Biomedical subjects

D J Deyo

Publications and source records attributed to D J Deyo.

At least 19 recordsLinked to original sources

PubMed2001

Safety and efficacy of a heparin removal device: a prospective randomized preclinical outcomes study.

BACKGROUND: Systemic protamine sulfate for heparin reversal after cardiopulmonary bypass (CPB) is associated with uncommon, but life-threatening adverse reactions. METHODS: In a prospective randomized 3-day outcomes study, a heparin removal device (HRD) group (n = 12; 60-, 80-, 100-kg subgroups) was compared with a matched systemic Protamine group (Protamine; n = 6) for safety and efficacy using an adult swine model of CPB (60 minutes, 28 degrees C). RESULTS: HRD run time was 25 to 38 minutes depending on weight without complications. After HRD, heparin concentration decreased from 4.77 +/- 0.17 to 0.45 +/- 0.06 U/mL (activated clotting time [ACT] 776 +/- 83 to 180 +/- 12 seconds), and in Protamine, 3.94 +/- 0.63 to 0.13 +/- 0.02 U/mL (ACT 694 +/- 132 to 101 +/- 5 seconds) (p = 0.01 between groups, but no significant differences 60 minutes later). No significant difference between HRD and Protamine to 72 hours was seen in plasma-free hemoglobin C3a, heparin concentration, thromboelastogram index, platelet count, activated partial thromboplastin time, anti-thrombin III, fibrinogen, ACT, and tissue histology. CONCLUSIONS: In a prospective randomized outcomes study, HRD achieved predictable reversal of systemic heparinization after CPB with no difference in safety or outcomes compared with protamine.

Adsorption↗

PubMed2001

Improved right heart function with a compliant inflow artificial lung in series with the pulmonary circulation.

BACKGROUND: We previously reported a 50% incidence of immediate right heart failure using a rigidly housed, noncompliant inflow artificial lung in series with the pulmonary circulation in a healthy ovine survival model. Three device modifications resulted: (1) an inflow cannula compliance chamber, (2) an inlet blood flow separator, and (3) modification of the artificial lung outlet geometry, all to reduce resistance and mimic the compliance of the pulmonary vascular bed. METHODS: In 7 sheep, arterial grafts were anastomosed end-to-side to the proximal and distal main pulmonary artery, with the paracorporeal artificial lung interposed. A pulmonary artery snare between anastomoses diverted full pulmonary blood flow through the artificial lung for up to 72 hours. RESULTS: Six of 7 sheep exhibited good cardiac function throughout the test period: mean central venous pressure was 6.8 mm Hg (range, 4 to 11 mm Hg), mean cardiac output, 4.17 +/- 0.12 L/min (range, 2.4 to 6.3 L/min); before and after device mean pulmonary arterial pressure, 21.8 and 18.5 mm Hg, and left atrial pressure, 10.8 mm Hg. CONCLUSIONS: This modified artificial lung prototype with an inflow compliance chamber, blood flow separator, and modified outlet geometry has greatly improved cardiac function and initial survival in our healthy ovine model.

Anastomosis, Surgical↗

PubMed2001

Percutaneous extracorporeal arteriovenous carbon dioxide removal improves survival in respiratory distress syndrome: a prospective randomized outcomes study in adult sheep.

