Biomedical subjects

R C Koehler

Publications and source records attributed to R C Koehler.

At least 73 records · Page 4Linked to original sources

PubMed1995

PPBP [4-phenyl-1-(4-phenylbutyl) piperidine], a potent sigma-receptor ligand, decreases brain injury after transient focal ischemia in cats.

BACKGROUND AND PURPOSE: We tested the hypothesis that administration of 4-phenyl-1-(4-phenylbutyl) piperidine (PPBP), a potent sigma-receptor ligand, during transient focal ischemia would affect early postischemic brain injury. METHODS: Halothane-anesthetized cats underwent left middle cerebral artery occlusion for 90 minutes followed by 4 hours of reperfusion. Control cats received saline (n = 10). Experimental cats (2 groups, n = 10 per group) were treated with PPBP at a rate of 0.1 mumol/kg per hour (PPBP-0.1) or administered 1 mumol/kg per hour (PPBP-1) intravenously from 75 minutes after initiation of ischemia and continuing during the 4 hours of reperfusion. RESULTS: As measured by the microsphere method, blood flow to the ipsilateral caudate nucleus was decreased similarly in all groups during ischemia. Blood flow to the ipsilateral inferior temporal cortex was decreased during ischemia in all groups but was higher in cats subsequently treated with PPBP at the highest dose, even before drug administration. There was no difference in blood flow to the ipsilateral caudate nucleus or inferior temporal cortex (area of greatest cortical injury) during reperfusion. Triphenyltetrazolium-determined injury volume of the ipsilateral cerebral hemisphere (control, 29 +/- 5%; PPBP-0.1, 17 +/- 3%; PPBP-1, 6 +/- 1% of ipsilateral hemisphere; mean +/- SEM) and caudate nucleus (control, 49 +/- 5%; PPBP-0.1, 39 +/- 6%; PPBP-1, 25 +/- 5% of ipsilateral caudate nucleus) was less in cats treated with 1 mumol/kg per hour of PPBP compared with cats treated with saline. Cats treated with 0.1 mumol/kg per hour had a 45% smaller hemispheric injury volume than the control group without differences in intraischemic blood flow. Recovery of somatosensory evoked potential amplitude was greater in cats treated with PPBP-1 compared with control (control, 18 +/- 11%; PPBP-0.1, 30 +/- 14%; PPBP-1, 54 +/- 14% of baseline). CONCLUSIONS: These data indicate that sigma-receptors may play an important role in the mechanism of acute injury in both the cortex and the caudate nucleus after 90 minutes of transient focal ischemia in the cat. Because PPBP afforded protection when administered at the end of ischemia and during reperfusion, sigma-receptors may contribute to the progression of injury in ischemic border regions.

Animals↗

PubMed1995

Somatosensory evoked potential and brain water content in post-asphyxic immature piglets.

Depression of somatosensory evoked potentials (SEP) after a single episode of complete asphyxia with near cardiac arrest was evaluated to determine whether persistent SEP depression is related to postresuscitation edema in cortical gray matter or subcortical white matter. Piglets (< 7 d of age) were anesthetized with sodium pentobarbital and fentanyl. Asphyxia was produced by occlusion of the endotracheal tube for 7 min. Arterial O2 saturation fell to 5%. Resuscitation was achieved in < 2 min with ventilation, epinephrine, and chest compressions. Regional brain water content was determined from the difference between wet and dry weight. Two control groups were also analyzed; one immediately after (n = 5) and one 6 h after induction (n = 7) of anesthesia. SEP amplitude became isoelectric during asphyxia and recovered to 50 +/- 13% (n = 7) of baseline 6 h after resuscitation. In the 6-h control group, SEP amplitude remained above baseline. The percent water content (mean +/- SEM) among the three groups (asphyxia versus time control versus brief anesthesia control) was not different in the cortical gray matter (83.0 +/- 0.7% versus 82.4 +/- 0.4% versus 83.2 +/- 0.3%) or subcortical white matter (75.6 +/- 0.8% versus 74.8 +/- 0.9% versus 75.6 +/- 0.5%). In seven other piglets, cerebral blood flow and O2 consumption recovered to baseline by 1 h after asphyxia. Therefore, we found that the sustained depression of SEP amplitude, after 7 min of asphyxia in immature piglets, is not related to brain edema or persistent decreases in global cerebral O2 consumption.

