Liposome accumulation in regions of experimental myocardial infarction.

The uptake of liposomes bearing positive, negative, or no net charge on their membrane and containing a radioactive tracer, [99mTc]diethylenetriamine pentaacetic acid, was studied in 12 intact dogs 24 hours after the induction of myocardial infarction, and compared to the relative regional myocardial blood flow determined from radioactive microspheres. Positively charged and neutral liposomes concentrate in infarcted regions against a flow gradient, while negative liposomes are passively distributed according to regional blood flow. Because positively charged and neutral lipisomes concentrate in infarct areas and have the ability to incorporate pharmacologic agents in their aqueous or lipid phase, they may serve as vehicles for drug delivery to infarct zones of low flow.

Regulation by insulin of myocardial glucose and fatty acid metabolism in the conscious dog.

In vivo small doses of insulin inhibit lipolysis, lower plasma FFA, and stimulate glucose disposal. Lowering of plasma FFA, either in the absence of a change in insulin or during combined hyperglycemia and hyperinsulinemia, promotes glucose uptake by heart muscle in vivo. In the isolated perfused heart, large doses of insulin directly stimulate heart glucose uptake. To assess the effect of physiological elevations of plasma insulin upon myocardial glucose and FFA uptake in vivo independent of changes in plasma substrate concentration, we measured arterial and coronary sinus concentrations of glucose, lactate, and FFA, and coronary blood flow in conscious dogs during a 30 min basal and a 2 h experimental period employing three protocols: (a) euglycemic hyperinsulinemia (insulin clamp, n = 5), (b) euglycemic hyperinsulinemia with FFA replacement (n = 5), (c) hyperglycemic euinsulinemia (hyperglycemic clamp with somatostatin, n = 5). In group 1, hyperinsulinemia (insulin = 73 +/- 13 microU/ml) stimulated heart glucose uptake (7.3 +/- 4.4 vs. 28.2 +/- 2.8 mumol/min, P less than 0.002), lowered plasma FFA levels by 80% (P less than 0.05), and decreased heart FFA uptake (28.4 +/- 4 vs. 1.5 +/- 0.9, P less than 0.01). When the fall in plasma FFA was prevented by FFA infusion (group 2), hyperinsulinemia (86 +/- 10 microU/ml) provoked a lesser (P less than 0.05) stimulation of glucose uptake (delta = 8.2 +/- 4.2 mumol/min) than in group 1, and there was no significant change in FFA uptake (25.3 +/- 16 vs. 16.5 +/- 4). Hyperglycemia (plasma glucose = 186 +/- 8 mg/100 ml) during somatostatin infusion resulted in only a small rise in plasma insulin (delta = 12 +/- 7 microU/ml), and although plasma FFA tended to decline, heart glucose uptake did not rise significantly (delta = 5.5 +/- 3.2 mumol/min, P = NS). There was no significant change in coronary blood flow during any of the three study protocols. We conclude that, in the dog, insulin at physiologic concentrations: (a) stimulates heart glucose uptake, both directly and by suppressing the plasma FFA concentration, and (b) does not alter coronary blood flow. Hyperglycemia per se has little effect on heart glucose uptake.

Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.

The regulation of protein metabolism in the human heart has not previously been studied. In 10 postabsorptive patients with coronary artery disease, heart protein synthesis and degradation were estimated simultaneously from the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine (PHE) and the dilution of its specific activity across the heart at isotopic steady state. We subsequently examined the effect of branched chain amino acid (BCAA) infusion on heart protein turnover and on the myocardial balance of amino acids and branched chain ketoacids (BCKA) in these patients. In the postabsorptive state, there was a net release of phenylalanine (arterial-cardiac venous [PHE] = -1.71 +/- 0.32 nmol/ml, P less than 0.001; balance = -116 +/- 21 nmol PHE/min, P less than 0.001), reflecting protein degradation (142 +/- 40 nmol PHE/min) in excess of synthesis (24 +/- 42 nmol PHE/min) and net myocardial protein catabolism. During BCAA infusion, protein synthesis increased to equal the degradation rate (106 +/- 24 and 106 +/- 28 nmol PHE/min, respectively) and the phenylalanine balance shifted (P = 0.01) from negative to neutral (arterial-cardiac venous [PHE] = 0.07 +/- 0.36 nmol/ml; balance = 2 +/- 25 nmol PHE/min). BCAA infusion stimulated the myocardial uptake of both BCAA (P less than 0.005) and their ketoacid conjugates (P less than 0.001) in proportion to their circulating concentrations. Net uptake of the BCAA greatly exceeded that of other essential amino acids suggesting a role for BCAA and BCKA as metabolic fuels. Plasma insulin levels, cardiac double product, coronary blood flow, and myocardial oxygen consumption were unchanged. These results demonstrate that the myocardium of postabsorptive humans is in negative protein balance and indicate a primary anabolic effect of BCAA on the human heart.

