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Biomedical subjects

A Albernaz

Publications and source records attributed to A Albernaz.

3 recordsLinked to original sources
PubMed1998

Beneficial effects of long-term selective endothelin type A receptor blockade in canine experimental heart failure.

OBJECTIVES: We examined the effects of chronic type A endothelin receptor (ETA) blockade in a dog model of pacing-induced cardiomyopathy. METHODS: Eight dogs received an ETA antagonist, LU 135252 (50 mg/kg orally daily) and nine dogs received a matching placebo starting at day three of pacing and continued for the remainder of the three weeks of pacing. RESULTS: In the placebo group, the mean pulmonary artery pressure and left ventricular end diastolic pressure increased from 16 +/- 3 and 8 +/- 2 mmHg, respectively, at baseline to 40 +/- 11 and 34 +/- 7 mmHg, respectively, at two weeks (both p < 0.001 versus baseline). Cardiac output declined from 3.5 +/- 0.7 to 1.9 +/- 0.6 l/min (p < 0.001). In the treatment group, LU 135252 attenuated the increase in mean pulmonary artery and left ventricular end diastolic pressure (16 +/- 3 and 9 +/- 1 mmHg at baseline to 29 +/- 3 and 27 +/- 3 mmHg, respectively, at two weeks (p < 0.001), and the decline in cardiac output (3.2 +/- 0.3 to 2.6 +/- 0.8 l/min, p < 0.01; p < 0.05 versus placebo for the three parameters). Systemic and pulmonary vascular resistance increased only in the placebo group. Left ventricular end-diastolic volume increased to a similar degree. However, LU 135252 attenuated the increase in plasma norepinephrine level (placebo, 1.2 +/- 0.5 to 3.7 +/- 1.9 pmol/l; treatment, 0.8 +/- 0.3 to 2.4 +/- 0.6 pmol/l; both p < 0.001 versus baseline; p < 0.05 versus placebo). CONCLUSION: Our results suggest that endothelin-1 plays a role in the hemodynamic perturbations in canine pacing-induced cardiomyopathy. The favourable hemodynamic effects without concomitant aggravation of neurohormonal activation suggests that ETA receptor blockade may be beneficial in the treatment of heart failure.

Administration, Oral↗
PubMed1998

Increased cardiac and pulmonary endothelin-1 mRNA expression in canine pacing-induced heart failure.

The canine model of pacing-induced heart failure (HF) simulates human dilated cardiomyopathy and is characterized by severe hemodynamic perturbations. We have previously demonstrated increased plasma endothelin-1 (ET-1) and left ventricular (LV) tissue peptide levels in this model. However, the gene expression of ET-1 has not been studied. Accordingly, we compared preproET-1 mRNA in the lungs and LV in control normal dogs, dogs with severe HF after 3 weeks of rapid pacing (pHF), and pHF dogs chronically treated with an ETA antagonist, LU135252 (pHF-LU). PreproET-1 mRNA expression was determined by ribonuclease protection assay and quantified by densitometry. In paced dogs, mean pulmonary artery pressure (PA) and LV end-diastolic pressure (LVEDP) increased markedly from 16 +/- 4 and 8 +/- 3 mm Hg, respectively, at baseline to 40 +/- 11 and 34 +/- 7 mm Hg, respectively, at 3 weeks (both p < 0.001). Treatment with LU135252 attenuated the increase in PA and LVEDP by 30% and 19%, respectively (p < 0.05 for both). Compared to controls, preproET-1 mRNA expression in the LV and lungs was markedly increased in pHF. This was not changed in the LV but was reduced in the lungs by treatment with the ETA antagonist. Increased pulmonary and LV expression of preproET-1 suggests that ET-1 plays a role in mediating the pulmonary hypertension and LV dysfunction characteristic of this model.

Animals↗