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Biomedical subjects

D W Busija

Publications and source records attributed to D W Busija.

At least 145 records · Page 8Linked to original sources
PubMed1985

Relationships among arteriolar, regional, and whole organ blood flow in cremaster muscle.

The relationship between microvessel and tissue blood flow (BF) was determined with two different techniques during changes in local vasomotor tone in the rat cremaster muscle. Whole organ and regional BF were measured with the radioactive microsphere technique (BFms) and compared with values calculated in individual arterioles (BFc) using the dual-slit cross-correlation technique. In the muscle prepared for microcirculatory observation (i.e., dissected, surgically divided into a flattened sheet, and covered with clear plastic), resting BFms was 43 +/- 3 ml X min-1 X 100 g-1, which was significantly higher than paired BFms in the contralateral undisturbed muscle (24 +/- 7 ml X min-1 X 100 g-1). Over a range in vasomotor tone, regional BFms to the edge of the tissue, which was exposed to the trauma of the surgery, was 56 +/- 7 ml X min-1 X 100 g-1 compared with 38 +/- 5 in the less traumatized center region, a significant difference of 79 +/- 31%. There was no linear relationship between arteriolar BFc and BFms. The correlation was not improved if the factors of vessel size, vasomotor tone, animal size, or muscle size were considered. Changes in arteriolar BFc (y) overestimated changes in total tissue BFms (x) by a factor of 2 (y = 2.01x - 0.6; r = 0.86), but changes in arteriolar BFc were proportional to changes in BFms if only the center region (x) of the tissue was considered (y = 1.08x - 0.1; r = 0.84). The general implication from these results is that factors that influence perfusion heterogeneity, such as surgical trauma, should be carefully considered when correlating macro- and microcirculatory measurements of BF.

Animals↗
PubMed1985

Prostanoids in cortical subarachnoid cerebrospinal fluid and pial arterial diameter in newborn pigs.

These studies were designed to investigate the relationship between cerebral prostanoid synthesis and pial arterial caliber in chloralose-anesthetized newborn pigs with normal blood gases and pH and during combined arterial hypoxia and hypercapnia. Piglets less than 5 days old were equipped with closed cranial windows to allow direct observation of pial vessels, application of prostaglandin E2, and sampling of cortical subarachnoid cerebrospinal fluid. We found that prostanoids accumulate in cerebrospinal fluid on the cortical surface. The only prostanoid detected in arterial blood was 6-keto-prostaglandin F1 alpha [442 +/- 74 pg/ml (radioimmunoassay)]. Only small quantities of 6-keto-prostaglandin F1 alpha (214 +/- 53 pg/ml) and thromboxane B2 (122 +/- 18 pg/ml) were found in cerebrospinal fluid from the cisterna magna. Higher concentrations of 6-keto-prostaglandin F1 alpha (1056 +/- 159 pg/ml), thromboxane B2 (229 +/- 64 pg/ml), and prostaglandin E2 (4235 +/- 269 pg/ml) were found in cortical subarachnoid fluid. In contrast to arterial and cisternal concentrations, the concentrations of 6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2 in cortical subarachnoid fluid were increased reversibly by ventilation with 9% carbon dioxide, 10% oxygen, (6-keto-prostaglandin F1 alpha, 5436 +/- 1576 pg/ml; thromboxane B2, 694 +/- 122 pg/ml; and, prostaglandin E2, 12,455 +/- 3688 pg/ml). Further, pial arteries dilated in response to topical application of prostaglandin E2 at the concentration that was found in cortical subarachnoid fluid during combined hypoxia and hypercapnia. Systemic administration of indomethacin trihydrate (5 mg/kg) markedly reduced cortical subarachnoid fluid prostanoid concentrations and attenuated the pial artery vasodilation induced by combined hypoxia and hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of indomethacin upon cerebral hemodynamics of newborn pigs.

