Quantification of peak blood flow velocity at the cardiac valve and great thoracic vessels by four-dimensional flow and two-dimensional phase-contrast MRI compared with echocardiography: a systematic review and meta-analysis.

AIM: To objectively examine the agreement and correlation between four-dimensional (4D) flow magnetic resonance imaging (MRI) and traditional two-dimensional (2D) phase-contrast (PC) MRI with the reference standard of Doppler echocardiography for measuring peak blood velocity at the cardiac valve and great arteries, and to assess if 4D flow MRI offers an advantage over the traditional 2D method. MATERIALS AND METHODS: The literature was searched systematically for studies that evaluate the degree of correlation and agreement between 4D flow MRI or 2D PC MRI and Doppler retrieved from PubMed, EMBASE, and the Cochrane Library. A meta-analysis was conducted to determine the peak velocity pooled bias with 95% limits of agreement (LoA) and correlation coefficient (r) for 4D flow MRI and 2D PC MRI compared with Doppler. RESULTS: Ten studies that compared 4D flow MRI with Doppler and 12 studies that compared 2D PC MRI with Doppler were included. 4D flow MRI showed an underestimation with bias and 95% LoA of -0.09 (-0.41, 0.24) m/s (p=0.079) while 2D PC MRI showed a poorer agreement with a bias and 95% LoA of -0.25 (-0.53, 0.03), p=0.596. 4D flow MRI and 2D PC MRI showed a strong correlation with R=0.80 (95% CI 0.75, 0.84; p<0.001) and R=0.83 (95% CI 0.79, 0.87; p<0.001), respectively. CONCLUSION: In this meta-analysis, 4D flow MRI provides improved assessment of peak velocity when compared with traditional 2D PC MRI. 4D flow MRI can be considered an important complement or substitute to Doppler echocardiography for peak velocity assessment.

Arterial Hypertension and Plasma Glucose Modulate the Vasoactive Effects of Nitroso-Sulfide Coupled Signaling in Human Intrarenal Arteries.

We have investigated the vasoactive effects of the coupled nitro-sulfide signaling pathway in lobar arteries (LAs) isolated from the nephrectomized kidneys of cancer patients: normotensive patients (NT) and patients with arterial hypertension (AH). LAs of patients with AH revealed endothelial dysfunction, which was associated with an increased response to the exogenous NO donor, nitrosoglutathione (GSNO). The interaction of GSNO with the H2S donor triggered a specific vasoactive response. Unlike in normotensive patients, in patients with AH, the starting and returning of the vasorelaxation induced by the end-products of the H2S-GSNO interaction (S/GSNO) was significantly faster, however, without the potentiation of the maximum. Moreover, increasing glycemia shortened the time required to reach 50% of the maximum vasorelaxant response induced by S/GSNO products so modulating their final effect. Moreover, we found out that, unlike K+ channel activation, cGMP pathway and HNO as probable mediator could be involved in mechanisms of S/GSNO action. For the first time, we demonstrated the expression of genes coding H2S-producing enzymes in perivascular adipose tissue and we showed the localization of these enzymes in LAs of normotensive patients and in patients with AH. Our study confirmed that the heterogeneity of specific nitroso-sulfide vasoactive signaling exists depending on the occurrence of hypertension associated with increased plasma glucose level. Endogenous H2S and the end-products of the H2S-GSNO interaction could represent prospective pharmacological targets to modulate the vasoactive properties of human intrarenal arteries.

Vasomotion as an oscillatory sign of functional impairment in the human internal thoracic artery: A study based on risk factors and vessel reactivity.

