The medial cord to musculocutaneous (MCMc) nerve transfer: a new method to reanimate elbow flexion after C5-C6-C7-(C8) avulsive injuries of the brachial plexus--technique and results.

The aim of this paper is to report on our ample experience with the medial cord to musculocutaneous (MCMc) nerve transfer. The MCMc technique is a new type of neurotization which is able to reanimate the elbow flexion in multilevel avulsive injuries of the brachial plexus provided that at least the T1 root is intact. A series of 180 consecutive patients, divided into four classes according to the quality of hand function, is available for a long-term follow-up after brachial plexus surgery. The patients enrolled for the study have in common a brachial plexus palsy showing multiple cervical root avulsive injuries at two (C5-C6), three (C5-C6-C7) and four (C5-C6-C7-C8) levels. The reinnervation of the musculocutaneous nerve is obtained via an end-to-end transfer from two donor fascicles located in the medial cord. The selected fascicles are those directed principally to the flexor carpi radialis, ulnaris and, to a lesser degree, the flexor digitorum profundus. Under normal anatomic conditions, they are located in the medial cord, and their site corresponds to the inverted V-shaped bifurcation between the internal contribution of the median nerve and the ulnar nerve. The technique has no failure and no complications when the hand shows a normal wrist and finger flexion and a normal intrinsic function. In case of suboptimal conditions of the hand, the technique has proved technically more challenging, but still with 67% satisfactory results. In the four-root avulsive injuries, however, this method shows its limitations and an alternative strategy should be preferred when possible. EMG analysis shows a reinnervation in both the biceps and the brachialis muscles, explaining the high quality of the observed results. Moreover, this technique theoretically offers the possibility of a "second attempt" at a more distal level in case of failure of the first surgery. This procedure is quick, safe, extremely effective and easily feasible by an experienced plexus surgeon. The ideal candidate is a patient harbouring a C5-C6 avulsive injury of the upper brachial plexus with a normally functioning hand.

Usefulness of N-terminal pro-B-type natriuretic peptide levels in predicting residual myocardial ischemia in patients with ST elevation acute myocardial infarction.

AIM: N-terminal pro-b-type natriuretic peptide (NT pro-BNP) is a neurohormone synthesized predominantly in ventricular myocardium. In patients with symptoms of heart failure, elevation in NT pro-BNP accurately identifies ventricular dysfunction. However, NT pro-BNP levels are not specific for ventricular dysfunction in patients who do not have overt symptoms of heart failure, suggesting that other cardiac processes such as myocardial ischemia may also cause elevation in NT pro-BNP. The study was aimed to determine whether NT pro-BNP elevations are associated with myocardial ischemia. METHODS: One hundred and thirty patients (104 males, 26 females, mean age 61+12 years), with ST elevation acute myocardial infarction (STEMI) and preserved left ventricular ejection fraction (>45%) at echocardiography performed at entry, from February 2003 and February 2004 were enrolled. In all patients NT pro-BNP plasma levels were checked at entry and 4-5 days after symptoms onset. In addition, maximal or symptom-limited exercise treadmill test (Bruce protocol), and myocardial perfusion scintigraphy using [(99m)Tc]Tetrofosmin single photon emission computed tomography (SPECT) imaging were performed within 30 days of STEMI. Ischemia was defined as reversible perfusion abnormalities. RESULTS: Of the 130 participants, 66 (51%) had inducible ischemia. Compared with patients in the lowest tertile, those in the highest tertile of NT pro-BNP had a greater significant risk of residual ischemia (odds ratio: 8.66; 95% CI, 3.90 to 19.24). Nevertheless patients in the highest tertile were older (64.19+/-10.80 years versus 55.90+/-9.67 years, P = 0.0001), had a lower left ventricular ejection fraction (49.70+13.46% versus 59.49+/-6.58%, P = 0.0001) and had a great rate of acute myocardial infarction (anterior acute myocardial infarction = 40.63% versus 25%). CONCLUSIONS: Elevated levels of NT pro-BNP are associated with residual myocardial ischemia among patients with STEMI and preserved left ventricular ejection fraction, as demonstrated by perfusion defect on SPECT imaging, suggesting that these patients may need further evaluation for stratification of the future risk of fatal events. The observed association between NT pro-BNP levels and ischemia may explain because tests for NT pro-BNP are not specific for ventricular dysfunction among patients with coronary artery disease.

Can losartan improve cardiac performance during the treadmill exercise test in hypertensive subjects?

