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Biomedical subjects

R C Koehler

Publications and source records attributed to R C Koehler.

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

Regional blood flow and O2 transport during hypoxic and CO hypoxia in neonatal and adult sheep.

We compared regional blood flow in unanesthetized newborn lambs with that in adult sheep during acute, isocapnic hypoxic hypoxia [HH, 40-50% reduction of arterial O2 content (CaO2)]. The HH response in lambs and adults was qualitatively similar in heart, brain, and skeletal muscle, where flow increased; and in spleen, where it decreased. The response differed in skin and kidney, where flow decreased in lambs and was unchanged in adults, and in small intestine, where it was unchanged in lambs and increased in adults. Thus vasoconstriction during HH was less prominent in skin, kidney, and small intestine in adults. However, the trend toward lesser vasoconstriction in the adult cannot be attributed to a diminishing carotid chemoreflex and/or a more prominent vasodilatory lung inflation reflex because the same trend occurred during carbon monoxide hypoxia (COH). COH reduces CaO2 but stimulates neither the carotid chemoreflex nor, since hyperpnea is absent, the lung inflation reflex. Within each age group the responses to COH and HH were qualitatively the same. These data therefore provide no evidence for an active carotid chemoreflex in unanesthetized postnatal sheep. This is either because the peripheral circulatory effect of the chemoreflex is suppressed by the lung inflation reflex or, less likely, because the chemoreflex does not operate in the sheep at this level of HH.

Animals↗
PubMed1985

Interaction of CO2 and ammonia on cerebral blood flow and O2 consumption in dogs.

Studies of acutely induced hyperammonemia and chronic hyperammonemia associated with liver dysfunction suggest that cerebral blood flow (CBF) and O2 consumption (CMRO2) become uncoupled and that CMRo2 may depend on arterial CO2 tension (PaCO2). We examined CBF (radiolabeled microspheres) and CMRO2 during hypercapnia (PaCO2 congruent to 74 Torr) and hypocapnia (PaCO2 congruent to 21 Torr) both before and during intravenous ammonium acetate infusion in pentobarbital-anesthetized dogs. Continuous infusion over 120 min produced stable increases of arterial ammonia levels (1,400 mumol/l) by 30 min, whereas CBF, CMRO2, and O2 extraction (measured at sagittal sinus) remained unchanged when PaCO2 was held constant (congruent to 35 Torr). Acute hyperammonemia attenuated the increase in CBF during hypercapnia by 44% and abolished the decrease in CBF during hypercapnia. Regional blood flow to pons and midbrain increased under normocapnic conditions, and midbrain blood flow increased further during hypocapnia. Sodium acetate infusion did not affect CBF responses to CO2. Thus we failed to observe an uncoupling of global CBF and CMRO2 during normocapnic hyperammonemia, or an interaction of CO2 and ammonia on CMRO2, although the increased pons and midbrain blood flow may reflect regional effects of ammonia on reticular activating system metabolism. On the basis of the literature, we suggest that the attenuated hypercapnic CBF response may arise from impaired glial regulation of extracellular potassium and bicarbonate concentrations and that lactic acid production, enhanced by combined alkalosis and hyperammonemia, may contribute to the abolition of hypocapnic vasoconstriction.

Acetates↗
PubMed1985

Cerebrovascular hypoxic and autoregulatory responses during reduced brain metabolism.

The effect of reducing cerebral oxygen consumption (CMRO2) on the cerebral blood flow (CBF) responses to isocapnic hypoxic hypoxia and hypotension was examined in sheep. Newborn and adult animals were studied because of their different base-line CMRO2. Microsphere-measured CBF responses during pentobarbital coma (i.e., electroencephalographic silence) were compared with responses in conscious or lightly sedated animals. Induction of barbiturate coma reduced both CMRO2 and CBF by 50% from the awake value and by 25% from the value obtained in animals sedated with pentobarbital. The CBF response to 30 and 50% reductions in arterial O2 content (CaO2) was attenuated during coma, but only in proportion to the decrease in CMRO2. Whether CMRO2 was normal or reduced, the normoxic cerebral O2 delivery (CaO2 X CBF) was maintained during hypoxia in both newborns and adults. The relative autoregulatory index (fractional change in CBF divided by fractional change in perfusion pressure) was determined during graded hemorrhage. The index was not significantly different from zero (which represents perfect autoregulation) in awake, lightly sedated, or comatose animals. The data demonstrate that both base-line CBF and responses to hypoxia are closely tied to CMRO2 and that 50% reduction of CMRO2 does not impair cerebrovascular autoregulation.

