Selective convective brain cooling during normothermic cardiopulmonary bypass in dogs

BACKGROUND: Neurologic complications, primarily resulting from ischemic insults, represent the leading cause of morbidity and disability, and the second most common source of death, after cardiac operations. Previous studies have reported that increases (as occur during the rewarming phase of cardiopulmonary bypass [CPB]) or decreases in brain temperature of a mere 0.5 degrees to 2 degrees C can significantly worsen or improve, respectively, postischemic neurologic outcome. The purpose of the present study was to evaluate a novel approach of selectively cooling the brain during hypothermic CPB and subsequent rewarming. METHODS: Sixteen dogs were anesthetized with either intravenous pentobarbital or inhaled halothane (n = 8 per group). Normocapnia (alpha stat technique) and a blood pressure near 75 mm Hg were maintained. Temperatures were monitored by placing thermistors in the esophagus (i.e., core), parietal epidural space, and brain parenchyma at depths of 1 and 2 cm beneath the dura. During CPB, core temperature was actively cycled from 38 degrees C to 28 degrees C, and then returned to 38 degrees C. Forced air pericranial cooling (air temperature of approximately 13 degrees C) was initiated simultaneous with the onset of CPB, and maintained throughout the bypass period. Brain-to-core temperature gradients were calculated by subtracting the core temperature from regional brain temperatures. RESULTS: In halothane-anesthetized dogs, brain temperatures at all monitoring sites were significantly less than core during all phases of CPB, with one exception (2 cm during systemic cooling). Brain cooling was most prominent during and after systemic rewarming. For example, during systemic rewarming, average temperatures in the parietal epidural space, and 1 and 2 cm beneath the dura, were 3.3 degrees +/- 1.3 degrees C (mean +/- standard deviation), 3.2+/-1.4 degrees C, and 1.6 degrees +/-1.0 degrees C, cooler than the core, respectively. Similar trends, but of a greater magnitude, were noted in pentobarbital-anesthetized dogs. For example, during systemic rewarming, corresponding brain temperatures were 6.5 degrees +/-1.7 degrees C, 6.3 degrees +/-1.6 degrees C, and 4.2+/-1.3 degrees C cooler than the core, respectively. CONCLUSIONS: The magnitude of selective brain cooling observed in both study groups typically exceeded the 0.5 degrees to 2.0 degrees C change previously reported to modulate ischemic injury, and was most prominent during the latter phases of CPB. When compared with previous research from our laboratory, application of cold forced air to the cranial surface resulted in brain temperatures that were cooler than those observed during hypothermic CPB without pericranial cooling. On the basis of the assumption that similar beneficial brain temperature changes can be induced in humans, we speculate that selective convective brain cooling may enable clinicians to improve neurologic outcome after hypothermic CPB.     

Inhibition of shivering increases core temperature afterdrop and attenuates rewarming in hypothermic humans

During severe hypothermia, shivering is absent. To simulate severe hypothermia, shivering in eight mildly hypothermic subjects was inhibited with meperidine (1.5 mg/kg). Subjects were cooled twice (meperidine and control trials) in 8 degrees C water to a core temperature of 35.9 +/- 0.5 (SD) degrees C, dried, and then placed in sleeping bags. Meperidine caused a 3.2-fold increase in core temperature afterdrop (1.1 +/- 0.6 vs. 0.4 +/- 0.2 degree C), a 4.3-fold increase in afterdrop duration (89.4 +/- 31.4 vs. 20.9 +/- 5.7 min), and a 37% decrease in rewarming rate (1.2 +/- 0.5 vs. 1.9 +/- 0.9 degrees C/h). Meperidine inhibited overt shivering. Oxygen consumption, minute ventilation, and heart rate decreased after meperidine injection but subsequently returned toward preinjection values after 45 min postimmersion. This was likely due to the increased thermoregulatory drive with the greater afterdrop and the short half-life of meperidine. These results demonstrate the effectiveness of shivering heat production in attenuating the postcooling afterdrop of core temperature and potentiating core rewarming. The meperidine protocol may be valuable for comparing the efficacy of various hypothermia rewarming methods in the absence of shivering.     

