Effect of diabetes mellitus and insulin use on survival after acute myocardial infarction in the elderly (the Cooperative Cardiovascular Project).

Using data from a retrospective cohort study of Medicare beneficiaries hospitalized with an acute myocardial infarction (AMI), we evaluated the role of diabetes mellitus on 30-day and 1-year mortality. We classified subjects as nondiabetics, diabetics controlled with diet alone, diabetics receiving an oral hypoglycemic agent, and diabetics on insulin at time of admission. We compared baseline admission characteristics of subgroups using chi-square and Wilcoxon rank-sum tests and evaluated the effect of each diabetic state using sequential logistic models. We identified 80,832 nondiabetic patients, 9,862 diet-controlled diabetic patients, 14,664 diabetics receiving an oral hypoglycemic agent, and 12,241 diabetic patients on insulin therapy. Although mean age was similar among the groups, prevalence of hypertension, prior AMI, prior congestive heart failure, and prior revascularization were higher among diabetic patients, particularly those taking insulin. Diabetic patients, particularly those taking insulin, were less likely to receive aspirin and beta blockers and to undergo coronary revascularization. Diabetic patients had higher 30-day and 1-year mortality than nondiabetic patients. After adjustment for demographics, clinical and hospital characteristics, and treatment strategies, insulin-treated diabetics had the highest risk of mortality, followed by diabetics receiving oral hypoglycemic agents, followed by diet-controlled diabetics. Thus, diabetes is highly prevalent among elderly patients with an AMI. Mortality rates for these patients, particularly insulin-using diabetics, are higher than among their nondiabetic counterparts. Preventive and therapeutic strategies must be developed to ensure improved short- and long-term outcomes for elderly patients with diabetes and AMI.

Time to presentation with acute myocardial infarction in the elderly: associations with race, sex, and socioeconomic characteristics.

BACKGROUND: Although prompt treatment is a cornerstone of the management of acute myocardial infarction (AMI), prior studies have shown that one fourth of AMI patients arrive at the hospital >6 hours after symptom onset. It would be valuable to identify individuals at highest risk for late arrival, but predisposing factors have yet to be fully characterized. METHODS AND RESULTS: Data from the Cooperative Cardiovascular Project, involving Medicare beneficiaries aged >65 years hospitalized between January 1994 and February 1996 with confirmed AMI, were used to identify patients who presented "late" (>/=6 hours after symptom onset). Patient characteristics were tested for associations with late presentation by use of backward stepwise logistic regression. Among 102 339 subjects, 29.4% arrived late. Significant predictors of late arrival (odds ratio, 95% CI) included diabetes (1.11, 1.07 to 1.14) and a history of angina (1.32, 1.28 to 1.35), whereas prior MI (0.82, 0.79 to 0.85), prior angioplasty (0.80, 0.75 to 0.85), prior bypass surgery (0.93, 0.89 to 0.98), and cardiac arrest (0.52, 0.46 to 0. 58) predicted early presentation. Additionally, initial evaluation at an outpatient clinic (2.63, 2.51 to 2.75) and daytime presentation (1.67, 1.59 to 1.72) predicted late arrival. Finally, female sex, black race, and poverty, which were evaluated with an 8-level race-sex-socioeconomic status interaction term, were also risk factors for delay. CONCLUSIONS: Delayed hospital presentation is a common problem among Medicare beneficiaries with AMI. Factors associated with delay include not only clinical and logistical issues but also race, sex, and socioeconomic characteristics. Education efforts designed to hasten AMI treatment should be directed at individuals with risk factors for late arrival.

Bradycardia is associated with development of coronary collateral vessels in humans.