Animals↗

PubMed1995

Role of nitric oxide scavenging in peripheral vasoconstrictor response to beta beta cross-linked hemoglobin.

Transfusion with many crosslinked hemoglobin solutions causes an increase in arterial pressure that may be mediated by scavenging of nitric oxide (NO). If so, we postulated that inhibiting synthesis of NO after hemoglobin transfusion would fail to cause vasoconstriction ordinarily seen with such inhibition. In pentobarbital anesthetized cats, we tested whether administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), produced peripheral vasoconstriction after isovolemic exchange transfusion with hemoglobin to the same extent as occurs with L-NAME infusion in time controls and in controls matched for reduced hematocrit (17%) with albumin transfusion. Bovine hemoglobin was treated aerobically with bis-(3,5-dibromosalicyl)fumarate to produce beta beta-81 lysine crosslinks. Hemoglobin exchange transfusion increased mean arterial blood pressure and there was no further increase after L-NAME. In contrast, L-NAME increased pressure in the time controls and albumin controls. Hemoglobin transfusion decreased intestinal and renal blood flow, and there was no further decrease after L-NAME. In contrast, L-NAME decreased intestinal and renal blood flow in time controls and albumin controls. With L-NAME pretreatment in a separate group of cats, there was little further increase in arterial pressure or visceral vasoconstriction after hemoglobin transfusion. We conclude that the increase in arterial blood pressure after isovolemic crosslinked hemoglobin transfusion is best explained by scavenging of NO in intestinal and renal vascular beds.

Animals↗

PubMed1994

Interaction of fentanyl and nitrous oxide on peripheral and cerebral hemodynamics in newborn lambs.

BACKGROUND: The ability of opioids to produce complete general anesthesia is controversial. Nitrous oxide (N2O) is often added to fentanyl-based anesthetics to produce unconsciousness and amnesia. The addition of N2O may adversely affects fentanyl's hemodynamic stability and safety. The purpose of this study was to determine the physiologic consequences of combining N2O with fentanyl in newborn animals. METHODS: The effects of 50% nitrous oxide in oxygen (O2), and 50% N2O in O2 combined with 3,000 micrograms/kg fentanyl, on cerebral and peripheral hemodynamics were studied in seven unanesthetized newborn lambs, in whom catheters were previously inserted. After a control period, lambs were placed in a hood in which inspired gas concentrations were controlled and which minimized external stimuli. After 30 min of breathing room air, the lambs breathed 50% N2O in O2 for an additional 30 min. The lambs were then given 3,000 micrograms/kg fentanyl by intravenous bolus and by infusion (1,000 micrograms.kg-1 x h-1) for 60 min while continuing to breathe 50% N2O in O2. RESULTS: All animals responded to pain (tail clamp) and alerted to sound when breathing room air or when N2O was used alone. Adding fentanyl to the N2O abolished all responses to pain, but not to sound. Additionally, fentanyl produced immediate apnea necessitating tracheal intubation and mechanical ventilation. Mean arterial pressure and heart rate increased 27% and 23%, respectively, after fentanyl administration, intubation, and ventilation. It did not change over the course of the fentanyl infusion. Cerebral blood flow, O2 consumption, and O2 delivery did not change when N2O was administered alone or in combination with fentanyl. Splanchnic blood flow was unaffected by treatment over time. Renal blood flow decreased by 21% after fentanyl administration, but was unaffected by N2O alone. Right and left ventricular blood flow increased (47% and 26%, respectively) after fentanyl administration, intubation, and ventilation, but not when N2O was administered alone. CONCLUSIONS: Fentanyl (3,000 micrograms/kg) when combined with 50% N2O in O2 produced a plane of general anesthesia in newborn lambs in which the behavioral responses to painful stimuli were abolished. The response to sound was never eliminated, nor was cerebral oxygen consumption decreased. The combination of 50% N2O in O2, 3,000 micrograms/kg fentanyl, tracheal intubation, and mechanical ventilation did not depress heart rate, blood pressure, or blood flow to any of the major organs, except the kidneys.

Anesthesia, General↗

PubMed1994

Hypoxia, alpha 2-adrenergic, and nitric oxide-dependent interactions on canine cerebral blood flow.