Systolic blood pressure (SBP) normally increases during exercise. This increase is frequently exaggerated in hypertensive individuals. The aim of our study was to evaluate the antihypertensive effects of losartan at peak exercise and on cardiac performance during the treadmill test in individuals with essential hypertension. Forty subjects with a mean age of 44.2 +/- 12.4 years and with mild-to-moderate essential hypertension were enrolled. After a 14-day washout period, all selected subjects were given a treadmill exercise test using the modified Bruce protocol for exercise. The test was performed at the end of the washout period (step 0), again after 1 month (step 1), after 3 months (step 2) and after 6 months (step 3) of losartan administration (50 mg/daily per oral). Heart rate, SBP and diastolic blood pressure (DBP) were measured at rest and at maximal exercise. Exercise duration and double product were also recorded. In all patients who completed the study, a significant reduction from baseline in SBP at rest was found at 3 and 6 months (p < 0.05). No significant reduction from baseline in SBP at peak exercise was observed. No significant changes from baseline were found in double product, DBP, heart rate or exercise time. The results of our study suggest that losartan is effective in reducing blood pressure only at rest but is unable to improve exercise BP response or cardiac performance in subjects with mild-to-moderate essential hypertension.

Increased reperfusion by glycoprotein IIb/IIIa receptor antagonist administration in case of unsuccessful and failed thrombolysis in patients with acute myocardial infarction: a pilot study.

BACKGROUND: The aim of this study was to evaluate the effectiveness of glycoprotein (GP) IIb/IIIa receptor inhibitors in acute myocardial infarction (AMI) patients in case of unsuccessful and failed thrombolysis. METHODS: Eighty-four patients hospitalized within 4 hours of symptom onset were randomized (single blind) into two groups. Regardless of the group, placebo or GP IIb/IIIa inhibitors were administered to patients who did not present with reperfusion signs (failed thrombolysis) 30 min after starting thrombolysis and 30-60 min after the end of full thrombolysis in patients with pain recurrence and ST-segment elevation (unsuccessful thrombolysis). Reperfusion was assessed by the creatine kinase peak occurring within 12 hours, by the observation of rapid ST-segment reduction (50-70% within 1 hour) in the 12-lead ECG continuous tracing, by the rapid regression of pain and by the development of early ventricular arrhythmias. Group 1 patients (n = 42) received, during failed thrombolysis or after 30-60 min of effective thrombolysis but with pain recurrence and ST-segment elevation (unsuccessful thrombolysis), treatment with i.v. GP IIb/IIIa inhibitors, heparin according to the TIMI 14 trial, and aspirin. Group 2 patients (n = 42) received a full dose of recombinant tissue-type plasminogen activator (rt-PA 100 mg) and placebo either during failed thrombolysis or, after 30 min of effective thrombolysis but with pain recurrence and ST-segment elevation, and standard heparin treatment and aspirin. RESULTS: In group 1, 39 patients showed rapid reperfusion (4 +/- 3 min); 22 patients received rt-PA 65 mg and 20 patients received rt-PA 100 mg and subsequent GP IIb/IIIa inhibitor treatment. Coronary angiography, performed after 12-72 hours showed patency of the infarct-related artery in 39 patients whose clinical picture was suggestive of rapid reperfusion during administration of a bolus of GP IIb/IIIa inhibitors. In group 2, no patients showed reperfusion and they were submitted to rescue coronary angioplasty (p < 0.05). Side effects occurred in 3 cases in group 1 and in 2 cases in group 2. Patients receiving GP IIb/IIIa inhibitors showed a reduced incidence of stent treatment (p = NS) and a significant reduction in the occurrence of events (angina) within 30 days of treatment (p = NS). CONCLUSIONS: Our data suggest that in patients with AMI and failed thrombolysis, treatment with GP IIb/IIIa receptor inhibitors is feasible. The increase in the risk of bleeding was acceptable. The most important result was that this combination is safe.

Additional beneficial effects of canrenoate in patients with anterior myocardial infarction on ACE-inhibitor treatment. A pilot study.