BACKGROUND: The development of mature coronary collateral vessels in patients with obstructive coronary artery disease (CAD) decreases the ischemic myocardial burden. Chronic bradycardia has been shown to stimulate formation of collateral vessels in experimental models. OBJECTIVE: To test our hypothesis that CAD patients with bradycardia would have better developed collateral circulation than would members of a control group. DESIGN: A retrospective study examining the relationship between bradycardia and the development of coronary collateral vessels in patients with obstructive CAD. METHODS: Admission electrocardiograms and rhythm tracings obtained during angiography of all patients presenting to the cardiac catheterization laboratory were screened from January to October 1997. Angiograms for patients with heart rates < or = 50 beats/min were reviewed. An equivalent number of consecutive patients with heart rates > or = 60 beats/min served as controls. Patients with acute myocardial infarction, with rhythms other than sinus, and without high grade obstructive CAD (< 70% stenosis) were excluded from the study. RESULTS: The study population consisted of 61 patients, 30 having heart rates < or = 50 beats/min (group A), and 31 controls with heart rates > or = 60 beats/min (group B). A significantly greater proportion of patients in group A than of matched controls was demonstrated to have developed collaterals (97 versus 55% in group B, P < 0.005). The mean collateral grades were 1.66 and 0.95 for subjects in groups A and B, respectively (P < 0.001). CAD patients with bradycardia are more likely (odds ratio 24, 95% confidence interval 5-146) to have angiographic coronary collaterals than are those with higher heart rates. CONCLUSION: Results of this study demonstrate that there is an association between bradycardia and growth of collateral vessels in patients with obstructive CAD. Bradycardic agents may be useful for promoting development of coronary collaterals in patients with atherosclerotic disease.

Primary coronary angioplasty vs thrombolysis for the management of acute myocardial infarction in elderly patients.

CONTEXT: Despite evidence from randomized trials that, compared with early thrombolysis, primary percutaneous transluminal coronary angioplasty (PTCA) after acute myocardial infarction (AMI) reduces mortality in middle-aged adults, whether elderly patients with AMI are more likely to benefit from PTCA or early thrombolysis is not known. OBJECTIVE: To determine survival after primary PTCA vs thrombolysis in elderly patients. DESIGN: The Cooperative Cardiovascular Project, a retrospective cohort study using data from medical charts and administrative files. SETTING: Acute care hospitals in the United States. PATIENTS: A total of 20683 Medicare beneficiaries, who arrived within 12 hours of the onset of symptoms, were admitted between January 1994 and February 1996 with a principal discharge diagnosis of AMI, and were eligible for reperfusion therapy. MAIN OUTCOME MEASURES: Thirty-day and 1-year survival. RESULTS: A total of 80356 eligible patients had an AMI at hospital arrival and met the inclusion criteria, of whom 23.2% received thrombolysis and 2.5% underwent primary PTCA within 6 hours of hospital arrival. Patients undergoing primary PTCA had lower 30-day (8.7% vs 11.9%, P=.001) and 1-year mortality (14.4% vs 17.6%, P=.001). After adjusting for baseline cardiac risk factors and admission and hospital characteristics, primary PTCA was associated with improved 30-day (hazard ratio [HR] of death, 0.74; 95% confidence interval [CI], 0.63-0.88) and 1-year (HR, 0.88; 95% CI, 0.73-0.94) survival. The benefits of primary coronary angioplasty persisted when stratified by hospitals' AMI volume and the presence of on-site angiography. In patients classified as ideal for reperfusion therapy, the mortality benefit of primary PTCA was not significant at 1-year follow-up (HR, 0.92; 95% CI, 0.78-1.08). CONCLUSION: In elderly patients who present with AMI, primary PTCA is associated with modestly lower short- and long-term mortality rates. In the subgroup of patients who were classified as ideal for reperfusion therapy, the observed benefit of primary PTCA was no longer significant.

Intravascular ultrasonic analysis of plaque characteristics associated with coronary artery remodeling.

We sought to determine the patient and plaque characteristics associated with the different forms of arterial remodeling as seen by intravascular ultrasound (IVUS) before coronary intervention. Remodeling in response to plaque accumulation may occur in the form of compensatory enlargement and/or focal vessel contraction. Previous studies report variation in the frequency and form of arterial remodeling. We performed preintervention IVUS imaging on 169 patients. Vessels were categorized as exhibiting compensatory enlargement or focal contraction if the arterial area at the lesion was larger or smaller, respectively, than both proximal and distal reference arterial areas; otherwise the artery was considered not to have undergone significant remodeling. Calcification was assessed and noncalcified plaque density was measured by videodensitometry. Sixty-one of 169 patients (66 narrowings) (46 men and 15 women, age 56+/-11 years) had adequate reference segments. Remodeling occurred in 43 of 66 patients (65%): compensatory enlargement in 27 of 66 (41%) and focal contraction in 16 of 66 (24%). Lesions with focal contraction had significantly smaller arterial area (13.3+/-3.3 vs. 18.1+/-7.0 mm2, p = 0.02) and plaque area (9.5+/-2.8 vs 13.7+/-5.5 mm2, p<0.01). Cross-sectional stenosis was similar (71+/-9% vs. 75+/-10%, p = NS), as was plaque density (p = 0.20), eccentricity, and calcium. Patient age, gender, and lesion location were not related to the form of remodeling. Similarly, history of diabetes, hypercholesterolemia, or hypertension was not predictive. Smoking was the only risk factor associated with focal contraction (p<0.01). Thus, whereas compensatory enlargement appears to be the most common form of coronary artery remodeling, focal contraction occurs more often in smokers.

