Evaluation of an indirect oscillometric blood pressure monitor in anaesthetised dogs at three different anatomical locations.

AIMS: To evaluate the agreement between invasive and non-invasive measurements of blood pressure (BP) using an oscillometer (PetTrust) at three different anatomical locations in anaesthetised dogs under different haemodynamic conditions. METHODS: Eight adult Greyhounds weighing 23.5-36.5 kg were anaesthetised with isoflurane and positioned in dorsal recumbency. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) were measured invasively via a dorsal pedal artery and non-invasively using the oscillometer with cuffs placed above the carpus, above the tarsus and around the tail base. Phenylephrine was administered to induce vasoconstriction, dobutamine was used to increase cardiac output and increased end-tidal concentrations of isoflurane were used to induce vasodilation. Correlation between measurements was analysed by linear regression and agreement was analysed using Bland-Altman plots. RESULTS: Seventy two representative measurements were obtained. Mean differences (bias) between invasive and non-invasive measurements were <5 mmHg except for DAP measured on the tail, and SD (precision) were <15 mm Hg except for SAP measured at the pelvic limb. Correlation coefficients were >0.9 except for SAP on the pelvic limb and DAP on the tail. More than 50 and 80% of values measured using oscillometry lay within 10 and 20 mmHg, respectively, of values measured invasively except for SAP on the tail. SAP tended to be overestimated when measured non-invasively at low BP, and be underestimated at high BP. DAP was underestimated during low BP and overestimated during high BP. Hypotension (MAP <60 mmHg) was detected by the oscillometer with a sensitivity ≥83% and specificity ≥98% at all locations. CONCLUSIONS: This oscillometric device met the 2007 American College of Veterinary Internal Medicine guidelines for measurement of BP on the thoracic limb. There was good agreement between the oscillometer and invasive measurement of MAP at all locations. CLINICAL RELEVANCE: MAP is the driving pressure for tissue perfusion, thus MAP measurement is clinically essential. This oscillometric device yields reliable MAP measurements at three anatomical locations over a wide range of BP and can identify hypotension with high sensitivity and specificity.

Beneficial effects of hydrogen gas on porcine liver reperfusion injury with use of total vascular exclusion and active venous bypass.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is a high risk factor in liver transplantation and it influences graft survival. One of the major events during I/R injury is the generation of cytotoxic oxygen radicals. Recently, hydrogen gas has been reported to have antioxidant properties and protective effects against organ dysfunction induced by I/R injury. The aim of this study is to investigate effects of hydrogen on porcine liver reperfusion injury. MATERIALS AND METHODS: Six outbred pigs weighing 20 kg were used for the experiment. Under general anesthesia, the venous bypass between the left femoral vein and the splenic vein to the left jugular vein was made using a centrifugal pump. Then, we used a total vascular exclusion clamp (all in- and out-flow to the liver was clamped) for 60 minutes. Hydrogen (5 ppm) saturated with lactate Ringer's solution was prepared. This solution was infused through the portal vein just before reperfusion (hydrogen group). RESULTS: Aspartate aminotransferase levels in the control versus hydrogen group in 30, 60, and 120 minutes after reperfusion were 1560.3, 1925.3, and 2342.5 versus 175.3, 200.7, and 661.00 IU/L, respectively. Lactate dehydrogenase (LDH) levels in the control versus hydrogen groups in 30, 60, and 120 minutes after reperfusion were 23,235.0, 3496.7, and 4793.5 versus 663.3, 802.0, and 983.7 IU/L, respectively. The hydrogen gas level in liver tissue increased to 954.6 ppm immediately after reperfusion; however, it disappeared within 30 minutes. CONCLUSION: The solution containing hydrogen gas was safe and had remarkably protective effects on the porcine during liver I/R and may be applied in the clinical setting.

Rewarming preservation by organ perfusion system for donation after cardiac death liver grafts in pigs.