Animals↗
PubMed1985

Effect of abdominal distension on central and regional hemodynamics in neonatal lambs.

Elevations of intraabdominal pressure (IAP) can occur during surgical repair of gastroschisis and omphalocele and lead to ischemia of abdominal organs. We examined the effect of elevated IAP on central hemodynamics and regional abdominal organ blood flow, measured by radiolabeled microspheres, in 11 pentobarbital-anesthetized neonatal lambs. Stepwise increases in IAP were obtained by inflating a large bag placed intraperitoneally with air to pressures of 15, 20, and 25 mm Hg. Measurements were made at 30 min of elevated IAP and 30 min after deflating the bag. Mean aortic pressure was not significantly altered at an IAP of 15 mm Hg (78 +/- 4 mm HG) (+/- SE) or 20 mm HG (76 +/- 4 mm Hg) compared to baseline (81 +/- 4 mm Hg), but was decreased at the highest IAP (68 +/- 5 mm Hg). Stepwise decreases in blood flow to all abdominal organs, except adrenal gland, occurred with elevated IAP, and blood flows to these organs (except spleen) returned to or above baseline on bag deflation. At IAP of 15, 20, and 25 mm Hg, cardiac output was reduced by 14, 21, and 35%, respectively. Similar percent reductions of renal blood flow occurred. However, regional gastrointestinal blood flow decreased by a greater extent (35, 50, and 54% at each respective IAP). Hepatic arterial blood flow more than doubled at each IAP, but this was not sufficient to maintain total liver blood flow, or presumably total oxygen delivery to liver.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1985

Cardiopulmonary resuscitation, brain blood flow, and neurologic recovery.

A review of survival rates and neurologic outcome after cardiac resuscitation indicates the importance of rapid initiation of cardiopulmonary resuscitation (CPR) and of finding ways to further improve cerebral blood flow during CPR. Mechanisms for generating blood flow to the brain during CPR and experimental strategies for enhancing cerebral viability are discussed.

Cerebrovascular Circulation↗
PubMed1985

Effect of mefenidil on cerebral and peripheral hemodynamics in dogs.

Mefenidil (5-methyl-2-phenyl-4-imidazole-acetonitrile) has been reported to be a selective cerebral vasodilator. We examined the specificity of this vasodilator by using the radiolabeled microsphere technique to compare changes in cerebral blood flow (CBF) with those in other organs. Measurements were made in pentobarbital-anesthetized dogs at 10 min of continuous i.v. infusion of mefenidil at rates of 0.025, 0.25 and 2.5 mg/min/kg. Systemic vascular resistance decreased at 0.25 mg/min/kg without a change in CBF. At the highest infusion rate, CBF increased by 54 +/- 15% (+/- S.E.; n = 9) accompanied by a 9-mm Hg rise in intracranial pressure and a 14-mm Hg fall in mean aortic pressure. However, cardiac output increased by 68 +/- 8%, which was distributed primarily to right ventricle (541 +/- 95%), left ventricle (488 +/- 109%), small intestine (136 +/- 31%) and large intestine (57 +/- 15%). Within the brain, thalamic and brainstem regions had larger increases in blood flow than cerebellum and cerebrum. Caudate nucleus had a greater percentage of response than white matter. Using the cerebral venous outflow technique in another series of seven dogs, mefenidil (40-mg/kg i.v. bolus) produced a 20 +/- 8% increase in CBF with no change in O2 uptake. These data show that mefenidil is capable of increasing CBF in healthy brain without stimulating O2 uptake. However, the clinical usefulness of mefenidil as a cerebral vasodilator may be limited by the accompanying arterial hypotension due to systemic vasodilation, which was most prominent in heart and gut.

Animals↗
PubMed1984

Comparison of cerebrovascular response to hypoxic and carbon monoxide hypoxia in newborn and adult sheep.