We tested the hypothesis that NO synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) and alpha 2-adrenoreceptor stimulation with dexmedetomidine (Dex) decreases the cerebral blood flow (CBF) response to hypoxia. In isoflurane-anesthetized dogs, CBF was measured during two episodes of hypoxic hypoxia. In a control group (n = 6), CBF increased similarly from 83 +/- 4 to 210 +/- 30 ml.min-1 x 100 g-1 and from 88 +/- 7 to 205 +/- 27 (+/- SE) ml.min-1 x 100 g-1 during two hypoxic episodes. In a second group (n = 6), hypoxia increased CBF from 88 +/- 15 to 204 +/- 38 ml.min-1 x 100 g-1. Dex (10 micrograms/kg i.v.) reduced normoxic CBF to 54 +/- 8 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 97 +/- 14 ml.min-1 x 100 g-1. In a third group pretreated with L-NAME (40 mg/kg i.v.) 1 h before anesthesia (n = 6), normoxic CBF was less than in the control group (52 +/- 2 vs. 83 +/- 4 ml.min-1 x 100 g-1). Hypoxia increased CBF to 177 +/- 13 ml.min-1 x 100 g-1. Dex after L-NAME further decreased normoxic CBF to 37 +/- 3 ml.min-1 x 100 g-1, and subsequent hypoxia increased CBF to 106 +/- 18 ml.min-1 x 100 g-1. Dex, L-NAME, and Dex + L-NAME each reduced cerebral O2 transport (CBF x arterial O2 content) during normoxia, but the increase in CBF during hypoxia was sufficient to prevent further decreases in O2 transport. Thus the response to hypoxia remained proportional to normoxic levels of CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMed1994

Cerebrovascular autoregulation during fetal development in sheep.

There are scant data regarding the development of cerebrovascular autoregulation in fetuses. We tested the hypothesis that a decrease in cerebrovascular resistance (CVR) at reduced cerebral perfusion pressure (CPP) is absent in midgestation and near-term fetal sheep. Catheters were chronically implanted for microsphere determination of cerebral blood flow (CBF) in 9 fetuses at 92 days and in 10 fetuses at 132 days gestation (full term = 145 days). CPP was reduced by ventricular infusion of artificial cerebrospinal fluid. In 92-day fetuses, CPP was reduced stepwise from 35 to 25 and 18 mmHg and CBF decreased from 52 +/- 5 to 43 +/- 4 and 27 +/- 5 (SE) ml.min-1 x 100 g-1, respectively. Half of the immature fetuses showed some reduction in CVR at moderate reduction in CPP; however, there was no significant change in CVR in the group as a whole (from 0.72 +/- 0.06 to 0.61 +/- 0.04 and 0.89 +/- 0.20 mmHg.ml-1.min.100 g). In 132-day fetuses, CPP was reduced from 45 to 33 and 28 mmHg and CBF was unchanged (from 105 +/- 7 to 97 +/- 11 and 89 +/- 8 ml.min-1 x 100 g-1). CVR decreased from 0.45 +/- 0.05 to 0.41 +/- 0.08 and 0.33 +/- 0.03 mmHg.ml-1.min.100 g. There were no significant changes in arterial blood gases at reduced CPP in either age group. We conclude that cerebrovascular autoregulation at reduced CPP is not well developed at 92 days (0.63 gestation) in fetal sheep but that autoregulatory capacity is evident near term. We speculate that poor autoregulation may place the premature fetal brain at risk for injury.

Animals↗

PubMed1994

Competitive N-methyl-D-aspartate receptor blockade reduces brain injury following transient focal ischemia in cats.

BACKGROUND AND PURPOSE: We tested the hypothesis that administration of the competitive N-methyl-D-aspartate (NMDA) receptor antagonist NPC 17742 (2R,4R,5S-[2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid]) during transient focal ischemia affects early postischemic brain injury. METHODS: Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 4 hours of reperfusion. Control cats received saline (n = 7). Experimental cats were treated with NPC 17742 at a dose of 5 mg/kg IV from 45 minutes of ischemia to 15 minutes of reperfusion and 2.5 mg/kg per hour for 4 hours of reperfusion (NPC-5; n = 7) or 50 mg/kg from 45 minutes of ischemia to 15 minutes of reperfusion and 25 mg/kg per hour for 4 hours of reperfusion (NPC-50; n = 5). RESULTS: Microsphere-determined blood flow to the ipsilateral inferior temporal cortex and caudate nucleus decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the three groups. Triphenyltetrazolium-determined injury volume of ipsilateral cerebral hemisphere (saline, 24 +/- 8%; NPC-5, 4 +/- 2%; NPC-50, 5 +/- 2% of hemisphere; mean +/- SE) and caudate nucleus (saline, 72 +/- 6%; NPC-5, 37 +/- 10%; NPC-50, 26 +/- 4%) was less in cats treated with both doses of drug compared with cats treated with saline. Recovery of somatosensory evoked potential amplitude was incomplete and similar in all groups (saline, 36 +/- 14%; NPC-5, 58 +/- 8%; NPC-50, 51 +/- 15% of baseline). CONCLUSIONS: These data indicate that activation of NMDA receptors plays an important role in the mechanism of acute injury in both cortex and caudate after 1 hour of transient focal ischemia in the cat. Because NPC 17742 afforded protection when administered at the end of ischemia and during reperfusion, NMDA receptor activation during reperfusion may contribute to the progression of injury in ischemic border regions.

