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Computerized thermistor technique for indirect studies of esophageal blood flow.

The aim of this study was to elaborate on a computerized microthermistor technique for indirect measurement of esophageal blood flow and to investigate if any changes in circulation could be found in patients who are provoked by esophageal acid perfusion of their acid-sensitive mucosa. A thermistor was mounted in a plastic catheter and placed in the esophagus 11 cm above the lower esophageal sphincter. The signal from the thermistor was transmitted to a personal computer. A 15 degrees C water bolus was injected into the catheter in order to cool the esophageal wall at the catheter side hole 1 cm above the thermistor. The reliability of the thermistor test was examined by repeating it in 29 patients. No statistical difference between the two test occasions was found. Twenty-five patients were provoked with an acid perfusion test, 14 of whom had a positive reaction with heartburn. Patients with a positive acid perfusion test had a shorter rewarming time before as well as after provocation than patients with a negative acid perfusion test. It is concluded that this thermistor technique is well suited for measuring intraluminal rewarming rate as an indirect sign of changes in esophageal blood flow. Furthermore, the results indicate that blood supply of the esophageal wall is increased in patients with a positive acid perfusion test.

Adult↗

Temperature dependent properties of sodium inward current of frog atrial trabecles.

From frog atrial trabecles sodium inward current in dependence on temperature was investigated using a double sucrose gap technique. For a first period of cooling the Arrhenius plot of time constants of activation and inactivation and peak current time tp show a break near 5 degrees C that is not detectable for the data of the succeeding period of rewarming. For the second and third cooling period the extreme delay of currents failed indicating an irreversible change of membrane structure after a temperature cycle. Rewarming always causes hysteresis of tp whose genuiness is proven by comparison of currents of temperature jump and ramp.

Animals↗

Effects of Na and K ions on the active Na transport in guinea-pig auricles.

1. The effect of Na and K ions on active Na transport was studied in guinea-pig auricles by means of flame photometry. 2. The Na influx into preparations rewarmed in Tyrode's solution after cooling was estimated to be about 1.05 mmole/l fibre water - min (l.f.w.-min) or c. 8 pmole/cm2 - s. Intracellular Na ions enhanced the active Na efflux over a wide range of concentrations. A decrease in the extracellular Na concentration ([Na]o) had no major effect on the active Na efflux. 3. Extracellular K ions initiated an active Na efflux from rewarmed auricles with an elevated [Na[i over a narrow range of K concentrations ([K]o). 4. Assuming Michaelis-Menten kinetics the maximal active Na efflux activated by internal Na ions was calculated to be about 4 mmole/l.f.w. - min (30 pmole/cm2 - s). Half maximal Na efflux occurred at about 22 mmole/l.f.w. [Na]i. The maximal K-activated active - min (28 pmole/cm2 - s) and was half maximal at a [K]o of about 0.2 mM. 5. It is tentatively concluded that the maximal active Na efflux from guinea-pig atria is 3--4 times larger than the physiological flux. Under normal conditions active Na efflux in heart is mainly regulated by variations of [Na]i.

Animals↗

The effects of cooling mouse oocytes.

