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Toshihiro Morita

Publications and source records attributed to Toshihiro Morita.

At least 19 recordsLinked to original sources
PubMed2006

Three-vessel coronary artery disease complicated with congestive heart failure in a highly aged patient with tetralogy of Fallot having undergone palliative surgeries.

An increasing number of patients with tetralogy of Fallot (TOF) are reaching older age. We encountered a 75-year-old woman with uncorrected TOF and concomitant severe coronary artery disease (CAD) with congestive heart failure. Her CAD risk factor was hyperlipidemia, which had been untreated. Successful percutaneous coronary interventions have improved her clinical condition and provided long-term survival. Although CAD is considered to be a rare complication in adults with TOF, both strict modification of CAD risk factors and early detection of CAD would be also required in this population, given the residual TOF lesions relating to acute exacerbation of clinical presentation.

Aged↗
PubMed2006

The beneficial effect of coronary-artery-bypass surgery on survival in patients with diabetic retinopathy.

OBJECTIVE: The presence of retinopathy is a predictor of mortality following coronary revascularization in diabetics. We studied whether revascularization by coronary-artery-bypass surgery (CABG), as compared with percutaneous coronary intervention (PCI), influences the prognosis in diabetics with retinopathy. METHODS: Between April 1996 and March 2004, 1489 patients underwent revascularization as an initial procedure. Among these a total of 319 diabetics underwent retinal examination prior to the initial revascularization. These patients were classified according to whether they had retinopathy and whether they had undergone CABG, either initially or after PCI. Mortality rates were estimated from the time of initial revascularization procedure. RESULTS: The average follow-up from the time of initial revascularization was 48.2+/-28.6 months. In 153 diabetics with retinopathy, 59 eventually underwent CABG. During the entire follow-up period, there were 2 (3.4%) deaths in diabetics with retinopathy who underwent CABG and 14 (14.9%) deaths in those who did not have CABG. Mortality curves differed significantly between the two groups (P = 0.007). After adjustment for risk factors, the relative risk of death was 0.13 afforded by CABG (95% CI, 0.03-0.62; P = 0.011). In 166 diabetics without retinopathy, mortality curves were similar between the patients who underwent CABG and those who did not have CABG (P = 0.94). CONCLUSIONS: CABG conferred a survival advantage in diabetics with retinopathy. In contrast, no survival advantage was evident in diabetics without retinopathy undergoing CABG. Retinal status should be taken into consideration when considering revascularization strategy for diabetics who have coronary artery disease.

Aged↗
PubMed2006

New insights in the treatment strategy for pulmonary arterial hypertension.

INTRODUCTION: Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. CASE REPORT: In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. FUTURE PERSPECTIVE: We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.

Anticoagulants↗
PubMed2006

Comparative effects of azelnidipine and other Ca2+-channel blockers on the induction of inducible nitric oxide synthase in vascular smooth muscle cells.

Overproduction of nitric oxide by inducible nitric oxide synthase contributes to the progression of cardiovascular disease. We investigated the effects of azelnidipine and other Ca2+-channel blockers on nitric oxide production by cultured aortic smooth muscle cells isolated from Wistar rats and human umbilical vein endothelial cells (HUVECs), using the Griess reaction and oxyhemoglobin method. Release of lactic dehydrogenase (LDH) was measured to evaluate cell damage, and immunohistochemistry was performed to examine the expression of inducible nitric oxide synthase and nitrotyrosine protein. Azelnidipine and other Ca2+-channel blockers inhibited the release of nitric oxide induced by lipopolysaccharide plus interferon-gamma. Azelnidipine inhibited it most potently among the Ca2+-channel blockers tested (azelnidipine, amlodipine, nifedipine, diltiazem, verapamil, and nicardipine) at a concentration of 10 microM. Longer stimulation with these agents induced the expression of inducible nitric oxide synthase and nitrotyrosine, with an increase of lactic dehydrogenase release, whereas azelnidipine suppressed these changes. In human umbilical vein endothelial cells, azelnidipine enhanced basal nitric oxide production by endothelial nitric oxide synthase. In conclusion, azelnidipine potently inhibited the induction of inducible nitric oxide synthase and then nitric oxide production in vascular smooth muscle cells, while enhancing constitutive nitric oxide production by endothelial cells. Azelnidipine may inhibit nitrotyrosine expression and cell damage caused by overproduction of nitric oxide, suggesting a mechanism for its cardiovascular protective effect.