Identification of entero-aggregative Escherichia coli based on surface properties

OBJECTIVES: Afterdrop in core temperatures after discontinuation of cardiopulmonary bypass (CPB) is reported to be a sign of inadequate total body rewarming on CPB. The purpose of this study was to compare the effects of three different drug regimens on hemodynamic stability and the uniformity of rewarming during the rewarming period of CPB. DESIGN: This prospective randomized study was performed in the Anesthesiology Department of the University of Istanbul. PARTICIPANTS: Sixty-six patients undergoing uncomplicated valve replacement and aortocoronary bypass grafting surgery were studied. INTERVENTIONS: Anesthesia was maintained with isoflurane and fentanyl infusion during the prebypass and the postbypass periods. Patients were allocated into three groups by the initiation of CPB. Group 1 (n = 22): fentanyl infusion + diazepam + sodium nitroprusside (SNP) in the rewarming period), group 2 (n = 22): fentanyl infusion + isoflurane, group 3, control (n = 22): fentanyl infusion + diazepam. Rectal, esophageal, and forearm temperatures were monitored throughout the study. MEASUREMENTS AND MAIN RESULTS: None of the durational and temperature data showed significant differences between groups 1 and 2. In the control group, afterdrop in esophageal temperature was significantly higher than groups 1 and 2 (group 1: -1.4 +/- 0.9 degrees C, group 2: -1.44 +/- 0.8 degrees C, group 3: -2.1 +/- 0.65 degrees C). In group 1, the number of patients whose mean arterial pressure (MAP) decreased below 45 mmHg was significantly higher than group 2 (p = 0.002). Mean SNP infusion rate and mean isoflurane concentration during the rewarming period were calculated as 1.55 +/- 0.8 micrograms/kg/min and 0.775 +/- 0.27%, respectively. CONCLUSIONS: Isoflurane produced more stable hemodynamic conditions than SNP during the rewarming period, improved the uniformity of rewarming, and permitted earlier extubation in the intensive care unit (ICU). It is concluded that isoflurane alone is capable of fulfilling the anesthesia needs during hypothermia and the rewarming period of CPB.     

Regional differences in body temperature in hypothermic and rewarmed young calves

One- to 7-day-old Holstein bull calves were anesthetized and cold-stressed until their core body temperature (CBT; colonic) was lowered by 10 C. The calves were then rewarmed in warm water, by heat pads or heat lamps, or allowed to recover naturally (unassisted). Temperatures of peripheral tissues, muscles, and the body core were recorded. The time required to lower the CBT of the cold-stressed calves was 168 +/- 11.7 minutes (mean +/- SE). Cold exposure caused a linear decrease in blood, colonic, rectal, and oral temperatures, whereas temperature decreases in the thigh and pectoral muscles, dorsal and ventral thoracic regions, and the hock joint region were generally of greater magnitude and were curvilinear in pattern. By the time the CBT had decreased 1 C, tissue temperatures during cooling were less than (P less than 0.01) the respective temperatures obtained before cooling. The mean time required to rewarm the calves in warm water (47.1 +/- 3.5 minutes) was less than (P less than 0.05) that for the other rewarming methods. The mean rewarming times for the heat pad (128 +/- 12.8) and heat lamp (125.4 +/- 10.9) methods were greater than (P less than 0.05) that for the warm water method, but less than (P less than 0.05) that for the unassisted calves (190.7 +/- 23.1). In general, there was a linear increase in most of the tissue temperatures during recovery although temperatures in the hock joint region were variable. Temperature differences were observed between the thigh and pectoral muscles and between subcutaneous tissues during cooling and recovery. There was poor correlation between the ages of the calves and the time required to decrease their CBT during cooling and also the time required to increase their CBT, regardless of the rewarming method used.     

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.     

Experimental hypothermia: effects of core cooling and rewarming on hemodynamics, coronary blood flow, and myocardial metabolism in dogs

Conflicting results have been reported as to the extent that cardiovascular function can be reestablished after rewarming from hypothermia. We measured hemodynamic function, myocardial metabolism and tissue water content in dogs core-cooled to 25 degrees C and later rewarmed. At 25 degrees C left ventricular (LV) systolic pressure (LVSP) was 54% +/- 4%, maximum rate of LV pressure rise (LV dP/dtmax) 44% +/- 5%, aortic pressure (AOP) 50% +/- 6%, heart rate (HR) 40% +/- 0%, cardiac output (CO) 37% +/- 5%, myocardial blood flow (MBF) 34% +/- 5%, and myocardial oxygen consumption (MVO2) 8% +/- 1%, compared to precooling. Stroke volume (SV) and LV end-diastolic pressure (LVEDP) were unchanged. As normothermia (37 degrees C) was reestablished, the depression of cardiac function and myocardial metabolism remained the same as that at 25 degrees C: LVSP 71% +/- 6%, LV dP/dtmax 73% +/- 7%, SV 60% +/- 9%, AOP 70% +/- 6%, CO 57% +/- 9%, MBF 53% +/- 8%, and MVO2 44% +/- 8% HR, in contrast, recovered to precooling values. The arterial concentrations of glucose and free fatty acids (FFA) did not change significantly during the experimental period, whereas an increase in lactate of nonmyocardial origin appeared after rewarming. Increased myocardial contents of creatine phosphate and water were found during both hypothermia and rewarming. The present study demonstrates a persistent depression of cardiac function after hypothermia and rewarming in spite of adequate energy stores. Thus, a direct influence on myocardial contractile function by the cooling and rewarming process is suggested.     

