The effect of nifedipine on myocardial perfusion and metabolism in systemic sclerosis. A positron emission tomographic study.

We assessed the effect of nifedipine on myocardial perfusion and metabolism in 9 patients with systemic sclerosis, using positron emission tomography with a perfusion tracer (potassium-38) and a metabolic tracer (18F-fluorodeoxyglucose [18FDG]). Nifedipine, 20 mg 3 times daily for 1 week, induced a significant increase in 38K myocardial uptake, a significant decrease in 18FDG myocardial uptake, and a significant increase in the myocardial 38K: 18FDG ratio. These results indicate that the increase in myocardial perfusion is associated with modifications in myocardial energy metabolism, which probably result from a beneficial anti-ischemic effect of nifedipine in patients with systemic sclerosis.

Nifedipine and thallium-201 myocardial perfusion in progressive systemic sclerosis.

Heart disease in patients with progressive systemic sclerosis may be due in part to myocardial ischemia caused by a disturbance of the coronary microcirculation. To determine whether abnormalities of myocardial perfusion in this disorder are potentially reversible, we evaluated the effect of the coronary vasodilator nifedipine on myocardial perfusion assessed by thallium-201 scanning in 20 patients. Thallium-201 single-photon-emission computerized tomography was performed under control conditions and 90 minutes after 20 mg of oral nifedipine. The mean (+/- SD) number of left ventricular segments with perfusion defects decreased from 5.3 +/- 2.0 to 3.3 +/- 2.2 after nifedipine (P = 0.0003). Perfusion abnormalities were quantified by a perfusion score (0 to 2.0) assigned to each left ventricular segment and by a global perfusion score (0 to 18) for the entire left ventricle. The mean perfusion score in segments with resting defects increased from 0.97 +/- 0.24 to 1.26 +/- 0.44 after nifedipine (P less than 0.00001). The mean global perfusion score increased from 11.2 +/- 1.7 to 12.8 +/- 2.4 after nifedipine (P = 0.003). The global perfusion score increased by at least 2.0 in 10 patients and decreased by at least 2.0 in only 1. These observations reveal short-term improvement in thallium-201 myocardial perfusion with nifedipine in patients with progressive systemic sclerosis. The results are consistent with a potentially reversible abnormality of coronary vasomotion in this disorder, but the long-term therapeutic effects of nifedipine remain to be determined.

Nifedipine and alpha 1-adrenergic blockade in Raynaud's phenomenon.

The efficacy of nifedipine and prazosin in the treatment of Raynaud's phenomenon was assessed in a prospective double-blind randomized cross-over trial in 15 patients. Each patient received one week of nifedipine 20 mg TID, one week of prazosin 1 mg TID, and 2 weeks of placebo. Nifedipine was shown to be effective in reducing both the frequency and the severity of Raynaud's phenomenon, whereas prazosin was ineffective. Before initiation of therapy in the 15 patients, pressor responses to the intravenous alpha 1-agonist phenylephrine were assessed in the basal state, 30 min after 20 mg oral nifedipine, and 30 min after 1 mg oral prazosin; the shift to the right of the log dose-vasopressor response curves to phenylephrine was similar with nifedipine and prazosin.

Nifedipine and Raynaud's phenomenon associated with connective tissue diseases.

We have evaluated the therapeutic effect of the calcium-channel blocking agent nifedipine in Raynaud's phenomenon associated with connective tissue diseases and in idiopathic digital vasospasm. Thirty patients were included in this study: Raynaud's phenomenon was associated with progressive systemic sclerosis (PSS) in ten patients, systemic lupus erythematosus (SLE) in five and rheumatoid arthritis (RA) in three; it was idiopathic (I) in twelve patients. Each patient received, in a double-blind manner and random order, on two consecutive weeks, nifedipine (20 mg three times daily) and placebo. Nifedipine proved to be effective: the mean number of digital vasospastic attacks per week decreased from 20.30 to 5.83 (p less than 0.01). The results in the SLE and RA groups were similar and were pooled. The improvement (in percent decrease) was better in the idiopathic group (90.95) than in the SLE and RA group (78.63, p less than 0.02) and the PSS group (64.02, p less than 0.01).

