Echocardiographic assessment of viable myocardium

Left ventricular function is one of the most important determinates of long-term prognosis in patients with coronary artery disease. In recent years, it has become apparent that left ventricular dysfunction in patients with coronary artery disease is not always an irreversible process stemming from myocardial necrosis and fibrosis. Myocardial tissue can undergo both a state of potential reversible dysfunction because of prolonged sustained ischemia (hibernating myocardium) or episodes of acute ischemia (stunned myocardium). Revascularization of this tissue may improve regional and global left ventricular function and therefore prognosis. Numerous studies have now firmly established dobutamine echocardiography as a safe, reliable, and accurate imaging modality in the assessment of reversible left ventricular dysfunction. Furthermore, dobutamine echocardiography has been shown to have good sensitivity, specificity, and, more importantly, positive predictive accuracy in identifying both acute and chronic reversible left ventricular dysfunction for risk satisfaction and prognosis.     

Beta-adrenergic receptor-stimulated apoptosis in cardiac myocytes is mediated by reactive oxygen species/c-Jun NH2-terminal kinase-dependent activation of the mitochondrial pathway

Stimulation of beta-adrenergic receptors (betaARs) causes apoptosis in adult rat ventricular myocytes (ARVMs). The role of reactive oxygen species (ROS) in mediating betaAR-stimulated apoptosis is not known. Stimulation of betaARs with norepinephrine (10 micromol/L) in the presence of prazosin (100 nmol/L) for 24 hours increased the number of apoptotic myocytes as determined by TUNEL staining by 3.6- fold. The superoxide dismutase/catalase mimetics Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin pentachloride (MnTMPyP; 10 micromol/L) and Euk-134 decreased betaAR-stimulated apoptosis by 89+/-6% and 76+/-10%, respectively. Infection with an adenovirus expressing catalase decreased betaAR-stimulated apoptosis by 82+/-15%. The mitochondrial permeability transition pore inhibitor bongkrekic acid (50 micromol/L) decreased betaAR-stimulated apoptosis by 76+/-8%, and the caspase inhibitor zVAD-fmk (25 micromol/L) decreased betaAR-stimulated apoptosis by 62+/-11%. betaAR-stimulated cytochrome c release was inhibited by MnTMPyP. betaAR stimulation caused c-Jun NH2-terminal kinase (JNK) activation, which was abolished by MnTMPyP. Transfection with an adenovirus expressing dominant-negative JNK inhibited betaAR-stimulated apoptosis by 81+/-12%, and the JNK inhibitor SP600125 inhibited both betaAR-stimulated apoptosis and cytochrome c release. Thus, betaAR-stimulated apoptosis in ARVMs involves ROS/JNK-dependent activation of the mitochondrial death pathway.     

Dressler's syndrome following pulmonary vein isolation for atrial fibrillation

Dressler's syndrome, characterized by features of fever, pericarditis and pericardial effusion typically occurs in the weeks to months following a myocardial infarction. The syndrome has also been described following several other myocardial and pericardial pathologies, including two reports of Dressler's syndrome following radio-frequency ablation. We describe a case of Dressler's syndrome following a pulmonary vein isolation procedure, which is being performed with increasing frequency as a treatment strategy for atrial fibrillation.     

Glucose Transporters and Glucose Utilization in Rat Brain after Acute Ethanol Administration

In the normal adult brain, glucose provides 90% of the energy requirements as well as substrate for nucleic acid and lipid synthesis. In the present study, effects of ethanol on glucose transporters (GLUT) and glucose utilization were examined in rat brain. Male Sprague-Dawley rats weighing 250-300 gms were given either ethanol 3 gm/kg BW or saline IP 4 hrs prior to the animal sacrifice and removal of the cerebral cortical tissue. The cortical plasma membranes analyzed by cytochalasin B binding assay showed a decrease in GLUT number but not in GLUT affinity in the ethanol treated rats as compared to the control rats. The estimated Ro values were 70 ± 8.9 Vs 91 ± 8.9 pmoles/mg protein (p < 0.05 N=4) and the estimated Kd values were 0.37 ± 0.03 and 0.28 ± 0.05 M (p: NS) in ethanol and control experiments respectively. Immunoblots of purified cerebral plasma membranes and low density microsomal fraction showed 17% and 71% decrease for GLUT1 and 54% and 21% (p<0.05 or less; n=6) for GLUT3 respectively in ethanol treated rats than in control animals. Immunofluoresence studies also showed reduction of GLUT1 immunoreactively in choroid plexus and cortical microvessels of ethanol treated rats as compared to control rats. The effect of ethanol on regional cerebral metabolic rates for glucose (CMR_Gle) was studied using [6-¹⁴C] glucose and showed statistically insignificant decrease in brain glucose utilization. These data suggest that ethanol invivo decrease GLUT number and protein content in rat cerebral cortex     

