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Influence of the sympathetic nervous system on renal function during hypothermia

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Abstract

Hypothermia increases preglomerular vasoconstriction leading to decreases in renal blood flow (RBF) and glomerular filtration rate (GFR). Since plasma catecholamine concentrations are increased during hypothermia, the present study was performed to determine the role of the renal sympathetic nervous system in the cold-induced renal vasoconstriction. In Inactin anaesthetized rats, hypothermia at 28 degrees C decreased GFR by 50% but failed to alter efferent renal sympathetic nerve activity (ERSNA). Since hypothermia causes shivering which could have influenced the ERSNA recording, Inactin anaesthetized rats were treated with pethidine or rats were anaesthetized with pentobarbital sodium or Saffan to eliminate cold-induced shivering. In these non-shivering rats, hypothermia produced a reversible decrease in ERSNA in association with a fall in GFR that was of a similar magnitude as in shivering rats. Further studies in Inactin anaesthetized rats showed that the fall in GFR was unaltered by renal denervation, bilateral adrenalectomy or intrarenal administration of the alpha 1-adrenoceptor antagonist prazosin. We conclude that cold-induced renal vasoconstriction is not due to an increase in ERSNA or adrenaline/noradrenaline-mediated activation of renal alpha 1-adrenoceptors.

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... Furthermore, moderate hypothermia consistently reduces renal blood flow (9,10). The effects on splanchnic blood flow are more controversial, and both increased and decreased blood perfusion have been reported (13,27). ...
... The present findings of a decreased renal blood flow during moderate hypothermia confirm previous results (9,10). In the present study, pretreatment with hexamethonium abolished the downregulation of renal blood flow in hypothermia, suggesting that the nervous system is involved in this response. ...
... This is compatible with recent results showing a ␤-receptor-mediated dilation in isolated renal afferent arterioles (51) and that they may be sensitized in hypothermia (54). Most of these effects are likely to emanate from circulating catecholamines, since denervation does not affect hypothermia-induced decreases in renal blood flow (10). Indeed, previous studies in human kidneys have shown that intrarenal ␣-adrenoceptors mediate a tonic renal vasoconstriction (1,15,35). ...
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The aim of the study was to characterize the effects of induced moderate hypothermia on splanchnic blood flow, with particular reference to that of the pancreas and the islets of Langerhans. We also investigated how interference with the autonomic nervous system at different levels influenced the blood perfusion during hypothermia. For this purpose, hypothermia (body temperature of 28 degrees C) was induced by external cooling, whereas normothermic (37.5 degrees C) anesthetized Sprague-Dawley rats were used as controls. Some rats were pretreated with either propranolol, yohimbine, atropine, hexamethonium, or a bilateral abdominal vagotomy. Our findings suggest that moderate hypothermia elicits complex, organ-specific circulatory changes, with increased perfusion noted in the pylorus, as well as the whole pancreas and the pancreatic islets. The pancreatic islets maintain their high blood perfusion through mechanisms involving both sympathetic and parasympathetic mediators, whereas the increased pyloric blood flow is mediated through parasympathetic mechanisms. Renal blood flow was decreased, and this can be prevented by ganglionic blockade and is also influenced by beta-adrenoceptors.
... In our previous studies [5,6], moderate hypothermia at 28°C (HT) was found to be accompanied by an approximately 50% reduction of total renal blood flow (RBF), and glomerular filtration rate (GFR) compared with normothermia (NT) at 37.5°C. Since the blood pressure remained largely unchanged, it was calculated that the renal vascular resistance increased twofold, of which 75% was attributed to active vasoconstriction of, primarily, the afferent arteriole. ...
... In search for the factor(s) underlying this pronounced vasoconstriction, an activation of the sympathetic nervous system, our major cold defence system [17], was an unlikely candidate since direct recordings showed that efferent renal sympathetic nerve activity was decreased [6,30,33]. Likewise, surgical renal denervation and α 1 -adrenoceptor blockade were found not to lessen the cold-induced vasoconstriction [6]. ...
... In search for the factor(s) underlying this pronounced vasoconstriction, an activation of the sympathetic nervous system, our major cold defence system [17], was an unlikely candidate since direct recordings showed that efferent renal sympathetic nerve activity was decreased [6,30,33]. Likewise, surgical renal denervation and α 1 -adrenoceptor blockade were found not to lessen the cold-induced vasoconstriction [6]. A study using micropuncture technique showed that both single nephron GFR, and proximal and distal tubular fluid flow decreased by approximately 50% during HT [5]. ...
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Hypothermia-induced reduction of metabolic rate is accompanied by depression of both glomerular perfusion and filtration. The present study investigated whether these changes are linked to changes in renal autoregulation and nitric oxide (NO) signalling. During hypothermia, renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced and urine production was increased, and this was linked with reduced plasma cGMP levels and increased renal vascular resistance. Although stimulation of NO production decreased vascular resistance, blood pressure and urine flow, intravenous infusion of the NO precursor L-arginine or the NO donor sodium nitroprusside did not alter RBF or GFR. In contrast, inhibition of NO synthesis by Nw-nitro-L-arginine led to a further decline in both parameters. Functional renal autoregulation was apparent at both temperatures. Below the autoregulatory range, RBF in both cases increased in proportion to the perfusion ±pressure, although, the slope of the first ascending limb of the pressure-flow relationship was lower during hypothermia. The main difference was rather that the curves obtained during hypothermia levelled off already at a RBF of 3.9 ± 0.3 mL/min then remained stable throughout the autoregulatory pressure range, compared to 7.6 ± 0.3 mL/min during normothermia. This was found to be due to a threefold increase in, primarily, the afferent arteriolar resistance from 2.6 to 7.5 mmHg min mL⁻¹. Infusion of sodium nitroprusside did not significantly affect RBF during hypothermia, although a small increase at pressures below the autoregulatory range was observed. In conclusion, cold-induced rise in renal vascular resistance results from afferent arteriolar vasoconstriction by the autoregulatory mechanism, setting RBF and GFR in proportion to the metabolic rate, which cannot be explained by reduced NO production alone.
