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Biomedical subjects

Ravi Pillai

Publications and source records attributed to Ravi Pillai.

14 recordsLinked to original sources
PubMed2006

5-methyltetrahydrofolate rapidly improves endothelial function and decreases superoxide production in human vessels: effects on vascular tetrahydrobiopterin availability and endothelial nitric oxide synthase coupling.

BACKGROUND: The circulating form of folic acid, 5-methyltetrahydrofolate (5-MTHF), may have beneficial effects on endothelial function; however, its mechanisms of action remain uncertain. Decreased nitric oxide (NO) bioavailability and increased vascular superoxide production in vascular disease states are due in part to endothelial NO synthase (eNOS) uncoupling related to deficiency of the eNOS cofactor tetrahydrobiopterin (BH4), but whether this mechanism is important in human atherosclerosis and represents a rational therapeutic target remains unclear. We hypothesized that 5-MTHF would improve endothelial function by decreasing superoxide and peroxynitrite production and by improving eNOS coupling, mediated by BH4 availability. METHODS AND RESULTS: Vascular superoxide/peroxynitrite production and vasomotor responses to acetylcholine and bradykinin were determined in saphenous veins and internal mammary arteries from 117 patients undergoing CABG. The effects of 5-MTHF were examined ex vivo (n = 61) by incubating vessels with 5-MTHF (1 to 100 micromol/L) and in vivo by intravenous infusion of 5-MTHF or placebo before vessel harvest (n = 56). 5-MTHF improved NO-mediated endothelium-dependent vasomotor responses and reduced vascular superoxide, both ex vivo and in vivo. These changes were not explained by direct superoxide scavenging by 5-MTHF in vitro or by changes in plasma total homocysteine in vivo. Rather, 5-MTHF was a strong peroxynitrite scavenger and increased vascular BH4 and the BH4/total biopterin ratio. Furthermore, 5-MTHF reversed eNOS uncoupling, as assessed by NG-nitro-l-arginine methyl ester-inhibitable superoxide production, increased the eNOS dimer:monomer ratio, and enhanced eNOS activity. CONCLUSIONS: 5-MTHF has beneficial effects on endothelial function and vascular superoxide production in human atherosclerosis, by preventing peroxynitrite-mediated BH4 oxidation and improving eNOS coupling.

Acetylcholine↗
PubMed2006

Transsternal thymectomy for myasthenia gravis: surgical outcome.

BACKGROUND: Transsternal thymectomy is well established in the treatment of myasthenia gravis. Surgical strategy and patient selection, however, remain controversial. This paper reports the experience of a supraregional center looking into the influence of different preoperative risk factors on surgical outcome. METHODS: Between 1987 and 1998, 85 consecutive patients (65 female; mean age, 30.5 years) were enrolled. The mean preoperative Myasthenia Gravis Foundation of America stage was 2.3. The preoperative, early, and late follow-up data were analyzed retrospectively. RESULTS: Mean follow-up was 4.5 years (range, 1 to 14; 376 follow-up years). Mean duration of disease before surgery was 31 months. There were no operative or late deaths. Eight patients had major complications. Seventy-two patients were free from any early or late morbidity. Immunosupression therapy patients were more prone to have complications. At their last visit, 15 patients (17%) were in complete remission; 67 reported clinical improvement. Sixty-three were asymptomatic or in stage I on no or minimal treatment. Remission and clinical improvement were not predicted by patient's age, sex, duration of disease prior to surgery, thymic pathology, or antiacetylcholine receptor antibodies titer. Greater severity of symptoms before surgery was associated with greater subsequent improvement. Remission at 1 year predicted remission at the end of follow-up. CONCLUSIONS: Transsternal thymectomy for myasthenia gravis is safe and effective. It benefits most patients, especially those with severe symptoms. The long interval from diagnosis to surgery demonstrates it is never too late for thymectomy.

Adolescent↗
PubMed2005

A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation.

