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Biomedical subjects

O Barnea

Publications and source records attributed to O Barnea.

33 records · Page 2Linked to original sources

Acute effects of 17 beta-estradiol on the rat heart.

OBJECTIVE: Our purpose was to study the acute effects of 17 beta-estradiol on mechanical and electrical activities of cardiac function and on coronary arteries in the rat heart. STUDY DESIGN: The effects of 17 beta-estradiol were studied on perfused working heart isolated from Charles River male rats. Heart rates, coronary flow, aortic flow, and left ventricular pressure were measured. To avoid coronary interaction, chronotropic and inotropic effects were also tested on isolated atria. Data were analyzed with the paired Student t test. RESULTS: 17 beta-Estradiol produced a dose-dependent negative chronotropic effect in right atria but did not affect the contractility of left atria. A decrease in heart rate was also observed in perfused hearts treated with 5 x 10(-6) mol/L 17 beta-estradiol. 17 beta-Estradiol (5 x 10(-6) mol/L) significantly increased coronary flow (p < 0.005) but had a negligible effect on cardiodynamic index values. A significant effect of 17 beta-estradiol on cardiac function was observed when coronary arteries were precontracted with acetylcholine. CONCLUSION: Both the experimental coronary vasodilatory effect and the negative chronotropic effect of 17 beta-estradiol support the clinical observations that suggest that this hormone may have an important role in prevention of cardiovascular diseases.

Acetylcholine↗

Autoregulation in the stenosed coronary circulation.

Coronary vessel stenosis increases vascular resistance and limits the dynamic range of autoregulation. In this study, the limitation imposed by stenosed vessels on oxygen delivery to the myocardium was investigated using a theoretical model. For different degrees of stenosis and for different levels of arteriovenous oxygen content difference, the model predicted the limits of the contractility range for which ventricular oxygen balance is positive. The model also predicted the existence of an optimal contractility level which minimizes the cost of arterial pressure generation and provides the largest coronary oxygen reserve. With severe stenosis, myocardial oxygen balance is extremely sensitive to changes in the level of stenosis. The range of contractility in which the coronary circulation can meet the myocardial oxygen needs is dramatically reduced by small increases in stenosis severity or small decreases in arteriovenous oxygen difference. When the optimal contractility level is maintained, the heart can tolerate these detrimental changes to a greater extent.

Animals↗

Balancing the circulation in hypoplastic left heart syndrome.

A mathematical model based on oxygen flow was developed to study the effects of pulmonary to systemic flow ratios (QP/QS) on systemic oxygen availability. The model suggests that QP/QS = 1 is the safest ratio that would provide the largest safety margin in either low cardiac output or low pulmonary oxygenation conditions. The optimal value of QP/QS that will result in maximum oxygen availability is smaller than unity and depends on several circulatory parameters such as cardiac output, maximal oxygen capacity, level of pulmonary oxygenation, and oxygen consumption. The values of these parameters also dictate the permissible range of QP/QS beyond which abrupt oxygen deficiency ensues. Decreased pulmonary resistance resulting in increased pulmonary flow may eventually result in QP/QS that is beyond the vital range.

Blood Circulation↗

A blood vessel model based on velocity profiles.

A simple model of pressure-flow relationship in blood vessels was developed. The calculation of the model components was based on velocity profiles in the vessels. The flat velocity profile in the entrance of the vessel was considered. By using mean pressure over the cross-section and assuming a polynomial approximation of the velocity profile, it is shown that the resistance of a vessel segment increases with increased flatness of the velocity profile. Moreover, the analysis provides a means to calculate the resistance of a vessel segment based on the shape of the velocity profiles in that segment. The analysis shows that the inertance element of the segment is not affected by the shape of the velocity profile.

Animals↗

A computer model for analysis of fluid resuscitation.

Injuries involving massive blood loss, such as burns, combat wounds, and injuries resulting from car accidents, require fluid resuscitation. The risk involved in fluid therapy is overloading of the circulation, resulting in pulmonary edema which can lead to death. The risk of pulmonary edema may be eliminated by proper determination of maximal infusion volume and rate. Reabsorption of fluid from the extravascular compartment and infusion of fluid following blood loss results in reduction of the hematocrit. This is accompanied by an increase in the heart's preload and afterload. Coronary driving pressure and flow increase due to increased volume. However, because of the reduced hematocrit this increase in coronary flow may not be sufficient to compensate the myocardium, in terms of oxygen supply, for the increase in oxygen consumption. A model of the cardiovascular system, including an extravascular compartment, was designed to analyze the effects of fluid infusion on hemodynamic variables, cardiac oxygen balance, and the redistribution of fluid between intravascular and extravascular compartments. The results indicate that edema is not the only possible adverse effect of overloading the cardiovascular system with fluid. The simulation demonstrated that in certain cases the heart's oxygen balance can become negative. Limiting the rate of infusion can reduce this risk.