Regulation of myocardial amino acid balance in the conscious dog.

The effects in vivo of physiologic increases in insulin and amino acids on myocardial amino acid balance were evaluated in conscious dogs. Arterial and coronary sinus concentrations of amino acids and coronary blood flow were measured during a 30-min basal and a 100-min experimental period employing three protocols: euglycemic insulin clamp (plasma insulin equaled 70 +/- 11 microU/ml, n = 6); euglycemic insulin clamp during amino acid infusion (plasma insulin equaled 89 +/- 12 microU/ml, n = 6); and suppression of insulin with somatostatin during amino acid infusion (plasma insulin equaled 15 +/- 4 microU/ml, n = 6). Basally, only leucine and isoleucine were removed significantly by myocardium (net branched chain amino acid [BCAA] uptake equaled 0.5 +/- 0.2 mumol/min), while glycine, alanine, and glutamine were released. Glutamine demonstrated the highest net myocardial production (1.6 +/- 0.2 mumol/min). No net exchange was seen for valine, phenylalanine, tyrosine, cysteine, methionine, glutamate, asparagine, serine, threonine, taurine, and aspartate. In group I, hyperinsulinemia caused a decline of all plasma amino acids except alanine; alanine balance switched from release to an uptake of 0.6 +/- 0.4 mumol/min (P less than 0.05), while the myocardial balance of other amino acids was unchanged. In group II, amino acid concentrations rose, and were accompanied by a marked rise in myocardial BCAA uptake (0.4 +/- 0.1-2.6 +/- 0.3 mumol/min, P less than 0.001). Uptake of alanine was again stimulated (0.9 +/- 0.3 mumol/min, P less than 0.01), while glutamine production was unchanged (1.3 +/- 0.4 vs. 1.6 +/- 0.3 mumol/min). In group III, there was a 4-5-fold increase in the plasma concentration of the infused amino acids, accompanied by marked stimulation in uptake of only BCAA (6.8 +/- 0.7 mumol/min). Myocardial glutamine production was unchanged (1.9 +/- 0.4-1.3 +/- 0.7 mumol/min). Within the three experimental groups there were highly significant linear correlations between myocardial uptake and arterial concentration of leucine, isoleucine, valine, and total BCAA (r = 0.98, 0.98, 0.92, and 0.97, respectively); P less than 0.001 for each). In vivo, BCAA are the principal amino acids taken up by the myocardium basally and during amino acid infusion. Plasma BCAA concentration and not insulin determines the rate of myocardial BCAA uptake. Insulin stimulates myocardial alanine uptake. Neither insulin nor amino acid infusion alters myocardial glutamine release.

Effect of chronic diabetes on myocardial fuel metabolism and insulin sensitivity.

To assess the effect of chronic insulin-deficient diabetes on myocardial fuel substrate metabolism in vivo, we measured the myocardial balance of glucose, free fatty acids (FFAs), and amino acids in nine postabsorptive conscious dogs 4-6 wk after treatment with streptozocin. The acute effect of insulin on the myocardial balance of these same substrates was measured in six dogs by use of the euglycemic insulin clamp technique. To further examine the effect of insulin on heart amino acid balance, we studied three additional dogs given a constant infusion of amino acids during the insulin clamp to blunt the insulin-induced hypoaminoacidemia. In these dogs, the fasting plasma glucose concentration was markedly elevated (258 +/- 3 mg/dl). In the basal period, there was no significant glucose uptake by the heart [arterial vs. coronary sinus concentration difference (delta) = 1.0 +/- 2.0 mg/dl]; furthermore, physiologic hyperinsulinemia did not stimulate glucose uptake (delta = 2.0 +/- 2.5 mg/dl). Postabsorptively, arterial FFAs were elevated (1550 +/- 320 microM) in diabetic animals, and there was a significant net extraction of FFAs by the heart (net uptake 26 +/- 9 mumol/min; extraction ratio 30 +/- 8%). During the insulin clamp, arterial FFAs declined (645 +/- 240 microM), as did heart FFA uptake (11 +/- 6 mumol/min), and the net extraction ratio for FFAs was unchanged (30 +/- 7%). Similarly, the arterial branched-chain amino acid (BCAA) concentration was elevated in the postabsorptive state, and there was a significant myocardial uptake of these amino acids and of alanine.(ABSTRACT TRUNCATED AT 250 WORDS)

Silent left ventricular dysfunction during routine activity after thrombolytic therapy for acute myocardial infarction.