Resource use and quality of care for Medicare patients with acute myocardial infarction in Maryland and the District of Columbia: analysis of data from the Cooperative Cardiovascular Project.

This study sought to evaluate the quality of care rendered to Medicare beneficiaries with acute myocardial infarction by establishing the use patterns of well-proven therapies in this population. We analyzed the quality of care rendered to 4300 Medicare beneficiaries seen at Maryland and District of Columbia hospitals with retrospectively confirmed acute myocardial infarction by evaluating the use of proven therapies. The proportion of patients ideal for therapies ranged from 10% for reperfusion to 100% for smoking cessation counseling. For ideal patients the following therapies were implemented: aspirin (87%), reperfusion therapy (64%), beta-blockers on discharge (60%), and smoking cessation counseling (41%). A substantial proportion of Medicare patients with acute myocardial infarction has one or more relative or absolute contraindications to standard regimens and therefore are not ideal therapeutic candidates. In the group of ideal patients, those with no therapeutic contraindications, a significant proportion do not receive these treatments.

Autoantibody titers to oxidized low-density lipoprotein in patients with coronary atherosclerosis.

Oxidation of low-density lipoprotein (LDL) is considered to be the initial step in the atherosclerotic process. Autoantibodies to oxidized LDL (ox-LDL) have been detected in human serum. We used an enzyme-linked immunosorbent assay technique to measure autoantibody titers in 63 normal subjects and patients with coronary artery disease. Thirty-five patients underwent coronary angiography for suspected coronary artery disease. Patients were divided into the following categories: group 1, 20 healthy young volunteers; group 2, 8 patients age-matched to the catheterization patients; group 3, 10 patients with normal coronary angiograms; and group 4, 25 patients with angiographic coronary artery disease. Autoantibody titers to ox-LDL were group 1, 0.142 +/- 0.023; group 2, 0.197 +/- 0.039; group 3, 0.183 +/- 0.038; and group 4, 0.340 +/- 0.026. There was no statistical difference among groups 1, 2, and 3, but the difference between these groups and group 4 was highly significant (p < 0.05). This study demonstrates that (1) autoantibodies to ox-LDL can be detected in normal subjects and in patients with abnormal coronary angiograms and (2) significantly higher titers of autoantibodies to ox-LDL were seen in patients with angiographic evidence of coronary artery disease.

Angiographic predictors of reocclusion after thrombolysis: results from the Thrombolysis in Myocardial Infarction (TIMI) 4 trial.

OBJECTIVES: This study attempted to determine which lesion characteristics are associated with reocclusion by 18 to 36 h. BACKGROUND: Reocclusion of the infarct-related artery after successful reperfusion is associated with significant morbidity and up to a threefold increase in mortality. METHODS: Two hundred seventy-eight patients with acute myocardial infarction were randomized to receive either anisoylated plasminogen streptokinase activator complex (APSAC) or recombinant tissue-type plasminogen activator (rt-PA) or their combination. Culprit arteries were assessed for Thrombolysis in Myocardial Infarction (TIMI) flow grade, lesion ulceration, thrombus, collateral circulation and eccentricity. Minimal lumen diameter, percent diameter stenosis and lesion irregularity (power) were calculated using quantitative angiography. RESULTS: Reocclusion was observed more frequently in arteries with TIMI 2 versus TIMI 3 flow (10.4% vs. 2.2%, p = 0.003), in ulcerated lesions (10.7% vs. 3.0%, p = 0.009) and in the presence of collateral vessels (18.2% vs. 5.6%, p = 0.03). Similar trends were observed for eccentric (7.3% vs. 2.3%, p = 0.06) and thrombotic (8.4% vs. 3.3%, p = 0.06) lesions. Reocclusion was associated with more severe mean percent stenosis (77.9% vs. 73.9%, p = 0.04). Lesion length, reference segment diameter and Fourier measures of lesion irregularity were not associated with reocclusion. CONCLUSIONS: Several simply assessed angiographic variables, such as the presence of TIMI grade 2 flow, ulceration, collateral vessels and greater percent diameter stenosis at 90 min after thrombolytic therapy, are associated with significantly higher rates of infarct-related artery reocclusion by 18 to 36 h and may aid in identifying the subset of patients who are at significantly higher risk of early reocclusion and who potentially warrant further early pharmacologic or mechanical intervention.

