Echocardiographic evaluation of deformity and enlargement of the canine mitral valve annulus associated with myxomatous degenerative mitral valve disease.

INTRODUCTION/OBJECTIVES: Quantitative evaluation of the morphology of the mitral valve annulus (MVA) in dogs with myxomatous mitral valve disease (MMVD) may improve the techniques of mitral valve plasty. This study aimed to compare the MVA morphology on echocardiography in normal dogs and dogs with MMVD and to compare the echocardiographic and intraoperative measurements of the MVA in dogs with MMVD. ANIMALS, MATERIALS AND METHODS: The study population comprised 59 healthy dogs (control group) and 371 dogs with MMVD (MMVD group). The anterior-posterior diameter and transversal diameter (TD) of the MVA and the aortic annulus diameter were measured by echocardiography to calculate the mitral valve flattening ratio, mitral annulus area (MAA), mitral annulus circumference (MAC), contraction ratio of the MAA and aortic annulus area. In the MMVD group, the mitral annulus diameter (MAD) was macroscopically measured during mitral valve plasty. Areas and lengths were divided by the body surface area (BSA) and √BSA, respectively, for comparative analyses. RESULTS: The systolic and diastolic anterior-posterior diameter/√BSA, transversal diameter/√BSA, MAA/BSA converted to a natural logarithm (Ln(MAA/BSA)), and MAC/√BSA was significantly higher in the MMVD group than the control group, whereas flattening ratio values and contraction ratio of the MAA was significantly lower. Neither the aortic annulus diameter /√BSA nor the Ln(aortic annulus area/BSA) significantly differed between groups. In the MMVD group, diastolic MAC/√BSA and MAA/BSA correlated significantly with the MAD/√BSA. CONCLUSIONS: The MVA is larger and rounder in dogs with MMVD than controls. Two-dimensional echocardiographic measures of MAA and MAC correlate well with intraoperative measures of MAD.

The relationship between oxygen consumption rate and viability of in vivo-derived pig embryos vitrified by the micro volume air cooling method.

The aim of this study was to assess the viability of vitrified-warmed in vivo-derived pig embryos after measuring the oxygen consumption rate. Six days after artificial insemination, blastocysts were collected from gilts and vitrified by the micro volume air cooling method. The oxygen consumption rate was measured in 60 vitrified-warmed embryos, which were then cultured for 48h to assess the viability. The survival (re-expansion) rate of embryos after warming was 85.0%. The average oxygen consumption rate of embryos immediately after warming was greater in embryos which could re-expand during subsequent culture (F=0.75±0.04) than that in those which failed to re-expand (F=0.33±0.05). Moreover, the oxygen consumption rate of vitrified-warmed embryos was greater in the hatched (F=0.88±0.06) than that in the not-hatched group (F=0.53±0.04). When the oxygen consumption rate of the vitrified-warmed embryos and the numbers of viable and dead cells in embryos were determined, there was a positive correlation between the oxygen consumption rate and the number of live cells (P<0.01, r=0.538). A total of 29 vitrified embryos after warming and measuring the oxygen consumption rate were surgically transferred into uterine horns of two recipients. Both of the recipients become pregnant and farrowed 12 healthy piglets. These results demonstrate that the oxygen consumption rate of vitrified-warmed pig embryos can be related to the number of live cells and that the measurement of oxygen consumption of embryos after cryopreservation may be useful for estimating embryo survivability.

Multipotency of equine mesenchymal stem cells derived from synovial fluid.

Cartilage regeneration with cell therapy following arthroscopic surgery could be used in racehorses with intra-articular fractures (IAF) and osteochondritis dissecans (OCD). The aims of this study were to investigate the origin and multipotency of stromal cells in the synovial fluid (SF) of horses with intra-articular injury and synovitis, and to provide a new strategy for regeneration of lost articular cartilage. Mesenchymal stromal cells were isolated from SF of horses with IAF and OCD. Multipotency was analysed by RT-PCR for specific mRNAs and staining for production of specific extracellular matrices after induction of differentiation. The total number of SF-derived mesenchymal stromal cells reached >1 × 10(7) by the fourth passage. SF-derived cells were strongly positive (>90% cells positive) for CD44, CD90 and major histocompatibility complex (MHC) class I, and moderately positive (60-80% cells positive) for CD11a/CD18, CD105 and MHC class II by flow cytometry. SF-derived cells were negative for CD34 and CD45. Under specific nutrient conditions, SF-derived cells differentiated into osteogenic, chondrogenic, adipogenic and tenogenic lineages, as indicated by the expression of specific marker genes and by the production of specific extracellular matrices. Chondrogenic induction in culture resulted in a change in cell shape to a 'stone-wall' appearance and formation of a gelatinous sheet that was intensely stained with Alcian blue. SF may be a novel source of multipotent mesenchymal stem cells with the ability to regenerate chondrocytes.