To investigate prospectively the occurrence and significance of postinfarction transient left ventricular dysfunction, 33 ambulatory patients who underwent thrombolytic therapy after myocardial infarction were monitored continuously for 187 +/- 56 min during normal activity with a radionuclide left ventricular function detector at the time of hospital discharge. Twelve patients demonstrated 19 episodes of transient left ventricular dysfunction (greater than 0.05 decrease in ejection fraction, lasting greater than or equal to 1 min), with no change in heart rate. Only two episodes in one patient were associated with chest pain and electrocardiographic changes. The baseline ejection fraction was 0.52 +/- 0.12 in patients with transient left ventricular dysfunction and 0.51 +/- 0.13 in patients without dysfunction (p = NS). At follow-up study (19.2 +/- 5.4 months), cardiac events (unstable angina, myocardial infarction or death) occurred in 8 of 12 patients with but in only 3 of 21 patients without transient left ventricular dysfunction (p less than 0.01). During submaximal supine bicycle exercise, only two patients demonstrated a decrease in ejection fraction greater than or equal to 0.05 at peak exercise; neither had a subsequent cardiac event. These data suggest that transient episodes of silent left ventricular dysfunction at hospital discharge in patients treated with thrombolysis after myocardial infarction are common and associated with a poor outcome. Continuous left ventricular function monitoring during normal activity may provide prognostic information not available from submaximal exercise test results.

Regional dysfunction by equilibrium radionuclide angiocardiography: a clinicopathologic study evaluating the relation of degree of dysfunction to the presence and extent of myocardial infarction.

The relation of degree of regional wall motion abnormality by equilibrium radionuclide angiocardiography to the presence and mural extent of regional necrosis or scar at autopsy was evaluated in 23 autopsy patients who had a history of myocardial infarction and had equilibrium radionuclide angiocardiography within 40 days of death. Of the 228 regions evaluated by equilibrium radionuclide angiocardiography, 135 had abnormal regional wall motion and 102 (76%) of these 135 regions had evidence of myocardial infarction at autopsy. The overall sensitivity, specificity and predictive values of regional wall motion abnormality for regional necrosis or scar were 69, 59 and 76%, respectively. Of the 33 false positive regions, 20 (61%) had severe narrowing of the coronary artery supplying that region, 13 (39%) were adjacent to a region with a myocardial infarction and almost half (16 [48%]) were in the lateral wall. Eighty-three (36%) of the 228 regions were akinetic or dyskinetic, 52 (23%) were hypokinetic and 93 (41%) were normal. Sixty-three (76%) of the 83 akinetic/dyskinetic segments had transmural myocardial infarction at autopsy, 14 (17%) had nontransmural myocardial infarction and only 6 (7%) contained no necrosis or scar. In contrast, 14 (27%) of 52 hypokinetic segments had transmural myocardial infarction, 11 (21%) had nontransmural myocardial infarction and 27 (52%) were normal. Thus, the most severe regional wall motion abnormality (akinesia/dyskinesia) almost always indicates regional myocardial infarction which is usually transmural whereas less severe dysfunction (hypokinesia) is not necessarily associated with regional necrosis or scar. The severity of regional dysfunction must be considered if equilibrium radionuclide angiocardiography is used to evaluate the presence and mural extent of myocardial infarction within a region.

Relevance of increased lung thallium uptake on stress imaging in patients with unstable angina and non-Q wave myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI)-IIIB Study.

