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Biomedical subjects

J Y Kresh

Publications and source records attributed to J Y Kresh.

14 recordsLinked to original sources

Theoretical and experimental analysis of right ventricular bypass and univentricular circulatory support.

In this paper we examine the dynamic coupling between cardiac pump events and vascular arterial-venous factors that regulate the rate of blood flow around the circulation. A series of experiments were designed to test the feasibility of maintaining vascular and pulmonary function in the absence of the right heart and to characterize the physiologic and hemodynamic consequence of such an exclusion. Theoretical analysis of the cardiovascular system (excluding neuro-humoral factors) using both lumped time invariant and distributed compartmental mathematical equivalent representations, demonstrated that a change in cardiac output (Q) has an inverse-linear effect on venous and direct-linear effect on arterial pressure. A single blood-pump, in a form of a mechanical substitute or the biologic left-heart, alone can support the circulation. Cardiac output reserve is limited (50 percent of normal) because of the rapidly diminishing pulmonary venous-pressure as outflow is increased, irrespective of the pump's specific characteristics. Experiments in animals combined with mock-circulatory studies and computer modeling confirm that near normal flow can be sustained by increasing the stressed blood volume or reducing selectively the systemic venous compliance (i.e., inflatable pressure suit, venous constriction, intra-abdominal compression maneuvers, etc.). The right heart is not essential for normal pulmonary circulation but serves to maintain low systemic venous pressure and relatively high left-heart flow reserve. Purely mechanical properties of the vascular system determine the control and stability of the circulation.

Animals

Model-based analysis of transmural vessel impedance and myocardial circulation dynamics.

The basic structure of a model of the coronary circulation has been developed to explain the relationship between transmural perfusion dynamics and intramyocardial mechanics. The model is in the form of a topologically isomorphic network representation and incorporates experimentally measured time-varying perfusion and intramyocardial pressure sources as driving inputs to the model. The intramyocardial vessels are treated as nonlinear impedance elements possessing regional external pressure-dependent resistance and capacitance. Three circuit branches, perfusing the epicardial, subepicardial, and subendocardial muscle layers, are mathematically modeled and are used to predict time-dependent flow within the left ventricular myocardium. The phasic coronary blood flow characteristics predicted by the model exhibit waveform patterns that correlate qualitatively with those patterns measured experimentally. In addition, the pressure-dependent vascular capacitance induces a sustained (out of phase with arterial inflow) venous systolic flow. The model also exhibits retrograde systolic subendocardial flow and stop-flow pressure, which are dependent on coronary resistive and capacitive properties and on the perfusion pressure decay time constant. Furthermore, the results predict an abrupt decrease in subendocardial flow with perturbation of either arteriolar or capillary bed compliance. The model describes time-dependent intramyocardial properties that have been confusing and controversial in the understanding of coronary circulation dynamics. Several steps are identified that are expected to improve and refine the model significantly.

Animals

Intramyocardial pressure: interaction of myocardial fluid pressure and fiber stress.

Previous measurements of intramyocardial pressure (IMP) have yielded systolic pressures that range from values lower than to far exceeding systolic left ventricular pressure (LVP). This study identifies a possible mechanism underlying these divergent observations by building on established morphology of the ventricular wall. It is hypothesized here that the generation of fiber stress as a manifestation of myocardial contraction increases fluid pressure in the myocytes and the interstitial spaces. This increase in fluid pressure in turn generates the pressure in the ventricular cavity. Thus there are two quantities of interest: intramyocardial fluid pressure (IFP) and intramyocardial fiber stress (IFS). To test the hypothesis, we conducted experiments on conditioned dogs, utilizing a side-mounted catheter-tip strain gauge transducer to sense IMP as the sum of IFP and some component of IFS. In addition, a recessed end-tip fiber-optic transducer with its sensing element shielded from local myocardial fibers was employed to sense IFP. Both IFP and IMP were measured at various depths in the left ventricular free wall. The effects of inotropic interventions by administration of epinephrine and propranolol, mechanical interventions via clamping of the aorta and ligation of the left anterior descending coronary artery, and neural interventions by stimulation of the ansa subclavian of the stellate ganglion and right vagus were recorded. A transmural gradient in the wall for both IMP and IFP was observed. Systolic values of IFP recorded in the endocardium match those of LVP, with peak IMP exceeding both. The results support the hypothesis and offer an interpretation of the long-standing controversy regarding the magnitude of IMP with respect to LVP.

