Microcystin-LR decreases hepatic and renal perfusion, and causes circulatory shock, severe hypoglycemia, and terminal hyperkalemia in intravascularly dosed swine.

Cross-bred, anesthetized female swine were given intravascularly a lethal (72 microg/kg; n = 6) or toxic-sublethal (25 microg/kg; n = 6) dose of microcystin-LR (MCLR), from Microcystis aeruginosa, or the vehicle (n = 4). At the high dose, from 12 to 18 min after administration, central venous pressure and hepatic perfusion were significantly lower, and shortly thereafter, portal venous pressure was significantly higher and aortic mean pressure was significantly lower than controls. By 45 min postdosing, serum bile acids, lactate, potassium, and total bilirubin, as well as blood pO2, were significantly higher, while hematocrit, platelet count, and blood bicarbonate, pCO2, and base excess were significantly lower than controls. By 90 min, serum arginase, urea nitrogen, inorganic phosphorus, and creatinine were significantly higher, while glucose and blood pH were significantly lower than in controls. By 150 min, serum alanine and aspartate aminotransferases, alkaline phosphatase, lactate dehydrogenase, and creatinine phosphokinase activities were significantly higher than controls. At the low dose, significant differences from controls occurred in hemodynamic, organ perfusion, and serum chemistry parameters, but such changes generally took longer to occur and were of a lesser magnitude than at the high dose. Livers of the high-dose swine were swollen and dark red-purple, and exuded excessive blood on the cut surface. Based on increases in liver weight and liver hemoglobin, 38% of the total blood volume was lost into the liver. Terminally, all high-dose swine experienced hyperkalemia, and most had severe hypoglycemia. Death due to acute MCLR toxicosis in intravascularly dosed swine appears to result from severe intrahepatic hemorrhage, partial obstruction of blood flow through the liver, circulatory shock, severe hypoglycemia, and/or terminal hyperkalemia.

Differential and non-uniform tissue and brain distribution of two distinct 14C-hexachlorobiphenyls in weanling rats.

Excretion and tissue retention of a coplanar and a non-coplanar hexachlorobiphenyl (HxCB) were determined 48 h after a single intraperitoneal (ip) dose of 8 mg/kg radiolabeled [14C]-HxCBs to weanling male and female Long-Evans rats. The objective was to understand the involvement of initial target organs of chlorobiphenyl (CB) accumulation following acute exposure in immature animals. During the short interval, both HxCBs remained sequestered predominantly in mesenteric fat (compared to subcutaneous fat) and less than 1% of the doses were excreted. Excretion was 4- to 8-fold lower than adult rats. Coplanar CB 169 (3,3',4,4',5,5'-HxCB) did not accumulate appreciably in the brain, but was retained at 3-fold higher levels in the liver than was non-coplanar CB 153 (2,2',4,4',5,5'-HxCB). Accumulation of 14C-CB 153 in brains was 4- to 9-fold higher than that of 14C-CB 169 and was adequate to detect non-uniform distribution in serial cryostat sections by phosphor imaging autoradiography. The autoradiographs showed a higher CB 153-derived radioactivity associated with fiber tracts throughout the brain. Specifically, the corpus callosum, internal and external capsules, medial lemniscus, tegmentum of the mesencephalon and metencephalon, and cerebellar peduncles showed significantly higher 14C-CB 153 than the other structures. The 14C-CB 153 was not found in the ventricular system and vascular spaces. These results suggest for the first time that an ortho-substituted PCB congener accumulated preferentially in brain in a structure-specific manner when compared to a non-ortho-substituted PCB congener.

Morphometry of the canine prostate vasculature.