The effects of cooling and warming on meiotic spindles of mouse oocytes have been assessed by transmission electron microscopy. Intact cumulus-oocyte complexes were immediately cooled from 37 to 15, 4, 0, and -7 degrees C (seeding temperature) for 15 min in a programmed biological freezer and fixed at these temperatures. Other complexes, cooled to these temperatures, were rapidly warmed to 37 degrees C and incubated for 2 hr before fixation at 37 degrees C. Of 334 oocytes assessed at various temperatures, at least 100 were examined for metaphase II spindles. Spindle microtubules completely disappear at 0 and -7 degrees C, while complete or partial depolymerization of microtubules was observed at 4 degrees C. Cooling to 15 degrees C did not cause major disruptions of spindle structure in most oocytes. Chromosomes tended to rotate or clump at lower temperatures but chromosome scatter outside the spindle zone was rarely observed. Centrosomal material was fragmented at 4 degrees C and occasionally at 15 degrees C and was not evident at the spindle poles at 0 and -7 degrees C. Kinetochores were seen at all temperatures. Spindle structure was evidently restored in the majority of oocytes on rewarming at 37 degrees C. Changes in the ooplasm induced by cooling were elongation and disruption of vesicular smooth endoplasmic reticulum, especially between lipid globules and disappearance of fibrillar inclusions. Cortical granule exocytosis was not observed on cooling, while microfilaments were intact. Swelling of membranous organelles was also observed in cumulus cells. Most of the cytoplasmic changes were also reversed on rewarming. The response of mouse oocytes to cooling is compared to that of human oocytes, reported previously.

Animals↗

Serum potassium levels during prolonged hypothermia.

Hypokalemia (mean serum potassium 2.3 +/- 0.4 mEq/l) was observed in six hypothermic patients (30 degrees - 32 degrees C) with head injuries or brain hypoxia. In the first three patients, potassium was administered to maintain serum levels above 3.5 mEq/l and on rewarming after 48 h of hypothermia hyperkalemia (peak serum potassium = 7.1 +/- 0.5 mEq/l) associated with cardiac arrhythmias developed. The remaining three patients received sufficient potassium to approximately replace measured losses during the hypothermic period. These patients did not become hyperkalemic on rewarming. Clinically insignificant sinus bradycardia, premature atrial contractions and junctional rhythms were seen during hypothermia with hypokalemia. We conclude that hypothermia produces hypokalemia by a shift of potassium from the extracellular to intracellular or extra vascular spaces. Potassium therapy during controlled hypothermia in the range 30 degrees - 32 degrees C should only replace measured losses.

Arrhythmias, Cardiac↗

Effects of hypothermia on energy metabolism of metabolically loaded liver.

The effects of hypothermia on adenine nucleotide level, mitochondrial metabolism and redox state of the remnant liver were studied in 25, 50, 70 and 93% hepatectomized rabbits. In 25% of the hepatectomized rabbits, energy charge levels and mitochondrial phosphorylative activities remained unchanged, while in 50 and 70% hepatectomized rabbits, the energy charge levels decreased maximally at 24 hours after hepatectomy with a concomitant rise of mitochondrial phosphorylative activity. In 93% hepatectomized rabbits, the energy charge levels decreased rapidly without enhancement in mitochondrial phosphorylative activity and these rabbits died within 12 hours after hepatectomy. Body cooling significantly increased the energy charge of the remnant liver with further enhancement in mitochondrial phosphorylative activity in 25, 50 and 70% hepatectomized rabbits, but did not increase the energy charge in 93% hepatectomized rabbits. On the other hand, during body rewarming, the energy charge levels of the remnant liver decreased. More than 60% of 70% hepatectomized rabbits died during body rewarming, while all of 50% or less hepatectomized rabbits remained alive. Thus, body cooling may provide remarkable protection for the remnant liver from an energy crisis under the condition that compensatory mitochondrial enhancements are present.

Adenine Nucleotides↗

Perfusion cooling by pulsatile flow.

Organ temperature changes and the temperature gradient between organs with cooling and rewarming were studied in rabbits using pulsatile flow perfusion. The temperature gradient between organs was within 3 degrees C. At the initial stage of cooling and rewarming, organ temperatures changed rapidly. During circulatory arrest, organ temperatures rose gradually. Brain temperature changes were similar to other organs.

Animals↗

Relationship between temperature and apoptosis of human peripheral blood mononuclear cells.