Temporal relation of ATP-sensitive potassium-channel activation and contractility before cardioplegia

BACKGROUND: Pharmacologic treatment using potassium-channel openers (PCOs) before cardioplegic arrest has been demonstrated to provide beneficial effects on left ventricular performance with subsequent reperfusion and rewarming. However, the PCO treatment interval necessary to provide protective effects during cardioplegic arrest remains to be defined. The present study was designed to determine the optimum period of PCO treatment that would impart beneficial effects on left ventricular myocyte contractility after simulated cardioplegic arrest. METHODS: Left ventricular porcine myocytes were assigned randomly to three groups: (1) normothermic control = 37 degrees C for 2 hours; (2) cardioplegia = K+ (24 mEq/L) at 4 degrees C for 2 hours followed by reperfusion and rewarming; and (3) PCO and cardioplegia = 1 to 15 minutes of treatment with the PCO aprikalim (100 micromol/L) at 37 degrees C followed by hypothermic (4 degrees C) cardioplegic arrest and subsequent rewarming. Myocyte contractility was measured after rewarming by videomicroscopy. A minimum of 50 myocytes were examined at each treatment and time point. RESULTS: Myocyte velocity of shortening was reduced after cardioplegic arrest and rewarming compared with normothermic controls (63+/-3 microm/s versus 32+/-2 microm/s, respectively; p < 0.05). With 3 minutes of PCO treatment, myocyte velocity of shortening was improved after cardioplegic arrest to values similar to those of normothermic controls (56+/-3 microm/s). Potassium channel opener treatment for less than 3 minutes did not impart a protective effect, and the protective effect was not improved further with more prolonged periods of PCO treatment. CONCLUSIONS: A brief interval of PCO treatment produced beneficial effects on left ventricular myocyte contractile function in a simulated model of cardioplegic arrest and rewarming. These results suggest that a brief period of PCO treatment may provide a strategy for myocardial protection during prolonged cardioplegic arrest in the setting of cardiac operation.     

Postanesthetic vasoconstriction slows peripheral-to-core transfer of cutaneous heat, thereby isolating the core thermal compartment

Forced-air warming during anesthesia increases core temperature comparably with and without thermoregulatory vasoconstriction. In contrast, postoperative forced-air warming may be no more effective than passive insulation. Nonthermoregulatory anesthesia-induced vasodilation may thus influence heat transfer. We compared postanesthetic core rewarming rates in volunteers given cotton blankets or forced air. Additionally, we compared increases in peripheral and core heat contents in the postanesthetic period with data previously acquired during anesthesia to determine how much vasomotion alters intercompartmental heat transfer. Six men were anesthetized and cooled passively until their core temperatures reached 34 degrees C. Anesthesia was then discontinued, and shivering was prevented by giving meperidine. On one day, the volunteers were covered with warmed blankets for 2 h; on the other, volunteers were warmed with forced air. Peripheral tissue heat contents were determined from intramuscular and skin thermocouples. Predicted changes in core temperature were calculated assuming that increases in body heat content were evenly distributed. Predicted changes were thus those that would be expected if vasomotor activity did not impair peripheral-to-core transfer of applied heat. These results were compared with those obtained previously in a similar study of anesthetized volunteers. Body heat content increased 159 +/- 35 kcal (mean +/- SD) more during forced-air than during blanket warming (P < 0.001). Both peripheral and core temperatures increased significantly faster during active warming: 3.3 +/- 0.7 degrees C and 1.1 +/- 0.4 degrees C, respectively. Nonetheless, predicted core temperature increase during forced-air warming exceeded the actual temperature increase by 0.8 +/- 0.3 degree C (P < 0.001). Vasoconstriction thus isolated core tissues from heat applied to the periphery, with the result that core heat content increased 32 +/- 12 kcal less than expected after 2 h of forced-air warming (P < 0.001). In contrast, predicted and actual core temperatures differed only slightly in the anesthetized volunteers previously studied. In contrast to four previous studies, our results indicate that forced-air warming increases core temperature faster than warm blankets. Postanesthetic vasoconstriction nonetheless impeded peripheral-to-core heat transfer, with the result that core temperatures in the two groups differed less than might be expected based on systemic heat balance estimates. Implications: Comparing intercompartmental heat flow in our previous and current studies suggests that anesthetic-induced vasodilation influences intercompartmental heat transfer and distribution of body heat more than thermoregulatory shunt vasomotion.     

