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Biomedical subjects

W Z Wang

Publications and source records attributed to W Z Wang.

At least 19 recordsLinked to original sources
PubMed2000

Platelet-activating factor contributes to postischemic vasospasm.

BACKGROUND: The purpose of the present study was to determine if platelet-activating factor is an important mediator that produces vasospasm during reperfusion after ischemia in skeletal muscle. MATERIALS AND METHODS: A vascular isolated cremaster muscle in male Sprague-Dawley rats was coupled with local intraarterial drug infusion as a model to study microcirculation responses to ischemia/reperfusion injury. Arteriole diameters and capillary perfusion were measured using intravital microscopy. Group 1: platelet-activating factor dose response. Group 2: Effects of a cyclooxygenase inhibitor; indomethacin, and a thromboxane synthetase inhibitor, imidazole, on the response to platelet-activating factor. Group 3: Effects of nitric oxide synthesis inhibitor; N(omega)-nitro-L-arginine methyl ester, on the response to platelet-activating factor. Group 4: Effects of a platelet-activating factor receptor antagonist, CV-3988, indomethacin, and imidazole after 4 h of warm ischemia and reperfusion. RESULTS: Intraarterial infusion of platelet-activating factor produced a dose-related but mild vasoconstriction. Pretreatment with indomethacin or imidazole resulted in significant vasodilation actually emanating from platelet-activating factor infusion. Nitric oxide inhibition (with N(omega)-nitro-L-arginine methyl ester) enhanced the vasoconstriction produced by platelet-activating factor. Pretreatment with CV-3988, indomethacin, or imidazole significantly attenuated ischemia/reperfusion-induced vasospasm and capillary no-reflow in the cremaster muscles. CONCLUSIONS: Ischemia/reperfusion-induced vasoconstriction is at least in part mediated by platelet-activating factor and thromboxane A(2).

Animals↗
PubMed2000

Initiation of microvascular protection by nitric oxide in late preconditioning.

The authors hypothesized that nitric oxide is induced by a brief period of ischemia/reperfusion (ischemic preconditioning, IPC) on postoperative day (POD) 1, and that this released nitric oxide is responsible for initiating a delayed microvascular protection against a prolonged period of ischemia in skeletal muscle on POD day 2. The cremaster muscle of male Sprague-Dawley rats underwent 4 hr of ischemia, and then 60 min of reperfusion. IPC consisted of 45 min of ischemia but was done 24 hr before the prolonged ischemia. Local intraarterial infusion of sodium nitroprusside (SNP, a donor of nitric oxide) or Nw-nitro-L-arginine (L-NA, a nonselective nitric oxide synthase antagonist) were also given 24 hr before prolonged ischemia. Arteriole diameters and capillary perfusion were measured using intravital microscopy. Four groups were compared: 1) control; 2) IPC; 3) SNP + sham IPC; and 4) L-NA + IPC. Four hours of ischemia followed by reperfusion created a significant vasoconstriction and capillary no-reflow in the microcirculation of cremaster muscles. These alterations were largely prevented by IPC. Local intraarterial infusion of SNP without IPC created a similar microvascular protection to that induced by IPC alone. In contrast, intraarterial infusion of L-NA prior to IPC eliminated the IPC-induced microvascular protection. In conclusion, in late preconditioning, nitric oxide contributes to the initiation of a delayed microvascular protection against prolonged ischemia in skeletal muscle.

Animals↗
PubMed1999

Microcirculatory changes following different temperature washouts in a free flap model.

In spite of the extensive experimental work on vascular washout in free flap surgery, an optimal temperature for the washout solution has not been established. This study was designed to determine the effect of the washout solution temperature on the degree to which the microcirculation is cleared of blood. The cremaster muscle flap in the rat was used, in which the microcirculation can be directly viewed and the presence of blood and perfusion parameters within various vessels can be measured during and after washout. Washout was started with a single, high-pressure infusion and continued at 130 mmHg for 15 minutes. The temperature of the washout solution was either 2-3, 20-22, or 35 degrees C. In all three groups, washout cleared the microcirculation almost completely within the first minute. However, we observed that a cold or room temperature washout cleared the microcirculation more completely than a warm washout did. The temperature of the washout solution did not effect post washout capillary perfusion and/or arterial diameters.

