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Biomedical subjects

R D Rakhit

Publications and source records attributed to R D Rakhit.

16 recordsLinked to original sources
PubMed2007

Antithrombotic and interventional treatment options in cardioembolic transient ischaemic attack and ischaemic stroke.

Peer-reviewed data pertaining to anti-thrombotic and interventional therapy for transient ischaemic attack (TIA) or ischaemic stroke patients with non-valvular atrial fibrillation, atrial flutter, interatrial septal abnormalities, or left ventricular thrombus were reviewed. Long-term oral anticoagulant therapy with warfarin is the treatment of choice for secondary stroke prevention following TIA or minor ischaemic stroke in association with persistent or paroxysmal non-valvular atrial fibrillation or atrial flutter. If warfarin is contraindicated, long-term aspirin is a safe, but much less effective alternative treatment option in this subgroup of patients with cerebrovascular disease. Management of young patients with TIA or stroke in association with an interatrial septal defect is controversial. Various treatment options are outlined, but readers are encouraged to include these patients in one of the ongoing randomised clinical trials in this area. It is reasonable to consider empirical anticoagulation in patients with TIA or ischaemic stroke in association with left ventricular thrombus formation following myocardial infarction or in association with idiopathic dilated cardiomyopathy. If warfarin is prescribed, one should aim for a target international normalised ratio of 2.5 (range 2-3) to achieve the best balance between adequate secondary prevention of cardioembolic events and the risk of major haemorrhagic complications.

Age Factors↗
PubMed2002

Local and systemic expression of basic fibroblast growth factor in a patient with familial glomangioma.

Glomangiomas are rare cutaneous tumours composed of glomus cells, which are modified smooth muscle cells. The aetiology of this condition is thought to involve a mutation in a novel gene acting to regulate angiogenesis. We report a patient from a large family with three generations affected by familial multiple glomangiomas. We hypothesized that the growth factors basic fibroblast growth factor and vascular endothelial growth factor, which stimulate/regulate angiogenesis could be involved in the pathogenesis of these lesions. Therefore, using enzyme-linked immunosorbent assays and immunohistochemistry, respectively, we measured systemic and tissue levels of these growth factors in a patient with familial glomangiomas. In addition, we investigated endothelial mitogenicity of the patient's serum as a functional assay of systemic growth factor activity.

Adult↗
PubMed2002

Antiarrhythmic and anti-ischaemic effects of angina in patients with and without coronary collaterals.

OBJECTIVE: To determine whether the changes in the manifestations of myocardial ischaemia during sequential angina episodes caused by exercise or coronary artery occlusion are collateral dependent. METHODS: 40 patients awaiting percutaneous transluminal coronary angioplasty for an isolated left anterior descending artery stenosis underwent three sequential treadmill exercise tests, with the second exertion separated from the first by 15 minutes, and from the third by 90 minutes; 28 patients subsequently completed two (> 180 s) sequential intracoronary balloon inflations with measurement of collateral flow index from mean coronary artery wedge, aortic, and coronary sinus pressures. RESULTS: On second compared with first exercise, time to 0.1 mV ST depression (mean (SD): 340 (27) v 266 (25) s) and rate-pressure product at 0.1 mV ST depression (22 068 (725) v 19 586 (584) beats/min/mm Hg) were increased (all p < 0.005), while angina and ventricular ectopic beat frequency were diminished (p < 0.05). This advantage, which had waned by the third effort, was independent of collateral flow index. Similarly, at the end of the second compared with the first coronary occlusion, ventricular tachycardia (21% v 0%, p < 0.05), ST elevation (0.47 (0.07) v 0.33 (0.05) mV, p < 0.005), and angina severity (6.1 (0.7) v 4.6 (0.7) units, p < 0.005) were reduced despite similar collateral flow indices. CONCLUSIONS: In patients with coronary artery disease, ventricular arrhythmias, ST deviation, and angina are reduced during a second exertion or during a second coronary occlusion. This protective effect can occur independently of collateral recruitment. These characteristics, together with the breadth and temporal pattern of protection, are consistent with ischaemic preconditioning.

Aged↗
PubMed2001

Role of G proteins and modulation of p38 MAPK activation in the protection by nitric oxide against ischemia-reoxygenation injury.