Animals↗

Optimal controller for intraaortic balloon pumping.

An optimal control algorithm was adapted to identify and track the optimal deflation time of the intraaortic balloon pump (IABP). Routines for handling physiologically imposed constraints were added to the algorithm which was implemented in a computer-controlled system. The system was designed to provide real time optimization for the clinical setting. The controller continuously maximizes a performance index while observing the constraints. The index is composed of clinically available hemodynamic variables which indicate changes in myocardial energy balance. Proper values for the algorithm parameters were determined and the system was tested in animal experiments. The results indicate that controlling deflation time relative to the R wave, which precedes the next ejection phase, reduces the time required for optimization when the heart rate varies.

Algorithms↗

Optimal control system for the intra-aortic balloon pump.

An optimal control system for the intra-aortic balloon pump (IABP) is presented. Control of the IABP is based on a performance index formulated to reflect a tradeoff between maximising cardiac oxygen supply and minimising cardiac oxygen consumption. In the performance index, mean diastolic pressure (MDP) was used to represent oxygen availability and peak systolic pressure (PSP) was used to represent oxygen consumption. An algorithm, implemented using an 8-bit microcomputer, changes the deflation time of the IABP to maximise this performance index by using an optimisation technique that employs both a search and an approximation. The search produces three equally spaced points which define a region that includes the maximum of the performance index. From these points, the optimum deflation time is estimated by a quadratic approximation. The algorithm has been successfully tested using performance index curves generated by computer simulations.

Algorithms↗

Computer simulation of the mechanically-assisted failing canine circulation.

A model of the cardiovascular system is presented. The model includes representations of the left and right ventricles, a nonlinear multielement model of the aorta and its main branches, and lumped models of the systemic veins and the pulmonary circulation. A simulation of the intra-aortic balloon pump and representations of physiological compensatory mechanisms are also incorporated in the model. Parameters of the left ventricular model were set to simulate either the normal or failing canine circulation. Pressure and flow waveforms throughout the circulation as well as ventricular pressure and volume were calculated for the normal, failing, and assisted failing circulation. Cardiac oxygen supply and consumption were calculated from the model. They were used as direct indices of cardiac energy supply and utilization to assess the effects of cardiac assistance.

Animals↗

Cardiac energy considerations during intraaortic balloon pumping.

Cardiac oxygen availability and oxygen consumption were used in a theoretical study as indexes of myocardial energy supply and utilization, respectively. A detailed computer simulation of the closed-loop canine cardiovascular system was utilized to study the dependence of these indexes on timing of the intraaortic balloon pump. Oxygen availability exhibited higher sensitivity to balloon timing than oxygen utilization. While maximum augmentation of oxygen availability was 58 percent, oxygen consumption could be reduced by only 13 percent. Animal experiments were initiated to validate the theoretical results. The results of both the animal experiments and the computer simulation suggested that neither balloon timing which maximizes oxygen availability nor timing which minimizes oxygen consumption correlates with timing which minimizes aortic end diastolic pressure. Thus, end diastolic pressure, presently used as a determinant of proper timing in patients undergoing cardiac assistance, was found to be a poor index of ventricular energy consumption. A performance index comprised of clinically available variables, was formulated to reflect myocardial energy balance. In this performance index, mean diastolic pressure was used to represent energy availability and peak systolic pressure was used as an index of oxygen consumption. Their relationship to oxygen balance and their dependence on timing were studied using the computer simulation of the canine cardiovascular system and animal experiments. Theoretical and experimental results suggest that such an index is capable of representing O2 balance and can be used to control phasing of the device.

Animals↗

Coronary autoregulation and optimal myocardial oxygen utilization.

