Beneficial effects of diltiazem during myocardial reperfusion: a randomized trial in acute myocardial infarction.

BACKGROUND: Although in experimental models of coronary occlusion diltiazem administration has been shown to reduce the degree of stunning and of reperfusion injury, the majority of clinical trials has failed to demonstrate significant benefits. The aim of this study was to evaluate the effect of diltiazem, administered before coronary reperfusion, on infarct size, residual myocardial viability and recovery of left ventricular function. METHODS: We studied 90 patients admitted within 3 hours of the onset of symptoms of acute myocardial infarction. They were immediately randomized to either intravenous diltiazem (10 mg bolus + 10 mg/hour for 3 days) (group 1, n = 43) or placebo (group 2, n = 47) and subsequently treated with recombinant tissue-type plasminogen activator. All underwent serial echocardiograms upon admission, 4 days post-admission during low-dose dobutamine stress echo, at discharge and after 6 months. We calculated the dysfunction score (1 = hypokinesia, 2 = akinesia, 3 = dyskinesia) on admission and its percent reduction after dobutamine (viability) and at follow-up (recovery). The 12-lead electrocardiograms were continuously monitored for 3 days and coronary angioplasty was performed whenever the residual stenosis was > 60%. RESULTS: Upon admission, there were no differences in age, sex, infarct location and size, degree of ST-segment elevation, time from onset of symptoms and dysfunction score. Creatine kinase peaked early in 70% of patients in both groups; the incidences of recurrent ischemia, infarct-related vessel patency and the need for coronary angioplasty were also similar. The creatine kinase peak was significantly higher in group 2 (2931 +/- 2456 vs 1726 +/- 1004 IU/l, p < 0.05). Conversely, in group 1 the residual viability was significantly higher (51 +/- 23 vs 36 +/- 30% improvement in dysfunction score, p < 0.05) and the early recovery of regional function was significantly greater (35 +/- 34 vs 18 +/- 22% at discharge, p < 0.05). On the other hand, the delayed recovery was not significantly different (15 +/- 29 vs 21 +/- 32% from the time of discharge to 6 months of follow-up). CONCLUSIONS: Intravenous diltiazem, started before coronary reperfusion, has beneficial effects on the infarct size, residual viability and recovery of regional function. If confirmed by larger trials, these preliminary results suggest the use of diltiazem as adjunctive therapy in patients with acute myocardial infarction and undergoing reperfusion.

[Inflammation and acute coronary syndromes]. / Inflamación y síndrome coronario agudo.

A great variety of stimuli, such as free radicals, oxidized LDL or some bacteria or virus infections, can act upon the vascular surface and lead to the development of an acute inflammatory reaction. There is more and more evidence supporting the hypothesis that the mechanism responsible for the transformation of a non-complicated atherosclerotic lesion into an hemorrhagic and ulcerated lesion, with the subsequent acute and unstable clinical status, is due to the onset of an inflammatory reaction. Many studies have tried to investigate the presence of any systemic marker able to predict the prognosis of patients at risk from developing acute events, and to distinguish them from those in stable status. The increase of the levels of C-reactive-protein has been related to the development of acute coronary syndromes, though often the results obtained in the different studies have had a quite poor prognostic value when applied to the general population. The lack of direct association between the increase of the levels of C-reactive-protein and Troponin I seems to rule out the possibility that the inflammatory stimulus might be the consequence of an irreversible injury, even though there is no doubt that severe ischemia is likely to play an active role in this sense.

Time course and determinants of left ventricular function recovery after primary angioplasty in patients with acute myocardial infarction.

OBJECTIVES: We sought to evaluate the importance of time in relation to treatment, time course and determinants of recovery of left ventricular (LV) function in patients with acute myocardial infarction (AMI) undergoing primary percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of AMI to reperfusion. METHODS: Left ventricular function was evaluated at hospital admission, after angioplasty, at 24 h and 6 months by both echocardiography and angiography and at 1, 7, 30, 90 and 180 days by echocardiography in 101 consecutive patients. RESULTS: Patients were allocated to three groups according to interval between symptom onset and angioplasty: <2 h (group A), 2 to 4 h (group B) and >4 h (group C). Patients in groups A and B showed a progressive improvement of LV function between day 7 and day 90, which became statistically significant at day 30 (p < 0.01). No LV function changes were noted in group C patients. Thrombolysis In Myocardial Infarction (TIMI) flow grade <3 at 24 h was not associated with any significant change in LV volume and function during the six-month follow-up period. Restenosis, when associated with TIMI flow grade 3 in the infarct-related vessel, did not influence LV function. Flow grade <3 of the infarct-related artery was not associated with any improvement of cardiac events independently from the time to treatment at the initial procedure. CONCLUSIONS: Patients undergoing primary PTCA for AMI have a good recovery of LV function if TIMI flow grade 3 is restored within 4 h. Coronary angioplasty limits further remodeling of the LV in patients treated after 4 h.

