Effects of inhaled nitric oxide and intravenous magnesium sulphate, alone and in combination, in a porcine model of hypoxic pulmonary hypertension.
BACKGROUND
In order to compare the effects of inhaled nitric oxide (NO) and magnesium (Mg) and their potential synergism on hemodynamics in pulmonary hypertension, we compared the effect of NO and Mg alone and in combination. The fact that simultaneous administration selectively increases pulmonary vascular relaxation would suggest that their association would allow for a decrease in the NO concentration required for optimal pulmonary vasodilation, thus lowering the risk of side effects.


METHODS
We compared the effects of 20 ppm inhaled NO, 25 mg/kg Mg, and combined therapy in a pig model of hypoxic pulmonary hypertension. Twelve animals were randomly assigned to one of 3 treatment groups: control (group 1); Mg+NO group, receiving Mg followed by NO 15 min later (group 2); NO+Mg group, receiving NO followed by Mg 15 min later (group 3). The cardiac index, pulmonary and systemic pressures, pulmonary and systemic resistance, and the pulmonary to systemic resistance ratio (PVR/SVR) were recorded at baseline, on hypoxia and 15 minutes after each drug alone and in combination.


RESULTS
PVR/SVR decreased with NO alone (0.32+/-0.07 to 0.18+/-0.04; p<0.05) but not with Mg alone. When NO was added to Mg, PVR/SVR decreased significantly (0.31+/-0.06 to 0.16+/-0.02; p<0.05) but not when Mg was added to NO.


CONCLUSIONS
Inhaled NO is a selective pulmonary vasodilator in a pig model of hypoxic pulmonary hypertension. The simultaneous administration of intravenous Mg does not enhance the selective pulmonary vasodilation induced by NO inhalation.
Beghetti
Maurice
M
Cardiology Unit, University of Geneva Hospital, Geneva, Switzerland. Maurice.Beghetti@hcuge.ch
Spahr-Schopfer
Isabelle
I
Mensi
Nouri
N
Morel
Denis R
DR
Rimensberger
Peter C
PC
D000280:Administration, Inhalation; D000818:Animals; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D000860:Hypoxia; D007275:Injections, Intravenous; D008274:Magnesium / Q000097:blood; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D009569:Nitric Oxide; D008278:Magnesium Sulfate; D006152:Cyclic GMP; D008274:Magnesium; D010100:Oxygen