Morphometric data of the tissue vasculature are fundamental to the development of models for blood perfused tissue mass and heat transfer. Vascular casts of six canine prostates were made and morphometry was performed on 14 transverse sections. The region sampled was restricted to the midsection within the parenchyma. General vascular features that were observed include the radially arranged arteries and veins within the parenchyma, the axially oriented periurethral venous plexae, and the parenchymal arteries ramifying less than the veins. The arterial and venous lumen diameters (mean +/- SD) are 84 +/- 31 (N = 42) and 125 +/- 51 (N = 117), respectively. The lengths for a single vessel generation are 2147 +/- 1196 microm (N = 14) and 1265 +/- 693 microm (N = 39) for the arteries and veins, respectively. Intervessel distances are 4056 +/- 2350 microm (N = 33) between arteries, 1526 +/- 982 microm (N = 330) between veins, and 1498 +/- 874 microm (N = 108) between arteries and veins. A simple vasculature model of evenly distributed vessels imbedded in tissue for heat transfer analysis was developed. The artery-artery distance being about three times that of the vein-vein distance suggested a rete-like configuration of arteries surrounded by veins. An effective distance of 1519 microm between vessels was used. Based upon this vasculature model, the vessel density was calculated to be 5.6 arteries/cm(2) and 44.5 veins/cm(2).

Comparison of push-pull versus discard method from central venous catheters for blood testing.

This article evaluates recent research results comparing two different methods for obtaining complete blood cell counts and chemistry profiles from central venous catheters. Complete blood cell count and chemistry profile samples were obtained from 25 patients at three hospital-based infusion clinics. The results indicate no appreciable difference between these two methods. Minimizing risks of blood loss, blood exposure to healthcare personnel, potential specimen contamination, and erroneous reporting are benefits of the push-pull method.

Risks associated with 72- and 96-hour peripheral intravenous catheter dwell times.

BACKGROUND: The risk of complications in peripheral intravenous therapy is higher on the second day of therapy and may continue to increase with time, making routine restarts after 3 days a common practice. The objective of the study was to determine whether the risks of complications after a peripheral i.v. catheter restart after 72 hours are less than the risks of complications if the therapy is continued to 96 hours. METHODS: A retrospective chart review was completed for 722 patients in a community hospital with peripheral i.v. catheters for i.v. fluids or saline locks. Measurements collected were i.v. therapy start date, number of restarts, termination date, and reason for termination; the data were analyzed using risk models. RESULTS: There were 596 uncomplicated therapies. Complications prompted termination in 188 cases. The average duration of therapy was 1.8 days. The probability of complications was least in the first 24 hours, (0.074; standard deviation [SD], 0.013), and increased to 0.176 (SD, +/- 0.026) in the 24- to 48-hour period. The probability of a complication in the 48- to 72-hour period and the 72- to 96-hour period was 0.130 (SD, 0.026). A restarted catheter has a significantly higher risk of complication in its first 24 hours than does an initial catheter. CONCLUSIONS: From these results, the authors conclude that restarting catheters at 72 hours does not reduce the risk of complication in the next 24 hours when compared with simply continuing the therapy with the original catheter. Additional studies should be conducted to justify a policy of automatically restarting therapy after 72 hours.

Thermoregulation in the canine prostate during transurethral microwave hyperthermia, Part I: Temperature response.

In this research, experiments were performed to study thermoregulation in the canine prostate during microwave hyperthermia. The transurethral thermal therapy (T3) system provided by Urologix, Inc. was used to impose microwave heating in the canine prostate. Five types of temperature responses to different microwave power levels as time varies, including both damped and sustained oscillatory temperature responses, have been observed. Decreases in prostatic tissue temperature during the microwave heating are believed to be caused by the increase in local blood flow stimulated by tissue temperature elevations. In this study, the characteristic temperatures and time associated with each response. This work will help to provide a better understanding of how tissue temperature is regulated within the canine prostate during transurethral microwave hyperthermia. Results of the present study offer an experimental foundation for a more detailed theoretical analysis on the temperature distribution based on the power input and local blood perfusion.

Thermoregulation in the canine prostate during transurethral microwave hyperthermia, Part II: Blood flow response.

Recent studies on transurethral-applied local hyperthermia in both the canine and human prostate have revealed significant effects of natural thermoregulation on the therapeutical results in the prostate. Using a thermal clearance method, blood perfusion rates were measured within different regions in the canine prostate under normal and hyperthermic conditions. It has been found that the canine-prostatic blood perfusion is strongly linked to the geometrical location within the gland, the local tissue temperature, and the imposed thermal dosage. Results from this research are expected to provide a better understanding of the thermoregulatory behaviour in the canine prostate, and thus lay an important foundation for predicting tissue temperature in the human prostate during transurethral microwave hyperthermia.

Blood perfusion measurements in the canine prostate during transurethral hyperthermia.

