Biomedical subjects
D L Wiegman
Publications and source records attributed to D L Wiegman.
Visualization of renal autoregulation in the split hydronephrotic kidney of rats.
The autoregulatory ability of the renal vascular system in the split hydronephrotic kidney was quantitated with intravital microscopy. The luminal diameters of the arcuate and interlobular arteries as well as the afferent and efferent arterioles were measured. Glomerular blood flow was determined by the dual slit technique. In the first series of experiments, the renal perfusion pressure was reduced by graded clamping of the abdominal aorta. Pressure reduction from 118 mm Hg to 95 mm Hg induced dilation of all preglomerular vessels except for the distal afferent arteriole; there was no change in the efferent arteriole and the blood flow was maintained. Further pressure reductions to 71 and 43 mm Hg caused additional dilations of the preglomerular vessels, a marginal reduction in diameter of proximal efferent arterioles and flow reductions by 15% and 41%, respectively. In the second series, systemic blood pressure was increased by continuous i.v. infusions of norepinephrine (NE). NE constricted pre- and postglomerular vessels except for the distal afferent arteriole; glomerular flow was decreased. Reduction of renal perfusion pressure during NE infusion to the preinfusion value did not diminish glomerular blood flow, but reduced the constrictor response to NE in preglomerular vessels. In a third series of experiments we examined the effect of atrial natriuretic factor (ANF) on renal autoregulation. Addition of ANF (10(-9) to 10(-7) M) to the renal bath induced a dose-dependent dilation of all preglomerular vessels and a constriction of the efferent arteriole. Pressure reduction from 120 to 95 mm Hg resulted in a further preglomerular vasodilation. These experiments demonstrate that autoregulation is mediated primarily by diameter changes in all preglomerular vessels excluding the distal segment of the afferent arteriole. Further, these data suggest that ANF induced dilation of preglomerular vessels does not impair the myogenic response of these vessels.
Angiotensin II control of the renal microcirculation: effect of blockade by saralasin.
The hydronephrotic rat kidney with intact circulation and innervation was split and spread out as a thin sheet in a tissue bath. The microvasculature was observed in vivo via television microscopy. We quantitated the effects of increasing concentrations (10(-9) to 10(-5) M) of saralasin (angiotensin II antagonist) applied locally in the tissue bath on microvascular diameters and on relative glomerular blood flow (measured using fluorescent labeled RBCs). Saralasin produced an increase in preglomerular diameters which was largest (37 +/- 11%) in the interlobular artery (there was no dilation in the afferent arteriole near the glomerulus), an increase in postglomerular diameters which was largest (17 +/- 4%) in the efferent arteriole near the glomerulus, and an increase in blood flow (19 +/- 4%). If these types of findings would hold for the normal kidney, it would suggest a role for angiotensin II in the control of total renal blood flow, in the regional distribution of flow, and in the control of filtration fraction. We also made control micropressure measurements using the servo-nulling approach. Pressures measured were: afferent arteriole, 65 +/- 5 mm Hg; intraglomerulus, 50 +/- 5 mm Hg; and efferent arteriole, 19 +/- 3 mm Hg. These data indicate that there is major vascular resistance near the glomerulus, especially in the efferent arteriole.
In vivo venular changes with the development of one-kidney, one-clip hypertension in the rat.
Television microscopy was used to quantify in vivo resting venular diameters and the responses to topically applied norepinephrine in the cremaster muscle of two groups of urethanchloralose anesthetized rats: normotensive rats (NT) and one-kidney, one-clip Goldblatt hypertensive rats (1K1C). Observations were made two weeks after the surgery which was used to induce renovascular hypertension. At this stage, we have previously observed an increase in arteriolar reactivity (1). In the current study, mean arterial blood pressures for 1K1C (149 +/- 5 mmHg) were significantly higher than pressures for NT (102 +/- 3 mmHg). Venules were categorized by branching order and venular diameters were measured at three different levels of the microcirculation: first (1V), second (2V), and third order (3V) venules. Reactivity to norepinephrine at all venular levels in the 1K1C group was similar to that recorded for the NT group. Resting venular luminal diameters, however, were significantly smaller (20%) for large (1V) venules of the HT group (137 +/- 9 micron) compared to those for the NT group (171 +/- 10 micron). Thus, in contrast to previously reported data for arterioles, a structural venoconstriction and not an increase in venular reactivity appears to characterize the early vascular changes associated with this form of renovascular hypertension.
Anesthetic depression of microcirculation, central hemodynamics, and respiration in decerebrate rats.
The objectives of this study were the development of a skeletal muscle microcirculatory preparation, in which the complications of drug anesthesia were minimized, and the quantitation of the effects of urethan and chloralose anesthesia on the microcirculation. Rats were initially anesthetized with urethan and chloralose and decerebrated by a midcollicular transection. The cremaster skeletal muscle, with intact circulation and innervation, was prepared for intravital microscopy by placement in a tissue bath. Arterioles (9-70 micrometers diam) at several anatomic levels were observed during the initial period of urethan-chloralose anesthesia (period 1), after recovery from the anesthesia (period 2), and again following reanesthetization (period 3). During period 2, respiratory rate, heart rate, and mean arterial pressure were significantly greater than during periods 1 and 3. Smaller arterioles (8-50 micrometers diam) exhibited vasomotion (mean amplitude 35% of mean diameter; mean frequency 31 cycles/min) during period 2. Urethan-chloralose anesthesia during periods 1 and 3 inhibited vasomotion and increased arteriolar diameters by 16-36%. This study quantitates the depressant effects of urethan-chloralose anesthesia on the cardiovascular system and demonstrates the feasibility of using decerebration to circumvent the necessity of continuous drug anesthesia for in vivo microvascular studies.