To examine the effect of various incubation temperatures on the apoptotic death of human peripheral blood mononuclear cells (PBMC), we incubated cells at 37 degrees C, 22 degrees C, and 4 degrees C for 1 and 24 hours. In addition, cells incubated at 4 degrees C for 3, 6, and 9 hours were rewarmed to 37 degrees C until a total incubation time of 24 hours was reached. The percentage of apoptotic cells was detected by a flow cytometric assay using propidium iodide staining. Incubation of PBMC at the above-mentioned temperatures for 1 hour did not affect the percentage of apoptotic cells. However, incubation at 4 degrees C for 24 hours resulted in the lowest percentage of apoptotic cells compared to those incubated at 22 degrees C and 37 degrees C. Rewarming of the cells to 37 degrees C increased the percentage of apoptotic cells to a level similar to that of the controls (incubated at 37 degrees C). Because PBMC are closely involved in the normal function of the immune system, the results of the study should be considered in cases in which these cells are exposed to various thermal conditions.

Apoptosis↗

Lidocaine prolongs the safe duration of circulatory arrest during deep hypothermia in dogs.

PURPOSE: To test the hypothesis that lidocaine prolongs the safe period of circulatory arrest during deep hypothermia. METHODS: Sixteen dogs were subjected to cooling, first surface cooling to 30 degrees C and then core cooling to 20 degrees C rectal temperature). The circulation was then stopped for 90 min. In the lidocaine group, 4 mg.kg-1 lidocaine was injected into the oxygenator two minutes before circulatory arrest and 2 mg.kg-1 at the beginning of reperfusion and rewarming. The control group received equivalent volumes of normal saline. Post-operatively, using a neurological deficit scoring system (maximum deficit score-100; minimum-zero indicating that no scored deficit could be detected). Neurological function was evaluated hourly for six hours and then daily for one week, the pharmacokinetic parameters were calculated using one compartment model. RESULTS: On the seventh day, the neurological deficit score and overall performance were better in the lidocaine (0.83 +/- 2.04) than in the control group (8.33 +/- 4.08 P < 0.05). During the experiment, the base excess values were also better in the lidocaine than in the control group (at 30 min reperfusion: -4.24 +/- 1.30 vs -8.20 +/- 2.82 P < 0.01, at 60 min reperfusion was -3.34 +/- 1.87 vs -7.52 +/- 2.40 (P < 0.01). On the eighth day the extent of pathological changes were milder in the lidocaine group than that in the control group. The elimination half life of lidocaine was 40.44 +/- 7.99 during hypothermia and 2.01 +/- 4.56 during rewarming. CONCLUSIONS: In dogs lidocaine prolongs the safe duration of circulatory arrest during hypothermia.

Anesthetics, Local↗

End-tidal carbon dioxide tension and temperature changes after coronary artery bypass surgery.

Variations in end-tidal carbon dioxide partial pressure (PETCO2) and temperature were measured for six hours following coronary artery bypass surgery in twenty patients. In the recovery room, the patients were mechanically ventilated with a tidal volume of 12 ml X kg-1. Arterial blood gases were drawn every two hours, and the respiratory frequency was adjusted to maintain arterial carbon dioxide pressure (PaCO2) in the range of 30-45 mmHg. Naso-pharyngeal temperature was recorded every 30 minutes, and PETCO2 was measured continuously. The mean difference between temperature-corrected arterial and end-tidal CO2 pressure measurements was 3.2 mmHg (SD = 2.8; r = 0.963). This difference did not vary with time, temperature or PCO2. The largest temperature increases (mean 1.7 degree C/hour) occurred at a mean of 253 minutes after the end of surgery. End-tidal PCO2 increased markedly as temperature rose, in spite of a coincident increase in ventilation and then decreased as temperature stabilized. Large increases in CO2 production, caused by the metabolic demands during rewarming, most likely account for these changes. It is concluded that end-tidal CO2 recordings are reliable, and can help in maintaining normocarbia during the short but unstable period associated with rewarming following cardiac surgery.

Aged↗

Intraspecific differences in behaviour and physiology: effects of captive breeding on patterns of torpor in feathertail gliders.

