Hemodynamics and metabolism during surface-induced hypothermia in the dog: a comparison of pH management strategies

The management of blood pH during hypothermia remains controversial. The present study was designed to determine whether hemodynamics and oxygen consumption during hypothermia are different between the alpha-stat and pH-stat strategies. Theoretical considerations of enzyme kinetics suggest that the alpha-stat strategy would result in a higher oxygen consumption during hypothermia. Because hypothermia is used to decrease oxygen consumption for protection during ischemia, a pH scheme that results in a greater oxygen demand for any level of ischemia would be detrimental. The core temperature of 22 dogs was lowered to 26 degrees C by combined surface cooling and gastric irrigation. Either the alpha-stat (N = 9) or the pH-stat (N = 13) pH strategy was used. The arterial pressure was different between the two groups at 26 degrees C (65 +/- 6 vs 85 +/- 6 mm Hg, alpha-stat vs pH-stat, respectively, P less than 0.05). Neither systemic oxygen consumption nor the Q10 was different between groups. There were no differences in any other hemodynamic parameters. In summary, during moderate hypothermia alpha-stat pH management results in an arterial pressure lower than that of pH-stat management, possibly resulting in improved peripheral perfusion. Despite theoretical predictions, the alpha-stat pH scheme does not result in an oxygen consumption higher than that of the pH-stat scheme.     

Importance of acid-base strategy in reducing myocardial and whole body oxygen consumption during perfusion hypothermia

During induced hypothermia with cardiopulmonary bypass, acid-base management usually follows one of two strategies: the so-called ectothermic or alpha-stat strategy, in which the pH of the arterial blood increases 0.015 pH units for every degree Celsius decrease in body temperature, or the pH-stat strategy, in which pH remains 7.4 at all temperatures. It has been assumed that oxygen consumption decreases approximately equally during hypothermia with either strategy, although there are biochemical reasons to hypothesize that oxygen consumption would be better maintained with the alpha-stat strategy. We also hypothesized that venous oxygen tension would be lower with the more alkaline alpha-stat strategy than with the pH-stat acid-base strategy, because of the Bohr effect. We tested these hypotheses by placing 10 anesthetized immature domestic pigs on cardiopulmonary bypass. We measured whole body oxygen consumption and myocardial oxygen consumption. Control measurements were made at 37 degrees C. Then the animals were cooled to 27 degrees C and the measurements were repeated. The alpha-stat strategy (pH 7.554 +/- 0.020 at 27 degrees C) was used in five animals and five animals received pH-stat management (pH 7.409 +/- 0.012 at 27 degrees C). Whole body and myocardial oxygen consumption rate decreased in both groups, but more so in the alpha-stat animals than in the pH-stat animals. The unexpectedly high oxygen consumption in the pH-stat animals also resulted in a lower than expected venous oxygen tension. Thus the effect of hypothermia in reducing oxygen consumption was less pronounced with pH-stat acid-base management.     

Optimal pH and PaCO2 during moderate hypothermia]

Effects of pH and PaCO2 on cerebral as well as systemic hemodynamics and oxygen consumption were investigated during moderate hypothermia under 0.5% halothane anesthesia. Twenty-seven adult mongrel dogs were cooled to 28 degrees C (brain temperature) with a surface cooling method. They were divided into 3 groups, pH-stat (pH 7.35 n = 9), alpha-stat (pH 7.48 n = 9), and alkalosis (pH 7.70 n = 9). During hypothermia cardiac index fell to 74%, 56%, and 45%, and cerebral blood flow to 54%, 42%, and 36% in pH-stat, alpha-stat and alkalosis groups, respectively. Cerebral and systemic oxygen consumptions decreased to approximately 54% and 47%, respectively in all groups. Cerebrospinal fluid pH rose from 7.36 precooling to 7.49 (pH-stat), 7.53 (alpha-stat), and 7.72 (alkalosis). We concluded from these results that pH-stat and alpha-stat management have no significant effect on either hemodynamics or metabolism during moderate hypothermia but alkalosis management has deleterious effects because of the alkalinity itself and of the hyperventilation by which the alkalosis is induced.     

