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Biomedical subjects

R Subramanian

Publications and source records attributed to R Subramanian.

At least 55 records · Page 3Linked to original sources
PubMed1993

Lack of change in MnSOD during ischemia/reperfusion of isolated rat heart.

Decreased endogenous superoxide dismutase (SOD) activity has been implicated in free radical-mediated reperfusion injury of the ischemic myocardium. Antioxidant enzymes have been added to the modalities of reperfusion therapy of acute myocardial infarction based on this observation. We measured the content of MnSOD specific protein, activity of Mn and Cu, ZnSODs, and MnSOD mRNA in the working isolated rat heart subjected to various durations of ischemia and reperfusion. Recovery of mechanical function was monitored and lactate and lactic dehydrogenase released in the coronary effluent before and after ischemia were measured. In this model with reversible or irreversible myocardial injury, we noted no change in the myocardial MnSOD specific protein content and, contrary to some previous observations, no change in the activity levels of Mn or Cu,ZnSODs. Our results suggest that free radical-mediated damage in the heart during ischemia and reperfusion is probably not due to impaired activity or degradation of native SODs.

Analysis of Variance↗
PubMed1993

Nonatherosclerotic narrowing of the atrioventricular node artery and sudden death.

OBJECTIVES: This study was undertaken to determine whether thickening of the atrioventricular (AV) node artery is a cause of sudden cardiac death. BACKGROUND: Thickening of the AV node artery has been implicated as a cause of sudden death primarily on the basis of case reports. Few pathologic studies have compared subjects who died of sudden cardiac death with normal control subjects who died traumatically. METHODS: The AV node artery in 27 patients with unexplained sudden cardiac death (mean age 24.8 +/- 7.4 years) was compared with that in 17 control subjects who died traumatically (mean age 25.6 +/- 7.0 years). No anatomic cause of death was found at autopsy in the subjects with sudden death, all of whom died of presumed cardiac arrhythmias. The conduction system of all hearts was studied by semiserial sections and Movat pentachrome stains. At the point of greatest narrowing of the AV node artery, the outer circumference and lumen outline were traced by computerized morphometry, the ratio of outer vessel area to lumen area was calculated and the histopathologic changes were noted. RESULTS: The rank-sum of ratios was significantly greater in the sudden death group than in the control group (p = 0.031, Wilcoxon rank-sum/Mann-Whitney statistic). A dysplastic AV node artery with significant acid mucopolysaccharide deposition was seen almost exclusively in the sudden death group (12 of 27 vs. 1 of 17, p = 0.006). In 10 subjects with sudden death a dysplastic AV node artery was narrowed > 2 SD over the control value; half of this subgroup died during exercise and one third had a family history of sudden unexplained cardiac death. CONCLUSIONS: Dysplasia of the AV node artery may contribute to death in a substantial portion of patients with unexplained sudden death, and such death is often associated with exercise and a family history of unexplained sudden death.

Adult↗
PubMed1993

Myocardial metabolism in chronic reperfusion after nontransmural infarction in pig hearts.

The purpose of these studies was to evaluate metabolic behavior in a 4-day reperfusion model in pigs after induction of subendocardial infarction. Two groups of swine [sham and intervention (Int) groups, n = 7) and 10 hearts per group, respectively] were prepared comparably with two surgical procedures separated over 4 days. In the Int group at the time of the first surgery, coronary flow in the left anterior descending (LAD) circulation was partially restricted (by 60%) for 60 min and was then reperfused. LAD myocardium at the time of the second surgery in both groups was extracorporeally perfused aerobically (5.9 +/- 0.2 ml.min-1.g dry wt-1) for 60 min and infused by equilibrium labeling with [U-14C]-palmitate and [5-3H]glucose to estimate fatty acid oxidation and exogenous glucose utilization. During extracorporeal perfusion, regional myocardial shortening and oxygen consumption were comparable between groups despite a marginal impairment in ATP resynthesis by mitochondria (26% decrease, P < 0.071) in Int hearts and a significant decline in mitochondrial respiration (45% decrease in respiratory control rate, P < 0.008; and 41% decrease in state 3 respiration, P < 0.032) as compared with sham hearts. Fatty acid oxidation described by 14CO2 production was 34.00 +/- 4.72 mumol.h-1.g dry wt-1 (averaged from 30-60 min of perfusion) in sham hearts but was decreased (by 48%, P < 0.004) in Int hearts. This reduction in fatty acid utilization may in part be explained by declines in the observed activity of the mitochondrial membrane transporter enzyme, carnitine palmitoyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Elements in hair and nails of urban residents of New Delhi. CHD, hypertensive, and diabetic cases.