NEW FINDINGS: What is the central question of this study? Vasomotion has been viewed as a rhythmic oscillation of the vascular tone that is physiologically important for optimal tissue perfusion. Also, it has been studied primarily in the microcirculation. However, the precise underlying mechanisms and the physiological significance remain unknown. What is the main finding and its importance? Vasomotion is not specific to the microcirculation, as shown by our findings. In human arteries from patients undergoing cardiac surgery, an increased incidence was associated with endothelial dysfunction settings. Therefore, this oscillatory behaviour might be a signal of functional impairment and not of integrity. ABSTRACT: Vasomotion has been defined as the rhythmic oscillation of the vascular tone, involved in the control of the blood flow and subsequent tissue perfusion. Our aims were to study the incidence of vasomotion in the human internal thoracic artery and the correlation of this phenomenon with the clinical profile and parameters of vascular reactivity. In our study, vasomotion was elicited with a single-dose contractile stimulation of noradrenaline (10 µm) in internal thoracic artery segments, from patients undergoing coronary artery bypass grafting, mounted in tissue organ bath chambers. The incidence was 29.1%. Vessel samples with vasomotion presented significantly higher contractility in response to both potassium chloride (maximal response or Emax of 7.65 ± 5.81 mN versus 4.52 ± 3.73 mN in control vessels, P = 0.024) and noradrenaline (Emax of 7.60 ± 5.93 mN versus 2.96 ± 4.41 mN in control vessels, P < 0.001). Predictive modelling through multivariable logistic regression analysis showed that female sex (odds ratio = 9.82) and increasing maximal response to noradrenaline (odds ratio = 1.19, per 1 mN increase) were associated with a higher probability of the occurrence of vasomotion, whereas increasing kidney function (expressed as estimated glomerular filtration rate) was associated with a lower probability (odds ratio = 0.97, per 1 ml min-1  (1.73 m)-2 ]. Our results provide a characterization of the phenomenon of vasomotion in the internal thoracic artery and suggest that vasomotion might be associated with endothelial dysfunction settings, as determined by a multivariable analysis approach. Considering the associations observed in our results, vasomotion might be a signal of functional impairment and not of integrity.

Preoperative and intraoperative assessment of volumetric blood flow velocity through the internal thoracic artery in patients with cad. / Predoperatsionnaia i intraoperatsionnaia otsenka ob''emnoi skorosti krovotoka po vnutrennei grudnoi arterii u bol'nykh IBS.

The left internal thoracic artery (ITA) is currently an artery of choice for revascularization of coronary arteries. Ultrasonographic duplex scanning (USDS) and ultrasound Doppler flowmetry (UDF) are sequential techniques to control patency of the ITA at stages of rendering care for patients on restoring coronary blood flow. We compared two methods of measuring the volumetric blood flow velocity: by means of USDS and UDF. The obtained results were statistically processed. It was determined that transthoracic USDS and intraoperative UDF in the assessment of the volumetric blood velocity through the ITA in patients with coronary artery disease are comparable methods, provided the patients have similar parameters of central haemodynamics.

Intercostal Artery Reconstruction: The Simple and Effective Technique on Spinal Cord Protection during Thoracoabdominal Aortic Replacement.

BACKGROUND: To retrospectively analyze the role of intercostal artery reconstruction in the spinal cord protection for patients undergoing extensive thoracoabdominal aortic aneurysm repair. METHODS: From August 2007 to 2014, thoracoabdominal aortas (Crawford II) of 81 consecutive patients with mean age 39.4 ± 10.32 years were repaired. Seventy-three of these patients (90.12%) were diagnosed with aortic dissection in our group, 25 (30.86%) with Stanford type A dissection and 48 (59.26%) with Stanford B aortic dissection. All 25 patients with type A dissection have previously undergone surgical procedures which include Bentall's procedures in 11 cases, ascending aortic replacement in 6 cases, and total aortic arch replacement in 8 cases. All procedures were performed under profound hypothermia with interval cardiac arrest after making a thoracoabdominal incision. Extracorporeal circulation was instituted with 2 arterial cannulae and a single venous cannula in the right atrium. T6-T12 intercostal arteries and L1 and L2 lumbar arteries were formed to a neo-intercostal artery in place and were connected to an 8 mm branch for maintaining spinal cord blood perfusion. Visceral arteries were joined into a patch and anastomosed to the end of the main graft. The left renal artery was anastomosed to an 8 mm branch or joined to the patch. The other 10 mm branches were anastomosed to iliac arteries. RESULTS: With 100% follow-up, early mortality was 7.4%. Six deaths were recorded; 1 patient died of cerebral hemorrhage, 3 of renal failure, 1 of heart failure because of myocardial infarction, and the last one died from the rupture of celiac artery dissection. The rate of postoperative spinal cord deficits was 3.7%, 2 patients with paraplegia and 1 patient with paraparesis. None had bladder or rectum dysfunction. Neo-intercostal arteries were clogged in 12 patients within follow-up period and formed pseudoaneurysm in 2 patients with Marfan syndrome. The mean survival time in this group was 54.22 ± 3.03 months (95% confidence interval 44.37-59.90 months) with survival rate of 92.37% after 1 year, 89.02% after 2 years, and 85.54% after 5 years. All patients were free from spinal cord deficits. CONCLUSIONS: Intercostal artery reconstruction is an effective technique for spinal cord protection in patients with the thoracoabdominal aortic repair. It can achieve favorable results and avoid spinal cord deficits with long-term follow-up.