Using a thermal pulse decay technique, blood perfusion rates were measured within different regions in the canine prostate under normal and hyperthermic conditions induced either by the microwave or the radio frequency heating. Results indicate that, under the normal condition, the periurethral region is most highly perfused with an average rate of 0.60 +/- 0.25 ml/min/gm (n = 4) while the perfusion rate is 0.34 +/- 0.22 ml/min/gm (n = 10) in parenchyma. An approximately 3.5 fold increase in perfusion from the respective baselines was observed in both regions when the local tissue temperature was raised to 41.5 degrees C by the microwave heating. Another 0.5 fold increase was found in parenchyma after the tissue was further heated to 43.1 degrees C at which oscillatory behaviors in tissue temperature have been observed. To further study the cause of these oscillatory behaviors, the instantaneous blood perfusion response to changes in local tissue temperature was investigated using the radio frequency heating. It has been revealed that blood flow acts as a feedback of local tissue temperature in a closed control system. The thermally stimulated blood perfusion increase appeared to be a function of tissue temperature and its temporal gradient. Results from this study have shown experimental evidences of local thermoregulation in the prostate during hyperthermia.

Microvascular architecture within the pig kidney cortex.

Corrosion casts of the plastic (Mercox Cl-2B) filled pig kidney cortex vasculature were sliced either parallel or perpendicular to the kidney surface. Scanning electron microscopy photographs were taken of the casts. Montages of the photographs were analyzed using a digitizing tablet and microcomputer-based software. For vessels having diameters larger than 0.05 mm, their sizes, numbers per unit area, and branching patterns were studied with respect to the kidney cortex depth. Vascular branching diameters and angles within the cortex compare favorably with those reported for other major vascular systems. The microvascular dimensions and densities were used to predict the average blood flow velocity within the kidney cortex. It is expected that the results will facilitate a better insight into the contribution of flowing blood to the heat transfer process in perfused tissues.

Recent developments in modeling heat transfer in blood perfused tissues.

Successful hyperthermia treatment of tumors requires understanding the attendant thermal processes in both diseased and healthy tissue. Accordingly, it is essential for developers and users of hyperthermia equipment to predict, measure and interpret correctly the tissue thermal and vascular response to heating. Modeling of heat transfer in living tissues is a means towards this end. Due to the complex morphology of living tissues, such modeling is a difficult task and some simplifying assumptions are needed. Some investigators have recently argued that Pennes' interpretation of the vascular contribution to heat transfer in perfused tissues fails to account for the actual thermal equilibration process between the flowing blood and the surrounding tissue and proposed new models, presumably based on a more realistic anatomy of the perfused tissue. The present review compares and contrasts several of the new bio-heat transfer models, emphasizing the problematics of their experimental validation, in the absence of measuring equipment capable of reliable evaluation of tissue properties and their variations that occur in the spatial scale of blood vessels with diameters less than about .2 mm. For the most part, the new models still lack sound experimental grounding, and in view of their inherent complexity, the best practical approach for modeling bio-heat transfer during hyperthermia may still be the Pennes model, providing its use is based on some insights gained from the studies described here. In such cases, these models should yield a more realistic description of tissue locations and/or thermal conditions for which the Pennes' model might not apply.

Theoretical analysis of the large blood vessel influence on the local tissue temperature decay after pulse heating.

The influence of a large blood vessel (larger than 500 microns in diameter) on the local tissue temperature decay following a point source heating pulse was determined numerically using a sink/source method. It was assumed that the vessel was large enough so that the temperature of blood flowing within it remained essentially constant and was unaffected by any local tissue temperature transients. After the insertion of a point source heating pulse, the vessel influence on the local tissue transient temperature field was estimated by representing the vessel as a set of negative fictitious instantaneous heat sources with strength just sufficient to maintain the vessel at a constant temperature. In the surrounding tissue, the Pennes' tissue heat transfer equation was used to describe the temperature field. Computations have been performed for a range of vessel sizes, probe-vessel spacings and local blood perfusion rates. It was found that the influence of a large vessel on the local tissue temperature decay is more sensitive to its size and location rather than to the local blood perfusion rate. For a heating pulse of 3s duration and 5mW of power, there is a critical probe-vessel center distance 7R (R, vessel radius) beyond which the larger vessel influence on tissue temperature at the probe can be neglected.