... RPF may also be decreased by hypothermia. Hypothermia was found to reduce GFR ex vivo in isolated perfused kidneys (109) and in vivo in nonhibernating mammals due to an increase in preglomerular resistance (19). Cold exposure increases circulating concentrations of epinephrine and norepinephrine in both unanesthetized and anesthetized human subjects (50). ...
... In rats, small changes in net glomerular permeability do not significantly affect GFR, as it is the rise in capillary oncotic pressure during filtration that limits the filtration of small solutes and water (16). It seems more likely therefore that alterations in glomerular plasma flow due to low cardiac output and possibly hypothermia-induced vasoconstriction (19) contribute more to the decline in GFR during torpor. ...
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Hibernators periodically undergo profound physiological changes including dramatic reductions in metabolic, heart and respiratory rates and core body temperature. This review discusses the effect of hypoperfusion and hypothermia observed during hibernation on glomerular filtration and renal plasma flow, as well as specific adaptations in renal architecture, vasculature, the renin-angiotensin system and upregulation of possible protective mechanisms during the extreme conditions endured by hibernating mammals. Understanding the mechanisms of protection against organ injury during hibernation may provide insights into potential therapies for organ injury during cold storage and re-implantation during transplantation.
... During hypothermia there may be an increase in the plasma and urinary concentrations of catecholamines (Granberg, 1991), and also an increased responsiveness to noradrenaline in various vascular beds (Speziali et al. 1994). However, a later report (Broman et al. 1998a) showed that cold-induced renal vasoconstriction is not due to an increased renal sympathetic nerve activity (RSNA) or catecholamine-mediated activation of renal α 1 -adrenoceptors. Nonetheless, altered patterning of renal nerve discharge could be another factor leading to the raised RVR during hypothermia. ...
Article
Acute hypothermia has a major impact on cardiovascular control and renal function, but the extent to which these can be correlated with and influenced by changes in the altered pattern of sympathetic outflow to the kidneys is unclear. Moreover, it is unknown whether these responses to acute hypothermia are altered by chronic cold exposure and this study aimed to examine these factors. Renal function and renal sympathetic nerve activity (RSNA) were measured in male Wistar rats, euthermic (control) or acclimatized (exposed to progressively lower environmental temperature and photoperiod over 8 weeks), anaesthetized with chloralose/urethane. Reduction of core temperature (Tc) to 25°C caused ∼40% reduction in heart rate (HR), ∼10% fall in mean arterial blood pressure (MABP), and decreased glomerular filtration rate (GFR) by ∼50% and ∼5% in euthermic and acclimatized rats, respectively. At 25°C, urine flow increased some two-fold and absolute and fractional sodium excretions by 4- to 6-fold in the euthermic rats and to a lesser extent in the cold acclimatized rats, while basal levels of fluid excretion were higher in the acclimatized rats. A loss of pulsatility in the RSNA signal with cooling was seen in both groups. One of the factors contributing to modest hypotension during acute hypothermia is a reduction in RSNA. There was a progressive fall in the proportion of RSNA power at HR frequency with cooling of 20% in euthermic and 80% in acclimatized rats. All variables were restored to basal levels on rewarming in both groups of rats. We conclude that natriuresis and diuresis in euthermic rats during hypothermia is a consequence of a reduction in nephron reabsorption, reduced urine osmolality and possibly altered patterning of RSNA. In acclimatized rats, the response was modified by altered renal haemodynamics and/or hormonal influences induced by chronic cold exposure to minimize the hypothermic stress on renal function.
... In our study settings, an external factor that may also play a relevant role is cold (Broman et al., 1998;Yoon et al., 2014). Cold weather could increase blood viscosity and also vasoconstriction. ...
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Background: Kidney health needs to be studied in low- and middle-income countries with populations living at high altitude and undergoing urbanization. We studied whether greater level of urbanization was associated with worse kidney function and higher hemoglobin was associated with worse kidney function at high altitude. Methods: Cross-sectional analysis of population-based studies in Peru including five sites at different altitude above the sea level and urbanization level (in decreasing order of urbanization): Lima (sea level), Arequipa (2335 m), urban Puno (3825 m), Tumbes (sea level), and rural Puno (3825 m). The exposures were urbanization and altitude as per study site, and hemoglobin (g/dL). The outcome was the estimated glomerular filtration rate (eGFR). Results: Four thousand two hundred eight people were studied: mean age was 57.4 years (standard deviation: 12.4) and 51.9% were women. In comparison to rural Puno, eGFR was similar in Lima; in comparison to rural Puno, Arequipa, urban Puno, and Tumbes had worse eGFR, for example, in Arequipa, β = -8.07 (95% confidence interval [CI]: -10.90 to -5.24). Intermediate (β = -8.60; 95% CI: -10.55 to -6.66) and high (β = -11.21; 95% CI: -14.19 to -8.24) altitude were negatively correlated with eGFR when only urban places were analyzed. At high altitude, there was a trend for a negative association between hemoglobin and eGFR: β = -1.09 (95% CI: -2.22 to 0.04). Conclusions: Apparently, higher altitude and level of urbanization, except for one highly urbanized site, were associated with worse kidney function. Our findings suggest that some of the adverse impact of high altitude on kidney function has been balanced by the lower risk conferred by rural environments.
