Search PubMed⌕ Search

Biomedical subjects

K G Proctor

Publications and source records attributed to K G Proctor.

72 records · Page 4Linked to original sources

Contribution of hyperosmolality to glucose-induced intestinal hyperemia.

To test the hypothesis that changes in tissue osmolality participate in glucose-induced absorptive hyperemia, the mucosa of the rat jejunum was suffused with isotonic or hypertonic glucose solutions. Blood flow was calculated from the product of a constant, arteriolar diameter, and red blood cell velocity, which were measured in the submucosal microcirculation. Isotonic glucose solutions (293 +/- 2 mosmol/kg) were prepared by diluting 5, 10, or 20 ml of 5% glucose, which is isotonic with plasma, to 100 ml with Ringer-bicarbonate buffer to concentrations of 250, 500, and 1,000 mg/100 ml. Glucose was added directly to Ringer-bicarbonate buffer to increase osmolality. The osmolalities of the 250, 500, and 1,000 mg/100 ml hypertonic solutions were 305 +/- 3,319 +/- 3, and 353 +/- 1 mosmol/kg, respectively. Glucose caused a concentration-related increase in estimated submucosal arteriolar blood flow that averaged 18-21% (n = 14), 24-27% (n = 14), and 34-45% (n = 14) at 250, 500, and 1,000 mg/100 ml glucose, respectively. There was no effect of solution osmolality on either the time course or the magnitude of the hyperemia at a given glucose concentration. Whereas the magnitude of the glucose-induced hyperemia averaged less than 50%, the application of 10(-2) M adenosine caused a fivefold increase in calculated blood flow (492 +/- 67%, n = 24). Thus, glucose caused relatively small increases in intestinal blood flow. If changes in luminal osmolality caused changes in intestinal tissue osmolality, then it is unlikely that hyperosmolality participates in the functional hyperemia associated with glucose absorption.

Adenosine↗

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↗

Differential effect of cyclooxygenase inhibitors on absorptive hyperemia.

To test whether the hydrolytic products of digestion could stimulate vasoactive prostaglandin synthesis in the intestine, the muscularis and mucosa of the rat jejunum were suffused with a bicarbonate-buffered Ringer vehicle containing cyclooxygenase inhibitors (meclofenamate or indomethacin; 3 X 10(-5) M). To evoke blood flow changes, either glucose (56 mM), oleic acid (20 or 40 mM), or sodium arachidonate was added to the mucosal vehicle. Bile salt (taurocholic acid, 10 mM) was added to emulsify oleic acid. Blood flow was calculated (BFc) in submucosal arterioles by use of video microscopy. Neither bile salt nor cyclooxygenase inhibitors altered resting BFc. Neither oleic acid concentration nor solution osmolality altered the magnitude of absorptive hyperemia. After 10 min of glucose, BFc increased 36 +/- 6% with vehicle (n = 16) and 39 +/- 8% with meclofenamate (n = 10). After 10 min of oleic acid, BFc increased 21 +/- 5% with vehicle (n = 17) and 34 +/- 6% with inhibitors (n = 17). In animals exposed twice to the same concentration of oleic acid, the paired difference between the vehicle and inhibitors (19 +/- 7%; n = 9) was significant. Arachidonate alone produced no dose-related (0.06-1.9 mM) effect on BFc (n = 41), but arachidonate (0.3 mM) combined with cyclooxygenase inhibitors (6 X 10(-5) M) produced a significant BFc increase of 35 +/- 7% (n = 6). These observations suggest that the absorption of oleic acid, but not glucose, stimulates the synthesis of a vasoactive metabolite of arachidonate. The mechanism for the differential effect of cyclooxygenase inhibitors is unknown but could involve nonprostaglandin metabolites of arachidonate, such as lipoxygenase or cytochrome P-450 products.

Animals↗

Inaccuracies in blood flow estimates in microvessels during arteriolar vasoconstriction.