Treatment of unanesthetized newborn pigs with indomethacin trihydrate (5 +/- 1 mg/kg, intravenous) decreased cerebral blood flow uniformly throughout the brain by 18-28% without changing cardiac output, arterial pressure, or arterial blood gases and pH. Breathing 10% O2, 9% CO2 with the balance N2 (hypoxia/hypercapnia) caused cerebral blood flow to increase from 102 +/- 12 to 218 +/- 19 ml/100 g . min. Intravenous administration of indomethacin during hypoxia/hypercapnia caused a uniform decrease in cerebral flow throughout the brain to levels (94 +/- 5 ml/100 g . min) indistinguishable from those when the piglet was breathing ambient air. Further, 2.5 h later, the cerebral hyperemia caused by hypoxia/hypercapnia was attenuated markedly (129 +/- 19 ml/100 g . min). Vehicle treatment did not alter resting cerebral blood flow or cerebral hyperemia in response to hypoxia/hypercapnia. Measurements of 6-keto-prostaglandin F1 alpha, thromboxane B2, and prostaglandin E2 demonstrated that intravenously administered indomethacin crossed the blood-brain barrier of newborn pigs in sufficient quantity to inhibit prostanoid release into the cerebrospinal fluid passing over the surface of the brain. The mechanism by which indomethacin reduces cerebral blood flow and attenuates cerebral hyperemia cannot be determined from the present experiments. We conclude that intravenous administration of indomethacin decreases cerebral blood flow and attenuates cerebral hyperemia induced by severe, combined hypoxia/hypercapnia in newborn pigs.

Animals↗
PubMed1985

Responses of newborn pig pial arteries to sympathetic nervous stimulation and exogenous norepinephrine.

The purpose of this study was to examine responses of pial arteries of newborn pigs to stimulation of sympathetic nerves and to exogenous norepinephrine. In the cerebral circulation, pial arteries are important resistance vessels. Diameters of pial arteries in anesthetized piglets, aged 1-6 days, were determined using the "closed" cranial window method. Electrical stimulation of the ipsilateral superior cervical ganglion (16 Hz; 2.5 msec; 10 V) reduced pial arterial diameter from 219 +/- 13 microns (mean +/- SEM) to 190 +/- 12 micron (n = 16) (p less than 0.05) without affecting arterial blood pressure. Pial arterial constriction during nerve stimulation was sustained over the 5-min stimulation period. Following cessation of stimulation, diameters returned to control levels. Exogenous norepinephrine in artificial cerebrospinal fluid constricted pial arteries from 149 +/- 19 to 133 +/- 18 microns at 2 X 10(-6) M (p less than 0.05) and from 159 +/- 20 to 123 +/- 16 microns at 2 X 10(-4) M (p less than 0.05) (18 arteries from nine piglets). Pial arterial responses to nerve stimulation and exogenous norepinephrine were not dependent on initial size of the vessels. The results of this study establish the existence of functional sympathetic innervation in the cerebral circulation at birth in pigs.

Animals↗
PubMed1984

Effects of activation of sympathetic nerves on cerebral blood flow during hypercapnia in cats and rabbits.

Effects of unilateral and bilateral activation of sympathetic nerves on cerebral blood flow (c.b.f.) and cerebrovascular resistance (c.v.r.) during hypercapnia were compared in anaesthetized cats and awake rabbits. Sympathetic nerves supplying cerebral vessels were sectioned on one or both sides in anaesthetized cats and unanaesthetized rabbits. Cerebral blood flow was measured with 15 micron radioactive microspheres. In cats, c.b.f. was greater than 110 ml/min per 100 g during hypercapnia (PCO2 greater than 65 mmHg). Unilateral section of sympathetic nerves did not change c.b.f. or c.v.r. but unilateral electrical stimulation decreased c.b.f. by 12 +/- 3% and increased c.v.r. by 15 +/- 4%. Bilateral section of sympathetic nerves decreased c.v.r. by 21 +/- 7% (P less than 0.005, compared with unilateral section) and electrical stimulation increased c.v.r. by 66 +/- 16% (P less than 0.005, compared with unilateral stimulation). In awake rabbits, c.b.f. was greater than 110 ml/min per 100 g during hypercapnia (PCO2 greater than 50 mmHg). Unilateral sympathetic denervation did not change c.v.r. but bilateral denervation decreased it by 18 +/- 8% (P less than 0.08, compared with unilateral section; P less than 0.03, compared with intact nerves). Thus, reflex activation of sympathetic nerves, as well as electrical stimulation, increases c.v.r. during hypercapnia. In addition, effects of bilateral stimulation or denervation of sympathetic nerves are greater than unilateral effects.