... During CPB, hypothermia induces a decrease in tubular reabsorption of sodium and water. 24 Reduced peritubular capillary oncotic pressure owing to extensive hemodilution also interferes with the active reabsorption of sodium and water. 25 In addition, the use of mannitol as a priming solution also leads to the high urinary flow. ...
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Urine output is closely associated with renal function and has been used as a diagnostic criterion for acute kidney injury (AKI). However, urine output during cardiopulmonary bypass (CPB) has never been identified as a predictor of postoperative AKI. Considering altered renal homeostasis during CPB, we made a comprehensible approach to CPB urine output and evaluated its predictability for AKI. Patients undergoing cardiovascular surgery with the use of CPB, between January 2009 and December 2011, were retrospectively reviewed. AKI was defined as an increase in serum creatinine ≥0.3 mg/dL in the first postoperative 48 hours. We extrapolated a possible optimal amount of urine output from the plot of probability of AKI development according to CPB urine output. After separating patients by the predicted optimal value, we performed stepwise logistic regression analyses to find potential predictors of AKI in both subgroups. A total of 696 patients were analyzed. The amount of CPB urine output had a biphasic association with the incidence of AKI using 4 mL/kg/h as a boundary value. In a multivariate logistic regression to find predictors for AKI in entire patients, CPB urine output did not show statistical significance. After separating patients into subgroups with CPB urine output below and over 4 mL/kg/h, it was identified as an independent predictor for AKI with the odds ratio of 0.43 (confidence interval 0.30–0.61) and 1.11 (confidence interval 1.02–1.20), respectively. The amount of urine output during CPB with careful analysis may serve as a simple and feasible method to predict the development of AKI after cardiac surgery at an early time point.
... Effects of whole-body cooling on LUT symptoms may be partly explained by changes in renal function in response to moderate hypothermia. Animal and human experiments have shown that hypothermia decreases antidiuretic hormone release and increases diuresis [4][5][6][7], which lead to an increase in voiding frequency and potentially to urgency. In addition, urgency symptoms can be evoked by cold stimuli that do not evoke significant central hypothermia or increased diuresis, suggesting that activation of peripheral cold sensors can directly influence bladder function. ...
Article
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Acute exposure of part of the skin to cold stimuli can evoke urinary urgency, a phenomenon termed acute cold-induced urgency (ACIU). Despite its high prevalence, particularly in patients with overactive bladder, little is known about the mechanisms that induce ACIU. To develop an animal model of ACIU and test the involvement of cold-activated ion channels transient receptor potential (TRP) M8 and TRPA1. Intravesical pressure and micturition were monitored in female mice (wild-type C57BL/6J, Trpa1(-/-), Trpm8(+/+), and Trpm8(-/-)) and Sprague Dawley rats. An intravesical catheter was implanted. Localized cooling of the skin was achieved using a stream of air or topical acetone. The TRPM8 antagonist (N-(3-aminopropyl)-2-{[(3-methylphenyl) methyl]oxy}-N-(2-thienylmethyl)benzamide (AMTB) or vehicle was injected intraperitoneally. Frequencies of bladder contractions and voids in response to sensory stimuli were compared using the Mann-Whitney or Kruskal-Wallis test. Brief, innocuously cold stimuli applied to different parts of the skin evoked rapid bladder contractions and voids in anesthetized mice and rats. These responses were strongly attenuated in Trpm8(-/-) mice and in rats treated with AMTB. As rodent bladder physiology differs from that of humans, it is difficult to directly extrapolate our findings to human patients. Our findings indicate that ACIU is an evolutionarily conserved reflex rather than subconscious conditioning, and provide a useful in vivo model for further investigation of the underlying mechanisms. Pharmacological inhibition of TRPM8 may be useful for treating ACIU symptoms in patients. Brief cold stimuli applied to the skin can evoke a sudden desire to urinate, which can be highly bothersome in patients with overactive bladder. We developed an animal model to study this phenomenon, and found that it depends on a specific molecular cold sensor, transient receptor potential M8 (TRPM8). Pharmacological inhibition of TRPM8 may alleviate acute cold-induced urinary urgency in humans. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
... Experimental Protocol. Surface cooling without giving anesthetics causes vigorous muscle shivering, preventing accurate nerve recordings in good conditions (17). Thus, we chose an experimental model using anesthesia and muscle relaxant. ...
... In our study settings, an external factor that may also play a relevant role is cold (Broman et al., 1998;Yoon et al., 2014). Cold weather could increase blood viscosity and also vasoconstriction. ...
