Biomedical subjects

J Dankelman

Publications and source records attributed to J Dankelman.

41 records · Page 3Linked to original sources

PubMed1992

Dynamic response of coronary regulation to heart rate and perfusion changes in dogs.

The rate of change of coronary adjustment in the anesthetized dog to a step change in heart rate (HR) and in perfusion was analyzed. The left main coronary artery was perfused either at constant pressure (CP) or at constant flow (CF). Coronary arterial pressure and flow were continuously measured and averaged per beat, after which their ratio, being an index of coronary resistance in steady state, was calculated. The rate of change of pressure-to-flow ratio was quantified by t50, the time required to establish half of the completed response. The t50 values for the dilating responses at CP were 5.5 +/- 0.4 (SE) s for an increase in HR and 5.5 +/- 0.1 s for a decrease in perfusion. At CF these values were 9.3 +/- 0.9 and 9.7 +/- 1.6 s, respectively. The t50 values for the constricting responses with CP were 6.6 +/- 0.5 s for a decrease in HR and 6.2 +/- 0.2 s for an increase in perfusion. At CF these values were 12.2 +/- 1.5 and 10.8 +/- 2.2 s. The responses in the dog are faster than in the goat. Furthermore, the directional sensitivity in responses with perfusion changes, observed earlier in goats, is normally absent in dogs.

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PubMed1990

System analysis of the dynamic response of the coronary circulation to a sudden change in heart rate.

In this study the response of driving pressure/flow ration on an abrupt change in heart rate was analysed. The difference between the response obtained with constant pressure and constant flow perfusion was also studied. The responses show a fast initial reversed phase followed by a slow phase caused by regulation. To test whether the initial phase could be the result of mechanical changes in the coronary circulation, a model for regulation was extended by the addition of four different mechanical models originating from the literature. These extended models were able to explain the fast initial phase. However, the mechanical model consisting of an intramyocardial compliance (C = 0.08 ml mm Hg-1 100 g-1) with a variable venous resistance, and the model consisting of a waterfall and a small compliance (C = 0.007 ml mm Hg-1 100g-1) both explained these responses best. The analysis showed that there is no direct relationship between rate of change of vascular tone and rate of change of pressure/flow ratio. However, on the basis of the two extended models, it can be predicted that the half-time for the response of regulation to be complete is about 9s with constant pressure perfusion and 15 s with constant flow perfusion.

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PubMed1989

Dynamics of coronary adjustment to a change in heart rate in the anaesthetized goat.

1. We have previously shown that steady-state coronary flow during auto-regulation and metabolic rate changes is predicted by a mathematically expressed theory which assigns control of coronary vascular resistance to tissue PO2. Our present purpose was to test the applicability of this theory to the non-steady state as exemplified by a sudden step change in heart rate. 2. The theory predicted that the response time of change of resistance in these circumstances would be slower with constant-flow perfusion of the coronary bed than with constant-pressure perfusion, and that with constant-pressure perfusion only, the rate of adaption of resistance would be dependent on the level of pressure used. 3. These predictions were tested in open-chest goats with cannulation of the left main coronary artery and perfusion with alternately constant pressure or constant flow. Sudden step changes in heart rate were induced by pacing to induce rapid transients in myocardial metabolic rate. 4. The half-time of subsequent change in perfusion pressure-flow ratio, which in the dynamical state is not equal to resistance, was 15.7 +/- 0.4 s (mean +/- S.E.M.), which was statistically shorter than for constant flow (22.2 +/- 0.5 s, P less than 0.001). 5. The half-time of subsequent change in perfusion pressure-flow ratio with constant-pressure perfusion was 14.4 +/- 0.6 s at low pressure and 17.0 +/- 0.6 s at high pressure (P less than 0.001). 6. The results differed from those predicted by the theory, in that the changes described above were preceded by a rapid (5 s) step change in pressure-flow ratio, up with an increase in heart rate and down with a decrease in heart rate. We postulated that this was a mechanical effect due to greater compression of the coronary microvasculature with more frequent contractions. 7. To test this hypothesis, we measured changes in coronary blood volume by integrating the difference between arterial inflow and venous outflow. These experiments showed a decrease in coronary blood volume with heart rate increase and vice versa. 8. Abolition of autoregulation and metabolic regulation was achieved with maximum vasodilatation of the coronary bed with adenosine. A sudden switch in heart rate then produced the initial step change in pressure-flow ratio, but not the subsequent adaptation over 13-25 s. This confirmed that the former effect is attributable to a passive mechanical mechanism.