Cerebral blood flow (CBF) responses to two types of isocapnic hypoxia, hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH), were examined in seven unanesthetized adult sheep by the radiolabeled microsphere technique. Comparisons were made with newborn lambs (5-12 days old) previously studied under similar conditions. The arterial O2 content (CaO2) was reduced in a graded manner to 50-60% of the control value. During HH, CBF increased to maintain cerebral O2 delivery (CaO2 X CBF) in both adults and newborns; however, cerebral O2 uptake (CMRO2) did not change. Although CMRO2 was higher in newborns, the responses of CBF/CMRO2 to HH did not differ significantly in newborns and adults. In newborns, regional CBF showed that brainstem areas were particularly responsive to HH. In both age groups, CBF increased to a greater extent with COH than with HH for similar reductions in CaO2. This resulted in an increase in cerebral O2 delivery with COH. The degree to which COH differed from HH correlated with the magnitude of the leftward shift of the oxyhemoglobin dissociation curve that accompanies COH. In adults, CMRO2 fell by 16% with COH but was maintained in newborns. We conclude that maintenance of cerebral O2 delivery during acute, isocapnic HH is a property of CBF regulation common to both newborn and adult sheep. During COH, the position of the oxyhemoglobin dissociation curve is an additional factor that sets the level of O2 delivery. The fetal conditions of low CaO2 and a left-shifted oxyhemoglobin dissociation curve may have provided the newborn with a microcirculation better suited for maintaining CMRO2 during COH.

Animals↗
PubMed1984

Mechanisms by which epinephrine augments cerebral and myocardial perfusion during cardiopulmonary resuscitation in dogs.

The goals of this study were to quantify the effects of epinephrine on myocardial and cerebral blood flow during conventional cardiopulmonary resuscitation (CPR) and CPR with simultaneous chest compression-ventilation and to test the hypothesis that epinephrine would improve myocardial and cerebral blood flow by preventing collapse of intrathoracic arteries and by vasoconstricting other vascular beds, thereby increasing perfusion pressures. Cerebral and myocardial blood flow were measured by the radiolabeled microsphere technique, which we have previously validated during CPR. We studied the effect of epinephrine on established arterial collapse during CPR with simultaneous chest compression-ventilation with the abdomen bound or unbound. Epinephrine reversed arterial collapse, thereby eliminating the systolic gradient between aortic and carotid pressures and increasing cerebral perfusion pressure and cerebral blood flow while decreasing blood flow to other cephalic tissues. Epinephrine produced higher cerebral and myocardial perfusion pressures during CPR with simultaneous chest compression-ventilation when the abdomen was unbound rather than bound because abdominal binding increased intracranial and venous pressures. In other experiments we compared the effect of epinephrine on blood flow during 1 hr of either conventional CPR or with simultaneous chest compression-ventilation with the abdomen unbound. Epinephrine infusion during conventional CPR produced an average cerebral blood flow of 15 ml/min . 100 g (41 +/- 15% of control) and an average myocardial blood flow of 18 ml/min . 100 g (15 +/- 8% of control). In our previous studies, cerebral and myocardial blood flow were less than 3 +/- 1% of control during conventional CPR without epinephrine. Although flows during CPR with simultaneous chest compression-ventilation without epinephrine were initially higher than those during conventional CPR, arterial collapse developed after 20 min, limiting cerebral and myocardial blood flow. The use of epinephrine throughout 50 min of CPR with simultaneous chest compression-ventilation maintained cerebral blood flow at 22 +/- 2 ml/min . 100 g (73 +/- 25% control) and left ventricular blood flow at 38 +/- 9 ml/min . 100 g (28 +/- 8% control). The improved blood flows with epinephrine correlated with improved electroencephalographic activity and restoration of spontaneous circulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Distribution of cardiac output in fetal and neonatal lambs with acute respiratory acidosis.

The effects of changes in PaCO2 on the circulation are complex, involving local vasodilation, vasodilation mediated by the pulmonary inflation reflex, and vasoconstriction due to effects on central vasomotor centers and peripheral chemoreceptors. One might anticipate that some or all of these might differ between the fetus in utero and the newborn. Distribution of cardiac output was measured in unanesthetized fetal (n = 6) and newborn (n = 7) sheep, using the radioactive microsphere technique. PaCO2 rose from 44 to 70 (fetus) and 38 to 60 torr (newborn) with the addition of CO2 to room air. In the fetus, there were significant increases in central nervous system (CNS), diaphragm, and lung blood flows. No organ showed a significant decrease in flow. Local vasodilation by CO2 was the likely cause of the increased flow to CNS. The large increase in pulmonary blood flow was most likely due to the associated rise in fetal PaO2 (23 to 28 torr) that accompanied respiratory acidosis and the presence of fetal breathing movements. The rise in diaphragmatic blood flow was likely the result of fetal breathing. In the newborn, CNS and diaphragm flows rose, but unlike the fetus, spleen and stomach flows decreased. These decreased flows in the hypercapnic newborn may have been due to stimulation of either central vasomotor centers or peripheral chemoreceptors.

Acidosis, Respiratory↗
PubMed1983

Precautions for measuring blood flow during anemia with the microsphere technique.

