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A variety of methods have been employed for the induction of hypothermia; however, there are still some inherent problems that remain with current techniques. Liquid ventilation, a process used in several other environmental and clinical research areas, may be a feasible method since it takes advantage of the effectiveness of the pulmonary architecture as a heat exchanger. Hypothermia induced by liquid ventilation was studied in 8 newborn lambs, mean age = 10 +/- 8 SEM days. Each lamb was anesthetized with sodium pentobarbitol (20 mg/kg) and intubated. Cardiopulmonary measurements were taken during a control period prior to induced hypothermia. Liquid temperatures of 20 and 30 degrees C were used in cooling the animal while monitoring rectal and surface temperatures. Temperatures decreased producing rectal cooling rates of 8.4 and 4.8 degrees C/hr, respectively. Blood gas analysis showed adequate physiological gas exchange for all lambs during the liquid ventilation period. Based on the data, the process of liquid ventilation offers a unique potential both in experimental and clinical areas as a new approach to the technique of induced hypothermia.
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PMID:A new approach to induced hypothermia. 394 49

We studied the effect of environmental hypothermia on arterial blood pressure, dorsal aortic blood flow, and vascular resistance in stage 18, 21, and 24 chick embryos. The arterial pressure was measured with a servonull micropressure system. Mean dorsal aortic blood flow was calculated from pulsed-Doppler measurement of mean dorsal aortic blood velocity and dorsal aortic diameter. Vascular resistance was calculated by dividing mean vitelline arterial blood pressure by dorsal aortic blood flow. Sequential data were obtained at temperatures of 34.7, 31.1, and 34.1 degrees C. At stage 21, the vitelline arterial blood pressure decreased from 0.82 +/- 0.03 (means +/- SEM) to 0.72 +/- 0.03 mm Hg on cooling and increased from 0.66 +/- 0.05 to 0.87 +/- 0.06 mm Hg on rewarming (p less than 0.05). At stage 21, mean dorsal aortic blood flow decreased from 0.49 +/- 0.02 to 0.33 +/- 0.02 mm3/s with cooling and increased from 0.34 +/- 0.02 to 0.47 +/- 0.02 mm3/s with rewarming. The vascular resistance in stage 21 embryos increased after cooling from 1.68 +/- 0.19 to 2.23 +/- 0.39 mm Hg/mm3/s (means +/- 95% confidence interval). The changes were similar in stage 18 and 24 embryos. We conclude that the reduction of vitelline artery blood pressure resulted from a decrease in cardiac output. In addition, we noted that the vitelline arterial vascular bed can constrict in response to hypothermia prior to autonomic innervation. These changes in hemodynamics may be a teratogenic mechanism for hypothermia-induced cardiac defects in the chick embryo.
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PMID:Effect of environmental hypothermia on vitelline artery blood pressure and vascular resistance in the stage 18, 21, and 24 chick embryo. 404 Jun 27

The present study was undertaken to demonstrate and characterize potentiation of ventricular overdrive suppression by adenosine. To substantiate that adenosine has an enhanced effect on overdrive suppression, it would be necessary to demonstrate that adenosine increases pause duration independent of slowing spontaneous pre-drive rate. In isolated perfused guinea pig hearts with surgically induced complete atrioventricular block, the effect of adenosine (2-20 microM) on pause duration was compared to two alternative means of slowing the pre-drive rate, i.e., hypothermia (28.0 degrees C to 34.0 degrees C) and cesium chloride (0.3-1.0 mM). The slope value of the linear regression line describing the relationship between pre-drive cycle length and pause duration for adenosine (15.8) was significantly greater than control (1.7), hypothermia (1.7), and cesium chloride (5.4). The competitive adenosine antagonist, aminophylline (60 microM), when infused at the initiation of overdrive during adenosine administration, significantly reduced the effect of adenosine on pause duration by 72.9 +/- 4.2% (mean +/- SEM). The reduction in pause duration by aminophylline was specific for adenosine and did not occur under control conditions or during cesium chloride administration. During hypoxia, aminophylline and adenosine deaminase, when infused at the initiation of overdrive, caused 72.3 +/- 5.6 and 63.3 +/- 6.1% reductions in pause duration, respectively. Endogenous adenosine levels rose significantly with hypoxia (1,687 +/- 202 vs. 36 +/- 4 pmol/min per g during normoxia) and increased significantly further during hypoxic overdrive (3,004 +/- 323 pmol/min per g). In isolated guinea pig Purkinje fibers (n = 4), adenosine (20 microM) increased pause duration by 73.6 +/- 9.9% while only minimally affecting the pre-drive cycle length (7.6 +/- 3.8%). These fibers, when stimulated at 1.5 Hz, also displayed an adenosine-induced reduction in action potential duration at 90% repolarization (16 +/- 2 msec). In addition, we demonstrated that adenosine had an enhanced effect on pause duration in the presence of ouabain (1 microM)-induced attenuation of overdrive suppression. Thus, in isolated Purkinje fibers, it is unlikely that the potentiating effect of adenosine on pause duration, which is independent of its chronotropic effect, is mediated via an enhancement of sodium potassium adenosine triphosphatase pump activity. The effect of adenosine is likely to be secondary to a direct action on outward potassium conductance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of adenosine on ventricular overdrive suppression in isolated guinea pig hearts and Purkinje fibers. 404 82