The complex relationship among myocardial contractility, preload, afterload, and coronary autoregulation was studied using both analytical and numerical methods. To study autoregulation and coronary reserve changes in response to changes in cardiac oxygen consumption and in arterial pressure generation, a new variable was introduced: myocardial resistance to oxygen flow (RO2). This variable was defined as the ratio of the coronary driving pressure to left-ventricular oxygen uptake. High values for this variable indicate small consumption relative to the generated aortic pressure. Conditions which produce the highest obtainable value for RO2 are considered as optimal. An expression relating RO2 to ventricular hemodynamic variables was developed and studied using a mathematical model of the cardiovascular system. The model included a mechanism of local autoregulation based on the assumption that, in steady state, the amount of oxygen consumed equals the amount extracted from coronary blood. Heart rate, peripheral resistance, end-diastolic volume, and myocardial contractility were varied while the coronary circulation was adjusted to meet ventricular oxygen consumption at each state. The model predicts that, for each state of the circulation, there is an optimal level of cardiac contractility for which the coronary reserve is maximized.

Animals↗

A theoretical unidirectional valve based on functional collapse of blood vessels in the penis.

A model of a vessel exposed to external pressure was developed. Analytical derivation resulted in closed-form expressions describing pressure-flow relation in the vessel. These expressions describe a behavior of a unidirectional leaky valve. The vessel model was used to represent internal arteries and veins in the penis. Together with a compliant chamber representing the corpus cavernosum, the model demonstrates the valve action of the partially collapsed vessels during penile erection. This explains observations regarding arterial backflow during erectile contraction of the ischiocavernous muscles and demonstrates the differences in development of tumescence and rigidity.

Arteries↗

Positive inotropic effect in the heart produced by acetylcholine.

The effect of acetylcholine on cardiac muscle contractility and hemodynamics was investigated in human atrial strips and in isolated working rat heart. Activation of the muscarinic receptor in the heart muscle is generally known to result in negative chronotropic and inotropic effects. In our study, positive inotropic effects of acetylcholine (ACh) were observed in both human right atrial strips and in the working rat heart. Exposure of the human right atrial strips to ACh (10(-7)-10(-4) M) produced a dose dependent tri-phasic (positive-negative-positive) inotropic effect in approximately 40% of the strips. In muscle strips that exhibited only a negative inotropic effect, a positive response was observed following washout of ACh. Both positive and negative effects were antagonized by atropine. Exposure of the paced working rat heart to ACh (10(-7) - 10(-5) M) resulted in a dose dependent decrease in mean coronary flow followed by depression in cardiac function. When the heart was initially treated with the vasodilator adenosine (2 x 10(-6) M), exposure to ACh (10(-7) - 10(-5) M) had no effect on coronary flow and produced a dose dependent augmentation of all cardiodynamic indices: left ventricular pressure, isovolumic pressure, cardiac output, maximal aortic flow and stroke work. This positive response was antagonized by atropine. Exposure of the rat ventricular strips increased the formation of [3H]phosphoinositide breakdown products (e.g. inositol phosphates IP, IP2, IP3). These observations demonstrate that cholinergic muscarinic stimulation may produce positive inotropic effects in both human and rat cardiac muscle. Furthermore, our results suggest that IP3 may be a mediator in this process.

Acetylcholine↗

Performance optimization of left ventricular assistance. A computer model study.

Performance of temporary parallel left ventricular assistance was investigated and the theoretic conditions leading to optimal behavior of the mechanical system were explored. Computer models of nonpulsatile and pulsatile left ventricular assist devices (LVADs) were incorporated into a previously reported closed-loop simulation of the canine cardiovascular system. Assuming the assisted heart was capable of recovery, LVAD performance was assessed based on both myocardial oxygen balance and cardiac output. With a synchronous LVAD, and operating in a counterpulsation mode, these variables were sensitive to the phasing of pump ejection. Maximum reduction in cardiac oxygen consumption, maximum increase in oxygen availability, and maximum increase in cardiac output with the atrio-aortic device were obtained when pump ejection immediately followed aortic valve closure. These variables were directly proportional to the magnitude of bypass volume. The pulsatile asynchronous and nonpulsatile LVAD models affected oxygen balance in a similar manner, but neither performed so well as the synchronous model when equal bypass volumes were used. Ventricular uptake of blood provided a further 27% decrease in oxygen consumption and further 78% increase in oxygen availability than atrial uptake. In summary, the model predicted that the pulsatile synchronous LVAD, filling from the ventricle during heart systole and ejecting into either the ascending or descending aorta just after ventricular systole, would be most beneficial to both myocardial oxygen balance and cardiac output.

Animals↗