Protein kinase C (PKC)-mediated regulation of the mitogen-activated protein kinases (MAPK) may play a role in the protection afforded by ischemic preconditioning (PC). Nitric oxide (NO) can influence MAPK activation via interaction with PKC or farnesylation of low-molecular-weight (LMWT) G proteins. However, we have recently reported the mechanism of NO-induced cardioprotection to be a PKC-independent process. Therefore, we investigated the role of LMWT G proteins and MAPK signaling in NO-induced cardioprotection against simulated ischemia-reoxygenation (SI-R) injury. Neonatal rat cardiomyocytes treated for 90 min with the NO donor S-nitroso-N-acetyl-l,l-penicillamine (SNAP) 1 mM were protected against 6 h of SI (hypoxic conditions at 37 degrees C with 20 mM lactate, 16 mM KCl at pH 6.2) and 24 h reoxygenation under normal culture conditions. NO-induced protection was blocked by the G protein inhibitor alpha-hydroxyfarnesylphosphonic acid (alphaHFP) 10 microM. We studied the time course of p42/44 and p38 MAPK dual-phosphorylation hourly during SI using phospho-specific antibodies. p38 was phosphorylated during SI and the peak phosphorylation was significantly delayed by SNAP pretreatment. The p38 inhibitor SB203580 1 microM, given during SI, protected against injury. Thus the delay in peak p38 activation may contribute to, rather than be the effect of, NO-induced cardioprotection. We have shown that p38beta does not contribute to the total p38 signal in our extracts. Thus there is no detectable beta isoform. We conclude that the main isoform present in these cells and thought to be responsible for the observed phenomenon, is the alpha isoform.

Adenoviridae↗
PubMed2001

Mitochondria as targets for nitric oxide-induced protection during simulated ischemia and reoxygenation in isolated neonatal cardiomyocytes.

BACKGROUND: As shown previously, exposure to NO donors initiates protective mechanisms in cardiomyocytes that persist after removal of the donor, a form of pharmacological preconditioning. Because NO also affects mitochondrial respiration, we studied the effect of NO on mitochondrial Ca(2+) uptake. METHODS AND RESULTS: Neonatal rat ventricular myocytes in primary culture were exposed to 1 hour of simulated ischemia and 1 hour of reoxygenation (sI/R). Pretreatment with the NO donor S-nitroso-N-acetyl-penicillamine (SNAP) (1 mmol/L for 90 minutes), followed by washing and incubation for 10 to 30 minutes, reduced sI/R-induced cell death to 25.4% compared with control (propidium iodide exclusion assay, P<0.001). Short (10-second) exposures to SNAP reversibly suppressed mitochondrial respiration without a detectable change in mitochondrial potential. In contrast, treatment with SNAP for 90 minutes caused a modest but sustained mitochondrial depolarization, as judged by JC-1 fluorescence. SNAP pretreatment limited cellular Ca(2+) overload during ischemia (fura-2 ratio rose to 226+/-40% versus 516+/-170% of baseline, n=5, P<0.05) and prevented loss of cell membrane integrity during reoxygenation. SNAP pretreatment also significantly reduced the ability of mitochondria to accumulate Ca(2+) in the face of a similar cytosolic Ca(2+) load (peak rhod-2 fluorescence 133+/-4% versus 166+/-7% of baseline at similar fluo-3 levels, P=0.0004, n=52 and 25, respectively). CONCLUSIONS: Pretreatment with an NO donor induces a modest, sustained mitochondrial depolarization and protects cardiomyocytes from sI/R injury. The demonstrated reduction in mitochondrial Ca(2+) uptake possibly reduces cytosolic Ca(2+) overload, providing a likely mechanism for NO-induced protection.

Animals↗
PubMed2000

Nitric oxide-induced cardioprotection in cultured rat ventricular myocytes.