Thirty-three patients undergoing cardiac surgery in general hypothermia were investigated during temporary pacemaker treatment for changes in right ventricular electrogram amplitudes (AMAX, UMAX) and maximum derivatives (DMAX, SMAX) from pre-to postoperative phase (AMAX = amplitude of the part of the electrogram with highest mean maximum derivative (SMAX), DMAX = maximum derivative, UMAX = maximum amplitude deflection). Standard commercially available electrodes were used in 28 of the patients. A paired comparison (n = 29) showed a fall in AMAX from 8.64 +/- 0.91 mV (mean +/- SEM) preoperatively to 4.94 +/- 0.43 mV (p < 0.001) between the 4th and 6th postoperative day; UMAX dropped from 11.09 +/- 0.95 mV preoperatively to 5.44 +/- 0.42 mV (p < 0.000001) from the fourth to the sixth postoperative day. In the same period DMAX fell from 1.57 +/- 0.13 V/s to 0.67 +/- 0.05 V/s (p < 0.000001), and SMAX from 0.76 +/- 0.06 V/s to 0.32 +/- 0.02 V/s (p < 0.000001). The most marked fall in amplitudes and maximum derivatives occurred during the first 24 hours. A slight, but nonsignificant increase occurred in amplitudes and maximum derivatives from the 4th to 6th postoperative day until the electrodes were removed the 10th to 19th postoperative day. Amplitudes and maximum derivatives were of the same value in patients with aortic valve compared with coronary heart diseases in spite of a more deteriorated myocardial function in the former group. The changes in amplitudes and maximum derivatives followed the same pattern in the two groups from the pre- to postoperative phase. This indicates that the additional local hyperthermia applied to the patients undergoing valve surgery was of no importance in the electrogram changes. Despite the fact that the electrogram maximum derivative and maximum amplitude needed to inhibit a temporary pulse generator are of a low magnitude, the values found were so small that they might provoke demand failure. This actually occurred in four patients.
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PMID:Temporary pacemaker treatment in open heart surgery: pre- to postoperative changes in the electrogram characteristics. 616 May 3

Over a 7-month period, 15 consecutive patients underwent resection and reconstruction of the transverse aortic arch for a variety of pathologic lesions using moderate systemic hypothermia (24 degrees C) and brief circulatory arrest. Simplified surgical techniques were developed to allow rapid repair. The "open" aortic technique facilitated repair of arch aneurysms, aortic dissections and obstructive lesions of the arch tributaries. The mean cerebral ischemic time was 11.2 +/- 1.5 minutes (mean +/- SEM). Moderate hypothermia afforded adequate cerebral and myocardial protection during circulatory arrest and shortened the duration of extracorporeal bypass necessary for the cooling and rewarming phases (87 +/- 8 minutes). Dacron grafts preclotted by a new method greatly reduced postoperative blood loss. Since these simplified techniques were adopted, 14 patients (93%) have survived aortic arch replacement, with minimal postoperative morbidity. One patients with severe preoperative left ventricular dysfunction died of cardiac failure after operation. These results suggest that aortic arch replacement can be performed safely and with low operative risk.
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PMID:Open aortic anastomosis: improved results in the treatment of aneurysms of the aortic arch. 621 Dec 97

