The effects of hypothermia on renal function and haemodynamics in the rat

Broman, Lars Mikael; Källskog, Örjan

doi:10.1111/j.1748-1716.1995.tb09849.x

Cited by 43 publications

(76 citation statements)

References 11 publications

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“…The trend towards a reduction in Na plasma concentration could be explained by cold-induced diuresis, reported to occur in mild [5] and moderate [31] hypothermia. Two mechanisms are expected to be responsible for the cold-induced diuresis: (1) hypothermia depresses Na reabsorbtion with consequent diuresis [32], and (2), in a single-nephron model, Broman and Kalskog [31] showed that cold-induced diuresis was due to diminished fluid reabsorbtion in the distal segments of the tubular system.…”

Section: Discussionmentioning

confidence: 99%

“…Two mechanisms are expected to be responsible for the cold-induced diuresis: (1) hypothermia depresses Na reabsorbtion with consequent diuresis [32], and (2), in a single-nephron model, Broman and Kalskog [31] showed that cold-induced diuresis was due to diminished fluid reabsorbtion in the distal segments of the tubular system. These authors pointed out, that in the distal segments an antidiuretic hormone (ADH) exerts its influence on the water permeability and suggested that the ADH system may also be responsible for increased diuresis observed in hypothermia.…”

Section: Discussionmentioning

confidence: 99%

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Influence of Mild Hypothermia after Hypoxia-Ischemia on the Pharmacokinetics of Gentamicin in Newborn Pigs

et al. 1999

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The renal function is often affected in asphyxiated newborn infants. The pharmacokinetics of drugs like aminoglycosides eliminated through the kidneys may be impaired and require a different than usual dosage regimen. A decrease in body temperature is associated with a decrease in glomerular filtration rate and may, therefore, impair the elimination of aminoglycosides. When hypothermia is applied as neuronal rescue therapy after birth asphyxia, the pharmacokinetics of kidney-eliminated drugs may be impaired even more. We used our well-established global hypoxia-asphyxia newborn pig model to evaluate the effect of mild hypothermia after hypoxia-ischemia on gentamicin pharmacokinetics. Newborn pigs underwent global hypoxia-ischemia followed by normothermia (39°C) for 72 h (n = 8) or mild hypothermia (35°C) for 24 h followed by normothermia (39°C) for 48 h (n = 8). Gentamicin pharmacokinetics was studied after three gentamicin doses: before hypoxia-ischemia, after hypoxia-ischemia during mild hypothermia or normothermia, and during normothermia 48 h after the first dose. The gentamicin pharmacokinetics variables were calculated using a SAAM II program. Hypoxia-ischemia altered renal function and gentamicin pharmacokinetics. The gentamicin clearance correlated with the creatinine plasma concentration (r = 0.89) and with the kidney pathology score (r = 0.55). There was no significant difference in gentamicin pharmacokinetics at 35 and 39°C in newborn pigs after hypoxia-ischemia. The gentamicin pharmacokinetics variables were not different in the hypothermic or normothermic pigs after all three studied doses. Mild hypothermia for 24 h after hypoxia-ischemia does not affect gentamicin pharmacokinetics.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Influence of Mild Hypothermia after Hypoxia-Ischemia on the Pharmacokinetics of Gentamicin in Newborn Pigs

et al. 1999

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“…24) In fact, the plasma concentration profile and pharmacokinetic parameters of FD-4 were markedly changed under the hypothermic condition at 28°C (Fig. 6, Table 3).…”

Section: Comparison Of Fd-4 Pharmacokinetics Between the Hypothermic mentioning

confidence: 99%

Change in Pharmacokinetics of Model Compounds with Different Elimination Processes in Rats during Hypothermia

Nishida

Okazaki

Sakamoto

et al. 2007

Biological & Pharmaceutical Bulletin

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Cerebral ischemia accompanied by head trauma, cerebral and cardiac infarction leads to neuron dysfunction and cell death, 1) and its after-effects such as dementia, perception injury and hemiplegia are serious problems. Excess glutamate released from the neuron, energy disorder from impaired circulation and free radical generation have been clarified as the causes leading to neuron death involved with cerebral ischemia.2,3) Busto et al. reported in 1989 4) that it was possible to prevent neuron dysfunction and cell death in the ischemia by lowering the body temperature of the rats, i.e. surface cooling to 32-33°C. The multiple mechanisms of hypothermia-induced neuroprotection were identified such as reduction in cerebral metabolism, energy depletion and stabilization of cell membranes as reported previously.4-10) Hypothermia therapy has been increasingly applied to the humans 11) since it was proved useful in rats and dogs to treat experimental ischemic brain injury in the early 1990s.On the other hand, hypothermia therapy possibly causes side effects such as arrhythmia, impaired immune function and coagulation disorders as reviewed by Schubert.12) In order to negate these side effects, several kinds of medicines such as antiarrhythmic drugs, antibiotics and anticoagulants are administered to the patients. 12) Moreover, like other critically ill patients, those with severe head injuries typically receive a large number of medications. In addition, although combination pharmacotherapy with an inhibitor of glutamate and calcium might act synergistically by attenuating an ischemia-induced release of neurotoxic glutamate, 2,3) it is possible for undesirable drug-interactions to occur. Although hypothermic patients tend to receive many different pharmacologic agents, most of them are administered according to dosing schedules derived from the normothermic host. These schedules do not take into consideration any changes in drug pharmacokinetics or pharmacodynamics associated with hypothermia therapy. Physiological and biochemical changes may happen during hypothermia therapy related to a reduction in blood flow 13) and energy deficiency. 14) Therefore, pharmacokinetics of a drug during hypothermia should differ largely from normothermic conditions. There have been a few reports that recently investigated the influence of hypothermia on drug pharmacokinetics and pharmacodynamics such as phenytoin, 15) neostigmine 16) and vecuronium. 17) As well, the possibility of side effects and drug-interactions caused by variations in drug pharmacokinetics during hypothermia must be sufficiently understood.In the present study, we assessed systematically the influence of hypothermia at 32°C on the pharmacokinetics of several compounds as models with different elimination processes. Moreover, we examined the pharmacokinetic change in hypothermia at 28°C, aiming to consider the unexpected conditions such as too much cooling and body temperature dependency on pharmacokinetic change of a drug in the patients fully by three different ...