OBJECTIVE: Arteriovenous carbon dioxide removal (AVCO(2)R) uses a simple arteriovenous shunt for CO(2) removal to minimize barotrauma/volutrauma from mechanical ventilation. We performed a prospective randomized outcomes study of AVCO(2)R in our new, clinically relevant model of respiratory distress syndrome. METHODS: Adult sheep (n = 18) received an LD(50) severe smoke inhalation and 40% third-degree burn. When respiratory distress syndrome developed (PaO (2)/FIO (2) < 200 at 40 to 48 hours), animals were randomized to the AVCO(2)R (n = 9) or sham group (n = 9) for 7 days. Ventilator management protocols mandated reductions in minute ventilation, first tidal volume to peak inspiratory pressure less than 30 cm H(2)O, then respiratory rate when PaCO (2) was less than 40 mm Hg. PaO (2) was kept above 60 mm Hg by adjusting FIO (2). When FIO (2) was 0.21, animals were weaned. RESULTS: The study required 2946 animal-hours of critical care with 696 AVCO(2)R hours. One died in each group during model development. AVCO(2)R flow from 820 mL/min to 970 mL/min (11% to 14% cardiac output) removed CO(2) at a rate of 92 to 116 mL/min (mean 103 mL/min; 93%-97% of CO(2) production). Heart rate, mean arterial pressure, cardiac output, and pulmonary arterial wedge pressure remained relatively constant. Within 48 hours, AVCO(2)R allowed significant ventilator reductions versus baseline in the following measurements: tidal volume (420 to 270 mL), peak inspiratory pressure (25 to 14 cm H(2)O), minute ventilation (13 to 5 L/min), respiratory rate (26 to 16 breaths/min), and FIO (2) (0.88 to 0.35). Ventilator-free days with AVCO(2)R were 3.9 versus 0.2 (P <.01) for sham animals, and ventilator-dependent days with AVCO(2)R were 2.4 versus 6.2 (P <.01) for the 3 sham survivors. All 8 AVCO(2)R animals and 3 of 8 sham animals survived 7 days after randomization. CONCLUSIONS: Percutaneous AVCO(2)R achieved significant reduction in airway pressures, increased ventilator-free days, decreased ventilator-dependent days, and improved survival in a sheep model of respiratory distress syndrome.

Animals↗

PubMed2001

Veno-venous perfusion-induced systemic hyperthermia: case report with perfusion considerations.

Cancer cells are more susceptible to destruction by heat than are their normal counterparts. However, optimization of this hyperthermic susceptibility for selective cancer cell kill has been difficult to define and technically difficult to achieve. A whole-body hyperthermic technique veno-venous perfusion-induced systemic hyperthermia (VV-PISH) was designed in in vitro and in swine experiments to achieve selective hyperthermic cancer cell destruction. In this case report, VV-PISH is studied for its safety and therapeutic efficiency in a Food and Drug Administration (FDA) approved phase-I study, where hyperthermia is used to treat advanced (Stage III B or IV) lung cancer. VV-PISH, utilizing the ThermoChem HT system in an extracorporeal circuit, was used to induce hyperthermia to 42.5 degrees C sustained for 120 min. Cooling returned the body temperature to 37 degrees C. After completion of the treatment, the patient was transferred to the intensive care unit on a ventilator, norepinephrine and diuretics. The patient remained somnolent for 36 h, developed pulmonary congestion requiring an additional 48 h before extubation, was transferred to the intermediate unit on day 4 and discharged in good condition on day 8. He did experience hyperthermia-related shrinkage of his lung cancer; however, he succumbed 270 days after this treatment from further progression of this disease. Hyperthermia is not a benign therapy; management techniques have been developed that have ameliorated many of the problems associated with extremely high temperatures, but pathophysiology still exists. Using these techniques, VV-PISH can be safety implemented, albeit not without temporary sequelae and further hospitalization.

Body Temperature↗

PubMed2001

Low-dose versus high-dose heparinization during arteriovenous carbon dioxide removal.

The purpose of this study was to compare low-dose (LD) and high-dose (HD) systemic heparinization in a prospective randomized study of arteriovenous carbon dioxide removal (AVCO2R) during acute respiratory distress syndrome, using a commercially available heparin-coated oxygenator. Adult sheep (n = 13) received an LD50 smoke inhalation and 40% TBSA third degree cutaneous flame burn injury. At 40-48 h post-injury, animals underwent cannulation of the carotid artery and jugular vein and were then randomized to HD heparin (activated clotting time, ACT > 300s, n = 6) and LD heparin (ACT < 200s, n =7) and placed on AVCO2R for approximately 72 h using an oxygenator with the Trillium Bio-Passive Surface. Mean ACTs were significantly different, as expected (HD: 446 +/- 26s, LD: 213 +/- 12s, p < 0.05). AVCO2R shunt flow averaged approximately 13% of cardiac output with mean CO2 removal similar in HD and LD, p = NS. The hematocrit, platelet count, and fibrin degradation products for the two groups were not different. No differences in thrombosis or bleeding were noted. In conclusion, LD systemic heparin (ACT < 200s) with a heparin-coated oxygenator does not increase thrombogenicity during AVCO2R for smoke/burn-induced severe lung injury in sheep.