ТRANSPLANTATION OF AUTOLOGOUS CELLS IN COMPLEX OF TREATMENT OF COMPLICATED ARTERIAL FORM IN THE THORACIC OUTLET SYNDROME.

Impact of the autologous cells transplantation in complex of treatment of complicated arterial form of thoracic outlet syndrome was estimated. In accordance to the proce' dure proposed 18 patients were operated on, in 16 patients a standard decompressive and reconstructive operative interventions were performed. The proposed procedure application have promoted improvement of the patients' treatment results due to opti' mization of microcirculation and angiogenesis.

Successful lung lobectomy for a lung cancer following thoracic endovascular aortic repair for a thoracic aortic aneurysm: report of a case.

Lung cancer and a thoracic aortic aneurysm were detected simultaneously in a 79-year-old male patient with diabetes. The aneurysm was first treated by thoracic endovascular aortic repair. A right lower lobectomy was subsequently performed after the blood flow of the bronchial and intercostal arteries was confirmed by computed tomographic angiography. The bronchial stump was covered with an intercostal muscle flap. The patient's postoperative course was uneventful. Thoracic endovascular aortic repair is a useful and less invasive treatment for such cases, but a blood flow evaluation of the aortic branches should be done following this procedure before a lung resection is considered.

On how whales avoid decompression sickness and why they sometimes strand.

Whales are unique in that the supply of blood to the brain is not by the internal carotid arteries, but by way of thoracic and intra-vertebral arterial retia. We found in the harbor porpoise (Phocoena phocoena) that these retia split up into smaller anastomosing vessels and thin-walled sinusoid structures that are embedded in fat. The solubility of nitrogen is at least six times larger in fat than in water, and we suggest that nitrogen in supersaturated blood will be absorbed in the fat, by diffusion, during the very slow passage of the blood through the arterial retia. Formation of nitrogen bubbles that may reach the brain is thereby avoided. We also suggest that mass stranding of whales may be due to disturbances to their normal dive profiles, resulting in extra release of nitrogen that may overburden the nitrogen 'trap' and allow bubbles to reach the brain and cause abnormal behavior.

Prenatal High-Sucrose Diet Induced Vascular Dysfunction in Thoracic Artery of Fetal Offspring.

SCOPE: Maternal nutrition during pregnancy is related to intrauterine fetal development. The authors' previous work reports that prenatal high sucrose (HS) diet impaired micro-vascular functions in postnatal offspring. It is unclear whether/how prenatal HS causes vascular injury during fetal life. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Pregnant HS increases maternal weight before delivery. Fetal thoracic aorta is separated for experiments. Angiotensin II (AII)-stimulated vascular contraction of fetal thoracic arteries in HS group is greater, which mainly results from the enhanced AT1 receptor (AT1R) function and the downstream signaling. Nifedipine significantly increases vascular tension in HS group, indicating that the L-type calcium channels (LTCCs) function is strengthened. 2-Aminoethyl diphenylborinate (2-APB), inositol 1,4,5-trisphosphate receptors (IP3Rs) inhibitor, increases vascular tension induced by AII in HS group and ryanodine receptors-sensitive vascular tone shows no difference in the two groups, which suggested that the activity of IP3Rs-operated calcium channels is increased. CONCLUSION: These findings suggest that prenatal HS induces vascular dysfunction of thoracic arteries in fetal offspring by enhancing AT1R, LTCCs function and IP3Rs-associated calcium channels, providing new information regarding the impact of prenatal HS on the functional development of fetal vascular systems.

Use of a surgeon-modified branched thoracic endograft to preserve an aortorenal bypass during treatment of an intercostal patch aneurysm.

A 72-year-old man presented with thoracic pain. Nine years earlier, a descending aortic dissection with aneurysmal degeneration had been treated by thoracoabdominal aortic graft placement with reimplantation of a visceral patch and an intercostal patch. A separate left aortorenal bypass had also been performed with the bypass originating from the thoracic portion of the graft. He now presents with a 7.2-cm intercostal patch aneurysm in the aortic segment containing the origin of the patent aortorenal bypass. We present the use of a surgeon-modified branched thoracic endograft to salvage an aortorenal bypass originating in a thoracic aneurysm after previous open thoracoabdominal aortic aneurysm repair.