Early effects of acid-base management during hypothermia on cerebral infarct volume,edema, and cerebral blood flow in acute focal cerebral ischemia in rats

BACKGROUND: Although the frequency for the use of moderate hypothermia in acute ischemic stroke is increasing, the optimal acid-base management during hypothermia remains unclear. This study investigates the effect of pH- and alpha-stat acid-base management on cerebral blood flow (CBF), infarct volume, and cerebral edema in a model of transient focal cerebral ischemia in rats. METHODS: Twenty Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h during normothermic conditions followed by 5 h of reperfusion during hypothermia (33 degrees C). Animals were artificially ventilated with either alpha- (n = 10) or pH-stat management (n = 10). CBF was analyzed 7 h after induction of MCAO by iodo[(14)C]antipyrine autoradiography. Cerebral infarct volume and cerebral edema were measured by high-contrast silver infarct staining (SIS). RESULTS: Compared with the alpha-stat regimen, pH-stat management reduced cerebral infarct volume (98.3 +/- 33.2 mm(3) vs. 53.6 +/- 21.6 mm(3); P > or = 0.05 mean +/- SD) and cerebral edema (10.6 +/- 4.0% vs. 3.1 +/- 2.4%; P > or = 0.05). Global CBF during pH-stat management exceeded that of alpha-stat animals (69.5 +/- 12.3 ml x 100 g(-1) x min(-1) vs. 54.7 +/- 13.3 ml x 100 g(-1) x min; P > or = 0.05). The regional CBF of the ischemic hemisphere was 62.1 +/- 11.2 ml x 100 g(-1) x min(-1) in the pH-stat group versus 48.2 +/- 7.2 ml x 100 g(-1) x min(-1) in the alpha-stat group ( P> or = 0.05). CONCLUSIONS: In the very early reperfusion period (5 h), pH-stat management significantly decreases cerebral infarct volume and edema as compared with alpha-stat during moderate hypothermia, probably by increasing CBF.     

Comparison of pH-state and Alpha-stat Cardiopulmonary Bypass on Cerebral Oxygenation and Blood Flow in Relation to Hypothermic Circulatory Arrest in Piglets

Background: Deep hypothermic circulatory arrest is used in neonatal cardiac surgery. Recent work has suggested improved neurologic recovery after deep hypothermic arrest with pH-stat cardiopulmonary bypass (CPB) compared with alpha-stat CPB. This study examined cortical oxygen saturation (ScO(2)), cortical blood flow (CBF), and cortical physiologic recovery in relation to deep hypothermic arrest with alpha-stat or pH-stat CPB.

Methods: Sixteen piglets were cooled with pH-stat or alpha-stat CPB to 19 [degree sign]C (cortex) and subjected to 60 min of circulatory arrest, followed by CPB reperfusion and rewarming and separation from CPB. Near infrared spectroscopy and laser Doppler flowmetry were used to monitor ScO(2) and CBF. Cortical physiologic recovery was assessed 2 h after the piglets were separated from CPB by cortical adenosine triphosphate concentrations, cortical water content, CBF, and ScO(2).

Results: During CPB cooling, ScO(2) increased more with pH-stat than with alpha-stat bypass (123 +/- 33% vs. 80 +/- 25%); superficial and deep CBF were also greater with pH-stat than with alpha-stat bypass (22 +/- 25% vs. -56 +/- 22%, 3 +/- 19% vs. -29 +/- 28%). During arrest, ScO(2) half-life was greater with pH-stat than with alpha-stat bypass (10 +/- 2 min vs. 7 +/- 2 min), and cortical oxygen consumption lasted longer with pH-stat than with alpha-stat bypass (36 +/- 8 min vs. 25 +/- 8 min). During CPB reperfusion, superficial and deep CBF were less with alpha-stat than with pH-stat bypass (-40 +/- 22% vs. 10 +/- 39%, -38 +/- 28% vs. 5 +/- 28%). After CPB, deep cortical adenosine triphosphate and CBF were less with alpha-stat than with pH-stat bypass (11 +/- 6 pmole/mg vs. 17 +/- 8 pmole/mg, -24 +/- 16% vs. 16 +/- 32%); cortical water content was greater with alpha-stat than with pH-stat bypass (superficial: 82.4 +/- 0.3% vs. 81.8 +/- 1%, deep: 79.1 +/- 2% vs. 78 +/- 1.6%).     

pH-Stat Management Reduces the Cerebral Metabolic Rate for Oxygen during Profound Hypothermia (17 degrees Celsius): A Study during Cardiopulmonary Bypass in Rabbits

Background: Greater cerebral metabolic suppression may increase the brain's tolerance to ischemia. Previous studies examining the magnitude of metabolic suppression afforded by profound hypothermia suggest that the greater arterial carbon dioxide tension of pH-stat management may increase metabolic suppression when compared with alpha-stat management.