Animals↗
PubMed1999

Late-preconditioning protection is evident in the microcirculation of denervated skeletal muscle.

We investigated whether ischemic preconditioning induces microvascular protection in skeletal muscle at the late phase (after 24 hours) when the same muscles are subjected to prolonged warm global ischemia. The cremaster muscle of the male Sprague-Dawley rat underwent vascular isolation and was subjected to 4 hours of ischemia and 60 minutes of reperfusion. Early preconditioning consisted of 45 minutes of ischemia followed by 15 minutes of reperfusion before prolonged ischemia/reperfusion; late preconditioning also consisted of 45 minutes of ischemia but was done 24 hours (24-hour period of reperfusion) before the prolonged ischemia/reperfusion. Arteriole diameters and capillary perfusion were measured with use of intravital microscopy. Four groups were compared: rats that underwent early preconditioning, their controls, rats that underwent late preconditioning, and their controls. Early and late preconditioning significantly attenuated vasospasm and capillary no-reflow compared with the controls for each. Average arteriole diameter was significantly larger in the rats that underwent late preconditioning than in any other rats; it was also significantly larger in the controls for late preconditioning than in those for early preconditioning. We introduce a model of the rat cremaster muscle that has been isolated from its vascular supply as a useful preparation to study the effects of late preconditioning on microcirculation in skeletal muscle. Late preconditioning provided better microvascular protection than did early preconditioning. The mechanism for this preconditioning protection is being investigated because it should provide a means for therapeutic intervention.

Animals↗
PubMed1999

Apoptosis in congestive heart failure induced by viral myocarditis in mice.

It has recently been speculated that progressive deterioration of left ventricular function in chronic heart failure is due to the ongoing loss of viable cardiac myocytes. However, as there is little direct evidence of significant apoptosis contributing to the pathogenesis in cardiac myocytes in vivo, the significance of apoptosis in heart failure remains to be clarified. We investigated the role of apoptosis in heart failure induced by encephalomyocarditis virus myocarditis. DBA/2 mice were inoculated with the virus (day 0), then killed, and their hearts were extracted 3 to 28 days later. Internucleosomal DNA fragmentation, chromatin binding dye staining, and in situ terminal transferase deoxyuridine triphosphate (dUTP) end-labeling were used to detect apoptosis. Internucleosomal DNA fragmentation (DNA ladder) was clearly demonstrated on days 5 to 14 in the virus-infected hearts when myocardial necrosis and infiltration of mononuclear cells were prominent in the hearts. Apoptotic cells demonstrated morphological changes typical of apoptosis (condensation of chromatin and nuclear fragmentation). Both Fas antigen and Fas ligand immunoreactivity were detected in the infiltrating mononuclear cells. The in situ terminal transferase dUTP end-labeling method demonstrated condensed nuclei of infiltrating mononuclear cells on day 7. However, nuclei of cardiac myocytes surrounded by the cellular infiltration were absent. The main source of apoptotic cells in the heart in mice with viral myocarditis appeared to be the infiltrating mononuclear cells.

Animals↗
PubMed1999

Prevention of stroke in urban China: a community-based intervention trial.