OBJECTIVES: This study sought to determine the significance of abnormal thallium-201 (Tl-201) lung uptake on stress imaging in the absence of perfusion abnormalities. BACKGROUND: Abnormal Tl-201 lung uptake, represented by an increased lung/heart ratio (LHR), on stress imaging is a marker of stress-induced left ventricular dysfunction and poor prognosis in patients with coronary artery disease. METHODS: We evaluate 1,271 patients from the Thrombolysis in Myocardial Infarction (TIMI)-IIIB trial (86% of TIMI-IIIB cohort) with unstable angina or non-Q wave myocardial infarction, who underwent predischarge exercise (92%) or dipyridamole stress (8%) Tl-201 imaging. An increased LHR (> or = 0.50) was related to perfusion abnormalities and adverse cardiac events at 1 year. RESULTS: Of 1,271 patients, there were 762 (60%) with and 509 (40%) without perfusion abnormalities. An increased LHR was seen in 227 patients (18%) (173 [23%] with, 54 [11%] without perfusion abnormalities). Patients with an increased LHR had a lower left ventricular ejection fraction, higher body weight, lower exercise capacity and a higher prevalence of angina on exercise than patients with a normal LHR. In the two groups with increased LHR, there was no difference in age, hypertension, previous myocardial infarction, total exercise time, frequency of angina and ST segment depression on exercise. However, the group with an increased LHR and normal myocardial perfusion had a preponderance of women (65% vs. 30%, p < 0.001). At 1-year follow-up, patients with an increased LHR had a higher cardiac event rate than those with a normal LHR (18% vs. 10%, respectively, p = 0.001) despite a higher revascularization rate (28% vs. 15%, p < 0.001). An increased LHR was associated with increased adverse cardiac events, irrespective of the presence or absence of perfusion abnormalities. CONCLUSIONS: An increased LHR continues to be associated with higher adverse cardiac events in the current era of aggressive interventional management of coronary artery disease. An increased LHR in the absence of myocardial perfusion abnormality is seen mostly in women and overweight patients. However, despite the apparent absence of perfusion abnormalities, an increased LHR in this group is also associated with a higher rate of adverse cardiac events.

Peak filling rate normalized to mitral stroke volume: a new Doppler echocardiographic filling index validated by radionuclide angiographic techniques.

The noninvasive measurement of left ventricular filling has relied predominantly on radionuclide-derived peak filling rate normalized to end-diastolic volume. Doppler echocardiography also has the ability to measure peak filling rate, but wide application of this technique has been limited by technical errors involved in quantitative echocardiographic determination of mitral anulus cross-sectional area and ventricular volumes. For Doppler echocardiography, normalization of peak filling rate to mitral stroke volume rather than end-diastolic volume permits the derivation of a diastolic filling index that is relatively free of errors caused by geometric assumptions, diameter measurements and sample volume positioning. This normalization process can be achieved by simply dividing early peak filling velocity by the time velocity integral of mitral inflow. To validate this new Doppler echocardiographic filling index, Doppler echocardiographic and radionuclide-derived peak filling rate, both normalized to mitral stroke volume, were compared in 30 patients; there was an excellent correlation (r = 0.91, SEE = 0.88). This variable was not influenced by the position of the sample volume in relation to the mitral apparatus in contrast to early filling velocity, which increased 37%, and early/late filling (E/A) ratio, which increased 43% as the sample volume was moved from the anulus to the tips of the mitral leaflets. In a cohort of 22 normal patients, the mean peak filling rate normalized to mitral stroke volume (SV) was 5.25 +/- 1.47 SV/s. The mean peak filling rate for a subgroup of eight normal patients aged 57 to 89 years (mean 71 +/- 9) was 3.9 +/- 1 SV/s.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of behavioral and psychological factors in mental stress-induced silent left ventricular dysfunction in coronary artery disease.

OBJECTIVES: We examined the relationship of the psychological profile to left ventricular dysfunction induced during mental stress. BACKGROUND: The contribution of psychological factors to mental stress-provoked silent myocardial ischemia has not been explored. METHODS: Thirty patients with chronic stable coronary artery disease and a reversible defect on stress thallium-201 imaging completed a psychological assessment by questionnaire and Structured Interview, serially administered mental stress and brief walking exercise. Blood pressure, electrocardiogram (ECG) and left ventricular indexes were obtained by ambulatory serial radionuclide ventriculography. Silent ventricular dysfunction was defined by a decrease > or = 0.05 in ejection fraction or > or = 1 mm in ST segment on the ECG in the absence of symptoms. RESULTS: Of the 30 patients, 15 (Group I) had evidence of silent left ventricular dysfunction during mental arithmetic. The other 15 (Group II) showed no change. In addition, 18 of 30 patients had this dysfunction during the Structured Interview. Both ischemic and nonischemic groups developed comparable and significant increases in heart rate and blood pressure. Group I patients were distinguished by higher scores on measures of aggressive responding (p < 0.001), trait anger (p < 0.0001), hostile affect (p < 0.003) and an index of behavioral reactivity (p < 0.003) and a lower score on anger control (p < 0.001). No other variables, including historical and clinical indexes, discriminated between the two groups. CONCLUSIONS: Patients with coronary artery disease and mental stress-provoked silent ventricular dysfunction were distinguished by a psychological profile consistent with emotional reactivity to social interaction and mental provocation, with anger as the predominant affective state. Patients with such a profile may be at risk of frequent silent left ventricular dysfunction.

Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state.