Matrix metalloprotease-9 activity in the cerebrospinal fluid and spinal injury severity in dogs with intervertebral disc herniation.

We investigated whether matrix metalloproteinase (MMP)-9 expression in the cerebrospinal fluid (CSF) of dogs with intervertebral disc herniation (IVDH) is associated with the severity of neurological signs and prognosis. CSF from the cisterna magna (C-CSF) and the lumbar spine (L-CSF) of 34 dogs with IVDH was analyzed using zymography. Activity of MMP-9 in L-CSF was detected in 6 of 34 dogs with IVDH, often for more than 7 days after injury. MMP-9 activity was not detected from any of the C-CSF samples. Of the six cases that were MMP-9 positive, all four cases with grade V that had loss of deep pain were non-ambulatory 6 months after treatment. The remaining two cases with grade III and IV could recover mobility. In dogs with grade V thoracolumbar IVDH, MMP-9 expression in the CSF may indicate severe spinal cord injury with poor prognosis.

Comparative study of chronic kidney disease in dogs and cats: induction of myofibroblasts.

We investigated the kidneys of dogs and cats to clarify whether renal myofibroblasts induction is associated with the severity of chronic kidney disease (CKD). Immunohistochemical expression of myofibroblast markers, alpha-smooth muscle actin (SMA) and vimentin, were evaluated quantitatively. The degrees of glomerulosclerosis, glomerular hypertrophy, interstitial cell infiltration, and interstitial fibrosis were also evaluated quantitatively. The plasma creatinine (pCre) concentrations correlated with glomerulosclerosis, cell infiltration, and fibrosis in dogs, and only with fibrosis in cats. The alpha-SMA expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, and with pCre and fibrosis in cats. Tubular vimentin expression correlated with fibrosis in cats, but not in dogs. Interstitial vimentin expression correlated with pCre, glomerulosclerosis, cell infiltration, and fibrosis in dogs, but only with pCre in cats. In conclusion, it was suggested that the severity of CKD in dogs and cats was mediated by different pathways associated with myofibroblasts expression.

Immunohistochemical analysis of cyclooxygenase-2 induction during wound healing in dog skin.

Cyclooxygenase (COX)-2 is an inducible isoform of COX and is expressed under abnormal health conditions. This study elucidated the cutaneous induction of COX-2 during the wound healing processes in dog skin. Dog skin was sutured after punch biopsy and investigated histologically and immunohistochemically on days 0 (normal), 1, 3, 5, 7, 10, and 14 after injury. Histological changes, including infiltration of inflammatory cells and proliferation of fibroblast-like cells, were observed as predicted, and there was a close and significant correlation between these 2 events. COX-2-positive cells were detected in the epidermis between days 1 and 7, and bimodal peaks were observed in the case of the percentage of COX-2-positive cells. In inflammatory cells, COX-positive signals were detected on day 3 only. Here, we clarified the localization and pattern of the induced COX-2 expression during wound healing in dog skin.

Sandwich ELISA system for cartilage oligomeric matrix protein in equine synovial fluid and serum.

