Prodromal angina limits infarct size. A role for ischemic preconditioning.

BACKGROUND: In the experimental setting, it has been demonstrated that preconditioning myocardium before prolonged occlusion with brief ischemic episodes affords substantial protection to the cells by delaying lethal injury, thereby limiting infarct size. Whether the same occurs in humans remains unknown. METHODS AND RESULTS: This study was undertaken to determine whether new-onset prodromal angina, defined as chest pain episodes limited to the 24 hours before myocardial infarction, is the clinical correlate of the ischemic preconditioning phenomenon. Twenty-five patients with their first anterior myocardial infarction treated with thrombolysis (recombinant tissue plasminogen activator [r-TPA], 100 mg/3 hours) were retrospectively included in the study because they met the following criteria: (1) < 120 minutes from onset of symptoms to reperfusion therapy, (2) < 90 minutes from the beginning of thrombolytic therapy to reperfusion (defined as rapid ST elevation reduction > 50%), (3) a patient infarct-related coronary artery with TIMI 3 flow and complete absence of collateral circulation to the infarct related artery (assessed at 24 +/- 5 days), and (4) the presence of new-onset prodromal angina, ie, typical chest pain episodes occurring at rest within 24 hours or, alternatively, a complete absence of symptoms before onset of infarction. Therefore, on the basis of their clinical status before infarction, the patients were divided into two groups: group 1, 13 patients without prodromal angina, and group 2, 12 patients with prodromal angina. Despite no difference in time to treatment (81 +/- 19 versus 75 +/- 21 minutes in group 1 and group 2, respectively; P = NS) and time to reperfusion (58 +/- 34 versus 46 +/- 24 minutes; P = NS), the peak of CKMB release was markedly lower in group 2 (86.3 +/- 66 versus 192.3 +/- 108.3 IU/L; P < .01). In addition, although both groups were comparable in terms of area at risk (amount of myocardium beyond the infarct-related stenosis; 15.1 +/- 4.6 versus 13.7 +/- 4.6 hypokinetic segments in group 1 and group 2, respectively, P = NS), the final infarct size (11 +/- 7.5 versus 5.6 +/- 4 hypokinetic segments, P < .04) was smaller in group 2. Thus, the limitation of the infarct size was significantly greater in group 2 (69% versus 36%; P < .05), and this represents an additional 33% reduction (95% confidence intervals, 7.1% to 58.9%; P = .01) in the group of patients with prodromal angina. Also, the third index, that is, the ECG, showed a favorable trend toward a lesser number of Q waves and a higher sigma R waves, although the values did not reach statistical significance. CONCLUSIONS: Despite a similar area at risk, patients with new-onset prodromal angina showed a significantly smaller infarct size compared with patients without prodromal symptoms. Since the two groups had similar times to reperfusion and no evidence of collateral circulation to the infarct related artery, the protection afforded by angina in group 2 patients might be explained by the occurrence of ischemic preconditioning.

[Transesophageal echocardiography in patients free of carotid disease with an ischemic stroke]. / L'ecocardiografia transesofagea in pazienti, esenti da patologia carotidea, colpiti da ictus ischemico.

BACKGROUND: Cardioembolism is the cause of cerebral infarct in 15 to 30% of cases. The aim of the present work is to detect, by transesophageal echocardiography (TEE), potential cardioembolic sources in patients with cerebral ischemia without atherosclerotic carotid disease at duplex carotid ultrasound examination. METHODS: From 1991 onwards, 420 consecutive patients who presented with cerebral ischemia, detected by computerized axial tomography, underwent an echotomography examination of the cerebral afferent vessels and a transthoracic echocardiogram (TTE). Three hundred and thirty out of these patients were excluded since they had carotid plaques; of the remaining 90, 80 (mean age 61.6 years range: 25-86, 50 males and 30 females) underwent a transesophageal examination. The patients were studied with an HP Sonos 1000 system with 2.5 and 3.5 MHz frequency probes for TTE; 7.5 and 5 MHz probes were used for echotomography and TEE respectively. RESULTS: The TEE identified cardioembolic sources in 81% of the cases, versus 46.2% using TTE (p < 0.0001) with a significant statistical difference for thrombus, spontaneous echo contrast and paradoxic shunt (p < 0.0001). When the patients with cerebral ischemic events (group A) were compared with the 156 cardiac patients (group B) (mean age: 59.7, range: 19-86, 92 males and 64 females), without ischemic events, group A showed a significant higher prevalence of thrombus, spontaneous echo contrast, calcification of the mitral anulus, interatrial aneurysm and paradoxic shunt. CONCLUSIONS: Our experience confirms that TEE is very useful and more sensitive than TTE for diagnosing cardioembolic sources; so, this new diagnostic tool should become a useful part of the diagnostic iter for patients with ischemic stroke and normal carotid vessels. The prevalence of some heart conditions in the stroke group poses the problem of whether to advise anticoagulant or antiplatelet therapy and, in selected cases, a surgical approach. The absence of heart and vascular conditions in the extracranial regions of patients who have had a cerebral stroke, suggests an intracranial condition and the problem of performing an angiographic examination arises.