BACKGROUND: Recent evidence suggests that, via the mineralocorticoid receptors present in cardiovascular tissues, aldosterone exerts profibrotic effects, and that partial aldosterone escape occurs during ACE-inhibitor treatment. METHODS: A double-blind, randomized study was performed in order to evaluate the feasibility, tolerability, and the effects of the administration of 25 mg/day of canrenoate plus captopril versus captopril alone to patients with anterior acute myocardial infarction (AMI) unsuitable for or not receiving thrombolytic treatment and to patients in whom such treatment resulted or did not result in reperfusion. One hundred eighty-seven patients with anterior AMI were included in the present study. In all cases serum creatinine concentrations and serum K concentrations were < 2.0 mg/dl and < 5.5 mmol/l respectively. The patients were randomized in two groups: the canrenoate group included 94 patients who received captopril and 25 mg i.v. of canrenoate (1 mg/hour for the first 72 hours and then orally 25 mg/day) whereas the placebo group (93 patients) received captopril and placebo. On admission and on days 10, 90 and 180 all patients underwent echocardiography in order to determine the end-systolic volume (ESV), the ejection fraction (EF), the end-diastolic diameter, the E/A ratio, the E deceleration time as well as the isovolumetric relaxation time (IVRT) and the E and A peak velocities. RESULTS: Unreperfused patients did not show patency of the infarct-related artery whereas in reperfused patients this vessel was patent (7-10 days after AMI). The two groups were similar in age, sex, incidence of diabetes, smoking habits, hypertension, creatine kinase enzymatic peak, adjuvant therapy, baseline EF, ESV, and incidence of coronary artery bypass grafting/coronary angioplasty. Following 10 days of treatment (canrenoate group), only 9 patients presented with serum K and creatinine concentrations respectively > 5.5 mmol/l and > 2.0 mg/dl. Among those patients receiving canrenoate, the mitral E/A ratio was higher compared to the placebo group (p = 0.001) whereas the ESV was significantly reduced (p < 0.05). The deceleration time for reperfused patients receiving canrenoate was higher than that observed for reperfused patients in the placebo group. The intragroup EF was significantly increased (p = 0.042). Compared to the placebo group, the IVRT was significantly higher for unreperfused patients receiving canrenoate than in the placebo group (p = 0.001). Serum creatinine, blood urea and K levels as well as the incidence and extent of vessel disease were similar for both groups. No side effects were observed during the study period. CONCLUSIONS: Our data suggest that the combination of captopril plus canrenoate is feasible for the initial treatment of patients presenting with AMI. Besides, compared to captopril alone it is more efficacious in improving the E/A ratio, the ESV, the EF, and the IVRT.

The combination ace-inhibitors plus canreonate in patients with anterior myocardial infarction: safety and tolerability study.

BACKGROUND: There is recent evidence that aldosterone (ALDO) exerts pro-fibrotic effects, acting via the mineral-corticoid receptors in cardiovascular tissues and partial aldosterone escape during ACE-inhibition treatment occurs. METHODS: A double blind randomised study was performed to evaluate the feasibility, and tolerability of the administration of the 25 mg/day of canreonate plus captopril versus captopril alone in patients with anterior AMI unsuitable for thrombolysis and/or not receiving thrombolytic treatment, and unreperfused after thrombolysis. Fifty five patients hospitalised for anterior AMI,with a serum creatinine concentration <2.0 mg/dl and a serum K concentration <5.0 mmol per liter were randomised in 2 groups: Group A included 27 patients who received captopril and 25 mg i.v. of canreonate (1 mg/h for the 1st 72 h and then orally 25 mg/day. Group B (28 patients) received captopril and placebo. Ten days after admission they underwent echocardiography to determine end systolic volume (ESV), ejection fraction (EF), End diastolic diameter EDD, E/A ratio, E deceleration time (dec. time) and isovolumetric relaxation time (IVRT), E and A peak velocities. RESULTS: All patients did not show patency of the infarct related artery (7-10 days after AMI) and the 2 groups were similar in regard to age, sex, diabetes, smoking habits, hypertension, CK enzymatic peak, adjuvant therapy, EF, ESV, and incidence of CABG/PTCA. One patient only showed increase of serum K>5.5 mmol/dl and creatinine >2.0 mg per liter after 10 days of treatment (group A). The mitral E/A ratio was higher in group A than group B (0.85+/-0.18 and 0.75+/-0.14) respectively, P=0.024. Creatinine, blood urea and serum K did not show significant differences between groups. No side effects were observed during the study period. The incidence of vessel diseases was similar in both groups. CONCLUSIONS: Our data suggest that the combination of captopril plus canreonate in feasible in early treatment of AMI patients.

ACE-inhibition plus mineralocorticoid antagonism versus ACE-inhibition alone in patients with anterior myocardial infarction.