The concentrations of Cd, Cr, Cu, Mn, Ni, Pb, and Zn were estimated in hair and nails of urban residents of New Delhi. Particularly, hair levels of Cu and Mn in hypertensive males, Cr and Zn in hypertensive females, and Zn in CHD and diabetic females, and nail levels of Zn in CHD and hypertensive females were significantly lower than controls. Thus, it is observed that there exists some positive correlation between element levels in hair and nails and CHD, hypertension, and diabetes of these subjects.

Coronary Disease↗
PubMed1992

Elements in hair and nails of residents from a village adjacent to New Delhi. Influence of place of occupation and smoking habits.

Samples of hair and nails collected from the residents of Wazirpur, a village adjacent to New Delhi, were analyzed for Cd, Cr, Cu, Mn, Ni, Pb, and Zn, and correlated with the residents' rural and urban places of occupations. It was observed that Pb and Cd hair levels of males working in rural areas were lower than in male businessmen and officers working in an urban area of New Delhi, thereby showing the different levels of elements exposure of the rural subjects. Such differences in the hair levels of elements were not observed among female subjects. The tobacco smoking habits of male and female rural subjects using hookah were associated with increased Cd levels in hair and nails.

Adult↗
PubMed1992

Effects of duration of ischaemia during preconditioning on mechanical function, enzyme release and energy production in the isolated working rat heart.

Repeated brief episodes of ischaemia "precondition" the myocardium and protect it during a subsequent period of sustained ischaemia. We subjected isolated rat hearts to sustained ischaemia with or without reperfusion after different schedules of preconditioning. We demonstrated that preconditioning with three 5 min periods of ischaemia separated by 10 min periods of reperfusion permits better functional recovery than preconditioning with three 2 min ischaemic periods separated by 10 min of reperfusion. Preconditioned hearts had creatine phosphate and adenine nucleotide levels comparable to those in the aerobically perfused controls, and showed good functional recovery. Although the mechanisms by which preconditioning protects the heart from subsequent ischaemic damage are unclear, we speculate that preservation of mitochondrial function and oxidative energy production is involved.

Adenine Nucleotides↗
PubMed1992

Trace elements in scalp hair of manufacturers of fireworks from Sivakasi, Tamil Nadu.

The concentrations of Cd, Cr, Cu, Mn, Ni and Pb were analysed by AAS in the hair of male and female, controls and workers from firework cottage industries from Sivakasi, Tamil Nadu. When compared with controls, significantly higher levels of Mn and Cr were found in male healthy workers and unhealthy workers with chronic headaches and dizziness. In the case of female workers, higher Mn and lower Pb levels were found, but the level of any element was not significantly different in the workers with ulcers and asthma. There is a possibility of occupational exposure of both male and female workers to the risk of Cr and Mn pollution.

Body Burden↗
PubMed1992

An animal model of chronic coronary stenosis resulting in hibernating myocardium.

An experimental animal model of hibernating myocardium is presented. Sixteen animals were initially prepared of which seven were selected for final review. Hearts were instrumented in two separate surgical procedures such that maximum phasic flow velocity in the left anterior descending (LAD) coronary artery was reduced by 50% and followed over 1 wk. Regional shortening declined at 1 wk to 62% of aerobic values (P less than 0.048) and did not improve over 2 h reperfusion. Metabolic determinations, obtained after 1 wk of coronary stenosis and immediately sampled before and after release of the LAD flow constrictor, showed no evidence of acidosis, hypercarbia, or an inability to extract oxygen at the tissue level. Thereafter, during the 2-h reperfusion period, hearts were able to respond to dobutamine (10 micrograms/kg infusion over 1 min) challenge with an appropriate shift in an end-systolic length estimate of contractility. Mitochondrial respiration at the conclusion of the studies in the reperfused bed demonstrated near normal recovery compared with aerobic values. None of the seven hearts showed gross evidence of infarction and only one heart was noted to have a few microfocal changes of healing infarction. Thus a new model of coronary stenosis is presented, which affected substantial reductions in mechanical function consistent with the concepts of hibernating myocardium. These mechanical events were not associated with marked metabolic abnormalities, reflecting advanced ischemia or mitochondrial dysfunction and could be transiently improved with inotropic stimuli. This model may prove beneficial as a tool in understanding mechanistic events underlying the hibernating heart.