The effect of vasomotor tone on blood flow estimates was evaluated in the hamster cheek pouch and cremaster muscle microcirculation. The products of arteriolar cross-sectional area and red blood cell velocity were calculated in three different cases: (1) at arteriolar bifurcations, (2) in short segments of an arteriole constricted by iontophoretic application of norepinephrine, and (3) at randomly selected second- and third-order arterioles. Vasodilation of the microcirculation was induced by topical application of adenosine. Vasoconstriction was induced by elevation of superfusion solution PO2. If true volume flow is accurately estimated by this method then: the sum of measured branch flows at a bifurcation should equal feed flow; measured flow through constricted arteriolar segments should equal flow proximal or distal to the constricted segment; and, following experimental manipulations, relative changes in estimated flow in second- and third-order arterioles should be equal. Our findings suggest that the blood flow estimates were not always accurate. The sum of branch flows was equal to feed flow only across bifurcations with low or resting vascular smooth muscle tone. During vasoconstriction, feed flow averaged 40% higher than the sum of downstream flows. In addition, estimated flow was 15% lower in constricted segments of an arteriole compared to dilated contiguous segments of the vessel. During alterations in vasomotor state, estimated fractional changes in flow in second- and third-order arterioles differed by more than sixfold. Therefore, blood flow estimates with the dual-slit method may not be reliable under conditions of high vasomotor tone. We speculate that the error may result largely from uncertainties in the diameter measurement.

Adenosine↗

Reduction of contraction-induced arteriolar vasodilation by adenosine deaminase or theophylline.

To test the hypothesis that adenosine mediates striated muscle blood flow, the cremaster muscle microcirculation was exposed to a continuous superfusion (10-30 min) of either a control, adenosine deaminase (7 micrograms protein/ml), or theophylline (10(-5) M) solution before, during, and following twitch contraction. Small arteriolar diameter and (dual-slit) blood flow velocity were continuously measured for 3 min before and after 2 min of electrical stimulation at 10, 5, or 2 Hz. Estimated arteriolar volume flow was calculated at 10-s intervals. The peak and average arteriolar diameter, peak and average estimated volume flow, duration of the exercise evoked response, and the total estimated volume of blood delivered in the 3-min postexercise period were reduced by deaminase as a function of stimulus frequency relative to a paired control. Deaminase reduced total estimated blood flow by 44, 35, and 22% at 10, 5, and 2 Hz, respectively. Although theophylline was more damaging to the tissue at a dose that was equieffective with deaminase, it produced a consistent reduction in peak and average arteriolar diameter and estimated volume flow after 5-Hz exercise. If changes in small arteriolar diameter are proportional to tissue blood flow changes, then these observations support the hypothesis that adenosine contributes to contraction-induced hyperemia in skeletal muscle in free-flow conditions and that its regulatory contribution depends on the intensity of the metabolic stimulus. Alternatively, these data could implicate adenosine in exercise-induced capillary recruitment.

Adenosine Deaminase↗

The effect of sympathomimetic drugs on post-lymphadenectomy aspermia.

A double-blind controlled study of the effects on semen quality of 4 alpha-adrenergic agents with and without antihistamines was conducted in a patient who had failure of emission secondary to retroperitoneal lymphadenectomy for testis cancer. No other controlled studies are available. All of the alpha-adrenergic drugs allowed the patient to produce an ejaculate. The effects were similar. The addition of antihistamine did not improve the semen quality. Four days of treatment were consistently more effective than a single dose, especially for sperm motility. A pregnancy resulted. It is concluded that long-term treatment with alpha-adrenergic drugs is indicated in men with failure of emission secondary to retroperitoneal lymphadenectomy.

Adult↗

Adenosine and free-flow functional hyperemia in striated muscle.

Striated muscle arteriolar responses to 1.5 min of 1-Hz contraction and/or increased tissue O2 partial pressure (PO2) were observed during exposure of the tissue interstitial space to adenosine deaminase (ADA) to evaluate the role of adenosine (ADO) as a regulator for blood flow. The microvasculature of the hamster cremaster muscle was continuously superfused with a bicarbonate buffer containing 11 micrograms ADA/ml and equilibrated with 5% CO2 and various O2 concentrations. Arterioles (resting diameter less than 30 micrometers) constricted a maximum of 55% when the superfusate gas tension was increased from 0 to 95% O2, but ADA had no effect on this behavior. Arterioles dilated during exercise, but the diameter change was decreased 20-25% during exercise with ADA treatment at both normal and elevated tissue PO2. As ADA had no effect on either the vasodilation to 2-chloroadenosine or resting arteriolar diameter, it was probably specific in its action. Assuming that all extracellular ADO was accessible to ADA and that ADA neutralized most newly formed ADO, we conclude that ADO is one component of a multifactor system mediating short periods of free-flow exercise hyperemia and that the release of ADO is not necessarily dependent on tissue hypoxia.

Adenosine↗

Tissue PO2 and arteriolar responses to metabolic stimuli during maturation of striated muscle.