Hyperosmolality, acetate, and lactate: dilatory factors during peritoneal dialysis.
Factors that alter peritoneal blood flow may influence the clearance of solutes during peritoneal dialysis. Arteriolar vasodilation, for instance, could increase the delivery of solutes to the capillaries and venules leading to an increase in solute transport into the peritoneal cavity. This study was designed to identify the vasoactive effects of several major components of McGaw and Dianeal peritoneal dialysis solutions to understand how the composition of these solutions may alter in vivo blood flow in the peritoneum. Because the major differences between these solutions and Krebs solution are a high osmolality, a high dextrose concentrations, and an acetate or lactate buffer system, we investigated the effects of these components. Rats were anesthetized with the combination of urethane and chloralose. The cremaster muscles, with the nerve and blood supplies from the rat still intact, was placed in a specially designed tissue chamber that was filled with Krebs solutions. A port permitted microscopic observations of the blood vessels. In vivo television microscopy observations was used to quantitate changes in small arteriole diameters induced by changes in the composition of the solution bathing the cremaster or by the addition of nitroprusside. Hyperosmolality produced by the addition of dextrose, sucrose, or sodium chloride to the Krebs solution induced a submaximal dilation of the small arterioles of the cremaster. The rate of dilation differed depending on the substance used to increase osmolality. A normal osmolality acetate (74 mM) or lactate (45 mM) solution produced a slow, submaximal dilation of the cremaster arterioles. Hyperosmolar acetate (37 or 74 mM) or lactate (45 mM) solutions produced a rapid, maximal dilation of these vessels. Because the rate of dilation and maximal effect produced by the commercial dialysis solutions were similar to these same parameters produced by the high-osmolality acetate or lactate solutions, the dilatory effects of McGaw and Dianeal solutions appear to be due to the combinations of high osmolality and the buffer anion acetate or lactate.
muscle microcirculation: effects of tissue pH, PCO2, and PO2 during systemic hypoxia.
The responses of arterioles and venules to systemic hypoxia (fractional inspired O2 concentration 0.10) were determined for the rat cremaster muscle that was positioned with intact nerve and vascular supplies in a tissue bath that had controlled pH, O2 tension (PO2), CO2 tension (PCO2), and temperature. Blood pressure and heart rate were decreased significantly during systemic hypoxia. First- and second-order arterioles actively constricted during systemic hypoxia, whereas most first-, second-, and third-order venules had biphasic responses (dilation followed by constriction). There were no significant differences in the active arteriolar responses to systemic hypoxia when cremaster bath pH was altered from 6.9 to 7.2, or when bath PCO2 was changed from 60 +/- 2.2 to less than 5 mmHg; but, there was significantly greater arteriolar constriction with high bath PO2 (139 +/- 1.3 mmHg) in comparison to low bath PO2 (4.5 +/- 0.5 mmHg). Decreased bath pH, decreased PO2, and increased PCO2 had no effect on the dilation responses of first-, and second-, and third-order venules to systemic hypoxia; however, these bath alterations attenuated the constriction responses of third-order venules. alpha-Adrenergic receptor blockade did not alter the arteriolar responses to systemic hypoxia. Our data indicate 1) that there is a centrally mediated stimulus for constriction of first-order arterioles during systemic hypoxia, 2) that changes in local cremaster PO2, but not PCO2 or pH, can attenuate this centrally mediated arteriolar constriction, and 3) that the centrally mediated arteriolar constriction does not involve alpha-adrenergic receptors.
Decreased vascular sensitivity to norepinephrine following exercise training.
Twenty Sprague-Dawley rats (230 +/- 9 g; mean +/- SE) were exercised daily for 6 wk by swimming 1 h/day with weights (5% of body wt) attached to their tails. Nineteen additional rats (237 +/- 8 g) remained sedentary in their cages. All animals were anesthetized with urethan (800 mg/kg) and alpha-chloralose (60 mg/kg). In the first series of experiments, increasing doses of norepinephrine were injected into the jugular vein and the responses in mean arterial blood pressure was recorded from a cannulated femoral artery. Exercise training had no effect on the maximal increase in blood pressure, but significantly decreased blood pressure sensitivity to norepinephrine, expressed as a pD2 value (=-log ED 50), from 5.64 +/- 0.07 to 5.20 +/- 0.06. In the second series, the cremaster muscle with intact circulation and innervation was suspended in a tissue bath and norepinephrine in increasing concentrations was added to the cremaster bath. The responses of the main arteriole (approximately 110 micron) and venule (approximately 170 micron) were recorded by television microscopy. Exercise training had no effect on vessel diameters of resting muscle or on the maximal vessel constrictions obtained in response to high concentrations of norepinephrine. Arteriole sensitivity to norepinephrine was significantly decreased (pD2 of 6.69 +/- 0.24 vs. 5.96 +/- 0.18) and there was some tendency for reduced venule sensitivity. These data suggest that exercise training in rats produces a decrease in alpha- or an increase in beta-adrenergic receptor sensitivity.
Calcium modulation of microvascular sensitivity during renovascular hypertension.
Explore the source record for details and available documents.
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.
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.
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.
Peritoneal dialysis solutions and the microcirculation.
Explore the source record for details and available documents.
Effects of vasodilators and peritoneal dialysis solution on the microcirculation of the rat cecum.
Explore the source record for details and available documents.
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.
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.
Comparison of the effects of lactate and acetate on clinical peritoneal clearances.
Peritoneal clearances of urea, creatinine, inulin and dialyzate protein concentration were compared in ten patients using dialysis solutions containing either lactate or acetate. No significant differences were found between solutions containing lactate or acetate.
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%.