Carbon dioxide management and the cerebral response to hemodilution during hypothermic cardiopulmonary bypass in dogs.

BACKGROUND: Increases in blood flow support oxygen (O2) delivery with hemodilution. However, with alpha-stat management, the cerebral response to hemodilution is blunted. We tested the hypothesis that carbon dioxide (CO2) management is a primary determinant of the cerebral blood flow (CBF) response to hemodilution during hypothermic bypass. METHODS: Following Animal Care Committee approval, 15 dogs underwent bypass at 18 degrees C (pH-stat, n = 7 or alpha-stat, n = 8). Measurements were obtained after progressive hemodilution, and cerebral blood flow was determined by sagittal sinus outflow. Arterial pressure was maintained at 60 to 70 mm Hg. The CBF response to hemodilution and cerebral metabolic rate were compared in the two groups of animals. RESULTS: In both groups, hemodilution increased CBF. At every hematocrit, CBF and O2 delivery in the pH-stat group exceeded that of alpha-stat group, although O2 demand did not differ between groups. While absolute CBF in the pH-stat group was greater at every hematocrit, the relative change in CBF from control and the slope of the CBF-Hct relationship did not differ between groups. CONCLUSIONS: pH-stat management is associated with a greater absolute CBF and a greater ratio of cerebral O2 supply to demand for any degree of hemodilution. However, over the range of hematocrits common in practice, CO2 management per se does not determine the cerebral response to hemodilution.

Hierarchy of regional oxygen delivery during cardiopulmonary bypass.

BACKGROUND: Relative to the nonbypass state, cardiopulmonary bypass may decrease whole-body oxygen (O2) delivery. We predicted that during cardiopulmonary bypass, a hierarchy of regional blood flow and O2 delivery could be characterized. METHODS: In 8 46.5 +/- 1.2-kg pigs, fluorescent microspheres were used to determine blood flow and O2 delivery to five organ beds before and during 37 degrees C cardiopulmonary bypass at four randomized bypass flows (1.4, 1.7, 2.0, and 2.3 L/min/m2). At completion, 18 tissue samples were obtained from the cerebral cortex (n = 4), renal cortex (n = 2), renal medulla (n = 2), pancreas (n = 3), small bowel (n = 3), and limb muscle (n = 4) for regional blood flow determination. RESULTS: At conventional cardiopulmonary bypass flow (2.3 L/min/m2), whole-body O2 delivery was reduced by 44 +/- 6% relative to the pre-cardiopulmonary bypass state (p < 0.05). Over a range of cardiopulmonary bypass flows (2.3 to 1.7 L/min/m2), brain and kidney maintained their perfusion. Blood flow and O2 delivery to both regions were reduced when the cardiopulmonary bypass flow was reduced to 1.4 L/min/m2. However, perfusion and O2 delivery to other visceral organs (pancreas, small bowel) and skeletal muscle showed pump flow dependency over the range of flows tested. CONCLUSIONS: This study characterizes the organ-specific hierarchy of blood flow and O2 distribution during cardiopulmonary bypass. These dynamics are relevant to clinical decisions for perfusion management.

Time and dose effect of transdermal nicotine on endothelial function.

Nicotine patches are available as an over-the-counter medication for aid in smoking cessation. This study was designed to determine how nicotine patch therapy over time and dose ranges used in smoking cessation programs in humans affects endothelium-dependent relaxations. Dogs were treated with nicotine patches (11, 22, or 44 mg/day) for 2 and 5 wk. Circulating nicotine and oxidized products of nitric oxide (NOx) were measured. Coronary arteries were prepared for measurement of isometric force and aortic endothelial cells were prepared for measurement of mRNA or NO synthase (NOS) activity. Circulating nicotine increased with increasing concentrations of nicotine patches. After 5 wk of treatment with 22 mg/day patches, circulating NOx was reduced but NOS activity was increased. NOS mRNA was similar among groups. Only after 5 wk of treatment with 22 mg/day patches were endothelium-dependent relaxations reduced to alpha(2)-adrenergic agonists, ADP, and the calcium ionophore A-23187. These results suggest a time and biphasic dose effect of nicotine treatment on endothelium-dependent responses that may be related to bioavailability of NO. This complex relationship of duration and dose of nicotine treatment may explain, in part, discrepancies in effects of nicotine on endothelium-dependent responses.

Differential perfusion: a new technique for isolated brain cooling during cardiopulmonary bypass.