Acute Disease↗

PubMed2000

Venovenous perfusion-induced systemic hyperthermia: hemodynamics, blood flow, and thermal gradients.

BACKGROUND: Thermal events during extracorporeal venovenous perfusion-induced systemic hyperthermia (VV-PISH) were studied and related to determination of whole-body and regional thermal isoeffect doses. METHODS: Swine (n = 6, 77+/-4.5 kg) were heated to a target temperature of 43 degrees C for 120 minutes using VV-PISH. Colored microspheres were injected during preheat, heat induction, maintenance, cool down, and after decannulation. The esophageal, tympanic, rectal, pulmonary artery, bladder, bone marrow, kidney, brain, blood, lung, and airway temperatures were recorded continuously. The thermal dose, thermal exchange, metabolic heat production, heat loss to the environment, the change in body heat, and the thermal isoeffect dose were studied at 15-minute intervals. RESULTS: VV-PISH increased heart rate and cardiac output and caused a redistribution of blood flow favoring the thoracoabdominal organs. Greatest thermal exchange occurred during the heating phase (total 2,162+/-143 kJ), metabolic heat production contributed in all phases (274+/-9 kJ), the greatest change in body heat occurred during heating (1,310+/-309 kJ) with a total delivered thermal dose of 298+/-21 kJ, and the total whole body thermal isoeffect dose at 100+/-5 minutes. CONCLUSIONS: VV-PISH is feasible, is capable of transferring sufficient heat, causes a redistribution of blood flow favoring the thoracoabdominal organs, and facilitates calculation of whole-body and regional thermal isoeffect doses.

Animals↗

PubMed2000

Effects of pentobarbital and isoflurane on conditioned learning after transient global cerebral ischemia in rabbits.

BACKGROUND: The acquisition of a conditioned eyeblink response has been used extensively to study the neurologic substrates of learning and memory. We examined the effects of the anesthetics isoflurane and pentobarbital, or hypothermia (30 degrees C), on the ability of rabbits to acquire an eyeblink conditioned response after 6.5 min of cerebral ischemia. METHODS: New Zealand white rabbits (n = 48) were randomly assigned to sham, normothermic, hypothermic, isoflurane, or pentobarbital groups. In the normothermic, hypothermic, isoflurane, and pentobarbital groups, 6.5 min of global cerebral ischemia was produced. In animals randomized to the isoflurane and pentobarbital groups, a pattern of burst suppression was achieved on the electroencephalogram before the start of the ischemic episode. Animals in the hypothermia group were cooled to 30 degrees C before ischemia. Seven days after ischemia, eyeblink training was started using an audible tone presented for 100 ms as the conditioned stimulus. The unconditioned stimulus was an air puff directed at the cornea. The delay between the end of conditioned stimulus and the start of the unconditioned stimulus (the trace interval) was 300 ms in duration. A conditioned response was defined as an eyeblink that was initiated during the trace interval. Eighty trials per day and 15 days of training were delivered. RESULTS: Neurologic deficits were greatest in the normothermia group, and these animals also had fewer conditioned responses than those in the sham, hypothermia, or pentobarbital groups. Animals in the isoflurane group had an intermediate number of conditioned responses that was not significantly different from the normothermia group. CONCLUSIONS: This study demonstrates that a brief episode of cerebral ischemia results in the impairment of associative learning. Hypothermia and burst-suppressive doses of pentobarbital were able to improve neurobehavioral outcome as measured by ability to acquire a trace conditioned response.

Adjuvants, Anesthesia↗

PubMed2000

New clinically relevant sheep model of severe respiratory failure secondary to combined smoke inhalation/cutaneous flame burn injury.

