An electrode array that minimizes blood loss for radiofrequency-assisted hepatic resection.

Hepatic resection is currently the standard treatment for liver cancer. During hepatic resection part of the liver containing the tumor is surgically removed. This type of surgery is accompanied by high blood loss of approximately 0.6-1.35 L. Blood loss is associated with increased complication rates, prolonged hospital stay, and reduced patient survival, especially when transfusion is required. Other researchers have suggested using radiofrequency (rf) or microwave ablation to coagulate a tissue slice before resection to reduce blood loss, but conventional devices typically take several hours. We developed a device consisting of a linear array of blade-shaped, 1 cm wide radiofrequency (rf) electrodes 1.5 cm apart. Bipolar rf power is applied between pairs of adjacent electrodes, leading to high tissue temperatures between the electrodes that promote coagulation of large vessels (>3 mm) in the resection plane. Rapid switching of applied power between pairs of adjacent electrodes allows simultaneous heating and coagulation of the entire resection plane within 3-6 min. In seven in vivo trials in a porcine model, resection along a plane pre-coagulated with the device resulted in little (<20 mL) to no blood loss, while coagulating all vessels (up to 4.5 mm diameter in this study). Average treatment time (from placement of the device to transection) was 6.8+/-0.5 min when four electrodes were used, and 11.3+/-1.2 min when 5-7 electrodes were used. This device may reduce blood loss related morbidity during resection and reduce treatment time by coagulating all vessels in the resection plane.

Effects of phenobarbitone, cinnarizine, and zoxazolamine on the development of right ventricular hypertrophy and hypertensive pulmonary vascular disease in rats treated with monocrotaline.

The results of this experiment suggest that the addition of zoxazolamine to the diet may prolong the survival and reduce the incidence of right ventricular hypertrophy and hypertensive pulmonary vascular disease in male rats given a single subcutaneous injection of monocrotaline. Phenobarbitone and cinnarizine were ineffective.

Relation between pulmonary transvascular fluid filtration rate and measured Starling's forces after major burn.

Our purpose was to determine the reliability of the currently used measurements of pulmonary vascular hydrostatic and oncotic pressures in monitoring pulmonary water after a major burn. The flow of pulmonary lymph, a reliable indicator of the rate of filtration of pulmonary transvascular fluid (Qf), was measured before and for 72 hours after a third-degree burn over 40 to 55 percent of the total body surface in sheep. Changes in Qf were correlated with measured changes in pulmonary microvascular (Pmv), plasma colloid osmotic pressure (pi p), and interstitial colloid osmotic pressure (pi i), as measured in the pulmonary lymph. The periods from 0 to 24 hours (resuscitation), from 24 to 48 hours (early mobilization of fluid), and from 48 to 72 hours (early recovery) were compared with baseline. Regression equations and correlation coefficients for Qf vs Pmv, Qf vs Pmv minus pi p, and Qf vs Pmv minus (pi p -ph i), the oncotic gradient, were calculated. There were significant differences in slopes between the periods of time, with all three comparisons indicating that the response of the microcirculation to the same changes in pressure was different in each of the periods. The correlation between Qf and the comparisons of pressures was clearly best in the period from 48 to 72 hours. The comparison of Pmv minus pi p was not better than Pmv alone, while the comparison of Pmv minus the gradient (pi p -- pi i) was significantly better than either of the other comparisons in predicting Qf.

Prolonged perfusion with a membrane oxygenator in awake ponies.

Prolonged extracorporeal membrane oxygenation (PEMO) was performed in 6 adult ponies with the membrane oxygenator in vein-to-artery bypass circuit. A flow rate equal to 46 per cent of control cardiac output was diverted through the PEMO circuit of 10 to 24 hours. Three of the 6 ponies were perfused for at least 20 hours and developed no complications. Immediately following initiation of PEMO, left ventricular output decreased; however, in the interval between 6 and 24 hours, left ventricular output was increased above control levels. Aortic pressure and left ventricular work were markedly elevated during PEMO. Pulmonary ventilation and oxygen uptake also decreased initially but were elevated during later stages of bypass. Pulmonary compliance did not change, except in those studies in which problems were encountered with perfusion techniques. Hepatic glycolysis and hyperglycemia occurred and were more severe in ponies with catheter-produced thrombi. Marked diuresis, which could be attributed only partially to the hyperglycemia, was present throughout PEMO. Based on the minimal morphologic changes observed in the ponies, extracorporeal circulation diverting one half of the cardiac output through a membrane oxygenator can be safely performed for up to 24 hours.

Comparison of iodinated contrast media-induced renal vasoconstriction in human, rabbit, dog, and pig arteries.

