Comparison of the results and reproducibility of arm and leg exercise tests in men with angina pectoris

The results and reproducibility of arm and leg exercise tests were compared in 11 men with angina pectoris induced by both forms of testing. Leg testing was performed using a bicycle ergometer; arm testing was performed using the same apparatus modified to permit arm cranking. Subjects performed 2 days of arm and 2 days of leg testing over a 2 week period. Four tests were performed on each test day. The duration of exercise, oxygen uptake, heart rate, systolic and diastolic blood pressures and the rate-pressure product were determined at the onset of angina. Within day and between day coefficients of variation were low and similar for arm and leg tests, indicating that both forms of testing are highly reproducible. Performing four tests on a single day did little to reduce variability. Oxygen uptake increased between the first and second arm or leg test on a single day, but there was little change after the second test. Repetition of the arm and leg tests did not affect performance over the study period.It is concluded that the reproducibility of arm exercise testing in men with angina pectoris is comparable with that of leg exercise. Subjects with angina induced by arm exercise who cannot perform leg testing can be evaluated and followed up with arm exercise tests.     

Production of a critical coronary arterial stenosis in closed chest laboratory animals: Description of a new nonsurgical method based on standard cardiac catheterization techniques

A nonsurgical method for producing a critical coronary arterial stenosis in a closed chest laboratory animal would enhance our ability to study the effects of reversible myocardial ischemia on many aspects of left ventricular function and also would facilitate experiments aimed at studying the effects of various interventions on regional myocardial blood flow distal to a severe stenosis. Accordingly, a new technique was developed for the production of a critical coronary arterial lesion in a closed chest laboratory animal. Under fluoroscopic control a small plastic truncated cone (5 mm long, outside diameter 3.5 mm tapering to 3.25 mm) with a narrow, central internal lumen (diameter 0.625 mm) was passed over a guide wire into the left anterior descending coronary artery of a closed chest, heparinized pig (n = 6). Regional myocardial blood flow (microsphere technique) distal to the artificial stenosis (distal zone) and in myocardium perfused by the circumflex coronary artery was determined under the following conditions: at rest (control I), at the 10th minute of atrial pacing (190 min^?1) and 10 to 15 minutes after discontinuation of pacing (control II). At rest, transmural blood flow distal to the stenosis (1.29 ± 0.32 ml/min per g, mean ± standard deviation) was almost identical to that in the circumflex zone (1.31 ± 0.31, r = 0.93, p < 0.01). During atrial pacing transmural flow increased significantly (p < 0.01 versus control) in the circumflex zone (1.73 ± 0.27) and then returned to control value (1.34 ± 0.38) after pacing was discontinued. In contrast, transmural flow in the distal zone (1.45 ± 0.40) failed to increase significantly with pacing. In addition, during atrial pacing the endocardial to epicardial blood flow ratio distal to the stenosis decreased from 0.99 ± 0.13 (control I) to 0.68 ± 0.14 (p < 0.01), whereas it remained unchanged in the circumflex zone (1.1 ± 0.11 to 1.1 ± 0.08, difference not significant). Finally, the artificial intraluminal stenosis remained patent for the duration of the study (5.1 ± 0.05 hours) in all animals. Thus the intracoronary plastic stenosis is a promising new method for the production of a critical coronary arterial lesion in closed chest laboratory animals.     

Efficacy of repeat percutaneous transluminal coronary angioplasty for coronary restenosis

The short- and long-term outcome of patients within the NHLBI PTCA Registry who underwent repeat PTCA for coronary restenosis were analyzed. Of 1,880 patients in whom an initial PTCA was successful, 203 had a repeat PTCA attempted after restenosis developed. Repeat PTCA was usually performed within 6 months of the first procedure. The success rate of repeat PTCA was 85.2%. As a direct result of repeat PTCA, 1.5% of patients had an MI and 2% required emergency CABG. No patien died as a result of the attempted second procedure. One to 3 years of follow-up information was available in 94% of eligible patients. Most patients (75,9%) did not have a subsequent (third) PTCA, CABG or an MI. The late mortality rate was 0.8%. Angiographic follow-up information was available in 62 patients. Sustained enhancement of the diameter of the redilated lesion was observed in 66%. Thus, repeat PTCA has a high success and a low complication rate. Most patients did not have subsequent restenosis and are free of angina. Hence, repeat PTCA should be recommended for patients who have restenosis and should be considered as an integral component of PTCA therapy.     

