Synthetic atrial natriuretic peptide improves systemic and splanchnic circulation and has a lung-protective effect during endotoxemia in pigs.
BACKGROUND
Pharmacological blockade of the renin-angiotensin system is thought to maintain gut perfusion during circulatory stress and thereby avoid later failure of distant organs. In this controlled experimental study, we investigated the effects of carperitide, a synthetic atrial natriuretic peptide that inhibits the renin-angiotensin system, on the systemic and splanchnic circulation during fluid-resuscitated endotoxemia in pigs.


METHODS
Sixteen domestic pigs of both sexes were randomly divided into 2 groups. The pigs were anesthetized and their lungs ventilated before receiving either saline (Group A: n = 8) or carperitide (Group B: n = 8). After a baseline measurement was taken, the pigs from both groups received a continuous infusion (1.7 microg x kg(-1) x h(-1)) of endotoxin for 240 min. Group B received a continuous infusion of carperitide (0.05 microg x kg(-1) x min(-1)) starting 30 min before the endotoxin infusion and lasting until the end of the study, whereas Group A received the same volume of saline. Fluid resuscitation was titrated to maintain pulmonary artery wedge pressure between 10 and 12 mm Hg. Systemic and regional hemodynamics, oxygenation variables, and the arterial-to-intestinal PCO(2) gap were measured at baseline and after endotoxin infusion for 240 min. The primary end points were cardiac index, superior mesenteric artery flow index, and PCO(2) gap at the end of this study (T240).


RESULTS
Cardiac index and superior mesenteric artery flow index in Group B were significantly higher than those in Group A at T240 (83 +/- 15 vs 135 +/- 23 mL x kg(-1) x min(-1), P < 0.001; 2.6 +/- 1.4 vs 7.9 +/- 4.8, P = 0.01), respectively. Carperitide administration resulted in a significantly better maintenance of intestinal mucosal perfusion assessed by the PCO(2) gap at T240 (33.0 +/- 14.5 vs 11.6 +/- 10.0 mm Hg, P = 0.004). The PaO(2)/FIO(2) ratio in Group B was significantly greater than that in Group A from T60 to T240.


CONCLUSIONS
In this porcine fluid-resuscitated endotoxemia model, a low dose of carperitide administered before endotoxemia maintained systemic and splanchnic circulation, and prevented the deterioration of oxygenation. Atrial natriuretic peptide infusion is a potentially beneficial therapy with respect to systemic and splanchnic circulation as well as the respiratory system during sepsis.
Sekino
Motohiro
M
Intensive Care Unit, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
Makita
Tetsuji
T
Ureshino
Hiroyuki
H
Sungsam
Cho
C
Sumikawa
Koji
K
D000758:Anesthesia; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D001775:Blood Circulation / Q000187:drug effects*; D001784:Blood Gas Analysis; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008171:Lung Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008638:Mesenteric Arteries; D010101:Oxygen Consumption / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine
D004731:Endotoxins; D008070:Lipopolysaccharides; C472955:NPPA protein, human; C044101:endotoxin, Escherichia coli; D009320:Atrial Natriuretic Factor