Amino Acids↗

PubMed1994

Tirilazad treatment does not decrease early brain injury after transient focal ischemia in cats.

BACKGROUND AND PURPOSE: We tested the hypothesis that administration of the antioxidant tirilazad mesylate improves electrophysiological recovery and decreases infarct volume after transient focal cerebral ischemia in cats. METHODS: Halothane-anesthetized cats underwent 90 minutes of left middle cerebral artery and bilateral common carotid artery occlusion followed by 180 minutes of reperfusion. Cats were assigned to receive tirilazad (1.5 mg/kg plus 0.2 mg/kg per hour IV infusion) either at the beginning (n = 9) or conclusion (n = 9) of ischemia. Control cats received an equal volume of diluent (citrate buffer, pH 3.0; n = 7) at the beginning and conclusion of ischemia in a blinded fashion. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. RESULTS: Blood flow to the left temporoparietal cortex decreased to less than 10 mL/min per 100 g with ischemia but was minimally affected on the right side. Blood flow distribution during ischemia or reperfusion was not different in the tirilazad-treated groups. No group demonstrated postischemic hyperemia or delayed hypoperfusion. Somatosensory evoked potential recorded over the left cortex was ablated during ischemia and recovered to less than 15% of baseline amplitude at 180 minutes of reperfusion in all groups. There were no differences among groups in infarct volume of left hemisphere (pretreatment, 25 +/- 6% [mean +/- SE]; posttreatment, 33 +/- 5%; control, 28 +/- 8% of hemisphere) or caudate nucleus (pretreatment, 46 +/- 7%; posttreatment, 41 +/- 10%; control, 55 +/- 13% of hemisphere). CONCLUSIONS: In an experimental model of focal ischemia involving severe reductions of blood flow followed by reperfusion in cats, administration of tirilazad at the onset of either ischemia or reperfusion does not ameliorate infarct volume assessed during early reperfusion. Our study does not address potential efficacy of tirilazad in the setting of a different dosing strategy or duration of reperfusion.

Analysis of Variance↗

PubMed1994

Nitric oxide synthase inhibition reduces caudate injury following transient focal ischemia in cats.

BACKGROUND AND PURPOSE: We tested the hypothesis that inhibiting nitric oxide production either before or during transient focal ischemia affects early postischemic brain injury. METHODS: Halothane-anesthetized cats underwent 1 hour of left middle cerebral artery occlusion plus 3 hours of reperfusion. Pretreatment groups received either intravenous N omega-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg, n = 10) or an equal volume of diluent (10 mL saline, n = 10) over 30 minutes before ischemia. Posttreatment groups received intravenous L-NAME (10 mg/kg) over 30 minutes from 45 minutes of ischemia to 15 minutes of reperfusion (n = 10) or intravenous L-NAME (10 mg/kg) plus L-arginine (200 mg/kg) over the same period followed by continuous L-arginine infusion (200 mg/kg per hour) for the remainder of reperfusion (n = 10). RESULTS: Microsphere-determined blood flow to ipsilateral caudate nucleus and inferior temporal cortex decreased to the same extent during ischemia and recovered to the same extent during reperfusion in the four groups. Triphenyltetrazolium-determined injury volume of ipsilateral caudate nucleus in cats treated with L-NAME before or during ischemia (42 +/- 7% and 42 +/- 3% of caudate nucleus, respectively; mean +/- SE) was less (P < .05) compared with that in cats pretreated with saline (72 +/- 5%) or cats treated with L-NAME plus L-arginine (68 +/- 5%). Ipsilateral cerebral hemispheric injury volume was similar among the four groups (23 +/- 5%, 13 +/- 3%, 18 +/- 5%, and 29 +/- 5% of hemisphere in groups treated with L-NAME before ischemia and during ischemia, the saline-treated group, and the group treated with L-NAME plus L-arginine, respectively). CONCLUSIONS: Inhibition of nitric oxide synthase decreases caudate injury volume from transient focal cerebral ischemia in cats. The beneficial effect is reversed by L-arginine and is not caused by favorable redistribution of blood flow during ischemia and reperfusion. Because L-NAME was efficacious when administered at reperfusion, nitric oxide generated during reperfusion appears to contribute to caudate injury.