Subvalvular left ventricular outflow tract obstruction caused by "rhinonodular" calcification.

Cardiac calcification is a common problem in patients with renal failure. Calcific deposits often affect the mitral annulus, the aortic valve, and the coronary arteries. We report an atypical case of cardiac calcification obstructing the left ventricular outflow tract with minimal aortic valve calcification.

Evaluating the potential cost-effectiveness of stenting as a treatment for symptomatic single-vessel coronary disease. Use of a decision-analytic model.

BACKGROUND: Coronary stenting appears to provide more predictable immediate results and lower rates of restenosis than conventional balloon angioplasty for selected lesion types, but its hospital costs are significantly higher. This study was designed to evaluate the potential cost-effectiveness of Palmaz-Schatz coronary stenting relative to conventional balloon angioplasty for the treatment of patients with symptomatic, single-vessel coronary disease. METHODS AND RESULTS: We developed a decision-analytic model to predict quality-adjusted life expectancy and lifetime treatment costs for patients with symptomatic, single-vessel coronary disease treated by either Palmaz-Schatz stenting (PSS) or conventional angioplasty (PTCA). Estimates of the probabilities of overall procedural success (PTCA, 97%; PSS, 98%), abrupt closure requiring emergency bypass surgery (PTCA, 1.0%; PSS, 0.6%), and angiographic restenosis (PTCA, 37%; PSS, 20%) were derived from review of the literature published as of September 1993. Procedural costs were based on the true economic (ie, variable) costs of each procedure at Boston's Beth Israel Hospital. On the basis of these data, coronary stenting was estimated to result in a higher quality-adjusted life expectancy than conventional angioplasty but to incur additional costs as well. Compared with conventional angioplasty, stenting had an estimated incremental cost-effectiveness ratio of $23,600 per quality-adjusted life year gained. Although the cost-effectiveness ratio for stenting changed with variations in assumptions about the relative costs and restenosis rates, it remained less than $40,000 per quality-adjusted year of life gained--and thus was similar to many other accepted medical treatments--unless the stent angiographic restenosis rate was > 23%, the angioplasty restenosis rate was < 34%, or the cost of stenting (including vascular complications) exceeded that of conventional angioplasty by more than $3000. The alternative strategy of secondary stenting (initial angioplasty followed by stenting only for symptomatic restenosis) was estimated to be both less effective and less cost-effective than primary stenting over a wide range of plausible assumptions and thus does not appear to be cost-effective when primary stenting is also an option. CONCLUSIONS: Decision-analytic modeling can be used to evaluate the potential cost-effectiveness of new coronary interventions. Our analysis suggests that despite its higher cost, elective coronary stenting may be a reasonably cost-effective treatment for selected patients with single-vessel coronary disease. Primary stenting is unlikely to be cost-effective for lesions with a low probability of restenosis (eg, < 30%) or for patients for whom the cost of stenting is expected to be much higher than usual (eg, because of a high risk of vascular complications). Given the sensitivity of the cost-effectiveness ratios to even modest variations in the relative restenosis rates and cost estimates, future studies will be necessary to determine more precisely the cost-effectiveness of coronary stenting for specific patient and lesion subsets.

Balloon postdilation can safely improve the results of successful (but suboptimal) directional coronary atherectomy.

This study investigates whether adjunctive balloon angioplasty can be safely used to improve acute results in cases where directional coronary atherectomy alone has provided a successful (but suboptimal) outcome. Between October 1, 1990, and October 1, 1992, directional coronary atherectomy was performed successfully in 198 of 228 lesions. Individual operators believed that most acute results were satisfactory after atherectomy alone (group I, n = 115) with a minimal lumen diameter that increased from 0.82 +/- 0.45 to 3.21 +/- 0.65 mm after atherectomy, for an acute gain in lumen diameter of 2.39 +/- 0.73 mm and a residual stenosis of 6 +/- 13%. In 42% of lesions (group II, n = 83), however, results were considered suboptimal after atherectomy alone, with a minimal lumen diameter that increased from 0.85 +/- 0.45 to 2.83 +/- 0.64 mm, a smaller acute gain of 1.96 +/- 0.72 mm, and a mean residual stenosis of 17 +/- 14% (although all residual stenoses were < 50%, 19% had a residual stenosis > 30%). Adjunctive balloon angioplasty in these group II lesions provided an additional gain of 0.34 +/- 0.38 mm, bringing the total acute gain for group II lesions to 2.32 +/- 0.78 mm and the residual stenosis to 9 +/- 13%, similar to that of group I patients who underwent atherectomy alone. This strategy resulted in a 7 +/- 13% overall residual stenosis for the study population, with no higher incidence of periprocedural complications or adverse late clinical outcomes in group II patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Economics of elective coronary revascularization. Comparison of costs and charges for conventional angioplasty, directional atherectomy, stenting and bypass surgery.

