A small dose of apomorphine counteracts the deleterious effects of middle cerebral artery occlusion in different models.

The present manuscript investigates in two animal species by using two different experimental models of middle cerebral artery occlusion (permanent and transient), the neuroprotective effects of the dopamine receptor agonist apomorphine. These effects were evaluated by measuring the infarct volume and by counting muscle strength at different time points following the ischemic insult. Apomorphine at the dose of 3 mg/Kg when adminsitered at two hours following the occlusion of the middle cerebral artery was able to reduce significantly the infarct volume in the cortex of mice and the ischemic volume of the basal ganglia perfused by the perforant branches of the middle cerebral artery in the rat. In this latter case the behavioral evaluation (i.e. muscle strength) was preserved most effectively in the contralateral side at 24 and 72 hours. The present findings contribute to foster the concept that DA agonists might be useful in the treatment of cerebral ischemia. At the same time the behavioral improvement induced by DA administration following basal ganglia ischemia may be interpreted as the effects of an authentic disease modifying effect rather than a simple symtomatic relief due to a potential loss of DA containing axons in the basal ganglia. These data add on previous evidence showing analogous effects induced by the DA precursor L-DOPA. Apart from providing an evidence of a neuroprotective effect induced by increased DA stimulation the present data call for further studies aimed at comparing the effects of apomorphine with other DA agonists. In fact the quinoline moiety of apomorphine was claimed to protect neurons from a variety of insults independently from a DA agonist activity. The induction of protein clearing pathways appears to be potentially relevant for these effects.

History of allergy is a predictor of adverse events in unstable angina treated with coronary angioplasty

Background: The aim was to investigate prognostic relevance of history of allergy in subjects with unstable angina treated with coronary angioplasty. Methods: Fifty-seven consecutive patients with unstable angina who underwent coronary angioplasty were enrolled in the study and were divided into two groups: those with a history of allergy (Group A, N=15); and controls (Group C, N=42). Major adverse cardiac events were recorded over a six-month follow-up period. Patients with primary or unsuccessful angioplasty and patients treated with drug eluting stent were excluded from the study. Results: Group A patients (history of allergy) showed a 46.67% incidence of major adverse cardiac events at six-month follow-up (vs. 9.52% Group C, p<0.01): results remained significant even in a multiple Cox regression analysis (hazard ratio 7.17, 95% CI 1.71–29.98, p<0.01). Conclusion: History of allergy is an independent predictor of major adverse cardiac events after coronary angioplasty in a six-month follow-up period in unstable angina(AU)

History of allergy is a predictor of adverse events in unstable angina treated with coronary angioplasty.

BACKGROUND: The aim was to investigate prognostic relevance of history of allergy in subjects with unstable angina treated with coronary angioplasty. METHODS: Fifty-seven consecutive patients with unstable angina who underwent coronary angioplasty were enrolled in the study and were divided into two groups: those with a history of allergy (Group A, N = 15); and controls (Group C, N =42). Major adverse cardiac events were recorded over a six-month follow-up period. Patients with primary or unsuccessful angioplasty and patients treated with drug eluting stent were excluded from the study. RESULTS: Group A patients (history of allergy) showed a 46.67% incidence of major adverse cardiac events at six-month follow-up (vs. 9.52% Group C, p < 0.01): results remained significant even in a multiple Cox regression analysis (hazard ratio 7.17, 95% CI 1.71-29.98, p < 0.01). CONCLUSION: History of allergy is an independent predictor of major adverse cardiac events after coronary angioplasty in a six-month follow-up period in unstable angina.

High pressure assisted coronary stent implantation accomplished without intravascular ultrasound guidance and subsequent anticoagulation.