OBJECTIVES: To develop a predictable, dose-dependent, clinically relevant model of severe respiratory failure associated with a 40% total body surface area, full-thickness (third-degree) cutaneous flame burn and smoke inhalation injury in adult sheep. DESIGN: Model development. SETTING: Research laboratory. SUBJECTS: Adult female sheep (n = 22). INTERVENTIONS: Animals were divided into three groups, determined by the number of smoke breaths administered (24, 36, 48) for a graded inhalation injury. The smoke was insufflated into a tracheostomy with a modified bee smoker at airway temperatures <40 degrees C. All animals concurrently received a 40% total body surface area (third-degree) cutaneous flame burn to the body (flanks). After injury, the animals were placed on volume-controlled ventilation to achieve PaO2 >60 mm Hg and PaCO2 <40 mm Hg. Arterial blood gases and ventilator settings were monitored every 6 hrs postinjury for up to 7 days. MEASUREMENTS AND MAIN RESULTS: All animals survived the induction of injury. In the 24 smoke breath/40% total body surface area burn (24/40) group, PaO2/F(IO2) never decreased below 300, and peak inspiratory pressure was consistently <14 cm H2O with normal arterial blood gases throughout the observation period. With 36 smoke breaths/40% total body surface area burn (36/40) (n = 7), all animals had PaO2/F(IO2) of <200 and peak inspiratory pressure of 26 cm H2O within 40-48 hrs, as 30% died during the study period. With 48 smoke breaths/40% total body surface area burn (48/40) (n = 12), all animals developed respiratory distress syndrome (RDS) in 24-30 hrs, but none survived the experimental period. CONCLUSIONS: Development of RDS by smoke and cutaneous flame bum injury depends on smoke inhalation dose. A combination of 36 breaths of smoke and a 40% total body surface area (third-degree) cutaneous flame burn injury can induce severe RDS (PaO2/F(IO2) <200) within 40-48 hrs to allow evaluation of various treatment modalities of RDS.

Algorithms↗

PubMed1999

Effects of hypothermia and lamotrigine on trace-conditioned learning after global cerebral ischemia in rabbits.

Acquisition of the trace-conditioned eye blink response (CR) is mediated by a variety of brain structures, including the cerebellum, the hippocampus, and brain stem nuclei. We examined the effects of a neuronal sodium channel antagonist (lamotrigine) on the ability of rabbits to acquire an eye blink CR after 6.5 min of cerebral ischemia. New Zealand white rabbits (n = 31) were randomly assigned to sham (S), normothermic ischemia (N), hypothermic (30 degrees C) ischemia-(H), or lamotrigine (50 mg/kg) treated (L) groups. In the N, H, and L groups, 6.5 min of global cerebral ischemia was produced using an inflatable neck tourniquet. Trace conditioning was started on the 7th postischemic day. The conditioned stimulus consisted of a tone (85 dB, 6 kHz) presented for 100 ms. The unconditioned stimulus was an air puff (150 ms duration) directed at the cornea. The interval between the end of the conditioned stimulus and the start of the unconditioned stimulus (the trace interval, TI) was 300 ms in duration. A trace-conditioned response was defined as an eye blink that was initiated during the TI. Eighty trials were delivered daily for 15 days. Neurologic deficits were greatest in the N group, and these animals had fewer CRs (149 +/- 157) than animals in the S (509 +/- 214) or H (461 +/- 149) groups (P < 0.05 by analysis of variance). Animals in the L group had a total number of CRs (380 +/- 253) that was intermediate between the S and N groups. Histologic evidence of neural injury was greatest in the N group. This study demonstrates that a brief episode of cerebral ischemia results in the impairment of this test of neurobehavioral function. Both hypothermia and lamotrigine were able to attenuate the impairment of eye blink trace-conditioned responses produced by cerebral ischemia.

Animals↗

PubMed1999

Reduced ventilator pressure and improved P/F ratio during percutaneous arteriovenous carbon dioxide removal for severe respiratory failure.

