M L Hudak

University of Florida Health Science Center-Jacksonville, Jacksonville, Florida, United States

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Publications (16)85.26 Total impact

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    ABSTRACT: Cerebral blood flow (CBF) increases as arterial oxygen content falls with hypoxic (low PO2), anemic (low hemoglobin) and carbon monoxide (CO) (high carboxyhemoglobin) hypoxia. Despite a higher arterial PO2, CO hypoxia provokes a greater increase in CBF than hypoxic hypoxia. We analyzed published data using a compartmental mathematical model to test the hypothesis that differences in PO2 in tissue, or a closely related vascular compartment, account for the greater response to CO hypoxia. Calculations showed that tissue, but not arteriolar, PO2 was lower in CO hypoxia because of the increased oxyhemoglobin affinity with CO hypoxia. Analysis of studies in which oxyhemoglobin affinity was changed independently of CO supports the conclusion that changes in tissue PO2 (or closely related capillary or venular PO2) are predictive of alterations in CBF. We then sought to determine the role of tissue PO2 in anemic hypoxia, with no change in arterial and little, if any, change in venous PO2. Calculations predict a small fall in tissue PO2 as hematocrit decreases from 55% to 20%. However, calculations show that changes in blood viscosity can account for the increase in CBF in anemic hypoxia over this range of hematocrits.
    Annals of Biomedical Engineering 12/1997; 26(1):48-59. · 3.23 Impact Factor
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    ABSTRACT: We used a cranial window preparation to observe the effects of direct application of group B streptococci to the surface of the brain in the adult rat. Continuous exposure to group B streptococci at concentrations of 10(3) and 10(5) organisms/mL caused progressive dilation of surface (pial) cerebral arterioles that became statistically significant (p less than 0.05) after 2.5 h. These results were reproduced with heat-killed organisms at the same concentration, but not with a bacteria-free filtrate of the growth medium. In separate studies, we found that infusion of alkaline cerebrospinal fluid (pH = 7.8) into the window did not reverse vasodilation, suggesting that it was not due to progressive cerebrospinal fluid acidosis. A solution of nitroblue tetrazolium infused into the window at the end of a 3-h exposure to the organism was promptly reduced, suggesting the presence of oxygen free radicals. Treatment with i.v. polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase in doses of 10,000 and 20,000 U/kg, respectively, was itself without effect on pial arterioles, but treatment with these compounds before exposure to group B streptococci eliminated the vasodilation. These data support a role for oxygen free radicals in the pathogenesis of pial arteriolar dysfunction induced by exposure to group B streptococci.
    Pediatric Research 07/1992; 31(6):640-4. · 2.67 Impact Factor
  • S M Helou, M L Hudak, M D Jones
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    ABSTRACT: We have reported recently that the cerebral blood flow (CBF) response to isocapnic hypoxic hypoxia is blunted in fetal sheep in utero at 93 days of gestation (term = 145-150 days), a time of rapid brain differentiation in this species. Cerebral O2 transport fell rather than being maintained, as it is in more mature fetuses. The reason for the blunted response was not clear. We hypothesized that the CBF response to hypercapnia also might be blunted. We studied 10 immature fetal sheep in utero at a mean gestational age of 92 days 24 h after catheters were placed into the superior sagittal sinus, axillary artery, and inferior vena cava. We raised the fetal arterial carbon dioxide tension (PaCO2) by changing the mother's inspired PCO2. CBF was measured before and during hypercapnia by the microsphere method. The overall increase in CBF in response to hypercapnia in immature fetuses was lower than in near-term fetuses. However, the difference was eliminated after correcting for differences in cerebral O2 consumption. This study failed to show any defect in the ability of cerebral vessels in immature fetal sheep to respond to carbon dioxide.
    The American journal of physiology 12/1991; 261(5 Pt 2):H1366-70. · 3.28 Impact Factor
