The effects of vasoactive intestinal peptide on monocrotaline induced pulmonary hypertensive rabbits following cardiopulmonary bypass: a comparative study with isoproteronol and nitroglycerine.
BACKGROUND
Vasoactive intestinal peptide (VIP) has regulatory effects on myocardial and vasomotor functions usually demonstrated by in vitro or isolated heart studies. We studied in vivo effects in monocrotaline induced pulmonary hypertensive rabbits immediately after cardiopulmonary bypass (CPB) and tested them versus calcium channel and beta-blockers.


METHODS
The study consisted of six groups (N=30; five rabbits/group): (1) Control with no pretreatment, monocrotaline injected groups: (solutions were perfused following termination of CPB for 60 min); (2) Control for pulmonary hypertension (PHT); (3) isoproteronol; (4) VIP 10(-6) M; (5) VIP 10(-5) M; (6) nitroglycerine. Normothermic CPB was instituted in thirty rabbits at a flowrate of 100 ml/kg/min for 120 min. Heart rate, mean arterial pressure (MAP), central venous, left atrium (LAP), pulmonary artery (PAP) pressures, pulmonary resistance (Rp), blood gases and ions were measured before and 15, 30, 45 and 60 min after CPB. The VIP 10(-5) M group was subjected to an additional 1.7 x 10(-6) M propranol and 2 mM verapamil infusions for a further 15 min.


RESULTS
LAP, PAP, Qp, and Rp were significantly higher in the PHT control group (P<0.001). VIP 10(-5) M increased MAP and decreased PAP significantly with respect to isoproteronol and VIP 10(-6) M (P<0.05). VIP 10(-5) M also decreased Rp significantly in the early post CPB 15th minute (P<0.05), but did not show any superiority to other agents in the following minutes. Verapamil inhibited VIP 10(-5) M effects but propranol did not.


CONCLUSIONS
VIP has dose responsive, positive inotropic and pulmonary vasodilatory effects in whole body CPB model acting via calcium channels.
Gunaydin
Serdar
S
Department of Pediatric Cardiac Surgery, Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan. gunaydin@marketweb.net.tr
Imai
Yasuharu
Y
Takanashi
Yoshinori
Y
Seo
Kazuhiro
K
Hagino
Ikuo
I
Chang
Dehua
D
Shinoka
Toshiharu
T
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002315:Cardiopulmonary Bypass; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary; D017380:Hypertrophy, Right Ventricular; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D016686:Monocrotaline; D005996:Nitroglycerin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011817:Rabbits; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D014660:Vasoactive Intestinal Peptide; D016686:Monocrotaline; D011433:Propranolol; D014700:Verapamil; D005996:Nitroglycerin; D007545:Isoproterenol