OBJECTIVE: To evaluate the effect of percutaneous arteriovenous carbon dioxide removal (AVCO2R) on ventilator pressures and P/F ratio in a clinically relevant large-animal model of severe respiratory failure. SUMMARY BACKGROUND DATA: AVCO2R was developed as a simple arteriovenous shunt with a commercially available low-resistance gas exchange device of sufficient surface area for near-total CO2 removal. With an AV shunt 10% to 15% of cardiac output, AVCO2R allows a reduction in ventilator airway pressures without hypercapnia or the complex circuitry and monitoring required for conventional ECMO. METHODS: AVCO2R was applied to a new, clinically relevant large-animal model of severe respiratory failure created by smoke inhalation and cutaneous flame bum injury. Adult sheep (n = 9, 38+/-6 kg) received a 40% total body surface area, third-deinsufflation. After injury, all animals were placed on volume-controlled mechanical ventilation to achieve PaO2 > 60 mmHg and PacO2 < 40 mmHg. Animals were placed on AVCO2R within 40 to 48 hours of injury when the PaO2/FiO2 was <200. Animals underwent cannulation of the carotid artery and jugular vein with percutaneous 10F arterial and 14F venous cannulas. Shunt flow was continuously monitored using an ultrasonic flow probe and calculated as a percentage of cardiac output. RESULTS: AVCO2R flows of 800 to 900 ml/min (11% to 13% cardiac output) achieved 77 to 104 ml/min of CO2 removal (95% to 97% total CO2 production) while maintaining normocapnia. Significant reductions in ventilator settings were tidal volume, 421.3+/-39.8 to 270.0+/-6.3 ml; peak inspiratory pressure, 24.8+/-2.4 to 13.7+/-0.7 cm H2O; minute ventilation, 12.7+/-1.4 to 6.2+/-0.8 L/min; respiratory rate, 25.4+/-1.3 to 18.4+/-1.8 breaths/min; and FiO2, 0.88+/-0.1 to 0.39+/-0.1. The P/F ratio increased from 151.5+/-40.0 at baseline to 320.0+/-17.8 after 72 hours. CONCLUSIONS: Percutaneous AVCO2R allows near-total CO2 removal and significant reductions in ventilator pressures with improvement in the P/F ratio.

Algorithms↗

PubMed1999

Laboratory testing of femoral venous cannulae: effect of size, position and negative pressure on flow.

Femoral venous cannulae (17-28 French) were tested to compare flows obtained by their placement in a simulated inferior vena cava (IVC) or right atrium (RA) and by varying drainage pressures using gravity siphon drainage or a centrifugal pump in the venous line. The circuit consisted of conventional tubing and equipment including a segment of thin-walled latex tubing to simulate the IVC connected to a flexible reservoir to simulate the RA. The test fluid was a 40% glycerin solution. Flow was measured at height differentials of 30-60 cm (cannula-to-inlet of hard-shell venous reservoir) and with a -10 to -80 mmHg negative pressure created by the centrifugal pump. A roller pump returned the test fluid to a flexible bag to maintain a filling pressure of 0-1 mmHg. Flow increased modestly with an increasing height differential. When negative pressure was applied with the centrifugal pump, flow increased 10% and 18% (IVC and RA positions, respectively) compared to gravity siphon drainage conditions. There also was a tendency for flow to plateau or cease when the centrifugal pump was used at higher levels of negative pressure or when larger cannulae were used. We conclude: (1) position of smaller cannulae in the RA yield better flows than when the cannulae are larger and placed in the IVC; (2) smaller-sized cannulae are capable of achieving higher flows when the centrifugal pump is used; (3) cannulae must be properly positioned to achieve maximum flow; (4) the centrifugal pump will augment flow, but should be regulated to avoid extreme negative pressures; and (5) cannula design has no demonstrable effect on flow.

Catheterization↗

PubMed1998

Extracorporeal heparin adsorption following cardiopulmonary bypass with a heparin removal device--an alternative to protamine.