RATIONALE AND OBJECTIVES: Contrast media (CM)-induced renal vasoconstriction is an important factor in the pathogenesis of CM-induced nephrotoxicity. The effects of ionic, high-osmolar CM sodium/meglumine diatrizoate and nonionic, low-osmolar CM iohexol and iopamidol were studied in rabbit, dog, and pig renal arteries and compared with human tissue in an organ bath. METHODS: Isometric contractions were induced by increasing concentrations of CM and high-osmolar glucose solution. RESULTS: Contrast media and glucose elicited contractions in human renal arteries of 32% (diatrizoate), 20% (iohexol), 30% (iopamidol), and 22% (glucose). Rabbit and dog renal arteries demonstrated contractions of 30% and 46% (diatrizoate), 15% and 23% (iohexol), 15% and 26% (iopamidol), and 11% and 40% (glucose), respectively, of the control. There was a vasorelaxing effect of all CM tested on pig renal artery. CONCLUSIONS: Responses in rabbit and dog renal arteries were similar to those in human renal arteries and could serve as models for investigating CM-induced renal vasoconstriction.

Anti-platelet agents reduce morphological changes of chronic hypoxic pulmonary hypertension.

The pathophysiologic mechanism by which chronic hypoxia causes pulmonary hypertension is unknown. If anti-platelet agents, or other pharmacologic interventions, altered the pulmonary vascular changes induced by hypoxia, information concerning the pathogenesis of the pulmonary hypertension or the potential therapeutic usefulness of the drugs might be obtained. In Study 1, rats exposed to chronic hypobaric hypoxia (PB = 520 mmHg) had a pulmonary arterial medial thickness of 6.7 +/- 0.6 mu compared to 4.1 +/- 0.2 mu* for control, normoxic rats (*p less than 0.05). Administration of dipyridamole (2mg/kg/day), or sulfinpyrazone (11 mg/kg/day) in the drinking water reduced the medial thickness to 5.0 +/- 0.3 mu* and 5.4 +/- 0.5 mu* respectively, thus suggesting the possible involvement of platelets in the response of the media to chronic hypoxia. In Study 2, hypoxic rats treated with the calcium blocker, flunarizine, were found to have less medial hypertrophy than a control group of hypoxic rats. This observation suggests that a decrease in transmembrane calcium flux may also reduce medial hypertrophy.

Response of the pulmonary microcirculation to fluid loading after hemorrhagic shock and resuscitation.

We compared the response of the pulmonary microcirculation to fluid overload before and 24 hours after hemorrhagic shock, resuscitated with either blood or crystalloid, to determine whether vascular permeability was altered, making the lung more susceptable to fluid overload after shock and whether this response differed depending on the type of resuscitation fluid. Fourteen unanesthetized sheep with chronic lung lymph fistula were given a fluid challenge (one half of blood volume) before and 24 hours after hemorrhagic shock. Seven sheep were resuscitated after whock with shed blood and seven sheep were resuscitated with Ringer's lactate alone equal to 2.5 times the amount of shed blood. Pulmonary vascular pressures and lung lymph flow Ql were at baseline in both groups 24 hours after resuscitation except for the decreased plasma oncotic pressure pi p in the crystalloid group. Interstitial oncotic pressure, pi i was also lowered in this group such that the gradient (pi p-pi i) remained at baseline. In the blood group, pulmonary vascular pressures and QL increased transiently after fluid loading before and after shock with the mean time for QL to return to baseline being 5.5 and 5.9 hours for the preshock and postshock periods, respectively. In the crystalloid group, fluid loading after shock produced an increase in pulmonary vascular pressures resulting in a significant increase in QL over the preshock fluid response with the mean time for QL to return to baseline being 10.1 hours. However, changes in the value of (pi p-pi i) were identical to those seen before shock. Therefore we noted that 24 hours after shock, lung permeability was not significantly altered but crystalloid resuscitation did make the lung more susceptible to volume overload.

The effect of plasma oncotic pressure on the pulmonary microcirculation after hemorrhagic shock.

