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Biomedical subjects

D S Prough

Publications and source records attributed to D S Prough.

At least 109 records · Page 6Linked to original sources
PubMed1990

Hypercarbia depresses cerebral oxygen consumption during cardiopulmonary bypass.

No human studies have systematically examined the relations among PaCO2, cerebral blood flow, and the cerebral metabolic rate for oxygen during hypothermic cardiopulmonary bypass. We varied PaCO2 during hypothermic (26-28 degrees C) cardiopulmonary bypass and estimated the cerebral metabolic rate for oxygen by multiplying cerebral blood flow (measured using xenon-133 clearance) by the cerebral arteriovenous difference in oxygen contents. Patients were randomly assigned to either of two methods of managing PaCO2 (uncorrected for body temperature). In group 1 (PACO2 32-48 mm Hg, n = 13) the mean +/- SD cerebral metabolic rate for oxygen was 0.40 +/- 0.11 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 36 +/- 2.0 mm Hg and 0.40 +/- 0.14 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 45 +/- 2 mm Hg. and 49-72 mm Hg, n = 12) the mean +/- SD cerebral metabolic rate for oxygen was 0.31 +/- 0.09 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 55 +/- 3 mm Hg and 0.21 +/- 0.07 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 68 +/- 2 mm Hg. Group 2 values differed significantly from those in Group 1 (p less than 0.05). In both groups, cerebral blood flow increased as PaCO2 increased. During cardiopulmonary bypass, increasing PaCO2 increases cerebral blood flow and decreases the cerebral metabolic rate for oxygen.

Arteries↗
PubMed1990

Regional cerebrovascular reactivity to carbon dioxide during cardiopulmonary bypass in patients with cerebrovascular disease.

In patients with cerebrovascular disease, hypercarbia may cause redistribution of regional cerebral blood flow from marginally perfused to well-perfused regions (intracerebral steal), as evidenced by regional cerebral blood flow studies during carotid endarterectomy. During hypothermic cardiopulmonary bypass, the pH-stat method of acid-base management produces relative hypercarbia. To determine whether pH-stat management produces relative hypercarbia. To determine whether pH-stat management induces intracerebral steals, we investigated nine patients with cerebrovascular disease undergoing coronary artery bypass grafting. During hypothermic cardiopulmonary bypass, arterial carbon dioxide tension was varied in random order between 40 mm Hg and 60 mm Hg (uncorrected for body temperature). Regional cerebral blood flow was measured by clearance of 133 xenon injected into the arterial inflow cannula. Nasopharyngeal temperature (26.8 degrees-28.0 degrees +/- 2.2 degrees-3.0 degrees C), perfusion flow rate (2.14-2.18 +/- 0.70-0.73 L/min/m2), mean arterial pressure (67-68 +/- 6-9 mm Hg), arterial carbon dioxide tension (302-308 +/- 109-113 mm Hg), and hematocrit (23% +/- 4%) were maintained within narrow limits in each patient during arterial carbon dioxide tension manipulation. Global mean cerebral blood flow values were similar to previously reported values in patients free of cerebrovascular disease; patients in this study averaged 15.2 +/- 2.5 ml/100 gm/min at an arterial carbon dioxide tension of 46.1 +/- 8.4 mm Hg and 25.3 +/- 6.1 ml/100 gm/min at an arterial carbon dioxide tension of 71.1 +/- 11.8 mm Hg. Carbon dioxide reactivity, defined as mean global cerebral blood flow (in ml/100 gm/min) divided by arterial carbon dioxide tension (in mm Hg), was similar in the region having the lowest regional cerebral blood flow and in the brain as a whole. No patient developed evidence of an intracerebral steal at the higher arterial carbon dioxide tension. During hypothermic cardiopulmonary bypass, higher levels of arterial carbon dioxide tension, such as those associated with the pH-stat management technique, are apparently not associated with potentially harmful redistribution of cerebral blood flow in patients with cerebrovascular disease.

Adult↗
PubMed1990

Heparin dosing and monitoring for cardiopulmonary bypass. A comparison of techniques with measurement of subclinical plasma coagulation.