Increased portal endothelin-1 level is associated with the liver function after cardiopulmonary bypass in rabbits: influence of hypothermia on the damage

The purpose of this study was to prove the hypothesis that ET-1 production is increased in the splanchnic-hepato circulation during cardiopulmonary bypass (CPB) with or without hypothermia and this greatly affects hepatocellular function after surgery. Twelve Japanese white rabbits were used. In group I (n = 6), the rectal temperature was kept at 37.0 degrees C during CPB (90 min). In group II (n = 6), the rectal temperature was lowered to 26 degrees C during the first 30 minutes and then increased to 37 degrees C for the following 60 minutes. In group I, surface liver tissue blood flow (LBF) remained stable during CPB. While, in group II, LBF was significantly reduced to 66.9% of baseline values during hypothermic CPB, but it increased during the rewarming phase to 84.3% of the baseline value (p = 0.0070). At the end of CPB, portal ET-1 levels were increased in both groups, but they were significantly higher in group II (7.32 +/- 0.50 pg/ml and 9.29 +/- 0.61 pg/ml, respectively). Serum GOT, GPT, LDH and arterial ammonia levels were also higher in group II. Portal ET-1 levels had a significant positive correlation with those liver enzymes. Histopathological examination after CPB showed severe damage of the hepatic parenchyma in zone 3 associated with microvesicular fatty infiltration in group II.     

Influence of body composition on rewarming from immersion hypothermia

BACKGROUND: This study was conducted to determine if the differences between efficacies of three treatments for immersion hypothermia are affected by body composition. METHODS: Twelve subjects were divided into equally sized low (LF) and high (HF) fat groups. On three occasions subjects were each immersed in cold water until esophageal temperatures (Tes) decreased to approximately 33.2 degrees C (LF) and approximately 35.8 degrees C (HF). They were then rewarmed by: 1) shivering; 2) application of external heat; or 3) treadmill exercise in a balanced design. RESULTS: For HF, the afterdrop during exercise (1.04 +/- 0.2 degrees C) was greater than during shivering (0.35 +/- 0.3 degrees C) and external heat (0.36 +/- 0.1 degree C) (p < 0.01). In LF, however, the exercise afterdrop (0.75 +/- 0.2 degree C) was greater than only external heat (0.35 +/- 0.2 degree C) (p < 0.05) but not shivering (0.58 +/- 0.4 degree C). There was a positive relationship between % fat and afterdrop for the exercise condition with a slope (95% C.I.) of 0.03 (0.01 to 0.05) degree C.% fat-1 (r2 = 0.37, p < 0.05). The exercise rewarming rate (3.48 +/- 1.1 degrees C.h-1) was greater (p < 0.01) than during both shivering (1.80 +/- 0.7 degrees C.h-1) and external heat (2.22 +/- 0.7 degrees C.h-1) in HF while no difference was seen between the three treatments (5.28 +/- 0.4, 4.86 +/- 1.1 and 5.16 +/- 0.7 degrees C.h-1, respectively) in LF. There were inverse relationships between % fat and rewarming rate in the exercise -0.12 (-0.23 to -0.01) degree C.h-1.% fat-1, (r2 = 0.38), shivering -0.27 (-0.38 to -0.16) degrees C.h-1.% fat-1, (r2 = 0.76) and external heat -0.26 (-0.35 to -0.17) degree C.h-1.% fat-1, (r2 = 0.83) conditions (p < 0.05). CONCLUSIONS: The inter-treatment differences between these techniques are accentuated in the HF, and attenuated (afterdrop) or even eliminated (rewarming rate) in the LF subgroup.     