BACKGROUND: Aldosterone exerts pro-fibrotic effects, acting via mineralo-corticoid reeptors in cardiovascular tissues. Aldosterone antagonism in combination with ACE inhibition may better protect against untoward effects of aldosterone than ACE inhibition alone. METHODS: In a double blind, randomised study the tolerability and efficacy of canreonate (25 mg/day) plus captopril versus captopril alone were evaluated in 187 patients with an acute anterior myocardial infarction (MI) and a serum creatinine concentration <2.0 mg/dL and a serum K concentration <5.0 mmol/L. Ninety-four patients received captopril and 25 mg canreonate (group A). Group B (93 patients) received captopril and placebo. At baseline and at 10 and 90 days after admission Doppler echocardiography was performed. RESULTS: Clinical and demographic aspects were similar in both groups. Also, baseline cardiac enzyme levels, left ventricular (LV) function and incidence of surgical interventions and angioplasty were comparable. Overall, creatinine, blood urea and serum K did not show significant differences between groups. However, in 9 patients in group A increases in serum K >5.5 mmol/dL and creatinine >2.0 mg/L were observed after 10 days of treatment. At 90 days, the mitral E/A ratio was higher (p = 0.001) and LV end systolic volume smaller (p = 0.021) inpatients treated with canreonate than in those receiving placebo. No further side effects were observed during the study period. CONCLUSIONS: Our data suggest that the combination of captopril plus canreonate is well tolerated following an acute myocardial infarction and has a beneficial effect on diastolic and systolic LV parameters and may decrease post-MI remodelling.

Comparison of the effects of felodipine and cilazapril on exercise performance in patients with mild to moderate hypertension. A crossover study.

This double-blind crossover study was designed to compare the effects of felodipine and cilazapril on exercise performance in hypertensive patients. After a 2-week placebo run-in period, 40 patients with mild to moderate hypertension were randomized into two parallel groups to receive either felodipine (10 mg) or cilazapril (5 mg) for 4 weeks. After another 2-week washout period, treatments were then crossed over for a further 4-week study period. All patients were given an extensive rest and exercise evaluation at the end of the placebo period. Extensive rest and exercise evaluations were repeated after a 4-week treatment period and again after the second washout period and after the second 4-week treatment period. Before each exercise test, epinephrine, norepinephrine and dopamine plasma levels and plasma renin activity were measured. Two groups were similar at baseline for systolic and diastolic blood pressure and heart rate as well as for laboratory and hormonal variables and duration of exercise test. At the end of treatment diastolic blood pressure was significantly reduced in the felodipine group (p = 0.019). Duration of exercise test was longer than at baseline (p = 0.031) in the felodipine group. Plasma dopamine levels were significantly increased in the cilazapril group. Plasma renin activity significantly increased in the felodipine group. In conclusion, our data show that the two drugs have the same effectiveness in resting conditions but that felodipine is more effective in lowering maximum exercise diastolic blood pressure and in improving exercise time with an double product increase (not significant); it has no statistically significant effect on maximal exercise systolic blood pressure.

Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital with acute chest pain.

It is common practice to hospitalize patients with chest pain for a period of observation and to perform further diagnostic evaluation such as exercise treadmill testing (ETT) once acute myocardial infarction (AMI) has been excluded. This study evaluates the safety and efficacy of immediate ETT for patients admitted to the hospital with acute chest pain. One hundred and ninety non-consecutive low-risk patients admitted to the hospital from emergency department with acute chest pain underwent ETT using Bruce protocol immediately on admission to the hospital (median time 165+30 min). Fifty-seven (30%) patients had positive exercise electrocardiograms, 44 (77.2%) of whom had significant coronary narrowing by angiography. An uncomplicated anterior non-Q-wave AMI was diagnosed in one patient. One hundred and eleven (58.4%) patients had negative and 22 (11.6%) patients had non-diagnostic exercise electrocardiograms. Of these 133 patients, 86 (64.7%) were discharged immediately after ETT, 19 (14.3%) were discharged within 24 h, and 28 (21%) were discharged after 24 h of observation. There were no complications from ETT. During the 17+/-6 months follow-up no patients died, and only eight (7.2%) patients with negative ETT experienced a major cardiac event (one AMI and seven angina). In conclusion, our results suggest that immediate ETT of low-risk patients with chest pain who are at sufficient risk to be designated for hospital admission, is effective in further stratifying this group into those who can be safety discharged immediately and those who require hospitalization.

