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A Mehra

Publications and source records attributed to A Mehra.

48 records · Page 3Linked to original sources
PubMed1990

Alterations in elastin and collagen related to the mechanism of progressive pulmonary venous obstruction in a piglet model. A hemodynamic, ultrastructural, and biochemical study.

We created an animal model to understand better the pathogenesis and underlying mechanism of progressive central pulmonary venous (PV) obstruction, a condition not amenable to current therapy. Twenty piglets underwent banding of their PVs, 18 had a sham operation, and 12 were nonoperated controls. After 1, 3, and 6 weeks hemodynamic data were obtained and correlated with ventricular weights, PV and pulmonary artery (PA) distensibilities (at 1 week), morphometric structural and ultrastructural analyses, and biochemical assessment of elastin determined gravimetrically (and by desmosine level at 1 week), collagen, and elastase activity. At 1 week, PV banding was associated with increased PV compliance (p less than 0.05). At 3 weeks, an increased PA pressure (Ppa) (p less than 0.05) was observed, unaccompanied by a rise in PV pressure (Pcw). In the PV, however, there was breakdown of the internal elastic lamina with apparent migration of smooth muscle cells from media to subendothelium. At 6 weeks, a rise in Pcw (p less than 0.01), a further rise in Ppa (p less than 0.01), and right ventricular hypertrophy (p less than 0.005) were observed. We also observed mild PV intimal thickening (p less than 0.01), complete degradation of elastic laminae (p less than 0.05), and an increase in collagen assessed morphometrically (p less than 0.01). The banding procedure resulted in an overall increase in PV elastin synthesis and in the proportion of elastin determined gravimetrically (p less than 0.05 for both) but not by desmosine level, suggesting the possibility of poor cross-linking of elastin, which might account for the early increased distensibility of the PV. However, our assay could not detect an increase in elastase activity associated with either the increased distensibility or the ultrastructural changes of elastin degradation. The increased Ppa was not associated with significant PA biochemical or structural changes. We speculate that in response to distal venous obstruction, early remodeling of the PVs increases distensibility, protecting the lung from venous congestion and blunting a rise in Pcw. PA hypertension precedes the rise in Pcw, likely because of reflex vasoconstriction. The subsequent modest rise in Pcw is already associated with extensive fibrosis of the PV, suggesting a reason for unsuccessful current therapy and a need for consideration of earlier assessment and intervention.

Animals↗
PubMed1990

Warm induction blood cardioplegia in the infant. A technique to avoid rapid cooling myocardial contracture.

The use of profound hypothermia and total circulatory arrest for repair of heart defects in neonates usually involves a period of systemic and myocardial bypass cooling. Rapid cooling of muscle (skeletal, smooth, and myocardial) can result in contracture through elevation of cytosolic calcium levels. The increased myocardial tone caused by cooling might render the heart more vulnerable to a subsequent period of cardioplegic ischemic arrest. Infants may be more susceptible to contracture because their small body mass allows more rapid myocardial temperature change when prearrest bypass cooling is used. The influence of avoiding rapid myocardial cooling before induced cardioplegic arrest was analyzed in a group of infants weighing less than 6 kg at the time of open cardiac operation. Myocardial ischemic arrest by warm (37 degrees C) induction blood cardioplegia was used in 57 infants and compared with results in 440 infants treated with standard blood cardioplegia. Multivariate logistic regression analysis revealed that patient diagnosis, weight, and age at operation were significant risk factors for operative mortality. The use of warm induction blood cardioplegia had a strongly positive independent effect on survival (p = 0.0003) for any patient weight, age, or diagnostic group. We recommend the avoidance of rapid myocardial cooling on bypass in all patients before induction of cardioplegic ischemic arrest.

Blood↗
PubMed1984

Recovery of native proteins from preparative electrophoresis gel slices by reverse polarity elution.

A technique for high yield recovery of native, biologically active proteins from preparative polyacrylamide gel slices by reverse polarity elution is described. No apparatus other than the standard slab gel electrophoresis system is required. Several proteins have been recovered in biologically active form at a 90% yield, in quantities ranging from 0.4 mg to 4.2 mg. The method is effective with both small (9,000 dalton) and large (186,000 dalton) polypeptides. Both simple and complex proteins are recovered intact. For example, the copper-zinc and manganese superoxide dismutases from crude soybean extracts are active upon recovery. Similarly, the vitamin D-dependent calcium binding proteins from rat kidney and intestine are isolated by this method in homogeneous, active form.

Animals↗
PubMedDate not supplied

Modeling of oxygen transport in blood-perfluorocarbon emulsion mixtures: Part I: oxygen uptake in tubular vessels.