Anesthesia, General↗
PubMed1984

Hypercapnia potentiates renal vasoconstriction during hemorrhagic hypotension in awake rabbits.

Although both hemorrhagic hypotension and hypercapnia increase renal vascular resistance (RVR) modestly, effects of interaction between these stimuli on RVR have not been examined systematically in unanesthetized animals. The purpose of this study was to test the hypothesis that renal vasoconstriction during hemorrhagic hypotension is affected by arterial CO2 tension (PCO2). Unanesthetized rabbits were placed into an environmental chamber, and six were exposed to normocapnia (PCO2 approximately 29 mmHg) and six to hypercapnia (PCO2 approximately 62 mmHg). Renal blood flow (RBF) was measured with 15-micrograms microspheres during 1) normotension [mean arterial pressure (MAP) 84-88 mmHg]; 2) moderate hemorrhagic hypotension (MAP 61-64 mmHg); and 3) severe hemorrhagic hypotension (MAP 44-50 mmHg). When MAP was normal, RBF was 437 +/- 59 and 345 +/- 59 ml X min-1 X 100 g-1 in the normocapnic and hypercapnic groups, respectively (NS; P greater than 0.05). In addition, RVR (MAP/RBF) was 0.22 +/- 0.04 in the normocapnic group and 0.32 +/- 0.08 mmHg X ml-1 X min X 100 g in the hypercapnic group (NS; P greater than 0.05). During moderate hypotension, RVR was 0.48 +/- 0.18 in the normocapnic group and 1.74 +/- 0.36 mmHg X ml-1 X min X 100 g in the hypercapnic group (P less than 0.05, comparison between groups). During severe hypotension, RVR was 0.46 +/- 0.14 and 3.13 +/- 1.13 mmHg X ml-1 X min X 100 g during normocapnia and hypercapnia, respectively (P less than 0.05, comparison between groups). Thus, in unanesthetized rabbits, although hypercapnia does not increase RVR compared with normocapnia when arterial pressure is normal, hypercapnia greatly potentiates renal vasoconstriction during hemorrhagic hypotension.

Animals↗
PubMed1984

Sympathetic nerves reduce cerebral blood flow during hypoxia in awake rabbits.

Effects of sympathetic nerves on cerebral blood flow (CBF) during normoxia or hypoxia combined with hemorrhagic hypotension were examined in awake rabbits. One superior cervical ganglion was excised and sham surgery was performed on the other side. Five rabbits each were exposed to normoxia [arterial O2 tension (Pao2) greater than or equal to 78 mmHg] or hypoxia (Pao2 less than or equal to 39 mmHg). Cerebral blood flow was measured with 15-micron microspheres three times in each group: normotension [mean arterial pressure (MAP) 80-86 mmHg]; moderate hypotension (MAP 62-65 mmHg); and severe hypotension (MAP 49-50 mmHg). During normoxia, blood flow to cerebrum was 70 +/- 8 (SE) ml X min-1 X 100 g-1 during normotension and did not decrease during hypotension. Sympathetic nerves had no effect on CBF during normoxia. During hypoxia, blood flow to cerebrum was 243 +/- 21 ml X min-1 X 100 g-1 during normotension and fell as arterial pressure was lowered. Blood flow to denervated cerebrum was higher than on the intact side during normotension (13 +/- 4%), moderate hypotension (11 +/- 5%), and severe hypotension (12 +/- 4%). Similarly, blood flow to denervated cortical gray matter was higher during normotension (19 +/- 4%), moderate hypotension (16 +/- 6%), and severe hypotension (17 +/- 6%) when compared with the innervated side. In addition, blood flow to denervated cerebellum was higher than the innervated side during severe hypotension (27 +/- 17%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Interaction between hemorrhagic hypotension and hypoxia in regulation of renal vascular resistance in unanesthetized rabbits.