OBJECTIVES: The present study evaluated our experience with coronary artery bypass grafting in patients with severe left ventricular dysfunction. BACKGROUND: Despite the ominous prognosis of advanced ischemic cardiomyopathy, coronary artery bypass grafting in this setting remains controversial because of concerns over operative risk and lack of functional or survival benefit. METHODS: We analyzed the data of 83 consecutive patients (69 men, 14 women, aged 42 to 83 years [mean 66.8]) with a left ventricular ejection fraction < or = 30% who underwent isolated coronary artery bypass grafting (without aneurysmectomy, valve replacement or other open heart procedures) performed by one surgeon during a 6-year period. The ejection fraction ranged from 10% to 30% (mean 24.6%). Preoperatively, 49% of patients had angina, 52% had congestive heart failure (17% with pulmonary edema) and 30% manifested significant ventricular arrhythmia. The mean number of grafts was 2.7/patient. The internal mammary artery was used in 82% of grafts to the left anterior descending coronary artery. The intraaortic balloon pump was required therapeutically (for angina or pump failure) in 19% of patients and was prophylactically placed preoperatively in another 43% of patients. RESULTS: The hospital mortality rate was 8.4% (7 of 83). The mortality rate was 3.3% (2 of 61) in those patients who did not require admission to an intensive care unit immediately before operation. Canadian Cardiovascular Society angina class improved postoperatively by 1.9 categories and New York Heart Association congestive heart failure class by 1 category. Left ventricular ejection fraction (assessed postoperatively in 68 of 76 hospital survivors) improved from 24.6% preoperatively to 33.2% postoperatively (36% increase) (p < 0.001). At 1 and 3 years, respectively, all-cause survival was 87% and 80% and freedom from cardiac death was 89.8% and 84.5%. CONCLUSIONS: In patients with coronary artery disease and advanced ventricular dysfunction: 1) coronary artery bypass grafting can be performed relatively safely, 2) good medium-term survival is attained, 3) improvement in left ventricular function can be documented objectively after bypass grafting, 4) quality of life is improved (as reflected by improvement in anginal and congestive heart failure status), and 5) the internal mammary artery can safely be used as a conduit. The use of coronary artery bypass grafting is encouraged for this group of patients and may provide a viable alternative to transplantation in selected patients.

Thallium-201 for assessment of myocardial viability: quantitative comparison of 24-hour redistribution imaging with imaging after reinjection at rest.

Redistribution thallium-201 imaging 2 to 4 h after exercise may be incomplete and therefore may be inadequate to fully assess myocardial variability. Late redistribution imaging 24 h after exercise has been proposed to overcome this limitation of thallium stress imaging. However, because of poor count density the image quality on these studies is often suboptimal. In the present study the diagnostic information on 24-h planar thallium redistribution images was compared with that on images obtained after a reinjection of thallium at rest. Eighty-four patients with a stress thallium-201 defect had delayed redistribution imaging after 2 to 4 h and 24 h later, and again after an injection of thallium at rest. Defect reversibility on 24-h redistribution images was compared quantitatively with that on images after injection of thallium at rest. The quality of thallium images at rest was consistently better than that of 24-h redistribution images. Poor quality studies occurred in 13% of 24-h redistribution images compared with 0.4% of the studies at rest. Significantly more defect reversibility was detected on images after the reinjection at rest. Of 41 patients who appeared to have a fixed defect at 2- to 4-h redistribution imaging, 11 (27%) had a reversible defect by 24-h redistribution imaging compared with 29 (71%) after thallium-201 reinjection. No clinical variables at the time of stress testing were predictive of late defect reversibility. It is concluded that in patients with fixed a thallium defect at 2 to 4 h after exercise, reimaging after a reinjection at rest provides better diagnostic information than does 24-h late redistribution imaging.

Effects of mental stress on left ventricular and peripheral vascular performance in patients with coronary artery disease.