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Carrillo-Larco, Rodrigo M., J. Jaime Miranda, Robert H. Gilman, Offdan Narvaez-Guerra, Karela Herrera-Enriquez, Josefina Medina-Lezama, Liam Smeeth, William Checkley, and Antonio Bernabe-Ortiz; on behalf of the CRONICAS Cohort Study Group. Urbanization and altitude are associated with low kidney function in Peru. High Alt Med Biol 00:000-000, 2019. Background: Kidney health needs to be studied in low- and middle-income countries with populations living at high altitude and undergoing urbanization. We studied whether greater level of urbanization was associated with worse kidney function and higher hemoglobin was associated with worse kidney function at high altitude. Methods: Cross-sectional analysis of population-based studies in Peru including five sites at different altitude above the sea level and urbanization level (in decreasing order of urbanization): Lima (sea level), Arequipa (2335 m), urban Puno (3825 m), Tumbes (sea level), and rural Puno (3825 m). The exposures were urbanization and altitude as per study site, and hemoglobin (g/dL). The outcome was the estimated glomerular filtration rate (eGFR). Results: Four thousand two hundred eight people were studied: mean age was 57.4 years (standard deviation: 12.4) and 51.9% were women. In comparison to rural Puno, eGFR was similar in Lima; in comparison to rural Puno, Arequipa, urban Puno, and Tumbes had worse eGFR, for example, in Arequipa, β = -8.07 (95% confidence interval [CI]: -10.90 to -5.24). Intermediate (β = -8.60; 95% CI: -10.55 to -6.66) and high (β = -11.21; 95% CI: -14.19 to -8.24) altitude were negatively correlated with eGFR when only urban places were analyzed. At high altitude, there was a trend for a negative association between hemoglobin and eGFR: β = -1.09 (95% CI: -2.22 to 0.04). Conclusions: Apparently, higher altitude and level of urbanization, except for one highly urbanized site, were associated with worse kidney function. Our findings suggest that some of the adverse impact of high altitude on kidney function has been balanced by the lower risk conferred by rural environments. KEYWORDS: Peru; altitude; chronic kidney disease; glomerular filtration; kidney function; urbanization
... Under pentobarbital-induced anesthesia, BAT activity is readily elicited by NE injection as shown elsewhere(1) and demonstrated herein Figure 1. The initial drop in rectal and iBAT temperature is due to the ablation of central thermoregulation and hypothermic shivering by pentobarbital anesthesia (22),but this drop is arrested and reversed by the injection of NE. NE induces NST in BAT, which leads to an increase in iBAT temperature followed quickly by an increase in rectal temperature. ...
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... Sabharwal (50) reported that whole body hypothermia reduces renal SND in anesthetized, cold-acclimated rats. Broman et al (8) reported that, in the absence of muscle shivering, whole body hypothermia reduces renal SND in nonacclimated, anesthetized rats. The results of previous studies (11,14,15,25,30,36,47,49) indicate that hypothermia alters immune system regulation. ...
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... Experimental Protocol. Surface cooling without giving anesthetics causes vigorous muscle shivering, preventing accurate nerve recordings in good conditions (17). Thus, we chose an experimental model using anesthesia and muscle relaxant. ...
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Hypothermia is associated with cardiovascular complications and is thought to produce potent activation of the sympathetic nervous system (SNS). However, the influence of acute heat loss on important functional characteristics of the SNS has not been addressed. We used autospectral and coherence analyses to determine the influence of hypothermia on sympathetic nerve discharge (SND) patterns and on the relationships between the activity patterns of different sympathetic nerves. Renal, adrenal, and lumbar SND recordings were completed in chloralose-anesthetized rats during decreases in internal body temperature from 38° to 28°C. Key findings include: 1) the basic cardiac-related discharge pattern of renal, adrenal, and lumbar SND was transformed to a lower frequency, noncardiac-related pattern during progressive cooling; 2) the afferent discharge pattern in the aortic depressor nerve remained cardiac-locked during hypothermia and was not associated with changes in the SND pattern; and 3) renal and lumbar SND patterns remained coupled during cooling; however, the synchronized discharges in renal and adrenal nerves were uncoupled during hypothermia. These results indicate that hypothermia changes the basic pattern of SND and selectively alters the coupling between sympathetic nerve pairs.
Article
Abstract—An improved method for the measurement of catecholamines in brain parts has been developed, based on reverse-phase ion-pair chromatography. The new method offers the advantages of high efficiency microparticulate liquid chromatography packings and the flexibility of ion-pair chromatography. By this approach norepinephrine and dopamine (DA) have been measured in the hypothalamus and corpus striatum of the rat brain during various stages of development (15, 21, 30 days). Data are reported on the basis of the whole part and per weight of tissue. For the adult animals, the following concentrations (ng/g wet tissue) were observed for the hypothalamus: NE = 2261 ± 274, DA = 440 ± 103, and for the corpus striatum: DA = 11,888 ± 1840. The overall precision of the method was ±5.6% relative s.d. The absolute recovery was 60 ± 5% relative s.d. and was constant over the range of 1 ng to 1 μg of dopamine or norepinephrine per tissue sample. The relative retention behavior of 18 neurologically important catechol derivatives is reported for reverse-phase chromatography with octyl sulfate as the stationary phase modifier.
Article
Peripheral hyperosmolality produced by the intravenous infusion of hypertonic saline (HTS) increases mean arterial blood pressure (MAP) in experimental animals. The mechanisms mediating the pressor response have not been fully ascertained, but likely involve vasopressin and/or activation of the sympathetic nervous system. The primary aim of this study was to determine if HTS infusion produces regionally uniform or nonuniform changes in sympathetic nerve discharge (SND). For this purpose we recorded renal, splanchnic and lumbar SND during intravenous HTS infusion (2.5 M NaCl, 10 μl/100 g BW per min) in chloralose-anesthetized, Sprague-Dawley rats. In rats with intact arterial baroreceptors, HTS infusion significantly increased MAP (17 ± 2 mmHg) and lumbar SND (29 ± 13%) but reduced splanchnic (−52 ± 7%) and renal SND (−33 ± 8%). After sinoaortic denervation (SAD), HTS infusion significantly increased MAP (28 ± 6 mmHg) and lumbar SND (27 ± 9%) and decreased renal SND (−22 ± 8%). The increase in lumbar SND occurred significantly sooner in SAD compared with baroreceptor-intact rats. In contrast, splanchnic SND remained unchanged from control levels during HTS infusion after SAD. These results demonstrate that HTS infusion produces regionally nonuniform changes in SND, and suggest that the pressor and lumbar sympathoexcitatory responses to HTS infusion are opposed by the arterial baroreceptors.
