Inducible NO Synthase mRNA Expression and Infiltration of Rats Myocardium with Inflammatory Cells in 2-4 Hours after Modeled Permanent Ischemia or Ischemia/Reperfusion.

Expression of inducible NO-synthase mRNA and myocardial infiltration with neutrophils were studied in rats with modeled permanent ischemia and ischemia/reperfusion models. Expression of inducible NO synthase mRNA in the ischemic region increased significantly in 3, 3.5, and 4 h in modeled ischemia/reperfusion and in 3.5 and 4 h in permanent ischemia. Myocardial infiltration with neutrophils was significantly higher than in intact controls throughout the experiment without significant intergroup differences. In non-ischemic myocardium, enhanced expression of inducible NO synthase mRNA and moderate neutrophilic-lymphocytic myocardial infiltration were also observed in 3.5, and 4 h after ischemia.

Changes in Sympathetic Innervation of the Heart in Rats with Experimental Myocardial Infarction. Effect of Semax.

The effect of peptide Semax on remodeling of cardiac sympathetic innervation was examined in rats with experimental myocardial infarction. In 28 days after ischemia/reperfusion injury, Semax diminished the growth of sympathetic innervation of ventricular septum, although it produced no effect on the density of ß1 and ß2 adrenoceptors.

[Self-organization in the ontogeny of multicellular organisms: a computer simulation].

The progress in understanding the patterns of evolution of ontogeny is hindered by the fact that many features of ontogeny are counterintuitive (as well as the features of other processes related to self-organization, self-assembly, and spontaneous increase in complexity). The basic principle of ontogeny of multicellular organisms is that it is the process of self-assembly of ordered multicellular structures by means of coordinated behavior of many individual modules (cells), each of which follows the same set of"rules" encoded in the genome. These rules are based on the genetic regulatory networks. We hypothesize that many specific features of ontogeny that seem nontrivial or enigmatic are, in fact, the inevitable consequences of this basic principle. If so, they do not need special explanations. In order to verify this hypothesis, we developed the computer program "Evo-Devo" based on the above principle. The program is designed to model the self-assembly of ordered multicellular structures from an aggregation of dividing cells that originate from a single original cell (zygote). Each cell follows a set of rules of behavior ("genotype") that can be specified arbitrarily by the experimenter, and is the same for all cells in the embryo (each cell is programmed in exactly the same way as all other cells). It is not allowed to specify rules for groups of cells or for the whole embryo: only local rules that should be followed at the level of a single cell are possible. The analysis of phenotypic implementation of different genotypes revealed several features which are present in the ontogeny of real organisms and are regularly reproduced in the model. These include: inherent stochasticity; inescapable necessity of development of stabilizing adaptations based on negative feedback in order to decrease this stochasticity; equifinality (noise resistance) resulting from these adaptations; the ability of ontogeny to respond to major perturbations by generating new morphological structures that differ from the "normal" ones, but have similar level of complexity; the similarity of phenotypic manifestations of different mutations; channeling of possible evolutionary transformations of ontogeny; Waddington's creodes; high probability of destabilization of ontogeny (e.g., because of mutations); the possibility of a new morphological character to appear initially as a rare anomaly (low penetrance of many mutations); pleiotropy of mutations affecting ontogeny; spontaneous emergence of morphogenetic correlations; integrity of the developing organism. The fact that these features are regularly reproduced in the model implies that they are probably the inevitable consequences of the basic principle of ontogeny of multicellular organisms formulated above.

Fructose-1,6-diphosphate in the treatment of oleander toxicity in dogs.

Oleander, a flowering plant that grows in the Mediterranean and southern US, contains the cardiac glycosides oleandrin, digitoxigenin and nerium, which inhibit Na(+)-K+ ATPase. Clinical manifestations of oleander toxicity include gastrointestinal irritation, marked hyperkalemia, A-V block, ventricular dysrhythmia, and not uncommonly death. Because fructose-1,6-diphosphate (FDP) has been shown to attenuate digoxin toxicity, we determined whether this agent would be effective in the treatment of the toxicity of these similarly-structured cardiac glycosides. Anesthetized dogs (n = 12) were infused i.v. for 5 min with 40 mg oleander extract/kg and then 6 dogs randomly selected from that group received a 50 mg/kg bolus of 10% FDP followed by a constant infusion. The other control animals received the same dosage of 10% dextrose. Within 5 min after oleander administration, all dogs developed dysrhythmias. The FDP-treated animals reverted to sinus rhythm within 1.58 +/- 0.15 h; none in the control group returned to sinus rhythm. One control dog died at 3 h from ventricular fibrillation. Marked hyperkalemia was observed in the control group; plasma K+ remained unchanged in the FDP group. Throughout the 4 h experimental period the FDP group maintained normal arterial pressures; in the control dextrose group, pressures were profoundly depressed. Cardiac output declined in both groups but remained higher in the FDP group. To determine the mechanism whereby FDP attenuates oleander toxicity, we studied the in vitro effect of FDP on oleander poisoned myocardial sarcolemmal membranes. At concentrations of 1 and 2 mg oleander inhibited Na(+)-K+ ATPase activity and addition of 500 microM FDP restored myocardial sarcolemmal Na(+)-K+ ATPase function. FDP effectively prevented hyperkalemia, reversed dysrhythmias and improved hemodynamics in vivo in this canine model of oleander toxicity and also restored sarcolemmal Na(+)-K+ ATPase activity in vitro.