Cardiovascular effects of epinephrine during rewarming from hypothermia in an intact animal model

Abstract

Rewarming from accidental hypothermia is often complicated by "rewarming shock," characterized by low cardiac output (CO) and a sudden fall in peripheral arterial pressure. In this study, we tested whether epinephrine (Epi) is able to prevent rewarming shock when given intravenously during rewarming from experimental hypothermia in doses tested to elevate CO and induce vasodilation, or lack of vasodilation, during normothermia. A rat model designed for circulatory studies during experimental hypothermia and rewarming was used. A total of six groups of animals were used: normothermic groups 1, 2, and 3 for dose-finding studies, and hypothermic groups 4, 5, and 6. At 20 and 24 degrees C during rewarming, group 4 (low-dose Epi) and group 5 (high-dose Epi) received bolus injections of 0.1 and 1.0 microg Epi, respectively. At 28 degrees C, Epi infusion was started in groups 4 and 5 with 0.125 and 1.25 microg/min, respectively. Group 6 served as saline control. After rewarming, both CO and stroke volume were restored in group 4, in contrast to groups 5 and 6, in which both CO and stroke volume remained significantly reduced (30%). Total peripheral resistance was significantly higher in group 5 during rewarming from 24 to 34 degrees C, compared with groups 4 and 6. This study shows that, in contrast to normothermic conditions, Epi infused during hypothermia induces vasoconstriction rather than vasodilation combined with lack of CO elevation. The apparent dissociation between myocardial and vascular responses to Epi at low temperatures may be related to hypothermia-induced myocardial failure and changes in temperature-dependent adrenoreceptor affinity.

Is oxygen supply a limiting factor for survival during rewarming from profound hypothermia?

“…A factor in CO depression in group 3 is a higher TPR than in group 2. The demonstration in a recent study using the present model that a low afterload was a prerequisite for an increase in CO during rewarming supports the idea that hypothermia induces cardiac failure (18). The elevation of SV in rat hearts in response to hypothermia also shown in the present experiments is consistent with results from other in vivo as well as in vitro experiments.…”

Negative inotropic effects of epinephrine in the presence of increased β-adrenoceptor sensitivity during hypothermia in a rat model

“…However, hypothermia-induced b-adrenoceptor hypersensitivity is disputed, as several studies have observed reduced inotropic effects of b-adrenoceptor agonists [30,12,7,14]. Kunos and Nickerson proposed a hypothermia-induced reduction in receptor sensitivity caused by conversion from b-to a-properties of adrenoceptors [16].…”

“…Numerous preclinical studies support this careful approach to pharmacologic treatment of hypothermic patients: They report hypothermia-induced changes in pharmacodynamics and pharmacokinetics of potent drugs like Epi and isoproterenol [30,12,7,14]. This is supported by studies showing that reduced core temperature induces a decline in cytochrome P450 activity and other important enzymes for drug elimination [37].…”

“…3 different temperature protocols were used: Animals in the hypothermic Epi group (n = 8) were core cooled to 15°C and maintained at this temperature for 4 h, before a 5 min infusion of 1.25 lg/min Epi was administered through a catheter in the femoral vein at the end of experiments. This dose of Epi was selected according to other studies in the same model [30,12]. Rewarmed (n = 6) Epi animals underwent the same protocol as the hypothermic Epi group but were rewarmed to 37°C prior to 5 min infusion of 1.25 lg/min Epi.…”

Conséquences cardiovasculaires de l’hypothermie

“…Accessoirement, on peut noter la possibilité de réponses particulières à l'hypothermie selon les différentes circulations régionales. Expérimentalement en HA, il semble exister à basse température une dissociation entre les réponses diminuées myocardique et vasculaire [59,60]. Un changement d'affinité des récepteurs adrénergiques des vaisseaux dépen-dant de la température pourrait en être la cause.…”