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Biomedical subjects

K Bhagat

Publications and source records attributed to K Bhagat.

47 records · Page 3Linked to original sources
PubMed1997

Flow associated or flow mediated dilatation? More than just semantics.

Dilatation of the brachial artery occurs after flow is increased, and an attenuation in this response is seen in subjects with cardiovascular risk factors, and in those with established coronary artery disease. The mechanisms linking ischaemia, flow changes, and brachial artery dilatation are unclear, and it is not known how these are affected by arterial disease. For the present it might be more appropriate to refer to flow associated rather than flow mediated dilatation, to describe the phenomenon in the brachial artery. Despite these caveats, the non-invasive measurement of brachial artery following ischaemic dilatation represents a significant advance, and its suitability as a surrogate marker for coronary artery dysfunction appears promising. The technique has potential as a tool for screening those at high risk of vascular disease, and as a surrogate endpoint in intervention studies. Further research should clarify the mechanisms involved, and lead to greater insights into the nature of endothelial dysfunction and cardiovascular disease.

Brachial Artery↗
PubMed1996

Local venous responses to endotoxin in humans.

BACKGROUND: Septic shock is characterized by arterial and venous dilatation and decreased responsiveness to vasoconstrictors. We have developed a method to explore the effects and mechanisms of action of administration of endotoxin into a blood vessel in vivo. METHODS AND RESULTS: Endotoxin was instilled into a dorsal hand vein for 1 hour and then removed. A dose-response curve to norepinephrine was constructed before and 1, 2, 3, and 4 hours after endotoxin. In a separate study, dose-response curves to norepinephrine were constructed in two separate veins on the same hand, only one of which received endotoxin. Sympathetic-mediated venoconstrictor responses were also studied. Cyclooxygenase inhibitors, nitric oxide synthase inhibitors, and hydrocortisone were used to explore the mechanisms of the effects seen. Endotoxin caused a rightward shift in the dose-response curve to norepinephrine. The effect was greatest at 1 hour (maximal constriction: before endotoxin, 87 +/- 4%; after endotoxin, 52 +/- 8%; occlusion n = 4; P < .05) and returned to normal by 4 hours. In addition, deep-breath venoconstrictor responses were abolished in the endotoxin-treated vein. Instillation of endotoxin daily for 3 days resulted in the development of tolerance (maximal constriction to norepinephrine after endotoxin; day 1, 39 +/- 6%; day 2, 67 +/- 7%; day 3, 85 +/- 7%). Cyclooxygenase and/or nitric oxide synthase inhibitors did not alter the response to endotoxin, whereas prior administration of hydrocortisone abolished the effects. CONCLUSIONS: Instillation of endotoxin caused a glucocorticoid-inhibitable hyporesponsiveness to the constrictor effects of norepinephrine and abolished sympathetically induced and drug-induced venoconstriction. This acute response does not appear to be mediated by nitric oxide or prostanoids. Direct vascular tolerance to endotoxin occurs on repeated administration.

Adult↗
PubMed1996

Endothelial "stunning" following a brief exposure to endotoxin: a mechanism to link infection and infarction?

BACKGROUND: There is an association between infection, inflammation and acute cardiovascular events. In an attempt to explore the mechanism of this association we have developed a model to examine the effects on endothelial function of a brief exposure to endotoxin. METHODS AND RESULTS: Endotoxin was instilled into isolated superficial hand veins of healthy volunteers. The vein was isolated by means of two wedges and endotoxin instilled into the isolated segment. After 1 h the contents of the vein were aspirated and the wedges removed. Dose-response curves to bradykinin (a stimulator of nitric oxide synthesis), arachidonic acid (the precursor of prostanoid production) and GTN (a nitric oxide donor) were constructed before and 1 h after endotoxin. Endotoxin caused a glucocorticoid-inhibitable attenuation in the dose-response curves to bradykinin and arachidonic acid (P < 0.05). This effect persisted for 48 h and took 7 days to recover. Exposure of saphenous vein to endotoxin in vitro also caused selective impairment of endothelium-dependent relaxation (P < 0.05) yet microscopy of the vessels exposed to endotoxin showed no endothelial denudation or structural damage. CONCLUSION: The results demonstrate that a brief local exposure to endotoxin caused endothelial dysfunction that persists for 48 h and takes up to 7 days to recover. The endothelial dysfunction is not due to expression of the inducible isoform of nitric oxide synthase and persists for far longer than the effects of endotoxin on vascular smooth muscle function. We have coined the term endothelial "stunning" to describe the transient endothelial dysfunction and suggest it might provide a mechanism underpinning the association between infection or inflammation and increased cardiovascular risk. Endothelial stunning appears to provide a novel, transient, variable and modifiable potential cardiovascular risk factor.

Adult↗
PubMed1995

Vasodilatation to arachidonic acid in humans. An insight into endogenous prostanoids and effects of aspirin.

BACKGROUND: Human endothelial and vascular smooth muscle cells synthesize prostanoids. Several of these have been implicated in the physiological and pathophysiological regulation of vascular tone; however, there is no direct evidence that human blood vessels synthesize sufficient prostanoid to alter vessel tone. METHODS AND RESULTS: We explored the effects of local infusions of arachidonic acid on the tone of preconstricted superficial hand veins in healthy volunteers. Aspirin was used to assess the contribution of prostanoids to the responses seen. Local infusion of arachidonic acid produced a dose-dependent dilatation of preconstricted veins. This was abolished by local infusion of aspirin. Oral aspirin was also effective: a high (anti-inflammatory) dose of aspirin (1 g) taken 2 hours before the experiment blocked the arachidonic acid-induced venodilatation; however, a low (cardioprotective) dose of aspirin (75 mg) did not. Unlike the responses to arachidonic acid, responses to glyceryltrinitrate and bradykinin were unaltered by aspirin (1 g). Ex vivo platelet aggregation was inhibited by aspirin in both high and low doses. Aspirin (1 g) inhibited arachidonic acid-induced venodilatation for up to 5 days. The time course was similar for vascular and platelet effects. CONCLUSIONS: The present findings demonstrate that local generation of prostanoids in a human vessel in vivo alters vascular tone. The predominant prostanoid synthesized is a dilator and its synthesis can be blocked by an anti-inflammatory but not a cardioprotective dose of aspirin. The results suggest that selective inhibition of platelet aggregation by oral aspirin might be a function of dose rather than the interval between doses.

Acetaminophen↗
PubMed1995

Direct measurement of nitric oxide in human beings.

Nitric oxide is a short-lived radical involved in various biological processes. We have used an electrochemical microsensor to detect nitric oxide signals in blood vessels of healthy volunteers. The sensor was inserted into a hand vein, and the vessel was stimulated with acetylcholine or bradykinin. Dose-dependent signals were detected and were attenuated by an inhibitor of nitric oxide synthase. The results provide further evidence that endothelium-derived relaxing factor is nitric oxide and demonstrate a method for monitoring the L-arginine/nitric-oxide pathway in human beings.

Acetylcholine↗