Influence of indapamide and chlorthalidone on reperfusion-induced ventricular fibrillation in isolated guinea pig hearts

The delayed rectifier potassium current (IK) is a major repolarizing current in guinea pig ventricular myocytes. Blockade of IK or other repolarizing currents is of increasing interest for development of antiarrhythmic drugs; however, these interventions may also be proarrhythmic. In the present study, we compared the potential antiarrhythmic properties of indapamide and chlorthalidone, two structurally related sulfonamide diuretics which differ in their ability to block the slow component of the delayed rectifier (IKs) in isolated, buffer-perfused guinea pig hearts. Hearts underwent 30-min global no-flow ischemia and 10-min reperfusion. Dose-response (10(-7)-10(-4) M) effects of indapamide or chlorthalidone on reperfusion-induced arrhythmias, coronary flow, and heart rate (HR) were evaluated in a randomized blinded fashion. There was no significant difference in the incidence of ventricular fibrillation (VF) for either compound as compared with untreated controls. However, VF duration was reduced to < 40 s in all hearts treated with indapamide 10(-4) M). Mean VF duration with indapamide 10(-4) M was 31 +/- 4 versus 70 +/- 40 s in controls (p < 0.05). Chlorthalidone did not protect against reperfusion-induced arrhythmias. HR was unchanged with either compound; coronary flow during the control perfusion period increased approximately 43% with indapamide 10(-4) M (p < 0.05 vs. all treatment groups). These results demonstrate that indapamide, but not chlorthalidone, confers significant protection against reperfusion-induced VF in this experimental preparation and suggest that selective block of IKs may be antiarrhythmic.     

Reduced calcium current density in single myocytes isolated from hypertrophied failing guinea pig hearts

The present study explored the possibility that an alteration in the transmembrane calcium current (ICa), through its ability to modulate Ca2+ release from the sarcoplasmic reticulum, could contribute to the depressed peak [Ca2+]i we previously observed in hypertrophied failing myocardium. Whole-cell patch clamp was used to measure ICa in single guinea pig ventricular myocytes isolated from hearts of normal guinea pigs and from guinea pig hearts in which hypertrophy and failure were induced by gradually developing left ventricular pressure overload subsequent to ascending aortic banding of young animals. Membrane capacitance (Cm) was significantly greater. and ICa, normalized for Cm, was significantly lower in myocytes from hypertrophied failing hearts. Myocytes from hypertrophied failing hearts did not differ significantly from normal myocytes in terms of the voltage-dependence of the activation variable (d) of ICa (except at -30 mV), the time course of removal of inactivation of ICa, and the time constant of decay of ICa. Measurement of the voltage dependence of the inactivation variable (f) of ICa showed that significantly more steady-state inactivation was present at 0, -10, and -20 mV in myocytes from hypertrophied failing hearts. Multiple regression analysis of all data indicated that ICa density decreased with increasing myocyte membrane area (as reflected by Cm) irrespective of any specific effects of hypertrophy and heart failure. We conclude that ICa, normalized for Cm, is significantly reduced in myocytes isolated from hypertrophied failing hearts, probably by a process associated with increased cell size, per se.     

Effects of vasodilators and perfusion pressure on coronary flow and simultaneous release of nitric oxide from guinea pig isolated hearts

