The effects of transient cerebral ischemia on vasopressin-induced vasoconstriction in rabbit cerebral vessels.

BACKGROUND: Vasopressin is a drug of choice for use during cardiopulmonary resuscitation because several experimental studies have shown that it is better than epinephrine at increasing systemic perfusion pressure and improving cerebral perfusion pressure without increasing myocardial oxygen consumption. We used a pial window preparation to determine the effects of vasopressin when applied topically to pial vessels and whether any effects were altered after cerebral ischemia in rabbits (n = 27). METHODS: We first examined the effects of topical application of arginine-vasopressin (AVP) (10(-11) M, 10(-9) M, 10(-7) M, and 10(-5) M, sequentially). We then examined the effects of topical application of AVP (10(-9) M and 10(-7) M, sequentially) before and after a 5-min intervention consisting of cerebral ischemia produced by inflation of a neck tourniquet plus systemic hypotension or systemic hypotension alone. RESULTS: Pial arteriolar diameters were (a) dilated by 10(-11) M AVP [7% +/- 11% (P = 0.014 versus baseline)], but constricted by 10(-9) M, 10(-7) M, and 10(-5) M AVP [7% +/- 14%, 20% +/- 14%, and 16% +/- 16% (each P < 0.05), respectively], and (b) constricted before hypotension (7% +/- 10% at 10(-9) M, 20% +/- 15% at 10(-7) M) or ischemia (7% +/- 11% at 10(-9) M, 21% +/- 15% at 10(-7) M). However, after the 5-min of ischemia, the decrease in diameter induced by 10(-7) M AVP was significantly reduced but not by hypotension alone [hypotension control group: 7% +/- 10% at 10(-9) M, 19% +/- 14% at 10(-7) M; ischemia group: 5% +/- 11% at 10(-9) M, 10% +/- 13% at 10(-7) M (P = 0.35 versus hypotension control)]. CONCLUSIONS: Topical application of AVP (except at the lowest concentration used here) induced concentration-dependent vasoconstriction of pial arterioles in anesthetized rabbits. The vasoconstrictor effect of 10(-7) M AVP was reduced after transient (5-min) cerebral ischemia.

The comparative effects of intravenous nicardipine and prostaglandin E1 on the cerebral pial arteriolar constriction seen after unclamping of an aortic cross-clamp in rabbits.

BACKGROUND: The potent vasodilators nicardipine and prostaglandin E1 (PGE1) are useful for the treatment of systemic hypertension or pulmonary hypertension during aortic surgery. METHODS: We measured cerebral pial arteriolar diameters, using a rabbit closed cranial window preparation: before (baseline) and 15 min after the start of an IV infusion (preclamp) (0.9% saline [control group], nicardipine [at 0.1, 1.0, or 10 microg x kg(-1) x min(-1)], or PGE1 [at 0.1 or 1.0 microg x kg(-1) x min(-1)]), just after aortic clamping, 20 min after clamping, and at 0-60 min after unclamping. RESULTS: In the control group, a significant decrease in diameter persisted for at least 60 min after unclamping (maximum [at 60 min], -16% for large [> or =75 microm], and -27% for small [<75 microm] arterioles versus baseline). Although the aortic unclamping-induced vasoconstriction was unaffected under the smallest dose of nicardipine, it was significantly attenuated under larger doses in both large and small arterioles (residual vasoconstriction, -10% and -6% for large and -18% and -10% for small arterioles; at 60 min). The pial arteriolar constriction observed at 5 min or more after unclamping in the control group was not altered by PGE1 in either large or small arterioles. CONCLUSIONS: The larger doses of nicardipine, but neither dose of PGE1, attenuated aortic unclamping-induced sustained cerebral pial arteriolar constriction.

Both milrinone and colforsin daropate attenuate the sustained pial arteriolar constriction seen after unclamping of an abdominal aortic cross-clamp in rabbits.

We previously reported that unclamping of an abdominal aortic cross-clamp causes initial dilation of pial arteries followed by sustained constriction. Both milrinone and colforsin daropate have a vasodilator action, and both have been used in such critical conditions as abdominal aortic aneurysmectomy. We measured cerebral pial arteriolar diameters using a rabbit closed cranial window preparation before (baseline) and 15 min after the start of an IV infusion of 0.9% saline (control group), milrinone, or colforsin daropate (0.05 and 0.5 microg . /kg(-1) . min(-1)) (pre-clamp), just after aortic clamping, 20 min after clamping, and at 0 to 60 min after unclamping. In the control group, a significant decrease in diameter persisted for at least 60 min after unclamping (maximum, -15% for large and -26% for small arterioles versus baseline). These values were significantly smaller after both doses of milrinone and the larger dose of colforsin daropate (-5% and -8%, 10% and 12%, and -2% and -5%, respectively vs baseline, at 60 min). In a second experiment, changes in regional cerebral blood flow and tissue oxygen tension reflected changes in vascular variables. Thus, sustained cerebral pial arteriolar constriction induced by aortic unclamping can be attenuated by IV milrinone or colforsin daropate.

Intrathecal neostigmine prevents intrathecal clonidine from attenuating hypercapnic cerebral vasodilation in rabbits.

We previously demonstrated that lumbar intrathecal alpha(2) agonists attenuate hypercapnia-induced cerebral vasodilation. The combination of intrathecal clonidine and neostigmine is being investigated as pain therapy. The effects of their combination on cerebrovascular reactivity are unknown. We allocated rabbits anesthetized with pentobarbital to two groups: (a) clonidine (normal saline followed 30 min later by clonidine 2 microg/kg, both into the lumbar intrathecal space; n = 6), and (b) neostigmine-pretreatment (neostigmine 2 microg/kg followed 30 min later by clonidine 2 microg/kg, both into the lumbar intrathecal space; n = 6). We then evaluated the hypercapnia-induced changes in pial arteriolar diameter in these two groups using the closed cranial window preparation. The pial arteriolar dilator response to hypercapnia was significantly attenuated in the clonidine group (14% +/- 4%, 4% +/- 4%, 6% +/- 6%, and 5% +/- 7% for before and 30, 60, and 90 min, respectively). Neither normal saline nor neostigmine alone induced any change in the cerebral reactivity to hypercapnia. Pretreatment with neostigmine completely prevented the clonidine-induced attenuation of the hypercapnic cerebral vasodilation attenuated by intrathecal clonidine (16% +/- 7%, 15% +/- 6%, 12% +/- 6%, and 16% +/- 8%, respectively).