REASONS FOR PERFORMING STUDY: Measurement of cartilage oligomeric matrix protein (COMP) in serum has potential for diagnosis of equine osteoarthritis (OA), but clinical use is currently limited by the lack of specificity of an inhibition ELISA as well as by baseline increases due to exercise. Improved methods for ELISA with increased antigen specificity and sensitivity are therefore required for reliable measurement. HYPOTHESIS: Measurement of the serum level of COMP by sandwich ELISA allows identification of horses with OA. METHODS: New monoclonal antibodies (mAbs) were elicited against equine cartilage COMP, their epitopes were determined and a sandwich ELISA was developed. The concentrations of COMP in synovial fluid (SF; n=100) and sera (n=100) from OA cases were measured by sandwich ELISA as well as by inhibition ELISA and compared with concentrations in normal joints (n=95) and horses (n=50). RESULTS: Immunoblots of enzymatically cleaved COMP showed that the new mAbs recognised different epitopes located on a 20 kDa fragment between K63 and K238 of the EGF-like repeats. Inhibition ELISA with any mAb detected significantly increased levels of COMP in OA SF compared with normal SF, whereas no significant difference was detected between serum levels of COMP in OA and normal horses. Conversely, sandwich ELISA with the combination of unlabelled 2A11 x biotinylated 11F10 mAbs detected a significant increase in COMP levels in both serum and SF from OA cases compared with levels in normal animals. CONCLUSIONS AND POTENTIAL RELEVANCE: Measurement of serum COMP with sandwich ELISA may be useful in identifying horses with OA.

Mucinous Cystadenocarcinoma of the Colon during Pregnancy.

A rare case of mucinous adenocarcinoma of the cecum in a pregnant woman is described. A 32-year-old Korean woman was diagnosed as having an abdominal tumor immediately after giving birth. Abdominal computed tomography demonstrated a smooth mass measuring 10 cm in diameter on the right side of the abdomen. Acute abdomen developed 3 days after birth. At emergency surgery, volvulus of a polypoid tumor was detected at the cecum apart from the normal appendix. We successfully performed a tumorectomy; however, histopathological examination demonstrated mucinous adenocarcinoma with a massive blood clot.

Urine cartilage oligomeric matrix protein (COMP) measurement is useful in discriminating the osteoarthritic Thoroughbreds.

OBJECTIVE: To quantify the urinary concentration of cartilage oligomeric matrix protein (COMP), and to evaluate the relationship between urinary COMP concentration and the catabolic activity of synovial fluid (SF) in diseased horses. METHODS: COMP in horse urine was detected by immunoblotting with a monoclonal antibody (mAb; 14G4) raised against equine COMP from articular cartilage. Urine and serum samples were obtained from 83 Thoroughbred horses with aseptic joint diseases (AJD, 79 horses) or septic joint diseases (SJD, four horses) at the time of anesthesia induction, and samples of SF were obtained during surgery. Control samples of urine (n=111) were collected from normal horses free of any orthopedic diseases after they had been racing. COMP concentration was determined in all samples using inhibition enzyme-linked immunosorbent assay (ELISA) with mAb 14G4. SF samples were also used for the quantification of gelatinase activity. RESULTS: Positive bands of COMP fragments were determined on the immunoblots with mAb 14G4. The urinary COMP concentrations in AJD and SJD horses (1.02+/-0.75 and 1.55+/-1.17 microg/100mg creatinine, respectively) were significantly higher than normal (0.57+/-0.29 microg/100mg creatinine). In 55 horses with fractures in the AJD group there was a logarithmic relationship (r=-0.45, P<0.001) between the urinary and SF COMP measurements, while the urinary COMP level was positively correlated with matrix metalloproteinase (MMP)-2 and -9 activities (r=0.30, P<0.05 and r=0.51, P<0.001, respectively) in SF. CONCLUSIONS: The urinary COMP assay with mAb 14G4 is useful for discriminating horses with osteoarthritis. The higher COMP levels in urine from such horses would be indicative of enhanced proteolytic activity, in addition to the increased COMP levels in the diseased joints.

Analysis of cartilage oligomeric matrix protein (COMP) degradation and synthesis in equine joint disease.