OBJECTIVE: The aims were to validate the use of a direct reading NO electrode, to compare the effects of diverse acting drugs on altering coronary flow (CF) and NO release, and to examine the effects of altered perfusion pressure on flow-induced changes in NO concentration [NO] in the hemoglobin free effluent of guinea pig isolated hearts. METHODS: Hearts were isolated and perfused initially at a constant perfusion pressure (55 mmHg) with a modified Krebs-Ringer's solution equilibrated with 97% O2 and 3% CO2 at 37 degrees C. Heart rate, left ventricular pressure, CF, and effluent pH, pCO2, pO2, and NO generated current were monitored continuously on-line. Effluent was sampled for L-citrulline. Percent O2 extraction and O2 consumption were calculated. [NO] was quantitated with a sensitive amperometric sensor (sensitivity > or = 1 nmol/l approximately 3 pA) and a selective gas permeable membrane. RESULTS: The electrode was not sensitive to changes in solution pO2, flow, or pressure. The electrode was sensitive to pCO2 (-0.50 nmol/l/mmHg) and temperature (+24.5 nmol/l/degree C), so coronary effluent pCO2 was measured to compensate for a small decrease in pCO2 that occurred with an increase in coronary flow, and effluent temperature was rigidly controlled. Serotonin, bradykinin, and nitroprusside increased NO release along with CF, whereas nifedipine, butanedione monoxime, zaprinast, and bimakalim comparably increased CF but did not increase [NO] or NO release. Increases in CF (ml/g/min) and NO release (pmol/g/min), respectively, were 5.0 +/- 1 and 100 +/- 17 for 1 mumol/l serotonin, 7.5 +/- 1 and 148 +/- 18 for 100 nmol/l bradykinin, and 7.8 +/- 1 and 173 +/- 28 for 100 mumol/l nitroprusside. The increases in effluent NO by bradykinin were proportional to the increases in L-citrulline. Tetraethylammonium decreased CF, but did not change NO release, indomethacin changed neither CF nor NO release, and NG-nitro-L-arginine methyl ester (L-NAME) reduced CF by 2.6 +/- 1 ml/g/min and NO release by 25 +/- 8 pmol/g/min. An increase of CF of 8.0 +/- 0.3 ml/g/min, produced by increasing perfusion pressure from 25 to 90 mmHg, increased [NO] by 30 +/- 4 nmol/l; L-NAME but did not reduce the pressure-induced increase in CF, but reduced the increase in [NO] to 10 +/- 5 nmol/l. CONCLUSIONS: This study demonstrates in intact hearts real-time release of NO by several vasodilator drugs and by pressure-induced increases in flow (shear stress) and attenuation of these effects by L-NAME.     

Frequency-dependent effects of propafenone decrease with duration of ventricular tachycardia in isolated guinea pig hearts

Na+ channel blockers terminate tachyarrhythmias primarily by rate-dependent effects. The purpose of this study was to investigate the use-dependent effects of propafenone in isolated guinea pig and rabbit hearts perfused by the method of Langendorff. In the presence of propafenone (0.3 microM) during ventricular pacing, an abrupt decrease of the pacing cycle length (220 ms to 120 ms) slowed the intraventricular conduction with a transient peak QRS prolongation of 33.8 +/- 2.0% after 5.7 +/- 0.5 s (P < 0.01) which subsequently decreased to a steady state of 14.0 +/- 2.5% after 38.0 +/- 5.5 s (mean +/- S.E.M.; n = 10; P < 0.01). The ventricular effective refractory period was significantly prolonged if evaluated by a train of 10 basic stimuli (S1) (interstimulus interval: 120 ms) followed by a premature stimulus (S2). However, when the train of basic stimuli was increased the effective refractory period diminished progressively. An initial increase in total activation time vanished with continued rapid ventricular stimulation. These effects may be explained by a shortening of the action potential during high rates resulting in a decreased binding of propafenone to Na+ channels.     

Disparate effects of adhesion and degranulation of platelets on myocardial and coronary function in postischaemic hearts

Pre-mRNA splicing is an important regulatory step in the expression of most eukaryotic genes. In vitro studies have shown splicing to occur within 50-60 S multi-component ribonucleoprotein (RNP) complexes termed spliceosomes. Studies of mammalian cell nuclei have revealed larger complexes that sediment at 200 S in sucrose gradients, termed large nuclear RNP (lnRNP) particles. These particles contain all factors required for pre-mRNA splicing, including the spliceosomal U snRNPs and protein splicing factors. Electron microscopy has shown them to consist of four apparently similar substructures. In this study, mass measurements by scanning transmission electron microscopy of freeze-dried mammalian lnRNP preparations, both confirm the similarity between the lnRNP particles and reveal the mass uniformity of their subunits. Thus, the tetrameric lnRNP particle has a mass of 21.1(+/-1.6) MDa, while each repeating subunit has a mass of 4.8(+/-0.5) MDa, which is close to the estimated mass of the fully assembled 60 S spliceosome. The 1.9 MDa discrepancy between the lnRNP particle's mass and the cumulative masses of its four subunits may be attributed to an additional domain frequently observed in the micrographs. Notably, strands and loops of RNA were often seen emanating from lnRNP particles positively stained with uranyl formate. Our results support the idea that the nuclear splicing machine is a supraspliceosome complex. For clarity, we define spliceosomes devoid of pre-mRNA as spliceosome cores, and propose that the supraspliceosome is constructed from one pre-mRNA, four spliceosome cores, each composed mainly of U snRNPs, and additional proteins. In this way a frame is provided to juxtapose exons about to be spliced.     