OBJECTIVES: The purpose of this study was to determine the efficacy of treatment with antiplatelet therapy and no anticoagulation after high pressure assisted coronary stent implantation performed without intravascular ultrasound (IVUS) guidance. BACKGROUND: Previous studies have shown that during IVUS-guided Palmaz-Schatz coronary stenting, it is safe to withhold anticoagulation when stent expansion has been optimized by high pressure balloon dilation. METHODS: Patients that had successful coronary stenting without IVUS guidance were treated with ticlopidine, 500 mg/day, and aspirin, 325 mg/day, for 1 month and then received only aspirin, 325 mg/day, indefinitely. Patients were not treated with warfarin (Coumadin) or heparin after successful stenting. Clinical and angiographic events were assessed at 1 month. RESULTS: A total of 201 intracoronary stents were implanted in 127 patients with 137 lesions. The average number of stents per lesion was 1.4 +/- 0.8, and the average number of stents per patient was 1.6 +/- 1.1. Stent deployment was performed for elective indications in 79% of procedures and for emergency indications in 21%. There were four stent thrombosis events for a per patient event rate of 3.1% and a per lesion event rate of 2.9%. CONCLUSIONS: After high pressure assisted stenting performed without IVUS guidance, there was an acceptable incidence of 3.1% of stent thrombosis with the combination of short-term ticlopidine and aspirin therapy and no anticoagulation. Although the study involved only 127 patients, the results support the relative safety of stenting without IVUS guidance and with antiplatelet therapy only in comparison to historical trials on stenting performed with postprocedure anticoagulation.

Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance.

BACKGROUND: The placement of stents in coronary arteries has been shown to reduce restenosis in comparison to balloon angioplasty. However, clinical use of intracoronary stents is impeded by the risk of subacute stent thrombosis and complications associated with the anticoagulant regimen. To reduce these complications, the hypothesis that systemic anticoagulation is not necessary when adequate stent expansion is achieved was prospectively evaluated on a consecutive series of patients who received intracoronary stents. METHODS AND RESULTS: From March 1993 to January 1994, 359 patients underwent Palmaz-Schatz coronary stent insertion. After an initial successful angiographic result with < 20% stenosis by visual estimation had been achieved, intravascular ultrasound imaging was performed. Further balloon dilatation of the stent was guided by observation of the intravascular ultrasound images. All patients with adequate stent expansion confirmed by ultrasound were treated only with antiplatelet therapy (either ticlopidine for 1 month with short-term aspirin for 5 days or only aspirin) after the procedure. Clinical success (procedure success without early postprocedural events) at 2 months was achieved in 338 patients (94%). With an inflation pressure of 14.9 +/- 3.0 atm and a balloon-to-vessel ratio of 1.17 +/- 0.19, optimal stent expansion was achieved in 321 of the 334 patients (96%) who underwent intravascular ultrasound evaluation, with these patients receiving only antiplatelet therapy after the procedure. Despite the absence of anticoagulation, there were only two acute stent thromboses (0.6%) and one subacute stent thrombosis (0.3%) at 2-month clinical follow-up. Follow-up angiography at 3 to 6 months documented two additional occlusions (0.6%) at the stent site. At 6-month clinical follow-up, angiographically documented stent occlusion had occurred in 5 patients (1.6%). At 6-month clinical follow-up, there was a 5.7% incidence of myocardial infarction, a 6.4% rate of coronary bypass surgery, and a 1.9% incidence of death. Emergency intervention (emergency angioplasty or bailout stent) for a stent thrombosis event was performed in 3 patients (0.8%). The overall event rate was relatively high because of intraprocedural complications that occurred in 16 patients (4.5%). Intraprocedural complications, however, decreased to 1% when angiographically appropriately sized balloons were used for final stent dilations. There was one ischemic vascular complication that occurred at the time of the procedure and one ischemic vascular complication that occurred at the time of angiographic follow-up. By 6 months, repeat angioplasty for symptomatic restenosis was performed in 47 patients (13.1%). CONCLUSIONS: The Palmaz-Schatz stent can be safely inserted in coronary arteries without subsequent anticoagulation provided that stent expansion is adequate and there are no other flow-limiting lesions present. The use of high-pressure final balloon dilatations and confirmation of adequate stent expansion by intravascular ultrasound provide assurance that anticoagulation therapy can be safely omitted. This technique significantly reduces hospital time and vascular complications and has a low stent thrombosis rate.

Clinical and angiographic outcome after Palmaz-Schatz stent implantation guided by intravascular ultrasound.

