Clinical Science (2003) 104, 491–492 (Printed in Great Britain) 491
+ C O M M E N T
Coronary and sympathetic responses to core
hypothermia: answers and questions
It is a time-honoured clinical observation that in patients number of intriguing questions. This is also the case for
with coronary heart disease exposure to cold environ- the present investigation [1], which raises at least three
ments may trigger the development of anginal attacks, questions. Do the results apply to patients with coronary
thereby aggravating the unbalanced condition of cor- heart disease ? Would the coronary and sympathetic
onary perfusion already displayed by these subjects. It is responses to core hypothermia described in young
also believed that the pathophysiological mechanism subjects be affected by the aging process ? Do the study’s
leading to the acute myocardial ischaemic event is findings rule out the pathophysiological participation
represented by a decrease in coronary blood flow induced of neurohumoral and vasoactive systems, other than the
by the sudden exposure to cold environmental tempera- neuro-adrenergic one, in coronary responses to cold
tures. exposure ?
The first question has been already addressed by Frank
et al. [1] by quoting the results of a previously published
Cardiovascular and adrenergic effects of
study [2] showing that cold exposure triggered coronary
core hypothermia vasodilation in healthy subjects, but coronary vasocon-
In this issue of Clinical Science, a study by Frank and co-
striction in patients with ischaemic heart disease. It
workers [1] is an important step forward in our under-
should be noted, however, that other evidence of the
standing of the coronary and myocardial responses (and
differential effects of a given stimulus in healthy and
related mechanisms) to hypothermia. The new major
diseased coronary vessels have been shown. It has been
findings provided by the study [1] can be summarized as
shown, for example, that immersion of the face in cold
follows. First, in young healthy subjects, a reduction in
water (the so-called ‘ diving reflex ’) may cause a different
core temperature by 1 °C, achieved by systemic infusion
degree of coronary vasoconstriction in patients with
of cold saline, elicited an increase in coronary per-
coronary artery disease, according to the less or more
fusion coupled with a tachycardic and a pressor response
marked degree of the impairment in resting myocardial
(mainly systolic), thereby resulting in an increase in
perfusion [3]. It has also been shown that acute cigarette
the heart rate–pressure product and myocardial oxygen
smoking, which is known to cause a marked increase in
demand. Secondly, these marked systemic and coronary
blood pressure and heart rate mediated by a sympathetic
haemodynamic responses are accompanied by a con-
stimulation [4], while not inducing a substantial change in
sistent increase in circulating plasma noradrenaline
coronary blood flow in healthy subjects, elicits coronary
and adrenaline levels. Finally, administration of a
vasoconstrictor effects in patients with ischaemic heart
β-adrenergic blocker abolished the observed tachycardic
disease [5,6]. It would be thus of major clinical relevance
response, and also attenuated the concomitantly reported
to investigate the sympathetic and coronary vasomotor
increase in plasma catecholamines and systolic blood
responses to core hypothermia in patients with coronary
pressure.
artery stenosis of different angiographic severity.
As properly discussed by Frank et al. [1], these three
It will also be of major clinical relevance to examine
sets of data lead to the conclusion that cold exposure does
how aging affects the coronary and adrenergic responses
not cause coronary vasoconstriction, but rather vaso-
to core hypothermia, given the evidence that elderly
dilatation. They also show that a reduction in core
individuals : (i) display an age-related increase in cardio-
temperature increases cardiac work and markedly stimu-
vascular sympathetic drive [7], (ii) are characterized
lates the release of the adrenergic neurotransmitters at the
by an endothelial dysfunction which may impair the
level of both peripheral nerves and the adrenal medulla,
coronary vasomotor responses to hypothermic stimuli
suggesting that a neuro-adrenergic activation is respon-
[8], and (iii) show a functional impairment in the vascular,
sible for some of the cold-induced haemodynamic effects
as well as the sympathetic, components involved in the
(tachycardia and systolic blood pressure increase). This
thermoregulatory process [9].
conclusion is strengthened by the evidence that acute
Finally, the evidence provided by the study by Frank
β-blockade abolishes or attenuates the heart rate, blood
et al. [1] that acute blockade of β-adrenergic receptors
pressure and catecholamine responses to cold stimuli.