Effects of interaction between hemorrhagic hypotension and hypoxia on the renal circulation were examined in awake rabbits. The hypothesis tested was that renal vasoconstriction during hemorrhagic hypotension is affected by arterial PO2 (PaO2). Awake rabbits were placed into an environmental chamber and exposed to either normoxia (PaO2 greater than 100 mmHg) or hypoxia (PaO2 less than or equal to 40 mmHg). Renal blood flow (RBF) was measured with 15 micron microspheres during normotension (mean arterial pressure = 86-97 mmHg), moderate hemorrhagic hypotension (mean arterial pressure = 62-65 mmHg), and severe hemorrhagic hypotension (mean arterial pressure = 49-50 mmHg). During normotension, RBF was 461 +/- 46 and 330 +/- 30 ml/min per 100 g (mean +/- SEM) in the normoxic and hypoxic groups, respectively (P less than 0.05), and renal vascular resistance (RVR) was 0.21 +/- 0.03 and 0.31 +/- 0.04 mmHg per ml/min per 100 g in the normoxic and hypoxic groups, respectively (NS). Renal blood flow fell progressively in each group during hypotension, but the magnitude of this response was unaffected by the level of PaO2. In contrast, RVR during severe hypotension was 0.42 +/- 0.11 and 2.08 +/- 0.57 mmHg per 100 g for normoxia and hypoxia, respectively (P less than 0.05), and the increase in RVR during severe hypotension compared to normotension was greater in the hypoxic than normoxic group (P less than 0.05). Thus, in unanesthetized rabbits, hypoxia reduces RBF but does not change RVR significantly during normotension, and hypoxia potentiates the increase in RVR during hemorrhagic hypotension.

Animals↗
PubMed1983

Mechanisms of protection against stroke in stroke-prone spontaneously hypertensive rats.

The purpose of this study was to examine mechanisms by which sympathetic nerves protect against cerebral hemorrhage and ischemic infarction (i.e., "stroke") in stroke-prone spontaneously hypertensive rats (SHRSP). When unilateral superior cervical ganglionectomy was performed in SHRSP at 1 mo of age, development of cerebral vascular hypertrophy was inhibited and stroke developed only in the denervated hemisphere in 79% of the rats (P less than 0.05). Because "trophic" effects of sympathetic nerves on vascular growth may be less in older animals, unilateral sympathetic denervation was performed in SHRSP at 3 mo of age. The incidence of stroke was similar in the innervated and denervated hemispheres. In another group of rats that had unilateral ganglionectomy at 1 mo, we examined regulation of cerebral blood flow (CBF) when the rats were 4-5 mo of age, before neurologic signs of stroke. CBF, measured with microspheres, was similar in the innervated and denervated hemispheres during control conditions and during maximal vasodilatation produced by bicuculline. In contrast, when mean arterial pressure was raised acutely, CBF increased more in the denervated hemisphere than in the innervated hemisphere. We conclude that 1) in contrast to effects of denervation at 1 mo, sympathetic denervation at 3 mo of age (when trophic effects are less) does not lead to stroke, and 2) chronic denervation impairs the cerebral vasoconstrictor response to acute increases in arterial pressure.

Animals↗
PubMed1983

Effects of indomethacin on cerebral blood flow during hypercapnia in cats.

To study the contribution of prostaglandins to cerebral vasodilatation during hypercapnia, we inhibited prostaglandin synthesis with indomethacin. We measured cerebral blood flow (CBF) in anesthetized cats with 15-micrometers microspheres during normocapnia (PCO2 approximately 33 Torr), moderate hypercapnia (PCO2 approximately 49 Torr), and severe hypercapnia (PCO2 approximately 65 Torr) before and after intravenous administration of vehicle or indomethacin (3 and 10 mg/kg). Hypercapnia produced graded increments in blood flow to all areas of the brain. Administration of indomethacin did not change control CBF or significantly attenuate increases in CBF during hypercapnia. We examined efficacy and specificity of inhibition of prostaglandin synthesis by indomethacin using the cranial window method. Arachidonic acid (100 and 200 micrograms/ml) and acetylcholine (10(-7) and 10(-6)M or 10(-6) and 10(-5) M), dissolved in artificial cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of indomethacin blocked vasodilatation produced by arachidonic acid but did not affect the response to acetylcholine. Thus indomethacin, at a dose that effectively blocks prostaglandin synthesis, did not alter resting CBF or attenuate the increase in CBF during hypercapnia. This study suggests that steady-state cerebral vasodilatation during hypercapnia is largely preserved after inhibition of prostaglandin synthesis.