Intracoronary stents can be implanted with a low incidence of stent thrombosis (< 1%) when the stent procedure is guided by intravascular ultrasound. The long-term clinical and angiographic effects, however, have not been reported. This study assesses the 6 month clinical and angiographic results of a consecutive series of patients with intravascular ultrasound guided Palmaz-Schatz stent deployment that were not treated with subsequent anticoagulation after a successful stent implantation procedure. From March, 1993 to April 1994, 411 patients underwent Palmaz-Schatz stent implantation. There were 26 patients that had uncomplicated Palmaz-Schatz stent implantation that were treated with a standard anticoagulation regimen that are not evaluated in this study. Thus, this study includes an assessment of 385 patients that had either a successful intravascular ultrasound guided stent implantation procedure and did not receive post procedure anticoagulation or had a procedural complication. Procedural success was achieved in 369 patients (96%). Clinical success (procedure success without early post procedure event) was achieved in 363 patients (94%). There were 2 acute stent thrombosis events (0.5%) and 1 subacute stent thrombosis (0.3%) in the group of 369 patients with 454 lesions treated without anticoagulation. At 6 month clinical follow-up the incidence of myocardial infarction was 4.9% and the rate of coronary bypass surgery was 6.2%. There was a 2.1% incidence of death. Emergency intervention (emergency angioplasty or bailout stent implantation was necessary in 3 patients (0.8%). The total incidence of repeat percutaneous intervention was 11.4%. By 6 months clinical follow-up, major events had occurred in 19.2% of patients. The angiographic lesion restenosis rate, according to 50% diameter stenosis criteria, was 19%. The incidence of restenosis per patient was 22%. In conclusion, intravascular ultrasound guided Palmaz-Schatz can be performed without subsequent anticoagulation with a low incidence of stent thrombosis and acceptable clinical and angiographic outcome at 6 month clinical follow-up.

"Kissing" stents for bifurcational coronary lesion.

The coronary stents implantation into each vessel of a bifurcational lesion ("kissing" stents) in two patients is reported. The first patient had two short "kissing" stents implanted in an ostial lesion of the left anterior descending and the intermediate branch. The second patient had successful "kissing" stents implantation in the bifurcational lesion of the left main coronary artery.

On-line assessment of left ventricular function by automatic border detection echocardiography during rest and stress conditions.

A new echocardiographic system, automatic boundary detection (ABD) echocardiography, provides automatic on-line quantification of the left ventricular cavity area. To assess the potential of ABD echocardiography in measuring left ventricular dimensions and detect stress-induced changes in left ventricular function, we studied 25 patients. Thirteen were studied to compare left ventricular cavity areas and fractional area change by using 2DE and ABD echocardiography during routine studies in multiple views; 12 patients were studied during transesophageal atrial pacing by ABD-echocardiography in 4-chamber or short-axis views. End-diastolic and end-systolic left ventricular areas measured by ABD echocardiography were not significantly different from two-dimensional ones for all the echocardiographic views, except the apical 4-chamber view; fractional area change values obtained with ABD were slightly lower than 2DE ones, although not significantly. High correlation values were found between the 2 techniques for end-diastolic area (r = 0.94, SEE = 3.69 cm2), end-systolic area (r = 0.90, SEE = 4.49 cm2) and fractional area change (0.73, SEE = 9.7%); similar results were obtained for each single echocardiographic view. A decrease was found from rest to peak-pacing in end diastolic area (25.2 +/- 5.1 cm2 versus 21.1 +/- 4.3 cm2, p < 0.003), end systolic area (16.2 +/- 6.0 cm2 versus 14.8 +/- 5.3 cm2, p < 0.016) and fractional area change (38.5 +/- 12.7% versus 31.8 +/- 9.6%, p < 0.003) with a return to baseline values in post-pacing (26.3 +/- 4.3 cm2 and 17.0 +/- 5.4 cm2 and 37.3 +/- 11.3%, p < 0.003 versus peak-pacing, NS versus rest for each parameter).(ABSTRACT TRUNCATED AT 250 WORDS)

Integrated ultrasound evaluation of dissecting aneurysm of the aorta by the combined use of transesophageal echocardiography and intravascular ultrasound.

