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Biomedical subjects

D L Wiegman

Publications and source records attributed to D L Wiegman.

15 recordsLinked to original sources

Modification of alpha-adrenergic responses of small arteries by altered PCO2 and pH.

Closed-circuit television microscopy was used to measure in vivo small artery (75--140 microns) and vein (105--230 microns) diameters to determine if changes in tissue PCO2 and/or pH would alter the microvascular responses to norepinephrine. Sprague-Dawley rats were anesthetized with a combination of urethane (800 mg/kg) and alpha-chloralose (60 mg/kg). The cremaster muscle with intact circulation and innervation was suspended by sutures in a 60-ml bath which contained a modified Krebs solution (31 degrees C) that was buffered by Tris of bicarbonate. There were four groups of animals with different combinations of bath PCO2 and pH: (1) PCO2 less than 10 mm Hg and pH = 7.2, (2) PCO2 less than 10 mm Hg and pH = 6.9, (3) PCO2 = 60--70 mm Hg and pH = 7.2, and (4) PCO2 = 60--70 MM Hg and pH = 6.9. The maximal responses of the small artery and vein to norepinephrine were similar for the four groups. The artery sensitivity to norepinephrine was significantly lower for group 4 when compared to groups 1, 2 and 3, but there was no effect on small vein sensitivity. Thus, the combination of decreased pH and increased PCO2 reduces small artery sensitivity to norepinephrine in the cremaster muscle of the rat.

Animals

Microvascular and clinical effects of altered peritoneal dialysis solutions.

Blood flow in the peritoneum is one of the more important factors governing the efficiency of peritoneal dialysis. Yet there have been no previous studies which relate alterations and control of the peritoneal microcirculation to dialysis efficiency. Thus, we used closed-circuit television microscopy to quantitative the in vivo response (changes in diameter) to dialysis solutions of the small arteries on the mesothelial surface of the rat cecum and arterioles of the rat cremaster muscle. These responses were correlated wiht solute clearances from multiple peritoneal dialysis performed in humans. In the cremaster, a transient constriction was followed by a prolonged dilation. pH adjustments of the dialysis solution from 5.6 to 7.4 had no effect on the microvascular response and no effect on solute clearances during human peritoneal dialysis. In the cecum, dialysis solution caused a prolonged dilation which reached a maximum in about 10 min. Since dilation appears to be an important determinant of solute clearances during human peritoneal dialysis, the effects of a vasodilator, sodium nitroprusside, were determined. Sodium nitroprusside decreased the time to maximal dilation, which correlated clinically with an increased solute clearance during exchanges with this drug. Since nitroprusside increased clearances of the larger molecular weight solutes proportionally more than the smaller molecular weight solutes did, we hypothesize that nitroprusside increases solute clearances by both a vasodilatory effect and by an effect on vascular membrane permeability and area for solute exchange.

Animals

Microvascular responses to norepinephrine in renovascular and spontaneously hypertensive rats.

Closed-circuit television microscopy was used to quantitate the responses of in vivo small arteries (50-140 micrometer diam) and veins (95-265 micrometer) to topically applied norepinephrine in the cremaster muscle of four groups of urethan-chloralose anesthetized rats. The rat groups were: Sprague-Dawley control (SDC), Sprague-Dawley renovascular hypertensive (RVH), Wistar-Kyoto control (WKY), and spontaneous hypertensive (SHR). The cremaster muscle with intact circulation and innervation was suspended by sutures in a 60-ml bath of bicarbonate-buffered Krebs solution. The vascular responses to the addition of progressively higher concentrations of norepinephrine to the bath were quantitated to obtain concentration-response curves. We found that the RVH (vs. SDC) had a decreased small-artery control diameter and decreased sensitivity to norepinephrine, whereas the SHR (vs. WKY) had tachycardia and decreased small-vein control diameter. Thus, the microvascular characteristics of these two types of hypertension appear to be quite different.

Animals

Peritoneal clearances with three types of commerically available peritoneal dialysis solutions. Effects of pH adjustment and intraperitoneal nitroprusside.

Peritoneal clearances were measured in multiple patients with different types of peritoneal dialysis solution to assess the effects of pH, choice of buffer anion (acetate versus lactate), and the effects of nitroprusside (a vasodilator) in combination with different buffer anions and varying pH. The studies show no differences in peritoneal clearances at very low solution pH (less than 6 as is commonly available) as compared to a pH nearer to 7 or above. There were no diffences between solutions with acetate as compared to those with acetate. Nitroprusside significantly increased clearances in all solutions to a similar extent.

Acetates

Clinical studies with a nonvasoactive peritoneal dialysis solution.

Topical application of dialysis solution to the rat microcirculation causes a transient vasoconstriction for 2 to 3 min. We assessed the clinical importance of this vasoconstriction by developing a dialysis solution without vasoactive properties, as assessed in the microcirculatory laboratory. The solution was of similar composition to human extracellular fluid. We tested its effects on Cur, Ccr, Cin, and dialysate protein concentration. We found that compared to commercial solutions, the lower osmolality of the NVS resulted in loss of ultrafiltration and decreases in clearance of urea and creatinine. The clearance of inulin was unchanged, and dialysate protein increased, suggesting a major increase in diffusive transport of large solutes. Increased diffusive transport of large solutes with NVS suggests that initial vasoconstriction seen in the rat could be present and clinically important during peritoneal dialysis in humans.

Adolescent

Survival and microvascular responses to hemorrhage with three anesthetic combinations.