Animals↗
PubMed2006

Amiodarone and N-desethylamiodarone enhance endothelial nitric oxide production in human endothelial cells.

Amiodarone (AM) is a potent vasodilator and exhibits diverse cardiovascular protective effects in vivo, but their underlying mechanisms remain unsettled. We investigated the effects of AM and N-desethylamiodarone (DEA), the major metabolite of AM, on endothelial nitric oxide (NO) production using cultured human umbilical vein endothelial cells (HUVECs). The release of NO was evaluated as measured by nitrite, a stable metabolite of NO, using the Griess reaction and also measured directly by a NO-selective electrode. The expression of each nitric oxide synthase (NOS) mRNA was examined by reverse transcriptase-polymerase chain reaction (RT-PCR), and the effects of AM on eNOS mRNA expression were studied by quantitative real-time RT-PCR. AM and DEA (1-30 microM) enhanced NO production in a concentration-dependent manner. DEA was capable of producing more NO than AM. L-NAME, a nonselective NOS inhibitor, EGTA, a Ca(2+)-chelating agent, and nickel, a nonspecific Ca(2+) blocker, all inhibited AM-induced NO production. However, LY294002, an Akt pathway inhibitor and SB202190, a MAP kinase inhibitor, did not significantly suppress the production. In RT-PCR analysis, only eNOS mRNA was detected. Treatment with AM for 4 hours did not show a significant increase in the expression of eNOS mRNA. AM lower than 30 microM did not induce apoptosis, net cell loss, or LDH release from cells. The present study provides the first evidence that therapeutic concentrations of AM and DEA enhance eNOS-mediated NO production without any toxic or apoptotic effects. This mechanism may underlie the cardiovascular protective effects of AM and its metabolite observed in a clinical setting.

Amiodarone↗
PubMed2006

Reconstruction of an extensive chest wall defect using an external oblique myocutaneous flap following resection of an advanced breast carcinoma: report of a case.

We reconstructed a large chest wall defect, resulting from the resection of a locally advanced breast carcinoma, using an external oblique myocutaneous flap. The patient, a 58-year-old Japanese woman, presented with an inoperable breast carcinoma (Stage IV). Combination chemotherapy with cyclophosphamide (CPA) and epirubicin hydrochloride (EPI) resulted in a reduction in size of both the primary tumor and the metastatic lesions. However, the patient continued to experience purulent discharge accompanied by an unpleasant odor, as well as contact bleeding from the residual breast lesion. To address these complaints, we removed much of the remaining tumor surgically. The resulting skin defect measured 440 cm(2) and was covered using an external oblique myocutaneous flap. The patient's postoperative course was excellent, and she was still alive and well after 40 months of chemotherapy. This case is a demonstration of the effectiveness of the external oblique myocutaneous flap for the coverage of large ipsilateral chest wall defects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow.

We investigated the hemodynamic and hormonal responses to a short-term low-intensity resistance exercise (STLIRE) with the reduction of muscle blood flow. Eleven untrained men performed bilateral leg extension exercise under the reduction of muscle blood flow of the proximal end of both legs pressure-applied by a specially designed belt (a banding pressure of 1.3 times higher than resting systolic blood pressure, 160-180 mmHg), named as Kaatsu. The intensity of STLIRE was 20% of one repetition maximum. The subjects performed 30 repetitions, and after a 20-seconds rest, they performed three sets again until exhaustion. The superficial femoral arterial blood flow and hemodynamic parameters were measured by using the ultrasound and impedance cardiography. Serum concentrations of growth hormone (GH), vascular endothelial growth factor (VEGF), noradrenaline (NE), insulin-like growth factor (IGF)-1, ghrelin, and lactate were also measured. Under the conditions with Kaatsu, the arterial flow was reduced to about 30% of the control. STLIRE with Kaatsu significantly increased GH (0.11+/-0.03 to 8.6+/-1.1 ng/ml, P < 0.01), IGF-1 (210+/-40 to 236+/-56 ng/ml, P < 0.01), and VEGF (41+/-13 to 103+/-38 pg/ml, P < 0.05). The increase in GH was related to neither NE nor lactate, but the increase in VEGF was related to that in lactate (r = 0.57, P < 0.05). Ghrelin did not change during the exercise. The maximal heart rate (HR) and blood pressure (BP) in STLIRE with Kaatsu were higher than that without Kaatsu. Stroke volume (SV) was lower due to the decrease of the venous return by Kaatsu, but, total peripheral resistance (TPR) did not change significantly. These results suggest that STLIRE with Kaatsu significantly stimulates the exercise-induced GH, IGF, and VEGF responses with the reduction of cardiac preload during exercise, which may become a unique method for rehabilitation in patients with cardiovascular diseases.