Amino Acid Oxidoreductases↗

PubMed1994

Diabetic chronic hyperglycemia and cerebral pH recovery following global ischemia in dogs.

BACKGROUND AND PURPOSE: We determined the effect of chronic hyperglycemia associated with diabetes on recovery of cerebral pH after global incomplete cerebral ischemia. METHODS: 31P magnetic resonance spectra and cerebral blood flow (radiolabeled microspheres) were measured in three groups of dogs: (1) chronic hyperglycemic diabetes (pancreatectomy followed by blood glucose > 10 mmol/L for 3 months; n = 8); (2) acute hyperglycemia during ischemia and reperfusion in nondiabetic dogs (n = 8); and (3) normoglycemic controls (n = 8). Incomplete ischemia was produced for 20 minutes by ventricular fluid infusion followed by 3 hours of reperfusion. RESULTS: Cerebral blood flow was reduced to approximately 5 mL/min per 100 g in all groups during ischemia with individual values ranging from 1 to 11 mL/min per 100 g. Blood flow returned to preischemic values by 30 minutes of reperfusion in the normoglycemia group but remained elevated during reperfusion in the acute hyperglycemia and diabetes groups. Cerebral pH at the end of ischemia was lower in acute hyperglycemia (5.94 +/- 0.05; +/- SE) and diabetes (5.97 +/- 0.08) groups than in the normoglycemia group (6.27 +/- 0.02). However, recovery of pH through 90 minutes of reperfusion in the normoglycemia (7.08 +/- 0.05) and diabetes (7.00 +/- 0.04) groups was significantly greater than in the acute hyperglycemia group (6.74 +/- 0.11). Persistent acidosis in the acute hyperglycemia group was associated with a delayed reduction of cerebral oxygen consumption and high-energy phosphates and with greater cortical water content and impairment of somatosensory evoked potentials compared with the diabetes group. CONCLUSIONS: This study shows that cerebral pH recovery after global incomplete ischemia is improved in chronic hyperglycemia compared with acute hyperglycemia, despite similar decreases in blood flow and pH during ischemia and similar levels of blood flow and glucose levels during ischemia and reperfusion. In addition, cerebral pH recovery in chronic hyperglycemic dogs was not different from that in normoglycemic controls. These results suggest that an adaptation occurs with chronic hyperglycemia that improves recovery of cerebral pH during reperfusion and that is associated with better maintenance of energy metabolism and evoked potentials and with less edema over 3 hours of reperfusion compared with acute hyperglycemia.

Acidosis↗

PubMed1994

Reduced blood-brain barrier permeability after cardiac arrest by conjugated superoxide dismutase and catalase in piglets.

BACKGROUND AND PURPOSE: Cardiac arrest and resuscitation in immature piglets result in a delayed increase in blood-brain barrier permeability. We tested the hypothesis that pretreatment with oxygen radical scavengers reduces postischemic permeability. METHODS: Permeability was assessed by measuring the plasma-to-brain transfer coefficient of the small amino acid, alpha-aminoisobutyric acid, in 2- to 3-week-old anesthetized piglets. Three groups were studied: (1) a nonischemic time control group (n = 5), (2) an ischemia group (n = 8) pretreated with 5 mL of polyethylene glycol vehicle, and (3) an ischemia group (n = 8) pretreated with polyethylene glycol conjugated to superoxide dismutase (10,000 U/kg) and to catalase (20,000 U/kg). The ischemia protocol consisted of 8 minutes of ventricular fibrillation, 6 minutes of cardiopulmonary resuscitation, defibrillation, and 4 hours of spontaneous circulation. RESULTS: The mean +/- SEM of the transfer coefficient of alpha-aminoisobutyric acid in cerebrum was (in microL/g per minute): 1.54 +/- 0.37 in the nonischemic group, 2.04 +/- 0.26 in the ischemia group treated with vehicle, and 1.29 +/- 0.25 in the ischemia group treated with oxygen radical scavengers. Postischemic values with scavenger treatment were significantly lower than those with vehicle treatment in cerebrum, cerebellum, medulla and cervical spinal cord. CONCLUSIONS: Pretreatment with oxygen radical scavengers reduces postischemic blood-brain barrier permeability by a small amino acid. These data are consistent with oxygen radical-mediated dysfunction of cerebral endothelium in a pediatric model of cardiopulmonary resuscitation.