Volatile anesthetics do not alter bradykinin-induced release of nitric oxide or L-citrulline in crystalloid perfused guinea pig hearts

Trimethylamine N-oxide (TMAO) is an abundant compound of tissues of marine fish and invertebrates. During fish spoilage, certain marine bacteria can reduce TMAO to nauseous trimethylamine (TMA). One such bacterium has been isolated and identified as a new Shewanella species, and called Shewanella massilia. The anaerobic growth of S. massilia is greatly increased when TMAO is added, indicating that TMAO reduction involves a respiratory pathway. The TorA enzyme responsible for TMAO reduction is a molybdenum cofactor-containing protein of 90 kDa located in the periplasm. Whereas TorA is induced by both TMAO and dimethylsulfoxide (DMSO), this enzyme has a high substrate specificity and appears to only efficiently reduce TMAO as a natural compound. The structural torA gene encoding the TMAO reductase (TorA) and its flanking regions were amplified using PCR techniques. The torA gene is the third gene of a TMAO-inducible operon (torECAD) encoding the TMAO respiratory components. The torC gene, located upstream from torA encodes a pentahemic c-type cytochrome, likely to be involved in electron transfer to the TorA terminal reductase. TorC was shown to be anchored to the membrane and, like TorA, is induced by TMAO. Except for the TorE protein, which is encoded by the first gene of the torECAD operon, all the tor gene products are homologous to proteins found in the TMAO/DMSO reductase systems from Escherichia coli and Rhodobacter species. In addition, the genetic organization of these systems is similar. Although these bacteria are found in different ecological niches, their respiratory systems appear to be phylogenetically related, suggesting that they come from a common ancestor.     

Halothane, isoflurane, and sevoflurane reduce postischemic adhesion of neutrophils in the coronary system

BACKGROUND: Polymorphonuclear neutrophils (PMNs) contribute to postischemic reperfusion damage in many organs and tissues, a prerequisite being adhesion of PMNs to vascular endothelial cells. Because adhesion processes involve orderly interactions of membrane proteins, it appeared possible that "membrane effects" of volatile anesthetics could interfere. We investigated the effects of halothane, isoflurane, and sevoflurane on postischemic adhesion of human PMNs in the intact coronary system of isolated perfused guinea pig hearts. METHODS: The hearts (n = 7-10 per group) were perfused in the "Langendorff" mode under conditions of constant flow (5 ml/min) using modified Krebs-Henseleit buffer equilibrated with 94.4% oxygen and 5.6% carbon dioxide. Global myocardial ischemia was induced by interrupting perfusion for 15 min. In the second minute of reperfusion (5 ml/min), a bolus dose of 6 x 10(5) PMNs was injected into the coronary system. The number of cells reemerging in the coronary effluent was expressed as a percentage of the total number of applied PMNs. Halothane, isoflurane, and sevoflurane, each at 1 and 2 minimal alveolar concentration (MAC), were vaporized in the gas mixture and applied from 14 min before ischemia until the end of the experiment. RESULTS: Under nonischemic conditions, 24.7 +/- 1.3% of the injected neutrophils did not reemerge from the perfused coronary system. Subjecting the hearts to global ischemia augmented retention (36.4 +/- 2.8%, P < .05). Application of halothane reduced adhesion of neutrophils to 22.6 +/- 2.1% and 24.2 +/- 1.8% at 1 and 2 MAC, respectively (P < .05). Exposure to 1 and 2 MAC isoflurane was similarly effective, whereas basal adhesion was not significantly influenced. Sevoflurane-treated hearts (1 and 2 MAC) also showed decreased adhesion of PMNs (23 +/- 2.3% and 24.8 +/- 1.8%, respectively; P < .05) and an identical reduction resulted when sevoflurane (1 MAC) was applied only with the onset of reperfusion. CONCLUSIONS: Although the mechanism of action of volatile anesthetics remains unclear in these preliminary studies, their inhibitory effect on ischemia-induced adhesion of PMNs may be beneficial for the heart during general anesthesia.     