Plasma oncotic pressure is considered to be an important factor in controlling lung water after hemorrhagic shock. However, it is the gradient between plasma and interstitial oncotic pressure which affects the pulmonary transvascular fluid filtration rate, Qf. Our objective was to determine the effect of decreasing plasma oncotic pressure, pip, on Qf, on interstitial oncotic pressure pii, and on the oncotic gradient. Chronic lung lymph fistulas were created in 16 sheep. Lymph flow, a reliable index of Qf, plasma and lymph (equal to interstitial) oncotic pressures, and vascular pressures were monitored in unanesthetized sheep, before and during hemorrhagic shock (50% blood volume), during resuscitation (3 hours), and during recovery (24 hours). Resuscitation was either with shed blood or lactated Ringer's solution in sufficient quantity to return left atrial pressure and cardiac output to baseline levels. During resuscitation with blood, lymph flow increased by 115%. The pip remained constant, while pii decreased, increasing the oncotic gradient. Crystalloid resuscitation produced on increase in lymph flow equal to that in the blood group at 120% over baseline; however, pip decreased by 50%, producing an oncotic gradient 4 mm Hg less than that of blood group. This was not reflected by a difference in Qf between the groups. During recovery Qf returned to baseline in the blood group and in most of the crystalloid group, as the oncotic gradient returned to baseline, despite a significant decrease in pip due to a compensatory decrease in pii. We conclude that during resuscitation Qf does not appear to be increased by a decrease in the oncotic gradient. During recovery a major decrease in pip can be compensated for rapidly by a decrease in pii, leading to no change in interstitial fluid content.

Pulmonary pressor responses in sheep to chemically defined precursors of E. coli endotoxin.

The toxicity of various monosaccharide and disaccharide endotoxin precursors has now been studied in sheep. We measured the early pulmonary arterial pressure responses after injections of the monosaccharides lipid X (2,3-diacylglucosamine 1-phosphate) and MAGP (2-monoacylglucosamine 1-phosphate), of the tetraacyl disaccharide diphosphate precursor of lipid A, IV-A (Federation Proc. 43: 1567, 1984), and of Escherichia coli bacterial endotoxin (lipopolysaccharide). We also measured the response of lipid X after prior administration of indomethacin and MAGP. Lipid X, at a total cumulative dose of 40 micrograms/kg, produced an immediate, but transient dose-dependent pulmonary arterial vasoconstrictive response. MAGP, at a total dose of 40 micrograms/kg, had no pulmonary pressure activity but did increase extravascular lung water and produce some histological changes in the lung. Disaccharide precursor IV-A, at a total dose of 40 micrograms/kg, produced an immediate dose-dependent pulmonary arterial vasoconstrictive response that was prolonged for greater than 2 h. E. coli endotoxin caused a delayed (15-min) increase in the pulmonary arterial pressure but one that also persisted for greater than 2 h. Prior administration of indomethacin blocked the pulmonary pressor activity of lipid X, whereas prior administration of MAGP increased both the magnitude and the duration of the pulmonary pressure response of lipid X. We conclude that the initial pulmonary hypertension seen after lipid X injection may involve cyclooxygenase-dependent formation of prostaglandins and that the genesis of this pulmonary pressor activity is at least in part dependent on the ester-linked hydroxymyristoyl moiety at position 3 of the lipid X molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary pathophysiological changes in sheep caused by endotoxin precursor, lipid X.

The chemical structure of the biologically active lipid A portion of Gram-negative endotoxin [lipopolysaccharide (LPS)] has recently been elucidated. This was greatly facilitated by the isolation of an Escherichia coli mutant that accumulates large quantities of lipid X, a novel monosaccharide precursor of lipid A (C. R. H. Raetz, Rev. Infect. Dis. 6: 463-471, 1984). We now report on the activity of lipid X in the lung-lymph model in sheep. We have measured the response to cumulative bolus injections of lipid X (2,3-diacylglucosamine 1-phosphate) in six chronically instrumented unanesthetized sheep. Lipid X at a total dose of 40 micrograms/kg produced a biphasic pattern of changes. The early phase was characterized by a rapid transient pulmonary arterial constrictive response that was dose dependent, accompanied by a delayed transient increase in lung-lymph flow (P less than 0.05), a significant (P less than 0.01) decrease in arterial blood O2 tension and an increase (P less than 0.05) in lung-lymph protein clearance. Protein permeability changes in the first phase are not usually seen following endotoxin injection. However, like endotoxin, lipid X also produced a late phase (3-6 h later) of increased lung vascular permeability to fluid and protein as reflected by significant (P less than 0.05) increases in both lung-lymph flow and lung-lymph protein clearance in the presence of stable pulmonary vascular pressures at or below base-line levels. We conclude that some of the pulmonary pressor activity of the endotoxin molecule can be attributed to the lipid X substructure. Furthermore, changes in vascular permeability may also be initiated by this substance.

Enhancement by histamine of the contractile effects of leukotriene D4 on extralobar pulmonary arteries isolated from the guinea pig.

