plus or minus 6 mm Hg). After administration of isosorbide dinitrate mean left ventricular end-diastolic pressure was significantly decreased at rest and remained normal when pacing was interrupted during P2 and P3. Brachial arterial pressure, cardiac index, tension-time index, left ventricular stroke work index and maximal rate of rise of left ventricular pressure were all diminished at rest before and during P2 and P3. S-T segment depression was less during P2 and P3 than during P1. Before isosorbide dinitrate was given, resting myocardial lactate extraction was 15 plus or minus 11 percent during P1 lactate extraction decreased to minus2 plus or minus 25 percent. Lactate extraction was significantly greater during P2 and P3 than during P1. This study demonstrates that sublingual administration of 5 mg of isosorbide dinitrate has a significant protective effect against pacing-induced myocardial ischemia at 10 and 65 minutes after administration.     

Effects of digoxin on left ventricular function in coronary artery disease patients

To assess whether digitalis modifies or prevents the deterioration of the left ventricular ejection fraction and wall motion during acute ischemia, we performed gated blood pool radionuclide ventriculograms in 15 patients with angiographically documented coronary artery disease. All patients were studied in the resting state and during maximal supine bicycle exercise, both before and 1 hour after 1 mg intravenous digoxin.There was no significant difference, pre-digoxin vs post-digoxin, in exercise tolerance (415 ± 84 vs 418 ± 107 seconds), number of segments with abnormal resting wall motion (12 vs 11) or exercise wall motion (21 vs 19). Ten patients developed angina during the same exercise load, irrespective of digoxin administration. Twelve patients had subnormal left ventricular ejection fraction during exercise pre-digoxin, vs 13 patients post-digoxin (P = ns). In the resting state, the left ventricular ejection fraction was higher after digoxin (53 ± 14% pre vs 58 ± 14% post, P < 0.05). During exercise, however, the left ventricular ejection fraction was not significantly improved after digoxin (50 ± 16% pre vs 53 ± 17% post, P = ns).These data indicate that although acute administration of digoxin improves the resting left ventricular function, it does not improve exercise tolerance to angina. Furthermore, intravenous digoxin does not appear to prevent the deterioration of left ventricular wall motion and ejection fraction during exercise induced ischemia.     

Global and regional left ventricular response to bicycle exercise in coronary artery disease. Assessment by quantitative radionuclide angiocardiography.

The left ventricular response to bicycle exercise was evaluated in 60 patients with coronary artery disease and in 13 normal control subjects. Left ventricular ejection fraction, mean normalized ejection rate and regional wall motion were determined using first-pass radionuclide angiocardiograms obtained at rest and again during peak graded bicycle exercise. All normal subjects demonstrated improved left ventricular function with exercise. Left ventricular ejection fraction increased significantly from 67 ± 3 per cent (mean ± SE) at rest to 82 ± 4 per cent with exercise (p < 0.001). Similarly, the left ventricular ejection rate increased significantly from 3.47 ± 0.31 sec^?1 to 6.53 ± 0.42 sec^?1(p < 0.001). In contrast, in 44 of 60 patients with coronary artery disease, the ejection fraction or ejection rate either decreased or remained the same with exercise. New or exaggerated regional wall motion abnormalities were detected in 28 of 60 patients with coronary artery disease. Over-all, global or regional evidence of compromised left ventricular reserve was found in 48 of 60 patients with coronary artery disease.The major determinant of an abnormal left ventricular response to exercise was the presence or absence of electrocardiographic evidence of myocardial ischemia. Left ventricular ejection fraction decreased or remained the same with exercise in all patients with coronary artery disease and electrocardiographic ischemia. New regional wall motion abnormalities were detected in 20 of these patients. In this group, the left ventricular ejection fraction decreased from 66 ± 2 per cent at rest to 58 ± 2 per cent with exercise (p < 0.001), whereas the ejection rate was unchanged by exercise (rest 3.33 ± 0.21 sec^?1; exercise 3.34 ± 0.22 sec^?1, p > 0.05). Of the 30 patients with coronary artery disease who exercised to symptom-limiting fatigue without electrocardiographic ischemia, 18 demonstrated compromised left ventricular reserve with exercise. Twelve of the remaining patients with coronary artery disease had normal left ventricular reserve, in eight of whom ventricular function was completely normal both at rest and during exercise. In this group exercised to fatigue, the left ventricular ejection fraction increased from 53 ± 4 per cent at rest to 58 ± 2 per cent with exercise (p < 0.001). The ejection rate also increased from 2.48 ± 0.24 sec^?1 to 3.67 ± 0.39 sec^?1 (p < 0.001). The direction and magnitude of the left ventricular responses to exercise were not affected by long-term oral propranolol administration in 22 patients. Based upon either abnormal exercise left ventricular reserve or abnormal global and regional left ventricular function at rest, the over-all sensitivity of this radionuclide technic for the detection of coronary artery disease was 87 per cent (52 of 60 patients). These data demonstrate that exercise ventricular performance studies provide important physiologic insights into left ventricular functional reserve as well as a sensitive noninvasive approach for the detection of coronary artery disease.     

