We studied papillary muscle mechanics and energetics, myosin phenotype, and ATPase activities in left ventricles from rats bearing a growth hormone (GH)-secreting tumor. 18 wk after tumor induction, animals exhibited a dramatic increase in body weight (+101% vs. controls) but no change in the ventricular weight/body weight ratio. The maximum isometric force of papillary muscles normalized per cross-sectional area rose markedly (+42%, P < 0.05 vs. controls), whereas the maximum unloaded shortening velocity did not change. This was observed despite a marked isomyosin shift towards V3 (32±5% vs. 8±2% in controls, P < 0.001). Increased curvature of the force-velocity relationship (+64%, P < 0.05 vs. controls) indicated that the muscles contracted more economically, suggesting the involvement of V3 myosin. Total calcium-and actinactivated myosin ATPase activities assayed on quickly frozen left ventricular sections were similar in tumor-bearing rats and in controls. After alkaline preincubation, these activities only decreased in tumor-bearing rats, demonstrating that V3 enzymatic sites were involved in total ATPase activity. These data demonstrate that chronic GH hypersecretion in the rat leads to a unique pattern of myocardial adaptation which allows the muscle to improve its contractile performance and economy simultaneously, thanks to myosin phenoconversion and an increase in the number of active enzymatic sites. (J. Clin. Invest.

The rapid and sustained cardiac improvement seen in our patients shows that octreotide therapy for patients with acromegaly may be highly beneficial, even in those patients with advanced cardiac failure.

Bromocriptine is currently and successfully used for the treatment of pituitary prolactinomas. However, bromocriptine appears unable to normalize plasma prolactin levels in about 10% and to reduce tumour size in one-third of cases. The lack of normalization of plasma prolactin levels in spite of a daily dose of bromocriptine equal to or higher than 15 mg suggests a bromocriptine resistance. We compared the long-term effects of bromocriptine and CV 205-502 (a non-ergot derivative D2 dopamine agonist) on plasma prolactin levels and tumour size in seven bromocriptine-resistant prolactinomas. Bromocriptine reduced significantly (P less than 0.001) plasma prolactin levels (from 2307 +/- 518 to 568 +/- 279 micrograms/l) (conversion to Sl units: 1 microgram/l = 20 mU/l). Visual field defects observed in five patients improved in four. However, CT scan analysis showed a decrease in tumour size in only three patients. Except for transient and minor side-effects at the beginning of the treatment, CV 205-502 was well tolerated in five of seven patients. In the remaining two patients nausea and vertigo occurred with high dosages of CV 205-502 and it was necessary to reduce the daily dose. CV 205-502 lowered plasma prolactin to levels similar to those obtained after bromocriptine therapy in four cases. In the three remaining patients, CV 205-502 was more potent than bromocriptine as demonstrated by the further 90% reduction in plasma levels obtained in one case and by the normalization of plasma prolactin levels in the two other cases. One woman became pregnant during CV 205-502 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Lp(a) may contribute to the increased prevalence of atherosclerotic disease in diabetic patients and patients with chronic renal failure, especially in IDDM patients whose lipoprotein pattern was not different from that of the control group.

Hypertriglyceridemia is the most frequent modification of lipid metabolism observed in acromegaly. The somatostatin analog, octreotide (Sandostatin), widely used in the treatment of acromegaly, is able to produce a decrease in levels of growth hormone (GH), insulin, and Insulin-like Growth Factor 1 (IGF1). We have attempted to evaluate the influence of this treatment on the lipid status of acromegalic patients. Seventeen patients with active acromegaly were treated with octreotide, 100 to 500 micrograms/injection subcutaneously three times daily. The levels of fasting serum triglycerides (TG), total cholesterol, High Density Lipoprotein (HDL) cholesterol and IGF1, as well as mean plasma GH and insulin levels during a diurnal profile, were evaluated before and after three months of octreotide therapy. GH, insulin and IGF1 decreased by 61%, 42% and 36% respectively (p less than 0.05). Mean levels (+/- SEM) of TG and total cholesterol fell from 2.2 +/- 0.4 mmol/l to 1.6 +/- 0.3 mmol/l (p less than 0.05) and 6.4 +/- 0.39 mmol/l to 5.6 +/- 0.27 mmol/l (p greater than 0.05), respectively. There was no correlation between triglyceride decrease and hormonal changes or clinical status (BMI, age, sex). In conclusion, the administration of octreotide over a three month period to acromegalic patients is associated with a decrease in TG levels.