BACKGROUND AND PURPOSE: Stroke has been the second leading cause of death in large cities in China since the 1980s. Meanwhile, the prevalences of hypertension and smoking have steadily increased over the last 2 decades. Therefore, a community-based intervention trial was initiated in 7 Chinese cities in 1987. The overall goal of the study was to evaluate the effectiveness of an intervention aimed at reducing multiple risk factors for stroke. The primary study objective was to reduce the incidence of stroke by 25% over 3.5 years of intervention. METHODS: In May 1987 in each of 7 the cities, 2 geographically separated communities with a registered population of about 10 000 each were selected as either intervention or control communities. In each community, a cohort containing about 2700 subjects (>/=35 years old) free of stroke was sampled, and a survey was administered to obtain baseline data and screen the eligible subjects for intervention. In each city, a program of treatment for hypertension, heart disease, and diabetes was instituted in the intervention cohort (n approximately 2700) and health education was provided to the full intervention community (n approximately 10 000). A follow-up survey was conducted in 1990. Comparisons of intervention and control cohorts in each city were pooled to yield a single summary. RESULTS: A total of 18 786 subjects were recruited to the intervention cohort and 18 876 to the control cohort from 7 cities. After 3.5 years, 174 new stroke cases had occurred in the intervention cohort and 253 in the control cohort. The 3.5-year cumulative incidence of total stroke was significantly lower in the intervention cohort than the control cohort (0.93% versus 1.34%; RR=0.69; 95% CI, 0.57 to 0.84). The incidence rates of nonfatal and fatal stroke, as well as ischemic and hemorrhagic stroke, were significantly lower in the intervention cohort than the control cohort. The prevalence of hypertension increased by 4.3% in the intervention cohort and by 7.8% in the control cohort. The average systolic and diastolic blood pressures increased more in the control cohort than in the intervention cohort. Among hypertensive individuals in the intervention cohort, awareness of hypertension increased by 6.7% and the percentage of hypertensives who regularly took antihypertensive medication increased 13.2%. All of these indices became worse in the control cohort. The prevalence of heart diseases and diabetes increased significantly in the both cohorts (P<0.01). The prevalence of consumption of alcohol increased slightly, and that of smoking remained constant in both cohorts. CONCLUSIONS: A community-based intervention for stroke reduction is feasible and effective in the cities of China. The reduction, due to the intervention, in the incidence of stroke in the intervention cohort was statistically significant after 3.5 years of intervention. The sharp reduction in the incidence of stroke may be due to the interventions having blunted the expected increase in hypertension that accompanies aging as well as to better and earlier treatment of hypertension, particularly borderline hypertension. Applied health education to all the residents of the community may have prevented some normotensive individuals from developing hypertension and improved overall health awareness and knowledge.

Cerebrovascular Disorders↗
PubMed1999

The role of humic substances in drinking water in Kashin-Beck disease in China.

We conducted in vitro and in vivo assays in a selenium-deficient system to determine if organic matter (mainly fulvic acid; FA) is involved in a free radical mechanism of action for Kashin-Beck disease. Cartilage cell culture experiments indicated that the oxy or hydroxy functional groups in FA may interfere with the cell membrane and result in enhancement of lipid peroxidation. Experiments with rats demonstrated that toxicity from FA was reduced when the hydroxy group was blocked. Induction of lipid peroxidation by FA in liver and blood of rats was similar to that exhibited by acetyl phenyl hydrazine. FA accumulated in bone and cartilage, where selenium rarely concentrates. In addition, selenium supplementation in rats' drinking water inhibited the generation of oxy-free radicals in bone. We hypothesized that FA in drinking water is an etiological factor of Kashin-Beck disease and that the mechanism of action involves the oxy and hydroxy groups in FA for the generation of free radicals. Selenium was confirmed to be a preventive factor for Kashin-Beck disease.

Animals↗
PubMed1998

Do leukocytes contribute to impaired microvascular tissue perfusion after arterial repair?

Impaired capillary perfusion may result in flap failure. Platelet emboli, polymorphonuclear leukocytes (PMNs), and/or vasospasm have been identified as possible causes. This study investigates the role of PMNs in causing impaired capillary perfusion in a free flap model. PMN concentrations were depleted using antineutrophil serum. The cremaster muscles of 20 Sprague-Dawley rats were isolated on a single neurovascular pedicle and after a simulated technically poor arterial anastomosis upstream and reperfusion, capillary perfusion was measured each hour for 6 hours. Even though the number of PMNs was significantly reduced in the animals treated with antineutrophil serum, capillary perfusion was not changed compared with controls. These results demonstrate that depleting circulating PMNs does not protect capillary perfusion in our model. These findings suggest that reduced capillary perfusion downstream from an anastomotic repair is not mediated by the presence of PMNs in the microcirculation.

Anastomosis, Surgical↗
PubMed1998

Protective effects of Mu-Fang-Ji-Tang against myocardial injury in a murine model of congestive heart failure induced by viral myocarditis.