Acute coronary occlusion in the pig: Effect of nitroglycerin on regional myocardial blood flow

Myocardial blood flow was studied in 10 closed chest, anesthetized pigs after an acute balloon catheter occlusion of the left anterior descending coronary artery. With use of radioactive microspheres (15 μ), myocardial blood flow was measured before and during an intravenous nitroglycerin infusion and during a combined nitroglycerin-phenylephrine infusion. A significant zone of ischemia (myocardial blood flow less than 50 percent of normal zone flow) was produced by the occlusion and involved 15 percent of the combined left ventricular and interventricular septal mass. More than 50 percent of this ischemic zone was intensely ischemic (myocardial blood flow 0 to 3 percent of normal). Nitroglycerin resulted in a 20 to 30 mm Hg decrease in systolic blood pressure. Myocardial blood flow was unchanged in intensely ischemic areas but varied directly with the product of heart rate and systolic blood pressure in the moderately ischemic area (myocardial blood flow 26 to 50 percent of normal). S-T segment elevation was significantly increased during nitroglycerin infusion and returned to control level with the added infusion of phenylephrine sufficient to restore the systemic blood pressure to prenitroglycerin values. No improvement in ischemic zone perfusion could be demonstrated during the infusion of nitroglycerin alone or with phenylephrine. The endocardial/epicardial flow ratio in moderately ischemic areas was slightly lower than the normal zone flow ratio and decreased slightly during infusion of nitroglycerin. With the addition of phenylephrine, the ratios rose slightly and no longer differed from prenitroglycerin values.

Blood flow distribution in acutely ischemic pig myocardium differs considerably from that observed in the dog. Nitroglycerin was not shown to have any beneficial effects with or without its relative hypotensive effect. More extensive study in animal models other than the dog is needed.     

Coronary circulatory dynamics before and after successful coronary angioplasty

The hypothesis that successful percutaneous transluminal coronary angioplasty restores normal coronary circulatory dynamics was tested. Regional coronary blood flow, myocardial oxygen consumption and lactate extraction were measured at rest and during sustained pacing tachycardia. Before angioplasty, tachycardia stress was associated with an attenuated blood flow and oxygen consumption response and the induction of anaerobic metabolism. After successful angioplasty, blood flow and myocardial oxygen consumption increased during tachycardia stress and aerobic metabolism was sustained. The influence of basal alpha-adrenergic tone in modifying the time course of blood flow response to abrupt pacing was also assessed. Patients with normal coronary arteries demonstrated delayed increase in blood flow after alpha-adrenergic blockade. Alpha-adrenergic blockade did not affect the time course of blood flow response in patients with coronary artery disease, suggesting that alpha-adrenergic tone was chronically withdrawn. In patients undergoing coronary angioplasty, flow response before angioplasty was delayed, consistent with withdrawal of basal alpha-adrenergic tone. After coronary angioplasty, a brisk flow response was observed, indicating that basal alpha-adrenergic tone had been restored. Thus, successful coronary angioplasty restores the normal responsiveness of the coronary circulation.     

Effect of intraaortic balloon counterpulsation on regional myocardial blood flow and oxygen consumption in the presence of coronary artery stenosis: Observations in an awake animal model