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    ABSTRACT: We used the closed cranial window technique to observe the responses of pial arterioles to topical application of cocaine in 29 anesthetized cats. Alterations in arteriolar diameter were dependent on the concentration of cocaine applied. Cocaine dissolved in artificial cerebrospinal fluid at concentrations of 10(-8) or 10(-7) M was without effect. Concentrations of 10(-6) and 10(-5) M produced dilation (4.9 +/- 1.5% [mean +/- SEM] and 5.9 +/- 2.0%, respectively) in large arterioles (greater than 100 microns) but no significant change in the diameter of small arterioles (less than 100 microns). A concentration of 10(-4) M dilated both large and small arterioles (20.3 +/- 3.1% and 12.0 +/- 7.1%, respectively). Pretreatment with 1 mg/kg i.v. propranolol blocked the increase in pial arteriolar diameter after application of 10(-4) M cocaine and produced significant vasoconstriction in small arterioles (-8.3 +/- 3.1%). Cocaine produces vasodilation of cat cerebral arterioles. This effect appears to be mediated, at least in part, by mechanisms that depend on stimulation of beta-adrenergic receptors.
    Stroke 01/1991; 21(12):1710-4. · 6.16 Impact Factor
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    ABSTRACT: Cerebral blood flow (CBF) rises as hematocrit (Hct) falls. We previously attributed this rise in CBF to two independent factors of equal importance, decreased arterial O2 content and decreased blood viscosity. We hypothesized that decreased arterial O2 content would dilate cerebral arterioles and that the magnitude of the vasodilation would depend on the magnitude of the passive fall in vascular resistance attributable to decreased viscosity. The present study was designed to test the hypothesis that anemia is accompanied by cerebral vasodilation. Using a closed cranial window, we measured the diameters of 42 pial arterioles (35-305 microns) in 7 cats as serial isovolemic hemodilution lowered Hct by 44% from 31 +/- 4 to 17 +/- 3%. Hemodilution increased CBF (microsphere technique) but did not change mean arterial blood pressure or arterial blood gases. Anticipated vasodilation did not occur; instead, pial arterioles constricted as Hct fell. Maximum vasoconstriction was observed when Hct reached 65-70% of the initial value. Vasoconstriction lessened as Hct was lowered further, but arteriolar diameters at the lowest Hcts remained less than base-line levels. Constriction was greater in small (less than 100 microns) than in large (greater than or equal to 100 microns) arterioles. The initial constriction of pial arterioles may represent myogenic vasoconstriction in response to flow-induced vasodilation of more proximal portions of the cerebrovascular bed and/or to washout of an endogenous vasodilator. Arteriolar relaxation with more profound hemodilution may reflect superimposed metabolic vasodilation.
    The American journal of physiology 10/1989; 257(3 Pt 2):H912-7. · 3.28 Impact Factor
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    ABSTRACT: Individual effects of hypoxic hypoxia and hypercapnia on the cerebral circulation are well described, but data on their combined effects are conflicting. We measured the effect of hypoxic hypoxia on cerebral blood flow (CBF) and cerebral O2 consumption during normocapnia (arterial PCO2 = 33 +/- 2 Torr) and during hypercapnia (60 +/- 2 Torr) in seven pentobarbital-anesthetized lambs. Analysis of variance showed that neither the magnitude of the hypoxic CBF response nor cerebral O2 consumption was significantly related to the level of arterial PCO2. To determine whether hypoxic cerebral vasodilation during hypercapnia was restricted by reflex sympathetic stimulation we studied an additional six hypercapnic anesthetized lambs before and after bilateral removal of the superior cervical ganglion. Sympathectomy had no effect on base-line CBF during hypercapnia or on the CBF response to hypoxic hypoxia. We conclude that the effects of hypoxic hypoxia on CBF and cerebral O2 consumption are not significantly altered by moderate hypercapnia in the anesthetized lamb. Furthermore, we found no evidence that hypercapnia results in a reflex increase in sympathetic tone that interferes with the ability of cerebral vessels to dilate during hypoxic hypoxia.
    Journal of Applied Physiology 04/1989; 66(3):1065-70. · 3.48 Impact Factor
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    ABSTRACT: We have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O2 content (CaO2). In the present study, we tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). E is the ratio of O2 demand (cerebral O2 consumption, CMRO2) to supply (cerebral O2 transport: OT = CBF x CaO2) and is assumed to be inversely related to tissue O2 availability. Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia [arterial CO2 partial pressure (PaCO2) = 15.3 +/- 0.7 mmHg, means +/- SE; n = 7] or hypercarbia (PaCO2 = 62.7 +/- 1.1 mmHg; n = 5), respectively. A second isovolemic exchange transfusion with pure methemoglobin-containing adult sheep red cells then raised Hct (to 38.5 +/- 0.5%) with no significant increase in CaO2. PaCO2 was maintained and other variables (oxyhemoglobin affinity, pH, mean arterial blood pressure) with potential effect on CBF did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
    The American journal of physiology 02/1988; 254(1 Pt 2):H156-62. · 3.28 Impact Factor
