Mathematical three-dimensional solid modeling of biventricular geometry

The characterization of regional myocardial stress distribution has been limited by the use of idealized mathematical representations of biventricular geometry. State-of-the-art computer-aided design and engineering (CAD/CAE) techniques can be used to create complete, unambiguous mathematical representations (solid models) of complex object geometry that are suitable for a variety of applications, including stress-strain analyses. We have used advanced CAD/CAE software to create a 3-D solid model of the biventricular unit using planar geometric data extracted from anex vivo canine heart. Volumetric analysis revealed global volume errors of 4.7%, −1.3%, −1.6%, and −1.1% for the left ventricular cavity, right ventricular cavity, myocardial wall, and total enclosed volumes, respectively. Model errors for 34 in-plane area and circumference determinations (mean ±SD) were 5.3±6.7% and 3.8±2.7%. Error analysis suggested that model volume errors may be due to operator variability. These results demonstrate that solid modeling of theex vivo biventricular unit yields an accurate mathematical representation of myocardial geometry which is suitable for meshing and subsequent finite element analysis. The use of CAD/CAE solid modeling in the representation of biventricular geometry may thereby facilitate the characterization of regional myocardial stress distribution.     

Nucleic acid vaccines

There are no adequate vaccines against some of the new or reemerged infectious scourges such as HIV and TB. They may require strong and enduring cell-mediated immunity to be elicited. This is quite a task, as the only known basis of protection by current commercial vaccines is antibody. As DNA or RNA vaccines may induce both cell-mediated and humoral immunity, great interest has been shown in them. However, doubt remains whether their efficacy will suffice for their clinical realization. We look at the various tactics to increase the potency of nucleic acid vaccines and divided them broadly under those affecting delivery and those affecting immune induction. For delivery, we have considered ways of improving uptake and the use of bacterial, replicon or viral vectors. For immune induction, we considered aspects of immunostimulatory CpG motifs, coinjection of cytokines or costimulators and alterations of the antigen, its cellular localization and its anatomical localization including the use of ligand-targeting to lymphoid tissue. We also thought that mucosal application of DNA deserved a separate section. In this review, we have taken the liberty to discuss these enhancement methods, whenever possible, in the context of the underlying mechanisms that might argue for or against these strategies.     

Cigarette smoking and the intention to quit among pregnant smokers

Research has demonstrated that smoking during pregnancy has deleterious effects on the health of the unborn child as well as the mother. The present study examined whether pregnant smokers would have a greater intention to quit smoking, whether the stage of pregnancy would influence the intention to quit, and whether variables which have predicted cessation among pregnant smokers would also predict intention to quit. The results indicated that pregnant women did not have a significantly greater intention to quit smoking compared to nonpregnant smokers, despite the health risks to their child. Women who were further along in their pregnancy and women who smoked more cigarettes on a daily basis demonstrated the least intention to quit. Notably, women in the first trimester showed the greatest intention to quit, suggesting that pregnant women may be most receptive to quitting during their first trimester.     

Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes

Umbilicoplacental embolization (UPE) in sheep has been used to investigate the effects of placental insufficiency on fetal development. However, its specific effects on the heart have been little studied. The aim of this study was to determine the effects of placental insufficiency, induced by UPE, on cardiomyocyte size, maturation and proliferation. Instrumented fetal sheep underwent UPE for either 10 or 20 days. Hearts were collected at 125 ± 1 days (10 day group) or 136 ± 1 days (20 day group) of gestation (term ∼145 days). Cell size, maturational state (as measured by the proportion of binucleated myocytes) and cell cycle activity (as measured by positive staining of cells for Ki-67) were determined in dissociated cardiomyocytes. UPE fetuses were hypoxaemic, but mean arterial pressures were not different from controls. UPE fetuses were lighter than control fetuses (10 days: −21%, P < 0.05; 20 days: −27%, P < 0.01) and had smaller hearts, but heart weight was appropriate for body weight. Neither lengths nor widths were different between control and UPE cardiomyocytes at either age. Ten days of UPE did not significantly alter the proportion of binucleated myocytes or cell cycle activity in either ventricle. However, 20 days of UPE reduced cell cycle activity in both ventricles by ∼70% ( P < 0.05); the proportion of binucleated myocytes was also lower in UPE fetuses at this age (left ventricle: 31.1 ± 12.0 versus 46.0 ± 6.6%, P < 0.05; right ventricle: 29.4 ± 12.3 versus 46.3 ± 5.3%, P < 0.05). It is concluded that in the absence of fetal arterial hypertension, placental insufficiency is associated with substantially depressed growth of the heart through suppressed proliferation and maturation of cardiomyocytes.     