Animals↗
PubMed1992

High density lipoprotein deficiency syndrome in chickens is not associated with an increased susceptibility to atherosclerosis.

A spontaneous high density lipoprotein (HDL) deficiency syndrome in chickens associated with a Z-linked (sex-linked) mutation has been reported (F. Poernama et al, J Lipid Res 1990;31:955-963). The mutant, called WHAM (Wisconsin hypo-alpha mutant), has a 70-90% reduction in plasma HDL cholesterol and apolipoprotein A-I (apo A-I) concentrations. In the present study, the effect of the HDL deficiency on diet-induced or spontaneous atherosclerosis was assessed. Control chickens maintained on a high-cholesterol diet for 28 weeks experienced a 2.4-fold rise in the plasma very low density lipoprotein cholesterol concentration, while the same diet induced a 3.7-fold rise in the low density lipoprotein cholesterol concentration in WHAM chickens. The high-cholesterol diet did not elevate the plasma HDL cholesterol or apo A-I concentrations in either group. Both the aortic area of involvement and the width of lesions were quantified by gross and microscopic examination, respectively. Cholesterol feeding produced a significant increase in the area of the aorta with atherosclerotic lesions in both control and mutant chickens. The HDL deficiency in WHAM chickens did not correlate with a higher lesion area or increased lesion thickness. To assess the effect of HDL deficiency on spontaneous atherosclerosis, a separate group of control and WHAM chickens was maintained on a low-fat, cholesterol-free diet for 3 years. At the end of the 3-year period, the area and thickness of the spontaneous aortic lesions in control and WHAM chickens were not significantly different. Spontaneous HDL deficiency in chickens is therefore not associated with increased susceptibility to atherosclerosis.

Animals↗
PubMed1992

Release of endothelin during reperfusion of ischemic myocardium. ET-1 release from reperfused heart.

Endothelin, the most potent endothelium-derived vasoconstrictor, was found to be released from the isolated ischemic rat heart after a prolonged period of reperfusion. No endothelin release was observed up to 1 hour of reperfusion following 30 minutes of global ischemic arrest. Although most of the endothelin release occurred as a burst after 1 hour of reperfusion, the endothelin release increased progressively at a slower rate up to 2 hours of reperfusion. The calcium slow channel blocker, nifedipine, and the phospholipase inhibitor, mepacrine, but not the free radical scavengers, superoxide dismutase (SOD) and catalase, prevented the endothelin release from the heart. Unlike endothelin release that did not occur until after 1 hour of reperfusion, lipid peroxidation assessed by thiobarbituric acid reactive product formation, and cellular injury as monitored by creatine kinase (CK) release, occurred upon reperfusion, and increased progressively with the duration of reperfusion. All the interventions including nifedipine, mepacrine, and SOD plus catalase, prevented the lipid peroxidation and CK release significantly. Coronary flow was reduced significantly after 1 hour of reperfusion, when endothelin release occurred, an event that also coincided with myocardial endothelial injury as assessed by transmission electron microscopy. These results indicate that endothelin is released only after a prolonged period of reperfusion, and the release process seems to be controlled by calcium and phospholipase, but not by free radicals.

Analysis of Variance↗
PubMed1991

Improved diagnosis and characterization of postinfarction left ventricular pseudoaneurysm by cardiac magnetic resonance imaging.