Recent experimental and clinical studies from our institution have shown that the administration of cold, bicarbonate-buffered, hyperkalemic crystalloid cardioplegic solution resulted in a significant rise in intramyocardial pH. This rise could theoretically be caused by (1) the alkalinity of the solution administered (pH 8.2 at 25 degrees C), (2) the washout of acid metabolites with each administration, and (3) hypothermia per se. To investigate the relative effects of each of these three factors on intramyocardial pH, dogs on cardiopulmonary bypass received crystalloid cardioplegic solution either at 10 degrees C (n = 9) or at 37 degrees C (n = 8) every 30 min during 2 hr of aortic cross-clamping. Myocardial temperature, intramyocardial pH, and CO2 tension (Pmco2) were measured continuously. Needle biopsy specimens were taken every 30 min for biochemical and ultrastructural analysis. Before aortic cross-clamping, intramyocardial pH was 7.07 +/- 0.06 in both groups (+/- SEM). Upon each administration of cardioplegic solution, hearts in the 10 degrees C group cooled to 10 degrees to 15 degrees C and intramyocardial pH increased on the average by 0.31 +/- 0.03 units (p less than .001). In the 37 degrees C group intramyocardial pH was unaffected by cardioplegic solution. At the end of the cross-clamping period, intramyocardial pH had declined to 6.49 +/- 0.13 in the 10 degrees C group and to 5.60 +/- 0.08 in the 37 degrees C group, the fall in pH being significantly greater in the 37 degrees C group than in the 10 degrees C group (p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The relative importance of alkalinity, temperature, and the washout effect of bicarbonate-buffered, multidose cardioplegic solution. 643 May 94

Body cooling, respiratory heat loss, and the physiological effects of liquid ventilation at various temperatures were studied in 10 adult cats with applications to the deep sea diver. The animals were stabilized on mechanical gas ventilation with 100% oxygen during a control period and then mechanically ventilated for 1 h with liquid fluorocarbon. Fluorocarbon (Rimar 101) temperatures of 10 degrees C, 20 degrees C, and 30 degrees C were used to ventilate the animals while rectal and subcutaneous body temperatures were being measured. For the 3 temperature conditions, respective cooling rates of 9.0 degrees C/h, 7.8 degrees C/h, and 3.6 degrees C/h, as well as respiratory heat losses of 65,637 J X kg-1 X h-1, 33,488 J X kg-1, X h-1, 18,036 J X kg-1 X h-1 were observed while maintaining effective physiological gas exchange [mean PaO2 = 353 +/- 28 (SEM) mmHg, mean PaCO2 = 30 +/- 2 (SEM) mmHg]. Changes in cardiovascular variables were noted as mild (35 degrees C-30 degrees C) and moderate (30 degrees C-25 degrees C) levels of hypothermia were reached. Cardiac output, oxygen consumption, heart rate, and mean blood pressure were significantly correlated with rectal temperature. The data presented herein quantitate the effects of liquid ventilation on body cooling and respiratory heat loss. Furthermore, the physiological alterations associated with the observed hypothermic condition could severely limit the effectiveness of a human diver if not carefully controlled.
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PMID:Physiological effects of ventilation with liquid fluorocarbon at controlled temperatures. 650 39