Adaptation, Physiological↗
PubMed2005

Comparison of various bone marrow fractions in the ability to participate in vascular remodeling after mechanical injury.

In contrast to conventional assumption, recent reports propose the possibility that hematopoietic stem cells (HSCs) may have broader potential to differentiate into various cell types. Here, we tested the pluripotency of HSCs by comparing vascular lesions induced by mechanical injury after bone marrow reconstitution with total bone marrow (TBM) cells, c-Kit+ Sca-1+ Lin- (KSL) cells, or a single HSC cell (Tip-SP CD34-KSL cell, CD34- c-Kit+ Sca-1+ Lin- cell with the strongest dye-efflux activity) harboring green fluorescent protein (GFP). The lesions contained a significant number of GFP-positive cells in the TBM and KSL groups, whereas GFP-positive cells were rarely detected in the HSC group. These results suggest that transdifferentiation of a highly purified HSC seems to be a rare event, if it occurs at all, whereas bone marrow cells including the KSL fraction can give rise to vascular cells that substantially contribute to repair or lesion formation after mechanical injury.

Animals↗
PubMed2005

Analysis of the factors related to a decrease in jugular venous oxygen saturation in patients with diabetes mellitus during normothermic cardiopulmonary bypass.

PURPOSE: We sought to examine what factors, including cerebrovascular carbon dioxide (CO(2)) reactivity, are related to a decrease in internal jugular venous oxygen saturation (SjvO(2)) during normothermic cardiopulmonary bypass (CPB) in patients with diabetes mellitus. METHODS: Twenty-three diabetic patients scheduled to undergo elective coronary artery bypass grafting were studied. As a control, 27 age-matched control patients without diabetes mellitus were also examined. After the induction of anesthesia, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to continuously monitor SjvO(2). Arterial and jugular venous blood gases were measured during CPB. The cerebrovascular CO(2) reactivity was measured after the induction of anesthesia and before the start of surgery using a 2.5-MHz pulsed transcranial Doppler probe. RESULTS: The SjvO(2) values in the diabetic group were lower than those in the control group at the initiation of CPB and at 20, 40, and 60 min after the start of CPB. The values for pre- and post-CO(2) reactivity in the control group did not significantly differ (pre-CPB: 4.8% +/- 2.3% mmHg(-1); post-CPB: 5.9% +/- 4.4% mmHg(-1)). In contrast, the values for CO(2) reactivity were lower post CPB than pre-CPB in the diabetic group (Pre-CPB: 6.3% +/- 2.9% mmHg(-1); post-CPB: 4.7% +/- 2.6% mmHg(-1); P < 0.05). In the diabetic group, glycosylated hemoglobin A1c (HbA1c) is considered to be a factor related to a decrease in SjvO(2) during CPB. CONCLUSIONS: Cerebrovascular CO(2) reactivity in diabetic patients decreased after the cessation of CPB but not in the control patients. In addition, HbA1c is also thought to be a factor related to a decrease in SjvO(2) in diabetic patients.

Aged↗
PubMed2005

Molecular and pharmacological characteristics of transient voltage-dependent K+ currents in cultured human pulmonary arterial smooth muscle cells.