In order to obtain complete ultrasound imaging of the entire aorta, transesophageal echocardiography and intravascular ultrasound were performed on 3 patients with acute (2 cases) or chronic (1 case) aortic dissection. In each case the integrated use of transesophageal echocardiography and intravascular ultrasound provided an accurate evaluation of the dissection and of its anatomic extension.

Coronary tandem lesions: effect of exercise.

Coronary vasomotion of two stenoses in series (i.e., tandem lesion) was studied in 10 patients with coronary artery disease. Percent area stenosis was 69% +/- 23% for the first (S1) lesion and 70% +/- 37% for the second (S2). Quantitative coronary arteriography was carried out at rest, during two levels of exercise (2 minutes, 75 W and 1.9 minutes, 100 W), and at 5 minutes after sublingual administration of 1.6 mg nitroglycerin. Both stenoses showed exercise-induced vasoconstriction (S1: -29%, p less than 0.01 versus rest; S2: -29%, p less than 0.01 versus rest), which was reversible after sublingual administration of nitroglycerin (S1: +15%, not significant versus rest; S2: +13%, not significant versus rest). The vessel segment between the two stenoses showed no vasomotion during exercise, whereas the pre- and poststenotic "normal" vessel segment elicited exercise-induced vasodilation. There was an inverse relationship between percent area stenosis of the second lesion and exercise-induced vasoconstriction of the first lesion (correlation coefficient = 0.84). The more severe the distal stenosis was, the less exercise-induced stenosis narrowing of the proximal lesion was observed. Thus it is concluded that coronary vasomotion of two stenoses in series is dependent on both active and passive mechanisms because both lesions show exercise-induced vasoconstriction, but vasomotion of the proximal lesion is dependent on the severity of the second one.

Regression of coronary artery dimensions after successful aortic valve replacement.

BACKGROUND: The effect of regression of myocardial hypertrophy on coronary artery dimensions was evaluated in patients with aortic valve disease who underwent valve replacement. METHODS AND RESULTS: Cross-sectional area (CSA) of the three major coronary arteries (left anterior descending [LAD], left circumflex [LCx], and right coronary artery) was determined by quantitative coronary arteriography in 15 patients with aortic valve disease before and 38 months (range, 14-113 months) after successful aortic valve replacement. Twelve normal subjects served as controls. Left ventricular (LV) angiographic mass was calculated according to the method of Rackley. CSA of the left coronary artery was larger in aortic valve disease than in controls (LAD, 15 versus 8 mm2, p less than 0.001; LCx, 14 versus 6 mm2, p less than 0.001). After valve replacement, CSA of the left coronary artery decreased (LAD, 12 mm2, p less than 0.05 versus before surgery; LCx, 11 mm2, p less than 0.05 versus before surgery) but remained significantly larger than in controls. CSA of the right coronary artery in patients with aortic valve disease was not different from controls. LV muscle mass was significantly increased in aortic valve disease patients before (364 g) and after (250 g) valve replacement compared with controls (135 g). The appropriateness of coronary artery size with respect to muscle mass was evaluated by normalizing CSA of the left coronary artery (LAD + LCx) per 100 g of LV muscle mass (mm2/100 g). This index amounted to 11 mm2/100 g in controls, to 8 mm2/100 g in preoperative patients (p less than 0.05 versus controls), and to 10 mm2/100 g in postoperative patients with aortic valve disease (p = NS versus controls). CONCLUSIONS: In patients with aortic valve disease, CSA of the proximal LAD and LCx is increased, but this increase is not sufficient to keep CSA per 100 g of LV mass within normal limits. The postoperative decrease in muscle mass is associated with a decrease in the size of LAD and LCx, whereas the size of the right coronary artery remains unchanged. In contrast to the preoperative state, the residually hypertrophied LV myocardium after aortic valve replacement is supplied by an enlarged but adequately sized LAD and LCx.

Normalization of coronary vasomotion after percutaneous transluminal coronary angioplasty?