Delivery of cardioplegic (CP) solutions to all regions of the myocardium is critical for optimal myocardial protection during cardiac surgery. However, there are little data regarding the effects of CP agents upon coronary vascular resistance (CVR) and CP delivery. Accordingly, we evaluated blood CP (Hct 30) delivery and CVR during 75 minutes of multi-dose hypothermic blood CP arrest in an in vivo isolated dog heart preparation. Three groups of dogs were studied: K(K+ = 30 mEq/L; n = 6), L (Lidocaine = 400 mg/L; K+ = 4 mEq/L; n = 6), and KL (K+ = 30 mEq/L, Lidocaine 400 mg/L; n = 6) during total cardiopulmonary bypass and moderate systemic hypothermia (28 C). Basal CVR was calculated by measuring total coronary flow (HR 120/min; mean aortic pressure = 80 mmHg) in the empty beating heart. After aortic cross-clamping, the blood CP solution was infused into the aortic root at a constant pressure (80 mmHg) and constant temperature (16 +/- 2 C) for 60 seconds at 15 minute intervals for a total arrest time of 75 min. Total CP flow, CVR, O2 consumption, lactate extraction/production, and K+ balance during 75 minutes of arrest and 30 minutes of reperfusion were determined. The distribution of the CP solution in the left ventricle was measured with radioactive microspheres (9 +/- 1 mu). Biopsy specimens were taken to measure wet to dry ratios. Values are mean +/- SEM. Data were analyzed by BMDP-P2V. During the first CP infusion, after aortic cross-clamping, no differences in CVR or CP distribution were found among the three groups. However, CVR was increased significantly in the K group during the second CP infusion (O': 0.98 +/- 0.20 mmHg/ml/min/100 g; 15': 2.66 +/- 0.82; p less than 0.001). The CVR remained high for the remainder of the arrest period. Moreover, total, epi- and endocardial flow decreased significantly (54%, p less than 0.001). In groups L and KL, no significant changes in CVR were seen. Groups K and KL showed a significant K+ extraction during the first CP infusion. During the early reperfusion period, K+ washout occurred in these two groups, which was not seen in the L group. There was no significant difference between the three groups in myocardial O2 consumption, lactate metabolism, and water content during the arrest and the reperfusion period. In conclusion, high concentrations of K+ (30 mEq/L) can markedly increase CVR and impair blood CP delivery and distribution. These effects can be prevented by lidocaine. These findings warrant reassessment of the various additives to CP solutions and their effects on CVR and CP distribution during multi-dose hypothermic CP arrest.
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PMID:Blood cardioplegia delivery. Deleterious effects of potassium versus lidocaine. 661 50

Power spectrum analysis of 4-channel EEGs was performed during cooling and rewarming using cardiopulmonary bypass. During rewarming, linear correlations of temperature with the total power and with peak power frequency of the high-frequency band were observed in a significant number of cases (85%, P less than 0.0001 and 76%, P less than 0.002, respectively). The magnitude of these changes were 1,215 microV2/degrees C (+/- 150 [SEM] ) and 0.39 Hz/degrees C (+/- 0.04 [SEM] ). Two other descriptors of the EEG power spectrum (the spectral edge and average frequencies) did not correlate with the temperature changes in a significant number of cases. Changes during cooling followed a similar trend but were more variable, presumably because of other physiologic changes associated with the start of bypass. Knowledge of the relationship of the EEG to temperature should permit distinguishing EEG changes secondary to hypothermia from those caused by acute hypoxia.
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PMID:Quantitative analysis of EEG changes during hypothermia. 670 84

The relative efficacy and safety of blood-based potassium cardioplegic solutions compared to crystalloid arresting solutions has been a major controversy in the field of intraoperative myocardial protection for cardiac operations. In this study multidose potassium (K+ = 30 mEq/L) blood cardioplegia was compared to multidose potassium crystalloid cardioplegia in a dog model in which hearts were arrested for periods of 4 1/2 and 6 hours. The cardioplegic solution was given as an initial bolus of 500 ml and then as 250 ml doses every 30 minutes of arrest. In the 4 1/2 hour arrest group, six animals received blood cardioplegia, six received a low-sodium crystalloid cardioplegia (modified Roe's solution), and 10 received a high sodium crystalloid cardioplegic solution of our own design. In the 6 hour arrest group, four animals received blood cardioplegia, four received the low-sodium solution, and four received the high-sodium solution. Myocardial temperature was precisely controlled at 27 degrees +/- 1 degree C in all groups. The hearts were reperfused for periods of 2 to 4 hours after the arrest periods and then examined morphologically for injury. The extent of myocardial damage was quantified in 5 mm thick transverse sections through the ventricles by using a tetrazolium enzyme-mapping technique. In the crystalloid groups the hearts arrested for 4 1/2 hours were significantly injured. The percentage (+/- SEM) of necrosis was 12.3 % +/- 5.6% in the low-sodium cardioplegic (modified Roe's) group and 9.3% +/- 3.4% in the high-sodium group. In the 6 hour arrest group the hearts were severely injured, with contracture occurring in all cases. The percentage of necrosis was 56.5% +/- 13% in the low-sodium cardioplegic group and 71.3% +/- 12% in the high-sodium group. In striking contrast all hearts protected with blood cardioplegia failed to show any evidence of tissue damage either on tetrazolium staining or on electron microscopic examination. We conclude that blood cardioplegia offers superior protection to the arrested heart at moderate hypothermia compared to crystalloid cardioplegia.
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PMID:Multidose blood versus crystalloid cardioplegia. Comparison by quantitative assessment of irreversible myocardial injury. 670 78


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