Studies on the physiology of mammals and birds are often conducted using captive-bred individuals and it is commonly assumed that the resulting data are representative of individuals living in the field. To investigate whether these assumptions are justified, we quantified morphological, behavioural, and physiological variables of the small marsupial feathertail glider (Acrobates pygmaeus). We compared three populations: (i) individuals from a cool-temperate, montane area, (ii) individuals form a subtropical, coastal area, and (iii) captive-bred individuals. Captive-bred gliders differed from the montane field gliders in morphology (longer tails and snouts), behaviour (longer activity periods) and physiology (less frequent torpor, shorter torpor, shallower torpor, higher metabolic rates during rest and torpor, and slower rates of rewarming). Most of these differences were also apparent between the captive-bred and the coastal field gliders. Unlike both field populations, captive-bred gliders often became hypothermic and were unable to rewarm. In contrast to the other physiological variables, the minimum body temperatures defended during torpor and the corresponding air temperatures differed between the montane and coastal field gliders, but were similar in coastal field and captive-bred gliders. Our study shows that morphology, behaviour and physiology can be strongly affected by breeding in or acclimation to captivity. The poor expression of torpor and thermal performance of the captive-bred gliders raises the question of whether they possess the physiological capability for survival in the wild. Even though captive breeding appears to have only minor effects on some physiological variables, data from captive-bred individuals should only be extrapolated to the field with caution.

Adaptation, Physiological↗

Using skin temperature gradients or skin heat flux measurements to determine thresholds of vasoconstriction and vasodilatation.

Forearm-fingertip skin temperature differentials (T(sk-diff)) are used to indicate vasomotor tone, vasoconstriction defined as having occurred when T(sk-diff)> or =4 degrees C (Sessler et al. 1987, 1988a, b). This study was conducted to determine whether T(sk-diff) or finger pad heat flux (HF) can be used to predict when vasoconstriction and vasodilatation occur. Seven subjects (one female) sat in water at [mean (SD)] 40.7 (0.8) degrees C until their core temperature (T(c)) increased by 1 degrees C, ensuring vasodilatation. The water was then cooled [at a rate of 0.6 (0.1) degrees C x min(-1)] until T(c) fell to 0.5 degrees C below pretesting values, causing vasoconstriction. Subjects were then rewarmed in water [41.2 (1.0) degrees C]. Skin blood flow (SkBF) was measured using laser Doppler flowmetry (LDF) on the left second finger pad [immersed in water at 10.4 (1.4) degrees C as part of another experiment], and infrared plethysmography on the third finger pad of both hands. T(sk-diff) and HF were measured on the right upper limb, which remained in air. When vasodilated, the subjects had a stable T(sk-diff) and HF. During cooling, rapid-onset vasoconstriction occurred coincidental with large gradient changes in HF and T(sk-diff) (inflection points). In two subjects the original vasoconstriction definition (T(sk-diff)> or =4 degrees C) was not attained, in the other five this was achieved 31-51 min after vasoconstriction. During rewarming, the T(sk-diff) and HF inflection points less accurately reflected the onset of vasodilatation, although with one exception they were within 5 min of the LDF changes. We conclude that T(sk-diff) and HF inflection points predict vasoconstriction accurately, and better than T(sk-diff)> or =4 degrees C.

Adult↗

Intranuclear accumulation of plant tubulin in response to low temperature.

