Contribution of ß-adrenergic receptors to exercise-induced bronchodilatation in healthy humans.

Exercise in healthy subjects is usually associated with progressive bronchodilatation. Though the decrease in vagal tone is deemed to be the main underlying mechanism, activation of bronchial ß(2)-receptors may constitute an additional cause. To examine the contribution of ß(2)-adrenergic receptors to bronchodilatation during exercise in healthy humans, we studied 15 healthy male volunteers during maximum exercise test at control conditions and after a non-selective ß-adrenergic blocker (carvedilol 12.5mg twice a day until heart rate decreased at least by 10beats/min) and inhaled ß(2)-agonist (albuterol 400µg). Airway caliber was estimated from the partial flow at 40% of control forced vital capacity (V˙(part40)) and its changes during exercise from the slope of linear regression analysis of V˙(part40) values against the corresponding minute ventilation during maximal exercise until exhaustion. At control, V˙(part40) increased progressively and significantly with exercise. After albuterol, resting V˙(part40) was significantly larger than at control increased but did not further increase during exercise. After carvedilol, V˙(part40) was similar to control but its increase with exercise was significantly attenuated. These findings suggest that ß(2)-adrenergic system plays a major role in exercise-induced bronchodilation in healthy subjects.

Myocardial scar and insulin resistance predict cardiovascular events in severe ischaemic myocardial dysfunction: a perfusion-metabolism positron emission tomography study.

BACKGROUND: Clinical outcome can be predicted by metabolism-perfusion positron emission tomography (PET) in patients with severe ischaemic left ventricular dysfunction. This study determined whether the amount of viable or non-viable myocardium detected with a PET scan or clinical-functional parameters might predict cardiovascular events. METHODS: All patients had previous myocardial infarction (>6 months previously) and left ventricular ejection fraction (LVEF) <40%. Metabolism-perfusion PET, echocardiogram and coronary angiography were provided. All subjects underwent short euglycaemic-hyperinsulinaemic clamp before the metabolism study. The dysfunctioning segment was defined as hibernating myocardium when metabolism was normal-moderately reduced with impaired perfusion (mismatch flow-metabolism). Cardiac death, hospital admission for myocardial infarction or heart failure were considered cardiovascular events. RESULTS: Ninety-three patients (71 males, aged 64.2 years) were studied. The LVEF was 30.2+/-7.7%; 48 (51.6%) suffered an anterior myocardial infarction. Fifty-three (54.1%) subjects were treated with coronary revascularization; all had optimal medical therapy. Cardiovascular events occurred in 20/93 patients at 1-year follow-up (event group). Age (P=0.7), diabetes mellitus (P=0.6) and rate of coronary revascularization (P=0.3) were not different in the two groups. Patients who experienced cardiovascular events had larger non-viable myocardium (5.8+/-2.7 vs. 4.1+/-2.6, P=0.01), lower metabolic rate glucose (1.3+/-0.6 vs. 1.7+/-0.7 ml . kg . min, P=0.04) but similar hibernating myocardium (1.6+/-1.6 vs. 1.7+/-2, P=0.8) and baseline LVEF (28.1+/-4.8 vs. 30.7+/-8.3%, P=0.08). Having more then five non-viable segments and a metabolic rate for glucose of <0.9 mg . kg . min predicted a worse prognosis (P=0.04, log rank, 3.89; and P=0.004, log rank, 8.1, respectively). CONCLUSION: Non-viable myocardium revealed with PET predicts mid-term clinical prognosis. Insulin resistance seems to influence the outcome.

Half-dose thrombolysis to begin with, when immediate coronary angioplasty in acute myocardial infarction is not possible.