Evidence for the involvement of phosphatidylinositol 3-kinase in fMLP-stimulated neutrophil adhesion to ICAM-1-transfected cells.

Phosphatidylinositol 3-kinase (PI-3K) controls important intracellular steps involved in inflammation, immunity, and cell growth. PI-3K also modulates leukocyte integrin adhesiveness. In this study we evaluated the role of PI-3K on neutrophil adhesion to intercellular adhesion molecule-1 (ICAM-1)-transfected cells. N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated neutrophil adhesion was inhibited by wortmannin and LY294002, two unrelated PI-3K inhibitors, whereas phorbol myristate acetate (PMA)-induced neutrophil adhesion was not inhibited by them. After fMLP stimulation, a rapid activation of AKT and ERK was observed. However, only activation of AKT was reversed by the PI-3K inhibitors. Neutrophil expression of the beta2-integrins Mac-1, lymphocyte function-associated antigen-1(LFA-1), and gp150.95 was not affected by wortmannin, nor was expression of the activation epitope recognized by MAB24. We conclude that (a) PI-3K is involved in fMLP-activated neutrophil adhesion to ICAM-1-transfected cells, (b) the mechanism involved is not mediated by the modulation of beta2-integrin expression or activation, and (c) another mechanism seems to involve the adhesion to ICAM-1 when a cellular system of adhesion is used.

Dobutamine stress echocardiography and the effects of trimetazidine on left ventricular dysfunction in patients with coronary artery disease.

Trimetazidine, a metabolic agent that is opening the way to a new class of 3-ketoacyl coenzymeA thiolase inhibitors, has been shown to improve exercise tolerance and increase the ischaemic threshold in patients with effort angina, both in monotherapy or in combination with other anti-anginal drugs. The aim of this study was to assess the effects of oral trimetazidine on the ischaemic threshold and left ventricular dysfunction of patients with coronary artery disease. Dobutamine stress echocardiography was used, a technique that allows direct visualisation of localised left ventricular dysfunction that occurs as a result of ischaemia. Dobutamine increases heart rate and contractility thus augmenting oxygen demand. In coronary artery disease, this increased demand leads to metabolic changes responsible for decreased wall thickness and abnormal wall motion.

Influence of treatment delay on long-term left ventricular function in patients with acute myocardial infarction successfully treated with primary angioplasty.

BACKGROUND: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of acute myocardial infarction (AMI) to reperfusion. The aim of this study was to evaluate the importance of time to reperfusion for left ventricular function recovery after primary angioplasty (percutaneous transluminal coronary angioplasty [PTCA]) for AMI. METHODS: Ninety-five patients undergoing long-term successful PTCA for AMI were studied. Echocardiography was performed before and 3, 7, 30, 90, and 180 days after PTCA. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI), ejection fraction, and left ventricular wall motion score index (WMSI) were evaluated. RESULTS: Patients were divided into group A, 23 patients reperfused within 2 hours; group B, 32 patients reperfused between 2 and 4 hours; group C, 22 patients reperfused between 4 and 6 hours; and group D, 18 patients reperfused between 6 and 12 hours. Both EDVI and ESVI were reduced in groups A and B at 90 days. Groups C and D did not show any changes of EDVI and ESVI at any stage throughout the study. Ejection fraction improved only in groups A and B at 30, 90, and 180 days. At study entry, WMSI was similar in all groups. After 7 days, in group A and in group B, WMSI was improved, no changes were observed in group C, and a mild deterioration was observed in group D at 3 and 7 days. Subsequent evaluations showed progressive improvement of WMSI in all groups. CONCLUSIONS: Myocardial salvage is achieved only in patients revascularized within 4 hours from AMI onset. However, revascularization after 6 hours may be worthwhile by preventing ventricular remodeling.

Effect of sildenafil citrate upon myocardial ischemia in patients with chronic stable angina in therapy with beta-blockers.