REASONS FOR PERFORMING STUDY: Cartilage oligomeric matrix protein (COMP) is abundant within cartilage; its turnover and/or degradation have been investigated in various equine joint diseases and it has been suggested that COMP fragmentation might be useful for monitoring such conditions. OBJECTIVES: To determine whether COMP metabolism is compromised in equine osteoarthritis (OA) and whether COMP degradation is a useful joint marker representing cartilage destruction. HYPOTHESIS: A monoclonal antibody (mAb) with a higher affinity for degraded COMP allows discrimination of diseased joints by quantifying COMP levels and fragmentation. METHODS: A mAb (clone14G4) was generated against equine cartilage COMP. The NH2-terminal sequence of enzyme-cut COMP fragments recognised by 14G4 was determined, as was the efficiency of binding to COMP (using a generated COMP peptide). COMP concentration and fragmentation were analysed in synovial fluid (SF) from normal horses and those with OA. RESULTS: The mAb 14G4 had a higher affinity for the smaller fragments of equine COMP, compared with a mAb (clone 12C4) generated against human COMP. The 14G4 epitope was identified as between C134 and F147. The COMP values in OA (mean +/- s.d. 205.8 +/- 90.9 microg/ml) were significantly higher than in the normal (133.1 +/- 31.5 microg/ml) SF. On the immunoblots of OA sample, the proportions of intact COMP were significantly lower, while smaller fragments ranging from 75 to 290 kDa were higher compared with the normal SF. CONCLUSIONS AND POTENTIAL RELEVANCE: The mAb 14G4 reliably detects COMP degradation as well as synthesis, and fragmentation analysis combined with quantification in SF could be useful to study equine OA.

Serum level of cartilage oligomeric matrix protein (COMP) in equine osteoarthritis.

This study was designed to assay and compare cartilage oligomeric matrix protein (COMP) in horse sera, in samples from normal and joint diseased horses, and to investigate the relationships between COMP in sera and synovial fluids (SF) with keratan sulphate (KS) data. Sera from 38 horses free of any joint pathology (controls) and from horses with aseptic joint disease (AJD horses, n = 40) were assayed for COMP and KS concentrations. Of the 78 horses in the study, 53 were also assayed for COMP and KS concentrations in SF. COMP and KS were measured by inhibition ELISA, using monoclonal antibodies 12C4 and 5D4, respectively. The COMP concentration in sera from AJD horses (mean +/- s.d. 10.7 +/- 7.4 microg/ml) was significantly (P<0.02) lower than in control sera (14.8 +/- 7.8 microg/ml). The joint disease sera also had significantly lower (P<0.01) KS levels (180.5 +/- 61.8 ng/ml) than controls (237.1 +/- 116.1 ng/ml). A significant correlation (r = 0.52, n = 53, P<0.001) was seen between serum and SF in COMP levels; no such relationship was seen in KS levels. It is possible that serum COMP concentration could be a more specific marker of equine joint disease than any other described to date.

Increased plasminogen activator inhibitor activity and diabetes predict subsequent coronary events in patients with angina pectoris.

BACKGROUND: Plasminogen activator inhibitor (PAI) is a marker of recurrence of myocardial infarction. Diabetes mellitus is also an important risk factor of coronary artery disease, including myocardial infarction and angina pectoris. AIM: We examined baseline plasma PAI activity levels, clinical variables, and angiographic findings and assessed them as prospective values for subsequent coronary events, such as sudden death, nonfatal myocardial infarction and coronary revascularization by percutaneous transluminal coronary angioplasty or coronary artery bypass surgery during the follow-up period. METHODS: We conducted a prospective study for 4 years of 249 consecutive patients admitted with angina pectoris. Blood samples for PAI were drawn at discharge. RESULTS: In the multivariate Cox proportional hazard model, PAI activity and diabetes mellitus were significant and independent risk factors (the risk increased by 10% in those with a higher PAI concentration and by 70% in diabetic patients). Event-free survival was reduced by higher PAI activity (> or = 8.4 IU/mL) and the presence of diabetes. The patients with higher PAI activity and diabetes had a 4.2-fold risk in comparison with the patients with lower PAI activity and no diabetes. However, patients with lower PAI activity were less likely to have coronary events even when they had diabetes. CONCLUSIONS: Higher PAI activity and diabetes predict subsequent coronary events in patients with angina pectoris. Diabetes has less prognostic value for subsequent coronary events in patients with lower PAI activity.

Measurement of cartilage oligomeric matrix protein (COMP) in normal and diseased equine synovial fluids.