1. Dose-response curves for noradrenaline, phenylephrine and clonidine were determined isometrically on the mouse vas deferens at 26 degrees C, 15 degrees C and compared to the one obtained at 37 degrees C. 2. In the presence of noradrenaline, reducing temperature induced an increase of both maximal developed tension and sensitivity to the drug. Reduction by 50% of the extracellular calcium concentration abolished the maximal contraction potentiation. 3. When reducing temperature to 26 degrees C, the maximal contraction was increased and depressed in the presence of phenylephrine and clonidine respectively. 4. The results suggest (a) that cooling increases the reactivity of mouse vas deferens by activation of alpha 1 adrenoceptors and depresses it by activation of alpha 2 adrenoceptors (b) that calcium ions could play an important role in the potentiation of the maximal contraction.
Article
In order to minimize heat loss cold stress induces peripheral vasoconstriction via the sympathetic nervous system. This effect is most pronounced in the extremities. Vasoconstriction does not appear in the head-neck region--a fact of great importance in emergency situations. In order to compensate for heat loss shivering is an early event, where involuntary muscle contractions increase metabolic rate 2-6 fold. Early tachycardia and elevated blood-pressure, followed by progressive bradycardia and lowered pressure are common cardiovascular effects of hypothermia. Death due to ventricular fibrillation or asystole occurs between 28 degrees-25 degrees C. Cold stress causes an osmolal diuresis with sodium and chloride as the main constituents. The natriuresis is of tubular origin and could be due to impaired autoregulation in the kidney and/or depend on the natriuretic polypeptide. The augmented urine flow decreases blood volume, lowers physical working capacity and increases blood viscosity--all negative events in a hazardous situation. Sudden immersion initiates hyperventilation for 1-2 minutes with an increasing risk of drowning. Thereafter ventilation decreases to rates consistent with metabolic requirements. In severe hypothermia carbon dioxide retention causes respiratory and metabolic acidosis. Hypothermia induces progressive depression of mental functions starting with apathy and bizarre behaviour and ending in lethargy and coma often between 30 degrees-28 degrees C. The paradoxal feeling of heat with undressing in agony could depend on cerebral receptor disturbances.
Article
The goal of this study was to investigate changes in renal sympathetic outflow during hypotensive haemorrhage. Normotensive Wistar-Kyoto rats were anaesthetized with chloralose (50 mg kg-1) and bled to an arterial blood pressure of 50 mmHg for 30 min. Changes in heart rate (HR) and renal nerve activity (RNA) were registered. The hypotensive haemorrhage induced a short-lasting sympathetic excitation that was followed within 5-10 min by a powerful sympathetic inhibition and bradycardia. The average maximal decrease in sympathetic activity was 65% and the maximal decrease in heart rate was 45 beats min-1. There was a close correlation between changes in heart rate and renal sympathetic activity. The marked depressor response was due at least in part to activation of vagal afferents because the depressor responses were acutely reversed by bilateral cervical vagotomy. As cardiac afferents are known to be activated by prostaglandins and bradykinins, and these agents are released by myocardial ischaemia, haemorrhage was repeated after use of indomethacin and aprotinin (a protein inhibitor decreasing bradykinin formation), and a marked sympathetic inhibition could still be elicited upon haemorrhage. We therefore suggest that the likely mechanism for activation of the vagal afferents is a squeezing of the myocardium when the heart has to contract around an almost empty chamber. In conclusion, this study demonstrated that hypotensive haemorrhage triggers profound inhibition of RNA in rats and that this sympathoinhibition is mediated primarily by mechanically sensitive cardiac vagal afferents.
Article
To identify a physiological role for renal alpha 2 adrenergic receptors, renal vascular and tubular responses to administration of graded frequencies of renal nerve stimulation or graded doses of adrenergic agonists were determined in anesthetized spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats. Renal vasoconstrictor responses to renal nerve stimulation and alpha 1-adrenergic receptor agonists (norepinephrine, phenylephrine) were inhibited by an alpha 1-adrenergic receptor antagonist (prazosin) but not by an alpha 2-adrenergic receptor antagonist (rauwolscine). A semilog plot of renal vasoconstrictor responses a fraction of control renal blood flow versus agonist dose (in nanograms) was linear with the slope, k, taken as the fractional decrease in renal blood flow per nanogram. The alpha 2-adrenergic receptor agonists (clonidine, guanabenz) produced minimal renal vasoconstrictor responses (fractional decrease in renal blood flow per nanogram: norepinephrine, 0.011; phenylephrine, 0.003; clonidine, 0.00087; guanabenz, 0.000037). The small renal vasoconstrictor responses to clonidine and guanabenz were more inhibited by rauwolscine than by prazosin. Low frequency renal nerve stimulation produced antidiuresis and antinatriuresis without decreasing glomerular filtration rate or renal blood flow. The antidiuretic and antinatriuretic responses were inhibited by prazosin but unaffected by rauwolscine. The magnitude of the renal vascular and tubular responses and their adrenergic receptor mediation were not different between spontaneously hypertensive, Wistar-Kyoto, and Sprague-Dawley rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
To determine the efficacy of meperidine in controlling shivering during epidural anaesthesia for Caesarean section, forty-six parturients were studied. After delivery of the infant, shivering patients received either a single dose of intravenous meperidine 50 mg, or saline in a randomized double-blind fashion. Shivering was classified on a scale of 0 to 3 (grade 0 = none, grade 3 = severe shivering that was distressing to the patient and interfered with monitoring). Shivering and other variables were recorded at epidural placement, skin incision, delivery, and 2, 5, 15, 30 and 60 minutes following injection. Administration of meperidine resulted in a significant decrease in both the overall incidence of shivering (87 to 35 per cent, p less than 0.01) and severity of shivering (grade 3:57 to 0 per cent, p less than 0.01), compared with saline (incidence: 87 to 83 per cent, grade 3:57 per cent, no change). This effect was apparent within two minutes of drug injection and persisted throughout the study period. There were no differences in vital signs, oxygen saturation or temperature between groups. The incidence of nausea was similar, although patients receiving meperidine were more drowsy at two and five minutes following injection (p less than 0.01) compared with patients in the saline group. There were no differences in level of consciousness at the later intervals. The mechanism of action of meperidine on shivering remains to be elucidated.