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“…Both HI [14] and HT [6] may lead to necrotising enterocolitis. Posthypoxic renal failure, found in 40% of term infants after perinatal asphyxia [15,16] combined with 'cold diuresis' [17] in response to HT may result in unpredictable changes in electrolyte and fluid balance. Pulmonary hypertension after asphyxia [16] can be further aggravated by mild HT [11,18].…”

Section: Introductionmentioning

confidence: 99%

Effect of Global Hypoxia-Ischaemia followed by 24 h of Mild Hypothermia on Organ Pathology and Biochemistry in a Newborn Pig Survival Model

Šatas

Løberg²,

Porter³

et al. 2003

Neonatology

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Background: Perinatal asphyxia may lead to multiorgan damage as well as brain injury. Posthypoxic hypothermia (HT) may protect other organs in addition to the brain. The aim of this study was to assess the systemic effects of our global hypoxic-ischaemic (HI) insult and compare the effect of mild 24-hour HT with normothermia (NT) during unsedated recovery. Method: Thirty-eight newborn pigs were subjected to 45 min of global HI by ventilating them with ∼6% O₂. On reoxygenation, pigs were randomised to NT or HT. The 18 NT piglets were maintained at rectal temperature 39.0°C for 72 h. Twenty-three HT pigs (20 experimental HT and 3 sham controls) were cooled to rectal temperature 35°C for 24 h before NT was resumed and the animals then survived a further 48 h. Results: All lesions were small with no apparent clinical effect. The incidence of any damage to the heart (6 HT vs. 9 NT), liver (9 HT vs. 7 NT), kidney (6 HT vs. 9 NT) or intestinal injury (8 HT vs. 2 NT, p = 0.07) was not different in the two groups. More HT piglets developed lung injury, 10 HT and 3 NT. Plasma [Na], [K], [Ca] and [Mg] increased significantly after the HI insult as compared to baseline values. For the 24-hour period plasma [K] and [Ca] were significantly higher in the HT group, the mean area under the curve (AUC) being for [K] AUC_HT 4.4 mmol/l vs. AUC_NT 3.9 mmol/l, p = 0.04 and for [Ca] AUC_HT 2.7 mmol/l vs. AUC_NT 2.5 mmol/l, p = 0.01, respectively. Aspartate aminotransferase peaked at 48 h in the HT group and at 24 h in the NT group. Creatinine peaked at >72 h in the HT pigs and at 48 h in the NT pigs. White blood cells (WBC) peaked at 12 h for the HT pigs and at 6 h for the NT animals. AUC of the WBC during the cooling was significantly lower in the HT pig (AUC_HT 11.1 vs. AUC_NT 15.3 10³/mm³, p = 0.04). The HT pigs needed more glucose to maintain normal glucose during the last 12 h of HT. Also HT animals needed more oxygen during cooling to maintain PaO₂. Conclusion: Twenty-four hours of mild HT did not reduce damage in any organ. There was a slight increase in lung damage in the HT group. None of the biochemical or pathological changes were of clinical significance. We conclude that mild HT for 24 h does not affect the organ systems adversely when compared to NT. Additional glucose and oxygen is needed during cooling to maintain normal values.

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The effects of hypothermia on renal function and haemodynamics in the rat

Cited by 43 publications

References 11 publications

Influence of Mild Hypothermia after Hypoxia-Ischemia on the Pharmacokinetics of Gentamicin in Newborn Pigs

Influence of Mild Hypothermia after Hypoxia-Ischemia on the Pharmacokinetics of Gentamicin in Newborn Pigs

Change in Pharmacokinetics of Model Compounds with Different Elimination Processes in Rats during Hypothermia

Effect of Global Hypoxia-Ischaemia followed by 24 h of Mild Hypothermia on Organ Pathology and Biochemistry in a Newborn Pig Survival Model

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