BACKGROUND: It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers. METHODS: Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo. RESULTS: All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia. CONCLUSIONS: PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy.

Acute electrophysiologic effect of estradiol 17beta in menopausal women.

Sixteen postmenopausal women underwent electrophysiologic study before and 20 minutes after the administration of sublingual estradiol 17beta or placebo. Estradiol 17beta significantly affected electrophysiologic parameters, thereby suggesting its role in the development of palpitations in women.

Heart rate variability in patients with variant angina: effect of the presence of significant coronary stenosis.

BACKGROUND: The syndrome of variant angina occurs in patients with a wide spectrum of coronary disease ranging from angiographically normal coronary arteries to severe three-vessel disease. Survival and choice of therapy for these patients are determined by the extent of underlying fixed coronary obstruction. We examined whether heart rate variability (HRV) due to reduced vagal outflow may correlate with the severity of coronary stenoses in such patients. METHODS: Fifteen men and 2 women with clinically unstable variant angina underwent 24-hour Holter monitoring from which low and high-frequency power, standard deviation of mean 24-hour RR interval, proportion of adjacent RR intervals that differed by more than 50 ms, and mean root square of differences between successive RR intervals were extracted by power spectral analysis. Coronary angiography was later performed to determine coronary pathology and verify variant angina. As controls we studied an age-matched control group of 8 subjects (5 men, 3 women) with no clinical and/or electrocardiographic evidence of coronary heart disease or spasm as shown by negative treadmill exercise and hyperventilation tests. RESULTS: All measured components of HRV were significantly lower in the 9 patients with severe coronary artery disease compared to the 8 patients with normal coronary arteries or < 40% stenosis. The two groups were otherwise similar in terms of age and clinical parameters. CONCLUSIONS: These preliminary findings on a small but carefully selected group of patients with variant angina indicate that the analysis of HRV can select patients with severe disease for a more intensive approach. These findings require confirmation on a larger patient series.

Detrimental effects of acute heparin administration on ischemic threshold in patients with coronary artery disease.

BACKGROUND: Recent studies have indicated that heparin administration might decrease endothelial nitric oxide production. The aim of this study was to investigate the effect of heparin on ischemic threshold. METHODS: Eighteen patients with a positive exercise test and proven coronary artery disease were submitted to a randomized, placebo-controlled trial using i.v. 0.9% NaCl as placebo and i.v. heparin (5,000 IU bolus + 1,000 IU/h). After both saline and heparin bolus, the infusion was started and, after 10 min, the exercise test was performed. Blood samples for nitric oxide metabolites and free fatty acid determinations were taken before, at peak exercise, and at ECG recovery. RESULTS: As compared to placebo, heparin significantly decreased time to 1 mm ST segment depression (241 +/- 160 vs 303 +/- 175 s, p = 0.003) and prolonged recovery (573 +/- 177 vs 441 +/- 195 s, p = 0.003), while exercise duration was similar. Accordingly, rate-pressure product at 1 mm ST segment depression was lower after heparin, while it was similar at peak exercise. No significant differences were found for plasma nitric oxide metabolite levels. Conversely, free fatty acid levels were higher after heparin throughout the study in all patients. The increase in free fatty acids was not correlated with the difference in rate-pressure product at 1 mm ST segment depression between placebo and heparin (r = 0.34, p = NS). CONCLUSIONS: In patients with stable coronary artery disease, heparin significantly decreased exercise ischemic threshold. The lower rate-pressure product at 1 mm ST segment depression during heparin, compared to placebo, suggests an impairment of coronary blood flow, which does not seem to be mediated by decreased nitric oxide production/release. The increased free fatty acid release, on the other hand, might contribute to the detrimental effect of heparin on exercise-induced ischemia, but the lack of a correlation with changes in ischemic threshold suggests that other, still unknown, factors are involved.

Enoximone echocardiography for predicting recovery of left ventricular dysfunction after revascularization : a novel test for detecting myocardial viability.