BACKGROUND: The purpose of this study was to determine the feasibility of differential perfusion of the aortic arch and descending aorta during cardiopulmonary bypass using a cannula designed for aortic segmentation. METHODS: Pigs weighing 57 kg (n = 8), underwent cardiopulmonary bypass using the dual lumen aortic cannula. An inflatable balloon separated proximal (aortic arch) and distal (descending aorta) ports. During differential perfusion, the aorta was segmented and the arch and descending aorta perfused differentially using parallel heat exchangers. Ability to independently control brain and body temperature, cardiopulmonary bypass flow rate and mean arterial blood pressure was determined. RESULTS: During differential perfusion cerebral hypothermia (27 degrees C) with systemic normothermia (38 degrees C) was established in 23 minutes. Independent control of arch and descending aortic flow and mean arterial blood pressure was possible. Analysis of internal jugular venous O2 saturation data indicated an increase in the ratio of cerebral O2 supply to demand during differential perfusion. CONCLUSIONS: A cannulation system segmenting the aorta allows independent control of cerebral and systemic perfusion. This device could provide significant cerebral protection while maintaining the advantages of warm systemic cardiopulmonary bypass temperatures.

Effect of cerebral embolization on regional autoregulation during cardiopulmonary bypass in dogs.

BACKGROUND: Embolization during cardiopulmonary bypass probably alters cerebral autoregulation. Therefore, using laser Doppler flowmetry we investigated the cerebral blood flow velocity changes in response to changes in arterial pressure, before and after embolization in a canine bypass model. METHODS: After Institutional Animal Care and Use Committee approval, 8 anesthetized dogs had a laser Doppler flow probe positioned over the temporoparietal dura. During 37 degrees C cardiopulmonary bypass, the cerebral blood flow velocity response to changing mean arterial pressure (40 to 85 mm Hg in random order) was assessed before and after systemic embolization of 100 mg of 97-microm latex microspheres. RESULTS: Before embolization, cerebral blood flow velocity increased 39% as mean arterial pressure increased from 40 to 85 mm Hg. Following embolization, a 94% increase in cerebral blood flow velocity was demonstrated over the same mean arterial pressure range. The slopes of the curves relating cerebral blood flow velocity to mean arterial pressure were 0.21+/-0.74 and 1.31+/-0.87, before and after embolization (p = 0.016) respectively. CONCLUSIONS: Regional cerebral blood flow autoregulation may be impaired by microembolization known to occur during cardiopulmonary bypass, increasing the dependence of cerebral blood flow on mean arterial pressure.

Bypass flow, mean arterial pressure, and cerebral perfusion during cardiopulmonary bypass in dogs.

OBJECTIVE: To determine if normal cardiopulmonary bypass (CPB) pump flows maintain cerebral perfusion in the context of reduced mean arterial pressure at 33 degrees C. DESIGN: A prospective investigation. SETTING: Animal CPB research laboratory. PARTICIPANTS: Seven dogs that underwent CPB. INTERVENTIONS: Seven dogs underwent CPB at 33 degrees C using alpha-stat management and a halothane, fentanyl-midazolam anesthetic. Cerebral blood flow was measured using the sagittal sinus outflow technique. After control measurements at 70 mm Hg, cerebral physiologic values were determined under four conditions in random order: (1) mean arterial pressure of 60 mm Hg achieved by a reduction in pump flow, (2) mean arterial pressure of 60 mmHg determined by partial opening of a femoral arterial-to-venous reservoir shunt, (3) mean arterial pressure of 45 mm Hg by reduced pump flow, and (4) mean arterial pressure of 45 mm Hg by shunt. A 9F femoral arterial-to-venous reservoir shunt was controlled by a screw clamp. MEASUREMENTS AND MAIN RESULTS: Except for the controlled variables of mean arterial pressure and bypass flow, physiologic determinants of cerebral blood flow (temperature, PaCO2 and hematocrit) did not differ under any of the CPB conditions. Pump flow per se was not a determinant of cerebral perfusion. Cerebral blood flow and cerebral oxygen delivery did not differ with changes in pump flow if mean arterial pressure did not differ. Cerebral blood flow depended on mean arterial pressure under all pump flow conditions, however. CONCLUSIONS: Over the range of flows typical in adult CPB at 33 degrees C, pump flow does not have an effect on cerebral perfusion independent of its effect on mean arterial pressure. A targeted pump flow per se is not sufficient to maintain cerebral perfusion if mean arterial blood pressure is reduced.