Human atrial fibrillation (AF) has been associated with increased atrial oxidative stress. In animal models, inhibition of reactive oxygen species prevents atrial remodeling induced by rapid pacing, suggesting that oxidative stress may play an important role in the pathophysiology of AF. NAD(P)H oxidase is a major source of superoxide in the cardiovascular system; however, whether this enzyme contributes to atrial oxidative stress in AF remains to be elucidated. We investigated the sources of superoxide production (using inhibitors and substrates of a range of oxidases, RT-PCR, immunofluorescence, and immunoblotting) in tissue homogenates and isolated atrial myocytes from the right atrial appendage (RAA) of patients undergoing cardiac surgery (n=54 in sinus rhythm [SR] and 15 in AF). A membrane-bound gp91phox containing NAD(P)H oxidase in atrial myocytes was the main source of atrial superoxide production in SR and in AF. NADPH-stimulated superoxide release from RAA homogenates was significantly increased in patients with AF in the absence of changes in mRNA expression of the p22phox and gp91phox subunits of the NAD(P)H oxidase. In contrast with findings in SR patients, NO synthases (NOSs) contributed significantly to atrial superoxide production in fibrillating atria, suggesting that increased oxidative stress in AF may lead to NOS "uncoupling." These findings indicate that a myocardial NAD(P)H oxidase and, to a lesser extent, dysfunctional NOS contribute significantly to superoxide production in the fibrillating human atrial myocardium and may play an important role in the atrial oxidative injury and electrophysiological remodeling observed in patients with AF.

Atrial Fibrillation↗
PubMed2005

Seeding of stage I thymoma into the chest wall 12 years after needle biopsy.

It is known that benign encapsulated thymoma can pursue an aggressive clinical course on rare occasions. It may recur locally, it may be invasive, or it may metastasize. We present a case of local seeding into the chest wall, presenting 12 years after core needle biopsy and complete excision of the mediastinal tumor. We draw attention to the malignant clinical behavior of some benign stage I thymomas.

Aged↗
PubMed2004

Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins.

OBJECTIVE: Impaired endothelial function, characterized by nitric oxide scavenging by increased superoxide production, is a hallmark of vascular disease states. However, molecular mechanisms regulating superoxide production in human blood vessels remain poorly defined. METHODS AND RESULTS: We compared endothelial function, vascular superoxide production, and the expression of NAD(P)H oxidase subunits in arteries and veins from patients undergoing coronary bypass surgery (n=86). Superoxide release was similar in arteries and veins. Inhibitor studies revealed that the NAD(P)H oxidase system was a quantitatively and proportionately greater source of superoxide in veins, whereas xanthine oxidase also contributed significantly to superoxide production in arteries. Moreover, NAD(P)H oxidase molecular composition differed in veins and arteries; veins expressed more nox2 and p22phox, whereas the relative expression of nox4 was greater in arteries. However, there were strong correlations between p22phox and nox4 expression and between superoxide production, NAD(P)H oxidase activity, and endothelial function in arteries and veins from the same patient. CONCLUSIONS: In individuals with coronary artery disease, changes in vascular superoxide production, endothelial function, and NAD(P)H oxidase activity and expression are related in veins and arteries. These findings highlight the importance of systemic effects on the molecular regulation of the NAD(P)H oxidases in human vascular disease. Endothelial dysfunction is characterized by increased superoxide production. NAD(P)H oxidase activity and endothelial function are correlated in veins and arteries in coronary artery disease, suggesting regulation by systemic factors. The expression of the NAD(P)H oxidase subunits p22phox and nox4, although different in veins and arteries, are also correlated.

Acetylcholine↗
PubMed2004

Off-pump coronary artery bypass surgery.

Off-pump coronary artery bypass surgery has been adopted enthusiastically worldwide. However, despite more than 6 years' experience and refinement, many surgeons use it only sporadically and some hardly at all. This reluctance persists despite support for the procedure because of the lack of properly designed risk models and/or randomized studies. Although it has not been overwhelmingly shown that off-pump surgery is superior to the conventional on-pump procedure, the technique has its place in our specialty. It has been shown to be better for noncritical end points in selected patients in the hands of selected surgeons. That there are differences in surgical skill among surgeons is something we all know but rarely discuss in public. Until now, disparities in skill have been most salient with uncommon and extraordinarily challenging operations. Perhaps the off-pump procedure should be regarded as the "challenging" aspect of coronary artery bypass surgery, and self-restraint may need to remain in force if we are to continue to achieve the highest level of clinical excellence.

Clinical Competence↗
PubMed2002

Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase.