BACKGROUND: The possibility that enoximone, a nonglycoside, noncatechol, positive inotropic agent, in combination with 2-dimensional echocardiography may predict recovery of myocardial dysfunction after revascularization has not been yet evaluated. METHODS AND RESULTS: Forty-five patients with chronic coronary artery disease and left ventricular dysfunction underwent dobutamine (DE, 5 to 10 microg. kg(-1). min(-1)) and enoximone (EE, 1.5 mg/kg, over 10 minutes) echocardiography. Myocardial wall motion was scored from 1 (normal) to 4 (dyskinesia): an asynergic segment was considered to have contractile enhancement when the score decreased by >/=1 grade. Of 478 asynergic segments, 216 (45%) exhibited functional recovery after revascularization. Dobutamine- and enoximone-induced contractile enhancement was observed in 41% and 46% of segments, respectively. Compared with DE, EE had higher sensitivity (88% versus 79%, P<0.01) and negative predictive value (90% versus 84%, P<0.05) in predicting functional recovery. The specificity (89% versus 90%) and positive predictive value (87% for both EE and DE) were similar. Concordant interpretation of EE and DE findings was found in 85% (406 of 478) of affected segments. Prerevascularization coronary angiography showed that stenosis severity of vessels supplying areas which only improved with enoximone was significantly greater (89.9%) than that of vessels (77.7%) supplying areas that responded to both agents (P<0.02). Both dobutamine and enoximone increased heart rate (16% and 10%, respectively), whereas enoximone did not cause changes in systolic blood pressure that increased by 14% with dobutamine. CONCLUSIONS: Enoximone echocardiography provides a novel and reliable approach for the prediction of functional recovery after revascularization. Compared with dobutamine echocardiography, the test yields higher sensitivity and induces lesser hemodynamic alterations.

Association between minor elevations of creatine kinase-MB level and mortality in patients with acute coronary syndromes without ST-segment elevation. PURSUIT Steering Committee. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy.

CONTEXT: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation. OBJECTIVES: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased. DESIGN AND SETTING: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997. PATIENTS: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization. MAIN OUTCOME MEASURE: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality. RESULTS: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both). CONCLUSIONS: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction.

Short- and long-term evolution of unstented nonocclusive coronary dissection after coronary angioplasty.

OBJECTIVES: We assessed the short- and long-term clinical and angiographic outcome of nonocclusive unstented dissection after percutaneous transluminal coronary angioplasty (PTCA) and its correlation with restenosis. BACKGROUND: The use of stents has dramatically increased both the number and the cost of coronary revascularization procedures. However, this technique is not completely risk free, and its benefits have not been fully demonstrated in uncomplicated dissections. METHODS: We studied 129 consecutive patients with 49 nonocclusive dissections after PTCA (grades A to D of National Heart, Lung, and Blood Institute classification) and good distal flow (TIMI [Thrombolysis in Myocardial Infarction] flow grade 3). All patients underwent coronary angiography at 24 h and at six months post-PTCA. Clinical status was assessed every three months in the outpatient clinic. Study subjects were matched with 60 other patients in whom stenting was performed for the presence of dissection. RESULTS: In the former group, all but two patients (with type E dissection, which evolved to coronary occlusion and myocardial infarction) improved their dissection score during follow-up: at six months only 18 dissections were still angiographically visible, and no clinical adverse events were recorded. In the dissected vessels, the restenosis rate was significantly lower than in those without dissection (12% vs. 44%, p < 0.001); in the stented vessels, the restenosis rate was 25% (15/60). CONCLUSIONS: In the presence of TIMI flow grade 3, coronary dissection is associated with a favorable outcome and predicts a low restenosis rate. These results caution against the indiscriminate use of intravascular prostheses in the event of nonocclusive coronary dissection.

Magnetic resonance contrast enhancement with gadolinium-DTPA in patients with angina and angiographically normal coronary arteries: effect of chronic beta-blockade.