Methods: New Zealand White rabbits, anesthetized with fentanyl and diazepam, were maintained during cardiopulmonary bypass (CPB) at a brain temperature of 17 degrees Celsius with alpha-stat (group A, n = 9) or pH-stat (group B, n = 9) management. Measurements of brain temperature, systemic hemodynamics, arterial and cerebral venous blood gases and oxygen content, cerebral blood flow (CBF) (radiolabeled microspheres), and cerebral metabolic rate for oxygen (CMRO2) (Fick) were made in each animal at 65 and 95 min of CPB. To control for arterial pressure and CBF differences between techniques, additional rabbits underwent CPB at 17 degrees Celsius. In group C (alpha-stat, n = 8), arterial pressure was decreased with nitroglycerin to values observed with pH-stat management. In group D (pH-stat, n = 8), arterial pressure was increased with angiotensin II to values observed with alpha-stat management. In groups C and D, CBF and CMRO2 were determined before (65 min of CPB) and after (95 min of CPB) arterial pressure manipulation.

Results: In groups A (alpha-stat) and B (pH-stat), arterial pressure; hemispheric CBF (44 plus/minus 17 vs. 21 plus/minus 4 ml *symbol* 100 g sup -1 *symbol* min sup -1 [median plus/minus quartile deviation]; P = 0.017); and CMRO2 (0.54 plus/minus 0.13 vs. 0.32 plus/minus 0.10 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min sup -1; P = 0.0015) were greater in alpha-stat than in pH-stat animals, respectively. As a result of arterial pressure manipulation, in groups C (alpha-stat) and D (pH-stat) neither arterial pressure (75 plus/minus 2 vs. 78 plus/minus 2 mm Hg) nor hemispheric CBF (40 plus/minus 10 vs. 48 plus/minus 6 ml *symbol* 100 g sup -1 *symbol* min sup -1; P = 0.21) differed between alpha-stat and pH-stat management, respectively. Nevertheless, CMRO2 was greater in alpha-stat than in pH-stat animals (0.71 plus/minus 0.10 vs. 0.45 plus/minus 0.10 ml Oxygen2 *symbol* 100 g sup -1 *symbol* min sup -1, respectively; P = 0.002).     

Effect of hypothermia and cardioplegia on intramyocardial voltage and myocardial oxygen consumption

Intramyocardial voltage and myocardial oxygen consumption were measured in the fibrillating heart between the temperatures of 37 degrees C and 25 degrees C and in the arrested heart after infusion of potassium cardioplegic solution in 10 adult mongrel dogs. Electrical activity from the myocardium was recorded using specially designed plunge electrodes, and intramyocardial voltage was monitored by an in-line voltmeter. Myocardial oxygen consumption gradually decreased from 5.8 +/- 0.6 ml O2/min at 37 degrees C to 2.3 +/- 0.5 ml O2/min at 25 degrees C. In contrast, hypothermia did not cause a similar decrease in intramyocardial voltage which remained within a range of 1.8 +/- 0.5 mV to 2.4 +/- 0.5 mV between the temperatures of 37 degrees C and 25 degrees C. The infusion of potassium cardioplegic solution resulted in a dramatic decrease in voltage to 43 +/- 5 microV, and myocardial oxygen consumption fell to 0.5 +/- 0.3 ml O2/min. Our data demonstrated that the mean voltage of the fibrillating heart remains constant between the temperatures 37 degrees C and 25 degrees C and myocardial oxygen consumption decreases with hypothermia, which suggests that voltage does not correlate with the level of myocardial oxygen consumption. Myocardial oxygen consumption and intramyocardial voltage, however, decrease dramatically when cardioplegia is instituted.     

Continuous monitoring of blood oxygen saturation of internal jugular vein as a useful indicator for selective cerebral perfusion during aortic arch replacement.