BACKGROUND: Low-dose lytic drugs are sometimes administered to patients with ST-elevation acute myocardial infarction (AMI) as a bridge to coronary angioplasty (facilitated PTCA). Reports are scarce. The characteristics and outcomes of a recent series of consecutive patients treated in our Center are presented. METHODS: In August 2000 facilitated PTCA with half-dose reteplase was started in our Center in all cases when the cath lab was not immediately (< 30 min) available, or the patient had to be transferred to us. Since August 2000, 153 patients were admitted to our cath lab to undergo facilitated (n = 80) or primary (n = 73) PTCA. The data of all patients were prospectively collected, and were analyzed on an "intention-to-treat" basis. RESULTS: No significant differences were found between facilitated and primary PTCA patients with regard to: gender, diabetes, hypertension, previous PTCA/bypass surgery, heart rate at admission, systolic blood pressure, anterior AMI, number of leads with ST-segment elevation, total ST-segment deviation, collateral flow to the infarct-related artery, and three-vessel disease. In our series, facilitated vs primary PTCA patients had a better risk profile: they were younger (61 +/- 13 vs 66 +/- 11 years, p = 0.016), less frequently had a previous AMI (7 vs 24%, p = 0.01), had a shorter time from pain onset to first emergency room admission (122 +/- 104 vs 168 +/- 162 min, p = 0.045), and a trend to a shorter total time to the cath lab (209 +/- 121 vs 255 +/- 183 min, p = 0.073) despite a similar emergency room-to-cath lab component (89 +/- 50 vs 98 +/- 92 min, median 74 vs 65 min, p = NS). Moreover, they presented with a lower Killip class on admission (1.1 +/- 0.4 vs 1.5 +/- 0.98, p = 0.01), with more patients in Killip class 1 (95 vs 74%, p = 0.001). One vs 8% of patients were in shock. Facilitated vs primary PTCA patients had an initial TIMI 2-3 flow in 42 vs 25% of cases (p = 0.031), a final TIMI 3 flow in 82 vs 71% (p = NS), > or = 50% ST-segment resolution in 73 vs 58% (p = NS), and both of the latter in 62 vs 45% (p = 0.099); distal coronary embolization occurred in 9 vs 14% of cases (p = NS); intra-aortic balloon counterpulsation was used in 5 vs 12% and glycoprotein IIb/IIIa inhibitors in 10% of the whole population. The overall in-hospital mortality was 3.7 vs 9.6% (p = NS), and 2.5 vs 4.5% (p = NS) when patients in shock at admission were not considered. Reinfarction occurred in 2 patients submitted to facilitated PTCA (who had had no immediate PTCA, due to full reperfusion) and in none of the patients submitted to primary PTCA; no patient presented with stroke or major bleeding. CONCLUSIONS: Pre-treatment with thrombolysis often provides a patent vessel before PTCA, appears to be safe, and may improve reperfusion after PTCA. In this setting, the additional use of glycoprotein IIb/IIIa inhibitors before PTCA only in non-reperfused patients may be significantly risk- and cost-effective.

Management and outcomes of patients transferred for rescue coronary angioplasty in acute myocardial infarction.

BACKGROUND: Rescue coronary angioplasty (PTCA), though recommended by the guidelines, is not regularly performed after failed lysis in patients with ST-elevation acute myocardial infarction (AMI), and data from large contemporary studies are not available. The outcomes of a recent series of consecutive patients in our Center are presented. METHODS: Between August 2000 and November 2003, 270 patients with AMI < 12 hours were referred to our cath lab for emergency PTCA: 117 (43%) for rescue PTCA after failed lysis, and 153 for primary or facilitated PTCA. The baseline, procedural and outcome data of all patients were prospectively collected, analyzed on an "intention-to-treat" basis and compared. Cineangiographic data were reviewed by three angiographers who were unaware of the clinical data. RESULTS: No significant differences were found between rescue PTCA and primary/facilitated PTCA patients as to: age, female gender, diabetes, hypertension, previous AMI, time from pain onset to the first emergency room admission, heart rate at admission, systolic blood pressure, number of leads with ST-segment elevation, total ST-segment deviation, collateral flow to the infarct-related artery, initial TIMI 2-3 flow, and three-vessel disease. Patients with rescue PTCA, as compared to primary/facilitated PTCA, had a longer time from pain onset to the cath lab (336 +/- 196 vs 229 +/- 155 min, p = 0.0001) and more frequently had an anterior AMI (52 vs 38%, p = 0.027), a higher Killip class (1.5 +/- 0.98 vs 1.26 +/- 0.7, p = 0.02), shock (11 vs 5%, p = 0.073), and intra-aortic balloon pump use (17 vs 8%, p = 0.048); fewer patients were in Killip class 1 (74 vs 85%, p = 0.043). PTCA was performed immediately in 78 vs 95% of patients (p = 0.0001); 8 vs 3 patients had PTCA of the infarct-related artery and 8 vs 1 had bypass surgery later during hospitalization. Patients with rescue PTCA, as compared to primary/facilitated PTCA, had a final TIMI 3 flow in 62 vs 76% of cases (p = 0.017), > or = 70% ST-segment resolution in 36 vs 50% (p = 0.086), and both of the latter in 24 vs 45% (p = 0.006); the overall hospital mortality was 12 vs 6.5%, and 5.8 vs 3.4% when patients in shock on admission were not considered; reinfarction and stroke occurred in 0.9 vs 1.3% and in 2.6 vs 0% of the patients respectively. CONCLUSIONS: Due to referral, rescue PTCA patients were admitted to the cath lab later after the onset of infarction, and had a higher risk profile, as compared to primary/facilitated PTCA patients; both recanalization and reperfusion were less satisfactory, as were the outcomes. Thrombolysis is often ineffective but, as long as it remains a widespread treatment, efforts should be made to improve reperfusion and survival in these patients, possibly by an earlier referral for rescue PTCA.