Article
Changes in canine renal blood flow (RBF) during direct renal nerve stimulation (RNS) were measured with an electromagnetic flowmeter in the presence and absence of autonomic blocking drugs. The degree of renal vasoconstriction increases as frequency of RNS is increased from 2 to 10 cps. Above 20 cps the degree of vasoconstriction decreases. During continued RNS at high frequencies (>10 cps) RBF returns to control flow level. Renal vasoconstriction during RNS is blocked by alpha-adrenergic blockade, unaltered by beta-adrenergic or ganglionic blockade, and absent in reserpinized animals. These findings suggest that decrease in RBF during RNS is due to activation of alpha-adrenergic receptors by norepinephrine and that the pathway between constrictor fibers and renal vascular smooth muscle probably does not involve ganglionic synapses. No evidence for participation of cholinergic, or beta-adrenergic receptors during RBF responses to RNS, or for the occurrence of extrinsic renal vasodilator nerves was obtained.
Article
The renal functional effects of renal mechano- (MR) and chemoreceptor (CR) stimulation were examined in dogs and rats. In dogs increasing ureteral pressure (increases UP) increased ipsilateral (ipsi) renal blood flow and renin secretion rate, decreased contralateral (contra) renal blood flow, but did not affect contra renal excretion or renin secretion rate. Increasing renal venous pressure (increases RVP) increased ipsi renin secretion rate but did not affect contra renal function. Retrograde ureteropelvic perfusion with 0.9 M NaCl at unchanged UP did not affect either ipsi or contra renal function. In rats,increases UP and retrograde ureteropelvic perfusion with 0.9 M NaCl at unchanged UP did not affect mean arterial pressure, heart rate, contra renal blood flow, or glomerular filtration rate but increased contra urine flow rate and urinary sodium excretion. Increasing ureteral pressure with 0.1 M NaCl increased contra urine flow rate and urinary sodium excretion, whereas retrograde ureteropelvic perfusion with 0.1 M NaCl was without effect. Thus increases UP and retrograde ureteropelvic perfusion with 0.9 M NaCl stimulated renal MR and CR, respectively. The contra diuretic and natriuretic responses to renal MR and CR stimulation were abolished by either ipsi or contra renal denervation. Renal MR and CR stimulation increased ipsi afferent renal nerve activity (RNA) and decreased contra efferent RNA. These results indicate that in dogs renal MR stimulation results in a modest contralateral excitatory renorenal reflex, whereas in rats renal MR and CR stimulation produce a contralateral inhibitory renorenal reflex.
Article
The effect of renal nerve stimulation (RNS) on renal venous outflow and urinary excretion of endogenous norepinephrine, epinephrine, and dopamine was examined in anesthetized dogs. In the unstimulated denervated kidney, there was a negative venoarterial concentration difference for all catecholamines. Low-level RNS (LLRNS) caused small changes in renal hemodynamics and renal venous outflow of dopamine and increased norepinephrine outflow by 3.22 +/- 0.95 pmol X min-1 X g-1 (n = 5, P less than 0.05). High-level RNS (HLRNS) reduced renal blood flow by 50% and increased renal venous outflow of norepinephrine and dopamine by 9.58 +/- 0.67 and 0.46 +/- 0.05 pmol X min-1 X g-1, respectively (n = 27, P less than 0.01 for both). Renal uptake of epinephrine was unchanged by HLRNS. The urinary excretion of norepinephrine but not dopamine was increased to a similar degree following RNS at both levels. HLRNS caused a similar increase of the urinary norepinephrine excretion from the contralateral denervated and unstimulated kidney. This could be explained by the increase in arterial norepinephrine (from 0.74 +/- 0.08 to 1.20 +/- 0.14 nM, P less than 0.01) caused by HLRNS as shown by experiments with intravenous infusions of norepinephrine. The alpha-adrenoceptor antagonist phenoxybenzamine counteracted the hemodynamic response to HLRNS and enhanced the renal venous outflow and urinary excretion of norepinephrine and dopamine. Our results indicate that renal nerves release dopamine as well as norepinephrine and that urinary catecholamine excretion is a poor indicator of intrarenal catecholamine release.
Article
Hypothermia occurs frequently in the critically ill patient, yet little is known about the endogenous catecholamine response to this stress. To study this problem, we measured heart rate (HR), mean arterial blood pressure (MAP), and plasma levels of norepinephrine (NE) and epinephrine (Epi) in subhuman primates (baboons) during progressive hypothermia from 37 degrees to 29 degrees C and then during rewarming to 37 degrees C. As the core temperature decreased from 37 degrees to 33 degrees C, HR and MAP increased significantly (p less than 0.05), but as core temperature further decreased from 33 degrees to 29 degrees C, the HR and MAP fell to prehypothermic levels. Plasma concentrations of NE and Epi increased significantly (p less than 0.01) as core temperature fell from 37 degrees to 31 degrees C, but as core temperature dropped from 31 degrees to 29 degrees C, plasma NE and Epi levels decreased towards prehypothermic concentrations. These findings indicate that the sympathetic nervous system (SNS) responds quickly to hypothermia but may be "switched off" at a threshold temperature of about 29 degrees C. We speculate that hypotensive patients with temperatures less than or equal to 29 degrees C may benefit from infusions of exogenous catecholamines, especially if there have been only minimal benefits achieved with conventional therapy such as fluids, and an increase in ambient temperature.