OBJECTIVES: We sought to investigate the mechanism of a mental stress-induced fall in left ventricular ejection fraction (LVEF) in patients with coronary artery disease. BACKGROUND: Mental stress induces a fall in LVEF in a significant proportion of patients with coronary artery disease. This is accompanied by an increase in heart rate, blood pressure and rate-pressure product. Whether the mental stress-induced fall in LVEF is due to myocardial ischemia, altered loading conditions or a combination of both is not clear. METHODS: Left ventricular (LV) function was studied noninvasively by serial equilibrium radionuclide angiocardiography and simultaneous measurement of peak power, a relatively afterload-independent index of LV contractility, in 21 patients with coronary artery disease (17 men, 4 women) and 9 normal subjects (6 men, 3 women) at baseline, during mental stress and during exercise. Peripheral vascular resistance (PVR), cardiac output (CO), arterial and end-systolic ventricular elastance (Ea, Ees,) and ventriculoarterial coupling (V/AC) were also calculated. Patients underwent two types of mental stress-mental arithmetic and anger recall-as well as symptom-limited semisupine bicycle exercise. RESULTS: Nine patients (43%) had an absolute fall in LVEF of > or = 5% (Group I) in response to at least one of the mental stressors, whereas the remaining patients did not (Group II). Group I and Group II patients were similar in terms of baseline characteristics. Both groups showed a significant but comparable increase in systolic blood pressure (15+/-7 vs. 9+/-10 mm Hg, p=0.12) and a slight increase in heart rate (7+/-4 vs. 8+/-7 beats/min, p=0.6) and a comparable increase in rate-pressure product (2.2+/-0.9 vs. 1.9+/-1.2 beats/min x mm Hg, p=0.6) with mental stress. However, PVR increased in Group I and decreased in Group II (252+/-205 vs. -42+/-230 dynes x s x cm(-5), p=0.006), and CO decreased in Group I and increased in Group II (-0.2+/-0.4 vs. 0.6+/-0.7 liters/min, p=0.02) with mental stress. There was no difference in the change in peak power (p=0.4) with mental stress. With exercise, an increase in systolic blood pressure, heart rate, rate-pressure product and CO and a fall in PVR were similar in both groups. Of the two mental stressors, anger recall resulted in a greater fall in LVEF and a greater increase in diastolic blood pressure. Exercise resulted in a fall in LVEF in 7 patients (33%). However, exercise-induced changes in LVEF and hemodynamic variables were not predictive of mental stress-induced changes in LVEF and hemodynamic variables. Conclusions. Abnormal PVR and Ea responses to mental stress and exercise are observed in patients with a mental stress-induced fall in LVEF. Peripheral vasoconstrictive responses to mental stress contribute significantly toward a mental stress-induced fall in LVEF.

Regional myocardial dysfunction during coronary angioplasty: evaluation by two-dimensional echocardiography and 12 lead electrocardiography.

Balloon inflation performed during percutaneous transluminal coronary angioplasty causes transient total occlusion of the coronary artery and thus provides a model for evaluation of the regional myocardial responses to transient ischemia. Twenty patients with normal left ventricular function undergoing angioplasty of isolated stenosis of the proximal left anterior descending coronary artery were studied. In group A (14 patients) analysis of one inflation-deflation sequence per patient was performed. Group B (six patients) had multiple (greater than 5) inflations; the first and last sequences were analyzed. Assessment included continuous two-dimensional echocardiography with computerized quantitative analysis of regional left ventricular wall motion, and continuous 12 lead electrocardiographic recordings. The mean duration of inflation in group A was 62 +/- 6 seconds (mean +/- SD). The onset of regional left ventricular dysfunction was 12 +/- 5 seconds after inflation. Profound dysfunction was noted in all patients. After 60 seconds of balloon occlusion of the coronary artery, 29% of patients had severe hypokinesia of the ischemic region and 71% had akinesia or dyskinesia. With deflation there was prompt recovery of regional function, with full recovery at 43 +/- 17 seconds. Comparison of data from first and last inflations in group B revealed no significant differences in time to onset of dysfunction, magnitude of dysfunction or time to complete recovery of function. The onset of ischemic electrocardiographic changes lagged behind the onset of wall motion abnormalities, with only 64% of patients showing evidence of ischemia on 12 lead electrocardiograms at 20 seconds of inflation. After 60 seconds, 86% had ischemia detectable by electrocardiography. Thus, balloon inflation during coronary angioplasty leads to profound but reversible regional left ventricular dysfunction. Repeated occlusions of the coronary artery during angioplasty do not have a cumulative ischemic effect. It may be hazardous to apply these findings to patients who have underlying major left ventricular dysfunction and in whom the reversibility of dysfunction and lack of cumulative ischemic effect may not be assured.

Use of nonionic or low osmolar contrast agents in cardiovascular procedures. American College of Cardiology Cardiovascular Imaging Committee.

Low osmolar contrast agents produce less adverse electrophysiologic and hemodynamic alterations during cardiac catheterization. The nonionic agents probably reduce the risk of provoking myocardial ischemia during coronary arteriography or ventriculography. Patients also report less subjective sensation of discomfort during administration of low osmolar agents for cardiovascular procedures. However, nonionic agents have not been proved to reduce the incidence of several serious complications of cardiac catheterization, including acute renal failure and anaphylactoid reaction. Although evidence is inconclusive, there may be an increased risk of thromboembolic complications during cardiac catheterization when certain low osmolar nonionic agents are administered. Nonionic contrast agents have not been definitely proved to reduce the risk of death after cardiac catheterization.