Selective hypothermic perfusion of canine brain

A method for selective brain cooling by profound hemodilution with cold Ringer's lactate solution was previously reported in 1992. We recently modified this technique by combining it with an ultrafiltration and rewarming circuit between the left jugular vein and the inferior vena cava. We used 12 beagle dogs to study the efficacy of selective cerebral hypothermia induced by this modified technique. The brain temperature decreased to 28 degrees C within 5.4 +/- 2.7 minutes and to 20 degrees C within 15.5 +/- 9.4 minutes. The lowest brain and rectal temperatures were 17.0 +/- 1.8 degrees C and 32.1 +/- 2.2 degrees C, respectively. All animals survived in good condition without evidence of neurological deficits until they were killed at 10 weeks. Histological examination of the brains with 2,3,5-triphenyltetrazolim chloride demonstrated no evidence of ischemic lesions, and even in the hippocampus, there was no evidence of ischemic neuronal damage.     

Systemic hypothermia after spinal cord compression injury in the rat: does recorded temperature in accessible organs reflect the intramedullary temperature in the spinal cord?

This article addresses one basic issue regarding the use of systemic hypothermia in the acute management of spinal cord injury, namely, how to interpret temperature recordings in accessible organs such as the rectum or esophagus with reference to the spinal cord temperature. Thirty-six rats, divided into six groups, were randomized to laminectomy or to severe spinal cord compression trauma, and were further randomized to either a cooling/rewarming procedure or continuous normothermia (esophageal temperature 38 degrees C) for 90 min. The first procedure comprised normothermia during the surgical procedure, followed by lowering of the esophageal temperature from 38 degrees C to 30 degrees C (the hypothermic level), a 20-min steady-state period at 30 degrees C, rewarming to 38 degrees C, and finally a 20-min steady-state period at 38 degrees C. The esophageal, rectal, and epidural temperatures were recorded in all animals. The intramedullary temperature was also recorded invasively in four of the six groups. We conclude that the esophageal temperature is safe and easy to record and, in our setting, reflects the epidural temperature. The differences registrated may reflect a true deviation of the intramedullary temperature due to initial environmental exposure and secondary injury processes. Our results indicate that the esophageal temperature exceeds the intramedullary temperature during the initial recording and final steady state following rewarming, but not during the most crucial part of the experiment, the hypothermic period. The core temperature measured in the esophagus can therefore be used to evaluate the intramedullary temperature during alterations of the systemic temperature and during hypothermic periods.     

Microcirculatory studies of frostbite injury

Frostbite represents a spectrum of injury ranging from irreversible cellular destruction to reversible changes seen after rewarming. These changes include increases in tissue edema, circulatory stasis, and progressive thrombosis leading to further tissue necrosis. For this reason, it is often difficult at the time of surgical debridement to determine the extent of frostbite injury. This delayed tissue injury is similar to that seen in muscle during ischemia/reperfusion injury. Muscle that initially appears viable on reperfusion may subsequently necrose due to collapse of the microcirculation. Adherent neutrophils have been specifically cited as important components in ischemia/reperfusion injury and have also been suggested to play a role in frostbite injury. We have used an intravital microscopic muscle preparation to study microcirculatory changes carefully in frostbite injury during rewarming. The right gracilis muscle of male Wistar rats is dissected free from its primary vascular pedicle and the rat is positioned on a specially constructed microsurgical stage. Temperature changes of the muscle are recorded. The prepared axial pattern flap is transilluminated with a microscope and projected on a video screen, allowing measurement of arteriolar diameters and changes in the numbers of stuck and rolling neutrophils before frostbite, during rewarming, and for several hours later. Cold silicone oil is used to freeze the muscle to -5+/-2 degrees C in 2 to 3 minutes and to hold this temperature for 5 minutes. The muscle is rewarmed with 42 degrees C normal saline placed directly on the muscle surface. Baseline vessel diameter and leukocyte counts in 100-mm segments of the microvasculature are recorded as well as at 5, 15, and 30 minutes, and at 1, 2, and 3 hours postrewarming of frozen muscle. Observations from our initial 11 animals show that reperfusion of the muscle following freezing is varied temporally and spatially, with circulation to most vascular segments restored 5 to 10 minutes after rewarming. In 9 of 11 animals we observed the shedding of "white clots" in small arterioles and venules occurring as soon as 5 minutes after thawing. In some instances shedding continued for as long as 1 hour after rewarming. Microvascular hemorrhage was widespread 1 hour following the thaw, but there was no significant increase in neutrophil adherence observed until 3 hours following rewarming. The exact nature of the vascular injury and the composition of the "white clots" are now being determined from ultrastructural studies. Blood flow in microcirculation stops during freezing, but small-vessel perfusion returns immediately on thawing. This suggests that the vascular architecture is maintained during the freezing and thawing. Unlike ischemia/reperfusion injury, neutrophil adhesion plays a smaller role in the early response to frostbite injury. The early microcirculatory observations seen after rewarming suggest progressive and severe perturbations in platelet function and fibrin formation that are significantly different from ischemia/reperfusion injury.     