BACKGROUND: Coronary vasomotion was evaluated at rest and during bicycle exercise in 33 patients (age, 53 +/- 7 years) with coronary artery disease. In a first group of patients (n = 15), vasomotion was studied before and 4.3 +/- 2.3 months (early) after percutaneous transluminal coronary angioplasty (PTCA), whereas in a second group (n = 18), exercise coronary arteriography was performed 30 +/- 11 months (late) after successful PTCA. Patients with restenosis (percent area stenosis greater than or equal to 75% or percent diameter stenosis greater than or equal to 50%) were excluded. METHODS AND RESULTS: Luminal areas of a normal segment and the stenotic segment were determined at rest, during supine bicycle exercise, and 5 minutes after sublingual nitrate administration by using biplane quantitative coronary arteriography. Work loads before and early after PTCA were identical in group 1 and similar late after PTCA in group 2. Percent area stenosis decreased from 86% to 36% (p less than 0.001) in group 1 and from 93% to 46% (p less than 0.001) in group 2. Normal coronary arteries showed mild vasodilation during exercise before (+3%, NS versus rest), early (+7%, NS versus rest), and late after (+10%, p less than 0.05 versus rest) PTCA. Administration of sublingual nitrate was associated with significant vasodilation of the normal vessel segment before (+27%, p less than 0.001 versus rest), early (+31%, p less than 0.001 versus rest), and late (+21%, p less than 0.001 versus rest) after PTCA. In contrast, the stenotic vessel segments showed coronary vasoconstriction during exercise before PTCA (-25%, p less than 0.001 versus rest), whereas minimal vasomotion was observed early (+2%; NS versus rest) as well as late (+5%; NS versus rest) after PTCA. Individual post-PTCA (early and late) exercise data elicited vasodilation in 19, no vasomotion in four, and vasoconstriction in 10 instances. Sublingual administration of nitrate was associated with a significant increase in minimal luminal area before (+18%, p less than 0.05 versus rest), early (+24%, p less than 0.01 versus rest), and late (+16%, p less than 0.001 versus rest) after PTCA. An inverse linear correlation was found between the percent change in minimal luminal area during peak exercise and percent area stenosis at rest (r = 0.77, p less than 0.001). CONCLUSIONS: Exercise-induced stenosis narrowing is observed before PTCA but normal vasomotion is reestablished in two thirds of all patients early and late after PTCA. In one third, an abnormal reaction to exercise (i.e., vasoconstriction) persisted after PTCA, mainly in those patients with a residual area stenosis of 50% (percent diameter stenosis of 30%) or more. Thus, PTCA appears to have a salutary effect on coronary vasomotion during exercise, which, however, remains dependent on the severity of the residual stenosis.

[Invasive hemodynamic assessment and interventional therapy]. / Valutazione emodinamica invasiva e terapia interventistica.

Cardiovascular diseases are the main reason for hospitalization and usually followed by a conservative therapeutic approach. Due to the improvement over the last few years in the results of surgery in the elderly, the number of hemodynamic studies has increased. Hemodynamic studies are generally performed in elderly patients with symptomatic valvular heart disease and acute myocardial infarction with complications. The incidence of complications in the elderly during catheterization and coronarography is higher than in younger but still low. Cardiovascular hemodynamics in the elderly is determined by a combination of lifestyle, the presence of cardiac diseases that increase in prevalence with advancing age (e.g., coronary artery disease) and age-related changes in cardiovascular hemodynamic per se. With age, the tunica media of major blood vessels stiffens. This produces a elevation of systolic blood pressure (afterload) in many elderly patients which in turn increases left ventricular (LV) wall stress and results in mild compensatory LV hypertrophy. This compensatory hypertrophy normalizes wall stress, but produces pertubations in diastolic function such as: a reduction in the rate of both diastolic and LV peak filling, a diminished diastolic compliance associated with LV hypertrophy and a greater dependence upon left atrial contraction to maintain cardiac output. Recently the proportion of these patients who have percutaneous transluminal coronary angioplasty (PTCA) is growing. PTCA can be performed with a high rate of clinical success. Complete revascularization is low, particularly in patients with trivessel disease. The most common reasons for incomplete revascularization were: vessels with chronic total occlusion and vessels with diffuse disease. The rate of major cardiac complications was high among patients at high-risk in the presence of trivessel disease and low left ejection fraction. Long-term results were encouraging. For 90% of patients who had clinical success after PTCA, the end results continued to be beneficial. In conclusion, PTCA is a valid therapeutic alternative in elderly patients with coronary artery disease. In subsets of patients with single and bivessel disease, the short- and long-term outcome is very favourable. In patients with triple vessel disease, early clinical success rate is low but the long-term success rate is, however, acceptable.