OBJECTIVES: This study was designed to evaluate more closely the true in-hospital costs of elective revascularization by directional coronary atherectomy and intracoronary stenting and to compare these costs with those of the traditional revascularization alternatives (i.e., conventional balloon angioplasty and coronary artery bypass surgery). BACKGROUND: Previous studies have suggested that total hospital charges for directional coronary atherectomy or intracoronary stenting are significantly higher than those for conventional angioplasty. However, hospital charges do not necessarily reflect true economic costs, and their use may provide misleading data with regard to cost-effectiveness. METHODS: We analyzed in-hospital charges from the itemized hospital accounts of 300 patients undergoing elective angioplasty, directional atherectomy, Palmaz-Schatz coronary stenting or bypass surgery between January 1, 1990 and December 31, 1991. Costs were then derived by adjusting itemized patient accounts for department-specific cost/charge ratios. Catheterization laboratory costs were based on actual resource consumption, and daily room costs were adjusted for the intensity of nursing services provided. RESULTS: Length of hospital stay was similar for atherectomy (2.3 +/- 1.5 days) and conventional angioplasty (2.6 +/- 1.7 days) but significantly longer for stenting (5.5 +/- 2.6 days, p < 0.05). Total costs were also significantly higher for coronary stenting ($7,878 +/- $3,270, median $6,699, p < 0.05) than for angioplasty ($5,396 +/- $2,829, median $4,753) or atherectomy ($5,726 +/- $2,716, median $4,986). However, length of stay, resource consumption (laboratory and radiologic testing, drugs, blood products, for example) and total costs for bypass surgery were still greater than for any of the percutaneous interventional procedures. CONCLUSIONS: In contrast to previous studies utilizing only hospital charges, the in-hospital costs of angioplasty and directional coronary atherectomy were similar. Although the cost of coronary stenting was approximately $2,500 higher than that of conventional angioplasty, the magnitude of this difference was smaller than the $6,300 increment previously suggested on the basis of analysis of hospital charges. These findings reflect the inherent discrepancies between cost-based and charge-based methodologies and may have important implications for future studies evaluating the relative cost-effectiveness of newer coronary interventions.

Atherectomy of the subclavian artery for patients with symptomatic coronary-subclavian steal syndrome.

OBJECTIVES: This study addresses the efficacy of directional atherectomy in the subclavian artery for the relief of angina in patients with the coronary-subclavian steal syndrome. In addition, we review the histologic findings from the atherectomy specimens. BACKGROUND: The coronary-subclavian steal syndrome may occur after internal mammary-coronary artery bypass grafting. It is due to a stenosis in the subclavian artery proximal to the origin of the internal mammary artery and causes frank ischemia to the area supplied by the graft. Currently, surgery is the corrective procedure of choice. METHODS: In three patients with severe subclavian artery stenoses and unstable angina, directional atherectomy was performed using a peripheral atherectomy catheter through a percutaneous femoral approach. The patients ranged from 43 to 71 years of age and had undergone internal mammary-coronary artery bypass grafting 3 to 10 years previously. Each patient had severe peripheral vascular and cerebrovascular disease. RESULTS: All three patients had immediate symptomatic relief after the atherectomy, and postprocedure exercise testing demonstrated improved cardiac function. Two patients remain asymptomatic at 7 and 8 months, respectively; the third patient developed unstable angina 9 months later because of severe restenosis that was again successfully treated with atherectomy. Histologic examination of the specimens revealed atherosclerotic plaque, occasionally with adventitia. The specimen from the repeat atherectomy showed severe intimal hyperplasia. CONCLUSIONS: Directional atherectomy appears to be a safe and effective treatment for coronary-subclavian steal syndrome. This procedure may be the treatment of choice for patients in whom a vascular bypass operation is not feasible.

Effect of zatebradine on contractility, relaxation and coronary blood flow.