Calcium entry blocking agents in digital vasospasm (Raynaud's phenomenon).

We have evaluated the therapeutic effect of the calcium entry blocking agent nifedipine in Raynaud's phenomenon associated with connective tissue diseases and in idiopathic digital vasospasm. In a preliminary study 16 patients with a digital vasospasm that could be induced by hand-immersion in cold water (4 degrees C) were challenged a second time with cold water 1 and 6h after 20 mg oral nifedipine. Nifedipine provided an effective protection against this cold-induced vasospasm in 14 of the 16 patients. Thirty patients were included in a short-term ambulatory study: Raynaud's phenomenon was associated with progressive systemic sclerosis (PSS) in 10 patients, systemic lupus erythematosus (SLE) in five and rheumatoid arthritis (RA) in three; it was idiopathic (I) in 12 patients. Each patient received, in a double-blind manner and random order, on two consecutive weeks, nifedipine (20 mg three times daily) and placebo. Nifedipine proved to be effective: the mean number of digital vasospastic attacks per week decreased from 27.3 to 5.8 (P less than 0.01). The results in the SLE and RA groups were similar and were pooled. The improvement (in % decrease) was better in the idiopathic group (90.9) than in the SLE and RA group (78.6, P less than 0.02) and the PSS group (64.0, P less than 0.01).

[Controlled study of nifedipine in the treatment of Raynaud's phenomenon]. / Etude controlée de la nifédipine dans le traitement du phénomène de Raynaud.

In each of the 16 patients included in our first study [6 idiopathic Raynaud's phenomenon (I), 4 associated with systemic lupus erythematosus (SLE) and 6 with progressive systemic sclerosis (PSS)] digital vasospasm could be reproduced by immersion of both hands in cold water (4 degree C). Each patient received in a double-blind manner and random order on two consecutive days, the calcium-channel blocking agent nifedipine (20 mg) and placebo. Nifedipine protection against vasospasm provoked by cold water (4 degrees C) was considered good or excellent in 14 of the 16 patients (p less than 0.001 versus placebo). In the second study, 30 patients [12 I, 10 PSS, 5 SLE and 3 rheumatoid arthritis (RA)] received in a double blind manner and random order, on two consecutive weeks, nifedipine (20 mg 3 time daily) and placebo. The improvement with nifedipine (in percentage of the decrease of the number of vasospastic attacks) was 90.95 in the 1 group, 78.63 SLE and RA and 64.02 in PSS (p less than 0.01). An open study during 3 months has confirmed the effectiveness of nifedipine (10 mg 3 times daily). The improvement was 88.92 in the 1 group, 76.33 in SLE and RA and 59.16 in PSS, 7 out of 30 patients stopped the treatment because of side effects (headache, flush, nausea, oedema of the ankles). Thus nifedipine appears to be extremely useful in the treatment of Raynaud's phenomenon.

[Hydroxyapatite rheumatism (multiple tendon calcification disease). II. - Microscopic study - HL-A antigen - Experimental arthritis - Pathogeny]. / Le rhumatisme à hydroxyapatite (la maladie des calcifications tendineuses multiples). II - Etude microscopique - Antigène HLA - Arthrite expérimentale - Pathogénie.

Optical and electron microscopic studies of the articular fluid in multiple calcification disease reveals the existence of rounded intra- and extracellular crystalline formations. These crystalline formations of calcium and phosphorus are made up of accumulations of tiny crystals shaped like fine needles 200 nm X 15-20 nm and are highly suggestive of hydroxyapatite. Crystals injected into the plantar pads of rats or the knees of rabbits induce an acute inflammatory reaction maximal at 5 hours and recovering in 24 72 hours. Hydroxyapatite crystals are swiftly dissolved in serum and more rapidly still when cells are present. Their dissolution releases calcium into the surrounding area. HLA typing of patients with multiple tendinous calcification (28 cases) or single tendinous calcification (10 cases) shows an increased frequency of HLA A2 and BW 35 in comparison with controls.