Concurrently with cold-induced disintegration of microtubular structures in the cytoplasm, gradual tubulin accumulation was observed in a progressively growing proportion of interphase nuclei in tobacco BY-2 cells. This intranuclear tubulin disappeared upon rewarming. Simultaneously, new microtubules rapidly emerged from the nuclear periphery and reconstituted new cortical arrays, as was shown by immunofluorescence. A rapid exclusion of tubulin from the nucleus during rewarming was also observed in vivo in cells expressing GFP-tubulin. Nuclei were purified from cells that expressed GFP fused to an endoplasmic-reticulum retention signal (BY-2-mGFP5-ER), and green-fluorescent protein was used as a diagnostic marker to confirm that the nuclear fraction was not contaminated by nuclear-envelope proteins. These purified, GFP-free nuclei contained tubulin when isolated from cold-treated cells, whereas control nuclei were void of tubulin. Furthermore, highly conserved putative nuclear-export sequences were identified in tubulin sequences. These results led us to interpret the accumulation of tubulin in interphasic nuclei, as well as its rapid nuclear export, in the context of ancient intranuclear tubulin function during the cell cycle progression.

Amino Acid Sequence↗

Effect of cold cardioplegic solution and hypothermia on response to acetylcholine in perfused epicardial coronary artery of pig.

The effect of cold cardioplegic solution and hypothermia on the response to acetylcholine, a major postganglionic neurotransmitter of the parasympathetic nervous system, was studied using perfused epicardial coronary arteries of pigs. Cold crystalloid cardioplegic solution (5 degrees C) and hypothermia including topical cooling with slushed ice significantly augmented the coronary flow reduction by acetylcholine at one and two hours after rewarming. Cold Krebs-Henseleit solution (5 degrees C) with hypothermia showed similar effects. However, cardioplegic solution at 37 degrees C did not affect the responsiveness. The coronary flow reduction induced by potassium chloride (60 mmol/L) did not change even after the administration of cold cardioplegic solution (5 degrees C) or cold Krebs-Henseleit solution (5 degrees C), indicating that cooling did not necessarily augment the coronary contractile response generally. It is concluded that cooling and subsequent rewarming can potentiate the contractile response of the coronary artery of the pig to acetylcholine. This suggests that cold cardioplegic solution with hypothermia can promote intraoperative coronary spasm upon activation of the parasympathetic nervous system.

Acetylcholine↗

Optimizing myocardial hypothermia: I. Temperature probe design and clinical inferences.

Myocardial hypothermia is an essential component of myocardial preservation for most cardiac operations. Because of multiple causes of rewarming, it is necessary to monitor temperatures at specific sites (right and left ventricular epicardium and endocardium or cavity). Thus, plastic temperature probes have been designed and fabricated to facilitate temperature monitoring at these sites. Using a bare thermocouple as a standard, in vitro comparison of metallic probes and plastic probes revealed differences of 4.0 degrees +/- 0.9 degrees C and 0.7 degrees +/- 0.6 degrees C, respectively (p less than 0.005). Consequently, metallic probes do not have sufficient accuracy to detect transmural temperature gradients because of "stem effect." Using the plastic probes to evaluate temperature changes in porcine hearts after cardioplegia-induced hypothermia revealed a temperature rise of 1 degree C/min at all sites if control of systemic and venous return and local myocardial cooling are not provided. The use of temperature monitoring at multiple sites permits identification and prevention of various causes of myocardial rewarming and is facilitated by the use of plastic probes described herein which contain dual thermocouples.

Animals↗

Optimizing myocardial hypothermia: II. Cooling jacket modifications and clinical results.

After induction of myocardial hypothermia by cold cardioplegic solution, myocardial rewarming occurs at 0.5 degrees to 1.0 degrees C/min. In addition to preventing myocardial rewarming from systemic and pulmonary venous return, continuous cooling of the myocardial surface must be provided. Modifications of a previously reported cooling jacket are described. These modifications include decreased width and thickness of the metal skeleton for easier application and increased malleability, respectively. Also, the double-row flow channel markedly minimizes obstruction of flow secondary to kinking and allows inlet and outlet lines to attach at adjacent points of the jacket thus minimizing obstruction of the operative field. The effectiveness of the jacket in 36 patients undergoing valve replacement and 19 patients having pulmonary thromboendarterectomy was evaluated by measurement of myocardial temperatures at multiple sites throughout aortic cross-clamping. Temperatures at all sites were maintained at 12 degrees C or less. Temperatures measured in phrenic nerve pedicles ranged from 25 degrees to 27 degrees C. During cooling, heat removal by the jacket was 330 calories/min. During maintenance of myocardial hypothermia, heat flow was 190 calories/min. Modifications of a cooling jacket facilitate usability and an array of sizes enhances applicability.