The effects of Mu-Fang-Ji-Tang (TJ-36), a traditional Chinese herbal medicine, were studied in a murine model of congestive heart failure induced by viral myocarditis. In the group of animals treated with Mu-Fang-Ji-Tang in a dose of 1.5g/kg/day, the heart weight to body weight ratio was significantly lower than in the control group (p<0.01). Histopathological grades were also significantly lower in the Mu-Fang-Ji-Tang treated group than in the placebo group (p<0.05). Furthermore, survival was increased in the Mu-Fang-Ji-Tang treated group, versus the control group (p<0.05). In vitro, murine J774A.1 macrophages inoculated with encephalomyocarditis virus produced a significantly greater amount of nitrites compared to non-activated macrophages. Mu-Fang-Ji-Tang added to the cells (25, 50, 75, 100 microg/ml) concomitantly with the encephalomyocarditis virus inhibited nitrite formation in a concentration-dependent manner. Mu-Fang-Ji-Tang showed a protective effect against myocardial injury leading to congestive heart failure in this animal model.

Animals↗
PubMed1998

Ischemic preconditioning versus intermittent reperfusion to improve blood flow to a vascular isolated skeletal muscle flap of rats.

OBJECTIVES: We investigated whether intermittent restoration of blood flow just before reperfusion after ischemia could create beneficial effects similar to ischemic preconditioning, which involves intermittent stoppage of blood flow just before ischemia. METHODS: Male Sprague-Dawley rats were prepared with vascular isolated cremaster muscles, then subjected to 4 hours of ischemia and 60 minutes of reperfusion. Arteriole diameters and capillary perfusion were measured by using intravital microscopy. Four groups were used: (1) untreated, (2) ischemic preconditioning (IP), (3) intermittent reperfusion (IR), and (4) ischemic preconditioning plus intermittent reperfusion (IP+IR). RESULTS: Our results showed that IP significantly attenuated both ischemia/reperfusion-induced vasospasm and capillary noreflow. IR was effective in attenuating vasospasm in terminal arterioles. However, IR alone was unable to significantly attenuate capillary no-reflow. Combining both IP and IR achieved the best results. CONCLUSION: Our results suggest both ischemic preconditioning and intermittent reperfusion are useful techniques for attenuating ischemia/reperfusion injury.

Animals↗
PubMed1998

The B-cell repertoire in myasthenia gravis includes all four acetylcholine receptor subunits.

By enumerating cells secreting IgG antibodies of particular specificities using an enzyme-linked immunospot (ELISPOT) assay, the B-cell responses to Torpedo acetylcholine receptor (AChR) and its alpha-, beta-, gamma- and delta-subunits in peripheral blood from patients with myasthenia gravis (MG), and controls with other neurological diseases (OND) as well as healthy subjects were determined. Compared to controls, the patients with MG had elevated numbers of B cells secreting antibodies against AChR and its alpha-, beta-, gamma- and delta-subunits in peripheral blood in parallel. The mean numbers of anti-AChR antibody secreting cells were about 17 per 10(5) blood MNC, and for the subunits 10 to 15 in MG patients, compared to between 0.8 and 1.9 per 10(5) blood MNC in OND patients, and 0.1 to 0.3 in healthy controls. Such B cells detected in controls probably represent naturally occurring B cells responded to AChR and its subunits. The finding that most (60%) MG patients had B cells predominantly recognizing the alpha-subunit may be an indirect argument for the existence of a main immunogenic region (MIR). In the remaining 40% of patients with MG the predominant B-cell responses were directed to beta-, gamma- or delta-subunit. The data suggest that all four AChR subunits may function as strong immunogens in MG, though the alpha-subunit may be the major immune target in a substantial proportion of MG patients.

Adult↗
PubMed1998

Effects of long-term application of dopamine HCl on dopamine agonist-induced cAMP production in rat renal cortex.

AIM: To study the effects of long-term application of dopamine HCl (DA) on the functional changes of dopamine receptor subtypes coupled to adenyl cyclase in rat renal cortex. METHODS: cAMP levels were measured by radioimmunoassay as an index of dopamine receptor function. RESULTS: Injection of DA (30 mg.kg-1.d-1, i.p. 30 d) reduced the fenoldopam (Fen) (100 mumol.L-1)-induced increments of cAMP production from the control group of +1.26 +/- 0.04 to the DA-treated group of +0.63 +/- 0.22 nmol.min-1/g tissue and the propyl-butyl-dopamine (PBDA) (100 mumol.L-1)-induced decrements of cAMP production in the presence of Sch-23390 (Sch) from the control group of -0.38 +/- 0.18 to the DA-treated group of -0.11 +/- 0.08 nmol.min-1/g tissue with, however, comparable percentile changes for the 2 groups. Sch blocked both Fen- and PBDA-induced increase in cAMP production, while domperidone (Dom) blocked the decreasing effects of PBDA on cAMP accumulation in the presence of Sch. CONCLUSION: Long-term application of DA produced a marked "down regulation" of both DA1 and DA2 receptors in rat renal cortex with, however, the responsiveness of the remaining receptors unchanged.