BACKGROUND: The syndrome of angina and normal coronary arteries (syndrome X) comprises a heterogeneous group of patients with typical chest pain, a positive exercise test, angiographically smooth coronary arteries and no evidence of spasm. Magnetic resonance imaging (MRI) has been used to detect areas of myocardial ischemia and/or recent necrosis both in animal and human studies. Most of these studies have been conducted after intravenous administration of the paramagnetic contrast medium gadolinium-DTPA (Gd-DTPA), that is considered a sensitive marker of extracellular, probably ischemic in origin, edema. On the basis of these data, we used MRI to evaluate the possibility of myocardial Gd-DTPA deposition at rest in patients with syndrome X, and to assess the effects of oral treatment with atenolol. METHODS: We have studied 24 patients with syndrome X, 10 patients with coronary artery disease and 10 age-matched control subjects. The protocol was similar in all study subjects. Exercise testing and MRI were undertaken off therapy after coronary arteriography. Following MRI, patients underwent a 10 day treatment period with atenolol and repeated exercise stress test and MRI while on therapy. RESULTS: In all patients with syndrome X and coronary artery disease were observed effort diagnostic ST-segment changes that were associated with angina in 9 (37%) and 7 (70%) patients, respectively. Of 24 patients with syndrome X, 16 (66.6%) showed areas of myocardial enhancement after Gd-DTPA in comparison to the precontrast imaging. In 4 out of 10 patients with coronary artery disease (40%), Gd-DTPA accumulation was documented. Finally, focal Gd-DTPA myocardial enhancement was not observed in any normal control subject. After beta-blockade, 22 (92%) patients with syndrome X and 2 (20%) with coronary artery disease did not show any ischemic ST-segment changes on effort; 14 syndrome X patients (88%) and 2 coronary artery disease patients (50%) showed complete disappearance of the previously Gd-DTPA enhanced areas on MRI. CONCLUSIONS: Patients with syndrome X often exhibit regional accumulation of Gd-DTPA on MRI. The agent is believed to trace interstitial water accumulation as occurs during ischemia and its accumulation is reduced or abolished by treatment with atenolol, probably by different mechanisms. It is likely that an overactivation of the sympathetic outflow to the cardiovascular system can induce most of the abnormalities observed in syndrome X patients. In this context, beta-blockers probably represent the mainstay of the medical treatment of this condition.

Comparison of stress/rest myocardial perfusion tomography, dipyridamole and dobutamine stress echocardiography for the detection of coronary disease in hypertensive patients with chest pain and positive exercise test.

OBJECTIVES: Although different noninvasive tests have been proposed for detecting coronary artery disease (CAD) in patients with hypertension and chest pain symptoms, the relative performance of the available techniques has not been systematically assessed. BACKGROUND: Patients with hypertension frequently complain of chest pain and exhibit ischemic-like ST segment changes on the exercise electrocardiogram (ECG). However, the specificity of such changes for predicting significant CAD is very low, because these patients often exhibit a normal coronary angiogram. METHODS: In 101 patients with hypertension, chest pain and positive exercise ECG, we performed stress/rest myocardial single photon emission computed tomography with 99mTc-MIBI, dipyridamole and dobutamine stress echocardiography and coronary angiography. All patients had normal global ventricular function and 57 had left ventricular hypertrophy. All were kept on ACE inhibitors during the study period. RESULTS: No patients had significant side effects during perfusion scintigraphy. Dose-limiting side effects were observed in five patients with dipyridamole and in seven patients with dobutamine. Only 56% of study patients exhibited significant CAD. Sensitivity, specificity, accuracy, positive and negative predictive values were, respectively, 98%, 36%, 71%, 67% and 94% for perfusion scintigraphy, 61%, 91%, 74%, 90% and 64% for dipyridamole and 88%, 80%, 84%, 85% and 83% for dobutamine stress echocardiography. CONCLUSIONS: This study shows that stress echo in patients with hypertension yields a satisfactory diagnostic accuracy for identifying significant epicardial CAD. Our results indicate that dobutamine might be superior to dipyridamole. The low specificity of myocardial scintigraphy probably relates to the fact that this method traces perfusion abnormalities, not necessarily caused by epicardial CAD, possibly due to microvascular disease and not causing obvious wall motion abnormalities.

Biochemical consequences of electrical pacing in ischemic-reperfused isolated rat hearts.

It is still unclear if performance recovery in postischemic hearts is related to their tissue level of high-energy phosphates before reflow. To test the existence of this link, we monitored performance, metabolism and histological damage in isolated, crystalloid-perfused rat hearts during 20 min of low-flow ischemia (90% coronary flow reduction) and reflow. To prevent interference from different ischemia times and perfusing media compositions, the ischemic ATP level was varied by changing energy demand (electrical pacing at 330 min(-1)). Under full coronary flow conditions, work output, as well as ATP and phosphocreatine contents were the same in control, spontaneously contracting (n = 23) and paced (n = 21) hearts. During low-flow ischemia, the higher work output (p < 0.0001) in paced hearts decreased their tissue content of ATP, phosphocreatine and total adenylates and purines (p < 0.05), as opposed to maintained values in control hearts. During reflow, the recovery of mechanical performance and O2 uptake was 94 +/- 5% and 110 +/- 9% (p = NS vs. baseline) in controls, vs. 71 +/- 5% and 74 +/- 6% in paced hearts (p < 0.004 vs. baseline). The levels of ATP and total adenylates and purines remained constant in control, but were markedly depressed (p < 0.05 vs. baseline) in paced hearts. Phosphocreatine+creatine was the same in both groups. These data, together with the observed lack of creatine kinase leakage and of structural damage, indicate that myocardial recovery during reflow reflects the tissue level of ATP, phosphocreatine and total adenylates and purines during ischemia, regardless of physical cell damage.