Preliminary data from a study of the effects of anemia on organ blood flow showed large discrepancies between cardiac output measured with the microsphere technique and simultaneous values calculated by the Fick principle. The most likely explanation was that the reference sample drawn according to our standard procedure underestimated the microsphere concentration in arterial blood, resulting in erroneously high blood flow values. In the present experiments we compared our usual reference sample, from a small catheter advanced from a peripheral artery into the brachiocephalic artery (withdrawal rate 1.3 ml/min), with a simultaneous sample from a larger catheter withdrawn at the much higher rate (7.89 ml/min). At hematocrits above 32%, microsphere concentrations from the two catheters were similar, but below 32% the concentration of microspheres in blood from the larger catheter was 30-50% more than from the smaller. The discrepancy was not altered by changing the injection site from left ventricle to left atrium and thus was probably not the result of poor mixing within the heart. It may have been the result of nonhomogeneous distribution of microspheres within larger vessels, perhaps as a consequence of laminar flow and axial streaming of both red blood cells and microspheres during anemia. Whatever the cause, it was possible to eliminate the difference by withdrawing from the smaller catheter at a more rapid rate (2.46 ml/min).

Anemia↗
PubMed1983

Role of O2-hemoglobin affinity on cerebrovascular response to carbon monoxide hypoxia.

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.

Animals↗
PubMed1983

Augmentation of cerebral perfusion by simultaneous chest compression and lung inflation with abdominal binding after cardiac arrest in dogs.

Recent studies have demonstrated that for the same chest compression force during mechanical cardiopulmonary resuscitation (CPR), the carotid artery-to-jugular vein pressure gradient and carotid blood flow are increased when the phasic rise of intrathoracic pressure is enhanced by abdominal binding and simultaneous ventilation at high airway pressure with each chest compression (SCV). The objective of the present study was to assess whether cerebral blood flow is also enhanced, since it is known that fluctuations in intrathoracic pressure are transmitted to the intracranial space and affect intracranial pressure (ICP). In two series of pentobarbital-anesthetized dogs, one of two CPR techniques was initiated immediately after inducing ventricular fibrillation. Brain blood flow was measured by the radiolabeled microsphere technique immediately before cardiac arrest and at 1 and 3 minutes after commencing CPR. Evidence of adequate mixing of spheres and lack of sedimentation under these low-flow conditions was verified by correlation with brain venous outflow, comparison of the arterial concentration-time profile of spheres and a nonsedimentary marker (thallium-201 in solution), and use of multiple arterial sampling sites. During SCV CPR with abdominal binding, mean carotid artery pressure (60 +/- 3 mm Hg) was higher than that during conventional CPR (25 +/- 2 mm HG). Pulsations of ICP occurred that were in phase with chest compression and greater than jugular venous pressure. Mean ICP was higher during SCV (46 +/- 2 mm Hg) than conventional CPR (20 +/- 2 mm Hg). However, the net brain perfusion pressure gradient (carotid artery pressure - ICP) was greater with SCV (14 +/- 3 mm Hg) than with conventional CPR (5 +/- 0.4 mm Hg). Cerebral blood flow was significantly greater during SCV CPR (32 +/- 7% of prearrest cerebral flow) than during conventional CPR (3 +/- 2%). We conclude that SCV CPR combined with abdominal binding substantially improved brain perfusion by enhancing cerebral perfusion pressure in this experimental model.

Abdomen↗
PubMed1982

Oxygen delivery to the brain before and after birth.

We studied the relationship between cerebral oxygen consumption and cerebral oxygen delivery (cerebral blood flow x arterial oxygen content) in fetal, newborn, and adult sheep, Relative to the amount of oxygen consumed, cerebral oxygen delivery in the fetus exceeds that in the lamb and adult by 70 percent. This may represent a protective advantage for the fetus or simply a necessary adaptation to the low arterial oxygen pressure in the intrauterine environment.

Animals↗
PubMed1982

Cerebral circulatory response to carbon monoxide and hypoxic hypoxia in the lamb.

In 14 unanesthetized newborn lambs the relationship between cerebral blood flow (measured by radiolabeled microspheres) and arterial O2 saturation (SaO2) was compared during two types of hypoxia: hypoxic hypoxia and carbon monoxide (CO) hypoxia. Cerebral venous samples were obtained from the sagittal sinus. The Increase in blood flow was 47% greater during CO than during hypoxic hypoxia. Cerebral O2 consumption and O2 delivery were constant during hypoxic hypoxia. Thus fractional O2 extraction, which equals O2 consumption/O2 delivery, remained constant with hypoxic hypoxia. During CO hypoxia, although O2 consumption remained constant, O2 delivery increased and fractional O2 extraction decreased. This decline in fractional O2 extraction was correlated with the leftward shift of the oxyhemoglobin dissociation curve that accompanied CO hypoxia. We suggest that cerebral blood flow depends on both SaO2 and the position of the oxyhemoglobin dissociation curve in the newborn lamb. However, this correlation does not exclude other potential histotoxic effects contributing to the relative overperfusion with CO hypoxia.