Animals↗
PubMed1982

Pial artery diameter and blood flow velocity during sympathetic stimulation in cats.

The effects of sympathetic stimulation on the cerebral circulation in cats are in dispute. One unexplained observation is that sympathetic nerve stimulation constricts pial arteries but does not decrease cerebral blood flow (CBF). To reconcile these findings, we studied effects of sympathetic nerves on cerebral vessels using a new method that permits virtually continuous measurement of pial artery diameter and blood flow velocity, and calculation of change in CBF. Change in CBF was calculated as the product of cross-sectional area (CSA) and blood flow velocity in a large pial artery. Pial artery diameter was measured with the cranial window method and CSA was calculated (pi r2). Blood flow velocity was measured with a pulsed Doppler velocity meter. In 11 cats, CBF was measured duringg the control period and during electrical stimulation of sympathetic nerves. During stimulation, arterial diameter decreased 6 +/- 1%, but CBF did not change because velocity increased 19 +/- 5%. We also measured CBF with microspheres during control and after 60 s of sympathetic stimulation. Cerebral blood flow was 28 +/- 3 ml/min/100 g during control and 26 +/- 3 ml/min/100 g after 60 s of sympathetic stimulation (n = 5). It is likely that the increase in velocity durin sympathetic stimulation was due to compensatory dilatation of downstream arteries.

Animals↗
PubMed1982

Atropine does not attenuate cerebral vasodilatation during hypercapnia.

To study the contribution of cholinergic nerves to cerebral vasodilation during hypercapnia, we blocked muscarinic cholinergic receptors with atropine. We used two new approaches. First, total and regional cerebral blood flow (CBF) were measured with microspheres. Second, efficacy and specificity of muscarinic blockade by atropine were examined using the cranial window method. In anesthetized cats we measured CBF with 15-micrometers microspheres six times during each experiment: during normocapnia (PCO2 = 32-34 Torr), moderate hypercapnia (PCO2 = 48-50 Torr), and severe hypercapnia (PCO2 = 61-64 Torr), before and after intravenous administration of vehicle or atropine (0.5 mg/kg). Hypercapnia produced graded increases in blood flow in all areas of the brain. Atropine did not attenuate increases in CBF during hypercapnia. We examined efficacy and specificity of muscarinic blockade by atropine using the cranial window method. Acetylcholine (10(-7) and 10(-6) M) and adenosine (10(-7) and 10(-5) M), dissolved in artificial cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of atropine attenuated vasodilation produced by acetylcholine but did not affect the response to adenosine. Thus atropine, at a dose that effectively blocked muscarinic receptors, did not attenuate the increase in CBF during hypercapnia. The study suggests that cholinergic nerves are not involved in steady-state cerebral vasodilatation during hypercapnia.

Acetylcholine↗
PubMed1981

Effect of adenosine and dipyridamole on cerebral blood flow.

The purpose of these experiments was to determine whether infusions of adenosine and of dipyridamole, which raise levels of endogenous adenosine, increase cerebral blood flow (CBF). In anesthetized dogs and cats, intracarotid infusions of adenosine increased blood flow to cranial muscle but did not alter CBF (measured with microspheres). Anatomical limitations may prevent satisfactory examination of cerebral vascular responsiveness during intracarotid infusion of vasodilator drugs in these species. In anesthetized rabbits, infusion of adenosine 10 microM/min in the carotid artery produced a 2-fold increase in CBF. Infusion of dipyridamole 20 microM/min increased CBF 2.7-fold. Dipyridamole produced a small decrease in cerebral oxygen consumption, which indicates that the vasodilator effect of the drug is not an indirect effect secondary to increased metabolism. These data indicate that exogenous and endogenous adenosine increase CBF in rabbits.

