Effect of pentoxiphylline on oxygen transport during hypothermia.
At least two investigators have demonstrated a reduction in O2 extraction during induced hypothermia (Cain and Bradley, J. Appl. Physiol. 55: 1713-1717, 1983; Schumacker et al., J. Appl. Physiol. 63: 1246-1252, 1987). We hypothesized that administration of pentoxiphylline (PTX), a theobromine that lowers blood viscosity and has vasodilator effects, would increase O2 extraction during hypothermia. To test this hypothesis, we studied O2 transport in anesthetized, paralyzed, mechanically ventilated beagles exposed to hypoxic hypoxia during either 1) normothermia (38 degrees C), 2) hypothermia (30 degrees C), or 3) hypothermia + PTX (30 degrees C and PTX, 20 mg.kg-1.h-1). Measurements included arterial and mixed venous PO2, hemoglobin concentration and saturation, cardiac output, systemic vascular resistance (SVR), blood viscosity, and O2 consumption (VO2). Critical levels of O2 delivery (DO2, the product of arterial O2 content and cardiac output) were determined by a system of linear regression. Hypothermia significantly decreased base line cardiac output (-35%), DO2 (-37%), and VO2 (-45%), while increasing SVR and blood viscosity. Addition of PTX increased cardiac output (35%) and VO2 (14%), and returned SVR and blood viscosity to normothermic levels. Hypothermia alone failed to significantly reduce the critical level of DO2, but addition of PTX did [normothermia, 11.4 +/- 4.2 (SD) ml.kg-1.min-1; hypothermia, 9.3 +/- 3.6; hypothermia + PTX, 6.6 +/- 1.3; P less than 0.05, analysis of variance]. The O2 extraction ratio (VO2/DO2) at the critical level of DO2 was decreased during hypothermia alone (normothermia, 0.60 +/- 0.13; hypothermia, 0.42 +/- 0.16; hypothermia + PTX, 0.62 +/- 0.19; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Hershenson
M B
MB
Department of Anaesthesia, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115.
Schena
J A
JA
Lozano
P A
PA
Jacobson
M J
MJ
Crone
R K
RK
D000818:Animals; D001682:Biological Availability; D001692:Biological Transport / Q000187:drug effects; D001809:Blood Viscosity / Q000187:drug effects; D004285:Dogs; D007035:Hypothermia / Q000097:blood / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D010100:Oxygen / Q000097:blood* / Q000493:pharmacokinetics; D010101:Oxygen Consumption; D010108:Oxyhemoglobins / Q000378:metabolism; D010431:Pentoxifylline / Q000494:pharmacology*; D010827:Physiology / Q000295:instrumentation; D012016:Reference Values; D013805:Theobromine / Q000031:analogs & derivatives*; D014655:Vascular Resistance / Q000187:drug effects
D010108:Oxyhemoglobins; D013805:Theobromine; D010100:Oxygen; D010431:Pentoxifylline