OBJECTIVES: The purpose of this study was to compare the effects of zatebradine on heart rate, contractility and relaxation with those of its structural analog verapamil. We used isoproterenol, a potent beta-agonist, to see how these effects were modulated by sympathetic activation. We also compared the effects of zatebradine and verapamil on coronary blood flow and coronary blood flow reserve. BACKGROUND: Zatebradine, previously called UL-FS 49, is a new bradycardic agent believed to act selectively at the sinoatrial node. METHODS: Isolated isovolumetric pig hearts were prepared and left ventricular pressure, its first derivative (dP/dt), tau and heart rate were measured both before and after administration of either 0.975 mg of zatebradine (Group I, n = 8) or 125 micrograms of verapamil (Group II, n = 8). After the effects of each drug reached a plateau, a continuous infusion of isoproterenol was started and measurements were obtained again and compared with a third group of measurements from control hearts infused with isoproterenol after receiving only saline solution (n = 8). We also assessed the effects of zatebradine and verapamil on coronary vascular tone by measuring flow in the left anterior descending coronary artery in intact anesthetized open chest pigs both before and after the intracoronary administration of these drugs (n = 8 for each). All preparations were atrially paced to negate any bradycardiac effects of the drugs. RESULTS: In the group that received zatebradine, mean (+/- SE) heart rate decreased from 143 +/- 8 to 99 +/- 4 beats/min (p < 0.01) and there was no significant change in either peak left ventricular systolic pressure, dP/dt or tau. In contrast, verapamil produced a lesser decrease in heart rate (136 +/- 7 to 120 +/- 7 beats/min, p < 0.05) but produced substantial decreases in peak left ventricular pressure (100 +/- 3 to 45 +/- 4 mm Hg, p < 0.01) and dP/dt (68% decrease, p < 0.01) and an increase in tau (+26%, p < 0.05). Isoproterenol restored these variables toward normal values in the hearts treated with verapamil, although left ventricular systolic pressure and dP/dt were restored to control values only at the highest isoproterenol concentrations. In the hearts treated with zatebradine, isoproterenol significantly increased left ventricular pressure and contractility and decreased tau; however, heart rate remained unchanged at peak effect. Zatebradine had no effect on coronary blood flow and there was a 100% increase in flow with reactive hyperemia. Conversely, verapamil increased coronary flow by 100%, with no subsequent further increase by reactive hyperemia compared with control values. CONCLUSIONS: Although structurally similar to verapamil, zatebradine is a highly specific bradycardic agent. It has little direct effect on left ventricular developed pressure, contractility, relaxation and coronary vascular tone. Furthermore, the bradycardic effect of zatebradine unlike that of verapamil, is not overcome by doses of isoproterenol that increase developed pressure and contractility and improve relaxation. Because of its highly specific bradycardic effect, this drug may potentially be useful in treating patients with ischemic heart disease or congestive heart failure.

Coronary-subclavian steal: an unusual cause of angina pectoris after successful internal mammary-coronary artery bypass grafting.

Coronary-subclavian steal syndrome is a rare cause of angina pectoris after bypass grafting using the internal mammary artery. We report the 11th case in the literature and review the pathophysiology and treatment of this disorder. We also review appropriate screening for this possibly increasing, yet preventable disorder.

Effects of vasopressin on the coronary circulation: reserve and regulation during ischemia.

In 18 dogs, intracoronary infusion of vasopressin produced a 40% reduction in coronary flow without significantly affecting systemic hemodynamics. The blood flow reduction occurred in a uniform transmural pattern without evidence of a gradient. The reduction in coronary flow resulted in a decrease in regional contractility as determined by isometric strain gauge arches. The decrease in regional contractility was transiently reversed by bolus injection of adenosine into the perfusion line. This suggests that the reduction of blood flow due to vasopressin was causing ischemia. Evidence for ischemia was also supported by measurements of local vein and tissue lactate production. Despite the apparently ischemic conditions, the vascular bed demonstrated evidence for significant reserve and regulation. Pressure-flow relationships performed under control and during vasopressin infusion demonstrated that the coronary vasculature retained its ability to regulate or defend a given level of coronary flow over a range of coronary perfusion pressures. Vasopressin produced a mild decrease in the peak hyperemic flow after a 15-s coronary occlusion and shortened the duration of reactive hyperemia. These overall findings are compatible with a predominant vasoconstrictor effect on the distal coronary vasculature. A role for a myogenic factor in the control of the coronary circulation is suggested, which is amplified by vasopressin.