We continuously monitored blood oxygen saturation in the internal jugular vein during selective cerebral perfusion for aortic arch operations and evaluated its efficacy as an indicator of cerebral oxygen metabolism. The selective cerebral perfusion method was applied in 11 patients who underwent operations for aortic arch replacement. Blood oxygen saturation in the internal jugular vein was continuously monitored at the bulbus jugularis with a fiberoptic catheter during the operation. Perfusion flow of 500 ml/min was continued for 134.7 +/- 14.9 minutes under moderate hypothermia at 25 degrees C, and bilateral temporal arterial pressure was 40 to 60 mm Hg. Blood gas data were used to estimate oxygen consumption, oxygen extraction ratio, and lactate uptake in the cerebrum. No patients had postoperative cerebral complications. Cerebral oxygen consumption was 2.93 +/- 0.4 ml/min/100 gm under general anesthesia at 36 degrees C. While selective cerebral perfusion at 25 degrees C decreased consumption to 0.92 +/- 0.39 ml/min/100 gm, it fell to about 30% of its former value. Blood oxygen tension in the internal jugular vein showed no significant correlation with rectal temperature. Selective cerebral perfusion did not significantly affect cerebral lactate uptake. In contrast, blood oxygen saturation in the internal jugular vein was significantly affected by temperature and cerebral flow during selective cerebral perfusion, and blood oxygen saturation in the internal jugular vein correlated closely with cerebral oxygen extraction ratio (r = 0.91). Cerebral oxygen metabolism was thus well maintained, and continuous monitoring of blood oxygen saturation in the internal jugular vein was found to serve as a useful indicator under selective cerebral perfusion during operations for aortic arch replacement.     

Comparison of alpha-stat and pH-stat cardiopulmonary bypass in relation to jugular venous oxygen saturation and cerebral glucose-oxygen utilization

Jugular venous oxygen saturation (SJVO(2)) reflects the balance between cerebral blood flow and metabolism. This study was designed to compare the effects of two different acid-base strategies on jugular venous desaturation (SJVO(2) <50%) and cerebral arteriovenous oxygen-glucose use. We performed a prospective, randomized study in 52 patients undergoing cardiopulmonary bypass (CPB) at 27 degrees C with either alpha-stat (n = 26) or pH-stat (n = 26) management. A retrograde internal jugular vein catheter was inserted, and blood samples were obtained at intervals during CPB. There were no differences in preoperative variables between the groups. SJVO(2) was significantly higher in the pH-stat group (at 30 min CPB: 86.2% +/- 6.1% versus 70.6% +/- 9.3%; P < 0.001). The differences in arteriovenous oxygen and glucose were smaller in the pH-stat group (at 30 min CPB: 1.9 +/- 0.82 mL/dL versus 3.98 +/- 1.12 mL/dL; P < 0.001; and 3.67 +/- 2.8 mL/dL versus 10.1 +/- 5.2 mL/dL; P < 0.001, respectively). All episodes of desaturation occurred during rewarming, and the difference in the incidence of desaturation between the two groups was not significant. All patients left the hospital in good condition. Compared with alpha-stat, the pH-stat strategy promotes an increase in SJVO(2) and a decrease in arteriovenous oxygen and arteriovenous glucose differences. These findings indicate an increased cerebral supply with pH-stat; however, this strategy does not eliminate jugular venous desaturation during CPB. IMPLICATIONS: A prospective, randomized study in 52 patients during cardiopulmonary bypass revealed that pH-stat increased jugular venous oxygen saturation and decreased arteriovenous oxygen-glucose differences. There was no difference in the incidence of jugular venous desaturation. These findings suggest an increased cerebral blood flow with no protection against jugular venous desaturation during pH-stat.     

Optimal pH strategy for selective cerebral perfusion.

OBJECTIVE: Selective cerebral perfusion (SCP) affords brain protection superior to hypothermic circulatory arrest (HCA) for prolonged aortic arch procedures. Optimal pH strategy for HCA is controversial; for SCP it is unknown. We compared pH strategies during SCP in a survival pig model. METHODS: Twenty juvenile pigs (26+/-2.4 kg), randomized to alpha-stat (n=10) or pH-stat (n=10) management, underwent cooling to 20 degrees C on cardiopulmonary bypass (CPB) followed by 90 min of SCP at 20 degrees C. SCP was conducted with a mean pressure of 50 mmHg and hematocrit of 22.5%. Using fluorescent microspheres and sagittal sinus blood sampling, cerebral blood flow (CBF) and oxygen metabolism (CMRO2) were assessed at the following time points: baseline, after 30 min cooling (20 degrees C), 30 min of SCP, 90 min of SCP, 15 min post-CPB and 2h post-CPB. Visual evoked potentials (VEP) were assessed at baseline and monitored for 2h during recovery. Neurobehavioral recovery (10=normal) was assessed in a blinded fashion for 7 postoperative days. RESULTS: There were no significant differences between the groups at baseline. CBF was significantly higher at the end of cooling, and after 30 and 90 min of SCP in the pH-stat group (P=0.02, 0.007, 0.03). CMRO2 was also higher with pH-stat (P=0.06, 0.04, 0.10). Both groups showed prompt return to values close to baseline after rewarming (P=ns). VEP suggested a trend towards improved recovery in the alpha-stat group at 2h post-CPB, P=0.15. However, there were no significant differences in neurobehavioral score: (alpha-stat versus pH-stat) median values 7 and 7.5 on day 1; 9 and 9 on day 4, and 10 and 10 on day 7. CONCLUSIONS: These data suggest that alpha-stat management for SCP provides more effective metabolic suppression than pH-stat, with lower CBF. Clinically, the better preservation of cerebral autoregulation during alpha-stat perfusion should reduce the risk of embolization.     