Effects of sumatriptan on coronary flow and left ventricular function in the isolated perfused guinea pig heart

IBD is associated with an increased activation of intestinal immune cells, which causes overproduction of proinflammatory cytokines such as IL-1beta. IL-1beta is implicated in mediating the sustained inflammatory response. IL-1 receptor antagonist (IL-1Ra), the naturally occurring inhibitor of IL-1, has been shown to have beneficial effects in experimental models of colitis. In this study we investigated the hypothesis that an imbalance between IL-1 and IL-1Ra exists in IBD by measuring their secretion by explant cultures of colonic biopsies. Freshly homogenized biopsies from involved tissue in IBD patients exhibited significantly lower IL-1Ra/IL-1beta ratios than control and uninvolved IBD mucosal tissue. Using explant cultures, in vitro production of IL-1beta and IL-1Ra increased progressively during the 4-18-h culture periods. IL-1beta secretion was higher in supernatants from involved Crohn's disease (CD) and ulcerative colitis tissue compared with control tissue, and IL-1beta levels increased with severity of inflammation. IL-1Ra secretion was not elevated in involved IBD samples, but significantly higher levels were released when moderate to severely involved tissue samples were compared with noninflammatory controls. Similar to freshly homogenized tissue, explant studies showed that the IL-1Ra/IL-1beta ratios were significantly decreased in involved IBD tissue, but not in uninvolved CD or inflammatory control specimens. These data support the hypothesis of an imbalance between IL-1beta and IL-1Ra in IBD.     

Effect of electric charge on the adhesion of human blood platelets

The paper presents the results of research into the effect of the size and depth of the implanted electric charge on the adhesion of human blood platelets. The experiments were carried out on polyethylene terephthalate PET foil of 36 microns thickness. The electret formation process was carried out in an electron-beam device. The electrization conditions were such that electrets with the excess electric charge accumulated at various depths were obtained. The selection of conditions was verified by investigating the space charge distribution with the use of the virtual electrode method. The microscopic observation of non-electrified foils and electrets as well as the quantitative examination of the adhesion of human blood platelets has explicitly confirmed the positive influence of the electret effect on the thrombogenesis of PET foil. This made it possible to define the optimum electrization conditions. The research has additionally indicated that the relationship between the amount of adherent blood platelets and the size of the electric charge is not a simple relation of the kind: the larger negative charge, the more thrombogenic material. The decisive and positive effect of the space charge has been confirmed by analysing the effectiveness of the surface and space charge.     

Time course of the endocochlear potential in the isolated cochlea of the guinea pig

The temperature of Hanks' solution changed its potential (-0.48 mV/degrees C in Na(+)-Hanks' and -0.23 mV/degrees C in K(+)-Hanks' solution), but the pH had no clear effect on the potential. The time course of the endocochlear potential (EP) in the isolated cochlea of the guinea pig was measured under some different conditions. When the cochlea was moistened with Hanks' solution, negative EP increased gradually toward 0 mV at 124 min after death. When the cochlea was immersed in Hanks' solution, positive EP was obtained but it depended on the oxygen and the circulation of Hanks' solution. Moderate cooling (5 degrees C) of Hanks' solution had no significant effect on the EP of the isolated cochlea immersed in oxygen-saturated Hanks' solution circulated by oxygen bubbles. The space constant and the amplitude of the displacement responses were independent of the EP in the isolated cochlea. Thus, the positive EP might not show the physiological condition of the isolated cochlea.     

Different left ventricular relaxation parameters in isolated working rat and guinea pig hearts. Influence of preload, afterload, temperature, and isoprenaline

Six primary lung tumors with numerous multinucleated osteoclast-like giant cells (OLGCs) and no osteogenic component were evaluated histologically and immunohistochemically to examine pulmonary lesions inciting an OLGC response. The patients comprised four women and two men ranging in age from 61 to 80 years (average age, 69 years). The tumors consisted of one adenocarcinoma, two sarcomatoid carcinomas, and three giant cell variants of malignant fibrous histiocytoma. One tumor was endobronchial in location, while five were situated peripherally. Tumor diameter spanned from 1 to 6.5 cm (average, 2.7 cm). In addition to the giant cells, common characteristics included the malignant nature of the neoplasms and, in five of six cases, histologically malignant mesenchyme. This array of cases exemplifies the variability of lung lesions which may elicit an OLGC inflammatory response resulting in areas resembling the giant cell variant of malignant fibrous histiocytoma. The results of this study suggest that OLGCs occur preferentially in malignant rather than benign nonosteogenic lung tumors and that sarcomatoid regions of malignant tumors are more likely to be infiltrated by OLGCs than epithelial regions.     