Effects of high-dose furosemide and small-volume hypertonic saline solution infusion in comparison with a high dose of furosemide as a bolus, in refractory congestive heart failure.

BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory heart failure, but a lack of response is a frequent event. A randomised single blind study was performed to evaluate the effects of the combination of high-dose furosemide and small-volume hypertonic saline solution (HSS) infusion in the treatment of refractory NYHA class IV congestive heart failure (CHF). MATERIALS AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of different etiologies, unresponsive to high oral doses of furosemide, ACE-inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN

[The safety and efficacy of systemic salvage thrombolysis in acute myocardial infarct]. / Sicurezza ed efficacia della trombolisi di salvataggio per via sistemica nell'infarto miocardico acuto.

BACKGROUND: Thrombolysis reduces mortality in patients with acute myocardial infarction hospitalized within 6 hours of the symptom onset. Infarctions involving a small area of the myocardium show a lower mortality in comparison to those involving a large area. The aim of this study was to evaluate the safety and efficacy of rescue thrombolysis in patients with large acute myocardial infarction who had failed standard thrombolysis. METHODS: From January 1995 to December 1997, ninety patients (69 males, 21 females, mean age 56.7 +/- 9 years), hospitalized for suspected acute myocardial infarction within 4 hours of the symptom onset, suitable for thrombolysis (first episode), and who experienced pain and showed persistent ST segment elevation 120 min after starting thrombolysis, were randomized (single blind) into two groups: Group A (n = 45) received an additional thrombolytic treatment (rt-PA 50 mg), 10 mg as a bolus plus 40 mg in 60 min; Group B (n = 45) received conventional therapy. Positive non-invasive markers were defined as follows: resolution of chest pain; > 50% reduction in ST segment elevation; double marker of creatine phosphokinase (CPK) and CK-MB activity 2 hours after the start of thrombolysis; occurrence of reperfusion arrhythmias within the first 120 min of thrombolytic therapy. Blood pressure, heart rate and ECG were continuously monitored. Echocardiogram was carried out at entry and before discharge to control ejection fraction and segmental wall motion. Adverse events such as death, reinfarction, recurrent angina, incidence of major and minor bleeding, and emergency bypass surgery or coronary angioplasty were checked. RESULTS: Thirty-five patients (77.7%) showed reperfusion (10-50 min) after the start of additional rt-PA. In patients who did not receive additional thrombolysis, only 12 (26.6%) showed reperfusion 65-115 min after the end of rt-PA infusion. Group A showed an earlier and lower CK and CK-MB peak than Group B (p = 0.0001, p = 0.009, and p = 0.002, respectively). Mortality (n = 16, 17.7%) was higher in Group B (n = 13) than in Group A (n = 3) (28.8 vs 6.6%, p = 0.041). Seven patients from Group A showed non-fatal reinfarction. Angina was observed in 18 (40%) patients from Group A and 3 (6.6%) from Group B (p = 0.006). Ten of these patients underwent urgent coronary angioplasty (9 from Group A and 1 from Group B) and 3 from Group A urgent bypass surgery. Minor bleeding was higher in Group A than in Group B (44.4 vs 15.5%, p = 0.047). A major bleeding was observed in Group A (non-fatal stroke). At predischarge echocardiogram ejection fraction was higher in Group A than in Group B (46 +/- 8 vs 38 +/- 7%, p = 0.0001). CONCLUSIONS: Our data suggest that an additional dose of a thrombolytic drug in patients with unsuccessful thrombolysis is feasible, and the bleeding increase is an acceptable risk in comparison with the advantages obtained from a reduced infarct extension. Rescue thrombolysis could save time and allow mechanical revascularization to be carried out in patients admitted to a hospital without interventional cardiology laboratory or in those who have to be refereed to other hospitals for urgent bypass surgery.

Angiotensin-converting enzyme gene deletion polymorphism determines an increase in frequency of migraine attacks in patients suffering from migraine without aura.