BACKGROUND: Use of grafts from donors after cardiac death (DCD) would greatly contribute to the expansion of the donor organ pool. However, this requires the development of novel preservation methods to recover the organ from changes due to warm ischemia time (WIT). METHODS: Porcine livers were perfused with a newly developed machine perfusion (MP) system. The livers were perfused with modified University of Wisconsin solution (UW) - gluconate. All grafts were procured after acute hemorrhagic shock with the ventilator off. For group 1 (n = 6), grafts were procured after WIT of 60 minutes and preserved by hypothermic MP (HMP) for 3 hours. For group 2 (n = 5), grafts were preserved with 2 hours of simple cold storage (SCS) and HMP for 2 hours. For group 3 (n = 6), grafts were preserved with 2 hours of SCS and rewarming up to 25°C by MP for 2 hours (RMP). The preserved liver grafts were transplanted orthotopically. RESULTS: The alanine aminotransferase level in perfusate in RMP during perfusion preservation was maintained at less than that of HMP. The levels of aspartate aminotransferase and lactate dehydrogenase in the 2 hours after reperfusion were significantly lower in group 3. Histologically, the necrosis of hepatocytes was less severe in group 3. The survival rate in group 3 was 2/4, but 0/4 in the other group. CONCLUSION: RMP is expected to facilitate the recovery of the DCD liver grafts.

Interleukin-1beta and tumor necrosis factor-alpha induce chemokine and matrix metalloproteinase gene expression in human colonic subepithelial myofibroblasts.

BACKGROUND: Colonic subepithelial myofibroblasts may play a role in the inflammatory responses and in extracellular matrix (ECM) metabolism. In this study, we investigated the effects of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on chemokine (IL-8 and monocyte chemoattractant protein (MCP)-1) and ECM turnover (proliferation of subepithelial myofibroblasts, and secretion of ECM and matrix metalloproteinases (MMPs)) in colonic subepithelial myofibroblasts. METHODS: Human colonic subepithelial myofibroblasts were isolated using the method described by Mahida et al. Chemokine and MMP expressions were determined by ELISA and Northern blotting. Nuclear factor (NF)-kappaB and NF-IL6 DNA binding activities were evaluated by electrophoretic gel mobility shift assays (EMSA). RESULTS: IL-1beta and TNF-alpha did not affect the proliferation of subepithelial myofibroblasts, but stimulated the secretion of types I and IV collagens weakly. Unstimulated subepithelial myofibroblasts secreted a large amount of MMP-2, but a small amount of IL-8, MCP-1 and MMP-1. IL-1beta and TNF-alpha both induced a dose- and time-dependent increase in IL-8, MCP-1 and MMP-1 secretion, and weakly stimulated MMP-2 secretion. IL-1beta and TNF-alpha both rapidly evoked NF-kappaB DNA-binding activity. The inhibition of NF-kappaB activation markedly blocked both IL-1beta- and TNF-alpha-induced IL-8 and MCP-1 mRNA expression, but did not affect MMP-1 mRNA expression. CONCLUSIONS: These observations indicate that chemokine secretion and ECM metabolism are collectively regulated by the proinflammatory cytokines, IL-1beta and TNF-alpha, in colonic subepithelial myofibroblasts. Thus, colonic subepithelial myofibroblasts may play an important role in the pathophysiology of inflammation in the colon.

[Surface morphology of osteogenic cell].

In order to clear the relation between cell activity and morphology of their microvilli (MV), osteogenic MC3T3E-1 cells were cultured on plastic cover slips. Those cells have the capacity to differentiate into osteoblasts and mineralize in vitro. Histochemically, alkaline phosphatase (ALP) positive cells appeared with ALP staining at 4 days, and they increased gradually day by day. However ALP activity advanced rapidly in the culture adding dexamethasone (Dex) into the medium from 6 to 12 days culture. In scanning electron microscopic study, MV were observed on the surface of irregularly-shaped spread cells from 4 to 12 days. At the early stage, MV showed like fine filaments. Concentration, width and length of MV increased gradually with cultivation. On day 12, the long MV with a few particles were observed to some degree. In the presence of Dex, concentration and length of MV were much better than in the absence of Dex. Furthermore MV with many particles were seen more frequently. These results demonstrate that development of MV have close connection with differentiation of the cells.