Thermoregulatory vasoconstriction impairs active core cooling

BACKGROUND: Many clinicians now consider hypothermia indicated during neurosurgery. Active cooling often will be required to reach target temperatures < 34 degrees C sufficiently rapidly and nearly always will be required if the target temperature is 32 degrees C. However, the efficacy even of active cooling might be impaired by thermoregulatory vasoconstriction, which reduces cutaneous heat loss and constrains metabolic heat to the core thermal compartment. The authors therefore tested the hypothesis that the efficacy of active cooling is reduced by thermoregulatory vasoconstriction. METHODS: Patients undergoing neurosurgical procedures with hypothermia were anesthetized with either isoflurane/nitrous oxide (n = 13) or propofol/fentanyl (n = 13) anesthesia. All were cooled using a prototype forced-air cooling device until core temperature reached 32 degrees C. Core temperature was measured in the distal esophagus. Vasoconstriction was evaluated using forearm minus fingertip skin-temperature gradients. The core temperature triggering a gradient of 0 degree C identified the vasoconstriction threshold. RESULTS: In 6 of the 13 patients given isoflurane, vasoconstriction (skin-temperature gradient = 0 degrees C) occurred at a core temperature of 34.4 +/- 0.9 degree C, 1.7 +/- 0.58 h after induction of anesthesia. Similarly, in 7 of the 13 patients given propofol, vasoconstriction occurred at a core temperature of 34.5 +/- 0.9 degree C, 1.6 +/- 0.6 h after induction of anesthesia. In the remaining patients, vasodilation continued even at core temperatures of 32 degrees C. Core cooling rates were comparable in each anesthetic group. However, patients in whom vasodilation was maintained cooled fastest. Patients in whom vasoconstriction occurred required nearly an hour longer to reach core temperatures of 33 degrees C and 32 degrees C than did those in whom vasodilation was maintained (P < 0.01). CONCLUSIONS: Vasoconstriction did not produce a full core temperature "plateau," because of the extreme microenvironment provided by forced-air cooling. However, it markedly decreased the rate at which hypothermia developed. The approximately 1-h delay in reaching core temperatures of 33 degrees C and 32 degrees C could be clinically important, depending on the target temperature and the time required to reach critical portions of the operation.     

Differential cooling and perfusion: a reasonably safe method of systemic organ protection during surgery for acute type A aortic dissection

During surgery for acute type A aortic dissection we have developed a new technique of cerebral and systemic organ protection according to susceptibility to ischemic damage. After cardiopulmonary bypass is established, patient is cooled to the rectal temperature of 30 degrees C. Then cardiopulmonary bypass is temporarily discontinued, the ascending aorta is opened, and myocardial protection is achieved by retrograde coronary sinus cold blood cardioplegia. To perform distal open repair, all 3 brachiocephalic arteries are cannulated with 13 F balloon catheters through the aortic lumen, and perfused with cold blood (12 degrees C) (10 ml/kg/min), while an additional larger balloon catheter (24 F) is inserted in the true lumen of the descending aorta, and systemic perfusion with warmer blood (28 degrees C) (1-2 l/min) is started. When the distal repair is completed, cardiopulmonary bypass is resumed and the systemic rewarming is started, meanwhile proximal repair is accomplished. Between December 1993 and August 1994, 10 patients were operated on with this method. Mean duration of cardiopulmonary bypass was 182 minutes (113 to 290), and mean duration of DCP was 63 minutes (18 to 130). Operative mortality was 10% (1/10). The technique of "differential cooling and perfusion" has been demonstrated to provide excellent cerebral and visceral protection and to minimize drawbacks associated with deep hypothermic methods necessitating prolonged cardiopulmonary bypass.     