The mechanism by which intraaortic balloon pumping ameliorates myocardial ischemia in patients with unstable angina pectoris is uncertain. Accordingly, the following study was performed to determine the effect of intraaortic balloon pumping on regional myocardial blood flow and myocardial oxygen consumption (MVO₂) distal to severe coronary artery stenosis. Nine closed chest conscious pigs were instrumented with a 7.5 mm long plastic stenosis which reduced vessel diameter by 82%. Measurements of hemodynamics, regional myocardial blood flow (microsphere technique) and MVO₂ were made (1) before intraaortic balloon pumping, (2) at the end of 15 to 20 minutes of intraaortic balloon pumping, and (3) 20 minutes after its discontinuation.Control endocardial blood flow (ml · min^{? 1} · g^{? 1}) distal to the stenosis (1.04 ± 0.20, mean ± 1 standard deviation [SD]) was less than endocardial flow in myocardium perfused by the unobstructed circumflex coronary artery (1.67 ± 0 0.77, p < 0.01). Likewise, control distal zone epicardial flow (1.16 ± 0.36) was reduced in comparison with control circumflex zone epicardial flow (1.48 ± 0.60, p < 0.01In response to intraaortic balloon pumping rate-pressure product declined versus control (10,300 ± 2,090 [SD] mm Hg · min^{? 1} to 9,110 ± 2,010, p < 0.005), whereas aortic mean diastolic pressure (mm Hg) increased versus control (109.0 ± 9.9 to 121.0 ± 13.8, p < 0.01). Distal coronary mean diastolic pressure did not change in response to intraaortic balloon pumping (61.9 ± 13.0 to 68.7 ± 16.5, p = NS). Likewise, endocardial blood flow (ml · min^{? 1} · ^{? 1}) distal to the stenosis did not change during intraaortic balloon pumping (1.00 ± 0.24) versus control (1.04 ± 0.20). In contrast, during intraaortic balloon pumping epicardial blood flow distal to the stenosis declined versus control (1.16 ± 0.36 to 1.01 ± 0.27, p < 0.05). Regional MVO₂ (ml · min^{? 1} · 100 g^{? 1}) distal to the stenosis also decreased versus control in response to intraaortic balloon pumping (12.90 ± 3.55 to 10.30 ± 2.52, p < 0.05). Furthermore, regional MVO₂ correlated well (r = 0.74, p < 0.002) with rate-pressure product.Thus, intraaortic balloon pumping reduces myocardial oxygen demand but does not improve blood flow distal to a severe coronary stenosis; (2) blood flow distal to a severe stenosis may fail to increase with intraaortic balloon pumping because (A) distal coronary mean diastolic pressure may not increase, and (B) blood vessels distal to the stenosis tend to autoregulate in response to a decline in myocardial oxygen demand; and (3) intraaortic balloon pumping ameliorates myocardial ischemia in patients with unstable angina pectoris primarily by reducing oxygen demand rather than by increasing oxygen supply.     

Unreliability of exercise-induced R wave changes as indexes of coronary artery disease

To investigate the diagnostic value of exercise-related QRS amplitude changes, the responses of 40 young normal subjects and 28 patients with chest pain and no significant coronary arterial obstruction were compared with those of 73 patients with coronary arterial narrowing of various degrees of severity. All underwent submaximal, multiple lead multistaged treadmill exercise testing. The combined normal group showed an average decrease in R wave amplitude between rest and exercise of 1.1 ± 2.8 mm (mean ± standard deviation) in lead V₅; those with coronary artery disease had an increase of 0.6 ± 3.4 mm (P = 0.001). Similar but less pronounced differences were observed in lead II (a decrease of 1.9 ± 2.3 mm in normal subjects versus a decrease of 0.5 ± 3.1 mm in those with coronary disease, P = 0.01). When derived R wave criteria were used, the test sensitivity averaged 52 percent and the specificity 63 percent; these values were inferior to the sensitivity of 88 percent and specificity of 72 percent of S-T segment criteria in the same group of patients. No significant relation was found between the extent of coronary artery disease and R wave changes, and an analysis of multiple variables suggested possible correlations with factors not directly related to ischemia. It is concluded that exercise-induced QRS amplitude changes are unreliable predictors of the presence, absence or severity of coronary artery disease.     

Lack of ouabain effect on pacing-induced myocardial ischemia in patients with coronary artery disease

Sixteen patients with significant two and three vessel coronary artery disease but without clinical congestive heart failure were studied during rapid atrial pacing before and after infusion of 0.015 mg/kg of ouabain. Seven patients with a decreased (less than 50 percent) election fraction and nine patients with a normal election fraction had a significant (P < 0.05) increase in resting arterial systolic pressure after the administration of ouabain. However, resting values for coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and myocardial lactate extraction did not change significantly in either group. During pacing, patients with a decreased ejection fraction demonstrated more ischemia than patients with a normal ejection fraction; however, the administration of ouabain did not significantly alter pacing-related changes in coronary sinus flow, myocardial oxygen consumption, myocardial lactate extraction, ischemic electrocardiographic changes or onset of chest pain in either group. The administration of ouabain has a negligible effect on coronary hemodynamics, myocardial metabolism or clinical signs of ischemia in patients with coronary artery disease with normal or abnormal left ventricular function.     