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    ABSTRACT: The authors have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial Oâ content (Ca{sub Oâ}). In the present study, they tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia, or hypercarbia. A second isovolemic exchange transfusion with pure methemoglobin-containing adult sheep red cells then raised Hct with no significant increase in Ca{sub Oâ}. Pa{sub COâ} was maintained and other variables with potential effect on CBF did not change. CBF corrected for any individual alteration in CMRoâ. This study supports the hypothesis that the magnitude of the decline in CBF secondary to an increase in RBC concentration depends on the initial E. The effect of RBC concentration on CBF is greatest when E is low.
    The American journal of physiology 01/1988; · 3.28 Impact Factor
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    ABSTRACT: Cerebral blood flow (CBF) is lowered during polycythemia. Whether this fall is due to an increase in red blood cell concentration (Hct) or to an increase in arterial O2 content (Cao2) is controversial. We examined the independent effects of Hct and Cao2 on CBF as Hct was raised from 30 to 55% in anesthetized 1- to 7-day-old sheep. CBF was measured by the radiolabeled microsphere technique before and after isovolemic exchange transfusion with either oxyhemoglobin-containing erythrocytes (in 5 control animals) or with methemoglobin-containing erythrocytes (in 9 experimental animals). Following exchange transfusion in the control animals, Hct rose (30 +/- 1 vs. 55 +/- 1%, mean +/- SE), Cao2 increased (15.1 +/- 0.8 vs. 26.7 +/- 0.9 vol%), and CBF fell (66 +/- 9 vs. 35 +/- 5 ml X min-1 X 100 g-1). Because the fall in CBF was proportionate to the rise in Cao2, cerebral O2 transport (CBF X Cao2) was unchanged. Following exchange transfusion in the experimental animals, Hct rose (32 +/- 1 vs. 55 +/- 1%) but Cao2 did not change. Nevertheless, CBF still fell (73 +/- 4 vs. 48 +/- 2 ml X min-1 X 100 g-1) and, as a result, cerebral O2 transport also fell. The latter cannot be attributed to a fall in cerebral O2 uptake, as cerebral O2 uptake was unaffected during each of these conditions. Comparison of the two groups of animals showed that approximately 60% of the fall in CBF may be attributed to the increase in red cell concentration alone. It is probable that this effect is due largely to changes in blood viscosity.
    Journal of Applied Physiology 04/1987; 62(3):1090-6. · 3.48 Impact Factor
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    ABSTRACT: Cerebral blood flow (CBF) and cerebral O2 transport (CBF X arterial O2 content) in the fetal sheep are nearly twice that in the adult, despite similar rates of cerebral O2 utilization. We tested the hypothesis that the difference depends on the increased oxyhemoglobin affinity in the fetus, using P50 (PO2 at which hemoglobin is 50% saturated) as the index of oxyhemoglobin affinity. We studied 18 unanesthetized fetal sheep in utero. In six animals the P50 was raised from 16.6 +/- 1.2 (SD) mmHg to 31.7 +/- 4.7 mmHg by exchange transfusing the fetus with adult sheep red blood cells. We measured CBF (with radioactive microspheres) and the PO2, PCO2, pH, and O2 content in carotid artery and sagittal sinus blood twice at the original P50 and twice after exchange transfusion. Arterial O2 content fell significantly at the higher P50. Since the fall in O2 content was not accompanied by a corresponding rise in CBF, O2 transport fell by 45%. Cerebral O2 consumption (CMRO2) did not change and cannot be implicated in the fall of O2 transport. E (the ratio CMRO2/O2 transport) rose by 77%. Sham exchange transfusions in six fetuses showed that the exchange transfusion procedure itself was not responsible for this alteration. To determine whether the fall in O2 transport and the rise in E was reproducible over a range of arterial O2 contents, a third group of six fetuses was studied. Fetal arterial O2 content varied from 4 to 12 vol%, first at P50 = 17 +/- 1.8 mmHg and again after exchange transfusion at P50 = 29.6 +/- 3.9 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)
    The American journal of physiology 08/1986; 251(1 Pt 2):H56-62. · 3.28 Impact Factor
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    ABSTRACT: Cerebral blood flow (CBF) falls as hematocrit (Hct) rises. Investigators have differed on the relative importance of the increases in arterial O2 content (CaO2) and red blood cell concentration in mediating the fall. Our experimental protocol attempted to determine the independent effects of these two variables. In 13 unanesthetized lambs (less than 7 days old) we measured arterial and sagittal sinus blood gases, and O2 contents, and CBF (microsphere technique) at oxyhemoglobin Hcts of approximately 20 and 40% and after an isovolemic exchange transfusion with a mixture of normal and pure methemoglobin (MHb) containing red cells. Following MHb exchange, Hct rose (19.7 +/- 0.3 vs. 38.2 +/- 0.4%, mean +/- SEM) with little change in CaO2 (9.3 +/- 0.2 vs. 10.0 +/- 0.3 vol%). Arterial PCO2, pH, mean arterial blood pressure, and cerebral O2 consumption (CMRO2) did not change. However, CBF fell (153 +/- 11 vs. 110 +/- 7 ml . 