Animals↗
PubMed1982

Bicarbonate ion modulation of cerebral blood flow during hypoxia and hypercapnia.

The relative importance of changes in extracellular fluid (ECF) pH in mediating increases in cerebral blood flow (CBF) during hypoxia and hypercapnia was assessed by varying [HCO(-3)]ECF in pentobarbital-anesthetized dogs. Blood flow to one caudate nucleus (CNBF) that was bathed by cerebrospinal fluid (CSF) of varied [HCO(-3)] was compared with CNBF (measured by radiolabeled microspheres) on the contralateral side, which received a normal-[HCO(-3)]CSF perfusate. Raising [HCO(-3)]CSF from 25 to 60 meq/l for 150 min lowered CNBF by 16% and suppressed the slope of cNBF response to hypercapnia by 61% but suppressed the slope of CNBF response to hypoxia significantly less (22%). Lowering [HCO(-3)]CSF to 8 meq/l increased CNBF by 71% and augmented the response to hypercapnia by 126% but did not alter the slope of the response to hypoxia. These data indicate that changes in [H+]ECF can account for the increased CBF during hypercapnia but not for the entire hypoxic response. The increase in lactic acid production that would be necessary to solely account for the increase in CBF during hypoxia is much greater than what has been reported in the literature.

Animals↗
PubMed1980

Influence of CO2 on cardiovascular response to hypoxia in conscious dogs.

The modulating effect of CO2 on the circulatory response to hypoxia in chronically instrumented conscious dogs was examined over a wide range of arterial partial pressure of O2 [PaO2 (from 80 to 25 Torr)] during a 41-min rebreathing period at three CO2 levels: hypocapnia (from PaCO2 of 32 to 18 Torr), eucapnia (32 Torr), and mild hypercapnia (40 Torr). Eucapnic and hypercapnic hypoxic responses were also measured after sinoaortic denervation (SAD) to assess the arterial chemoreceptor and baroreceptor reflex contributions. Elevating PaCO2 attenuated the tachycardia during hypoxia and produced progressively greater systemic, renal, and splanchnic vasoconstriction before but not after SAD. Vagal block converted the rises in renal and splanchnic flows observed during hypocapnic hypoxia to declines. The increase in left ventricular dP/dtmax was not affected by varying PaCO2 either before or after SAD. Coronary flow increased an additional onefold during hypoxia when PaCO2 was elevated both before and after SAD, but the tension-time indices did not differ significantly. These results indicate that: a) cardiopulmonary vagal afferents effectively counteract chemoreflex-induced vasoconstriction during hypocapnic hypoxia; b) chemoreflex vasoconstriction predominates in the renal and splanchnic beds when PaCO2 is elevated; c) the sinoaortic reflexes restrain the heart rate, but not the contractility response to hypoxia when PaCO2 is increased; and d) the augmented coronary vasodilation produced by CO2 is probably mediated by local CO2-hypoxic interactions.

Animals↗
PubMed1980

Effect of lung volume on collateral ventilation in the dog.

We studied the effect of lung volume on resistance through collateral pathways (Rcoll) and small airways (Rsaw) before and after the injection of methacholine into obstructed segments of intact dogs. Before methacholine, Rcoll decreased 15.0 +/- 4.9 (SE)% per cmH2O increase in transpulmonary pressure (Ptp) and Rsaw decreased 5.1 +/- 7.0 (SE)% per cmH2O increase in Ptp. Following methacholine, lung inflation resulted in similar decreases in Rcoll and Rsaw. The fall in Rcoll was significantly greater than the fall in Rsaw. When pressure in an obstructed segment (Ps) was increased with constant Ptp (nonhomogeneous inflation), Rcoll fell approximately half as much for each cmH2O increase in pressure compared to when Ptp was increased (homogeneous inflation). We conclude 1) that increases in lung volume have small effects on Rsaw so that there is a relative increase in flow through collateral channels serving obstructed poritons of lung and 2) that Rcoll is a function of the size of the obstructed segment that increases more under homogeneous than nonhomogeneous conditions.

Airway Resistance↗