Quantitative radionuclide assessment of regional ventricular function after thrombolytic therapy for acute myocardial infarction: results of phase I Thrombolysis in Myocardial Infarction (TIMI) trial.

In Thrombolysis in Myocardial Infarction (TIMI) Phase I,290 patients with acute myocardial infarction were randomized to either intravenous recombinant tissue-type plasminogen activator (rt-PA) or intravenous streptokinase. Two hundred twenty-nine patients had radionuclide ventriculograms at discharge for assessment of global and regional left ventricular ejection fraction. Among these 229 patients 185 had totally occluded infarct-related arteries, and angiographic reperfusion of the infarct-related artery occurred in 69% of patients treated with rt-PA and 28% of patients treated with streptokinase (p less than 0.001). Mean global left ventricular ejection fraction was not different for rt-PA-treated patients compared with streptokinase-treated patients (0.46 versus 0.45). However, the average regional ejection fraction of the regions subtended by the infarct-related artery showed a trend toward better average infarct region ejection fraction in patients treated with rt-PA than in patients treated with streptokinase (0.40 versus 0.36; 0.05 less than p less than 0.06). Analysis of data according to perfusion status of the infarct-related artery showed no difference in mean global left ventricular ejection fraction between patients with sustained versus nonsustained reperfusion (0.47 versus 0.44). However, there was better average regional ejection fraction of the region subtended by the infarct-related artery in patients with sustained reperfusion (0.40 versus 0.36; p less than 0.01). Thus, quantitation of regional left ventricular function by radionuclide techniques provides a noninvasive means for evaluating the effects of thrombolysis. This study suggests a direct relation between improvement of regional left ventricular function and the greater infarct-related artery patency rate achieved by rt-PA compared with streptokinase.

Serial quantitative planar technetium-99m isonitrile imaging in acute myocardial infarction: efficacy for noninvasive assessment of thrombolytic therapy.

Technetium-99m isonitrile is a new myocardial perfusion imaging agent that accumulates according to the distribution of myocardial blood flow. However, unlike thallium-201, it does not redistribute over time. This imaging agent was used with serial quantitative planar imaging to assess the initial risk area of infarction, its change over time and the relation to infarct-related artery patency in 30 patients with a first acute myocardial infarction. Twenty-three of 30 patients were treated with recombinant tissue-type plasminogen activator (rt-PA) within 4 h after the onset of chest pain. Seven patients were treated in the conventional manner without thrombolytic therapy. Technetium-99m isonitrile was injected before or at the initiation of thrombolytic therapy, and imaging was performed several hours later. These initial images demonstrated the area at risk. Repeat imaging was performed 18 to 48 h later and at 6 to 14 days after the onset of myocardial infarction to visualize the ultimate extent of infarction. The initial area at risk varied greatly (range defect integral 2 to 61) both in patients treated with rt-PA and in those who received conventional treatment. For the total group, the initial imaging defect decreased in size in 20 patients and was unchanged or larger in 10 patients. Patients with a patent infarct-related artery had a significantly greater decrease in defect size than did patients with persistent coronary occlusion (-51 +/- 38% versus -1 +/- 26%, p = 0.0001). All patients with a decrease in defect size greater than 30% had a patent infarct-related artery. In 12 patients who also had predischarge quantitative exercise thallium-201 imaging, good agreement existed between the extent and severity of myocardial perfusion defect on the last technetium-99m isonitrile study before discharge and that noted on delayed thallium-201 imaging. It is concluded that serial planar technetium-99m isonitrile myocardial imaging in patients with acute myocardial infarction undergoing thrombolytic therapy offers a new quantitative noninvasive approach for assessment of the initial risk zone as well as the success of reperfusion.

Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis in Myocardial Infarction (TIMI) phase II study. The TIMI Study Group.