Perfluorocarbon (PFC) emulsions are usually used as mixtures with blood to enhance its capacity for oxygen, because stand alone PFC emulsions cannot perform the normal regulatory functions of blood. These mixtures have been found to be very effective in increasing the tissue oxygen tension, especially at high oxygen partial pressures, and many experimental observations exist in the literature in support of this fact. The explanations for these observations are still speculative and unquantified, however. In this work, models have been developed to describe oxygen transport in uniform and non-uniform mixtures of blood and PFCs. For the latter case, the extreme situation of central migration of erythrocytes is considered, wherein the erythrocytes occupy the central core region of the vessel surrounded by a plasma annulus. The predictions of the proposed models have been examined using a fixed wall oxygen tension, and the oxygen transport characteristics of mixtures have been presented with reference to blood alone. It was found that at high oxygen tensions the addition of PFCs significantly increases the oxygen wall flux into the tube. This increased flux, coupled with effects of competing oxygen sinks (erythrocytes and PFC droplets), leads to an anomalous increase in the average oxygen tension for short distances from the tube entrance. It has been shown that a near wall excess of PFC droplets is not necessary to cause this increase, as mentioned by Vaslef and Goldstick. For longer distances, however, the addition of PFCs leads to a decrease in the average oxygen tension.

Blood↗
PubMedDate not supplied

Modeling of oxygen transport in blood-perfluorocarbon emulsion mixtures: Part II: tissue oxygenation.

The models developed in the accompanying article in this issue for oxygen transport in uniform (pseudo-homogeneous model) and non-uniform (core annulus model) dispersions of erythrocytes and perfluorocarbons (PFCs) have been analyzed with a fixed wall flux boundary condition. Such a situation arises in the case of oxygen transport from a capillary to the surrounding tissue. The results reveal that PFCs are extremely effective in increasing the tissue oxygen tension during enriched air breathing. The increased oxygen capacity of blood on the addition of PFC emulsion is the main contributor toward this increase. If the contribution of the accompanying increase in the arterial oxygen tension also is considered, the resulting increase in the tissue oxygen tension was even larger than that observed by Braun et al, and hence other factors, such as an increase in the cardiac output or service of erythrocyte free capillaries, need not be invoked. A near wall excess of PFC droplets, if it occurs, has been shown to have a negligible effect on the tissue oxygen tension during normal rates of tissue oxygen consumption when the intracapillary gradients are small. In these conditions, the capillary phase may be taken to be uniform. A criterion has been developed to assess the magnitude of the gradients within the capillary. Accordingly, in cases of elevated rates of tissue oxygen consumption or low arterial oxygen tensions, the internal gradients become important and the capillary phase can no longer be taken to be uniform.

Arteries↗
PubMedDate not supplied

Therapeutic angiogenesis.

Coronary artery disease remains the leading cause of morbidity and mortality in the Western world. The initial approach to treatment involves risk factor modification in an attempt to halt or slow the progression of disease. Treatment of symptomatic disease aims at reducing myocardial oxygen demand with medical therapy. When this fails, revascularization to restore blood supply by percutaneous coronary intervention or coronary artery bypass grafting is often necessary. Advances in medical technology have both increased the success rate and lowered the morbidity and mortality of these 2 procedures. However, a significant number of patients have diffuse coronary artery disease, absent conduits after previous bypass surgery, small distal vessels, and comorbidities that may preclude either procedure. In a recent analysis of 500 consecutive patients at a tertiary referral center, approximately 12% of these patients fell into this category (1). With the widespread use of revascularization, it is likely that the number of patients who will not be suitable for revascularization in the future will increase significantly. Therapeutic angiogenesis is an exciting new method of improving blood supply to an ischemic segment of the myocardium to provide symptomatic relief to a large and growing population of patients.

Animals↗
PubMedDate not supplied

Modeling of oxygen uptake in perfluorocarbon emulsions. Some comparisons with uptake by blood.

The use of perfluorocarbons emulsified in water as blood substitutes (artificial blood), is well known. Although considerable research has been devoted to the study of stability, toxicity, and gas solubility properties of these emulsions, there is no quantitative guide to the oxygen transport behavior in such emulsions, especially with reference to this transport process in actual blood. This paper describes a mathematical model from which the oxygen flux into a straight, cylindrical tube carrying a perfluorocarbon emulsion may be computed. The solutions to the proposed model can be adapted to that for a capillary or for a single tube in a blood oxygenator. The rates of oxygen transfer, so obtained, have been compared with analogous transfer rates that can be achieved in natural blood flowing under identical conditions. Therefore, the minimal solubilization capacity for oxygen required of a perfluorocarbon emulsion can be estimated on a quantitative basis. The modeling approach used in this study is based on the well tested theory of mass transfer in microheterogeneous media reported in the chemical engineering literature.

Blood↗