Protective effects of the Hemopump left ventricular assist device in experimental cardiogenic shock.

The efficacy of the new cable-driven rotating left ventricular assist device Hemopump in cardiogenic shock was examined in experiments with adult sheep (n = 14; body weight 50-71 kg). Shock was induced by high frequency ventricular pacing. Aortic, pulmonary, central venous and left ventricular pressures as well as electromagnetic measurements of coronary blood flow were recorded continuously; cardiac output was measured by thermodilution technique. Blood samples for determination of oxygen content, electrolytes and lactate were taken under control conditions, in shock, and during pump intervention at different levels of pump speed. Vascular resistance, total body and myocardial oxygen consumption as well as myocardial uptake and release of lactate were calculated. High frequency pacing led to a significant decrease in cardiac output (from 3.8 +/- 0.8 to 2.2 +/- 1.6 l/min), mean aortic pressure (89.1 +/- 14.4 to 47.6 +/- 7.2 mmHg), and total body oxygen consumption (2.6 +/- 0.3 to 1.4 +/- 0.7 ml/min per kg), as well as myocardial release of lactate (arterial coronary-venous difference of lactate: 0.27 +/- 0.26 to -0.32 +/- 0.72 mmol/l). Hemopump assist in this condition resulted in a significant increase in cardiac output (to 2.8 +/- 0.6 l/min), mean aortic pressure (to 65.6 +/- 13.9 mmHg), and myocardial perfusion pressure (from 25.5 +/- 11.0 to 59.0 +/- 14.7), and led to nearly normal total body oxygen consumption (2.5 +/- 0.7 ml/min per kg), a decrease in myocardial oxygen consumption (from 6.1 +/- 2.1 in shock, to 4.8 +/- 1.7 ml/min per 100 g), and to normal arterial coronary-venous difference of lactate (0.24 +/- 0.26 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of alpha-stat vs. pH-stat strategies on cerebral oximetry during moderate hypothermic cardiopulmonary bypass

BACKGROUND AND OBJECTIVES: This study was undertaken to compare the effect of alpha-stat vs. pH-stat strategies for acid-base management on regional cerebral oxygen saturation (RsO2) in patients undergoing moderate hypothermic haemodilution cardiopulmonary bypass (CPB). METHODS: In 14 adult patients undergoing elective coronary artery bypass grafting, an awake RsO2 baseline value was monitored using a cerebral oximeter (INVOS 5100). Cerebral oximetry was then monitored continuously following anaesthesia and during the whole period of CPB. Mean +/- SD of RsO2, CO2, mean arterial pressure and haematocrit were determined before bypass and during the moderate hypothermic phase of the CPB using the alpha-stat followed by pH-stat strategies of acid-base management. Alpha-stat was then maintained throughout the whole period of CPB. RESULTS: The mean baseline RsO2 in the awake patient breathing room air was 59.6 +/- 5.3%. Following anaesthesia and ventilation with 100% oxygen, RsO2 increased up to 75.9 +/- 6.7%. Going on bypass, RsO2 significantly decreased from a pre-bypass value of 75.9 +/- 6.7% to 62.9 +/- 6.3% during the initial phase of alpha-stat strategy. Shifting to pH-stat strategy resulted in a significant increase of RsO2 from 62.9 +/- 6.3% to 72.1 +/- 6.6%. Resuming the alpha-stat strategy resulted in a significant decrease of RsO2 to 62.9 +/- 7.8% which was similar to the RsO2 value during the initial phase of alpha-stat. CONCLUSION: During moderate hypothermic haemodilutional CPB, the RsO2 was significantly higher during the pH-stat than during the alpha-stat strategy. However, the RsO2 during pH-stat management was significantly higher than the baseline RsO2 value in the awake patient breathing room air, denoting luxury cerebral perfusion. In contrast, the RsO2 during alpha-stat was only slightly higher than the baseline RsO2, suggesting that the alpha-stat strategy avoids luxury perfusion, but can maintain adequate cerebral oxygen supply-demand balance during moderate hypothermic haemodilutional CPB.     