OBJECTIVES: This study sought to determine the prognostic value of rest and exercise left ventricular ejection fraction in patients receiving thrombolytic therapy as part of the Thrombolysis in Myocardial Infarction (TIMI) trial. BACKGROUND: In the prethrombolytic era, ejection fraction at rest as well as during exercise was an important prognostic index in patients recovering from acute myocardial infarction. The prognostic value of these measurements in the thrombolytic era is not clear. METHODS: As part of the TIMI II protocol, we obtained radionuclide left ventricular ejection fraction at rest and during symptom-limited submaximal supine exercise. Measurements were related to 1-year all-cause as well as cardiac mortality. In addition, the relation between ejection fraction obtained at rest and 1-year cardiac mortality in this study was compared with the relation established previously in the prethrombolytic era by the Multicenter Postinfarction Research Group. RESULTS: A distinct relation was noted between left ventricular ejection fraction at rest and all-cause mortality. The highest mortality rate (9.9%) was noted in patients with an ejection fraction < 30%. Those not undergoing a study had a 1-year mortality rate of 6.2%. Peak exercise ejection fraction provided prognostic information similar to that of rest ejection fraction. Likewise, change in ejection fraction from rest to exercise did not appreciably improve prognostic impact. CONCLUSIONS: Rest left ventricular ejection fraction is an important prognostic index in patients receiving thrombolytic therapy. Peak exercise ejection fraction and the change in ejection fraction from rest to exercise do not provide appreciable prognostic data beyond those obtained at rest. Patients unable to exercise or those not having a rest study have a poor prognosis. When compared with the Multicenter Postinfarction Research Group data, there was strong evidence of a difference in survival in the two studies. At any level of ejection fraction, mortality was lower in TIMI II patients than in patients in the prethrombolytic era.

Gold-195m for serial first pass radionuclide angiocardiography during upright exercise in patients with coronary artery disease.

Sequential first pass radionuclide angiocardiography can be performed in rapid succession using gold-195m because of its low radiation dose and short half-life (30.5 seconds). In 25 patients with known or suspected coronary artery disease, first pass studies with gold-195m were obtained using a computerized multicrystal gamma camera at rest (n = 29), at the end of each 3 minute stage of exercise (n = 25) and immediately after exercise (n = 23). In 13 patients, assessment of left ventricular function during exercise with gold-195m was combined with thallium-201 stress scintigraphy. Left ventricular ejection fraction at rest assessed with technetium-99m and gold-195m correlated well (r = 0.93). In addition, repeat left ventricular ejection fractions at rest with gold-195m correlated closely (r = 0.96). Comparing peak exercise left ventricular ejection fraction with ejection fraction at rest, abnormal left ventricular reserve was found in 20 of 25 patients. Various abnormal patterns of left ventricular ejection fraction response were noted, showing the diagnostic potential of serial exercise angiocardiography. Thallium-201 myocardial images, obtained on a single crystal gamma camera after multiple gold-195m injections, were all of good diagnostic quality and were abnormal in 10 of 13 patients. Thus, multiple high count rate first pass studies can be obtained with gold-195m during and after exercise, allowing serial study of physiologic changes in left ventricular function during exercise. Thallium-201 myocardial imaging can be performed using the same exercise test, providing direct comparison of myocardial function and perfusion.

Myocardial risk area defined by technetium-99m sestamibi imaging during percutaneous transluminal coronary angioplasty: comparison with coronary angiography.

OBJECTIVES: The purpose of this study was to compare the assessment of myocardial area at risk in patients with coronary artery stenosis by coronary angiography and quantitative myocardial perfusion imaging with technetium-99m sestamibi. BACKGROUND: Decisions concerning patient management frequently rely on semiquantitative angiographic estimation of the myocardial area at risk, although this approach has not been well validated. Technetium-99m sestamibi is a perfusion imaging agent with little redistribution after initial myocardial uptake. This characteristic allows for injection during angioplasty and later imaging for visualization and quantitation of the nonperfused area at risk. METHODS: Thirty-nine patients referred for coronary angioplasty were studied. Technetium-99m sestamibi was injected intravenously during angioplasty balloon inflation. Planar (33 patients) or tomographic (6 patients) imaging was performed after completion of angioplasty. Imaging was repeated 24 to 48 h later. Myocardial risk area (perfusion defect on angioplasty image) was quantified as an integral using circumferential count distribution profiles and normal reference. Angiographic risk area was assessed using five scoring methods. RESULTS: The scintigraphic risk area was 14 +/- 15 on planar images and 39 +/- 16 on tomography. Scintigraphic risk area of patients with infarction was larger than in patients without (22 +/- 17 versus 7 +/- 8, p = 0.003). The left anterior descending coronary artery had a larger mean risk area than other vessels (22 +/- 15 versus 7 +/- 11, p = 0.002). The presence of angiographic collateral channels was associated with smaller risk areas. Angiographic risk scores correlated only moderately with the technetium-99m sestamibi risk area (r = 0.54 to 0.65), with considerable spread of data. CONCLUSIONS: Area at risk estimated from coronary angiography does not correlate well with that from quantitative myocardial perfusion imaging with technetium-99m sestamibi. These findings emphasize that the functional significance of coronary artery disease is not predicted by coronary anatomy alone.