Animals↗
PubMed1997

Beneficial effects of amlodipine in a murine model of congestive heart failure induced by viral myocarditis. A possible mechanism through inhibition of nitric oxide production.

BACKGROUND: Although calcium channel blockers have not been shown to be beneficial for the treatment of patients with heart failure, a recent clinical trial demonstrated a favorable effect of amlodipine on the survival of patients with heart failure resulting from nonischemic dilated cardiomyopathy. We investigated the effects of amlodipine on a murine model of congestive heart failure induced by the M variant of encephalomyocarditis virus (EMCV). METHODS AND RESULTS: Four-week-old male DBA/2 mice were inoculated with EMCV and administered amlodipine, diltiazem, or vehicle PO for 2 weeks. The heart weight-to-body weight ratio and the histopathological grades of myocardial lesions were significantly lower and survival was significantly increased in the amlodipine-treated group (P < .01, P < .05, and P < .05, respectively) than in the control group. In vitro, amlodipine added to murine J774A.1 macrophages concomitant with EMCV inhibited nitrite formation in a concentration-dependent manner, but diltiazem did not. Furthermore, NG-monomethyl-L-arginine, an inhibitor of NO synthesis, decreased myocardial lesions significantly in this murine model. Immunohistochemistry revealed that the number of cells stained with antibody against an inducible NO synthase decreased significantly in the amlodipine-treated group compared with that in the control group (P < .01). CONCLUSIONS: Amlodipine appears to have a protective effect against myocardial injury in this animal model of congestive heart failure. The therapeutic effect of amlodipine may be in part resulting from inhibition of overproduction of NO.

Amlodipine↗
PubMed1997

Endothelin-1 does not contribute to ischemia/reperfusion-induced vasoconstriction in skeletal muscle.

The experiment reported was designed to investigate whether endothelin-1 (ET-1) contributes to vasospasm and poor perfusion during the reperfusion after prolonged ischemia in skeletal muscle. Male Sprague-Dawley rats weighting 100 to 120 g were anesthetized with Nembutal. The vascular isolated rat cremaster muscle, coupled with local interarterial infusion, was the model used in this study. The diameters of feeding arterioles and terminal arterioles were measured utilizing intravital microscopy. The number of terminal arterioles with temporary cessation of flow were counted in each cremaster. Group 1: ET-dose response (8 rats)--various concentrations of ET-1 (from 10(-8) M to 10(-5) M) were infused into the cremaster to test whether this muscle was responsive to the agent in a dose-dependent manner. Group 2: ET-antagonist response (12 rats)--PD-142893, 10(-4) M (ETab receptor antagonist) plus ET-1 10(-7) M were infused into the cremaster to test whether vasospasm caused by exogenous ET-1 could be prevented by pretreatment with this specific ETab receptor antagonist. Group 3: ischemia/reperfusion response (12 rats)--PD-142893, 10(-4) M was infused into the cremaster before ischemia (4 hr warm ischemia) and during reperfusion to test whether ETab receptor antagonism was effective in preventing the vasospasm associated with ischemia/reperfusion injury. The results from this study show that a mixed ETab endothelin antagonist, PD-142893, infused before ischemia and during reperfusion at a dose which virtually abolished the vasoconstriction produced by a high concentration of exogenous endothelin-1, had no effect on ischemia/reperfusion-induced vasoconstriction in this model. These results suggest that ET-1 probably does not contribute to the ischemia/reperfusion-induced vasoconstriction and poor reflow in rat skeletal muscle.

Analysis of Variance↗
PubMed1997

Lack of nitric oxide contributes to vasospasm during ischemia/reperfusion injury.