Hemodynamic study of intravenous propionyl-L-carnitine in patients with ischemic heart disease and normal left ventricular function.

Propionyl-L-carnitine was given intravenously to ten patients with chronic ischemic heart disease who had normal left ventricular function and had not had a previous myocardial infarction. Subsequently, pulmonary and systemic circulation, left ventricular function, and the relationship between the ventricle and afterload were evaluated. This drug, at a dose of 15 mg/kg, improves ventricular function by easing the load and by enhancing cardiac efficiency. The ejection impedance is reduced with a consequent increase in stroke volume as a result of a) a decrease in systemic and pulmonary resistance and b) an increase in arterial compliance. Arterial pressure is maintained due to an increase in total external heart power. Since the tension time index shows a proportionally smaller increase in the energy requirement, it follows that cardiac efficiency has been improved and ventricle-afterload matching is optimal. These results suggest but do not prove that propionyl-L-carnitine exhibits a positive inotropic property.

Coronary vasomotion and coronary flow reserve during exercise.

Coronary vasomotion and coronary blood flow are important determinants of myocardial perfusion in patients with coronary artery disease. New digital angiographic techniques allow to study, not only the dimensions of a stenotic lesion (quantitative coronary arteriography), but also coronary flow reserve (parametric imaging). In a preliminary study both techniques were combined and coronary dimensions, as well as coronary flow reserve were determined in 15 patients (seven normals and eight patients with coronary artery disease) at rest, 45 s after 10 mg i.c. papaverine, during two levels of supine bicycle exercise, as well as 5 min after 1.6 mg sublingual nitroglycerin. Our results show that with modern digital subtraction techniques, not only stenosis geometry, but also coronary flow reserve can be determined at rest and during exercise conditions.

[Effects of gallopamil on coronary blood flow and vasomotility]. / Effetti del gallopamil sul flusso e sulla vasomotilità coronarica.

Using quantitative coronary arteriography, the luminal area was measured in the proximal, middle and distal third of a normal coronary vessel in basal condition and 15 min after 0.005 mg/Kg ic gallopamil (Group 1); 15 min after ic placebo (Group 2); 15 and 30 min after iv gallopamil at a dose of 0.03 mg/Kg (Group 3A) and 0.05 mg/Kg (Group 3B). A significant (p less than 0.001) vasodilation was observed in all segments in Group 1 and only in distal segment (p less than 0.05) in Group 3B. Neither did the heart rate, systolic blood pressure nor the coronary driving pressure show any changes. In the second section of this study, we analyzed the effects of the drug on coronary blood flow and resistance in 8 patients without clinical and/or objective evidence of coronary artery disease. Using thermodilution technique, the coronary sinus blood flow (CSBF) and coronary resistance (CR) were measured in basal condition and 5, 10, 15 and 30 min after 0.05 mg/Kg iv gallopamil. We observed a significant (p less than 0.001) increase of CSBF after 10 min and a significant decrease of CR after 10 min (p less than 0.001) and 15 min (p less than 0.05). In conclusion, our results suggest that the anti-ischemic effect of gallopamil can be related not only to the reduction of myocardial oxygen requirement, but also to an improvement of coronary blood flow with a decrease in coronary resistance.

Effect of intravenous propranolol on coronary vasomotion at rest and during dynamic exercise in patients with coronary artery disease.