Many authors have reported an association between the angiotensin-converting enzyme (ACE)-D allele and coronary heart disease and other cardiovascular diseases. The mechanism underlying the positive associations between the ACE-D alleles and diseases are not yet clear. Previous reports showed an association between migraine without aura and ACE-D allele polymorphism. The study is aimed to evaluate if the DD genotype could also be associated with the frequency and duration of migraine without aura. In 302 patients suffering from migraine without aura (at least for 1 year), with no history of cardiovascular diseases and major risk factors for ischemic events, the genotypes of the ACE gene, plasma ACE activity, and the frequency (weekly) and duration of migraine attacks were evaluated. No drugs were given before (4 weeks) and during the study. The same evaluations were performed in 201 subjects without migraine. The molecular biologist and the physician evaluating the patient data were blinded to the clinical history and ACE-DD gene determination. Genotypes were determined by polymerase chain reaction amplification. Plasma ACE activity was performed by the HPLC method. The groups were similar for sex, age and smoking habit (migraines: 302 patients (200 F/102 M), mean age 37.8 +/- 8.2 years; control: 201 subjects (127 F/74 M), mean age 37.5 +/- 9.3 years). Patients with migraine without aura showed higher incidence of the ACE-DD gene (48.34%) than control subjects (37.32%), p < 0.05. The frequency of migraine (average attacks per week) was higher in patients with DD (2.11 +/- 1.9) than in patients with ID (1.54 +/- 1. 44), p < 0.05. No difference in duration of migraine attacks (hours per week) was observed. Plasma ACE activity was increased in patients with the ACE-DD gene. Our data suggest that ACE-DD gene polymorphism could have an important role in determining migraine attacks and the frequency of these attacks. Further data are needed through further studies, especially on the biomolecular level.

Efficacy of rescue thrombolysis in patients with acute myocardial infarction: preliminary findings.

Thrombolysis reduces mortality in patients with acute myocardial infarction (AMI) who are hospitalized within 6 hours from the onset of symptoms. AMIs involving a small area of myocardium show a lower mortality in comparison with AMI involving a large area. The present study was aimed at evaluating the safety and efficacy of rescue thrombolysis in patients with large AMI who had failed thrombolysis. Ninety patients (69 Males and 21 Females), mean age 56.7 +/- 9 years, hospitalized for suspected AMI within 4 hours from the onset of symptoms, suitable for thrombolysis (First episode), and showing pain and persistent ST segment elevation 120 minutes after starting thrombolysis, were randomized (double-blind) into two groups. Group A (45 patients: 10 females and 35 males) received an additional thrombolytic treatment (rTPA 50 mg), 10 mg as bolus plus 40 mg in 60 minutes. Group B (45 patients: 11 females and 34 males) received placebo. Positive noninvasive markers were defined as follows: (1) resolution of chest pain, (2) > or = 50% reduction in ST segment elevation, (3) double marker of creatine kinase (CK) and CK-MB activity 2 hours after the start of thrombolysis, and (4) occurrence of reperfusion arrhythmias within the first 120 minutes of thrombolytic therapy. Blood pressure, heart rate, and ECG were continuously monitored. An echocardiogram was carried out at entry, and before discharge, to control ejection fraction and segmentary kinetics. Adverse events such as death, re-AMI, recurrent angina, incidence of major and minor bleeding, and emergency CABG/PTCA were checked. The groups were similar in terms of age, sex, diabetes, smoking habits, hypertension, and adjuvant therapy (beta-blockers). No significant difference was observed between the two groups regarding the time elapsed from the onset of symptoms to thrombolysis and AMI localization. Thirty-five patients (77.7%) showed reperfusion (10-50 minutes) after commencement of additional rTPA. Of the patients receiving placebo, 12 (26.6%) showed reperfusion within 35-85 minutes. Group A showed an earlier and lower CK and CK-MB peak than the control group, (respectively, p = 0.0001-0.009 and 0.002). Mortality (17.7%, 16 patients) was higher in group B than in the additional rTPA group, i.e., 6.6% (3 patients) in group A versus 28.8% (13 patients) in Group B (p = 0.041). Seven patients from group A showed nonfatal re-AMI. Angina was observed in 18 patients (40%) from group A and 3 (6.6%) from group B (p = 0.006). Ten of these patients underwent urgent PTCA (9 from group A and 1 from group B), and 3 from group A underwent urgent CABG. Minor bleeding was higher in group A than in group B (44.4% versus 15.5%, p = 0.047). Major bleeding was observed in group A (nonfatal stroke). At predischarge, the echocardiogram ejection fraction was higher in group A than in group B (46 +/- 8% versus 38 +/- 7%, p = 0.0001). Our data suggest that an additional dose of thrombolytic drug in patients with unsuccessful thrombolysis is feasible and also that the bleeding increase is an acceptable risk in comparison with the advantages obtained in reducing AMI extension. Rescue thrombolysis can allow a gain in time to perform mechanical revascularization in patients admitted to hospital without an interventionist cardiology laboratory or in those who have to be referred to another hospital for urgent CABG.