A 5 min pretreatment of the proximal half of the main pulmonary artery (PM) with a concentration of histamine that produced a small degree of contraction (about 8% of maximum) resulted in a large increase in the contractile responses produced by cumulatively increasing concentrations of leukotriene D4 (LTD4). LTD4-induced responses in the distal half of the main artery and the right and left main arterial branches were not markedly altered by concentrations of histamine that produced a magnitude of contraction similar to that produced in the PM segment. The data demonstrate that the potentiative interaction between histamine and LTD4 is not dependent on the contractile event per se.

Relaxation of isolated guinea pig trachea, bronchi and pulmonary arteries produced by vasoactive intestinal peptide (VIP).

Vasoactive intestinal peptide (VIP) relaxed isolated guinea pig airways contracted with carbamylcholine and isolated pulmonary arteries contracted with prostaglandin F2 alpha. VIP was more potent as a relaxant agonist on trachea than on bronchi but was equipotent on the main and branch pulmonary artery. The VIP-induced relaxation of either airway or artery segments was not altered by pretreatment of animals with reserpine or pretreatment of isolated tissues with propranolol, metiamide, indomethacin or theophylline. These results are consistent with a direct relaxant effect by VIP in guinea pig lung.

Studies on segmental differences in sensitivity to adrenergic agonists in pulmonary arteries isolated from the guinea-pig.

This study was designed to examine the existence and possible mechanisms of segmental differences in sensitivity to adrenergic substances in the pulmonary vasculature of the guinea pig. The main pulmonary artery was found to be less sensitive to epinephrine, norepinephrine and phenylephrine than its left and right main branches. Because there were no differences in sensitivities between the left and right branches, most comparisons were made between the main and left branches. The difference in sensitivity was larger for adrenergic agonists which are known to be taken up by adrenergic neurons (epinephrine, norepinephrine, phenylephrine) than for an agonist which is not taken up by these neurons (methoxamine). The left artery from reserpine-treated animals was only slightly more sensitive (1.5-fold) to barium chloride than the main pulmonary artery. Cocaine potentiated to a greater extent in the main than in the left pulmonary artery the amines which are taken up by adrenergic neurons. The left arterial branch was less responsive to transmural electrical stimulation than the main artery in the absence and presence of cocaine. [3H]Norepinephrine uptake was larger in main arterial segments than in the branches and histochemical fluorescence studies demonstrated a greater degree of adrenergic innervation in the proximal segments. The results indicate that a major explanation for the differences in sensitivity between the vascular segments is a smaller degree of adrenergic neuronal uptake of agonist in the arterial branches.

Effects of leukotrienes on isolated guinea-pig pulmonary arteries.

Leukotrienes C4 (LTC) and D4 (LTD) produced contractions of the isolated guinea-pig pulmonary arteries, but were much less potent in these segments than in the isolated trachea and parenchymal strip from the same species. Among the arterial segments, the leukotrienes were more effective in contracting the distal end of the main pulmonary artery than the arterial branches. FPL55712 was an effective competitive antagonist of LTC, but not LTD, in the arterial segments. The data suggest that the pulmonary arteries may possess leukotriene receptors which differ from those of airway smooth muscle.

Comparative vasodilation of peroxynitrite and 3-morpholinosydnonimine.

Vasorelaxation mediated by peroxynitrite (ONOO-) and 3-morpholinosydnonimine (SIN-1) were investigated in isolated bovine intramammary arteries. Both ONOO- and SIN-1 relaxed U 46619-precontracted rings in a dose-dependent, endothelium-independent manner. Pretreatment with an adenylyl cyclase inhibitor, SQ 22536 [(9-tetrahydro-2-furyl)adenine], resulted in an enhanced ONOO--mediated relaxation, but did not modulate the response to SIN-1. ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one), a potent and selective inhibitor of soluble guanylyl cyclase (sGC), did not significantly affect relaxant actions of ONOO-, but ODQ markedly attenuated SIN-1-elicited relaxation with a rightward shift in the dose-response curve and an unaltered maximal response. In the presence of carboxy-PTIO (2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide), a putative nitric oxide scavenger and ONOO- inactivator, the relaxant response to ONOO- was abolished, while relaxant actions of SIN-1 appeared to be unaffected. The results reveal a difference between ONOO- and SIN-1-mediated relaxation with regards to the role of the sGC and suggest that ONOO--evoked relaxation may not be associated with sGC activity, but rather depends on an sGC-independent mechanism triggered by ONOO- and/or NO itself. It also re-emphasizes that SIN-1 induces a vasorelaxant response, in part, via stimulation of sGC.

A new catheter design using needle electrode for subendocardial RF ablation of ventricular muscles: finite element analysis and in vitro experiments.

