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Biomedical subjects

I Sugo

Publications and source records attributed to I Sugo.

3 recordsLinked to original sources
PubMed1999

Hemodynamic and hormonal responses to nicorandil in a canine model of acute ischemic heart failure: a comparison with cromakalim and nitroglycerin.

The pharmacologic profiles of nicorandil in the cardiovascular system have been characterized by K-channel opening and nitrate activities. However, the effects of nicorandil on acute heart failure have yet to be elucidated. To investigate the effects of nicorandil under such pathophysiologic conditions, we administered nicorandil intravenously to dogs with acute ischemic heart failure induced by coronary embolization and compared the results with those induced by cromakalim and nitroglycerin. The heart failure in this experiment was demonstrated by a reduction of mean blood pressure (MBP) from 143+/-3 to 129+/-2 mm Hg (p < 0.01); cardiac output (CO) from 2.18+/-0.10 to 1.06+/-0.05 L/min (p < 0.01); stroke volume (SV) from 12.7+/-0.6 to 6.8+/-0.3 ml/min (p < 0.01); Vmax, an index of the contractility of the left ventricle, from 105.5+/-4.4 to 49.9+/-1.8 1/s (p < 0.01), and an increase in right atrial pressure (RAP) from 2.9+/-0.3 to 5.3+/-0.3 mm Hg (p < 0.01); left ventricular end-diastolic pressure (LVEDP) from 2.5+/-0.4 to 26.0+/-1.4 mm Hg (p < 0.01); and T, time constant of left ventricular relaxation, from 38.3+/-0.8 to 62.4+/-2.8 ms (p < 0.01). Furthermore, plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) increased (from 1.72+/-0.29 to 5.03+/-0.68 ng AngI/ml/h, p < 0.01; from 103.9+/-5.8 to 411.5+/-29.4 pg/ml, p < 0.01, respectively), whereas brain natriuretic peptide (BNP) remained unchanged (from 23.1+/-2.2 to 26.9+/-1.4 pg/ml). Nicorandil (10-40 microg/kg/min, i.v. infusion for 20 min for each dosing) or cromakalim (0.25-1 microg/kg/min) decreased MBP, systemic vascular resistance (SVR), RAP, and LVEDP, and increased CO, SV, and Vmax. However, the reduction of RAP in cromakalim was significantly smaller than those of nicorandil and nitroglycerin in comparison at similar hypotensive doses. Nitroglycerin (2.5-10 microg/kg/min) decreased MBP, RAP, and LVEDP, and increased Vmax but did not change CO or SV. Increased plasma ANP levels, an index of cardiac filling pressure after induction of acute ischemic heart failure, were decreased significantly by cromakalim and tended to decrease by nicorandil or nitroglycerin. Plasma BNP levels and PRA were not influenced by any of these drugs. These results suggest that nicorandil produces the reduction of both preload and afterload followed by an improvement of cardiac contractility in this model. The increase in CO may be mediated mainly by the drug's K-channel opening activities and the reduction of venous tone by its nitrate properties. Nicorandil may prove to be useful in the treatment of acute ischemic heart failure.

Acute Disease↗
PubMed1994

In vivo bronchodilator action of a novel K+ channel opener, KC 399, in the guinea pig.

We evaluated the in vivo bronchodilator effects of KC 399, a novel K+ channel opener. In anesthetized guinea pigs, i.v. administration of KC 399 (1-10 micrograms/kg), BRL38227 (lemakalim, 10-100 micrograms/kg) and salbutamol (0.3-3 microgram/kg) evoked a dose-related reduction in the histamine-induced bronchoconstriction. The dose of KC 399 producing a 50% inhibition of the bronchoconstriction induced by histamine was 2.6 (1.9-3.6) microgram/kg. In exerting this action, KC 399 was approximately 13 times more potent than BRL38227, but approximately 4 times less potent than salbutamol. The bronchodilator action of i.v. KC 399 (10 micrograms/kg) lasted for over 30 min, whereas that induced by either BRL38227 (100 micrograms/kg) or salbutamol (3 micrograms/kg) lasted less than 10 min. When given by inhalation, KC 399 (1-30 micrograms/ml) induced a more prolonged effect and was a more potent bronchodilator than BRL38227 (0.3-1 mg/ml) in the histamine-induced bronchoconstriction model. Inhaled KC 399 (30 and 100 micrograms/ml) also prevented the antigen-induced bronchoconstriction in sensitized guinea pigs under anesthetic. When given by the oral route, KC 399, BRL38227 and salbutamol protected conscious guinea pigs from asphyxic collapse in response to inhaled histamine, their effective doses being 0.03, 1 and 3 mg/kg, respectively. From these in vivo experimental results, we conclude that KC 399 is an orally active, potent and long lasting bronchodilator.

Administration, Inhalation↗