A patient with a ruptured left ventricular pseudoaneurysm complicating an acute posteroinferior myocardial infarction is described. Left ventricular pseudoaneurysms are a rare complication of acute myocardial infarction, usually occurring with inferior and/or posterior infarction. In contrast to true aneurysms, pseudoaneurysms are much more likely to rupture, regardless of size, causing hemopericardium and death. Therefore, once the diagnosis has been confirmed, prompt surgical resection is the current accepted treatment. The most accurate noninvasive diagnostic method has been echocardiography, with recent reports suggesting improved diagnosis with color flow Doppler echocardiography. Ventriculography confirms the diagnosis with more accurate anatomic detail, but is an invasive procedure. In our patient, two-dimensional and color Doppler echocardiography could not demonstrate the suspected pseudoaneurysm, which was demonstrated by ventriculography. However, magnetic resonance imaging (MRI) demonstrated the pseudoaneurysm, showing detailed anatomy not obvious on ventriculography. Before surgery could be performed, the patient died and was autopsied. Heart sections corresponding to MRI planes confirmed the MRI findings. A review of the literature has revealed no similar reports using MRI in the diagnosis of postinfarction pseudoaneurysms. Major advantages of MRI are generation of three-dimensional soft tissue images noninvasively, and generation of tissue contrast by rapid imaging sequences, obviating the need for contrast injection. Major disadvantages of MRI are the high cost of instrumentation, nonportability, and a requirement for patient immobility during the study. In cases of suspected pseudoaneurysm with equivocal echocardiography findings, MRI could provide early diagnosis, leading to early surgical intervention and increased patient survival.

Aged↗
PubMed1991

Protective effects of propionyl-L-carnitine during ischemia and reperfusion.

When cardiac function in isolated rat hearts was impaired by subjecting them to ischemia, subsequent perfusion with propionyl-L-carnitine and related compounds increased their rate of recovery. Thus at 11 mM, both propionyl-L-carnitine and, to a lesser extent, its taurine amide, and also acetyl-L-carnitine, significantly restored cardiac function in 15 minutes after 90 minutes of either low-flow or intermittent no-flow ischemia. Carnitine itself was ineffective. Propionyl-L-carnitine also increased tissue ATP and creatine phosphate compared with controls, but did not affect the levels of long-chain acyl carnitine and coenzyme. These esters also depleted fatty acid peroxidation, as shown with malonaldehyde, and were more effective than carnitine in preventing the production of superoxide. In myocytes, propionyl-L-carnitine alone stimulated palmitate oxidation, but in rat heart homogenates, both L-carnitine and propionyl-L-carnitine did so, while acetyl-L-carnitine was actually inhibitory. Possible mechanisms for the protective action of propionyl-L-carnitine against ischemia include an increased rate of cellular transport, stimulation of fatty acid oxidation, and a reduction of free radical formation.

Acetylcarnitine↗
PubMed1991

Growth kinetics of Bacillus stearothermophilus BR219.

Bacillus stearothermophilus BR219, a phenol-resistant thermophile, can convert phenol to the specialty chemical catechol. The growth kinetics of this organism were studied in batch, continuous, and immobilized-cell culture. Batch growth was insensitive to pH between 6.0 and 8.0, but little growth occurred at 5.5. In continuous culture on a dilute medium supplemented with 10 mM phenol, several steady states were achieved between dilution rates of 0.25 and 1.3 h-1. Phenol degradation was found to be uncoupled from growth. Immobilized cells grew rapidly in a rich medium, but cell viability plummeted following a switch to a dilute medium supplemented with 5 mM phenol.

Bacteriological Techniques↗
PubMed1991

Discordance between accumulation of C-14 deoxyglucose and Tl-201 in reperfused myocardium.