Radio-frequency (RF) cardiac ablation has been very successful for treating arrhythmias related with atrioventricular junction and accessory pathways with successful cure rates of more than 90%. Even though ventricular tachycardia (VT) is a more serious problem, it is known to be rather difficult to cure VT using RF ablation. In order to apply RF ablation to VT, we usually need to create a deeper and wider lesion. Conventional RF ablation electrodes often fail to produce such a lesion. We propose a catheter-electrode design including one or more needle electrodes with a diameter of 0.5-1.0 mm and length of 2.0-10 mm to create a lesion large enough to treat VT. One temperature sensor could be placed at the middle of the needle electrode for temperature-controlled RF ablation. From finite element analyses and in vitro experiments, we found that the depth of a lesion is 1-2 mm deeper than the insertion depth of the needle and the width increases as we increase the diameter of the needle and the time duration. We showed that a single needle electrode can produce a lesion with about 10-mm width and any required depth. If a wider lesion is required, more than one needle with suggested structures can be used. Or, repeated RF ablations around a certain area using one needle could produce a cluster of lesions. In some cases, a catheter with both conventional electrode and needle electrode at its tip may be beneficial to take advantage of both types of electrode.

Acute cardiotoxicity of moniliformin in broiler chickens as measured by electrocardiography.

Electrocardiography was used to examine the acute cardiotoxic effects of moniliformin on 3-week-old broiler chickens. Each of the seven pairs of anesthetized birds (pentobarbital sodium, 40 mg/kg body weight, intramuscular) was injected intravenously with moniliformin (1 mg/kg body weight) or an equal volume of normal saline (1 ml/kg body weight), and changes in electrocardiogram were monitored for 50 minutes. Three of the seven birds injected with moniliformin died within 50 minutes post-injection. Moniliformin caused a bradycardia, which became highly significant (P < 0.05) within 15 minutes post-injection. The P-R, Q-T, and S-T intervals of moniliformin-injected birds were significantly lengthened throughout the 50-minute observation (P < 0.05). The results indicate that the moniliformin-induced mortality is due primarily to cardiac failure.

In vivo measurements of heat transfer on the endocardial surface.

A catheter-based instrument was used to measure the heat transfer on the right atrial and ventricular endocardial surfaces of two pigs in vivo. The heat transfer parameters will assist in calculating the proper dose for radio-frequency ablation. The time constant of the device was 0.05 s. It was found that the average heat convection coefficient varies significantly both spatially and temporally on the endocardium. The average heat convection coefficients found were between 510 and 4800 W m(-2) K(-1).

Relationship between the measured and calculated colloid osmotic pressure of plasma and lung lymph in the sheep.

The colloid osmotic pressure of plasma, pi p, and lung lymph pi i, in the adult sheep was measured with a membrane osmometer and calculated from the protein content using the Landis and Pappenheimer equation. Measured (M) plasma oncotic pressure was 6 mm Hg lower than calculated (C), for normal sheep plasma. The difference between (M) and (C) decreased as protein content decreased. The (M) lymph value, considered to be equal to interstitial fluid, was only 1 mm Hg lower than (C) for normal lymph. This resulted in a difference between the calculated and measured oncotic gradient (pi p-pi i) of nearly 5 mm Hg. This difference decreased as protein content decreased in plasma and lymph. The difference between measured and calculated values may in part be explained by the differences in A/G ratio between human and sheep plasma and between sheep plasma and lymph. Measured oncotic pressure in plasma and lymph after severe hemorrhagic and endotoxic shock did not differ significantly from that in the normal animal.

Lactic dehydrogenase activity in lung lymph during hemorrhagic shock, resuscitation and recovery.

Lactic dehydrogenase activity was determined in lung lymph before, during and after hemorrhagic shock to determine if this insult produced pulmonary cellular damage. Lung lymph flow and lymph protein content, reliable indices of fluids filtration rate and microvascular protein permeability were also monitored. The experiment was performed in unanesthetized sheep with a chronic lung lymph fistula. Lymph flow, lymph LDH and protein content did not change during the period of shock. Lymph flow increased significantly during resuscitation but lymph LDH and protein content decreased in relation to plasma values indicating the sieving effect of the microvascular membrane for protein to be intact. The increased flow was most likely caused by an increase in microvascular hydrostatic pressure. Plasma LDH was significantly increased during the 72 hour recovery period with lymph flow, lymph protein and lymph LDH being normal. We therefore found that hemorrhagic shock produced a systemic cellular injury reflected in an increased plasma LDH activity. No pulmonary cellular damage was noted.