Subclinical plasma coagulation during cardiopulmonary bypass has been associated with marked platelet and clotting factor consumption in monkeys. To better define subclinical coagulation in man, we measured plasma fibrinopeptide A concentrations before, during, and after cardiopulmonary bypass. Patients were assigned to one of three groups of heparin management: group 1 (n = 10)--initial heparin dose 300 IU/kg, with supplemental heparin if the activated coagulation time fell below 400 seconds; group 2 (n = 6)--initial heparin dose 250 IU/kg, with supplemental heparin if activated coagulation time was less than 400 seconds; and group 3 (n = 5)--initial heparin dose 350 to 400 IU/kg, with supplemental heparin if whole blood heparin concentration was less than or equal to 4.1 IU/ml. Activated coagulation time and heparin concentration were measured every 30 minutes during cardiopulmonary bypass, and fibrinopeptide A was measured at hypothermia, normothermia, and whenever activated coagulation time was less than 400 seconds. Quantitative and qualitative blood clotting competence was assessed after cardiopulmonary bypass, including mediastinal drainage for the first 24 hours. Fibrinopeptide A values were markedly elevated during cardiopulmonary bypass but were well below the levels present before and after cardiopulmonary bypass. Fibrinopeptide A correlated inversely with heparin concentration during cardiopulmonary bypass (r = -0.46, p = 0.03), but higher fibrinopeptide A levels during cardiopulmonary bypass did not correlate with post-cardiopulmonary bypass coagulopathy. Group 3 patients received the highest heparin doses (p less than 0.05) and had the greatest postoperative blood loss (p less than 0.05). Protamine dose and heparin concentration during cardiopulmonary bypass correlated best with postoperative mediastinal drainage. Our findings support the following conclusions: (1) compensated subclinical plasma coagulation activity occurs during cardiopulmonary bypass despite activated coagulation time greater than 400 seconds or heparin concentration greater than or equal to 4.1 IU/ml; (2) post-cardiopulmonary bypass mediastinal drainage correlates strongly with increased heparin concentration during cardiopulmonary bypass (p less than 0.05) and protamine dose (p less than 0.05); and (3) during cardiopulmonary bypass at both normothermia and hypothermia, activated coagulation times greater than 350 seconds result in acceptable fibrinopeptide A levels and post-cardiopulmonary bypass blood clotting.

Blood Coagulation↗
PubMed1989

Cerebral blood flow is reduced in patients with sepsis syndrome.

The relationship between sepsis-induced CNS dysfunction and changes in brain blood flow remains unknown, and animal studies examining the influence of sepsis on cerebral blood flow (CBF) do not satisfactorily address that relationship. We measured CBF and cerebrovascular reactivity to CO2 in nine patients with sepsis syndrome using the 133Xe clearance technique. Mean CBF was 29.6 +/- 15.8 (SD) ml/100 g.min, significantly lower than the normal age-matched value in this laboratory of 44.9 +/- 6.2 ml/100 g.min (p less than .02). This depression did not correlate with changes in mean arterial pressure. Despite the reduction in CBF, the specific reactivity of the cerebral vasculature to changes in CO2 was normal, 1.3 +/- 0.9 ml/100 g.min/mm Hg. Brain blood flow is reduced in septic humans; the contribution of this reduction to the metabolic and functional changes observed in sepsis requires further study.

Adult↗
PubMed1989

Hemodynamic status following regional and general anesthesia for carotid endarterectomy.

We prospectively studied 23 patients undergoing carotid endarterectomy under regional (n = 13) or general (n = 10) anesthesia to determine the hemodynamic basis of increased frequency in the need for postoperative vasopressor support when regional anesthesia was used. Anesthesia and postoperative care were conducted without reference to hemodynamic data from pulmonary artery catheterization. Although mean arterial pressure was similar in the two groups postoperatively, 11 of the 13 patients undergoing regional anesthesia and 3 of the 10 patients undergoing general anesthesia required phenylephrine postoperatively. No patient required therapy postoperatively to reduce a systolic pressure exceeding 160 mm Hg. Mean arterial pressure remained below the preoperative baseline value in both groups (p < 0.05 with general anesthesia; p = 0.06 with regional anesthesia) during follow-up. In the general anesthesia group, systemic vascular resistance declined significantly below baseline (p < 0.05) following the operation, accompanied by a decline in mean arterial pressure (p < 0.05) and a higher cardiac output. Intraoperative fluid requirements were greater during general anesthesia than during regional anesthesia (p < 0.01). Pulmonary artery occlusion pressure was lower postoperatively than at baseline in both groups (p < 0.05). Pulmonary artery occlusion pressure was higher in the general anesthesia group despite the greater use of phenylephrine in the regional anesthesia group.

Journal Article↗
PubMed1989

The effects of regional and general anesthesia on blood pressure control after carotid endarterectomy.