Adenosine↗
PubMed1981

Continuous measurement of cerebral blood flow in anesthetized cats and dogs.

We have developed a method for virtually continuous measurement of changes in cerebral blood flow (CBF) in cats and dogs. CBF was computed by multiplying cross-sectional area (CSA) and mean blood velocity in a pial artery. CSA was determined by measuring pial artery diameter with an electronic micrometer every 2-4 s through a cranial window. Velocity was measured continuously with a pulsed Doppler crystal positioned under a pial artery. CBF was determined in 12 anesthetized cats during 1) control, 2) hypocapnia, 3) hypercapnia, and 4) hypercapnia plus hypertension. Microspheres were injected under steady-state conditions to compare the two methods. During control, the diameter of the cerebral arteries observed was 388 +/- 28 (SE) micrometers, and CBF measured with microspheres was 40 +/- 4 ml.min-1.100 g-1. CBF decreased 18 +/- 2% during hypocapnia and increased 152 +/- 36% during hypercapnia. During steady-state conditions, the correlation coefficient between changes in CBF (CSA X velocity and microspheres) was 0.94, and the slope of the regression line was 1.02. In similar studies on seven anesthetized dogs, the correlation coefficient between CSA X velocity and microspheres was 0.98, and the slope of the regression line was 0.94. We conclude that the product of CSA and blood velocity of a pial artery provides accurate on-line measurement of changes in CBF.

Anesthesia↗
PubMed1981

Effects of cholinergic nerves on cerebral blood flow in cats.

We studied the effects of parasympathetic nerves on cerebral blood flow (CBF). The greater superficial petrosal nerve, which apparently supplies cholinergic fibers to cerebral vessels and the lacrimal gland, was sectioned on one side at the internal auditory meatus in anesthetized cats. CBF was measured with 15-microns microspheres. Section of the petrosal nerve did not alter resting CBF. In addition, electrical stimulation of the distal cut end of the petrosal nerve had no effect on total CBF. In one area of the brain, the caudate nucleus, stimulation increased blood flow from 29 +/- 2 to 36 +/- 2 (mean +/- SE) ml/min per 100 g. Lacrimal gland blood flow increased from 42 +/- 7 to 198 +/- 32 ml/min per 100 g during petrosal stimulation, which indicates that the stimulus was potent. In the same experiments, CBF increased 3- to 4-fold during hypercapnia; thus, cerebral vessels were responsive to another dilator stimulus. In other experiments, petrosal nerve section did not alter the response of cerebral vessels to hypercapnia (PCO2 > 50 mm Hg) or hypoxia (PO2 < 34 mm Hg). We conclude: (1) there is little or no resting vasodilator tone provided to cerebral vessels by the petrosal nerve; (2) petrosal nerve stimulation has a major effect on blood flow to the lacrimal gland but does not increase CBF; and (3) petrosal nerve section has little effect on the response of cerebral vessels to hypercapnia or hypoxia.

Animals↗
PubMed1981

Methods for measurement of cerebral blood flow.

Difficulties in measuring total and regional cerebral flow have hindered advances in knowledge concerning the regulation of the cerebral circulation. Now, however, we can accurately measure total and regional cerebral blood flow with the labeled microsphere method. With this method, flow to cerebral and non-cerebral tissues in the head can be completely separated, and by using microspheres labeled with different radionuclides, six measurements can be obtained in each experiment. A disadvantage of the microsphere method is that flow is not monitored continuously. Therefore, transient changes in flow (less than 20 seconds) cannot be measured accurately, and it is difficult to determine the time course of changes in cerebral blood flow in response to a given stimulus. A new method, simultaneous measurements of velocity and diameter in a pial artery, complements the microsphere approach. With this new method, nearly continuous, accurate measurements of cerebral blood flow are obtainable. Now that several methods for measuring cerebral blood flow are available and appear to be valid, knowledge concerning the regulation of cerebral blood flow should advance more rapidly.

Animals↗