Aminoisobutyric Acids↗

PubMed1994

Effect of vest cardiopulmonary resuscitation on cerebral and coronary perfusion in an infant porcine model.

OBJECTIVES: To determine cerebral and myocardial blood flow rates during vest cardiopulmonary resuscitation (CPR) without direct cardiac compression in an infant porcine model. Also, to determine if circumferential chest compression without the chest deformity ordinarily associated with precordial compression maintains cerebral and myocardial blood flow rates during prolonged CPR. Finally, to establish the effect of compression rate and duty cycle on cerebral and myocardial blood flow rates during vest CPR in this model. DESIGN: Prospective, randomized comparison of two compression rates and two duty cycles in four groups during prolonged CPR. SETTING: University cerebral resuscitation laboratory. SUBJECTS: Thirty-two infant domestic swine. INTERVENTIONS: Microsphere-determined cerebral and myocardial blood flow rates, perfusion pressures, and chest dimensions, were measured before and during prolonged vest CPR. Immediately after ventricular fibrillation, epinephrine administration was started and thoracic vest CPR was performed using a single combination of compression rates of 100 or 150/min and duty cycles of 30% or 60%. Measurements were made before and at 5, 10, 20, 35, and 50 mins of CPR. MEASUREMENTS AND MAIN RESULTS: Five minutes into CPR, between-group comparisons showed that cerebral blood flow was 16 to 20 mL/min/100 g and myocardial blood flow was 34 to 45 mL/min/100 g (48% to 62% and 25% to 33% of prearrest values). When CPR was prolonged, cerebral blood flow deteriorated similarly in all groups. Myocardial blood flow decreased over time but was better maintained in the groups with a 30% duty cycle (24 vs. 4 mL/min/100 g; p < .006). There were no differences between the two compression rates. Chest deformity after cessation of 50 mins of compression was < 3%. CONCLUSIONS: Cerebral and myocardial blood flow rates produced by vest CPR are comparable with rates reported using other types of CPR in this model. Deterioration in blood flow during prolonged CPR occurs despite a lack of chest deformation. The deterioration in myocardial blood flow during prolonged CPR is greater when a long duty cycle is used in this model.

Analysis of Variance↗

PubMed1993

Shift reagent enhanced concurrent 23Na and 1H magnetic resonance spectroscopic studies of transcellular sodium distribution in the dog brain in vivo.

The intracellular to extracellular sodium distribution is one of the primary determinants of action potentials necessary for the electrical function of organs such as brain, heart and skeletal muscle. The ability of shift reagent enhanced 23Na MRS to directly measure the intracellular and extracellular sodium distribution in brain is controversial and centers on the relative contributions of bulk magnetic susceptibility and hyperfine interactions to the observed chemical shifts. In this study, infusion of dysprosium (III) triethylenetetraminehexacetate (Dy(TTHA)-3), resulted in a 23Na MRS spectrum of dog brain with two well resolved peaks at 9 and 0.4 ppm. The 9 ppm peak corresponded to the resonance seen in aspirated blood. After disruption of the blood brain barrier, the single peak at 0.4 ppm split into two peaks at 3 and 0 ppm. The ability of Dy(TTHA)-3 enhanced 23Na MRS to follow global changes in brain sodium distribution was tested during cardiac arrest. The expected rapid Na influx into the intracellular space produced a marked decrease in the 3 ppm signal and a parallel increase in the 0 ppm peak. This is consistent with the assignment of the 3 ppm peak as interstitial sodium and the 0 ppm peak as intracellular sodium.

Animals↗

PubMed1993

Cerebral blood flow and metabolism in dogs with chronic diabetes.

