Administration of the calcium agonist BAY K 8644 in endotoxic shock.
Septic shock is characterized by a decreased vascular tone and a depressed myocardial function. An impairment in cellular calcium availability has been incriminated in both phenomenons. The effects of BAY K 8644, a dihydropyridine-derivative agent acting as a slow calcium-channel activator, were studied and compared to those of norepinephrine (NE) on an experimental endotoxin shock model in the dog. Thirty minutes after intravenous administration of E. coli endotoxin (3 mg/kg), fluid therapy with normal saline was initiated to restore and maintain pulmonary artery capillary wedge pressure at baseline level. In the first part of the study (8 dogs), the effects of increasing doses of 1, 2, 4, and 8 mcg/kg/min of BAY K 8644 were evaluated. BAY K 8644 administration resulted in an increase in mean arterial pressure (MAP) (65 +/- 16 to 116 +/- 24 mmHg, P less than 0.001), systemic vascular resistance (SVR) (1,451 +/- 526 to 2,632 +/- 804 dynes.sec.cm-5, P less than 0.01), and left ventricular stroke work (LVSW) (0.08 +/- 0.04 to 0.16 +/- 0.07 g.m/kg, P less than 0.05), without change in mean pulmonary artery pressure, cardiac output, O2 transport, or O2 consumption (VO2). In the second part of the study (10 dogs), BAY K 8644 and NE were administered in a randomized order at increasing doses to achieve an identical increase in MAP. For a 20 mmHg increase in MAP, BAY K 8644 increased more SVR than NE (1,284 +/- 299 to 1,717 +/- 551 vs. 1,415 +/- 312 to 1,470 +/- 603 dynes.sec.cm-5, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Preiser
J C
JC
Department of Intensive Care, Erasme University Hospital, Free University of Brussels, Belgium.
Moulart
D
D
Cosyns
B
B
Vincent
J L
JL
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy*; D014655:Vascular Resistance / Q000187:drug effects
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009638:Norepinephrine