OBJECTIVES: To evaluate the therapeutic efficacy and applicability of a heparin removal device (HRD) based on plasma separation and poly-L-lysine (PLL) affinity adsorption as an alternative to protamine in reversing systemic heparinization following cardiopulmonary bypass (CPB). DESIGN: A prospective study. SETTING: University research laboratory. SUBJECTS: Adult female swine (n=7). INTERVENTIONS: Female Yorkshire swine (n=7, 67.3+/-3.5 [SEM] kg) were subjected to 60 mins of right atrium-to-aortic, hypothermic (28 degrees C) CPB. After weaning from CPB, the right atrium was recannulated with a two-stage, dual-lumen cannula which was connected to an HRD via extracorporeal circulation. Blood flow was drained at 1431.2+/-25.4 mL/min from the inferior vena cava, through the plasma separation chamber of the HRD (where heparin was bound to PLL), and reinfused into the right atrium. The HRD run time was determined by a previously established mathematical model of first-order exponential depletion. MEASUREMENTS AND MAIN RESULTS: Heart rate, mean arterial pressure, pulmonary arterial pressure, central venous pressure, kaolin and celite activated clotting time (ACT), activated partial thromboplastin time (APTT), heparin concentration, and plasma free hemoglobin were obtained before, during, and after the use of the HRD. Pre-CPB ACT was 167+/-89 secs (kaolin) and 99+/-7 secs (celite), and APTT was 34+/-5 secs. The HRD run time averaged 27.4 +/-1.5 mins targeted to remove 90% total body heparin. Use of the HRD was not associated with any adverse hemodynamic reactions or increases in plasma free hemoglobin. The heparin concentration immediately following CPB was 4.85+/-0.24 units/mL, with ACT >1000 secs and APTT >150 secs in all animals. During heparin removal, total body heparin content followed first-order exponential depletion kinetics. At the end of the HRD run, heparin concentration decreased to 0.51+/-0.09 units/mL, with kaolin ACT returning to 177+/-22 secs, celite ACT returning to 179+/-17 secs, and APTT returning to 27+/-3 secs (p > .05 vs. pre-CPB baseline for all variables). CONCLUSIONS: The HRD is capable of reversal of anticoagulation following CPB without significant blood cell damage or changes in hemodynamics. The HRD, therefore, can serve as an alternative to achieve heparin clearance in clinical situations where use of protamine may be contraindicated.

Adsorption↗

PubMed1997

Regional perfusion abnormalities with phenylephrine during normothermic bypass.

BACKGROUND: Hypotension and vasopressors during cardiopulmonary bypass may contribute to splanchnic ischemia. The effect of restoring aortic pressure on visceral organ, brain, and femoral muscle perfusion during cardiopulmonary bypass by increasing pump flow or infusing phenylephrine was examined. METHODS: Twelve anesthetized swine were stabilized on normothermic cardiopulmonary bypass. After baseline measurements, including regional blood flow (radioactive microspheres), aortic pressure was reduced to 40 mm Hg by decreasing the pump flow. Next, aortic pressure was restored to 65 mm Hg either by increasing the pump flow or by titrating phenylephrine. The animals had both interventions in random order. RESULTS: At 40 mm Hg aortic pressure, perfusion to all visceral organs and femoral muscle, but not to the brain, was significantly reduced. Increasing pump flow improved perfusion to the pancreas, colon, and kidneys. In contrast, infusing phenylephrine (2.4 +/- 0.6 micrograms.kg-1.min-1) increased aortic pressure but failed to improve splanchnic perfusion, so that significant perfusion differences existed between the pump flow and phenylephrine intervals. CONCLUSIONS: Increasing systemic pressure during cardiopulmonary bypass with phenylephrine causes significantly lower values of splanchnic blood flow than does increasing the pump flow. Administering vasoconstrictors during normothermic cardiopulmonary bypass may mask substantial hypoperfusion of splanchnic organs despite restoration of perfusion pressure.

Animals↗

PubMed1997

L-arginine and superoxide dismutase prevent or reverse cerebral hypoperfusion after fluid-percussion traumatic brain injury.

To determine whether treatment with L-arginine or superoxide dismutase (SOD) would prove effective in reducing cerebral hypoperfusion after traumatic brain injury (TBI), we measured cerebral blood flow (CBF) using laser Doppler flowmetry (LDF) in rats treated before or after moderate (2.2 atm) fluid-percussion (FP) TBI. Rats were anesthetized with isoflurane and prepared for midline FP TBI and then for LDF by thinning the calvaria using an air-cooled drill. Rats were then randomly assigned to receive sham injury, sham injury plus L-arginine (100 mg/kg, 5 min after sham TBI), TBI plus 0.9% NaCl, TBI plus L-arginine (100 mg/kg, 5 min post-TBI), TBI plus SOD (24,000 U/kg pre-TBI + 1600 units/kg/min for 15 min after TBI), or TBI plus SOD and L-arginine. A second group of rats received TBI plus saline, L-, or D-arginine (100 mg/kg, 5 min after-TBI). After treatment and TBI or sham injury, CBF was measured continuously using LDF for 2 h and CBF was expressed as a percent of the preinjury baseline for 2 h after TBI. Rats treated with saline or D-arginine exhibited significant reductions in CBF that persisted throughout the monitoring period. Rats treated with L-arginine alone or in combination with SOD exhibited no decreases in CBF after TBI. CBF in the SOD-treated group decreased significantly within 15 min after TBI but returned to baseline levels by 45 min after TBI. These studies indicate that L-arginine but not D-arginine administered after TBI prevents posttraumatic hypoperfusion and that pretreatment with SOD will restore CBF after a brief period of hypoperfusion.