BACKGROUND: Previously, the authors found that anesthetized diabetic dogs had increased cerebral blood flow (CBF) and oxygen consumption (CMRO2). These results may have been influenced by anesthesia or surgery. The aim of this study was to determine whether CBF and CMRO2 are increased in the awake or anesthetized state in the absence of acute surgical stress in diabetic dogs. A second aim was to determine whether increased CBF and CMRO2 in diabetic dogs are mediated through beta-adrenergic mechanisms. METHODS: Diabetic dogs (n = 8) underwent total surgical pancreatectomy followed by 4 months of insulin management (16 +/- 0.4 units/day, mean +/- SE) to maintain fasting and 3 PM blood glucose 10-17 mM. Control dogs (n = 8) underwent sham operation followed by a 4-month convalescence. Using previously inserted catheters, CBF (radiolabelled microspheres) and CMRO2 (sagittal sinus sampling) were measured before and after propranolol (2 mg/kg) in both the awake and anesthetized states. RESULTS: During the 4 months before CBF studies, the fasting blood glucose was greater in diabetic group than in the control group (11.0 +/- 0.3 vs. 4.0 +/- 0.1 mM, respectively). No difference occurred between groups in CBF or CMRO2. In the awake state, propranolol administration caused no CBF or CMRO2 changes. However, during anesthesia with 50 micrograms/kg fentanyl plus 10 mg/kg pentobarbital, propranolol administration decreased CBF in control, but not in diabetic, dogs. CONCLUSIONS: The authors' previous results showing increased CBF and CMRO2 with diabetes may be secondary to a differential response to acute surgical stress, a factor that was eliminated in this study. These results indicate that diabetes is associated with changes in the beta-adrenergic system that become evident under fentanyl/pentobarbital anesthesia.

Animals↗

PubMed1993

Diaphragmatic fatigue assessed by 31P-magnetic resonance spectroscopy in vivo.

We tested whether fatigue of the piglet diaphragm is associated with inadequate oxidative metabolism as measured by magnetic resonance spectroscopy (MRS). An MRS measured ratio of inorganic phosphate to phosphocreatine (Pi/PCr) > or = 1 was taken as evidence of inadequate oxidative metabolism. Piglets (n = 10) underwent phrenic nerve pacing for 90 min with stimulation frequency of 30 Hz and duty cycle of 0.33. In a separate group of six piglets PCr, Pi, ATP, and intracellular pH were measured by in vivo MRS, and diaphragmatic blood flow was measured with radioactive microspheres at control, 2, 10, 45, 60, and 90 min of pacing. Transdiaphragmatic pressure fell from 25 +/- 3 to 15 +/- 2 mmHg (61 +/- 5%) at 2 min and remained depressed in a separate group of four piglets (P < 0.05). Conversely, compound action potential amplitude remained constant for the first 10 min of pacing and fell to 68 +/- 5% of control at 45 min (P < 0.05). Pi/PCr rose from a control value of 0.32 +/- 0.06 to 0.92 +/- 0.23 at 2 min and 0.79 +/- 0.03 at 10 min (P < 0.05) before returning toward control at 45-90 min. O2 delivery increased from 4.6 +/- 1.2 to 24.7 +/- 4.8 ml.min-1.100 g-1 at 2 min and 18.4 +/- 2.2 ml.min-1.100 g-1 at 10 min (P < 0.05) but then fell to lower levels at 45-90 min. ATP and intracellular pH remained constant except for a decline in pH to 6.98 +/- 0.09 at 45 min (P < 0.05) from the control value of 7.26 +/- 0.06.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1993

Cerebral blood flow responsivity to CO2 in anesthetized chronically diabetic dogs.