Coverage of visible intercostal and lumbar segmental arteries can predict the volume of cerebrospinal fluid drainage in elective endovascular repair of descending thoracic and thoracoabdominal aortic disease: a pilot study.

OBJECTIVES: Our goal was to identify anatomical and physiological factors that could predict the amount of cerebrospinal fluid (CSF) drainage in patients undergoing elective endovascular repair of descending thoracic and thoracoabdominal aortic disease. METHODS: All consecutive elective endovascular procedures performed for descending thoracic or thoracoabdominal aortic disease between January 2015 and December 2017 were included in the study. Routine use of CSF drainage was established in all patients. The goal of drainage was to reach a spinal fluid pressure of 10-12 mmHg by draining in 5-15-ml aliquots. The number of visible intercostal and lumbar segmental arteries (SAs) was evaluated before and after endovascular repair. The covering ratio of SAs was calculated as covered preoperative SAs/total preoperative SAs. RESULTS: Twenty-four consecutive patients were included in the final analysis. The indication for the intervention was a descending thoracic aneurysm in 13 cases, a thoracoabdominal aneurysm in 4 cases and a chronic type B dissection in 7 cases. The procedure performed was thoracic endovascular aortic repair in 20 cases and fenestrated endovascular aneurysm repair in 4 cases. None of the patients developed spinal cord ischaemia. The mean volume of CSF drained was 46 ml. The mean length of aortic coverage was 231 mm. The mean number of total preoperative SAs and of covered preoperative SAs was, respectively, 22 and 9. The volume of CSF drained was significantly correlated with all these variables (length of aortic coverage, total visible SAs and covered SAs), but the most powerful correlation was individuated with the covering ratio of SAs. CONCLUSIONS: Our findings suggest that the percentage of intercostal and lumbar SAs covered by placement of a stent graft can predict the volume of CSF drained in patients undergoing elective endovascular repair of descending thoracic and thoracoabdominal aortic disease.

Intercostal artery management in thoracoabdominal aortic surgery: To reattach or not to reattach?

BACKGROUND: The need for intercostal artery (ICA) reattachment in surgery for descending thoracic aortic aneurysm (DTAA) or thoracoabdominal aortic aneurysm (TAAA) remains controversial. We reviewed our experience over a 14-year period to assess the effects of ICA management on neurologic outcome after DTAA/TAAA repair. METHODS: Intraoperative data were reviewed to ascertain the status of T3-12 ICAs and L1-4 ICAs. Arteries were classified as reattached, ligated, occluded, or not exposed. Temporality of reattachment or ligation in response to an intraoperative ischemic event (ie, loss of motor evoked potentials [MEPs]) was noted. Adjustment for other predictors of immediate or delayed paraplegia (DP) was performed by multiple logistic regression. The effects of specific artery level and type of reattachment technique were assessed using stratified contingency tables. RESULTS: A total of 1096 DTAA/TAAAs were performed between 2001 and 2014. The mean patient age was 64 ± 15 years, and 37% were female. Spinal cord ischemia was identified in 10% of patients, including 35 (3%) immediate cases and 77 (7%) DP cases. Overall DP resolution was 47% at discharge. ICA ligation and intraoperative MEP changes were strong predictors of postoperative paraplegia. Multivariable analysis demonstrated that T8-12 ICA ligation significantly increased the risk for paraplegia (odds ratio, 1.3/artery; P < .041) even after adjustment for age >65 years, glomerular filtration rate, extent of II/III aneurysm, increased operative time, and intraoperative MEP loss. CONCLUSIONS: Loss of intraoperative MEPs is serious, and increases the risk of paraplegia in any ICA management strategy. Even with intact MEP, ligation of T8-12 ICAs is associated with increased risk. These findings support reattachment of T8-12 ICAs whenever feasible.

Mechanics of arterial subfailure with increasing loading rate.

