Cardiovascular profile of 5 novel nitrate-esters: a comparative study with nitroglycerin in pigs with and without left ventricular dysfunction.

摘要

1. Four cumulative 10 min intravenous infusions of 0.05, 0.2, 0.5 and 2.0 mg min-1 were used to compare the cardiovascular profile of 5 novel nitrate-esters dissolved in Intralipid 10% to that of nitroglycerin (GTN) in conscious pigs. 2. Infusion of Intralipid 10% alone had no effect on any of the systemic haemodynamic parameters. GTN infusions decreased mean arterial blood pressure dose-dependently from 94 +/- 2 mmHg to 79 +/- 3 mmHg (P less than 0.05) and raised cardiac output from 2.74 +/- 0.09 l min-1 to 3.40 +/- 0.18 l min-1 (P less than 0.05) due to an increase in heart rate (by up to 43 +/- 3%), as stroke volume decreased slightly. Systemic vascular resistance decreased (by 32 +/- 3%) and left ventricular end-diastolic pressure fell from 5.2 +/- 0.4 mmHg to 2.2 +/- 0.5 mmHg (both P less than 0.05). 3. The novel compounds CEDO 8811, CEDO 8834 and CEDO 8901 increased cardiac output only at the highest dose (7%, 8% and 9%, respectively). There was no change in mean arterial blood pressure as the increase in cardiac output was counterbalanced by arterial vasodilatation. All three compounds reduced left ventricular end-diastolic pressure slightly. 4. CEDO 8816 was a more potent arterial and venodilator than the aforementioned CEDO compounds, as the decreases in systemic vascular resistance and left ventricular end-diastolic pressure were already significant at lower doses. The fall in stroke volume was fully compensated by the increase in heart rate and as a result cardiac output increased by 11 +/- 3% (P less than 0.05) at the highest dose.(ABSTRACT TRUNCATED AT 250 WORDS)