Effect of nimodipine on systemic, renal, and cerebral haemodynamics after a mild hypoxic-ischaemic insult in newborn piglets.
Because many Ca2+ channel blocking agents are known to cause adverse systemic effects, in this study we tested the haemodynamic side effects of nimodipine with and without a mild hypoxic-ischaemic (HI) insult in a newborn piglet model. Fifteen min after completing a brief period of asphyxia we gave i.v. nimodipine as 5 micrograms kg-1 bolus followed by 0.1 microgram kg-1 min-1 continuous infusion for 105 min in six piglets, while the same treatment was repeated in five animals without preceding HI insult. At third group of six served as sham operated controls. In the HI insult group by 105 min of nimodipine infusion the mean BP dropped by 30% and the cardiac output dropped by 23% of respective baseline. In this group, the renal blood flow dropped between 65% and 77% of baseline and regional cerebral blood flow dropped between 28% and 55% of respective baseline by 45 min and 105 min of nimodipine fashion. In the group with no prior HI insult, 105 min of nimodipine infusion caused no significant changes in these variables. Despite nimodipine infusion, HI insult caused a significant increase in the mean brain water content compared to the two control groups: 89 +/- 3.2% compared to 82.7 +/- 0.5% in the nimodipine control group, and 83.7 +/- 1.7% in the sham group (P < 0.0001). We conclude that while nimodipine therapy without prior asphyxial insult does not cause significant adverse haemodynamic effects, its infusion after even a mild HI insult could cause reduction in renal blood flow and moderate reduction in regional cerebral blood flow, BP, and cardiac output, suggesting a differential effect. A 15 min lag between HI insult and nimodipine therapy may be too long to prevent cerebral oedema.
Raju
T N
TN
Department of Pediatrics, University of Illinois at Chicago 60612, USA.
John
E
E
Shankararao
R
R
Fornell
L
L
Vasa
R
R
Abu-Harb
M
M
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D007511:Ischemia / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009553:Nimodipine / Q000494:pharmacology*; D013552:Swine
D002121:Calcium Channel Blockers; D009553:Nimodipine