Coronary stent thrombosis: time course and clinical outcome

The current clinical practice of stent implantation has changed over the last few years. We analysed the incidence and time course of stent thrombosis in patients undergoing successful coronary angioplasty and stenting over the last three years. All the patients were treated with aspirin and ticlopidine. A total of 13 patients experienced stent thrombosis. The mean age was 52+/-12 years; 12 were smokers and 10 had a recent history of myocardial infarction. None of these patients had received abciximab. The median time from stent implantation to stent thrombosis was 10 hours, with all the stent occlusions occurring within 18 hours of stent implantation procedure. All the patients underwent a repeat intervention at a median time of 30 minutes after the clinical suspicion of stent occlusion. On follow-up of 1 to 24 months, three patients developed reocclusion. In the present era of coronary angioplasty and stenting, when interventional procedures are not pre-planned and patients are treated with aspirin and ticlopidine or clopidogrel at the time of stent implantation, the incidence of stent thrombosis is low; it is seen mainly in patients with recent myocardial infarction, majority of them being smokers, and occurs within 18 hours in all the patients.     

Analysis of quantitative relationship between viability determination in leprosy by MFP,ATP bioluminescence and gene amplification assay

Two hundred twenty-one untreated, borderline lepromatous/lepromatous (BL/LL) leprosy patients have been investigated for viability by the mouse foot pad method (MFP), adenosine triphosphate (ATP) and polymerase chain reaction (PCR). The biopsies were collected at the beginning of and 12/24 months after treatment. The patient group was treated with a) immunotherapy (BCG/Mw) + MDT; b) MDT + pyrazinamide; c) control MDT; d) MDT + minocycline 100 mg once a month supervised + ofloxacin 400 mg once a month supervised. Biopsies were divided in three parts for use in the mouse foot pad, molecular and ATP investigations. In untreated and treated patients (at 12 and 24 months), there was a general agreement among all three techniques, and PCR and ATP showed higher positivity as compared to MFP. Further, there was good correlation among the viable biomass estimated by bacillary ATP levels, PCR assay and growth in mouse foot pads. The positivity was observed by MFP as well as PCR assay (18-kDa and 36-kDa) from all of the specimens when the ATP content was more than 3.6 pg/million. When the ATP content was below 3.5 pg/million, the positive takes in MFP decreased but the PCR positivity correlated with ATP bioluminescence up to 0.04 pg/million. When the ATP content was even lower, the uptake in the MFP was possibly a matter of chance, while PCR positivity was observed in 96% of the cases. For specimens with undetectable ATP, positivity was seen in 1% of the cases, showing the inability of ATP bioluminescence method to detect low background due to host ATP. PCR signals in some cases could be due to the higher sensitivity of the method or persistence of DNA after bacterial death in some cases. On the whole, the PCR methods even though targeting DNA have shown good correlations with biomass which confirm their usefulness in monitoring therapeutic responses in leprosy.     

Malaria during pregnancy and infancy, in an area of intense malaria transmission in central India

The clinico-epidemiological pattern of malarial infection in a cohort of pregnant women and infants was analysed during a malaria epidemic (1997-1998). The subjects were all members of tribal communities in an isolated and almost inaccessible area of central India. Overall, 151 (55%) of the 274 pregnant women investigated were found to have malarial infections at some time during the study, with Plasmodium falciparum predominating (88% of infections). All of the women investigated, whether primigravidae (42% found infected), secundigravidae (68%) or multigravidae (54%), were at great risk of developing severe malaria. When trimesters were compared, the highest prevalence of P. falciparum infection was recorded in the second (59% infected), irrespective of parity. Of the women found infected with P. falciparum, 3% had abortions, 4% stillbirths and 2% had babies who died while neonates. The small number of P. vivax infections observed prevented similar analyses for this species of parasite. Malarial infection was also seen in 218 (41%) of the 535 infants investigated. The values of age-specific prevalences revealed that > 30% of the infants examined at 2 months of age were then found to have P. vivax and/or P. falciparum parasitaemias. At 1 year of age, overall malaria prevalence was 50%, with P. vivax representing 25% of the infections and P. falciparum the rest. Subsequent follow-up revealed that three of the infants investigated, each of whom had had P. falciparum infections previously, died before their first birthdays. Re-infections (or treatment failures) were found to be common, both in the infants and the pregnant women. Pregnant women and infants from the study area clearly require systematic intervention to reduce their malaria-attributable morbidity.     

Endothelin as a therapeutic target in the treatment of cardiovascular disease

Endothelins, a family of peptides derived from the vascular endothelium and smooth muscle cells possess vasoconstrictor and mitogenic properties. By acting predominantly in a paracrine fashion, these peptides activate specific receptors and have protean effects in normal and diseased organ systems. The wide distribution of these receptors in various tissues mediate the multiplicity of physiologic actions attributed to endothelins. Much of our understanding about endothelins has come from the development of an array of receptor-specific and mixed receptor antagonists. Based on the promising results from animal studies, active research and drug development programs are under way to investigate the clinical potential of endothelin antagonism for treatment of cardiovascular disease.