100 g-1 . min-1). CBF declined further when CaO2 rose (17.3 +/- 0.5 vol%) at the higher oxyhemoglobin Hct (36.9 +/- 0.8%). We calculated that the increase in red cell concentration accounted for 56% of the decrease in CBF that ordinarily occurs as Hct rises from 20 to 40%. The effect of red cell concentration on CBF varied among individual animals. It correlated closely (r = -0.77) with the initial cerebral fractional O2 extraction [E = CMRO2/(CBF X CaO2)]. Animals with the most luxuriant O2 supply (CBF X CaO2) relative to demand (CMRO2) had the greatest decrements in CBF as red blood cell concentration rose.
    The American journal of physiology 08/1986; 251(1 Pt 2):H63-70. · 3.28 Impact Factor
  • M L Hudak, M D Jones, S W Brusilow
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    ABSTRACT: We reviewed clinical data in 33 patients with transient hyperammonemia of the newborn (THAN): six previously unreported cases and 27 from the literature. Thirteen neonates with urea cycle enzyme deficiencies (UCED) served for comparison. No differences were found in the incidence of perinatal complications, route of delivery, Apgar scores, sex, or incidence or time of onset of seizures. On the other hand, neonates with THAN had significantly lower birth weights (mean +/- SEM 2282 +/- 78 gm vs 3336 +/- 222 gm, P less than 0.001) and gestational ages (35.1 +/- 0.5 weeks vs 39.6 +/- 0.5 weeks, P less than 0.001). Mean time of onset of respiratory distress (3.9 +/- 1.4 hours vs 71.5 +/- 26.1 hours, P less than 0.001), ventilatory support (P less than 0.001), lethargy (P less than 0.005), and coma (P less than 0.005) occurred earlier in THAN. Distinctive laboratory findings in patients with THAN included abnormal chest radiographic findings and plasma ammonium concentrations that were higher (1871 +/- 209 microM vs 973 +/- 169 microM, P less than 0.02) at an earlier age. Respiratory distress occurred in all but one patient with THAN before 24 hours; in contrast, only 62% of infants with UCED had respiratory symptoms, and none before 30 hours. In this retrospective study, the clinical presentation alone differentiated THAN from UCED.
    Journal of Pediatrics 12/1985; 107(5):712-9. · 4.04 Impact Factor
  • M D Jones, M L Hudak, R J Traystman
    The Lancet 07/1985; 1(8444):1511. · 39.21 Impact Factor
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    ABSTRACT: Our previous studies showed that, in contrast to hypoxic and anemic hypoxia, CO hypoxia increased cerebral O2 delivery and decreased cerebral fractional O2 extraction. These changes were correlated with the accompanying decrease in P50 (PO2 at 50% saturation of non-CO bound sites on hemoglobin). To assess directly the role of P50 in the cerebrovascular response to CO, we first performed isovolemic exchange transfusions on unanesthetized newborn lambs, replacing their high-O2-affinity hemoglobin with low-affinity adult sheep donor blood. Exchange transfusion resulted in an average increase in P50 of 10 Torr and in a uniform decrease of regional cerebral blood flow and cerebral O2 delivery of 14%. Thus shifts in P50 can produce cerebrovascular changes during normoxia, implying that the mechanism regulating cerebral blood flow does not have a discrete threshold to an hypoxic stimulus. Induction of CO hypoxia (20-40% carboxyhemoglobin) after the exchange transfusion returned P50 to the control level, and with it restored both cerebral O2 delivery and fractional O2 extraction to the pretransfusion values. We conclude that the fall in P50, rather than a direct tissue effect of CO, is responsible for the relative cerebral overperfusion during CO hypoxia. The importance of the position of oxyhemoglobin dissociation curve as a determinant of cerebral blood flow supports the presence of a highly sensitive, tissue O2-dependent mechanism regulating the cerebral circulation.
    The American journal of physiology 01/1984; 245(6):H1019-23. · 3.28 Impact Factor
  • M. L. Hudak, M. D. Jones, S. rusilow
    Pediatric Research - PEDIAT RES. 01/1984; 18.
  • Pediatric Research - PEDIAT RES. 01/1984; 18.

Publication Stats

199 Citations
85.26 Total Impact Points

Institutions

  • 1997
    • University of Florida Health Science Center-Jacksonville
      Jacksonville, Florida, United States
    • Indian Institute of Technology Delhi
      • Centre for Atmospheric Sciences
      New Delhi, NCT, India
  • 1988–1992
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
  • 1991
    • University of Tsukuba
      • Institute of Basic Medical Sciences
      Tsukuba, Ibaraki-ken, Japan
  • 1985–1991
    • Johns Hopkins University
      • Department of Pediatrics
      Baltimore, MD, United States