We retrospectively reviewed the influence of preoperative blood pressure control and regional vs. general anesthetic techniques on the incidence of intraoperative and postoperative (recovery room and intensive care unit) hypotension and hypertension in 249 carotid endarterectomy patients. Preoperative blood pressure was classified as uncontrolled hypertension (systolic blood pressure >/= 170 mm Hg and/or diastolic blood pressure >/= 95 mm Hg), controlled hypertension (blood pressure <170/95 mm Hg on chronic antihypertensive therapy), or normotension (blood pressure <170/95 mm Hg without antihypertensive therapy). Hypotension, as defined by the requirement for vasopressor administration to maintain a systolic blood pressure of at least 120 mm Hg, occurred more frequently after regional than after general anesthesia (p < 0.05). Postoperative hypertension was defined as a systolic blood pressure >/= 200 mm Hg and/or a diastolic blood pressure >/= 110 mm Hg in the recovery room or in the Intensive Care Unit. Preoperative hypertension was not associated with acute postoperative hypertension in the intensive care unit in either the regional anesthesia (n = 190) or the general anesthesia (n = 59) groups, although with either type of anesthesia, preoperative hypertension was associated with an increased incidence of hypertension in the recovery room (p < 0.01 regional; p < 0.005 general).

Journal Article↗
PubMed1989

Thromboxane A2 receptor antagonist SQ29548 does not improve canine postischemic cerebral hypoperfusion.

The thromboxane receptor antagonist SQ29548 was administered to mongrel dogs after an 11-min period of global cerebral ischemia to test the hypothesis that it would improve delayed postischemic cerebral hypoperfusion (PIH) during concurrent elevations in cerebral venous thromboxane B2 (TxB2), the stable metabolite of thromboxane A2 (TxA2). Immediately following an 11-min period of aortic root cross-clamping, six dogs received 0.2 mg/kg of SQ29548 intravenously followed by continuous infusion of 0.2 mg/kg/h (TRA group) and six received a saline placebo (control). Over the next 120 min, cerebral venous outflow was measured from the confluence of the sagittal and lateral sinuses, while arterial and cerebral venous samples were obtained for measurement of TxB2. Delayed postischemic cerebral hypoperfusion, confirmed in the control group (p < 0.05) (16 +/- 2.7 vs. 32 +/- 2.4 ml/min baseline), was nearly identical in the TRA group (14 +/- 0.9 vs. 30 +/- 2.5 ml/min baseline). Cerebral venous TxB2 levels rose dramatically in both groups after ischemia (3670 +/- 440 vs. 1100 +/- 350 pg/ml baseline, control and 2720 +/- 170 vs. 580 +/- 100 pg/ml baseline, TRA group) (p < 0.05). There were no significant group mean differences in any of the other hemodynamic data except mean arterial pressure (MAP) at T120 and Hgb at baseline. We conclude that postischemic intravenous administration of the thromboxane receptor-specific antagonist SQ29548 fails to improve delayed postischemic cerebral hypoperfusion and does not alter cerebral venous TxB2 release in this canine model of global cerebral ischemia.

Journal Article↗
PubMed1989

Pentoxifylline increases cerebral blood flow in patients with cerebrovascular disease.

We determined the immediate effects of pentoxifylline on cerebral blood flow in 10 patients with cerebrovascular disease; four received 400 mg and six received 800 mg pentoxifylline orally. Regional cerebral blood flow was measured before (baseline) and 2, 4, and 6 hours after pentoxifylline administration using the xenon-133 clearance technique with 16 detectors (eight per hemisphere). Global cerebral blood flow as a percentage of the baseline value increased significantly after 800 mg but not 400 mg pentoxifylline (p = 0.017 and p = 0.29, respectively). Regional cerebral blood flow as a percentage of the baseline value at the detector with the lowest baseline value increased significantly 2 hours after both 400 mg and 800 mg pentoxifylline (p = 0.038 and p = 0.010, respectively). Cerebrovascular reactivity to carbon dioxide was preserved despite the increases in cerebral blood flow. Pentoxifylline increases cerebral blood flow and is not associated with "intracerebral steal" in patients with cerebrovascular disease.

Aged↗
PubMed1989

Cerebral blood flow does not change following sodium nitroprusside infusion during hypothermic cardiopulmonary bypass.