BACKGROUND: Increased superoxide production contributes to reduced vascular nitric oxide (NO) bioactivity and endothelial dysfunction in experimental models of diabetes. We characterized the sources and mechanisms underlying vascular superoxide production in human blood vessels from diabetic patients with coronary artery disease compared with nondiabetic patients. METHODS AND RESULTS: Vascular superoxide production was quantified in both saphenous veins and internal mammary arteries from 45 diabetic and 45 matched nondiabetic patients undergoing coronary artery bypass surgery. NAD(P)H-dependent oxidases were important sources of vascular superoxide in both diabetic and nondiabetic patients, but both the activity of this enzyme system and the levels of NAD(P)H oxidase protein subunits (p22phox, p67phox, and p47phox) were significantly increased in diabetic veins and arteries. In nondiabetic vessels, endothelial NO synthase produced NO that scavenged superoxide. However, in diabetic vessels, the endothelium was an additional net source of superoxide production because of dysfunctional endothelial NO synthase that was corrected by intracellular tetrahydrobiopterin supplementation. Furthermore, increased superoxide production in diabetes was abrogated by the protein kinase C inhibitor chelerythrine. CONCLUSIONS: These observations suggest important roles for NAD(P)H oxidases, endothelial NO synthase uncoupling, and protein kinase C signaling in mediating increased vascular superoxide production and endothelial dysfunction in human diabetes mellitus.

Biopterins↗
PubMed2002

Anterior spinal artery syndrome after elective coronary artery bypass grafting.

A 65-year-old patient with ischemic heart disease and hypertensive nephropathy had paraplegia develop after elective coronary artery revascularization caused by anterior spinal infarction. Spinal complications are rare after coronary artery bypass grafting. The possible mechanisms of spinal cord injury are discussed, and the relevant literature is reviewed.

Aged↗
PubMed2002

Minimally invasive vein harvesting significantly reduces pain and wound morbidity.

OBJECTIVES: Minimally invasive saphenous vein harvesting is advocated to reduce wound morbidity. Our early experience with minimally invasive techniques, however, suggested that increased tissue traction and trauma might follow. We aimed to test the hypothesis that minimally invasive harvesting reduces post-operative pain and inflammation. A secondary objective was to determine if minimally invasive harvesting could be performed efficiently. METHODS: Forty patients were prospectively randomised into minimally invasive harvesting (Minimal, n=22) and traditional open harvesting (Open, n=18). A modified bridging technique was used for minimally invasive harvesting (SaphLITE, Genzyme Surgical Products, Cambridge, MA, USA). One surgeon performed all operations. Primary end points were signs of impaired healing (a composite score) and pain (visual analogue score). Secondary end-points (operation variables) were also collected. Continuous variables were analysed by Student's t-test and categorical variables were analysed by Mann-Whitney U-test. RESULTS: There were no significant demographic differences between the two groups (height, weight, albumin, diabetes, and peripheral vascular disease). In the early post-operative period, Minimal group had significantly less leg wound pain (P=0.04) and wound sepsis scores (P=0.01). Sternal pain was the same in both groups. After 6 weeks, wound scores and leg pain scores were not significantly different. There were no significant differences in rate of harvest (1.1 cm/min in each group). In Minimal group, 4 cm veins were harvested for each 1 cm skin incision compared with 1 cm in Open group (P<0.01). CONCLUSIONS: Minimally invasive saphenous vein harvesting significantly reduces early post-operative leg pain and wound sepsis. Our study demonstrates that minimally invasive harvesting can be performed at a satisfactory speed and should be considered to help reduce early post-operative morbidity.

Coronary Artery Bypass↗
PubMed2002

Nitric oxide modulates superoxide release and peroxynitrite formation in human blood vessels.

Nitric oxide and superoxide have important roles as vascular signaling molecules. Nitric oxide (NO) reacts rapidly with superoxide, producing peroxynitrite. The relative balance between these radicals has important implications for vascular pathophysiology in hypertension and other vascular disease states. However, the relationships between superoxide, NO, and peroxynitrite formation in human blood vessels remain unclear. Accordingly, we systematically measured NO, superoxide, and peroxynitrite production from human internal mammary arteries, radial arteries, and saphenous veins from 78 patients undergoing coronary bypass surgery. Basal superoxide release was detected in all vessels at similar levels. However, endothelial removal or nitric oxide synthase inhibition increased mean superoxide release, with a corresponding reduction in peroxynitrite formation. Conversely, NO donors and superoxide scavengers both reduced superoxide release, whereas only NO donors increased peroxynitrite formation. These changes were much larger in arteries that in veins, but there were striking correlations between superoxide production, NO bioavailability, and peroxynitrite formation between the vessel types. Our findings provide direct evidence for coordinated vascular signaling mediated by interactions between NO, superoxide, and peroxynitrite and have important implications for studies of the functional effects of these radicals in human blood vessels.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