Tissue O2 tension (PO2) and small arteriolar diameter were measured in hamsters aged 32, 60, and 80 days. The cremaster muscle was isolated and superfused with a solution equilibrated with 0, 5, or 10% O2 stimulated to contract at 1 Hz. Resting muscle tissue PO2 was proportional to superfusate PO2 and was not different between age groups. The decrease in tissue PO2 during contraction was greatest in adult animals when the superfusate PO2 was low but was equal in all groups when the superfusate PO2 was high. Elevated superfusate PO2 was correlated with a vasoconstriction, the magnitude of which varied inversely with age. Resting and contraction-induced vascular diameter were largest in the youngest animals, relative to maximum diameter, but absolute resting and contraction-induced diameters were similar in all groups. We suggest that tissue PO2 at rest was similar because of an age-associated decrease in fiber O2 consumption to maintain a constant proportionality between O2 supply and demand. The relative stability of tissue PO2 during contraction in young animals might have reflected superior regulation. However, a simple numerical analysis predicts smaller tissue PO2 decreases during contraction in young animals because of short intercapillary distances and other altered O2 supply parameters, even if regulation had been identical in all age groups.

Aging↗

Exercise hyperemia in the absence of a tissue PO2 decrease.

The relationship between contraction-induced arteriolar vasodilation, estimated blood flow (BF), and tissue oxygen tension (PtO2) in skeletal muscle of young rats was investigated. Arteriolar diameters, BF, and PtO2 were measured during cremaster muscle stimulation at 2, 4, and 8 Hz. At a suffusate PO2 (PsO2) of 5-10 mm Hg, the caliber of second-order arterioles (2A, greater than 30 micrometer diameter) did not significantly increase after 8 Hz stimulation. In contrast, with the same PsO2, third-order arterioles (3A, less than 30 micrometer diameter) significantly dilated to 127 +/- 9 (SE), 135 +/- 12, and 160 +/- 13% of control, respectively at 2, 4, and 8 Hz stimulation. Third-order arteriolar BFs at the end of the stimulation periods were: 119 +/- 18, 176 +/- 14, and 258 +/- 43% of control, respectively. PtO2 remained essentially constant during and following 4 and 8 Hz stimulation if the systemic arterial blood pressure exceeded 80 mm Hg. When PsO2 was increased to 65-70 mm Hg, neither 3A diameters nor PtO2 during 8 Hz stimulation differed from paired comparisons of the response at low PsO2. These data indicate that dilation of small arterioles during increased muscle metabolic activity can occur without a mandatory change in PtO2. This circumstance is unaffected by a substantially increased supply of oxygen to the tissue.

Animals↗

Effect of inhalate thermal conductivity and high O2 in producing hypothermia.

The effect of an increase in inhalate thermal conductivity and the fraction of inspiratory O2 (FIO2) on the rate of cooling and rewarming using a surface-inhalate heat exchange method was evaluated. Male New Zealand White rabbits were divided into three groups: those ventilated with air, those with 20% O2 + 80% He, and those with 100% O2. All animals were cooled to an esophageal temperature of 22.5 degrees C (or for 180 min maximum). Following a 15-min exposure to room air, the animals were connected to the humidifying and warming system. He-O2 had the highest thermal conductivity and the animals ventilated with it had the fastest cooling rate. One hundred percent O2 and room air had similar thermal conductivities, but the animals ventilated with 100% O2 had significantly lower cooling rates. These data indicate that, while maintaining a constant surface heart exchange, the rate of heat exchange across the lung can be modified by altering the thermal conductivity of the inhalate gas mixture. Total heat exchange can also be modified by hyperoxemia-induced hemodynamic changes.

Acid-Base Equilibrium↗

Tissue oxygen available as a criterion for the effectiveness of continuous positive pressure breathing.