Effect of alpha-stat versus pH-stat strategy on oxyhemoglobin dissociation and whole-body oxygen consumption during hypothermic cardiopulmonary bypass.

To determine whether alpha-stat or pH-stat strategy should be used, 20 patients undergoing coronary artery bypass grafting during moderate hypothermic hemodilutional cardiopulmonary bypass were studied. The carbon dioxide management during bypass was randomly done according to alpha-stat strategy in 10 patients (i.e., temperature-uncorrected PaCO2 was kept near 40 mm Hg and uncorrected pHa was kept at about 7.4) and according to pH-stat strategy in the other 10 patients (i.e., temperature-corrected PaCO2 was kept near 40 mm Hg and uncorrected pHa was kept at about 7.4). In both groups, when the central venous temperature was stable at 26.5 +/- 2.5 degrees C, the perfusion flow was altered sequentially from 2.4 to 1.8 and 1.2 L.min-1.m-2. The mixed venous oxyhemoglobin saturation at the different perfusion flows was monitored by the Oxy-Stat meter and was correlated with the corresponding mixed venous oxygen tension to construct an oxyhemoglobin dissociation curve. Also, the whole-body oxygen consumption at the different perfusion flows was computed. The whole-body oxygen consumption and the oxyhemoglobin dissociation were not significantly different between the alpha-stat and the pH-stat groups. In both groups, the dissociation curve is shifted to the left, but the oxygen consumption per unit time does not significantly change despite decreasing the perfusion flow from 2.4 to 1.2 L.min-1.m-2. The results suggest that oxygen delivery is not impaired during moderate hypothermic cardiopulmonary bypass independent of whether alpha-stat or pH-stat strategy is used.     

Use of a pH-stat strategy during retrograde cerebral perfusion improves cerebral perfusion and tissue oxygenation

BACKGROUND: Although it is well documented that the use of a pH-stat strategy during hypothermic cardiopulmonary bypass improves cerebral blood flow, an alpha-stat strategy has been almost exclusively used during retrograde cerebral perfusion. We investigated the effects of pH-stat and alpha-stat management on brain tissue blood flow and oxygenation during retrograde cerebral perfusion in a porcine model to determine if the use of a pH-stat strategy during retrograde cerebral perfusion improves brain tissue perfusion. METHODS: Fourteen pigs were managed by an alpha-stat strategy (alpha-stat group, n = 7) or by a pH-stat strategy (pH-stat group, n = 7) during 120 minutes of hypothermic retrograde cerebral perfusion. Retrograde cerebral perfusion was established through the superior vena cava. Brain tissue blood flow and oxygenation were measured continuously with a laser flowmeter and near infrared spectroscopy, respectively. Brain tissue water content was determined at the end of the experiments. RESULTS: During cooling, brain tissue blood flow was significantly higher with use of the pH-stat strategy than with the alpha-stat strategy (86% +/- 10% versus 40% +/- 3% of baseline). During retrograde cerebral perfusion, brain tissue blood flow was also significantly higher (about three times higher) in the pH-stat group than in the alpha-stat group (15% +/- 4% versus 5% +/- 1% of baseline at 60 minutes of retrograde cerebral perfusion). Tissue oxygen saturation appeared to be higher during retrograde cerebral perfusion in the pH-stat group than in the alpha-stat group. Brain tissue blood flow during rewarming remained significantly higher with the use of pH-stat than with the use of alpha-stat. Brain tissue water contents were similar in both groups. CONCLUSIONS: In our pig model, the use of a pH-stat strategy during retrograde cerebral perfusion significantly improves brain tissue perfusion. Therefore, to improve retrograde cerebral blood flow during retrograde cerebral perfusion, it may be preferable to use a pH-stat strategy, rather than an alpha-stat strategy.     