Effects of propranolol and timolol on left ventricular volumes during exercise in patients with coronary artery disease

The hemodynamic effects of beta-receptor blocking agents on the ejection fraction of patients with coronary artery disease during exercise have been studied previously using radionuclide techniques. Left ventricular volume measurements and the peak systolic pressure/end-systolic volume (PSP/ESV) index have been shown to be variables of left ventricular function that are less influenced by preload and afterload than is ejection fraction. Left ventricular volumes and PSP/ESV were therefore measured in 18 patients with proven coronary artery disease in the control state and after 2 weeks of daily maintenance therapy with either 240 mg propranolol or 60 mg timolol. Values at rest and during symptom-limited upright exercise were compared using the first pass technique and a multicrystal scintillation camera. Left ventricular volumes were measured by the area-length method. Because there was no difference between the propranolol and timolol groups, the results for both groups were combined. The ejection fraction at rest after beta-receptor blocker treatment was not significantly different from pretreatment measurements because of an increase in both end-diastolic and end-systolic volumes (p less than 0.01). However, the value for peak systolic pressure/end-systolic volume (PSP/ESV) index at rest was lower after treatment. The exercise ejection fraction was greater after treatment (p less than 0.01), owing to an increase in end-diastolic volume and unchanged end-systolic volume. In addition, there was a significant improvement in the directional change in the PSP/ESV ratio between rest and exercise from pretreatment to treatment (-1.1 +/- 2.5 to +0.2 +/- 1.2, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

药物负荷超声心动图检测心功能减低者存活心肌

目的评价小剂量多巴酚丁胺、硝酸异山梨酯单用及合用的二维超声心动图(2DE)检测冠心病左心室收缩功能严重减低患者存活心肌的安全性和准确性。方法对40例陈旧性心肌梗死拟接受冠状动脉血运重建术患者进行多巴酚丁胺(3、5、10μg·kg-1·min-1)、硝酸异山梨酯及两药合用的负荷2DE检测。结果硝酸异山梨酯与多巴酚丁胺(3、5μg·kg-1·min-1)合用无诱发心肌缺血,检测敏感性和准确性均较两者单用时显著提高(P值均<0·05),且副作用发生率显著降低(P<0·05)。硝酸异山梨酯+多巴酚丁胺5μg·kg-1·min-12DE的敏感性、特异性和准确性均达多巴酚丁胺10μg·kg-1·min-12DE水平。多巴酚丁胺10μg·kg-1·min-1可诱发心肌缺血。结论多巴酚丁胺5~10μg·kg-1·min-12DE检测左心室收缩功能严重减低患者存活心肌效果较好,但可诱发心肌缺血。硝酸酯与多巴酚丁胺合用能提高检测敏感性和准确性,且更安全。     

Left ventricular aneurysm and congestive heart failure: Value of exercise stress and isosorbide dinitrate in predicting hemodynamic results of aneurysmectomy

In 12 patients with left ventricular aneurysm and chronic congestive heart failure, left ventricular functional reserve was assessed from the hemodynamic response to exercise stress after administration of isosorbide dinitrate. Two to 23 months (mean 8.6 months) after left ventricular aneurysmectomy hemodynamic measurements were made with the patient at rest and during exercise and were analyzed with respect to preoperative data. Left ventricular aneurysmectomy reduced mean left ventricular filling pressure from 25 to 17 mm Hg at rest (p < 0.02) and from 39 to 32 mm Hg during exercise (p < 0.05). There was no significant change in mean stroke volume index at rest or during exercise.Changes in resting and exercise hemodynamic indexes of left ventricular function produced by aneurysmectomy were inversely related to preoperative left ventricular function. Hence, hemodynamic status was less likely to improve In patients with good preoperative left ventricular function. Similarly, resting and exercise values for left ventricular function tended to improve in patients with reduced ejection fraction of the contractile section of the left ventricle. Left ventricular aneurysmectomy was generally effective in reducing left ventricular filling pressure but failed to achieve clinically important improvement in left ventricular performance during exercise. In patients with chronic congestive heart failure, left Ventricular aneurysmectomy should be performed only after careful assessment of preoperative left ventricular functional reserve.     

Nonischemic changes in right ventricular function on exercise. Do normal volunteers differ from patients with normal coronary arteries?

Factors other than ischemia may alter right ventricular function both at rest and on exercise. Normal volunteers differ from cardiac patients with normal coronary arteries with regard to their left ventricular response to exercise. This study examined changes in right ventricular function on exercise in 21 normal volunteers and 13 patients with normal coronary arteries, using first-pass radionuclide angiography. There were large ranges of right ventricular ejection fraction in the two groups, both at rest and on exercise. Resting right ventricular ejection fraction was 40.2 +/- 10.6% (mean +/- SD) in the volunteers and 38.6 +/- 9.7% in the patients, p = not significant, and on exercise rose significantly in both groups to 46.1 +/- 9.9% and 45.8 +/- 9.7%, respectively. The difference between the groups was not significant. In both groups some subjects with high resting values showed large decreases in ejection fraction on exercise, and there were significant negative correlations between resting ejection fraction and the change on exercise, r = -0.59 (p less than 0.01) in volunteers, and r = -0.66 (p less than 0.05) in patients. Older volunteers tended to have lower rest and exercise ejection fractions, but there was no difference between normotensive and hypertensive patients in their rest or exercise values. In conclusion, changes in right ventricular function on exercise are similar in normal volunteers and in patients with normal coronary arteries. Some subjects show decreases in right ventricular ejection fraction on exercise which do not appear to be related to ischemia.