Cardiac cultured

In a recent study, we tested the abihty of the hES ceU-derived cardiomyocytes to integrate structurally and functionally with host cardiac tissue both in vitro and in vivo [67]. Initially, the ability of the hES cardiomyocytes to form electromechanical connections with primary cardiac cultures was assessed using a high-resolution, in-vitro coculturing system (Eig. 12.3a). The contracting areas within the EBs were dissected and added to primary neonatal rat cardiomyocyte cultures. Within 24 hours of grafting it was possible already to detect microscopically, in all 22 cocultures studied, synchronous mechanical activity (as impressively shown in a video on the sup-... 

Boateng S, Lateef SS, Crot C, Motlagh D, Desai T, Samarel AM, Russell B, and Hanley L. Peptides bound to silicone membranes and 3D microfabrication for cardiac cell culture. Adv Mater, 2002, 14, 461 63. 

Figure 8. Effect of maitotoxin (MTX) on the time course of an increase in Ca uptake of cultured rat cardiac myocytes. Cbntrol ( ), and 10 g/mL MTX (o). Vertical lines indicate the standard error of mean (n=3). (Reproduced with permission from Ref. 20. Copyright 1987 Elsevier)...

Figure 3 PGG Dose-response in an E. coli Peritoneal Sepsis Challenge. Groups of 10 mice each received 0.2 mL of the various concentrations of PGG in sterile saline by bolus intravenous (iv) injection (transthoracic cardiac puncture). A control group received 0.3 mL of sterile saline. Mice were challenged 3-4 hours after administration of PGG by intraperitoneal injection with 0.1 mL (lxlO8 CFU/ml) of an E. coli culture. Survival was recorded at 48 hours after challenge.

Burton PBJ, Raff MC, Kerr P, Yacoub MH, Barton PJR 1999 An intrinsic timer that controls cell-cycle withdrawal in cultured cardiac myocytes. Dev Biol 216 659—670 Chen X, Ko LJ, Jayaraman L, Prives C 1996 p53 levels, functional domains, and DNA damage determine the extent of the apoptotic response of tumor cells. Genes Dev 10 2438—2451 Duesbery NS, Choi T, Brown KD et al 1997 CENP-E is an essential kinetochore motor in maturing oocytes and is masked during mos-dependent cell cycle arrest at metaphase II. Proc Natl Acad Sci USA 94 9165-9170... 

Generalized carnitine deficiency, in its primary form and inherited as an autosomal recessive trait, is due to a defect of the specific high-affinity, low-concentration, carrier-mediated carnitine-uptake mechanism. The defect has been documented in cultured fibroblasts and muscle cultures, but the same uptake system is probably shared by heart and kidney, thus explaining the cardiomyopathy and the excessive leakage of carnitine into the urine. Oral L-carnitine supplementation results in dramatic improvement in cardiac function [4,8]. 

Blaustein We have seen the same thing in cultured cells we see no evidence for CICR. There are two possible explanations. First, the smooth muscle cells have a different ryanodine receptor isoform. Second, the rate of rise of Ca2+ is much slower in smooth muscle. In cardiac muscle there is a blast of Ca2+, with a rapid rise. Perhaps the slower effect means that smooth muscle cells don t get to threshold at the ryanodine receptor. The question is whether it is the channel or the process in general. 

There have been several studies that underscore the importance of unbound concentration in cell-based studies of receptor function. In a model study of the effect of plasma protein binding on the renal transport of organic anions using the expression of various organic anion transporters (OATPs) in Xenopus oocytes, the transport of ochratoxin A, methotrexate, and estrone sulfate was found to be strongly inhibited by the addition of human serum albumin to the culture medium [16]. Similarly, the addition of oq-acid glycoprotein was found to reverse the blockade of sodium-ion current by cocaine in a preparation of cardiac myocytes [17]. 