The aim of this study was to investigate the role of nitric oxide (NO) in a cellular model of early preconditioning (PC) in cultured neonatal rat ventricular myocytes. Cardiomyocytes "preconditioned" with 90 min of stimulated ischemia (SI) followed by 30 min reoxygenation in normal culture conditions were protected against subsequent 6 h of SI. PC was blocked by N(G)-monomethyl-L-arginine monoacetate but not by dexamethasone pretreatment. Inducible nitric oxide synthase (NOS) protein expression was not detected during PC ischemia. Pretreatment (90 min) with the NO donor S-nitroso-N-acetyl-L,L-penicillamine (SNAP) mimicked PC, resulting in significant protection. SNAP-triggered protection was completely abolished by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) but was unaffected by chelerythrine or the presence of glibenclamide and 5-hydroxydecanoate. With the use of RIA, SNAP treatment increased cGMP levels, which were blocked by ODQ. Hence, NO is implicated as a trigger in this model of early PC via activation of a constitutive NOS isoform. After exposure to SNAP, the mechanism of cardioprotection is cGMP dependent but independent of protein kinase C or ATP-sensitive K(+) channels. This differs from the proposed mechanism of NO-induced cardioprotection in late PC.

Alkaloids↗
PubMed1999

Restrictive pericarditis.

BACKGROUND: Pericardial thickening is an uncommon complication of cardiac surgery. OBJECTIVES: To study pericardial thickening as the cause of severe postoperative venous congestion. SUBJECTS: Two men, one with severe aortic stenosis and single coronary artery disease, and one with coronary artery disease after an old inferior infarction. Both had coronary artery bypass grafting surgery. METHODS: Magnetic resonance imaging (MRI), Doppler echocardiography, and cardiac catheterisation. RESULTS: Venous pressure was raised in both patients. MRI showed mildly thickened pericardium, and cardiac catheterisation indicated diastolic equalization of pressures in the four chambers. Jugular venous pulse showed a dominant "Y" descent coinciding with early diastolic flow in the superior vena cava, and mitral and tricuspid Doppler forward flow proved restrictive physiology. The clinical background suggested pericardial disease so both patients had pericardiectomy. This proved the pericardium to be thickened; the extent of fibrosis also involved the epicardium. CONCLUSIONS: Although rare, restrictive pericarditis (restrictive ventricular physiology resulting from pericardial disease) should be considered to be a separate diagnostic entity because its pathological basis and treatment are different from intrinsic myocardial disease. This diagnosis may be confirmed by standard investigational techniques or may require diagnostic thoracotomy.

Aged↗
PubMed1996

An audit of lipid screening and management in patients undergoing diagnostic cardiac catheterization. Brompton House Officer Audit Group.

The aim of this study was to audit the management of hyperlipidaemia in a cohort of 206 consecutive patients, with known or suspected coronary artery disease, referred for diagnostic coronary angiography. The association of lipid subfraction values with the presence and extent of coronary artery disease was explored to identify the indices of greatest potential value to the hospital cardiologist, in the management of secondary prevention. Patients were questioned about previous lipid tests performed, advice received and treatment prescribed. Referral letters and hospital notes were reviewed to identify documentation of lipid results and treatment strategies. De novo fasting lipid estimations were obtained on 205 subjects at the time of catheterization. In only 46/206 (22%) cases was some form of lipid result recorded in the existing hospital notes or referral documentation. No patient was aware of the levels of the high or low density lipoprotein cholesterol subfractions (HDL, LDL) nor were these specifically recorded, or the subject of clinical comment, in any of the referral documentation. Patients who knew their total cholesterol (in mmol.1-1) result either as a value or as a "high' or "normal' categorization proved accurate witnesses. In keeping with other angiographic studies, we found that low values of HDL and high TC/HDL ratios were significantly associated with both disease presence and extent. Total cholesterol, calculated LDL and triglyceride levels had no such association. In the group as a whole and despite current therapy, 169/206 (82%) patients had a total cholesterol > 5.2 and 163/206 (79%) a TC/HDL ratio > 5. Only 22 (11%) patients were on drug therapy with a further 43 (21%) practising dietary modification. In the vast majority of subjects receiving some form of lipid intervention, target lipid levels had not been achieved. This study identifies the need for more intensive management of hyperlipidaemia in patients with coronary artery disease. Knowledge of HDL levels may be of value in guiding lipid secondary prevention management in the patient population evaluated at an angiographic centre.

Age Factors↗
PubMed1993

Sarcoid, amyloid and heart failure.

We report the case of an adult West Indian patient who presented with heart failure 20 years after an initial diagnosis of pulmonary sarcoidosis. Endomyocardial biopsy revealed AL type amyloid which was later found to be secondary to an underlying multiple myeloma.

Amyloid↗