Effects of trimetazidine administration before thrombolysis in patients with anterior myocardial infarction: short-term and long-term results.

Reperfusion may prevent or reduce the development and extent of necrosis, but may also lead to an increase in reperfusion damage. Experimental studies performed in various animal models of myocardial ischemia have demonstrated the anti-ischemic properties of trimetazidine (TMZ) and have suggested that TMZ has antioxidant properties, without any direct hemodynamic effects. Our study was aimed at investigating the effects of TMZ before thrombolysis in acute anterior myocardial infarction and included 81 patients, hospitalized within 4 hours of the onset of symptoms. Patients were randomly (double-blind) subdivided in two groups The first group (40 patients, Group A, TMZ-pretreatment), received 40 mg TMZ orally about 15 minute before thrombolysis and, subsequently, 20 mg every 8 hours. The second group (41 patients, Group B) received placebo before thrombolysis. Ventricular arrhythmias (VA) due to reperfusion were evaluated in the first 2 hours. VA occurred in 15 of patients in group A, versus 29 in group B, p<0.05. Creatine kinase (CK) normalization time was achieved after 55.7+/-12.5 hours in group A, versus 61.2+/-12.1 hour in group B, p = 0.048. CK peak was 1772+/-890 in group A vs. 2285+/-910 Ul/l in group B, (p = 0.012). In the follow-up (range 6-22 months), there were 4 deaths, two patients in each group. After 180 days from treatment, the TMZ group showed a smaller end systolic volume than the placebo group (echocardiographic data), 46.2+/-12 and 52.8+/-13 ml/m2, respectively, p = 0.037. Our data suggest that TMZ probably reduces reperfusion damage and/or infarct size in patients with anterior AMI subjected to thrombolysis and affects the post-AMI remodeling. Our data must be interpreted with caution because of the selection of patients. These findings require further extensive trials.

Does the addition of losartan improve the beneficial effects of ACE inhibitors in patients with anterior myocardial infarction? A pilot study.

OBJECTIVE: To verify the efficacy of the combination of captopril (75 mg day) and losartan (25 mg/day) in early postinfarction phases of reperfused anterior acute myocardial infarction. DESIGN AND PATIENTS: 99 patients, hospitalised for suspected anterior acute myocardial infarction within four hours from the onset of symptoms, were randomised into two groups: group A included 50 patients who received captopril 75 mg/day and placebo; group B included 49 patients who received captopril 75 mg/day within three days of admission plus losartan 12.5 mg, as a first dose, and 25 mg/day successively. An additional 23 patients with anterior acute myocardial infarction received losartan 25 mg alone and acted as controls (group C) to check the effects of losartan on plasma angiotensin II (AII) concentrations. Noradrenaline (norepinephrine) (NA) and AII plasma concentrations were measured on the third and 10th day after admission in 93 patients (35 from group A, 35 from group B, and 23 from group C). 90 days after admission patients underwent echocardiography to determine end systolic volume (ESV) and ejection fraction (EF). RESULTS: Patients in groups A and B were similar with regard to age, sex, creatine kinase peak, EF, ESV, and risk factors. Group B (captopril plus losartan) patients showed a significant reduction in mean (SD) systolic blood pressure within the group (basal 128 (10) mm Hg; 10 days after admission 105 (9) mm Hg, p < 0.001), and in comparison with group A (captopril) patients (basal 127 (11) mm Hg; 10 days after admission 116 (10) mm Hg, p < 0. 001). Diastolic blood pressure was also lower in group B patients versus group A (66 (11) v 77 (11) mm Hg). Group C (losartan) patients also showed a significant reduction in systolic blood pressure (131 (13) mm Hg down to 121 (12) mm Hg, p < 0.001). Neither NA nor AII plasma concentrations in groups A and B differed significantly in basal samples (NA 673 (138) v 675 (141) pg/ml; AII 12.77 (4.79) v 12.65 (4.71) pg/ml) or 10 days after admission (NA 283 (93) v 277 (98) pg/ml; AII 5.31 (2.25) v 6.09 (3.31) pg/ml). However, patients in group C had higher plasma concentrations of AII (14.79 (5.7) pg/ml on the third day and 7.98 (4.92) pg/ml on the 10th day) than patients in either group A or B (p = 0.006). After 90 days following treatment, group B (captopril plus losartan) patients had a smaller ESV than patients in group A (captopril) and group C (losartan). CONCLUSION: The data suggest that the combination of captopril plus losartan is feasible in the early treatment of acute myocardial infarction patients, and it appears that this combination has more effect on ESV than captopril alone in the short term.