Coronary vasomotion was studied at rest and during bicycle exercise with biplane quantitative coronary arteriography in 28 patients with coronary artery disease. Patients were divided into two groups; the first 18 patients served as controls (group 1), and the next 10 patients were treated with propranolol 0.1 mg/kg, which was infused intravenously before exercise (group 2). Luminal area of a normal and a stenotic vessel segment was determined at rest, during supine bicycle exercise, and 5 minutes after sublingual administration of 1.6 mg nitroglycerin after exercise. In group 1, the normal vessel showed vasodilation (+16%, p less than 0.001) during exercise, whereas the stenotic vessel segment showed vasoconstriction (-31%, p less than 0.001). After sublingual administration of nitroglycerin, there was coronary vasodilation of both normal (+36%, p less than 0.001 vs. rest) and stenotic (+20%, p less than 0.001) vessel segments. Patients with angina pectoris during supine exercise (n = 10) had significantly (p less than 0.05) more vasoconstriction (-36%) than patients without angina (-23%). In group 2, intravenous administration of propranolol at rest was associated with a decrease in luminal area of both normal (-24%, p less than 0.001) and stenotic (-43%, p less than 0.001) vessel segments; however, during subsequent exercise, both normal (-2%, p = NS vs. rest) and stenotic (-3%, p = NS vs. rest) vessel segments dilated when compared with the measurements after propranolol. Administration of nitroglycerin further increased luminal area of both vessel segments (normal segment, +23%, p less than 0.001; stenotic segment, +46%, p less than 0.001 vs. rest). It is concluded that dynamic exercise in patients with coronary artery disease is associated with coronary vasodilation of the normal and vasoconstriction of the stenotic coronary arteries. Patients with exercise-induced angina had significantly more stenosis vasoconstriction than patients without angina although minimal luminal area at rest was similar. Intravenous administration of propranolol is accompanied by a significant decrease in coronary luminal area of both normal and stenotic vessel segments at rest, which is overridden by dynamic exercise and sublingual nitroglycerin. The reduction in myocardial oxygen consumption and the prevention of exercise-induced stenosis vasoconstriction might explain the beneficial effect of beta-blocker treatment in most patients with coronary artery disease.

The poststenotic vessel segment during dynamic exercise: effect of oral isosorbide-dinitrate.

Coronary vasomotion of normal, stenotic, and poststenotic vessel segments was studied in 18 patients with coronary artery disease at rest, during submaximal bicycle exercise, and 5 min after sublingual nitroglycerin or oral isosorbide-dinitrate (ISDN) spray. Patients were divided into two groups: group 1 consisted of 10 patients with no premedication prior to exercise, and group 2 consisted of 8 patients receiving 120 mg long-acting ISDN orally 1 h before the procedure. Quantitative coronary arteriography was carried out in biplane projection using a semi-automatic computer system. The normal vessel segment showed a trend toward a small increase in cross-sectional area during exercise in both groups (+3% in group 1 and +4% in group 2, both NS). After sublingual nitroglycerin following exercise, there was a significant increase in group 1 (+29%, p less than 0.001 vs rest) but not after ISDN spray in group 2 (+5%, NS vs rest). The stenotic vessel segment showed exercise-induced stenosis narrowing in group 1 (-31%, p less than 0.01 vs rest) which was prevented by oral ISDN (+6%, NS vs rest). After exercise, sublingual administration of nitroglycerin or ISDN spray was associated with no significant change in stenosis area in either group. The poststenotic vessel segment showed no significant vasomotion during exercise in both groups (area change +6% in group 1 and +7% in group 2), but poststenotic luminal area increased after sublingual nitroglycerin (group 1: +15%, p less than 0.01 vs rest) or ISDN spray (group 2: +15%, p less than 0.05 vs rest). The mean pulmonary artery pressure increased during exercise from 22 to 39 mmHg (p less than 0.001) in group 1 and from 14 to 27 mmHg (p less than 0.001) in group 2. At rest (p less than 0.001) and during exercise (p less than 0.01) mean pulmonary pressure was lower in group 2 than in group 1. Thus, it is concluded that coronary vasomotion of the poststenotic vessel segment is only minimal during exercise and is not affected by coronary vasomotion of the stenotic vessel segment. Pretreatment with oral ISDN did not influence coronary vasomotion of the poststenotic vessel segment, but prevented exercise-induced stenosis narrowing. In the untreated patients, vasoconstriction of the stenotic vessel segment is limited to the site of the stenosis, and it appears that there is no release of vasoactive substances with vasoconstrictive influences on the poststenotic segment.