[Comparative effects of doxazosin and enalapril in patients with arterial hypertension and exercise-induced acute myocardial ischemia]. / Effetti comparativi di doxazosin ed enalapril in pazienti con ipertensione arteriosa ed ischemia miocardica acuta da sforzo.

The effects of doxazosin (alpha-1-inhibitor) and enalapril (ACE-inhibitor) on blood pressure and exercise stress test were assessed in 10 hypertensive patients (8 M, 2 F, age 58 +/- 9 years) with coronary artery disease and exertional myocardial ischemia. A single blind, cross-over, placebo controlled trial was performed. Placebo was administered for 2 periods of 2 weeks, doxazosin and enalapril for at least 3 weeks. The sequence of the active drugs was randomized and the single daily dose, obtained by titration, was 7 +/- 5 mg for doxazosin and 18 +/- 13 mg for enalapril. Blood pressure measurements and treadmill tests (Bruce protocol) were performed at the end of each period. Rest systolic and diastolic pressures after placebo were respectively 173 +/- 15 and 106 +/- 9 mmHg and were reduced to 153 +/- 11 and 93 +/- 12 mmHg (p less than 0.05) after doxazosin and to 150 +/- 24 and 93 +/- 12 mmHg (p less than 0.05) after enalapril. Total exercise time was 473 +/- 91 s after placebo and increased to 545 +/- 84 s (p less than 0.05) after doxazosin and 529 +/- 100 s (p less than 0.05) after enalapril. Time to 1 mm ST depression (ST1) was 297 +/- 102 s after placebo and increased to 414 +/- 96 s (p less than 0.05) after doxazosin and to 396 +/- 133 s (p less than 0.05) after enalapril. Double product at peak exercise and at ST1 were respectively 26.3 +/- 2.8 and 22.1 +/- 2.8 x 10(3) and remained unchanged after enalapril and doxazosin. Peak exercise diastolic blood pressure was 107 +/- 5 mmHg after placebo, was reduced to 94 +/- 15 mmHg (p less than 0.05) after doxazosin and was unchanged after enalapril (101 +/- 10 mmHg, NS). Thus, doxazosin and enalapril induced a comparable decrease of rest blood pressure and a similar increase of exercise time in hypertensive patients with exertional myocardial ischemia. Doxazosin but not enalapril reduced exercise diastolic blood pressure.

Dipyridamole technetium-99m-2-methoxy isobutyl isonitrile tomoscintigraphic imaging for identifying diseased coronary vessels: comparison with thallium-201 stress-rest study.

A same-day double injection protocol employing 99mTc-methoxyisobutyl isonitrile (MIBI) and myocardial single-photon emission computed tomography (SPECT) for detecting coronary artery disease (CAD) was assessed in 30 patients. SPECT was performed 1 hr after a first injection (250 MBq) of 99mTc-MIBI, given after 0.56 mg/kg dipyridamole (DPD) infusion. Patients were then reinjected at rest (750 MBq) and were reimaged 1 hr later. Within 1 wk, all patients underwent a complete stress-rest SPECT thallium study. Of the 330 myocardial segments evaluated, 25 were judged ischemic by both techniques, while persistent defects were demonstrated in 50 and in 47 with 99mTc-MIBI and 201TI, respectively. Six regions were considered for diseased vessels identification. Sensitivity and specificity for CAD were 100% and 75%, respectively, for both 201TI and 99mTc-MIBI. Sensitivity for identification of diseased vessels by 201TI was 68% for LAD, 89% for RCA, and 80% for LCX as opposed to 75%, 89% and 80%, respectively, by 99mTc-MIBI. Specificity was 93% in both cases for LAD, 73% and 63% for RCA, and 53% and 46% for LCX.