Control of myocardial tissue components and cardiocyte organelles in pressure-overload hypertrophy of the cat right ventricle

Previous studies have demonstrated that there is a disproportionate increase in connective tissue in right ventricular myocardium subjected to pressure-overload hypertrophy associated with depressed cardiac contractility. While the myocardium is primarily responsive to load, the aim of the present study was to determine whether catecholamines also modulate the response of myocardial tissue components and cardiocyte organelles in pressure-overload-induced cardiac hypertrophy. Four experimental groups of cats were examined: (1) a sham-operated control group, (2) a group which had their pulmonary arteries banded in order to induce a pressure overload, (3) a group which had been subjected to the same pressure overload, but in addition had β-adrenoceptor blockade produced prior to and during the pressure overloading, and (4) a group which had been subjected to the same pressure overload, but in addition had α-adrenoceptor blockade produced prior to and maintained during the pressure overloading. As in our previous study, there was a significant and equivalent degree of right ventricular hypertrophy in all experimental groups with pressure overload when assessed either as the ratio of right ventricular weight to body weight or as cardiocyte cross-sectional area. At the light microscopic level, the disproportionate increase in the volume density of myocardial connective tissue seen in banded animals was completely prevented by either α- or β-adrenoceptor blockade. At the electron microscopic level, there was a reduction in the mitochondrial and myofibrillar volume fractions following β-adrenoceptor blockade. The results of this study provide evidence for a modulatory role of catecholamines in the control of myocardial connective-tissue proliferation in pressure-overload-induced cardiac hypertrophy. There is also evidence to support the role of the adrenergic nervous system in regulating cardiocyte subcellular organelles, independent of the regulation of cardiocyte size.     

Ca2+ channel actions of the non-dihydropyridine Ca2+ channel antagonist Ro 40-5967 in vascular muscle cells cultured from dog coronary and saphenous arteries

Summary We studied the membrane effects of (1S,2S)-2-(2-[[3-2(benzimidazolyl) propyllmethylamino]ethyl)-6-fluoro-1,2,3,4-tetrahydro-l-isopropyl-2-naphthyl-methoxy-acetate dihydrochloride, Ro 40-5967, a new non-dihydropyridine (DHP) Ca²⁺ channel antagonist, on dog coronary and saphenous arterial vascular muscle cells using the whole-cell patch-clamp method. Long-lasting (L-type) inward currents in 20 mM Ba²⁺ were measured over a range of test potentials (300 ms) from –50 mV to + 90 mV from a holding potential of –80 mV in the presence of 1 M Bay k8644 (a DHP Ca²⁺ agonist). Ro 40-5967 caused a concentration-dependent suppression of Ca²⁺ channel currents in muscle cells from both arteries, with greater potency on coronary than saphenous arterial cells. The concentration of Ro 40-5967 which inhibited the magnitude of peak inward currents by 50% (IC₅₀) was estimated to be 1 M (n = 5) in muscle cells from coronary artery and 10 M (n = 4) in saphenous artery. Ro 40-5967 (1 M) decreased the amplitude of the activation current-voltage relationship for coronary L-type Ca²⁺ channel currents over a wider range of membrane potentials than verapamil, diltiazem, or nifedipine. In contrast, block of Ca²⁺ channel currents in saphenous artery cells by 1 M Ro 40-5967 was only observed at command potentials positive to 0 mV. Ro 40-5967 (1 M) significantly shifted the voltage-inactivation curve downward by 40% in coronary (n = 4), but only by 18% in saphenous arterial muscle cells (n = 3). The non-parallel shift of the coronary artery inactivation curve suggests that pronounced resting channel block is a notable feature of Ro 40-5967. The marked inhibition of Ba²⁺ current by 1 M Ro 40-5967 in the inactivation protocol in coronary arterial muscle cells was found over the entire range of membrane holding potentials tested, while inhibition in the saphenous artery inactivation curve occurred only from holding potentials more positive than –40 mV. Therefore, Ro 40-5967 is unique: 1) in acting over a wider range of voltages, on both instantaneous and resting Ca²⁺ currents, than other Ca²⁺ antagonists; 2) in producing more significant resting state block; and 3) in acting with selectivity for coronary over saphenous arteries.This research was supported by National Institutes of Health grants HL38537, HL38645, and by F. Hoffmann-La Roche, Basel, Switzerland     

Anaesthesia for the parturient with cystic fibrosis

Cystic fibrosis is an inherited disorder that primarily affects the exocrine glands of the gastrointestinal and respiratory systems. It is commonly diagnosed at birth or shortly thereafter, and until recently few of these patients lived to reproductive age. However, as a result of improved medical care, there are now an increasing number of pregnancies in women with cystic fibrosis. We present the histories of two parturients with cystic fibrosis and discuss the anaesthetic and perinatal implications of this complex disease to their management.