Termination of ventricular tachycardia by an implantable atrial pacemaker and external pacemaker activator.

An atrial pacemaker was implanted in a patient who had dilated cardiomyopathy, sinus node dysfunction, and drug-resistant ventricular tachycardia (VT). VT episodes were terminated by atrial overdrive pacing using an implanted pacemaker and a newly developed hand-held external programmer/transmitter. Although successful cases of termination of intractable VT by ventricular pacing have recently been reported, the ventricular method might increase the risk of accelerating VT. Atrial overdrive pacing is a safer method since it minimizes the possibility of tachycardia acceleration and, combined with antiarrhythmic drugs, it appeared to be a unique and useful approach for the treatment of drug-resistant VT.

[Left ventricular peak filling velocity and its relevant factors in hypertrophic hearts].

To evaluate the relevant factors of left ventricular peak filling velocity, M-mode echocardiograms showing the left ventricular cavity were recorded and digitized for 81 patients with hypertrophic hearts (HTH) due to hypertensive heart disease (HHD, n = 30), hypertrophic cardiomyopathy (HCM, n = 25), aortic valve stenosis (AS, n = 9), and HHD and HCM with congestive heart failure (HHD and HCM with CHF, n = 17). Peak rates of increase or decrease in dimension (Vf and Ve, respectively) and peak values of instantaneous circumferential fiber lengthening and shortening velocities (Vf/D and Ve/D, respectively) were determined by computer analysis of left ventricular internal dimensions. Systolic excursion (SE), percent fractional shortening (%FS), mean circumferential fiber shortening velocity (mVcf), thickness of the interventricular septum and posterior wall at end-diastole and the sum of them (WThivs, WThpw, and WThivs + pw, respectively) were also calculated. Their variables were compared with those of normal subjects (n = 24). The results obtained were as follows: Systolic functions in HTH without CHF were similar to those of the normal subjects, but Vf and Vf/D were significantly decreased. Differences in Vf and Vf/D between various HTH without CHF were not significant. In AS and HTH with CHF, Vf and Vf/D were significantly decreased together with systolic function. Vf correlated significantly with WThivs + pw, SE, Ve, and WThivs, and Vf/D with %FS, SE, Ve/D, and Ve.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes of left ventricular pressure-diameter-velocity relations by alterations of heart rate in conscious dogs.

Changes of left ventricular (LV) pressure-diameter-velocity relations by alterations in heart rate (HR) were investigated in 6 conscious dogs, instrumented with a pair of ultrasonic crystal probe, a micromanometer in LV and pacing electrodes on the left atrium. By atrial pacing the following four stages of HR were produced: stage (S)-I 112, S-II 134, S-III 158 and S-IV 179 bpm (mean HR). These alterations in HR were repeated before and during acute pressure loadings by methoxamine infusion. LV pressure-diameter and pressure-velocity relations were evaluated by the slope value of LV peak systolic pressure (LVSP)-end-systolic diameter, E (D) max, and by the ratio of changes in mV cf (mean velocity circumferential fiber shortening) and LVSP before and during pressure loading, delta mVcf/delta LVSP, respectively. The average of E(D) max at each stage of HR was 9.45, 12.63, 12.59, 11.22 mmHg/mm, and delta mVcf/delta LVSP was -0.009, -0.006, -0.007, -0.009 circ./sec.mmHg, respectively. E(D) max increased more at S-II and S-III than at S-I, and reversely, E(D) max decreased more at S-IV than at S-II. Similarly, delta mVcf/delta LVSP increased more at S-II than at S-I and decreased more at S-IV than at S-II, while delta LVSP and delta EDD (end-diastolic diameter) were not different between stages. These changes in E(D) max and delta mVcf/delta LVSP presented the mountainous pattern effected by alterations in HR, whose changes were almost similar to that of LV peak positive dp/dt and mVcf before pressure loading. Thus, E(D) max is augmented by an increase in HR, which suggests the Bowditch-effect. Reversely, a decrease in E(D) max at a higher rate indicates a depressed inotropic state. E(D) max is dependent on HR and is a sensitive indicator of the contractility of LV.