OBJECTIVE: This study was designed to assay cartilage oligomeric matrix protein (COMP) in equine synovial fluids and to compare the concentration in synovial fluids from normal horses with joint diseased horses. The relationship between the COMP degradation and the matrix metalloproteinase activity in synovial fluids was also investigated. DESIGN: Using COMP antigen prepared from equine articular cartilage and murine monoclonal antibody (12C4) raised against human COMP, an inhibition ELISA was developed. COMP in equine synovial fluids from normal and diseased joints was quantified. Metalloproteinase activities were evaluated in the same synovial fluids by a gelatin degradation ELISA. COMP fragments were evaluated qualitatively by Western blotting. RESULTS: The COMP inhibition ELISA was reliable at concentrations of equine COMP between 62.5 and 2000 ng/ml. COMP values in joint fluids in both aseptic and septic joint disease (19.7+/-15.3 and 16.1+/-11.2 microg/ml, respectively) were significantly (P < 0.001) lower than normal (53.2+/-29.0 microg/ml). The molecular sizes of COMP on immunoblots were different between normal and diseased synovial fluids; more fragments were seen in diseased fluids. The aseptic (26.6 +/- 20.6%) and septic joint disease synovial fluids (36.1 +/- 37.5%) had significantly higher (P < 0.02 and 0.002, respectively) gelatinolytic activities than normal (13.6 +/- 13.7%). There was a negative correlation (R = -0.31, P < 0.002) between COMP level and gelatinase activity. Conclusions We conclude that the fragment pattern and the absolute COMP concentration maybe useful for monitoring joint disease, and that COMP degradation in synovial fluids from progressed joint disease may be due to MMP gelatinolytic activity.

Evaluation of collagenase-induced mitral valve regurgitation in dogs.

OBJECTIVE: To investigate the hemodynamic changes induced by injecting collagenase into the mitral valve to induce mitral valve regurgitation (MVR) in dogs. ANIMALS: 9 healthy Beagles. PROCEDURE: Dogs were randomly assigned to 3 groups: control (saline [0.9% NaCl] solution; n = 3), single collagenase injection (C1; 3), and 2 collagenase injections (C2; 3). Open-heart surgery was performed, and saline or collagenase solutions were injected into the mitral valve. Before and weekly for 11 weeks after surgery, radiography, echocardiography, and phonocardiography were performed. Mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure (mPAWP) were measured before and 11 weeks after surgery. Postmortem examinations were performed after dogs were euthanatized. RESULTS: No changes were detected in the control group during the 11-week follow-up period. A systolic murmur and MVR developed 1 week after surgery in groups C1 and C2. The murmur changed from a protosystolic to a pansystolic murmur, and left atrial diameter and the left atrial-to-aortic root diameter ratio increased with time. Mean pulmonary arterial pressure and mPAWP were greater 11 weeks after surgery in groups C1 and C2, compared with presurgery values. During necropsy, tissue loss was detected in the mitral valve at the site of collagenase injection. Degree of regurgitation corresponded to lesion size. CONCLUSIONS AND CLINICAL RELEVANCE: Injection of collagenase into the mitral valve of healthy dogs induced MVR, and dogs with MVR developed progressive hemodynamic changes without acute overload. Collagenase-induced MVR may be an appropriate model for evaluation of prognostic markers of idiopathic MVR in dogs.

Uterine horn torsion in two non-gravid bitches.

Uterine torsion secondary to sacculation of the uterine horns was diagnosed in two non-gravid bitches which were presented with anorexia, polydipsia and an acutely swollen abdomen. On the basis of the radiological and ultrasonographic findings, which indicated the presence of an enlarged spherical or tubular structure filled with hypoechoic material in the caudal abdomen, a tentative diagnosis of pyometra was made. Exploratory laparotomy revealed unilateral uterine horn torsion along the longitudinal axis, with bilateral fluid-filled sacculations. Ovariohysterectomy was performed in both cases. Pathological examination of the uteri demonstrated haematometra in one dog and pyometra in the other.

The effect of heparin on tissue factor and tissue factor pathway inhibitor in patients with acute myocardial infarction.

We examined plasma TF and free TFPI levels in 26 consecutive patients with AMI, 26 patients with stable exertional angina, and 25 patients with chest pain syndrome. In patients with AMI, blood samples were obtained immediately after admission and at 4, 8, 16, 24, and 48 h, and the third, fifth, seventh, and fourteenth day after initiation of reperfusion therapy. Plasma TF levels in patients with AMI on admission were significantly higher than in the chest pain syndrome and stable exertional angina groups (248.0+/-117. 4 vs. 179.5+/-29.2 vs. 189.5+/-29.6 pg/ml, P<0.01). In patients with AMI, the level subsequently decreased after heparin administration and was maintained at significantly lower levels compared to those on admission. Plasma free TFPI levels in patients with AMI on admission were significantly higher than in the chest pain syndrome and stable exertional angina groups [33.5+/-12.4 vs. 26.0+/-7.6 ng/ml (P<0.01) vs. 27.5+/-6.3 ng/ml, P<0.05]. In patients with AMI, it reached the maximum level at 4 h after the administration of heparin, and gradually decreased over the time course. These data indicated that continuous administration of a low dose of heparin was effective in decreasing TF levels without affecting TFPI levels. Our results elucidate one of the mechanisms by which the administration of heparin is beneficial in AMI patients undergoing percutaneous revascularization.