As little as 3-5 cm H2O increase in proximal airway pressure applied to normal lung reduces cardiac output. It is postulated that decreased pulmonary compliance in respiratory distress syndrome (RDS) acts as a barrier thus offsetting this effect. Since cardiac output is not routinely measured, severe reduction in it could accompany regression of disease while maintaining the same airway pressure. This study was undertaken to determine whether tissue oxygen available (O2a) could be used to detect changes in perfusion during continuous positive pressure breating (CPPB). CPPB was evaluated in 10 normal rabbits (CL = 9.5 +/- 1.8 cc/g at 25 cm H2O) and in 10 pulmonary-damaged rabbits (CL = 5.5 +/- 1.4 cc/g at 25 cm H2O) produced by subjecting them to 100% O2. Airway pressure was increased from 0-15 cm H2O in 3 cm H2O increments at 10-min intervals. O2a and PaO2 were monitored continuously. In the normal group, O2a decreased at 3 cm H2O airway pressure, reaching 22% of control at 12 cm H2O, at which pressure PaO2 decreased. Breathing 100% O2 at this airway pressure increased PaO2 to 408 mm Hg, whereas O2a returned to 45% of control. In the experimental group, O2a decreased at 9 cm H2O airway pressure, at 12 cm H2O it was 36% of control at which pressure PaO2 decreased slightly. Breathing 100% O2 at this airway pressure increased PaO2 to 316 mm Hg, and increased O2a to 200% of control. These data indicate that with excessive airway pressure, muscle hypoxia may exist during systemic hyperoxemia and that a low compliance lung exerts a protective effect on O2a. Since changes in cardiac output during CPPB are compliance dependent, and since O2a is perfusion dependent, tissue oxygen available could provide a means of selecting optimal airway pressure during CPPB.

Animals↗

Effect of umbilical artery catheters on blood flow and oxygen supply to extremities.

The effect of catheter placement in the abdominal aorta on the blood flow and oxygenation of lower extremities was evaluated in 30 New Zealand rabbits, weighing 0.55-3.5 kg, by inserting 3.5 and 5.0 French polyvinyl chloride catheters, of the type commonly used for umbilical artery catheterization, through the femoral artery, advancing 15-20 cm, and leaving in place for 10-30 min. Arterial blood pressure (BP), common iliac artery blood flow (BF), gracilis muscle tissue oxygen availability (O2a), and subcutaneous temperature (T) in the foot were continuously monitored before and during catheter placement and after withdrawal. There were no changes in the physiologic variables measured in the contralateral leg when the catheter remained below the aortic bifurcation; however, when the catheter was advanced 15-20 cm into the abdominal aorta, a decrease in lower extremity BF, O2a, and T occurred. Because the length of catheter insertion was maintained constant in each animal, the decreases in BF, O2a, and T are related to the relative dimensions of the vessel and the catheter. The ratio of catheter to vessel diamter, in addition to the site of catheter placement, should be considered during the clinical application of arterial catheters. Reduction in blood flow could be detected by continuous differential monitoring of core and extremity temperature or extremity muscle oxygen availability.

Animals↗

Hypothermia and rewarming induced by surface and He-O2 inhalate temperature control.

Hypothermia and rewarming were induced by a combination of temperature-controlled surface and inhalate methods in rabbits. To facilitate respiratory heat exchange, inhalate-respiratory tract temperature and humidity gradients and thermal conductivity were increased. In addition, the upper respiratory tract was bypassed by an endotracheal tube. To aid in maintaining satisfactory circulatory dynamics, hypercapnia and hypoxia were induced. The combined surface and inhalate method produced a markedly more effective rate of cooling than surface temperature-controlled method alone. Animals survived core temperatures as low as 20.9 degrees C with no complications. The noninvasive simplicity of this method suggests its potential applicability in many clinical situations.

Animals↗

Fasting-induced reduction of intestinal reperfusion injury.

BACKGROUND: Fasting is associated with significant structural, functional, and metabolic alterations in the intestinal mucosa. Before abdominal surgery, patients are usually fasted the night before surgery or for a longer period of time if chronic illness is present. The splanchnic organs may experience varying degrees of ischemia/reperfusion as blood vessels are occluded during the various manipulations. METHODS: To study whether fasting alters intestinal reperfusion injury, rats were fasted for 0 to 2 days, and the mesenteric artery was occluded for 30 minutes and then reperfused for 1 hour. Mucosal atrophy was quantitated by measuring jejunal villus height and crypt depth, and mucosal injury was quantitated by measuring jejunal villus width to villus height and mucosal integrity. To determine whether any effect of fasting on reperfusion injury was due to the absence of luminal nutrients or to a systemic nutrient deficiency, rats were fed parenterally for 7 days before ischemia/reperfusion. RESULTS: A 1-day fast produced significant mucosal atrophy. Reperfusion in the 0-day and 1-day fasted animals produced mucosal injury and additional mucosal atrophy. After a 2-day fast, there was no mucosal injury or mucosal atrophy other than that produced by fasting alone. Parenteral feeding before ischemia/reperfusion did not prevent ischemia/reperfusion induced mucosal atrophy and injury. CONCLUSIONS: The protective effect of a 2-day fast before intestinal ischemia/reperfusion cannot be attributed to the physical and chemical absence of food within the intestinal lumen.

Animals↗