Coronary flow limitation during the development of ischemia: Effect of atrial pacing in patients with left anterior descending coronary artery disease

Atrial pacing-induced tachycardia causes increased myocardial oxygen demand and leads to the development of angina in patients with significant coronary arterial narrowing, when the ability to augment coronary flow is limited. This study evaluated the response of coronary flow in a single coronary bed as that bed was rendered ischemic by progressive increases in oxygen demand. Thermodilution measurements of great cardiac vein flow, representing the efflux from the territory of the left anterior descending coronary artery, were obtained in 20 patients as heart rate was increased by incremental atrial pacing until the maximal heart rate was reached or angina developed. Ten of the 20 patients had no significant coronary narrowing on angiography, and 10 had a lesion obstructing more than 50 percent of the diameter of the left anterior descending coronary artery but no other significant coronary narrowing. No significant difference was found between the two groups in resting heart rate, aortic pressure, left ventricular end-diastolic pressure or great cardiac vein flow. With each increment in heart rate throughout the pacing test, the patients without significant coronary stenosis showed a steady increase in great cardiac vein flow. During all submaximal pacing increments, the increase in great cardiac vein flow per increment in heart rate was similar in those with and without significant stenosis (mean ± standard deviation 1.05 ± 0.48 ml/beat versus 0.79 ± 0.31 ml/beat, respectively). However, over the final pacing increment, the patients with coronary stenosis had no increase in great cardiac vein flow, whereas those without disease continued to have increased flow (Δ = 0.10 ± 0.19 ml/beat versus 1.3 ± 0.69 ml/beat, respectively, p < 0.001). This flow limitation phenomenon was observed in all 10 patients with coronary stenosis and was accompanied by angina or S-T segment changes, or both, in all 10. This striking difference in coronary flow patterns between patients with and without significant left anterior descending coronary artery disease may prove useful in (1) further studies of the pathophysiology and therapy of myocardial ischemia in human beings, and (2) clinical evaluation of the hemodynamic importance of left anterior descending coronary arterial lesions in selected patients.     

Left ventricular volumes and function during atrial pacing in coronary artery disease: A radionuclide angiographic study

This study set out to determine the pathophysiologic changes in the left ventricle during atrial pacing in 22 patients with coronary artery disease. Graduated right atrial pacing to a rate of 160 beats/min, or the induction of angina pectoris or significant ST depression was undertaken. Ventricular volumes were measured at rest and at rates of 100, 120, 140 and 160 beats/min using radionuclide angiography. The volumes at a pacing rate of 100 beats/min were used as a reference standard (100%). In the 22 patients with coronary artery disease, left ventricular end-diastolic volume decreased from 118 ± 3% at rest to 80 ± 5% at a rate of 160 beats/min; stroke volume from 121 ± 3% to 54 ± 5%; and ejection fraction (EF) from 49 ± 3% to 37 ±5%. End-systolic volume decreased from 118 ± 4% at rest, reached its minimal value of 94 ± 5% at a rate of 120 beats/min and then increased slightly to 106 ± 9% at 160 beats/min. Cardiac output and blood pressure did not change significantly. Compared to the control group of 10 normal subjects, the patients had a significantly smaller decrease in end-diastolic volume and end-systolic volume than in normal control subjects. EF in the normal subjects did not change. Blood pressure, cardiac output and stroke volume were similar in both groups. Atrial pacing tachycardia induced reversible ventricular dysfunction with a decrease in EF. Stroke volume was maintained because of relative ventricular dilatation.     

Exercise-induced coronary spasm with S-T segment depression and normal coronary arteriography

The unique association of both exercise-induced coronary arterial spasm and S-T segment depression with normal findings on selective coronary arterlography is described. The patient had a prior history of typical effort angina that had recently progressed to angina at rest. Despite the change In anginal pattern, the electrocardiogram disclosed S-T segment depression that was consistent with subendocardial Ischemia, during both exercise testing and spontaneous chest pain. Exercise thallium-201 sclntigraphy demonstrated the presence of large perfusion defects of the anterior and septal walls of the left ventricle. Coronary arteriographie findings, in the absence of symptoms, were entirely normal. Severe localized, reversible coronary spasm of the proximal left anterior descending coronary artery was subsequently demonstrated during spontaneous angina, Isometric arm exercise and after the administration of ergonovine maleate. After treatment with isosorblde dlnitrate and nifediplne, the patient had no further chest pain or electrocardiographic changes, and a repeated thallium-201 stress test revealed nomal findings and greatly Improved exercise tolerance.     