Diabetes is hypothesized to cause cardiac protein acetylation and the acetylation alters the protein function (Fig. 3b). Hypoxia-inducible factor-1 (HIFl) is a transcription factor found in mammalian cells cultured under reduced oxygen tension that plays an essential role in cellular and systemic homeostatic responses to hypoxia. Diabetes interferes with cellular response to hypoxia. In hyperglycemic conditions HIFl degradation is increased because of enhanced HIFl acetylation by... 

Peruvoside (Fig. 4) is one of the major terpenoids produced by Thevetia peruviana, a small tree commonly used as an ornamental plant. As a cardiac glucoside, this natural product has been used to treat heart failure patients who are allergic to the commercial drug digoxin. Success in obtaining peruvoside from T peruviana was recently reported. Production of approximately 9.0 mg of peruvoside/L was achieved by elicitation of cell cultures with 100-mg/L methyl jasmonate. ... 

This process starts with the synthesis of novel chemical compounds. Substances with complex structures may be obtained from various sources, e.g., plants (cardiac glycosides), animal tissues (heparin), microbial cultures (penicillin G), or human cells (urokinase), or by means of gene technology (human insu-Un). As more insight is gained into structure-activity relationships, the search for new agents becomes more clearly focused. 

Seko Y, Takahashi N, Tobe K, etal. Vascular endothelilal growth factor (BEGF) activates Raf-1 mitogen-activated protein (MAP) kinases, and S6 kinase (p90rsk) in cultured rat cardiac myocytes. J Cell Physiol 1998 3 239-246. 

Circulating plasma norepinephrine levels correlate inversely with survival in CHE that is, higher levels of norepinephrine are associated with a decrease in survival. It appears that norepinephrine levels are more than just markers of disease severity norepinephrine is actually directly toxic to cardiac myocytes, at least in culture. The addition of either an a- or p-blocker confers partial protection from norepinephrine damage. Combined a- and (3-blockade confers additive protection. These data from animal studies may be relevant to human heart failure, since they suggest that both a- and (3- adrenoceptor blockade may be beneficial in the man-... 

Darrow J, Fast VG, Kleber AG, Beyer EC, Saffitz JE Functional and structural assessment of intercellular communication. Increased conduction velocity and enhanced connexin expression in dibutyryl cAMP-treated cultured cardiac myocytes. Circ Res 1996 79 174-183. 

Kimura H, Oyamada Y, Ohshika H, Mri M, Oyamada M Reversible inhibition of gap junctional communication, synchronous contraction and synchronism of intracellular Ca2+ fluctuation in cultured neonatal rat cardiac myocytes by heptanol. Exp Cell Res 1995 220 348-356. 

Laird DW, Puranam KL, Revel JP Turnover and phosphorylation dynamics of connexin43 gap junction protein in cultured cardiac myocytes. Biochem J 1991 273 67-72. 

Shibata Y, Miyahara A, Okayama T, Kuraoka A, Iida H Gap junction formation and regulation in cultured adult rat and guinea pig cardiac muscle cells in Kanno Y, Kataoka K, Shiba Y, Shibata Y Shimazu T (eds) Intercellular Communication through Gap Junctions. Progress in Cell Research, vol 4. Amsterdam, Elsevier, 1995, pp 151-154. 

Apart from AP-A, the best characterized of these polypeptides with respect to its biological activity is Anemonia sulcata toxin II (ATX II) [19]. This molecule is also cardioactive [28], as would be expected from its similarity to AP-A. Renaud et al. [29] have compared the activities of a number of sea anemone and scorpion toxins on isolated rat atria and found that anthopleurin-B (AP-B, also known as Ax II) had the highest potency and the greatest margin between the concentrations necessary for maximal inotropic activity and for provoking arrhythmias (0.3 versus 10 n . It was also found that sodium channels of rat cardiac cells in culture, which have a low affinity for tetrodotoxin (TTX), have a particularly high affinity for Type 1 anemone toxins [29], whereas Type 2 toxins [30] and scorpion toxins [31] had similar affinities for TTX-sensitive and TTX-insensitive channels in rat neuroblastoma cells and skeletal myotubes, respectively. 

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