Insonation of fixed porcine kidney by a prototype sector-vortex-phased array applicator.

The sector-vortex applicator, an ultrasound phased array with a geometric focus having multiple sectors and tracks, can directly synthesize, without scanning, diffuse focal patterns useful for hyperthermia. A perfused tissue phantom, consisting of an alcohol-fixed porcine kidney with thermocouples placed in the cortex, is insonated by a prototype sector-vortex applicator with 16 sectors and two tracks at an ultrasound frequency of 750 kHz. Steady-state temperature distributions are measured for a wide range of perfusion rates. Results demonstrate that the radius of the heated region can be controlled effectively by choosing the focal mode of the applicator as it is predicted by theoretical analysis.

Vascular anatomy of the pig kidney glomerulus: a qualitative study of corrosion casts.

Pig kidney glomerular vascular anatomy was studied by scanning electron microscopy of vascular corrosion casts. A generalized vascular architecture is presented to describe the pig kidney glomerulus based upon the observation of 3,800 vascular cast glomeruli. The relative simplicity of the pig glomerular vascular architecture has allowed the characterization of different vascular segments more completely than has been possible in other mammals. Based upon relationships to the afferent arteriole, a nomenclature and definition of primary, secondary, tertiary and anastomotic vessels is proposed for the distributing vessels comprising the glomerular tuft. The existence and formation of a large central hemispheric vessel deep within the confines of a glomerular hemisphere is micrographically documented. Micrographic evidence is presented supporting the formation of the single efferent arteriole by the merging of two central hemispheric vessels within the confines of the glomerular tuft. Failure of the merging of these two vessels may result in multiple efferent arterioles.

Use of a thermal pulse decay system to assess avian renal blood flow during reduced renal arterial perfusion pressure.

Using a simplified avian kidney model, renal arterial perfusion pressure (RAPP) was reduced from 120 (control) to 70 mmHg (near the glomerular filtration rate autoregulatory limit) and then to 46 mmHg (below the glomerular filtration rate autoregulatory range) in kidneys with ambient or partially restricted renal portal flow. Renal blood flow (RBF) was measured with a thermal pulse decay (TPD) system, using TPD thermistor probes inserted at three locations to evaluate regional differences in RBF. The clearance (CPAH) and extraction of p-aminohippuric acid were used to calculate renal plasma flow (RPF). CPAH, RPF, and RBF values were consistently lower for kidneys with restricted portal flow than for kidneys with ambient portal flow. Reducing RAPP to 46 mmHg did not significantly reduce CPAH, RPF, or RBF in the ambient group but did significantly reduce CPAH and RPF (regressed on RAPP) in the restricted group. RBF was not significantly affected when RAPP was reduced in the restricted group, although significant regional differences in blood flow were recorded. Renal vascular resistance decreased significantly as RAPP was reduced to 46 mmHg in the ambient group, confirming the renal autoregulatory response. In separate validation studies, significant reductions in RBF were detected by the TPD system during acute obstructions of portal and/or arterial flow. Overall, the results support previous evidence that avian RBF remains constant over a wide range of RAPPs. Observations of nonuniform intrarenal distributions of portal blood flow suggest that the portal system maintains the constancy of RBF in regions with proportionately high portal-to-arterial flow ratios.

Timed acid bath effects on kidney podocytes prepared for scanning electron microscopy.

In perfusion fixation of dog kidney glomeruli, observation of tear fractured surfaces by scanning electron microscopy reveals the deposition of "debris" on the surface of glomerular visceral epithelium (podocytes) that is not deposited on other kidney tissue surfaces. It is of concern to remove this debris without damage to tissue surfaces. A 5 minute bath in 8N HCl (hydrochloric acid) following postfixation in 1% OsO4 (osmium tetroxide) removes only some of the debris. A 10 minute acid bath removes this debris without visible damage to podocyte surface structures such as cilia, plicae or blebs. A 20 minute acid bath is destructive to these surface features.

Indomethacin attenuation of hepatic perfusion and plasma 6-ketoPGF1 alpha elevations following glutathione depletion in rabbits.