Vasospasm can be a complication after free tissue transfer and replant operations. Recent studies suggest that vasospasm may be due to endothelium dysfunction, resulting in impairment of nitric oxide production. The present experiment was designed to investigate acute responses of the microcirculation of skeletal muscle to local interarterial infusion of sodium nitroprusside (a direct donor of nitric oxide and thus an endothelium-independent vasodilator) or acetylcholine chloride (which stimulates endothelium release of endogenous nitric oxide) during reperfusion after 4 hours of warm ischemia. Male Sprague-Dawley rats, each weighing 100 to 120 gm, were anesthetized with sodium pentobarbitone and were surgically prepared with vascular isolated and denervated cremaster muscles that were subjected to 4 hours warm ischemia and 2 hours of reperfusion. Sodium nitroprusside (10(-3) M), acetylcholine chloride (10(-4) M), or normal saline (eight rats for each group) were administered by local infusion (0.1 ml/hour) through the femoral artery into the natural blood flow of the cremaster. The arterial tree in the cremaster was observed and arteriole diameters (A1-A4) were measured using intravital microscopy. The number of arteriole branches having temporary stoppage of flow were counted in each cremaster. The results from this study show that local infusion of sodium nitroprusside, but not acetylcholine chloride, prevents ischemia/reperfusion vasoconstriction in A3 and A4 arterioles and thus improves microvascular blood flow. Generalized vasoconstriction caused by topically applied norepinephrine (10(-6) M) to sham ischemia cremasters could be completely reversed by the local infusion of 10(-4) M acetylcholine chloride. These results indicate that vasospasm after ischemia/reperfusion may be related to temporary endothelial cell dysfunction, resulting in the inability to produce sufficient nitric oxide during early reperfusion. Vascular smooth muscle, however, is responsive to locally administered sodium nitroprusside infusion (which is thought to provide exogenous nitric oxide).

Acetylcholine↗
PubMed1997

Effect of low dose aspirin on thrombus formation at arterial and venous microanastomoses and on the tissue microcirculation.

In free flap/replantation surgery, failure is usually associated with thrombotic occlusion of a microvascular anastomosis (risk zone I) or, on occasion, flow impairment in the microcirculation of the transferred or replanted tissue (risk zone II). The objective of this study is to describe the effect of low dose aspirin on blood flow at both risk zones in microvascular surgery. Risk zone I: In rat femoral arteries and veins, thrombus formation was measured at the anastomoses using transillumination and videomicroscopy. Forty male Wistar rats were assigned in equal numbers to four groups: either arterial or venous injury with either aspirin (5 mg/kg systemically) or saline treatment. We found that aspirin significantly reduces thrombus formation at the venous anastomosis (p = 0.001). Risk zone II: In the isolated rat cremaster muscle downstream from an arterial anastomosis, we measured capillary perfusion, arteriolar diameters, and the appearance of platelet emboli for 6 hours in the muscle microcirculation. Sixteen male Wistar rats in two equal groups received either aspirin (5 mg/kg systemically) or saline. We found that in aspirin-treated animals, capillary perfusion is significantly (p = 0.002) improved, whereas arteriolar diameters and emboli only slightly increased. In conclusion, low dose aspirin inhibits anastomotic venous thrombosis and improves microcirculatory perfusion in our rat model. These studies provide quantitative data confirming and clarifying the beneficial effects of low dose aspirin in microvascular surgery.

Anastomosis, Surgical↗
PubMed1997

Amidative peptide processing and vascular function.

Substance P (SP), an amidated peptide present in many sensory nerves, is known to affect cardiovascular function, and exogenously supplied SP has been shown to activate nitric oxide synthase (NOS) in endothelial cells. We now report that SP-Gly, the glycine-extended biosynthetic precursor of SP (which is enzymatically processed to the mature amidated SP), causes relaxation of rat aortic strips with an efficacy and potency comparable to that of SP itself. Pretreatment of the aortic strips with 4-phenyl-3-butenoic acid (PBA), an irreversible amidating enzyme inactivator, results in marked inhibition of the vasodilation activity induced by SP-Gly but not of that induced by SP itself. Isolated endothelial cell basal NOS activity is also decreased by pretreatment with PBA, with no evidence of cell death or direct action of PBA on NOS activity. Both bifunctional and monofunctional forms of amidating enzymes are present in endothelial cells, as evidenced by affinity chromatography and Western blot analysis. These results provide evidence for a link between amidative peptide processing, NOS activation in endothelial cells, and vasodilation and suggest that a product of amidative processing provides intrinsic basal activation of NOS in endothelial cells.

Amino Acid Sequence↗