The effects of different anesthetic combinations on the responses to hemorrhage were investigated while using a single fixed protocol. Small artery (x +/- SE = 112 +/- 3 micron)) and vein (172 +/- 5 micron) responses to hemorrhage were quantitated in the cremaster muscle of 38 Sprague-Dawley rats via closed-circuit television microscopy. Rats were anesthetized intraperitoneally with pentobarbital (50 mg/kg), urethan (800 mg/kg), and alpha-chloralose (60 mg/kg), or urethan (600 mg/kg) and alpha-chloralose (120 mg/kg). After a 15-min control period, arterial blood pressure was lowered to 30 mmHg and maintained at that level for 60 min via hemorrhage from the femoral artery. The hemorrhaged blood was then reinfused, and recovery was monitored for 30 min. Survival was monitored for 7 days. Rats with heavier body weights (greater than or equal to 160 g) had a significantly greater survival rate, 81%, than did the lighter weight rats (less than 160 g), with a 32% survival rate. There were, however, no statistical differences in survival or microvascular responses among rats anesthetized with the three combinations of anesthetics. The combined data for all rats were: survival, 53%; small artery constriction, 45 +/- 2%; and small vein constriction, 21 +/- 3%.

Animals

Anesthesia-induced alteration of small vessel response to norepinephrine.

Closed-circuit television microscopy was used to quantitate the in vivo response of small arteries (approximately 100 micron) and small veins (approximately 150 micron) to topically applied norepinephrine in the rat cremaster muscle. Rats were anesthetized with pentobarbital (50 mg/kg), or urethane (1200 mg/kg) or a combination of urethane (800 mg/kg) and chloralose (60 mg/kg). Complete concentration-response curves were obtained for an artery and vein pair in each rat and pD2 values (-log ED50) were used to evaluate the vascular sensitivity to norepinephrine. Both the artery and the vein in urethane-anesthetized animals had decreased sensitivity to norepinephrine in comparison to the vessels of animals anesthetized with pentobarbital or urethane-chloralose. Pretreatment with cocaine (10(-5) M) significantly increased the sensitivity of both the artery and vein in pentobarbital-anesthetized animals but did not affect the vessels in urethane-chloralose-anesthetized animals. These results are consistent with two opposing effects of the urethane-chloralose combination. The first is an increased sensitivity to norepinephrine via blockade of neuronal uptake and the second is a decreased sensitivity of norepinephrine via a vascular inhibitory effect of urethane.

Anesthetics

Sensitivity of small subcutaneous vessels to altered respiratory gases and local pH.

Television microscopy was used to quantitate the responses of small arteries and veins, in the wings of unanesthetized bats, to alterations in the inspired concentrations of O2 and CO2. Mean arterial pressure, heart rate, and the diameters of small arteries (28-54 mum) and veins (50-128 mum) were measured during a 90-min protocol--30 min with an inspiratory gas mixture of 20% O2 and 80% N2 (control period); 30 min with a gas mixture containing 5% O2 (hypoxic period) or 12, 20, or 28% CO2 (hypercapnic period); and 30 min with the original control gas. The hypoxic responses were dilatation of arteries and no change in the veins in both innervated and surgically denervated wings. Hypercapnia resulted in artery dilatation in innervated wings. Hypercapnia resulted in artery dilatation in innervated wings and constriction in denervated wings. The veins constricted in both innervated and denervated wings during the hypercapnia period. In another series, topical application of Krebs solutions (pH ranging from 7.7 to 6.7) to exposed segments of small arteries and veins produced dilatation of both vessels with decreasing pH. Artery dilatation during hypoxia and vein constriction during hypercapnia involve non-neural mechanisms, while both a neural stimulus for dilatation and a non-neural stimulus for constriction are components in the response of innervated arteries to hypercapnia. The non-neural stimulus for artery and vein constriction during hypercapnia is not a local decrease in pH.

Animals

Continuous measurement of vascular diameters via television microscopy.

In the past 10 years, microcirculation studies have emphasized quantitative measurements of microvascular diameters to characterize in vivo small vessel responses to experimental forcings such as hemorrhage, anesthesia, and hypoxia. We have developed an instrument to obtain continuous diameter measurements of a small artery and vein (40-200 mu) via closed-circuit television microscopy. The outputs are analog voltages proportional to the vessel diameters. Video processing is limited to two image areas termed "windows," which are defined by markers on the monitor and positioned over separate vertically aligned vessels. Each vessel, which appears darker than the surrounding tissue, is located by comparing the video signal to a reference voltage that adapts to changes in the relative contrast within the window. In the presence of a vessel, a ramp voltage is generated, the peak value of which is proportional to the vessel diameter. These peaks are averaged over the 15-video lines of the window and over several video frames to reduce noise sensitivity. In order to accommodate preparation movement such as skeletal muscle contraction, window position and width automatically adapt to changes in vessel position and width. Visual verification of system performance is provided by clamping the video signal to white on that portion of the image which the instrument identifies as vessel.

Arteries

Effect of warm-up on metabolic responses to strenuous exercise.

Aerobic and anaerobic energy transformations were measured in two trained runners during 90-sec treadmill runs at 23.6 km/hr (2% grade). The runs were preceded by rest or either of two warm-ups: 1) 15-min run at 10 km/hr, or 2) 15-min run at 10 km/hr followed by 3-min standing. Compared with runs without warm-up, during the third half minute of runs following both types of warm-up 11% greater heart rates (HR), 8% greater oxygen consumption (Vo2), and unchanged ventilation were recorded. The rate constant of the approach of Vo2 to O2 in the first minute of work was unaffected by warm-up. Runs following either warm-up resulted in 25% lower lactate production; during these runs 3 to 4 degrees C higher gastrocnemius muscle temperatures (Tm) were maintained. The differences in HR, Vo2, and Tm continued throughout exhausting 5-min runs at 20.9 km/hr (2% grade). An elevated muscle temperature may therefore be requisite for the maximal aerobic response to a short exhausting run.

Adaptation, Physiological