Comparison of the multivariate analysis and CADENZA systems for determination of the probability of coronary artery disease

The accuracy of 2 discriminate systems for diagnosis of coronary artery disease (CAD), multivariate analysis (MVA) and Bayesian analysis (CADENZA), was evaluated in 113 patients undergoing electrocardiographic stress testing and coronary angiography. MVA uses weighting factors (F values) generated from our patient data, whereas CADENZA uses probabilities gleaned from an extensive review of the American literature. Overall accuracy was similar. MVA had a higher sensitivity for 1-vessel CAD (75 versus 33%), but CADENZA was better for determining the severity of CAD. The 2 systems provided posterior probabilities for disease that were highly correlated (r = 0.56; p less than 0.001). Both systems suggest the need for further testing based on the probability generated; herein lies their major strength. The application of such systems should help the clinician reach a diagnosis or make a decision as to management in a cost-effective manner.     

Effective treatment of supraventricular arrhythmias with acebutolol.

To evaluate the antiarrhythmic efficacy of the new beta adrenergic blocking agent acebutolol, 15 monitored patients with supraventricular arrhythmias received, in double-blind fashion, an intravenous infusion of either acebutolol or saline solution after a control period. Patients treated with saline solution demonstrated no change (P greater than 0.05) in heart rate or arterial blood pressure or conversion to sinus rhythm. After administration of acebutolol, significant (P less than 0.05) reductions in heart rate were noted at 5 minutes. Peak reduction occurred at 10 to 30 minutes and correlated with maximal acebutolol plasma concentrations, antiarrhythmic activity persisted for 24 hours. Mild reductions in systolic blood pressure were observed in the majority of patients. Two patients with atrial fibrillation and one with multifocal atrial tachycardia had conversion to sinus rhythm. Frequent premature atrial complexes noted in one patient were greatly suppressed after administration of the drug. In the nine patients with clinical evidence of chronic obstructive lung disease acebutolol was well tolerated. Adverse reactions were limited to transient dyspnea in one patient with prior heart failure and a decrease in systolic blood pressure to less than 90 mm Hg in three patients who remained asymptomatic. In the patients studied, acebutolol was an effective agent for the treatment of supraventricular arrhythmias and appeared to be of special value in those with chronic obstructive lung disease.     

Methionine intolerance: a possible risk factor for coronary artery disease

Homocystinuria, an inherited disorder associated with premature atherosclerosis, represents a severe form of methionine intolerance. To analyze the importance of milder forms of methionine intolerance in the genesis of vascular disease, the relation between provokable methionine intolerance and coronary artery disease was investigated. In a group of 138 men, aged 31 to 65 years (mean 53), referred for cardiac catheterization, plasma homocystine was measured before and 6 hours after an oral l-methionine load (0.1 g/kg). Thirty-nine subjects found to have normal coronary arteries had a mean post-load plasma homocystine level of 0.59 +/- 0.37 mumol/liter. A criterion at the 95th percentile (1.64 SD above the mean) was selected and applied to the remaining 99 subjects with coronary artery disease (0.70 +/- 0.68 mumol/liter). Sixteen (16%) of 99 subjects with coronary artery disease exceeded this level as compared with 1 (2%) of 39 subjects without coronary artery disease (p less than 0.04). The risk of coronary artery disease in men with provokable methionine intolerance was increased sevenfold as estimated by the odds ratio. By correlation matrix and multivariate regression analyses, provokable homocystinemia was predictive of coronary artery disease and was independent of tobacco smoking, hypertension, diabetes mellitus, serum cholesterol and age. It is proposed that men with mild methionine intolerance exposed to the high methionine content of the Western diet may develop intermittent homocystinemia and thus may be at greater risk for the development of coronary artery disease.     

Echocardiographic features of congenital mitral stenosis

The effects of 1 hour of occlusion of the left anterior descending coronary artery and subsequent reperfusion were studied for 3 hours in anesthetized closed chest pigs using an intracoronary balloon occluding technique. In 12 pigs subjected to reperfusion, S-T segment elevation decreased to control levels within 30 minutes and was significantly less than in 10 control pigs without reperfusion (P < 0.05). R wave amplitude was unaffected by the reperfusion. The more rapid fall of S-T segments in the reperfused group was accompanied by major hemorrhage in all reperfused hearts; hemorrhage occurred in only one control heart. The extent of hemorrhage was quantified and was significantly greater in the reperfused than in the control group (P < 0.01). Hemorrhage after reperfusion was unaffected by mannitol-induced increase in serum osmolallty but was greatly decreased by limitation of the occlusion period to 15 minutes. Myocardial wall motion was quantified angiographljcally. Shortening fraction of the area of the left ventricle most severely affected by occlusion decreased to similar levels in both groups. After reperfusion it remained similar in both groups at three hours. Adjacent left ventricular areas were likewise unaffected by reperfusion.This study thus documents the occurrence of postreperfusion myocardial hemorrhage in an animal with a coronary circulation similar to man's. Hemorrhage is directly related to the duration of occlusion but appears to be unaffected by mannitol given before reperfusion. Caution is advised both during bypass surgery, in which occlusion and reperfusion occur, and In efforts to restore coronary blood flow during acute myocardial infarction.     