Article
In anaesthetized 300 g rats, the influence of sympathetic nerve activity on the renal hemodynamics, glomerular filtration and fluid reabsorption was studied with direct stimulation at frequencies of 2 Hz and 5 Hz. The single nephron plasma flow at control conditions was 164 nl/min decreasing to 138 nl/min during 2 Hz and 68 nl/min during 5 Hz, reaching complete glomerular ischemia at about 10 Hz. At 2 Hz, the pressure drop over the two arterioles remained essentially unchanged, indicating an equal response to sympathetic discharge. At higher frequencies the afferent tone showed a more marked increase. The glomerular ultrafiltration decreased in parallel to the blood flow. The filtration fraction remained thereby constant at about 0.33. The fractional proximal fluid reabsorption up to the puncture site in early distal tubules showed a clear increase; the Tf/P-Inulin increasing from 6.0 to 7.1 and 7.2 for 2 Hz and 5 Hz, respectively. The absolute reabsorption decreased, however, and indeed not far from the decrement in glomerular filtration. It is concluded that sympathetic nerve activity acts in the direction of fluid conservation, by reducing the glomerular filtration and increasing the fractional reabsorption. The hemodynamic effects will play the dominant role even at 2 Hz stimulation.
Article
Acute unilateral renal denervation and the resultant antidiuresis and antinatriuresis are accompanied by a compensatory antidiuresis and antinatriuresis from the opposite kidney. The present study tested the hypothesis that the renal sympathetic nerves mediated this adaptive response. In the volume-expanded rat, acute left renal denervation increased left kidney fractional sodium excretion from 4.4 +/- 0.6 to 5.9 +/- 0.6%, while right kidney fractional sodium excretion decreased from 4.3 +/- 0.6 to 3.5 +/- 0.5%. Subsequent acute right renal denervation increased right kidney fractional sodium excretion from 3.5 +/- 0.5 to 4.7 +/- 0.6%. Measurement of efferent left renal sympathetic nerve activity before and after acute right renal denervation showed an increase from 10.9 +/- 0.8 to 16.0 +/- 1.4 Hz. When both kidneys were simultaneously subjected to acute renal denervation, fractional excretion of sodium increased bilaterally. In uninephrectomized rats subjected to acute denervation of the remaining kidney, fractional excretion of sodium increased. Glomerular filtration rate was unchanged throughout in all studies. These results demonstrate that the compensatory renal response to acute contralateral renal denervation is mediated by the efferent renal sympathetic nerves.
Article
Meperidine hydrochloride was evaluated in a prospectively randomized double-blind study for its effectiveness in stopping shaking chills occurring with amphotericin B infusions. Seven patients were randomized on multiple occasions for a total of 19 reactions. In the meperidine group, nine of nine reactions stopped within 30 minutes of the administration of meperidine, with a mean cessation time of 10.8 minutes. The placebo group had a mean time of 37.4 minutes to cessation of reactions with three of ten reactions subsiding spontaneously. The mean dose of meperidine hydrochloride for cessation of reaction was 45 mg. The comparisons between meperidine and placebo for cessation of reaction within 30 minutes and the mean time to cessation of reaction were significantly different. Side effects with meperidine were minimal and less severe than the shaking chills and fever seen with amphotericin B infusions. Meperidine can eliminate these reactions more effectively and more rapidly than simply discontinuing the amphotericin B.
Article
Pethidine is reported to be more effective than equi-analgesic doses of other opioids as an inhibitor of postanaesthetic shivering. The aim of this study was to verify whether this action resulted from a local anaesthetic effect of pethidine or from inadequate fentanyl dosage in previous studies. We studied 52 ASA 1 or 2 patients. They were randomly allocated, in a double-blind fashion, to one of four groups to receive either pethidine (0.85 mg.kg-1) or fentanyl (1.7 micrograms.kg-1) or lignocaine (1 mg.kg-1) or 0.9% saline. All the patients were shivering and had a core temperature below 36 degrees C during recovery from non-septic abdominal or orthopaedic surgery. After 15 min, all the patients given saline were still shivering, as were 92% in the lignocaine group. In contrast, only 23% of the patients who were given fentanyl still shivered (p < 0.01 versus saline) and 8% in the pethidine group (p < 0.001 versus saline). The mean (SD) core temperature in the pethidine group was slightly lower than that in the fentanyl group (35.1 (0.6) and 35.9 (0.5)) when the patients stopped shivering. Furthermore, shivering restarted in 6/10 patients in the fentanyl group after 15 min compared with 1/12 in the pethidine group. Our results show that fentanyl (1.7 micrograms.kg-1) can inhibit postanaesthetic shivering but this effect is less pronounced and of shorter duration than with pethidine (0.85 mg.kg-1).
Article
The effects of 1-2 h of hypothermia at 28 degrees C and rewarming on renal function were investigated in anaesthetized rats, using conventional clearance methods and the micropuncture technique. Renal blood flow (RBF) decreased from 7.3 +/- 0.51 mL min-1 at 37.5 degrees C (control) to 4.0 +/- 0.47 at 28 degrees C, with almost complete restoration to 6.9 +/- 0.59 mL min-1 after rewarming. Systemic blood pressure remained essentially unaltered. The RBF reduction seen during hypothermia was due to a 75% increase in vascular resistance, mainly attributable to constriction of the afferent arteriole and increased blood viscosity. This was accompanied by a decline in glomerular capillary pressure from 56.7 +/- 0.6 to 46.4 +/- 1.3 mmHg, overshooting to 59.0 +/- 0.7 mmHg. The glomerular filtration rate (GFR) decreased from 1.1 +/- 0.08 to 0.6 +/- 0.04 mL min-1, returning to 1.0 +/- 0.07 after rewarming, a pattern also observed for single nephron GFR. This resulted from a decrease in net driving force for glomerular filtration, whereas the filtration coefficient was not affected. Both proximal and distal tubular fluid flow decreased, but fractional reabsorption remained unchanged. In contrast, urine flow increased from 1.8 +/- 0.16 to 5.7 +/- 1.08 microL min-1, returning to 2.1 +/- 0.18, the increase during hypothermia mainly resulting from a disproportionately reduced fluid reabsorption beyond the mid-distal tubule.