attenuates, but not completely normalizes, the coronary
blood flow responses to core hypothermia, suggests that
Outstanding questions neurohumoral, as well as vasoactive systems other than
As often happens in research, the findings provided by the adrenergic one, participate in the phenomenon. These
a well-designed and accurately performed study raise a may include endothelial function, given the evidence that
# 2003 The Biochemical Society
+ C O M M E N T
Coronary and sympathetic responses to core
hypothermia: answers and questions
It is a time-honoured clinical observation that in patients number of intriguing questions. This is also the case for
with coronary heart disease exposure to cold environ- the present investigation [1], which raises at least three
ments may trigger the development of anginal attacks, questions. Do the results apply to patients with coronary
thereby aggravating the unbalanced condition of cor- heart disease ? Would the coronary and sympathetic
onary perfusion already displayed by these subjects. It is responses to core hypothermia described in young
also believed that the pathophysiological mechanism subjects be affected by the aging process ? Do the study’s
leading to the acute myocardial ischaemic event is findings rule out the pathophysiological participation
represented by a decrease in coronary blood flow induced of neurohumoral and vasoactive systems, other than the
by the sudden exposure to cold environmental tempera- neuro-adrenergic one, in coronary responses to cold
tures. exposure ?
The first question has been already addressed by Frank
et al. [1] by quoting the results of a previously published
Cardiovascular and adrenergic effects of
study [2] showing that cold exposure triggered coronary
core hypothermia vasodilation in healthy subjects, but coronary vasocon-
In this issue of Clinical Science, a study by Frank and co-
striction in patients with ischaemic heart disease. It
workers [1] is an important step forward in our under-
should be noted, however, that other evidence of the
standing of the coronary and myocardial responses (and
differential effects of a given stimulus in healthy and
related mechanisms) to hypothermia. The new major
diseased coronary vessels have been shown. It has been
findings provided by the study [1] can be summarized as
shown, for example, that immersion of the face in cold
follows. First, in young healthy subjects, a reduction in
water (the so-called ‘ diving reflex ’) may cause a different
core temperature by 1 °C, achieved by systemic infusion
degree of coronary vasoconstriction in patients with
of cold saline, elicited an increase in coronary per-
coronary artery disease, according to the less or more
fusion coupled with a tachycardic and a pressor response
marked degree of the impairment in resting myocardial
(mainly systolic), thereby resulting in an increase in
perfusion [3]. It has also been shown that acute cigarette
the heart rate–pressure product and myocardial oxygen
smoking, which is known to cause a marked increase in
demand. Secondly, these marked systemic and coronary
blood pressure and heart rate mediated by a sympathetic
haemodynamic responses are accompanied by a con-
stimulation [4], while not inducing a substantial change in
sistent increase in circulating plasma noradrenaline
coronary blood flow in healthy subjects, elicits coronary
and adrenaline levels. Finally, administration of a
vasoconstrictor effects in patients with ischaemic heart
β-adrenergic blocker abolished the observed tachycardic
disease [5,6]. It would be thus of major clinical relevance
response, and also attenuated the concomitantly reported
to investigate the sympathetic and coronary vasomotor
increase in plasma catecholamines and systolic blood
responses to core hypothermia in patients with coronary
pressure.
artery stenosis of different angiographic severity.
As properly discussed by Frank et al. [1], these three
It will also be of major clinical relevance to examine
sets of data lead to the conclusion that cold exposure does
how aging affects the coronary and adrenergic responses
not cause coronary vasoconstriction, but rather vaso-
to core hypothermia, given the evidence that elderly
dilatation. They also show that a reduction in core
individuals : (i) display an age-related increase in cardio-
temperature increases cardiac work and markedly stimu-
vascular sympathetic drive [7], (ii) are characterized
lates the release of the adrenergic neurotransmitters at the
by an endothelial dysfunction which may impair the
level of both peripheral nerves and the adrenal medulla,
coronary vasomotor responses to hypothermic stimuli
suggesting that a neuro-adrenergic activation is respon-
[8], and (iii) show a functional impairment in the vascular,
sible for some of the cold-induced haemodynamic effects
as well as the sympathetic, components involved in the
(tachycardia and systolic blood pressure increase). This
thermoregulatory process [9].
conclusion is strengthened by the evidence that acute
Finally, the evidence provided by the study by Frank
β-blockade abolishes or attenuates the heart rate, blood
et al. [1] that acute blockade of β-adrenergic receptors
pressure and catecholamine responses to cold stimuli.
attenuates, but not completely normalizes, the coronary
blood flow responses to core hypothermia, suggests that
Outstanding questions neurohumoral, as well as vasoactive systems other than
As often happens in research, the findings provided by the adrenergic one, participate in the phenomenon. These
a well-designed and accurately performed study raise a may include endothelial function, given the evidence that
# 2003 The Biochemical Society