Animals↗

PubMed1989

Dynamic response of the coronary circulation to a rapid change in its perfusion in the anaesthetized goat.

1. We tested predictions of a mathematical formulation of a hypothesis of dynamic control of coronary blood flow by tissue oxygen tension. 2. The rate of change of adjustment of the coronary circulation to a step change in arterial perfusion was analysed in the cannulated main stem preparation of the anaesthetized goat. The variable studied was the ratio between driving pressure and coronary flow, each averaged per heart beat. The response of this ratio was measured following a sudden change in perfusion pressure with constant-pressure perfusion and a sudden change in flow with constant-flow perfusion. 3. The rate of change of the pressure-flow ratio was quantified by t50, the time required to establish half of the completed response. For a pressure decrease t50 was 4.9 +/- 0.2 s (n = 35) (mean +/- S.E.M., n = number of individual measurements), 11.3 +/- 1.2 s (n = 25) for a flow decrease, 14.5 +/- 1.6 (n = 34) for a pressure increase and 25.1 +/- 2.3 (n = 19) for a flow increase. 4. No effect of the level of flow or pressure on t50 was found for a decrease in perfusion. Furthermore, with a flow increase, the t50 value did not depend on the level of flow, which is in agreement with the outcome of earlier experiments where the response to a change in heart rate was measured. With a pressure increase, the mean t50 value of the pressure-flow ratio was lower at high perfusion pressure but the difference with low perfusion pressure was not significant (P = 0.11). 5. The t50 value in the cases of an increase in pressure and flow are similar to those found for a change of heart rate in an earlier study. 6. Unlike step changes of metabolic rate, some of the measured responses to mechanical step changes were not predicted by the oxygen hypothesis. It is suggested that the increased rate of coronary adjustment induced by the reduction of coronary perfusion is due to arteriolar smooth muscle mechanics which apparently differ in strength depending on the direction of change of the arteriolar dimensions. 7. This suggestion is strengthened by the results of experiments in which smooth muscle responses were abolished with adenosine.

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PubMedDate not supplied

Model of the coronary circulation based on pressure dependence of coronary resistance and compliance.

The effect of pressure-dependent changes in vascular volume, resistance and capacitance in the coronary micro-circulation, has been studied by a distributed mathematical model of the coronary micro-vasculature in the left ventricular wall. The model does not include regulation of coronary blood flow and is evaluated only for the fully dilated coronary vasculature. The left ventricular wall was thought to consist of eight parallel layers, each of them with an arteriolar, capillary and venular compartment. The resistance of each vessel was thought to depend on the inverse of squared volume, according to Poiseuille's Law for tubes with constant length. Tissue pressure has been assumed to be equal to left ventricular cavity pressure at the endocardium and to decrease linearly to atmospheric level at the epicardium. The pressure-volume relation of the vessel compartments were assumed to be sigmoidal. There is a rest volume at transmural pressure zero and delta V/delta P decreases with increasing transmural pressure. Simulation of experimental protocols described by other authors yielded results which were similar to the experimental outcomes, illustrated by: (1) a parallel shift to the flow axis of the pressure-flow curves due to cardiac arrest (2) steady-state endo/epi ratio of flow as a function of heart rate. It is concluded that interpretation of transients in coronary flow and/or pressure by models containing fixed resistance and capacitance may seriously underestimate intramyocardial capacitative effects and characteristic time constants for pressure-induced resistance changes.

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