Reconsideration of heart rate-cardiac output relationships and resting cardiac function in patients with brady-arrhythmias.

Different types of heart rate (HR)-cardiac output (COP) relationships were compared with their clinical features and hemodynamic findings in 56 patients with brady-arrhythmias (BA). HR was raised by increments of 10 beats per minute (bpm) at 3 min intervals, from spontaneous rates to 100 or 110 bpm by right ventricular pacing. Cardiac and left ventricular (LV) functions at BA were evaluated by intra-cardiac pressures, COP measured by the thermo-dilution method and echocardiographic data. HR-COP relationships were divided into the following 3 types: 24 patients of flat (F), 18 of peaked (P) and 14 of increased (I) type. There were more patients with complete atrio-ventricular block, particularly His-ventricular block, and cardiomyopathic patients with the "P" type than with the other types. Cardiac index, stroke index, stroke work index and systemic vascular resistance were greater in "I", but these differences were not significant. LV peak systolic pressure (LVSP) and end-diastolic pressure (EDP) in "I" increased more than in "F". EDP, LV end-diastolic and end-systolic dimension (ESD) in "P" increased more than in "F". Systolic excursion and LVSP/ESD ratio in "I" increased more than in the other types. Heart failure prior to implantation of pacemaker (PM) and post-PM occurred more frequently in "P". "F" and "I" patients showed comparatively good clinical courses after PM. Thus, cardiac and LV function during BA are maintained in "F" and are impaired in "P", as reported previously. On the other hand, cardiac functions are maintained in "I" as they are in "F", mainly due to contributions of the Frank-Starling mechanism and partly due to maintenance or slight augmentation of contractility.

[Left ventricular performance during exercise in patients with constant heart rate].

In order to evaluate the response of left ventricular (LV) performance in pacemaker implanted patients (PMI pts) with constant heart rate during exercise, supine bicycle ergometer exercise was performed simultaneously in 21 PMI pts and 4 age-matched normal subjects. PMI pts were classified into two groups; Group I consisted of 16 pts with relatively good physical work capacity (maximal load: male; 80 watt or more, female; 60 watt or more), and Group II consisted of 14 pts with depressed physical work capacity (maximal load: male; 60 watt or less, female; 40 watt or less). During dynamic exercise LV end-diastolic dimension (EDD), stroke excursion (SE), percent fractional shortening (%FS) and posterior wall velocity (PWV) showed a significant increase and LV end-systolic dimension (ESD) showed a significant decrease in Group I in contrast with Group II and normal subjects. Systolic blood pressure (sBP) and sBP/ESD ratio significantly increased in Group I and normal subjects than in Group II. Furthermore, resting cardiac parameters were more impaired in Group II than Group I. Thus, it was suggested that Group I adapted to exercise according to Frank-Starling mechanism (increased EDD) and contractility due to probably increasing circulatory catecholamine (increased PWV and decreased ESD). On the other hand, Group II did not adapt sufficiently to exercise because of the limitation of preload-reserve and contractility-reserve on exercise and also at rest.

Effect of clinofibrate, a new hypolipidemic agent, on biliary and serum lipids in patients with hyperlipidemia.

