A mathematical model of the regulation process of the heat shock protein hsp70 in the cell is presented. The model describes the damaging effect of elevated temperature on proteins; the interaction of free hsp70 with injured proteins and its chaperone role in nascent protein translation; the relation between the amount of free hsp70 and the formation of the activated trimer form of the heat shock factor protein (HSF); the binding of activated HSF with the heat shock elements on the DNA; the transcription of mRNA of hsp70 and the synthesis of hsp70. The reaction of the model to a temporal rise in temperature shows an initial decline and a subsequent sharp rise to an ultimately increased level of free hsp70 in the cell. The response of the model to both a single and two consecutive heat shocks appears to closely resemble experimental data on hsp70 synthesis. This general agreement demonstrates the structure of the model to be sound and suitable as a basis for further modelling the complex tolerance mechanism of the cell.
Heterogeneity in the hypoxic state of Tyrode-perfused rat hearts was studied using NADH and Pd-porphine videofluorometry. Ischemic as well as high-flow anoxia resulted in a homogeneous rise of tissue NADH fluorescence, whereas normoxic recovery from both types of anoxia caused transiently persisting patchy fluorescent areas. Patterns were always the same for a given heart. PO2 distribution in the vasculature measured by Pd-porphine phosphorescence showed patterns similar to the NADH fluorescence patterns. Microsphere embolization of the capillaries, but not of arterioles, elicited identical NADH fluorescence patterns as seen during recovery from anoxia without microspheres. High heartbeat rates also caused patchy fluorescent areas but not in the presence of adenosine. Patterns corresponded to those seen during normoxic recovery from anoxia under low beat rates. It is concluded that there are circulatory units in the rat heart at the capillary level that result in the temporary persistence of anoxic areas during recovery from anoxia. These vulnerable areas are the first to be compromised during high heartbeat rates.
Normally systolic coronary blood flow is almost entirely forward. As perfusion pressure was lowered through the autoregulatory range in open-chest dogs, net systolic back flow appeared at approximately 70 mm Hg. Imposing a series resistance (Rs), which impedes both forward and back flow, abolished this reverse flow and resulted in net forward systolic flow. Thus we conclude that under normal perfusion conditions the pattern of net forward systolic flow contains a substantial reverse flow component.
Compliance of small arteries is important for the interpretation of arterial pressure-flow relations. Six coronary small arteries (mean diameter 189 +/- 46 microns) were cannulated. Pressure-cross-sectional area (CSA) relations were obtained from isolated vessels by slowly varying pressure between 10 and 120 mmHg. Subsequently, small pressure variations were superimposed on constant mean pressures of 10, 30, and 50 mmHg with frequencies of 0.1-10 Hz. Normalized compliance (C0) was calculated as the compliance divided by the CSA at 50 mmHg. In vessels without tone, static C0 was 27.5 +/- 8.9, 6.4 +/- 1.1, and 3.8 +/- 1.0 x 10(-3) mmHg-1 at 10, 30, and 50 mmHg, respectively. At a frequency of 0.1 Hz, C0 decreased to one-third of static C0 at any pressure. Under these conditions, the phase shift between pressure and CSA was rather constant and ranged from -21 to -5 degrees. In four small arteries, smooth muscle tone was induced by the administration of acetylcholine. Activation decreased dynamic C0 by 60%. Two models of coronary input impedance were evaluated: the first model includes viscoelastic properties of the arterial wall and the second takes into account the blood inertia effect. The second model predicts much better the wall mechanics of single small arteries. The viscoelastic model overestimates the frequency dependence of compliance by a factor of 2 and the phase lag by a factor of 4. Moreover this model predicts a strong frequency dependence of induction of tone on compliance and phase lag, whereas this dependence is absent in the experimental results.
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