The A-type voltage-dependent K(+) current (I(A)) has been identified in several types of smooth muscle cells including the pulmonary artery (PA), but little is known about the pharmacological and molecular characteristics of I(A) in human pulmonary arterial smooth muscle cells (hPASMCs). We investigated I(A) expressed in cultured PASMCs isolated from the human main pulmonary artery, using patch-clamp techniques, reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR and immunocytochemical studies. With high EGTA and ATP in the pipette, the outward currents were dominated by a transient K(+) current (I(A)), followed by a relatively small sustained outward current (I(K)). I(A) was inhibited by 4-aminopyridine (4-AP) concentration-dependently, and could be separated pharmacologically into two components by tetraethylammonium (TEA) sensitivity. A component was sensitive to TEA, and the second component was insensitive to TEA. I(A) was inhibited by blood depressing substrate (BDS)-II, a specific blocker of K(V)3.4 subunit, and phrixotoxin-II, a specific blocker of K(V)4.2 and 4.3. Flecainide inhibited I(A) concentration-dependently, but it inhibited it preferentially in the presence of TEA (TEA-insensitive I(A)). Systematic screening of expression of K(V) genes using RT-PCR showed the definite presence of transcripts of the I(A)-encoding genes for K(V)3.4, K(V)4.1, K(V)4.2 and K(V)4.3 as well as the I(K)-encoding genes for K(V)1.1, K(V)1.5 and K(V)2.1. The real-time RT-PCR analysis showed that the relative abundance of the encoding genes of I(A) alpha-subunit and K(V) channel-interacting proteins (KChIPs) was K(V)4.2 > K(V)3.4 > K(V)4.3 (long) > K(V)4.1, and KChIP3 >> KChIP2, respectively. The presence of K(V)3.4, K(V)4.2 and K(V)4.3 proteins was also demonstrated by immunocytochemical studies, and confirmed by immunohistochemical staining using intact human PA sections. These results suggest that I(A) in cultured hPASMCs consists of two kinetically and pharmacologically distinct components, probably K(V)3.4 and K(V)4 channels.

Calcium-Binding Proteins↗
PubMed2005

Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain.

AIMS: The principal site for the metabolism of propofol is the liver. However, the total body clearance of propofol is greater than the generally accepted hepatic blood flow. In this study, we determined the elimination of propofol in the liver, lungs, brain and kidneys by measuring the arterial-venous blood concentration at steady state in patients undergoing cardiac surgery. METHODS: After induction of anaesthesia, propofol was infused continuously during surgery. For measurement of propofol concentration, blood samples were collected from the radial and pulmonary artery at predetermined intervals. In addition, blood samples from hepatic and internal jugular vein were collected at the same times in 19 patients in whom a hepatic venous catheter was fitted and the other six in whom an internal jugular venous catheter was fitted, respectively. In six out of 19 patients fitted with a hepatic venous catheter, blood samples from the radial artery and the renal vein were also collected at the same time, when the catheter was inserted into the right renal vein before insertion into the hepatic vein. RESULTS: Hepatic clearance of propofol was approximately 60% of total body clearance. The hepatic extraction ratio of propofol was 0.87 +/- 0.09. There was no significant difference in the concentration of propofol between the radial, pulmonary arteries and internal jugular vein. However, a high level of propofol extraction in the kidneys was observed--the renal extraction ratio being 0.70 +/- 0.13. CONCLUSIONS: We have demonstrated substantial renal extraction of propofol in human. Metabolic clearance of propofol by the kidneys accounts for almost one-third of total body clearance and may be the major contributor to the extrahepatic elimination of this drug.

Adult↗
PubMed2004

Ursodeoxycholic acid inhibits endothelin-1 production in human vascular endothelial cells.