Animals↗

PubMed1997

Cerebral blood flow during experimental endotoxemia in volunteers.

OBJECTIVE: To measure cerebral blood flow, cerebral metabolic rate for oxygen, cerebral oxygen delivery, and cerebral vascular resistance during experimental endotoxemia in volunteers. DESIGN: Experimental, prospective study. SETTING: University general clinical research center. SUBJECTS: Healthy volunteers (six male, four female, 30.1 +/- 1.9 yrs of age). INTERVENTIONS: Volunteers had radial, pulmonary arterial, and jugular venous bulb catheters inserted. All volunteers received a bolus of Escherichia coli endotoxin (4 ng/kg). Cerebral blood flow was measured, using the Kety-Schmidt technique. MEASUREMENTS AND MAIN RESULTS: Cerebral and systemic hemodynamics and oxygenation variables were measured at baseline and hourly for 5 hrs after endotoxin administration. A systemic hyperdynamic response characterized by an increase in body temperature (97.9 +/- 0.02, 100.2 +/- 0.02, and 99.7 +/- 0.02 degrees F [36.6 +/- 0.01, 37.9 +/- 0.1, and 37.6 +/- 0.1 degrees C] at baseline, 3, and 5 hrs, respectively), cardiac index (3.7 +/- 0.2, 6.2 +/- 0.2, and 5.7 +/- 0.2 L/min/m2 at baseline, 3, and 5 hrs), and heart rate (70 +/- 2.6, 96 +/- 2.6, and 93 +/- 2.9 beats/min at baseline, 3, and 5 hrs), and a decrease in mean arterial pressure (99.3 +/- 2.2, 84.4 +/- 2.8, and 84 +/- 3.4 mm Hg at baseline, 3, and 5 hrs) and systemic vascular resistance (1498 +/- 53, 788 +/- 37, 849 +/- 36 dyne.sec/cm5.m2 at baseline, 3, and 5 hrs) followed the endotoxin bolus. Cerebral blood flow (65.4 +/- 4.3, 57.7 +/- 3.1, and 58.6 +/- 3.0 mL/100 g/min at baseline, 3, and 5 hrs), cerebral oxygen delivery (11.6 +/- 0.7, 9.8 +/- 0.6, and 9.5 +/- 0.6 mL/100 g/min at baseline, 3, and 5 hrs), cerebral metabolic rate for oxygen (3.8 +/- 0.4, 3.3 +/- 0.3, and 3.0 +/- 0.3 mL/100 g/min at baseline, 3, and 5 hrs), and cerebral vascular resistance (1.4 +/- 0.2, 1.4 +/- 0.2, and 1.3 +/- 0.2 mm Hg/mL/100 g/min at baseline, 3, and 5 hrs) were unchanged throughout the 5-hr study period. Signs of cerebral dysfunction were not apparent, although the volunteers appeared drowsy during the latter part of the study. CONCLUSION: A dose of endotoxin sufficient to induce systemic vasodilation in healthy subjects does not influence cerebral blood flow or the cerebral metabolic rate for oxygen.

Adult↗

PubMed1997

Nitric oxide synthase inhibition restores hypoxic pulmonary vasoconstriction in sepsis.