[Cardiac tamponade after coronary angioplasty induced by treatment with ReoPro]. / Tamponamento cardiaco post angioplastica coronarica indotto da trattamento con ReoPro.

We report a complication observed in a 77-year-old man admitted to another hospital for "de novo" angina, in which coronary angiography showed a proximal 65% stenosis of the left anterior descending artery. The patient was medically stabilized, but one month later he developed unstable angina that was not controlled by heparin, nitrate and calcium antagonist infusions. Therefore, he was started on ReoPro (0.25 mg/kg bolus and 10 micrograms/min infusion) but because of persisting symptoms, he was transferred to our unit for urgent PTCA. Angioplasty plus stenting was successful and angina disappeared. The ReoPro infusion was stopped (6 hours after it had been started) for mild oral bleeding. Blood analysis was normal (including platelet count) except for the activated partial thromboplastin (PTT) and prothrombin (PT) time, which exceeded the laboratory limits of determination. Consequently, heparin infusion was also stopped. Eight hours after PTCA, he suddenly developed hypotension, bradycardia and loss of consciousness. The echocardiogram revealed a large pericardial effusion with diastolic collapse of the right cardiac chambers. The patient was treated with volume expanders, plasma and platelet units in an attempt to reestablish a normal hemodynamic pattern and normal platelet function. Elective pericardiocentesis was performed 24 hour later, with drainage of 800 ml of hematic effusion. Severe hemorrhagic complication was induced by ReoPro despite a normal platelet count. This was successfully counteracted with plasma and platelet infusion.

Left ventricular dysfunction during dobutamine stress echocardiography in patients with syndrome X and positive myocardial perfusion scintigraphy.

AIMS: A sizeable proportion of patients with angina, angiographically smooth coronary arteries and positive exercise test (syndrome X) have stress/rest myocardial perfusion defects. The aim of the study was to assess whether perfusion defects are dependent upon a reduction in coronary flow reserve causing regional left ventricular dysfunction in syndrome X patients. METHODS AND RESULTS: Twenty-two syndrome X patients underwent dobutamine stress echocardiography (DSE). All had stress-induced perfusion defects documented by 99m-Tc-MIBI scintigraphy. Resting and peak DSE wall motion score index (WMSI) were evaluated. Six patients exhibited resting wall motion abnormalities in 10 segments (WMSI 1.05 +/- 0.11). DSE was positive in 12 patients (53%), in whom 16 myocardial segments were involved: of these, 12 were normokinetic and 4 hypokinetic at rest. Peak WMSI was 1.17 +/- 0.17 (p < 0.05 vs rest). Of the 12 patients with a positive DSE, 9 also showed diagnostic ECG changes and 6 complained of angina. Of the 10 patients with negative DSE, 5 had angina and 5 (one with angina) showed ECG changes. In 7 patients (7 segments) (32%), the location of dobutamine-induced wall motion abnormalities coincided with the area where exercise-induced hypoperfusion was observed with MIBI. CONCLUSIONS: More than a half of syndrome X patients with myocardial perfusion abnormalities also develop regional LV dysfunction during DSE. However, the site of perfusion defects and wall motion abnormalities can be different. Reversible ischemia, defined as a parallel limitation of flow reserve and inducible dysfunction, could be identified as the cause of chest pain in almost one-third of patients.

Long-term preservation of left ventricular function in medically treated patients with coronary artery disease and persistent exercise-induced ischemia.

Little information is available on the long-term evolution of left ventricular function of medically treated patients with coronary artery disease and gross limitation of coronary flow reserve. The aim of this study was to assess the long-term evolution of effort tolerance and left ventricular function and their relation to the control of ischemic events in patients with coronary artery disease and prolonged inducible exercise-induced myocardial dysfunction who either declined or were ineligible for cardiac revascularization.