The effect of diabetes mellitus on the cerebrovascular response to CO2 is unclear. We examined the effects of diabetes on cerebral blood flow (CBF) and cerebral oxygen uptake (CMRO2) during CO2 alterations. Four groups of dogs were studied: nondiabetic, normoglycemic controls; non-diabetic acute hyperglycemia; diabetic (pancreatectomy) with high-dose insulin treatment to maintain blood glucose between 4.0 and 6.0 mM; and diabetic with low-dose insulin treatment to maintain blood glucose at 13.2 +/- 0.4 mM. Six weeks after either sham surgery or pancreatectomy, dogs were anesthetized with fentanyl (50 micrograms/kg) plus pentobarbital (10 mg/kg), and microsphere determinations of CBF were made during normo-, hypo-, and hypercapnia. On the day of the study, arterial glucose levels in the control, acute hyperglycemia, and high- and low-dose insulin diabetic groups were 4.0 +/- 0.3, 14.9 +/- 2.5, 3.3 +/- 0.8, and 13.3 +/- 0.7 mM, respectively, at control. The corresponding baseline CMRO2 levels were 2.8 +/- 0.2, 3.0 +/- 0.2, 4.1 +/- 0.4, and 4.0 +/- 0.3 ml O2.100 g-1 x min,1, and the values in both diabetic groups were higher than control. Normocapnic CBF in the acute hyperglycemia, high-dose insulin, and low-dose insulin groups was elevated from control (54 +/- 3, 50 +/- 3, 51 +/- 3 vs. 36 +/- 1 ml x 100 g-1 x min-1) and cerebrovascular resistance was lower (2.24 +/- 0.15, 2.51 +/- 0.14, 2.38 +/- 0.21 vs. 3.35 +/- 0.18 mmHg.ml-1 x 100 g.min). CBF responses to both hypercapnia and hypocapnia were similar among groups. Thus both acute hyperglycemia and diabetes decrease cerebrovascular resistance and increase CBF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Effect of hypoxemia on the cardiovascular response to intracranial hypertension in postnatal lambs.

Large increases in intracranial pressure in fetal sheep result in more potent peripheral vasoconstriction and better maintenance of cerebral O2 consumption (CMRO2) than in postnatal sheep. The fetus is exposed to a lower PO2. We tested the hypothesis that low PO2 in postnatal lambs potentiates peripheral vasoconstriction and better maintains cerebral perfusion pressure and CMRO2. Pentobarbital-anesthetized lambs, 2-7 days old, were ventilated with either room air (n = 7) or a low O2 mixture to reduce arterial O2 saturation to 50% (n = 7). Elevation of intracranial pressure to within 3-5 mmHg of baseline mean arterial pressure for 30 min by ventricular fluid infusion initially caused a similar increase in arterial pressure in the normoxic [11 +/- 3 (SE) mmHg] and hypoxic (14 +/- 2 mmHg) groups. Plasma catecholamines increased more rapidly in the hypoxic group. However, plasma vasopressin levels were substantially elevated by hypoxia alone and failed to increase further with elevated intracranial pressure. Moreover, there was no significant difference between groups in the steady-state increase in arterial pressure, and microsphere-determined blood flow to intestines, kidney, skin, and muscle did not decrease in either group. Consequently, cerebral perfusion pressure, regional cerebral blood flow, and CMRO2 were reduced similarly in both groups. Therefore, hypoxemia failed to potentiate the postnatal pressor response. Low PO2 is unlikely to be the major mechanism for the potent Cushing response in the fetus.

Animals↗

PubMed1993

Effect of nitric oxide synthase inhibition on cerebral blood flow and injury volume during focal ischemia in cats.

BACKGROUND AND PURPOSE: We tested the hypothesis that inhibition of nitric oxide synthase activity in brain before ischemia alters cerebral blood flow and decreases brain injury after 4 hours of middle cerebral artery occlusion in cats. METHODS: Halothane-anesthetized cats underwent 4 hours of left middle cerebral artery occlusion after they were randomly assigned to receive either intravenous N omega-nitro-L-arginine methyl ester, at a dose that completely inhibited cortical nitric oxide synthase activity (10 mg/kg, n = 10), or an equal volume of diluent (10 mL saline, n = 10). Serial blood flow measurements were made with radiolabeled microspheres, and injury volume was measured by triphenyltetrazolium staining. RESULTS: Blood flow to caudate nucleus and inferior temporal cortex decreased to the same extent in both groups during middle cerebral artery occlusion. Somatosensory evoked potential amplitude was reduced to less than 10% of baseline values in both groups. Injury volume of ipsilateral caudate nucleus in cats pretreated with nitroarginine (52 +/- 5%, mean +/- SE) was less (P < .05) compared with the saline group (80 +/- 4%), whereas ipsilateral cerebral hemispheric injury volume was similar between the two groups (30 +/- 6% and 32 +/- 4% of hemisphere in saline and nitroarginine groups, respectively). CONCLUSIONS: These results suggest that inhibition of nitric oxide synthase decreases caudate injury volume at 4 hours of middle cerebral artery occlusion without an alteration in distribution of cerebral blood flow.

Amino Acid Oxidoreductases↗