Endothelin-1 is known to be implicated in the pathogenesis of hepatobiliary diseases such as cirrhosis, especially in portal hypertension. This study aimed to investigate the effects of ursodeoxycholic acid on endothelin-1 production in human endothelial cells. The effects of ursodeoxycholic acid and its conjugates (tauroursodeoxycholic and glycoursodeoxycholic acids) on endothelin-1 production as well as nitric oxide (NO) in human umbilical vein endothelial cells (HUVECs) were examined. The production of endothelin-1 and nitric oxide in culture medium was measured using enzyme-linked immunosorbent assay (ELISA) and the Griess method, respectively. Endothelin-1 and endothelial nitric oxide synthase (eNOS) mRNA expression were investigated by real-time quantitative reverse transcriptase/polymerase chain reaction (RT-PCR). Ursodeoxycholic acid (30-1000 microM) inhibited endothelin-1 production in a concentration-dependent manner, and ursodeoxycholic acid at concentrations higher than 300 microM increased nitric oxide production in culture medium. The conjugates of ursodeoxycholic acid also increased nitric oxide production and decreased endothelin-1 production, which was less effective than ursodeoxycholic acid. N-nitro-L-arginine-mythel-ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, suppressed the ursodeoxycholic acid-induced nitric oxide production, but it did not antagonize the inhibitory effects of ursodeoxycholic acid on endothelin-1 production. Ursodeoxycholic acid also induced a concentration-dependent decrease in endothelin-1 mRNA expression without significant changes in eNOS mRNA expression. These results provide novel evidence that ursodeoxycholic acid inhibits endothelin-1 production in human endothelial cells, but nitric oxide is not responsible for the inhibitory effect of ursodeoxycholic acid on endothelin-1. Thus, ursodeoxycholic acid therapy may prevent the development of several pathogenesis such as portal hypertension observed in patients with cirrhosis due to the improvement of endothelial function.

Cell Line↗
PubMed2004

Long-term results of high-dose extracorporeal and endocavitary radiation therapy followed by abdominoperineal resection for distal rectal cancer.

PURPOSE: To examine the complications, local effects, survival, and prognostic factors of preoperative high-dose radiation therapy in patients with advanced carcinomas of the distal rectum. METHODS: Forty-one patients with tethered or fixed rectal cancer located a median distance of 3.0 cm from the anal verge were treated with extracorporeal and endocavitary radiation therapy (70 Gy), followed 2 weeks later by abdominoperineal resection (APR). RESULTS: This combined radiotherapy achieved acceptable results. Postoperative complications developed in 18 patients (43.9%), 10 (24.3%) of which involved perineal dehiscence. Two patients (4.8%) suffered more than grade 3 toxicity. Destructive changes were histologically confirmed in all specimens, and there were four (9.8%) sterile specimens. Recurrence developed in 11 patients and there were 6 cancer-related deaths. Among six cases of local recurrence, three were found just outside of the radiation field. The 5-year survival and disease-free survival rates were 82.9% and 71.8%, respectively. Multivariate analysis revealed that nodal involvement was the sole independent prognostic factor for survival. Sexual function was maintained in the most recent patients who underwent APR with autonomic nerve-preserving surgery. CONCLUSION: Although the original aim of our treatment focused on curability, this combination therapy may be an option for selected patients, because of potential prevention of local recurrence, relatively low morbidity, and promising autonomic nerve function.

Adult↗
PubMed2004

Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding.

OBJECTIVE: Cardiopulmonary bypass is known to result in a reduction in the plasma binding of drugs. The resulting effect on the hepatic clearance of drugs with low extraction is well understood. However, the situation with those that are highly extracted is less clear. Studies were, therefore, undertaken with one such drug, propofol, for which plasma binding was changed during cardiac surgery with cardiopulmonary bypass. METHODS: After induction of anesthesia with midazolam in 19 patients, propofol was infused continuously at a rate of 4 mg. kg(-1). h(-1) during surgery. Propofol's concentration was measured by HPLC in blood samples collected from the radial artery and hepatic vein during surgery at predetermined intervals. The drug's unbound fraction in arterial plasma was estimated via equilibrium dialysis. RESULTS: The total concentration of propofol in blood was unchanged during surgery except shortly after the initiation of cardiopulmonary bypass. By contrast, the fraction of unbound propofol in blood increased by 2-fold during cardiopulmonary bypass and then decreased after the completion of cardiopulmonary bypass. The hepatic extraction ratio of propofol was greater than 0.8 and remained constant throughout surgery. The ratio of propofol concentration in erythrocytes to that in blood increased by 1.6-fold during cardiopulmonary bypass. CONCLUSIONS: During cardiopulmonary bypass, a significant increase in the concentration of unbound propofol occurred without alteration in the total propofol concentration in blood. The effect of the changes of propofol's protein binding on its kinetics was consistent with the predictions based on the well-stirred model of hepatic elimination for an intravenously infused high-clearance drug. Our finding on propofol pharmacokinetics may be the first example demonstrating the theoretic prediction of the well-stirred model.

