Abstract
Because a mixture of sodium nitroprusside (SNP) and trimetaphan (TMP) induces hypotension at a dose much lower than that of either agent, SNP and TMP are believed to act synergistically. However, the mechanism of this synergy remains to be elucidated. Sixteen dogs were anesthetized with halothane in oxygen. After a baseline period, mean arterial pressure (MAP) was reduced to 60 mmHg for 60 minutes by infusion of 0.02% SNP (n=8) or a SNP (0.02% ) -TMP (0.2%) mixture (n= 8) . The MAP in both groups decreased to approximately 50% of baseline values (P<0.01) . Hypotension induced by SNP and by the SNP-TMP mixture was associated with similar reductions (P<0.01) in systemic vascular resistance. The cardiac index (CI) increased during the hypotensive period (P<0.05) and 10 minutes (P<0.05) after infusion of SNP was stopped. In contrast, CI decreased at 30 minutes (P<0.01) and 60 minutes (P<0.05) of the hypotensive period in the SNP-TMP group. Furthermore, CI was significantly lower in the SNP-TMP group than in the SNP group. Stroke volume index (SVI) increased (P<0.01) during and after hypotension induced with SNP, whereas SVI remained unchanged during the hypotensive period in the SNP-TMP group. With the SNP-TMP mixture, decreases (P<0.01) in heart rate (HR) were observed throughout the observation period. In contrast, HR did not change during hypotension induced by SNP. This study shows that both SNP and a SNP-TMP mixture were equally effective in reducing afterload during induced hypotension but had different effects on CI. The differences in CI between SNP and the SNP-TMP mixture may be attributed to different effects on SVI and HR.
