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      Effect of CLS 2210 (Calcium Dobesilate) on Survival and Myocardial Infarction Size in the Rat: Influence of Dose and Duration of Treatment



      S. Karger AG

      Infarct size, CLS 2210 (calcium dobesilate), Dose-response, Mortality

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          CLS 2210 (calcium dobesilate) has been shown to reduce the volume of myocardium infarcted after coronary artery occlusion in the dog. This study, in rats, was designed to determine whether CLS 2210 would reduce mortality and infarct size after coronary occlusion. Another goal was to ascertain whether a duration of administration exceeding 6 h improves survival. Experiments were performed in rats with myocardial infarction induced by coronary artery ligation. In one series, rats were blindly randomized into four groups receiving, over a period of 6 h, either 200,400 or 800 mg/kg of CLS 2210 or a placebo. In a second series, the animals were randomized to receive as initial dose a bolus of either 50 mg/kg of CLS 2210 by intravenous infusion or placebo followed by 25 mg/kg/h of the same drug or placebo over 24 h: mortality and infarct size were assessed after 24 h. A third series of rats received the same dosage schedule of CLS 2210 or placebo, but mortality was evaluated after 1 week, to ascertain whether CLS 2210 merely postponed death. Our first goal in this study was to ascertain whether CLS 2210 would improve survival after coronary artery occlusion in the rat. In the placebo group, death occurred in 61 of 112 rats (54.5%). In the CLS-2210-treated group, mortality was sharply reduced, to 68 of 182 (37.3%; p < 0.01). Mortality in rats receiving CLS 2210 for 6 h was significantly lower, 35.6%, when compared to the placebo which was 51.9% (p < 0.05). No evidence of a dose-response relationship was apparent with the 3 dosages of CLS 2210. Mortality in rats treated for 24 h with either CLS 2210 (38 %) or placebo (56.5 %) was similar to that associated with 6 h of treatment, indicating that all of the benefit was gained during that crucial early interval. A nonparametric assessment of the percentage of left ventricle infarcted among survivors in the second series revealed a statistically significant difference: 22 out of 27 survivors in the CLS 2210 group had an infarct that was less than the mean placebo value (p < 0.05). CLS 2210 favorably influences both survival and infarct size. Moreover, it appears that the entire impact of this drug is exerted during the first crucial 6 h after myocardial infarction. A threshold dose is not yet defined.

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          Author and article information

          S. Karger AG
          12 November 2008
          : 80
          : 1
          : 28-33
          Department of Radiology and Medicine, Brigham and Woman’s Hospital and Harvard Medical School, Boston, Mass., USA
          174976 Cardiology 1992;80:28–33
          © 1992 S. Karger AG, Basel

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          Page count
          Pages: 6
          General Cardiology, Basic Research


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