Adult↗
PubMed2003

Inhibitory effects of ursodeoxycholic acid on the induction of nitric oxide synthase in vascular smooth muscle cells.

The expression of inducible nitric oxide synthase (iNOS) and the resultant increased nitric oxide production are associated with endotoxemia and atherosclerotic lesions observed in transplant hearts or balloon-injured artery. Ursodeoxycholic acid has been shown to have cardiovascular protective effects, such as inhibition of the development of transplant arteriosclerosis, but its mechanism remains unclear. Here, we investigated the effects of ursodeoxycholic acid on nitric oxide production and the expression of iNOS in vascular smooth muscle cells isolated from adult rat aorta and rabbit coronary artery. Nitrite released from cells in the culture medium was measured with the Griess reaction. iNOS mRNA and protein were measured by Northern and Western blot analyses. Treatment with ursodeoxycholic acid (30-1000 microM) significantly inhibited lipopolysaccharide plus interferon-gamma-induced nitric oxide production in a concentration-dependent manner, but ursodeoxycholic acid showed only small inhibitory effects on nitric oxide production that had already been induced by lipopolysaccharide plus interferon-gamma. Ursodeoxycholic acid by itself did not affect basal nitric oxide production. Ursodeoxycholic acid also suppressed lipopolysaccharide plus interferon-gamma-induced expression of iNOS mRNA and protein. Ursodeoxycholic acid had the most potent inhibitory effect among various kinds of bile acids examined, i.e. chenodeoxycholic acid, deoxycholic acid, cholic acid and conjugated bile acids such as tauroursodeoxycholic acid. These results suggest that ursodeoxycholic acid inhibits the induction of iNOS and then nitric oxide production in aortic and coronary artery smooth muscle cells, suggesting a possible mechanism for the cardiovascular protective effect of ursodeoxycholic acid under various pathophysiological conditions such as endotoxemia and atherosclerosis.

Animals↗
PubMed2003

Increased plasma concentrations of the mature form of adrenomedullin during cardiac surgery and hepatosplanchnic hypoperfusion.

Adrenomedullin is a potent vasodilatory peptide. Plasma adrenomedullin (AM) concentrations increase during and after cardiopulmonary bypass (CPB). However, the cause of this increase and its site of production have not been identified. We investigated the role of the hepatosplanchnic and cerebral circulations in the increase of plasma AM and investigated whether tissue hypoxygenation is a cause of the AM increase seen during CPB. We measured plasma total AM (AM-T) and the biologically active form of AM, mature AM (AM-m), in seven patients undergoing CPB. Both plasma AM-T and AM-m concentrations increased significantly 60 min after weaning from CPB. At this time point, arterial AM-T and AM-m concentrations were 18-fold and 10-fold larger, respectively, than baseline values measured after the induction of anesthesia. The plasma AM-m concentration and the ratio of AM-m/AM-T in blood from the hepatic vein were significantly larger than those from the radial artery or jugular bulb. The AM-m/AM-T ratio decreased during CPB, suggesting that production of the intermediate form of AM, AM-glycine, is more than that of AM-m. The oxygen tension of the hepatic venous blood (PhvO2) was significantly less during CPB. Plasma AM-m concentrations sampled from the hepatic vein showed a significant negative correlation with PhvO2 at 10 min (r = 0.824; P < 0.02) and 60 min (r = 0.828; P < 0.02) after the onset of CPB. These data suggest that the hepatosplanchnic circulation is an important source of AM-m during CPB. Furthermore, hypoxygenation of the hepatosplanchnic region may be an important cause of this AM-m increase.

Adrenomedullin↗