Glutathione (GSH) is important in detoxification and regulating cyclooxygenase activity. Since the liver has high levels of GSH, xenobiotic-induced changes in hepatic GSH could affect hepatic tissue blood perfusion (HP) via alterations in prostaglandin synthesis. In anesthetized male New Zealand rabbits, elevating GSH with GSH monoethyl ester had no affect on HP. Treatment of rabbits with diethyl maleate to deplete GSH also had no affect on HP in animals previously given GSH monoethyl ester. However, HP increased within 20 min in rabbits treated with diethyl maleate prior to GSH monoethyl ester. In another experiment, a similar rise in HP following GSH depletion was accompanied by arterial plasma 6-ketoPGF1 alpha (the stable metabolite of prostacyclin) levels that were 4-times higher than in the controls. Plasma TxB2 (the stable metabolite of thromboxane) also increased following diethyl maleate, but only to levels that were 25-times lower than for 6-ketoPGF1 alpha. Since indomethacin blocked the rise in HP, as well as the increases in 6-ketoPGF1 alpha and TxB2, these results indicate changes in HP may occur following GSH depletion as a result of increased synthesis of one or more arachidonic acid metabolites and implicate prostacyclin as a possible mediator of this phenomenon.

A perfused tissue phantom, for ultrasound hyperthermia.

A perfused tissue phantom, developed as a tool for analyzing the performance of ultrasound hyperthermia applicators, was investigated. The phantom, consisting of a fixed porcine kidney with thermocouples placed throughout the tissue, was perfused with degassed water by a variable flow rate pump. The phantom was insonated by an unfocused multielement ultrasound applicator and the temperatures in the phantom were recorded. The results indicate that for testing protocols where tissue phantoms are needed, the fixed kidney preparation offers an opportunity to use a more realistic phantom than has previously been available to assess the heating performance of ultrasound hyperthermia applicators.

A technique for measuring the thermal conductivity and evaluating the "apparent conductivity" concept in biomaterials.

A simple technique for measuring thermal conductivity of biomaterials is described. The method is based on depositing a pulse of heat into the material of choice, and fitting the subsequent local temperature decay to that predicted by a theoretical model. This transient method is most suitable in situations where frequent measurements of the thermal conductivity are desired. The method was evaluated by calculating the thermal conductivity of several inert materials. The measured conductivities compared well with published values. The developed technique was also used to examine the applicability of the "apparent conductivity" index to combine both conductive and blood-convective thermal effects in living, blood perfused tissues. Using both simulated and experimental results, it was shown that the changes in the apparent conductivity are highly correlated with changes in blood flow. However, quantitative application of this index must be restricted to conditions that are similar to those which existed at the time the apparent conductivity was measured.

Relationships between renal hemodynamics and plasma levels of arginine vasotocin and mesotocin during hemorrhage in the domestic fowl (Gallus domesticus).

1. Renal tissue blood flow (renal perfusion) and plasma levels of arginine vasotocin (AVT) and mesotocin (MT) were measured in anesthetized chickens before and during hemorrhage. 2. Renal perfusion did not decrease (P less than 0.05) until nearly 50% of the blood volume had been removed. The decrease in renal perfusion was not related to arterial blood pressure but was concomitant with an increase (P less than 0.05) in plasma AVT levels. 3. Renal perfusion during hemorrhage was positively correlated with plasma MT levels by the regression equation: renal perfusion = 0.091 (MT)-1.1459 which was highly significant (P less than 0.001, r2 = 0.95). 4. The results of this study suggest that MT as well as AVT may participate in regulating blood flow in the avian kidney.

Effect of hemorrhage on hepatic tissue blood flow in the domestic fowl (Gallus domesticus).

1. Thermal Pulse Decay (TPD) methodology was used to monitor hepatic tissue blood flow (hepatic perfusion) in anesthetized birds prior to and during hemorrhagic hypotension. 2. Hemorrhage was accomplished by periodic removal of blood through a carotid cannula. Reducing the estimated blood volume (BV) from 100 to less than 50% decreased hepatic perfusion from 4.36 +/- 0.7 to 1.88 +/- 0.7 ml/min/g. 3. Changes in hepatic perfusion during the experiment were related to mean arterial blood pressure (MABP) by the following linear regression equation: hepatic perfusion = -1.79 +/- 0.0807x (r2 = 0.57).