Miniature equipment for the perfusion of rat limbs

Nagel, K.; Ghussen, F.; Krüger, I.; Isselhard, W.

doi:10.1007/bf01854962

Cited by 12 publications

(9 citation statements)

References 12 publications

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“…Higher flow rates resulted in lower temperatures of cold infusate because of the inverse relation of total heat transfer to flow rate. The decrease in heat transfer with increasing flow rate has been reported elsewhere (43). Figure 3 shows the radial temperature distribution 60 min after different rates of saline infusion along the V-shaped A-B line, which starts at a latitude of 45°, descends to the centerbase of the brain, and ascends back to the same latitude, in a longitudinal plane from ϭ Ϫ135°to ϩ45°.…”

Section: Resultssupporting

confidence: 60%

A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain

Konstas¹,

Neimark²,

Laine³

et al. 2007

Journal of Applied Physiology

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Konstas AA, Neimark MA, Laine AF, Pile-Spellman J. A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain. J Appl Physiol 102: 1329 -1340, 2007. First published December 14, 2006; doi:10.1152/japplphysiol.00805.2006.-A threedimensional mathematical model was developed to examine the transient and steady-state temperature distribution in the human brain during selective brain cooling (SBC) by unilateral intracarotid freezing-cold saline infusion. To determine the combined effect of hemodilution and hypothermia from the cold saline infusion, data from studies investigating the effect of these two parameters on cerebral blood flow (CBF) were pooled, and an analytic expression describing the combined effect of the two factors was derived. The Pennes bioheat equation used the thermal properties of the different cranial layers and the effect of cold saline infusion on CBF to propagate the evolution of brain temperature. A healthy brain and a brain with stroke (ischemic core and penumbra) were modeled. CBF and metabolic rate data were reduced to simulate the core and penumbra. Simulations using different saline flow rates were performed. The results suggested that a flow rate of 30 ml/min is sufficient to induce moderate hypothermia within 10 min in the ipsilateral hemisphere. The brain with stroke cooled to lower temperatures than the healthy brain, mainly because the stroke limited the total intracarotid blood flow. Gray matter cooled twice as fast as white matter. The continuously falling hematocrit was the main time-limiting factor, restricting the SBC to a maximum of 3 h. The study demonstrated that SBC by intracarotid saline infusion is feasible in humans and may be the fastest method of hypothermia induction. therapeutic hypothermia; ischemic stroke; spatial and temporal brain temperature distributions THE CENTRAL NERVOUS SYSTEM is vulnerable to focal and global ischemia resulting from acute ischemic stroke (63) and cardiac arrest (21). Therapeutic hypothermia has been repeatedly shown to be effective in limiting the damage of global and focal ischemia in animal models and clinical studies (6,21).In most clinical studies, hypothermia is induced by surface cooling. Although this is the simplest and most cost-effective option for inducing hypothermia (14), it has two major drawbacks. 1) Several hours are required to reach the target body core temperature. All studies report a 3-to 7-h period for cooling to 32-34°C (26, 52); however, endovascular systemic cooling may be able to accelerate the rate of cooling and improve the efficacy of hypothermia (15).2) The incidence of adverse effects, such as impaired immune function, decreased cardiac output, pneumonia, and cardiac arrhythmias/bradycardias, is high (14, 31). Selective brain cooling (SBC) without reducing body core temperature can theoretically address both problems of whole body cooling.Different methods for SBC have been reported (18). Noninvasive methods most commonly used are cooling caps and helmets. However, th...

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Section: Resultssupporting

confidence: 60%

A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain

Konstas¹,

Neimark²,

Laine³

et al. 2007

Journal of Applied Physiology

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“…Therefore, a standardized experimental animal model which allows the study of numerous interdependencies of the perfusion parameters is necessary to optimize the meticulous procedure of ILP. Although a few reports on limb perfusion of rats were published [12Ϫ18] in our opinion only the model described by Nagel and coworkers [19] is close to the clinical situation. …”

mentioning

confidence: 67%

“…Therefore, we improved the model developed by Nagel et al [19] to carry out reproducible ILPs corresponding to the clinical situation. We adapted this miniaturized extracorporeal circulation system and developed it further, particularly with respect to computer-aided simultaneous monitoring of vital perfusion parameters such as temperature (perfusate, various tissues, and rectum), perfusion pressure, pH (in perfusate), and pO 2 (one of the most critical parameters in ILP) in perfusate and tissue, respectively, with a novel type of O 2 microoptode.…”