Changes in cerebral blood flow (CBF) associated with decreases in mean arterial pressure (MAP) produced by sodium nitroprusside (SNP) infusion were measured by intra-aortic injection of 133Xe in 17 patients during hypothermic cardiopulmonary bypass (CPB). In each patient, CBF was determined at baseline and then again following SNP-induced reduction of MAP. Two groups were studied. In Group I (n = 9), PaCO2 was maintained near 42 mm Hg uncorrected for nasopharyngeal temperature (NPT). In Group II (n = 8), PaCO2 was maintained near 60 mm Hg, uncorrected for NPT. Nasopharyngeal temperature, MAP, pump oxygenator flow, PaO2, and hematocrit were maintained within a narrow range in each patient during both studies. Since the baseline CBF determinations were conducted at the higher MAP in all subjects, we corrected post-SNP CBF data for the spontaneous decline that occurs over time during CPB. In Group I, a reduction in MAP from 76 +/- 9 mm Hg (mean +/- SD) to 50 +/- 6 mm Hg was associated with a reduction in CBF from 17 +/- 5 to 13 +/- 3 ml.100 g.min-1 (P less than 0.01), a decrease that became statistically insignificant once the time correction factor had been applied (16 +/- 4 ml.100 g-1.min-1). In Group II, MAP declined from 75 +/- 5 mm Hg to 54 +/- 5 mm Hg, and CBF declined from 25 +/- 10 to 17 +/- 7 ml.100 g.min-1 (P less than 0.01), but, again, after time correction, the CBF decline was statistically insignificant (22 +/- 8 ml.100 g-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Physiology and pharmacology of cerebral blood flow and metabolism.

In many critically ill patients, long-term neurologic outcome may depend on the adequacy of regional or global CBF. Despite this possibility, clinical protocols for the management of the cerebral circulation in acute neurologic disease have developed slowly. Perhaps progress in central nervous system monitoring, coupled with recent advances in cerebrovascular pharmacology, will alter the management and prognosis of patients with critical neurologic illness.

Brain↗
PubMed1989

The effect of age on cerebral blood flow during hypothermic cardiopulmonary bypass.

Cerebral blood flow was measured in 20 patients by xenon 133 clearance methodology during nonpulsatile hypothermic cardiopulmonary bypass to determine the effect of age on regional cerebral blood flow during these conditions. Measurements of cerebral blood flow at varying perfusion pressures were made in patients arbitrarily divided into two age groups at nearly identical nasopharyngeal temperature, hematocrit value, and carbon dioxide tension and with equal cardiopulmonary bypass flows of 1.6 L/min/m2. The range of mean arterial pressure was 30 to 110 mm Hg for group I (less than or equal to 50 years of age) and 20 to 90 mm Hg for group II (greater than or equal to 65 years of age). There was no significant difference (p = 0.32) between the mean arterial pressure in group I (54 +/- 28 mm Hg) and that in group II (43 +/- 21 mm Hg). The range of cerebral blood flow was 14.8 to 29.2 ml/100 gm/min for group I and 13.8 to 37.5 ml/100 gm/min for group II. There was no significant difference (p = 0.37) between the mean cerebral blood flow in group I (21.5 +/- 4.6 ml/100 gm/min) and group II (24.3 +/- 8.1 ml/100 gm/min). There was a poor correlation between mean arterial pressure and cerebral blood flow in both groups: group I, r = 0.16 (p = 0.67); group II, r = 0.5 (p = 0.12). In 12 patients, a second cerebral blood flow measurements was taken to determine the effect of mean arterial pressure on cerebral blood flow in the individual patient. Changes in mean arterial pressure did not correlate with changes in cerebral blood flow (p less than 0.90). We conclude that age does not alter cerebral blood flow and that cerebral blood flow autoregulation is preserved in elderly patients during nonpulsatile hypothermic cardiopulmonary bypass.

Aged↗
PubMed1988

The effects of traumatic brain injury on regional cerebral blood flow in rats.

Alterations in cerebral blood flow (CBF) are among the most important secondary pathophysiologic consequences of traumatic brain injury. The present study compared CBF in control rats (n = 20) and in rats that received a calibrated experimental traumatic brain injury (n = 17). The traumatized rats were anesthetized with ketamine (25 mg/kg) and xylazine (10 mg/kg), and prepared for fluid percussion injury (FPI). Twenty-four hours later, the rats were anesthetized with 1% halothane in nitrous oxide-oxygen (70:30) and the left atrium was catheterized via a thoroacotomy. The atrial cannula was used to inject 15 microns radiolabeled microspheres to measure CBF. Following surgery, the concentration of halothane was reduced to 0.5% and the rats were paralyzed with pancuronium bromide (0.1 mg/kg). Thirty minutes later, baseline microsphere determinations were made, and the rats were injured (2.47 +/- 0.08 atm). Each rat received additional injections of microspheres at two of the following four times (T): 5, 15, 30, and 60 min after the brain injury. The procedures for the control group rats were the same as described above except that the rats were not subjected to the craniotomy and the FPI. The traumatized group exhibited heterogeneous decreases in CBF following trauma. Global CBF in this group was 78% (p less than 0.01), 64% (p less than 0.05), 52% (p less than 0.001) of those in the control group at T5, 15, 30, and 60, respectively. In rats, the most prominent cerebral circulatory changes following fluid percussion injury were early reductions of CBF and an increasingly heterogeneous CBF pattern. Hemorrhage, edema, and elevated prostagandin levels are mechanisms that may contribute to these changes.