The role of ions on histamine-induced depolarization in isolated guinea pig adipocytes

Effects of ions on histamine (Hi)-induced depolarization were studied in guinea pig adipocytes. Depolarization induced by Hi in guinea pig adipocytes was decreased by removal of K+ from the medium or pretreatment with ouabain at concentrations that showed no significant effect themselves. The decrease in membrane potentials induced by Hi was also abolished potently by replacement of Na+ by choline or pretreatment with tetrodotoxin at a concentration that caused no significant action alone. Pretreatment with monensin at a concentration lower than that eliciting the action resulted in a potentiation of Hi-induced depolarization. The depolarization induced by Hi was not affected by the presence of Ca2+ in the medium or pretreatment of the cells by diltiazem.     

Pyruvate reverses fatty-acid-induced depression of ventricular function and calcium overload after hypothermia in guinea pig hearts

OBJECTIVE: High levels of free fatty acids have been shown to impair mechanical recovery and calcium homeostasis of isolated rat hearts following hypothermic perfusion. The objective of the present study was to investigate whether inhibition of fatty acid oxidation through activation of pyruvate dehydrogenase by millimolar concentrations of pyruvate could influence functional recovery and Ca2+ homeostasis after a hypothermic insult. METHODS: Ventricular function and myocardial calcium ([Ca]total) were measured in 3 different groups of Langendorff-perfused guinea pig hearts exposed to 40 min hypothermic (15 degrees C) perfusion, followed by 30 min rewarming at 37 degrees C. The hearts were perfused with either 11.1 mM glucose (G), glucose and 1.2 mM palmitate (GP), or glucose, palmitate and 5 mM pyruvate (GPP) as energy substrates. RESULTS: All groups showed marked elevations in [Ca]total during hypothermia (from 0.6-0.7 mumol.g dry wt-1 to 9.3-12.2 mumol.g dry wt-1 at 40 min hypothermia, P < 0.05), associated with a pronounced increase in left ventricular end-diastolic pressure (LVEDP from 0-2 to 50-60 mmHg). Following rewarming, GP-perfused hearts showed significantly lower recovery of mechanical function compared to both G- and GPP-perfused hearts (% recovery of left ventricular developed pressure: 27 +/- 8 vs. 62 +/- 3 and 62 +/- 8%, respectively, P < 0.05). The reduced mechanical recovery of GP-perfused hearts was associated with elevated [Ca]total. In separate experiments we found that addition of 1.2 mM palmitate reduced glucose oxidation ([14C]glucose) from 1.77 +/- 0.28 mumol.min-1.g dry wt-1 (G-perfused hearts) to 0.15 +/- 0.04 mumol.min-1.g dry wt-1 (GP-perfused hearts, P < 0.05), implying that fatty acids had become the major substrate for oxidative phosphorylation. Fatty acid oxidation was, however, less pronounced after further addition of 5 mM pyruvate. Thus, palmitate oxidation ([3H]palmitate) was more than 40% lower in GPP-perfused than in GP-perfused hearts (0.83 +/- 0.22 vs. 1.41 +/- 0.12 mumol.min-1.g dry wt-1, P < 0.05). CONCLUSIONS: The present results demonstrate impaired ventricular function and calcium homeostasis after hypothermia in guinea pig hearts perfused with fatty acids in addition to glucose, as compared to hearts perfused with glucose alone. Furthermore, we show that these unfavourable effects of fatty acids can be overcome by an exogenous supply of pyruvate.     

Inhibitory effect of tetrahydropalmatine on calcium current in isolated cardiomyocyte of guinea pig

AIM: To study the effect of tetrahydropalmatine (THP) on calcium channels in ventricular single cells of guinea pig heart. METHODS: Patch-clamp technique (whole cell recording) was used to observe calcium current in ventricular myocytes. RESULTS: THP decreased ICa in ventricular myocytes with a dose and frequency-dependent manner. THP (0.1, 1, and 10 mumol.L-1) decreased ICa from 1.15 +/- 0.22, 0.91 +/- 0.18, and 1.60 +/- 0.42 nA (control) to 0.9 +/- 0.21 (P < 0.01), 0.56 +/- 0.21 (P < 0.01), and 0.83 +/- 0.21 nA (P < 0.05), respectively, number of cells is five in each group (n = 5), and the rates of the depression of ICa were 22%, 38%, and 48%, respectively. The effect was easily reduced by washing the cell with the Tyrode's solution. The current-voltage relation curve showed that the potential producing peak value of ICa was 0 mV at which THP had the most markedly inhibited action on ICa. When the stimulating frequency was changed, ICa varied in a frequency-dependent manner 5 min after THP was given, and the inhibition of THP was stronger at 2 Hz than that at 0.1 Hz. CONCLUSION: THP possessed a Ca2+ channel blocking effect.     