Recovery of left ventricular function after hypothermic global ischemia. Age-related differences in the isolated working rabbit heart

The immature myocardium has a greater tolerance for ischemia than does the mature heart. The effect of ischemia when combined with hypothermia on the newborn heart is poorly understood but has important clinical applications. This study examined the metabolic and functional recovery after 90 minutes of global ischemia at 20 degrees C in neonatal (1 week), immature (1 month), and mature (4 month) isolated working rabbit hearts. Following ischemia, aortic flow, cardiac output, heart rate, and stroke work remained at baseline values for neonatal hearts. Only coronary flow was significantly reduced from a control level of 4.5 +/- 1.4 (standard error of the mean) to 3.3 +/- 1.1 ml/min, p less than 0.05. In the immature group, hemodynamic parameters were below baseline, although no statistical differences were noted. Among mature hearts, however, all hemodynamic values were significantly below preischemic control. Water content was significantly higher in immature (73.2% +/- 1.4%) and mature (75.3% +/- 2.5%) hearts when compared with the neonatal group (46.8% +/- 4.6%), p less than 0.001. Coronary sinus creatine kinase was unchanged from baseline at 10 and 30 minutes following ischemia in the neonatal group. Although demonstrating substantial increases from baseline, statistical significance was not seen in the immature group because of the wide variation about the mean. In the mature group, creatine kinase rose significantly from preischemic levels of 15.4 +/- 4.3 IU/L/gm to 184.2 +/- 51.6 IU/L/gm at 10 minutes (p less than 0.01) and 123.7 +/- 31.9 IU/L/gm at 30 minutes (p less than 0.05). This study demonstrated improved tolerance to prolonged hypothermic ischemia in neonatal rabbit hearts when compared with older hearts subjected to the same conditions. The role of cardioplegic solutions in protecting the neonatal heart during cardiac operations when deep hypothermia is used may be of lesser importance than in the older patient.     

pH-stat blood gas management provides better cerebral perfusion during deep hypothermic retrograde cerebral perfusion

We performed a retrospective comparative clinical study to evaluate whether pH-stat (n=14) or alpha-stat strategy (n=15) provides better perfusion or oxygen metabolism during hypothermic retrograde cerebral perfusion (RCP). The pH-stat group showed significantly lower superior vena cava (SVC) pressure (21+/-4 versus 27+/-6 mmHg, P<0.0001), apparently lower retrograde cerebral vascular resistance index (7.4+/-2.1 versus 10.1+/-3.8 dynes/s cm(-5) m(-2), P=0.009) but there were no significant differences in RCP flow index, oxygen supply or oxygen extraction between groups. Further studies are necessary to determine which blood gas management is better for RCP, however, pH-stat strategy should be useful in deep hypothermic RCP.     

Comparison of neurologic outcome after deep hypothermic circulatory arrest with alpha-stat and pH-stat cardiopulmonary bypass in newborn pigs

OBJECTIVE: Deep hypothermic circulatory arrest for neonatal heart surgery poses the risk of brain damage. Several studies suggest that pH-stat management during cardiopulmonary bypass improves neurologic outcome compared with alpha-stat management. This study compared neurologic outcome in a survival piglet model of deep hypothermic circulatory arrest between alpha-stat and pH-stat cardiopulmonary bypass. METHODS: Piglets were randomly assigned to alpha-stat (n = 7) or pH-stat (n = 7) cardiopulmonary bypass, cooled to 19 degrees C brain temperature, and subjected to 90 minutes of deep hypothermic circulatory arrest. After bypass rewarming/reperfusion, they survived 2 days. Neurologic outcome was assessed by neurologic performance (0-95, 0 = no deficit and 95 = brain death) and functional disability scores, as well as histopathology. Arterial pressure, blood gas, glucose, and brain temperature were recorded before, during, and after bypass. RESULTS: All physiologic data during cardiopulmonary bypass were similar between groups (pH-stat vs alpha-stat) except arterial pH (7.06 +/- 0.03 vs 7.43 +/- 0.09, P <.001) and arterial PCO (2) (98 +/- 8 vs 36 +/- 8 mm Hg, P <.001). No differences existed in duration of cardiopulmonary bypass or time to extubation. Performance was better in pH-stat versus alpha-stat management at 24 hours (2 +/- 3 vs 29 +/- 17, P = 0.004) and 48 hours (1 +/- 2 vs 8 +/- 9, P =.1). Also, functional disability was less severe with pH-stat management at 24 hours (P =.002) and 48 hours (P =.053). Neuronal cell damage was less severe with pH-stat versus alpha-stat in the neocortex (4% +/- 2% vs 15% +/- 7%, P <.001) and hippocampal CA1 region (11% +/- 5% vs 33% +/- 25%, P =.04), but not in the hippocampal CA3 region (3% +/- 5% vs 16% +/- 23%, P =.18) or dentate gyrus (1% +/- 1% vs 3% +/- 6%, P =.63). CONCLUSIONS: pH-stat cardiopulmonary bypass management improves neurologic outcome with deep hypothermic circulatory arrest compared with alpha-stat bypass. The mechanism of protection is not related to hemodynamics, hematocrit, glucose, or brain temperature.     