Animals↗
PubMed1988

Experimental traumatic brain injury elevates brain prostaglandin E2 and thromboxane B2 levels in rats.

Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) levels were measured in rats following experimental traumatic brain injury. Rats (n = 36) were prepared for fluid percussion brain injury under pentobarbital anesthesia. Twenty-four hours later, rats were lightly anesthetized using methoxyflurane, injured (2.3 atm), and killed 5 or 15 min later. Twelve of the rats died before and are not included in the analyses. The following groups were used for data analysis: group I (n = 6) were sham-injured rats prepared for injury but not injured: group II (n = 6) were injured and killed 5 min later; group III (n = 12) were injured and killed 15 min posttrauma. Thirty seconds prior to sacrifice by decapitation into liquid nitrogen, all rats were injected with indomethacin (3 mg/kg, intravenously [IV]) to prevent postmortem PG synthesis. After sacrifice, brains were removed, weighed, and homogenized in a small quantity of phosphate buffer with indomethacin (50 micrograms/ml). PGE2 and TxB2 levels were determined using double-label radioimmunoassays. Posttraumatic convulsions were observed in 5 of 12 rats in group III and these rats were analyzed separately. PGE2 and TxB2 levels increased significantly (p less than 0.05) in both hemisphere and brainstem 5 min posttrauma. Fifteen minutes after injury, both PGE2 and TxB2 levels remained elevated but the levels were lower than at 5 min in the rats that did not exhibit posttraumatic seizures. This decrease in PG levels at 15 min was not observed in the rats that had seizures after injury and both PGE2 and TxB2 levels remained high in hemispheres and brainstem. Thus, fluid percussion brain injury results in substantial elevations in PGE2 and TxB2 levels and posttraumatic seizures exacerbate the observed increases.

Animals↗
PubMed1988

Response of cerebral blood flow to phenylephrine infusion during hypothermic cardiopulmonary bypass: influence of PaCO2 management.

Twenty-eight adult patients anesthetized with fentanyl, then subjected to hypothermic cardiopulmonary bypass (CPB), were studied to determine the effect of phenylephrine-induced changes in mean arterial pressure (MAP) on cerebral blood flow (CBF). During CPB patients managed at 28 degrees C with either alpha-stat (temperature-uncorrected PaCO2 = 41 +/- 4 mmHg) or pH-stat (temperature-uncorrected PaCO2 = 54 +/- 8 mmHg) PaCO2 for blood gas maintenance received phenylephrine to increase MAP greater than or equal to 25% (group A, n = 10; group B, n = 6). To correct for a spontaneous, time-related decline in CBF observed during CPB, two additional groups of patients undergoing CPB were either managed with the alpha-stat or pH-stat approach, but neither group received phenylephrine and MAP remained unchanged in both groups (group C, n = 6; group D, n = 6). For all patients controlled variables (nasopharyngeal temperature, PaCO2, pump flow, and hematocrit) remained unchanged between measurements. Phenylephrine data were corrected based on the data from groups C and D for the effect of diminishing CBF over time during CPB. In patients in group A CBF was unchanged as MAP rose from 56 +/- 7 to 84 +/- 8 mmHg. In patients in group B CBF increased 41% as MAP rose from 53 +/- 8 to 77 +/- 9 mmHg (P less than 0.001). During hypothermic CPB normocarbia maintained via the alpha-stat approach at a temperature-uncorrected PaCO2 of approximately equal to 40 mmHg preserves cerebral autoregulation; pH-stat management (PaCO2 approximately equal to 57 mmHg uncorrected for temperature, or 40 mmHg when corrected to 28 degrees C) causes cerebrovascular changes (i.e., impaired autoregulation) similar to those changes produced by hypercarbia in awake, normothermic patients.

Aged↗