Article
Hypothermia is the major factor influencing autoregulatory properties of the cerebral circulation in human infants undergoing hypothermic cardiopulmonary bypass. The present investigation evaluated the effect of decreased temperature on the contractility of isolated middle cerebral arteries obtained from newborn lambs. Reducing bath temperature from 37 to 21 degrees C caused a temperature-dependent increase in contractile tension, achieving 1.32 +/- 0.09 g above resting tension (0.75 g). Pretreatment with nonselective (alpha 1 and alpha 2) alpha-adrenoceptor antagonist, phentolamine (10(-5) M), with an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester hydrochloride (10(-4) M), and with a cyclooxygenase inhibitor, indomethacin (10(-5) M), did not affect the contractile response to a decrease in bath temperature from 37 to 21 degrees C. Furthermore, cerebral arteries were responsive to both norepinephrine (constriction) and sodium nitroprusside (relaxation) and the sensitivity of cerebral arteries to the sympathetic neurotransmitter norepinephrine appears to be enhanced at low temperatures. We postulate that direct cerebral vasoconstriction and enhanced adrenergic contractility may be responsible for increased cerebrovascular resistance during and after hypothermic cardiopulmonary bypass with possible ischemic cerebral injury and neurological sequelae.
Article
Little is known about the effect of hypothermia on neural regulation. We investigated the effects of hypothermia during cardiopulmonary bypass (CPB) on control of renal (RSNA) and lumbar sympathetic nerve activity (LSNA), and plasma catecholamine levels. We directly measured RSNA (n = 14) and LSNA (n = 6) during CPB in anesthetized rabbits. CPB was performed via cannulae in the aortic root for arterial perfusion and the right atrium for venous drainage. Systemic hypothermia was induced by core cooling. RSNA and LSNA were recorded at the nasopharyngeal temperature of 37, 30, 24, and 18 degrees C and after rewarming up to 37 degrees C while keeping mean arterial pressure at 70 mmHg by altering perfusion flow. Other variables such as blood gases or electrolytes were kept constant. RSNA at the temperature of 30, 24, and 18 degrees C significantly decreased by 91, 97, and 95% from control (37 degrees C), respectively. LSNA decreased by 18, 57, and 89% from control as well. The decreases in RSNA at 30 and 24 degrees C were greater than those in LSNA (P < 0.05). At 18 degrees C both RSNA and LSNA nearly disappeared. Circulatory arrest for 20 min during hypothermia at 18 degrees C caused no increase in RSNA while it increased LSNA. Plasma catecholamine levels at 18 degrees C were not different from those at 37 degrees C. Rewarming to 37 degrees C increased RSNA and LSNA by 321 and 92% from control (37 degrees C before cooling), respectively (P < 0.01). Hypothermia progressively decreased and rewarming markedly increased sympathetic nerve activity, but the effects of hypothermia on RSNA and LSNA were not uniform.
Article
Hypertonic solutions act in the central nervous system (CNS) to increase mean arterial blood pressure (MAP) by activation of the sympathoadrenal axis. However, adrenal nerve activity (pre- and postganglionic nerve fibers) has not been determined during central osmotic stimulation. Therefore, these experiments evaluated adrenal (AdSNA) and renal (RSNA) sympathetic nerve activity, MAP, and heart rate (HR) following CNS administration of isotonic, hypertonic, and hypotonic sodium chloride solutions in chloralose-anesthetized rats. Injection of isotonic saline (5 microliters) did not alter MAP, HR, RSNA, or AdSNA. However, injection of hypertonic saline (5 microliters of 0.5 M) into the anteroventral portion of the third cerebral ventricle increased MAP (12 +/- 2 mmHg) and decreased HR (16 +/- 6 bpm). In addition, hypertonic saline significantly decreased RSNA (58 +/- 5% control), whereas AdSNA increased (158 +/- 10% control). Injection of hypotonic (5 microliters of 0.05 M) NaCl produced the opposite responses in RSNA (119 +/- 7% control) and AdSNA (86 +/- 5% control) and had no significant effect on MAP or HR. Furthermore, pre- and postganglionic adrenal nerve fibers responded similarly to changes in CNS osmolality. These results demonstrate that osmotic stimulation produces differential responses in RSNA and AdSNA, but not in pre- and postganglionic adrenal nerve fibers.
In¯uence of renal nerve activity on arteriolar resistance, ultra®ltration dynamics and ¯uid reabsorption. P¯uÈgers Arch 389, 85±90. Holobut, W. 1963. The content of catechol hormones: Adrenaline and noradrenaline in peripheral blood in moderate hypothermia
  • K Hermansson
  • M Larsson
  • Ka Èllskog
  • O È Wolgast
Hermansson, K., Larsson, M., Ka Èllskog, O È. & Wolgast, M. 1981. In¯uence of renal nerve activity on arteriolar resistance, ultra®ltration dynamics and ¯uid reabsorption. P¯uÈgers Arch 389, 85±90. Holobut, W. 1963. The content of catechol hormones: Adrenaline and noradrenaline in peripheral blood in moderate hypothermia. Acta Physiol Pol 14 (6), 563±572.
Pattern of sympathetic responses produced by intracerebroventricular injection of hypertonic saline
  • Shi L. B.