Arterial subfailure leads to delayed symptomatology and high morbidity and mortality rates, particularly for the thoracic aorta and carotid arteries. Although arterial injuries occur during high-velocity automotive collisions, previous studies of arterial subfailure focused on quasi-static loading. This investigation subjected aortic segments to increasing loading rates to quantify effects on elastic, subfailure, and ultimate vessel mechanics. Sixty-two specimens were axially distracted, and 92% demonstrated subfailure before ultimate failure. With increasing loading rate, stress at initial subfailure and ultimate failure significantly increased, and strain at initial subfailure and ultimate failure significantly decreased. Present results indicate increased susceptibility for arterial subfailure and/or dissection under higher-rate extension. According to the present results, automotive occupants are at greater risk of arterial injury under higher velocity impacts due to greater body segment motions in addition to decreased strain tolerance to subfailure and catastrophic failure.

Vascular disease in COPD: Systemic and pulmonary expression of PARC (Pulmonary and Activation-Regulated Chemokine).

INTRODUCTION: The role of Pulmonary and Activation-Regulated Chemokine (PARC) in the physiopathology of Chronic Obstructive Pulmonary Disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC in lung tissue and its relationship with the vascular remodeling of the systemic and pulmonary arteries of COPD subjects. METHODS: To achieve this objective, protein and gene expression experiments, together with ELISA assays, were performed on the lung tissue, intercostal arteries and serum samples from COPD patients, non-obstructed smokers (NOS) and never-smokers (NS). RESULTS: A total of 57 subjects were included in the analysis (23 COPD, 18 NOS and 16 NS). In the comparisons between groups, a significantly increased lung protein expression of PARC was observed in the COPD group compared to the NOS group (1.96±0.22 vs. 1.29±0.27, P-adjusted = 0.038). PARC was located predominantly in the smooth muscle cells of the remodeled pulmonary muscular arteries and the macrophage-rich area of the alveolar parenchyma. No differences were detected in PARC gene expression analyses. The protein content of PARC in the intercostal arteries were similar between groups, though little remodeling was observed in these arteries. Circulating levels of PARC were numerically higher in patients with COPD compared to NOS and NS. CONCLUSION: The results of the present study suggest an increased lung protein expression of PARC in COPD subjects. This protein was mainly localized in the smooth muscle cells of the pulmonary muscular arteries and was associated with the severity of intimal thickening, indicating its possible role in this remodeling process.

Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats.

BACKGROUND AND OBJECTIVE: Several studies have found that chronic treatment with the dietary flavonoid quercetin lowers blood pressure and restores endothelial dysfunction in hypertensive animal models. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase protein expression and activity, and reduced reactive oxygen species might be involved in the improvement of endothelial function induced by quercetin in spontaneously hypertensive rats (SHR). DESIGN AND METHODS: Male SHR and Wistar-Kyoto (WKY) rats (5 weeks old) were treated with quercetin (10 mg/kg) or vehicle for 13 weeks. Changes in vascular expression of eNOS, caveolin-1 and p47 were analysed by Western blot, eNOS activity by conversion of [H]arginine to L-[H]citrulline, and NADPH oxidase activity by NADPH-enhanced chemoluminescence of lucigenin. RESULTS: In SHR, quercetin reduced the increase in blood pressure and heart rate and enhanced the endothelium-dependent aortic vasodilation induced by acetylcholine, but had no effect on the endothelium-independent response induced by nitroprusside. However, quercetin had no effect on endothelium-dependent vasoconstriction and aortic thromboxane B2 production. Compared to WKY, SHR showed upregulated eNOS and p47 protein expression, downregulated caveolin-1 expression, increased NADPH-induced superoxide production but, paradoxically, eNOS activity was reduced. Chronic quercetin treatment prevented all these changes in SHR. In WKY, quercetin had no effect on blood pressure, endothelial function or the expression or activity of the proteins analysed. CONCLUSIONS: Enhanced eNOS activity and decreased NADPH oxidase-mediated superoxide anion (O2) generation associated with reduced p47 expression appear to be essential mechanisms for the improvement of endothelial function and the antihypertensive effects of chronic quercetin.

The position of 'shunt restriction' along an arterialized vein affects venous congestion and flap perfusion of an arterialized venous flap.