Hypoxic pulmonary vasoconstriction (HPV) is inhibited by inhaled nitric oxide (NO) in healthy animals and is blunted in endotoxemia. We investigated whether the loss of HPV during sepsis could be reversed by NO synthase (NOS) inhibition. Hypoxic challenges were induced in intubated, awake sheep breathing 100% nitrogen to the left lung and 100% oxygen to the right lung. HPV was assessed as the decrease in left pulmonary blood flow during hypoxia, measured with an ultrasonic flow probe around the left pulmonary artery. Group I (n = 5) received carrier solutions and Groups II (n = 6) and III (n = 8) received an infusion containing Pseudomonas aeruginosa. After 24 h, Group III also received an infusion of 6.6 mg.kg.h-1 N omega-monomethyl-L-arginine (L-NMMA). After 24 h of sepsis, HPV decreased from 60 +/- 9% in Group II and 56 +/- 4% in Group III to 27 +/- 2% and 26 +/- 4%, respectively. Group I showed no change in HPV. During infusion of L-NMMA, HPV increased to 38 +/- 4%. Pulmonary shunt during hypoxia increased in Group III to 161 +/- 10% of its baseline value, and decreased to 121 +/- 11% during infusion of L-NMMA. We conclude that L-NMMA improves but does not restore HPV, indicating that other vasodilatory mediators besides NO also influence HPV in sepsis.

Animals↗

PubMed1996

Validation in volunteers of a near-infrared spectroscope for monitoring brain oxygenation in vivo.

Cerebral oximeters based on near-infrared spectroscopy may provide a continuous, noninvasive assessment of cerebral oxygenation. We evaluated a prototype cerebral oximeter (Invos 3100; Somanetics, Troy, MI) in 22 conscious, healthy volunteers breathing hypoxic gas mixtures. Using the first 12 subjects (training group), we developed an algorithm based on the mathematic relationship that converts detected light from the field surveyed by the probe to cerebral hemoglobin oxygen saturation (CSfO2). To develop the algorithm, we correlated the oximeter result with the estimated combined brain hemoglobin oxygen saturation (CScombO2, where CScombO2 = SaO2 x 0.25 + SjO2 x 0.75 and SjO2 = jugular venous saturation). We then validated the algorithm in the remaining 10 volunteers (validation group). A close association (r2 = 0.798-0.987 for individuals in the training group and r2 = 0.794-0.992 for individuals in the validation group) existed between CSfO2 and CScombO2. We conclude that continuous monitoring with cerebral oximetry may accurately recognize decreasing cerebral hemoglobin oxygen saturation produced by systemic hypoxemia.

Adult↗

PubMed1996

The influence of carbon dioxide and body position on near-infrared spectroscopic assessment of cerebral hemoglobin oxygen saturation.

Near-infrared spectroscopy may allow continuous and noninvasive monitoring of regional brain hemoglobin oxygen saturation by measuring the differential absorption of infrared light by oxyhemoglobin and deoxyhemoglobin. We have previously examined the correlation between the spectroscopic signal generated by a prototype cerebral oximeter (Invos 3100; Somanetics, Troy, MI), and global brain hemoglobin oxygen saturation calculated from arterial and jugular venous bulb oxygen saturations. Because the technology does not distinguish between arterial and venous hemoglobin saturation, changes in the proportion of cerebral arterial and venous blood volume, which may result from changes in blood flow or venous distending pressure, may confound measurements. In eight conscious volunteers breathing hypoxic oxygen mixtures, we examined the influence of supine, 20 degrees Trendelenburg, and 20 degrees reverse Trendelenburg positions on the correlation of the spectroscopic measurement of cerebral oxygen saturation in the field assessed by the probe (CSfO2) and the calculated brain hemoglobin oxygen saturation (CScombO2), estimated as 0.25 x arterial saturation plus 0.75 x jugular venous bulb oxygen saturation. We found that changes in position did not influence the association between CSfO2 and CScombO2 (r2 = 0.69-0.885) during hypoxic challenge. In a second set of eight volunteers, we studied the influence of hypercapnia and hypocapnia and body position on the association between CSfO2 and CScombO2, and found that they were less well correlated (r2 = 0.366-0.976) in individual patients. Because changes in body position and Paco2 confound the relationship between CSfO2 and CScombO2, changes in CSfO2 can best be assessed if position and Paco2 are constant.

Adult↗