Usefulness of three-dimensional visualization of coronary arteries using electron-beam computed tomography data with volume rendering.

Three-dimensional images of the coronary arteries using electron-beam computed tomography (EBCT) data with shaded surface rendering makes it possible to achieve images easily with a short reconstruction time. However, a lower threshold is required to estimate vessel diameters and there is a quantitative problem compared with conventional coronary arteriography. In combination with volume rendering, EBCT may be useful to detect the normal coronary artery wall, the major components of the atherosclerotic plaque (lipid, fibrous connective tissue and calcium). EBCT scans offer a new, non-invasive alternative to conventional coronary arteriography for diagnosis of coronary artery disease.

Increased plasma level of soluble E-selectin in acute myocardial infarction.

BACKGROUND: E-selectin, also known as endothelial cell leukocyte adhesion molecule-1, is a member of the selectin family of adhesion molecules and is expressed on vascular endothelial cells in inflammatory reactions. The induction of surface E-selectin expression by endothelial cells is considered a marker of activation. METHODS AND RESULTS: We examined the plasma soluble E-selectin (sE-selectin) level in 41 patients within 6 hours after the onset of acute myocardial infarction (AMI) and in 37 patients with stable exertional angina and 27 control patients. Blood samples were obtained on admission, after reperfusion therapy, and at 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 3 days, 5 days, 1 week, and 2 weeks after admission in the AMI group. In this group, 21 patients had a history of prodromal unstable angina before infarction and 20 had sudden onset of infarction. The plasma sE-selectin level (ng/mL) on admission was higher in the AMI group than in the stable exertional angina group and control group (38.5 +/- 3.1 vs 28.5 +/- 1.5, P <.01, 26.0 +/- 1.8, P <.01, respectively). In addition, plasma sE-selectin levels were higher in the patients with AMI with prodromal unstable angina than in those with a sudden onset of infarction on admission (44.7 +/- 5.4 vs 32.0 +/- 2.1, P <.05). The plasma sE-selectin level decreased slowly during the chronic phase both in patients with AMI with prodromal unstable angina (from 44.7 +/- 5.4 to 33.8 +/- 3.4, P <.01) and those with a sudden onset of infarction (from 32.0 +/- 2.1 to 24.9 +/- 2.4, P <.01). CONCLUSIONS: These results suggest that an increase of sE-selectin may reflect enhanced endothelial cell activation in patients with AMI. The higher sE-selectin level in patients with AMI with prodromal unstable angina may have been associated with repeated episodes of myocardial ischemia and reperfusion.

Hemodynamic effects of intravenous administration of olprinone hydrochloride on experimental pulmonary hypertension.

To examine acute effects of olprinone hydrochloride (CAS 106730-54-0, Coretec) on pulmonary hypertension, hypoxic pulmonary hypertension was produced in 6 adult Beagle dogs. Using this pulmonary hypertension model, single intravenous bolus injections of olprinone at doses of 10, 30 and 100 micrograms/kg were administered at 5-min intervals and hemodynamic parameters were evaluated. Heart rate increased at doses of 30 and 100 micrograms/kg, but did not change at a dose of 10 micrograms/kg. Mean aortic pressure, mean pulmonary arterial pressure, pulmonary vascular resistance and systemic vascular resistance and right ventricular stroke work index did not change at doses of 10 and 30 micrograms/kg, but they decreased significantly at a dose of 100 micrograms/kg. On the other hand, cardiac index and the first derivative value of the left ventricular pressure did not show significant change at all doses. These results indicate the vasodilating effects on peripheral and pulmonary vessels in hypoxic model at high doses of olprinone. Its application in right heart failure accompanied by pulmonary hypertension therefore is expected to yield promising results.