Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The DEFIANT-I study (Doppler Flow and Echocardiography in Functional cardiac Insufficiency: Assessment of Nisoldipine Therapy) was a multicenter, multinational double-blind randomized study of the effects of the new calcium channel blocking drug nisoldipine on left ventricular (LV) size and function after acute myocardial infarction. Randomization to placebo or to long-acting nisoldipine core coat (20 mg once daily) was performed in 135 eligible patients with mild to moderate systolic LV dysfunction (LV ejection fraction < or = 50%) 20 days (range 7-35) after infarction, with serial clinical, echocardiographic, and Doppler cardiographic measurements during a 4 week follow-up period. At the end of the follow-up period, exercise capacity was determined by bicycle ergometry. Nisoldipine improved indices of diastolic LV function. Early diastolic transmitral blood flow velocity increased, with an increase in peak E wave of 0.06 m/sec (95% confidence intervals [CI], 0.01, 0.11) and an increase in time velocity integral of 1.2 cm (95% CI, 0.16, 2.27). Isovolumic relaxation time was reduced by 14.7 msec (95% CI, -22.5, -6.9), a change not explained by the very small (and not significant) changes in systemic arterial pressure, heart rate, or cardiac output. There was no change in systolic and diastolic LV volume, nor in LV ejection fraction. Exercise capacity was greater by 12 watts (95% CI, 0.8, 23.3) in patients receiving nisoldipine, while the incidence of > or = 1 mm ST-segment depression (relative occurrence 0.54, 95% CI, 0.30-0.97) and the incidence of angina pectoris (relative occurrence 0.67, 95% CI, 0.42-1.08) during exercise testing tended to be lower in this group. Although the relations were not exact, peak exercise workload 7 weeks after infarction correlated with resting measurements of diastolic LV function. Exercise workload was inversely related to peak late diastolic transmitral blood flow velocity (A wave, slope, -86.6; 95% CI, -120.9, -52.2) and directly to the E/A ratio (slope, 20.5, 95% CI, 6.0, 35.1). The relations between exercise workload and peak late diastolic flow velocity remained significant after correction for age, sex, resting heart rate, and usage of beta-blocking drugs or nisoldipine. Exercise capacity was not related to measurements of systolic LV function (LV end-diastolic and end-systolic volume, LV ejection fraction, stroke volume, cardiac index). In summary, the calcium channel blocker nisoldipine improved measurements of diastolic LV function in patients recovering from acute myocardial infarction. Exercise capacity was higher in patients receiving the drug, and there was less exercise induced ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The DEFIANT study of left ventricular function and exercise performance after acute myocardial infarction. Doppler Flow and Echocardiology in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy Study Group. 794 83

We examined the cardioprotective effect of nisoldipine against myocardial dysfunction during ischemia and reperfusion in comparison with those of diltiazem and nifedipine in rabbit hearts perfused at constant pressure. These calcium antagonists were administered to the hearts before 60 min of ischemia. They inhibited the increase of end-diastolic pressure during ischemia in a dose-dependent manner. Diltiazem at 1.0 microM, nifedipine at 3.0 microM and nisoldipine at 0.01 microM produced the maximal cardioprotective effect. Nisoldipine had a beneficial effect with less negative inotropic effect than those of diltiazem and nifedipine and it produced a significant increase of coronary flow during reperfusion. When the vascular component was eliminated under constant flow perfusion, nisoldipine also showed the cardioprotective effect. Nisoldipine did not produce any beneficial effect without the inhibition of the increase in end-diastolic pressure during ischemia nor did it do so without the increase of reperfusion flow. Therefore, the nisoldipine-increased coronary flow during reperfusion as well as the inhibition of ischemic contracture by nisoldipine seems to play a crucial role in improving the myocardial dysfunction of ischemic-reperfused hearts.
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PMID:Improvement of ischemic myocardial dysfunction by nisoldipine in relation to its coronary vasodilating action. 834 Oct 23

Exercise ECG is an established method of evaluating the anti-ischemic properties of drugs. However, there are considerable methodologic limitations to this procedure and its use is restricted to patients with exercise-provoked ECG alterations which can be interpreted as ischemia. The principal, earlier onset of wall motion abnormalities according to the ischemic cascade can be detected by stress echocardiography and might be utilized as a pharmacological stress testing modality. Sixteen consecutive patients (15 men, one woman; 53 +/- 9 years old) with angiographically proven coronary artery disease (8 with one-, 5 with two-, and 3 with three-vessel disease) and exercise-induced wall motion abnormalities were examined by dynamic stress echocardiography (50 watt followed by 20-watt increases/min). Anti-ischemic drugs were withdrawn prior to and on day 1; on the following day 2, 0.2 microgram/kg/min nisoldipine was infused intravenously during the test after a 3 micrograms/kg bolus was given. At maximum comparable workload 15/16 patients showed an improved wall motion score on treatment (day 1: 22.9 +/- 4.9 vs day 2: 20.0 +/- 3.9; normal score: 12; one-sided binomial test: p = 0.0003). Eight of 16 patients demonstrated ST-segment deviations on day 1 and day 2. The double product did not differ at any workload stage until the maximum of 130 watt (day 1: 14,101 +/- 3140 vs day 2: 13,365 +/- 2865; n.s.). Dynamic stress echocardiography seems to be a valuable tool in pharmacologic stress testing and in terms of accuracy is supposed to be superior to conventional exercise ECG. Nisoldipine reduces exercise-induced wall motion abnormalities in patients with and without exercise-induced ECG alterations. The data result from a controlled pilot study, and further studies are required to confirm these promising methodological and therapeutic findings.
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PMID:Dynamic stress echocardiography for evaluating anti-ischemic drug profiles in post-MI patients. 941 50


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