Radiolabeled deoxyglucose (FDG) has been advocated as a marker of viability of reperfused myocardium during acute infarction. However, data for such recommendation are few. We investigated cardiac deposition of C-14 deoxyglucose (C-14 DG) and of Thallium -201 (Tl-201) in rabbits subjected to coronary occlusion (15, 30, 60 or greater than 100 min) and reperfusion (75 min and 24 h). Measured myocardial concentrations of C-14 DG and Tl-201 in macroautoradiograms were quantitatively correlated in a 24 h reperfusion group with presence of myocardial necrosis evaluated by light microscopy. The major finding in this investigation was that with 30 min or 60 min of ischemia followed by reperfusion there were myocardial regions with significant hypoperfusion (Tl-201) and histologic necrosis. However, in the same myocardial areas, the deposition of C-14 DG was not correlated with the extent of necrosis (r = 0.27). Also, the deposition of C-14 DG in acute myocardial infarction was higher than that of Tl-201 (P = 0.05 by paired T test and by nonparametric Wilcoxon's test). It was also demonstrated that when the occlusion time was varied (15-130 min) and early reperfusion was provided for 75 min or omitted altogether, the myocardial accumulation of Tl-201 was variable and that myocardial sequestration of C-14 DG was higher than perfusion in central and peripheral portions of the area-at-risk. These observations do not support a role for the use of radiolabeled deoxyglucose for the detection of myocardial viability in recently infarcted cardiac muscle.

Animal Nutritional Physiological Phenomena↗
PubMed1991

Effects of propionyl-L-carnitine in chronically hypoperfused ("hibernating") myocardium.

The purpose of this report was to test the effects of systemic treatment with propionyl-L-carnitine in a new model of chronically hypoperfused ("hibernating") myocardium. Adolescent swine were instrumented to undergo a period of mild partial coronary constriction for 1 week (50% reduction of the maximum phasic flow velocity in the anterior descending coronary artery). This reduced regional mechanical function by 56%. The system satisfied criteria defining "hibernating" myocardium, in that the chronic hypoperfusion did not produce massive tissue necrosis and that the reduction in regional contraction remained responsive to inotropic stimulation. Treatment with 50 mg/kg propionyl-L-carnitine by mouth twice daily for 1 week significantly (p less than 0.0005) increased concentrations of free and total carnitine in the myocardial tissue by 39% and 31%, respectively. Treatment with propionyl-L-carnitine did not alter regional systolic shortening in either hibernation or reperfusion for 2 hours, but enhanced one estimate of contractility reserve based on the rate of left ventricular emptying with occlusion of the inferior vena cava. Propionyl-L-carnitine did not reverse the observed impairments in mitochondrial respiration (diminutions in state 3 respiration and the respiratory control ratio), but limited the number of lesions seen on histological examination. Six out of eight placebo hearts showed one or more changes of ischemia, infarction or reperfusion injury, while the same was true in only two out of eight hearts treated with propionyl-L-carnitine (p less than 0.003). Carnitine and various analogues have been proposed to benefit ischemic myocardium. The present data suggest that this general sparing effect may also occur with the propionyl derivative in chronically underperfused myocardium.

Animals↗
PubMed1991

Pulmonary and systemic fluid filtration after continuous versus bolus interleukin-2 infusion.

Interleukin-2 has been widely investigated as adjuvant therapy for advanced cancer and is administered by either bolus or continuous infusion. We compared the effects of bolus and continuous interleukin-2 infusion on pulmonary (QL) and systemic microvascular fluid filtration in 11 adult sheep prepared with chronic lung and soft-tissue lymph fistulas. Interleukin-2 was administered as a bolus infusion (100,000 units/kg) every 8 hours for 3 days or as a continuous infusion at the same dose for 3 days. No significant changes in pulmonary hydrostatic pressures or pulmonary vascular resistance were noted after either bolus or continuous interleukin-2 infusion. However, significantly decreased (p less than or equal to 0.05) systemic vascular resistances were observed in both groups. QL increased steadily throughout the infusion period in both groups, peaking at three times baseline on the third infusion day. The plasma/interstitial protein clearance (QL X lymph/plasma protein ratio) rose similarly in both groups, indicating increased barrier permeability. Increased lymphocyte clearance into lung lymph occurred by day 3 but was not associated with lymphocytic sequestration in the lung interstitium. We conclude that pulmonary and systemic microvascular fluid and protein flux exhibit similar changes after bolus or continuous interleukin-2 infusion. These changes are associated with increased clearance of lymphocytes into lung lymph that are not sequestered in the pulmonary interstitium after infusions of shorter duration.

Animals↗