Effect of differing acid-base regulation on cerebral blood flow autoregulation during cardiopulmonary bypass.

Cerebral dysfunction following cardiopulmonary bypass may be aggravated by altered autoregulation of cerebral blood flow. We have used trans-cranial Doppler to measure middle cerebral artery blood flow velocity during cardiopulmonary bypass managed by either pH-stat or alpha-stat acid-base protocols. Fourteen patients were studied, 7 in each group. During bypass at 28 degrees C, patients underwent incremental alterations in mean arterial pressure from 20-90 mmHg, maintaining systemic perfusion flow at 1.75 L/min per m2. The cerebral extraction ratio of oxygen was measured to indicate matching of cerebral blood flow to demand. The pH-stat group showed a pressure passive cerebral circulation with significant (r = 0.999, P less than 0.05) increase in blood flow velocity with increasing arterial pressure. This also occurred in alpha-stat group during the pressure range of 20-50 mmHg (r = 0.951, P less than 0.05). During the pressure range of 50-90 mmHg in alpha-stat group the change in flow velocity (0.16 cm/sec per mmHg) was significantly (P less than 0.05) less than that in pH-stat group (0.58 cm/second per mmHg). The cerebral extraction ratio of oxygen was less depressed in the alpha-stat group than in the pH-stat group, indicating more appropriate matching of cerebral blood flow and tissue demand. These results suggest that, during alpha-stat managed cardiopulmonary bypass, cerebral blood flow velocity is less subject to wide pressure alteration than pH-stat.     

Comparison of pH-stat versus Alpha-stat during hypothermic cardiopulmonary bypass in the prevention and control of acidosis in cardiac surgery

OBJECTIVES: To compare the effects of blood-gas management using either alpha-stat (temperature-uncorrected blood-gas management) or pH-stat (temperature-corrected blood-gas management) strategies, 30 patients undergoing coronary artery bypass surgery allocated randomly to either one of the approaches were studied. Acid-base balance, tissue oxygenation, and biochemical parameters were measured at distinct times: before bypass, after 15 min of hypothermia at 32 degrees C, after 45 min of hypothermia at 32 degrees C, after 15 min of rewarming at 37 degrees C, and 45 min after the end of bypass in normothermic conditions. RESULTS: The groups were similar with regard to physical characteristics, physiological parameters, and bypass time. In the pH-stat group, CO2 administered with the aim of correcting pH for the patients hypothermic temperature caused a significant increase in temperature-uncorrected PaCO2 and a decrease in arterial temperature-uncorrected pH at 45 min. During the rewarming period and following bypass, the pH was lower and PaCO2 higher in the pH-stat group (P < 0.001). CONCLUSION: It was found that during the rewarming period and following bypass, the resulting acidosis caused by the procedure was less in the alpha-stat group. It was found that there were no difference between the two groups, with regard to tissue perfusion, as is seen by the tissue oxygenation parameters and lactic acid concentration.     

Right ventricular free wall isolation: effects on regional myocardial blood flow

The right ventricular isolation procedure was developed to treat medically refractory, nonischemic right ventricular tachycardia. The effect of this procedure on regional myocardial blood flow to the isolated right ventricle was evaluated in 10 adult mongrel dogs. There were no significant changes in aortic pressure, right ventricular systolic or diastolic pressure, or cardiac index following right ventricular isolation when the left ventricle and right ventricular free wall were synchronously paced. Myocardial blood flow to the isolated right ventricle was unchanged following the procedure (0.85 +/- 0.07 ml/min/gm to 0.87 +/- 0.08 ml/min/gm; p = not significant). Analysis of regional flow revealed that only a thin rim of right ventricular tissue near the ventriculotomy showed a significant decrease in blood flow (1.10 +/- 0.1 ml/min/gm to 0.29 +/- 0.04 ml/min/gm; p less than 0.05). Thus, this procedure leaves intact the blood supply to the great percentage of the right ventricular free wall. This finding supports the concept that the right ventricular isolation procedure is effective in isolating abnormal electrical activity without compromising regional myocardial blood flow.