UNLABELLED: Restriction of arteriovenous (AV) shunting has been shown to enhance peripheral perfusion and also reduce venous congestion of an arterialized venous flap. Thus, this study is designed to investigate the effect of 'shunt-restriction' location on venous congestion and flap perfusion in a 'shunt-restricted' arterialized venous flap (AVF). METHODS: Abdominal flaps based on the thoracoepigastric vessels of Sprague-Dawley rats were raised. The inferior epigastric vein was repaired to the femoral artery in order to create an AVF. The superior epigastric vein was preserved for drainage. Microcirculation and laser Doppler flowmetry results were compared between AVFs with 'shunt restriction' at a proximal third (SR-proximal) distance and 'shunt restriction' at a distal third (SR-distal) distance. RESULTS: Bidirectional sluggish flow was detected at the proximal part of venous flaps in both groups. Unidirectional normal flow was observed in more capillaries of the distal flaps in the SR-proximal group. In the middle of the flaps, blood flow was sluggish and intermittent in the veins and was absent in most capillaries of the SR-distal group. The flow was prompt and unidirectional in more capillaries of the SR-proximal group. Using laser Doppler flowmetry, the average perfusion of the whole SR-proximal flaps was found to be higher than that of SR-distal flaps (p = 0.017). The average flux at the middle and distal portions of the SR-proximal group was significantly higher than those of the SR-distal group (p = 0.049). CONCLUSION: 'Shunt restriction' at the proximal third of the AV shunt resulted in enhanced perfusion and reduced venous congestion in an AVF.

Coronary or thoracic artery calcium score in provoked and unprovoked pulmonary embolism: a case-control study.

UNLABELLED: Essentials Patients with unprovoked pulmonary embolism (PE) are at increased risk of arterial thromboembolism. Coronary and thoracic aorta calcium were evaluated in patients with and without (unprovoked) PE. No association was found between (unprovoked) PE and coronary or aortic calcification. Assessment of both calcium scores on computed tomography pulmonary angiography was highly reproducible. SUMMARY: Objective To evaluate the potential association between (unprovoked) pulmonary embolism (PE) and the presence and extent of coronary artery calcium (CAC) and thoracic aorta calcium (TAC). Methods CAC and TAC derived from computed tomography pulmonary angiography of 100 patients with PE were compared to that of 100 patients in whom PE was ruled out. Results Intraobserver and interobserver agreements for both TAC and CAC were excellent (intraclass correlation > 0.95 for both). In patients with PE vs. patients without PE, no significant differences were found in the presence of CAC or TAC (CAC 64% vs. 67%, odds ratio [OR] 1.0, 95% confidence interval [CI] 0.67-1.6; TAC 46% vs. 59%, OR 1.2, 95% CI 0.80-2.1). Mean CAC and TAC scores were significantly lower in patients with PE than in patients without PE (CAC 3.4 vs. 4.9, absolute difference 1.5, 95% CI 0.2-2.8; TAC 1.1 vs. 1.8, absolute difference 0.9, 95% CI 0.2-1.2). No significant differences were found in the presence of CAC or TAC or in mean CAC and TAC scores between patients with unprovoked PE vs. patients with provoked PE, or between patients with unprovoked PE vs. no PE. Conclusion No significant differences were found between the extent of CAC and TAC in patients with unprovoked PE compared to those with provoked PE or without PE. The observed difference in the extend of CAC and TAC between patients with and without PE was dependent on prevalent cardiovascular risk factors.

Involvement of rho-kinase in agonists-induced contractions of arteriosclerotic human arteries.

Coronary artery spasm plays an important role in the pathogenesis of a wide variety of ischemic heart diseases. We have recently demonstrated that Rho-kinase plays a key role in the spasm in our porcine model. However, it remains to be elucidated whether Rho-kinase-mediated pathway also contributes to vasoconstriction of human arteries. From 15 patients who underwent coronary artery bypass operation, segments of isolated left internal thoracic arteries were obtained, and the endothelium was gently removed. Serotonin and histamine caused contractions, which were markedly inhibited by a specific Rho-kinase inhibitor, hydroxyfasudil. Western blot analysis showed that, during the serotonin-induced contractions, the extent of phosphorylation of myosin-binding subunit of myosin phosphatase (MBS, one of the major substrates of Rho-kinase) was significantly increased in the specimens. Hydroxyfasudil again significantly suppressed the serotonin-induced increase in MBS phosphorylation. There was a significant positive correlation between the extent of MBS phosphorylation and that of the serotonin-induced contractions and between hydroxyfasudil-sensitive components of the contractions and the extent of arteriosclerosis. These results indicate that Rho-kinase plays an important role in vascular smooth muscle contractions of arteriosclerotic human arteries, suggesting that Rho-kinase could be regarded as an important target for the treatment of arteriosclerotic vascular diseases in humans.