Clinofibrate was given to 15 patients with hyperlipidemia, for 6-8 weeks at the daily dose of 600 mg, and its effect on 3 biliary lipid components (cholesterol, bile acids and phospholipids) and on the lithogenic index was investigated. After clinofibrate treatment, 6 of the patients were given 1.5 g/day clofibrate for 6-8 weeks to compare the effect of clofibrate with that of clinofibrate. The molar percentages of biliary cholesterol and phospholipids to the total mol number of the 3 biliary lipid components decreased, and that of bile acids increased during clinofibrate administration. In this way, the molar ratio of bile acids to cholesterol increased during the treatment. Neither the lithogenic index calculated by the formula of Admirand and Small nor that of Hegardt, Dam and Holzbach was altered significantly by the treatment. There was no apparent relationship between the effect of the drug on the lithogenic index and any of the factors initial lithogenic index, rate of decrease of serum lipids, or type of hyperlipidemia. Although clofibrate had no significant effect on the maximum solubility of cholesterol in the bile, the molar percentage of biliary cholesterol was elevated and the lithogenic index increased as compared with the control and clinofibrate period. No significant influence on bile acid composition in the bile was observed, with either clinofibrate or clofibrate.

[Diastolic murmur in non-obstructive hypertrophic cardiomyopathy].

Diastolic murmur (DM) in patients with non-obstructive hypertrophic cardiomyopathy (non-obst HCM) was studied regarding incidence, phonocardiographic disposition, mechanism, and also clinical characteristics of patients with DM. The results were as follows: 1) DM was recorded in 17 of 115 patients with non-obst HCM (15%), and was classified into three types of a mid-diastolic murmur, presystolic murmur, presystolic murmur and these combination. Mid-diastolic murmur showed low-pitched character mimicking a flow rumble around apical area in most patients. On the other hand, a presystolic murmur was relatively medium-pitched and spindle-shaped over the 4th left sternal border. Additionally, there were 7 patients of mitral opening sound coincided with the "O" point of the apex cardiogram, and 3 patients of an undefined sound or vibration during atrial contraction. 2) Impaired left ventricular (LV) compliance by pressure-volume analysis and decreased diastolic descent rate (DDR) in the mitral echocardiogram observed in patients with DM suggested that mechanism of these DM is mainly attributed to the disturbance of LV filling. Furthermore, mitral regurgitation was detected by LV angiography in a half of patients, indicating that DM might be partially related to increased mitral flow. 3) Clinically, DM was more common in younger patients of familiar occurrence and death, and with impaired physical work capacity. Therefore, auscultatory or phonocardiographic assessment of DM was clinically useful in the evaluation of patients with non-obst HCM.

Serum lipids and lipoproteins in patients with gallstone (relationship between serum lipids and types of stones in roentgenograms and sectional views).

Serum lipids and lipoproteins of gallstone patients were analyzed and compared with lithogenesity of bile and type of stones by roentgenographic and cross-sectional views. Incidences of hypercholesterolemia and triglyceridemia were higher in patients with radiolucent gallstones than with radiopaque stones. Furthermore, an incidence of hypertriglyceridemia was higher in patients with radiolucent solitary stones than with radiolucent multiple stones. The degrees of hyperlipidemia were moderate. Lipoprotein disc electrophoresis of sera of hyperlipidemic patients revealed type IIa, IIb or IV. More solitary and less multiple stones were seen in the hyperlipoproteinemic patients than normolipoproteinemic. Multiple stones with normolipoproteinemia were more accompanied by unsaturated bile (lithogenic index less than 1.0) than those with hyperlipoproteinemia and solitary stones with hyperlipoproteinemia or without. Solitary stones obtained surgically from normolipoproteinemic patients were pure cholesterol, combination or mixed stones, while multiple stones not including pure cholesterol and combination stones with pure cholesterol in the center. Solitary stones in hyperlipoproteinemic patients proved mostly either pure cholesterol or combination stones with pure cholesterol ins the center, while multiple stones containing all types of stones inclusive of a small number of other miscellaneous stones except cholesterol stones. Collectively more mixed and other miscellaneous stones except cholesterol stones, and less pure cholesterol and combination stones with pure cholesterol in the center were shown in normolipidemic patients, and vice versa in hyperlipoproteinemic patients. These results suggested serum lipids and lipoproteins being closely related to the initial precipitation, aggregation of cholesterol crystals and development of cholesterol gallstones through lipid metabolism of the whole body.