Tolerability and efficacy of high-dose furosemide and small-volume hypertonic saline solution in refractory congestive heart failure.

Thirty patients aged 65-85 years, with refractory New York Heart Association (NYHA) class IV congestive heart failure (CHF) were treated with an intravenous infusion of furosemide (250-2000 mg/d) and small-volume hypertonic saline solution (150 mL of 1.4-4.6% NaCl) twice a day for 6 to 12 days. A daily fluid oral intake of 1000 mL and previous cardiac therapy were maintained. Clinical signs and symptoms of CHF, such as dyspnea, edema and weakness, improved, as did severity of illness as defined by NYHA class. The infusion was well tolerated. After a 12-month follow-up, 24 patients (80%) were alive and in the NYHA class assigned on discharge from the hospital. This therapeutic combination is effective and well tolerated and should represent an innovative approach to the management of refractory CHF.

Succinate sumatriptan evaluation by Doppler echocardiography in patients with migraine.

Recent reports show that sumatriptan administration increases blood pressure and vascular resistance both in systemic and pulmonary circulation. This study was performed to evaluate by echo-Doppler technique the hemodynamic effects of subcutaneous sumatriptan administration. Forty-one migraine subjects (26 males, 15 females), mean age 36 +/- 2 years (range 36-39 years), and 20 healthy control subjects (14 males, six females), mean age 36 +/- 2 years (range 36-39 years) were randomized (double-blind) to receiving sumatriptan (group A) or placebo (group B). After a 2-week complete pharmacological washout, clinical examination, electrocardiogram, and Doppler echocardiography were performed at baseline, 15, 30, 45, and 60 min after sumatriptan or placebo administration. No significant differences were found between the two groups regarding Doppler echocardiographic parameters (aortic integral, pulmonary integral, end-systolic and end-diastolic diameters) and heart rate; only a slight but not significant increase in arterial blood pressure was observed in group A. Our data show that succinate sumatriptan can be used with safety in patients without hypertension and other cardiovascular disease.

Safety, tolerability, and neurohormonal changes of the combination captopril plus losartan in the early postinfarction period: a pilot study.

Suppression of formation of angiotensin II (A-II) is thought to be a major contributor to the hemodynamic response to angiotensin-converting enzyme inhibition (ACE-in) therapy. However, angiotensin II (A-II) plasma levels may rebound during ACE-in treatment. The study sought to verify the feasibility, safety, and tolerability of the combination of captopril (75 mg/d) plus losartan (25 mg/d). We also wished to establish whether the combination was able to avoid the increase of angiotensin II resulting from losartan treatment in early postinfarction phases of reperfused anterior acute myocardial infarction (AMI). Forty-four patients, hospitalized for suspected anterior AMI within 4 hours from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-II and reperfused, receiving 75 mg/d of captopril within 3 days from admission, and with systolic blood pressure (BP) >120 mmHg were randomized (single-blind) into two groups: Group A included 22 patients (6 women and 16 men) and received captopril 75 mg/d and placebo. Group B included 22 patients (5 women and 17 men) and received captopril 75 mg/d within 3 days from admission plus losartan 12.5 mg, as the first dose, and 25 mg/d (BP >110 mmHg) successively. Norepinephrine (NE) and A-II levels were measured on the 3rd and 10th days after admission. The two groups were similar with regard to age, sex, creatinine kinase peak, ejection fraction, end-systolic volume, and risk factors. Group B (captopril plus losartan) showed a significant reduction of BP, from 124 +/- 8.5 mmHg to 108 +/- 6.4 mmHg, P < 0.001, at 10 days after admission. In group A, BP was 122 +/- 9 mmHg, and 10 days after admission BP was 118 +/- 11 mmHg. NE and A-II values did not show significant differences in basal samples. At 10 days after admission values were NE 298 +/- 90 versus 272 +/- 86 pg/mL and A-II 6.07 +/- 2.97 versus 5.29 +/- 2.05 pg/mL for the two groups. Our data suggest, for the first time, that the combination of captopril plus losartan is feasible and does not produce serious side effects. When losartan was added to ACE-in treatment, there was no significant increase in A-II.