Section: Evaluation Of Perfusion Parametersmentioning

confidence: 99%

Construction and Validation of a Microprocessor Controlled Extracorporal Circuit in Rats for the Optimization of Isolated Limb Perfusion

Gürtler

Fuchs

Stangelmayer

et al. 2004

Archiv der Pharmazie

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Although a few experimental approaches to isolated limb perfusion (ILP) are described in the literature, none of these animal models mimics the clinical perfusion techniques adequately to improve the technique of ILP on the basis of valid preclinical data. Therefore, we developed an ILP setup in rats allowing online monitoring of essential perfusion parameters such as temperature (in perfusate, various tissues, and rectum), pH (perfusate), perfusion pressure, and O(2) concentration (in perfusate, tissue), by a tailor-made data acquisition system. This setup permits close supervision of vital parameters during ILP. Various interdependencies, concerning the flow rate and the pressure of perfusate as well as tissue oxygenation were registered. For the measurement of pO(2) values in the perfusate and in different regions of the perfused hind limb, a novel type of microoptode based on quenching of a fluorescent dye was devised. Stable normothermic (37 degrees C) perfusion conditions were maintained at a constant perfusion pressure in the range of 40-60 mm Hg by administration of the spasmo lytic moxaverine (0.5 mg/mL of perfusate as initial dose) at a perfusate flow rate of 0.5 mL/min for 60 min. At the end of an ILP, there were no signs of tissue damage, neither concerning laboratory data (K(+), myoglobin, creatine kinase, lactic dehydrogenase) nor histopathological criteria. The reported ILP model is not only well suited to investigate the effects of hyperthermia but also to assess the efficacy of new antineoplastic approaches, when nude rats, bearing human tumours in the hind limbs, are used.

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“…A single-pass ILP of the tumour-bearing extremity was performed (in contrast to the earlier attempts of Nagel et al (1987) where a closed blood circuit was used) using a perfusion system consisting of a peristaltic roller pump (mp13GJ-4, Ismatec, Zürich, Switzerland), a capillary oxygenator (SPS40002-P, Fresenius, Bad Homburg, Germany), a water-filled heat exchanger used to maintain a perfusate blood temperature of 36.5 to 37.58C, polyethylene cannulas and silicone tubing (Figure 1). The perfusion medium was heparinised blood (20 i.u.…”

Section: Isolated Limb Perfusionmentioning

confidence: 99%

Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion

et al. 2002

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Isolated limb perfusion allows the direct application of therapeutic agents to a tumour-bearing extremity. The present study investigated whether the dihydropyridine-type Ca 2+ -channel blocker nifedipine could improve blood flow and oxygenation status of experimental tumours during isolated limb perfusion. Perfusion was performed by cannulation of the femoral artery and vein in rats bearing DS-sarcoma on the hind foot dorsum. Perfusion rate was adjusted to maintain a perfusion pressure of 100 -140 mmHg throughout the experiment. Following equilibration, nifedipine was continuously infused for 30 min (8.3 mg min 71 kg 71 BW). During constant-pressure isolated limb perfusion, nifedipine can significantly increase perfusion rate (+100%) and RBC flux (+60%) through experimental leg tumours. 'Steal phenomena' in favour of the surrounding normal tissue and oedema formation were not observed. Despite the increased oxygen availability (+63%) seen upon application of this calcium channel blocker, nifedipine does not result in a substantial reduction of tumour hypoxia, most probably due to an increase in O 2 uptake with rising O 2 supply to the tumour-bearing hind limb. Nifedipine application during isolated limb perfusion can enhance tumour microcirculation and may therefore promote the delivery (pharmacokinetics) of anti-cancer drugs to the tumour and by this improve the efficacy of pressure-controlled isolated limb perfusion.

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Miniature equipment for the perfusion of rat limbs

Cited by 12 publications

References 12 publications

A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain

A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain

Construction and Validation of a Microprocessor Controlled Extracorporal Circuit in Rats for the Optimization of Isolated Limb Perfusion

Nifedipine improves blood flow and oxygen supply, but not steady-state oxygenation of tumours in perfusion pressure-controlled isolated limb perfusion

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