Failure of hyaluronidase to alter the early course of acute myocardial infarction in pigs

The effect of hyaluronidase on the early course of acute myocardial infarction was evaluated in closed chest anesthetized pigs. One hour after balloon catheter occlusion of the left anterior descending coronary artery, hyaluronidase (500 units/kg body weight) was rapidly infused in 10 animals while 9 received no treatment. The animals were then observed over the next 4 hours. Cardiac output, heart rate, mean arterial pressure and left atrial pressure were not significantly affected by treatment. Heart rate increased and arterial pressure decreased in each group to a comparable degree by 5 hours, but left atrial pressure and cardiac output were unaffected.Precordial S-T segment mapping revealed no significant difference between the two groups. S-T segments rose to a comparable degree in each group and peaked before 1 hour. Hyaluronidase had no acute effects on the S-T segment map in the first 30 minutes after infusion or during the subsequent return of the map toward control level. Slightly lower S-T segments in the hyaluronidase-treated group at 5 hours was of borderline significance but was attributed to factors other than the drug intervention. Changes in ventricular wall motion were assessed angiographically, and all animals manifested akinetic or dyskinetic segments. A significant reduction in shortening fraction of involved segments was seen after occlusion, but no difference was observed between the two groups at 5 hours. Shortening fraction of the combined anterior and anteroapical segments decreased from 66 ± 10 to 20 ± 6 percent at 5 hours in the hyaluronidase group (no. = 7) whereas in the control group (no. = 6) it decreased from 68 ± 6 to 28 ± 9 percent. Comparable increases in end-dlastolic volume were also present at 5 hours in each group. Volumes increased from 80.6 ± 5.1 to 97.5 ± 6.4 ml³ at 5 hours (P < 0.05) in the hyaluronidase-treated group (no. = 10) compared with 86.9 ± 8.9 to 104.8 ± 11.0 ml³ (P < 0.05) in the control group (no. = 8).Hyaluronidase did not alter the early course of acute myocardial infarction in pigs. Species differences may contribute to different results reported to date.     

Enhanced transcardiac I-norepinephrine response during cold pressor test in obstructive coronary artery disease

An increase in cardiac sympathetic activity can enhance coronary vasomotor tone and lower the ventricular fibrillation threshold. We compared the transcardiac I-norepinephrine responses during cold pressor test of 20 patients with normal coronary arteries with those of 23 patients with obstructive coronary artery disease. Baseline hemodynamic data did not differ in the 2 patient groups except for left ventricular end-diastolic pressures; mean values (± standard deviation ¦SD¦) were 10 ± 3.7 and 15 ± 4.5 mm Hg in patients with normal and abnormal coronary arteries (p < 0.01). Baseline I-norepinephrine contents averaged 295 ± 152 (normal coronary arteries) and 250 ± 134 pg/ml (coronary artery disease) in the arterial blood, and 273 ± 152 and 250 ±115 pg/ml, respectively, in the coronary sinus blood. Hemodynamic responses during cold stimulus were similar in both groups. Also, cold pressor-induced increases in arterial and coronary sinus I-norepinephrine contents were balanced in patients with normal coronary arteries, averaging 19 ± 30 and 17 ± 37%, respectively. In patients with coronary artery disease, however, a 26 ± 58% increase in arterial I-norepinephrine contents was associated with a 58 ± 62% increase in coronary sinus I-norepinephrine contents (p < 0.02), suggesting myocardial I-norepinephrine net release. It is concluded that transcardiac I-norepinephrine responses during cold stimulus are enhanced in patients with obstructive coronary artery disease. This response to a relatively mild sympathetic stress, reproducible by a variety of analogous stressful situations during daily life, could present an increased risk for acute cardiac events.