Creep after loading in the relaxed and contracted smooth muscle (taenia coli of the guinea pig) under various osmotic conditions

Skin reactivity to tuberculin has been studied during the course of experimental leptospirosis in guinea pigs. A depression of the delayed hypersensitivity to tuberculin was demonstrated in the infected animals. The depression was most pronounced when icterus had developed. The depression was not correlated with the amount of infectious units administered or with the demonstration of live leptospirae in the peritoneal cavity. In the infected animals there was no correlation between the initial and the final skin tests which is in contrast to findings in the control group.     

Stereospecific effect of bupivacaine isomers on atrioventricular conduction in the isolated perfused guinea pig heart

BACKGROUND: The local anesthetic bupivacaine is an equal mixture of two optically active isomers known to exert different cardiotoxic profiles in vivo. Enantiomer-specific forms of bupivacaine may have differential effects on cardiovascular function, specifically on cardiac electrophysiology. The authors' aim was to determine if there were any direct functional differences in the cardiac effects of bupivacaine isomers. The isolated heart was used to avoid possible indirect cardiac effects of bupivacaine, such as autonomic nervous and hormonal influences, as well as preload and afterload factors. METHODS: The hearts of 12 ketamine-anesthetized guinea pigs were perfused with Krebs-Ringer's solution (97% oxygen, 3% carbon dioxide) at constant perfusion pressure using the Langendorff technique. Atrial and ventricular bipolar electrodes were placed to measure heart rate (HR) and atrioventricular (AV) conduction time. Left ventricular pressure (LVP), coronary flow, and inflow and outflow oxygen tensions were also measured. Oxygen delivery, oxygen consumption (MVO2), and percentage of oxygen extraction were calculated. Each heart was perfused with increasing randomized concentrations (0.5, 1, 5, 10 microM) of both isomers and the racemate of bupivacaine. RESULTS: Racemic and isomeric bupivacaine equally and dose dependently decreased cardiac function. At 10 microM bupivacaine these changes were HR, -17 +/- 2%; LVP, -50 +/- 3%; coronary flow, -20 +/- 4%; and MVO2, -46 +/- 4%. The (+) isomer significantly prolonged AV conduction compared with the racemate and the (-) isomer at all concentrations. At 10 microM, AV time was 54 +/- 6% longer with the (+) isomer and 30 +/- 4% longer with the (+/-) racemate than with the (-) isomer. The greater delay in AV time with the (+) than the racemate or (-) isomer led to a second-degree AV dissociation in 10 of 12 of hearts treated with (+) bupivacaine. CONCLUSIONS: This study shows that bupivacaine has an enatiomer-specific effect to delay AV conduction and to produce second-degree AV dissociation in the isolated perfused heart. This suggests that bupivacaine isomers probably have differential effects on one or more ion-specific channels regulating AV conduction. Other measured direct cardiac effects of bupivacaine appear to be independent of the isomeric form.     

The effects of flunarizine and pentoxifylline on vestibular blood flow in the guinea pig

Several authors have proposed that complications arising from vestibular disorders are the result of compromised circulation. The purpose of the current study was to assess the ability of flunarizine and pentoxifylline to increase peripheral vestibular blood flow (VBF), since flunarizine is a selective calcium-channel entry blocker that inhibits calcium-related contraction of smooth muscle, while pentoxifylline is a xanthine derivative that promotes microcirculation by affecting red blood cell malleability. Both of these treatment strategies have received considerable attention in clinics and laboratory, but their effects on blood flow are unclear. Changes in VBF were evaluated from the posterior semicircular canal ampulla in guinea pigs using a laser Doppler flowmeter. One group of animals was infused with pentoxifylline at concentrations of 10-40 mg/ml, while a second group was treated with 0.3-1.5 mg/kg flunarizine. VBF, blood pressure (BP) and heart rate (HR) were monitored continuously. Findings showed that pentoxifylline induced a concentration-dependent increase in VBF. In contrast, no increase in VBF occurred in response to flunarizine infusions. These studies suggest that the effectiveness of pentoxifylline in the clinical treatment of vestibular disorders may be the result of improved blood flow.