Body Temperature↗

Cerebral perfusion during canine hypothermic cardiopulmonary bypass: effect of arterial carbon dioxide tension.

Cerebral blood flow (radioactive microspheres), intracranial pressure (subdural bolt), and retinal histopathology were examined in 20 dogs undergoing 150 minutes of hypothermic (28 degrees C) cardiopulmonary bypass to compare alpha-stat (arterial carbon dioxide tension, 40 +/- 1 mm Hg; n = 10) and pH-stat (arterial carbon dioxide tension, 61 +/- 1 mm Hg; n = 10) techniques of arterial carbon dioxide tension management. Pump flow (80 mL.kg-1.min-1), mean aortic pressure (78 +/- 2 mm Hg), and hemoglobin level (87 +/- 3 g/L [8.7 +/- 0.3 g/dL]) were maintained constant. During bypass, intracranial pressure progressively increased in the alpha-stat group from 6.0 +/- 1.0 to 13.9 +/- 1.8 mm Hg (p less than 0.05) and in the pH-stat group from 7.7 +/- 1.1 to 14.7 +/- 1.4 mm Hg (p less than 0.05), although there was no evidence of loss of intracranial compliance or intracranial edema formation as assessed by brain water content. With cooling, cerebral blood flow decreased by 56% to 62% in the alpha-stat group (p less than 0.05) and by 48% to 56% in the pH-stat group (p less than 0.05). However, 30 minutes after rewarming to 37 degrees C, cerebral blood flow in both groups failed to increase and remained significantly depressed compared with baseline values. Both groups showed similar amounts of ischemic retinal damage, with degeneration of bipolar cells found in the inner nuclear layer in 67% of animals. We conclude that, independent of the arterial carbon dioxide tension management technique, (1) cerebral perfusion decreased comparably during prolonged hypothermic bypass, (2) intracranial pressure increases progressively, (3) ischemic damage to retinal cells occurs despite maintenance of aortic pressure and flow, and (4) a significant reduction in cerebral perfusion persists after rewarming.

Animals↗

Cerebral lactate release after circulatory arrest but not after low flow in pediatric heart operations.

Arteriovenous (jugular bulb) differences in blood lactate were followed throughout the procedure and until 18 hours postoperatively in 17 children undergoing congenital heart operations during profound hypothermia. Transcranial Doppler sonography was used to monitor changes in blood flow velocity in the middle cerebral artery. Ten children had a period of total circulatory arrest (39 +/- 6 minutes) during profound hypothermia (arrest group). Another 7 children had continuous but reduced pump flow (0.6 to 1.2 L/m2) throughout hypothermic cardiopulmonary bypass (low-flow group). The mean age was 7.3 +/- 1.3 months in the arrest group and 7.9 +/- 2.2 months in the low-flow group. The mean time on bypass was 90 +/- 10 minutes in the arrest group and 75 +/- 9 minutes in the low-flow group. The velocity of blood flow in the middle cerebral artery decreased significantly (p < 0.05) in both groups to less than 50% of the preoperative level during hypothermia and increased during and after rewarming. Differences in blood lactate level were significantly less than zero (p < 0.05) from the start of rewarming until 3 hours after the end of cardiopulmonary bypass in the arrest group, whereas differences in blood lactate level remained close to zero in the low-flow group. We conclude that circulatory arrest during profound hypothermia is followed by a period with release of lactate from the brain, indicating anaerobic cerebral metabolism and possibly disturbed cerebral aerobic metabolism. This study argues for the avoidance of circulatory arrest whenever possible.

Blood Flow Velocity↗