Physiological and histological characterisation of a pig kidney in vitro perfusion model for xenotransplantation studies

A pig kidney perfusion model aimed for use in immunological and physiological xenotransplantation research has been developed. Organ viability was characterised by clearance studies, functional response to hormones/diureticum and by light microscopical examination. The pig kidney was perfused in a specially designed plexiglass chamber, using a roller pump and a small membrane oxygenator (O2/CO2, 95/5). The recirculating perfusate used was autologous pig blood diluted by Tyrodes solution to a hematocrit of 30%, at a total starting volume of 600-650 ml. The temperature was 37 degrees C. It was crucial for good organ function that the nephrectomy operating time, as well as the warm (1-2 min) and cold ischemia (average 43 min) times were minimized. The average total perfusion time was 151 minutes. Physiological parameters were measured during 10-15 minute periods at average times of 40, 63, 88 and 142 minutes. The clearance values of inulin in these periods were 54 +/- 13, 59 +/- 15, 48 +/- 23, 27 +/- 5 and for PAH; 103 +/- 14, 121 +/- 14, 106 +/- 30, 114 +/- 34 ml/min/100 g tissue weight. The plasma flows were 123 +/- 12, 155 +/- 17, 136 +/- 36 and 206 +/- 57 ml/min/100 g. The injection of 0.5 micrograms of alpha ANP to the perfusate resulted in a significant decrease in vascular resistance, and increase in urine production (+107%), as well as sodium (+112%) and potassium (+46%) excretion. Ten mg furosemide doubled the urine production and sodium excretion, while potassium excretion increased marginally. The number of leucocytes decreased by 39% during the perfusion, while the platelet count was unaffected. Light microscopy of the renal tissue after termination of the experiments revealed endothelial damage to variable extent. Loss of endothelial cells was most obvious at the level of arcuate and interlobular arteries, while the endothelium was intact in larger arteries and veins. Accumulation of polymorphonuclear granulocytes was found predominantly in the peritubular vessels, and to a lesser degree in the cortical venules. In the tubular cells, only minimal epithelial swelling and irregular cytoplasmic vacuolisation was found. Thus, a good functional viability can be maintained during 2 hours in vitro perfusion, although a decline in function as well as structural damage can be seen at the end of the experiment.     

Autologous platelet collection and storage to support thrombocytopenia in patients undergoing high-dose chemotherapy and circulating progenitor cell transplantation for high-risk breast cancer

The differential diagnosis of recurrent hepatitis C following orthotopic liver transplantation (OLT) may be difficult. We evaluated the diagnostic significance of IgM anti-hepatitis C virus (anti-HCV) core antibodies in 27 patients undergoing OLT because of HCV-associated cirrhosis. Serial serum samples collected before and after OLT were tested for the presence of IgM anti-HCV core antibodies. Results were compared with the histological evidence of liver damage, the presence, level, and genotype of serum HCV RNA and the degree of immunosuppression. All patients underwent recurrent HCV infection. Recurrent hepatitis was diagnosed histologically in 21 patients an average of 48 weeks after OLT (range 2-209 weeks): 18 had persistence or (re-)appearance of the IgM anti-HCV core after OLT, one lost the IgM anti-HCV core after OLT, and two never secreted IgM anti-HCV core either before or after OLT. The remaining six patients did not develop recurrent hepatitis after a follow-up of 44-241 weeks from OLT; in these patients, IgM anti-HCV core either disappeared (1 case) or decreased (1 case) after OLT or were persistently negative throughout the study (4 cases). Thus, 18/21 patients with recurrent hepatitis, but only one of six without recurrent hepatitis, secreted IgM anti-HCV core after OLT (P < 0.05). The IgM anti-HCV core levels were not correlated with the level or genotype of serum HCV RNA or the degree of immunosuppression. In conclusion, secretion of IgM anti-HCV core antibodies after OLT seems associated with recurrence of HCV-associated liver disease and may have diagnostic significance.     

Comparison of brain tissue metabolic changes during ischemia at 35 degrees and 18 degrees C

BACKGROUND: We evaluated brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2) and pH during ischemia with brain temperature at 35 degrees and 18 degrees C in the same patient. METHODS: Surgery was performed in a 60-year-old woman to clip a large aneurysm in the left internal carotid artery (ICA). A Paratrend 7 probe measuring PO2, PCO2, and pH was inserted into tissue at risk for ischemia during ICA occlusion and brain protection was provided with 9% desflurane. One week later, hypothermic circulatory arrest with brain temperature at 18 degrees C was performed for aneurysm clipping and tissue measurements were obtained during ischemia and rewarming. RESULTS: At 35 degrees C, ICA occlusion for 16 minutes produced tissue hypoxia (PO2 = 0) and acidosis (pH = 6.70). The rate of increase of hydrogen ion (H+) reached 50 nEq.L(-1).min(-1) during ICA occlusion and there was a slow recovery of acidosis at the end of the ischemic period. During hypothermic circulatory arrest, tissue PO2 was sensitive to decreases in blood pressure and decreased rapidly during exsanguination. Although tissue pH decreased to 6.5 with 30 min of no pump flow, the rate of H+ increase during hypothermic arrest was one-third of that seen during ischemia at 35 degrees C. During rewarming from profound hypothermia, two phases of recovery from acidosis were observed, one during CO2 clearance and one after tissue reoxygenation. Recovery of acidosis occurred sooner at 18 degrees C than at 35 degrees C. CONCLUSIONS: These results show that tissue acidosis develops more slowly and recovers more rapidly with hypothermic ischemia. This may be an important mechanism of reduced ischemic injury during hypothermia.     

Myocardial preservation by continuous perfusion of Krebs-Henseleit solution--the temperature dependency of the optimal perfusion pressure

The aim of this study was to determine the temperature dependency of the optimal pressure in myocardial preservation by continuous perfusion with Krebs-Henseleit bicarbonate buffer (KHBB) solution. Hearts from Wistar male rats were perfused with KHBB solution and cardiac function (aortic flow) was measured using an isolated working rat heart preparation. In the preliminary experiment, hearts were then preserved using Langendorff perfusion with KHBB solution of 37, 20 or 4 degrees C for 2 hours at a perfusion pressure of 100 cmH2O. This was followed by 15 min of Langendorff perfusion (37 degrees C, 100 cmH2O) and 20 min working perfusion. The 37 degrees C group and 20 degrees C group exhibited better functional recoveries of aortic flow (%AF) in the post-preservation period compared to the 4 degrees C group. In the test experiment, hearts were preserved using Langendorff perfusion for 4 hours at 37 degrees C or for 8 hours at 20 degrees C at various perfusion pressures. At 37 degrees C, %AF after 4 hours of the preservation were 64.7 +/- 2.6, 69.0 +/- 3.2, 81.9 +/- 3.1, 94.7 +/- 3.3 and 63.5 +/- 4.0% (p < 0.05 vs the 100 cmH2O group) at the perfusion pressure of 100, 60, 20, 15 and 10 cmH2O, respectively. %AF after 8 hours of the preservation at 15 cmH2O was 56.3 +/- 2.5%. At 20 degrees C, %AF after 8 hours of the preservatin was 78.9 +/- 3.3, 81.9 +/- 2.3, 67.4 +/- 1.9 and 65.9 +/- 2.2% (p < 0.05 vs the 60 cmH2O group) at the perfusion pressure of 60, 30, 10 and 15 cmH2O, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in myocardial ultrastructure induced by cooling as well as rewarming

The aim of the present study was to investigate if hypothermia and rewarming, without accompanying cardiac ischaemia or cardioplegia, causes myocardial damage. Anaesthetized rats were subjected to a cooling procedure (4 h at 15-13 degrees C) where spontaneous cardiac electromechanical activity was maintained, followed by rewarming. Control rats, hypothermic rats and posthypothermic rats were perfusion-fixed, the hearts removed and the ventricles examined using an electron microscope. Based on morphometric methodology volume fractions as well as absolute volumes of cellular and subcellular components of the ventricles were assessed. In hypothermic hearts capillary volume fraction was significantly decreased, which was probably due to a decrease in perfusion pressure. The cytosolic volume increased in both absolute values and as a fraction of the myocyte: from 25 +/- 11 in controls to 43 +/- 8 microliters and from 0.067 +/- 0.023 to 0.102 +/- 0.013, respectively. There was a corresponding relative decrease in the volume fraction of myofilaments from 0.598 +/- 0.030 to 0.548 +/- 0.024. In posthypothermic hearts significant tissue swelling was apparent, dominated by a significant increase in myocyte volume from 372 +/- 66 in controls to 522 +/- 166 microliters. Similar changes were measured in mitochondrial and cytosolic volumes. In conclusion, the myocardial ultrastructure was altered during hypothermia as well as after rewarming. Posthypothermic myocardium showed generalized cellular swelling and areas of cellular necrosis.