Animals

Autoperfusing ectothermic heart-lung preservation system.

A portable heart-lung preservation system was developed to enable distant organ procurement. In 8 dogs, a functioning heart-lung system was isolated, cannulated in situ, removed en bloc, and placed into a Plasmalyte-filled, temperature-controlled (15-38 degrees C) chamber. The perfusion circuit consisted of an adjustable-height, autologous-blood reservoir. The heart ejected through the aortic cannula with venous return (VR) into the superior vena cava. Respiration was maintained with a positive pressure ventilator. Intramyocardial tissue pressure (IMP), tissue pH, right atrial (RAP), aortic pressure (AOP), and cardiac output (CO) were monitored. Autoperfusion at normothermia and CO of 50 mL/min/kg resulted in early (3 h) deterioration of pulmonary function with progressive interstitial lung edema. Pulmonary dysfunction always preceded changes in regional myocardial contractile viability (peak IMP and d(IMP)/dt) and global function (CO, AOP). When tissue pH was regulated ectothermically (as in cold-blooded animals) (delta pH/degrees C = -0.015) the heart maintained a stable pumping mode (greater than 6 h) at myocardial temperatures of 17-28 degrees C, pH = 7.70-7.55, and heart rate of 25-50 bpm, respectively. The results indicate that a viable (greater than 6 h) autoperfused, working heart-lung system can be achieved by reducing the circulating blood flow to 30-50% of normal CO. More significantly, ectothermic alpha-stat modulation of perfusate pH and pCO2 allows a substantial reduction in organ temperature and metabolic demand without endangering induction of fibrillation and ultimate allograft failure.

Animals

The relative buffering power of cardioplegic solutions.

Those factors that prolong myocardial tolerance to global ischemia constitute an important prerequisite for effective cardioplegia. This study contrasts the relative buffering power of bicarbonate-based and tromethamine-based hyperkalemic crystalloid cardioplegic solution with histidine protein-type buffer (Bretschneider) solution. In addition, the solutions were compared with titration of whole blood and myocardial muscle homogenate.

Buffers

A model-based system for assessing ventricular chamber pressure-volume-dimension relationship: regional and global deformation.

A system has been developed for measuring and relating in a non-beating isolated canine left ventricle dynamic changes in chamber pressure, volume, diameter, regional segment length, and wall thickness. The measurement system consists of a pulsatile blood pump whose stroke-volume and frequency can be adjusted selectively. The external pump system is used as a primary means for controlling instantaneous intraventricular volume. The relationship between left ventricular volume change, intraventricular pressure, minor axis diameter, and regional dimensions were studied as a function of pump rate. In addition to the basic constitutive properties, this system provided the means for measuring and comparing regional and global pressure-strain relationship including the effect of strain rate and its relationship to viscoelastic myocardial muscle model. The dynamic relationship between global dimensions and regional dimensions, circumferential segment length, and wall thickness were also investigated. The instantaneous relationship between intraventricular pressure resulting from periodic oscillations of chamber volume, including minor equator diameter, wall thickness, and regional segment dimensions were plotted and fitted to an exponential pressure-strain model, assuming a quasi-static large deformation. The observed difference between global and regional pressure-dimension strain stiffness coefficients can be attributed in part to basic constitutive and geometric considerations and not necessarily to the complex anisotropic or heterogeneous nature of cardiac muscle properties. This methodology provides indices which appropriately characterize the regional and global left ventricular chamber deformation and stiffness.

Animals

The intramyocardial pressure: a parameter of heart contractility.

A method of monitoring was developed to directly measure the intramyocardial pressure and to objectively assess the viability and contractility of a heart allograft before it is harvested, during its period of preservation and following its implantation. Intramyocardial pressure was measured in the subendocardial and subepicardial regions using implantable solid state sensors. The data demonstrated that a normally contracting in situ heart exhibits a transmural intramyocardial pressure gradient, the systolic subendocardial pressure being consistently greater than the left ventricle and subepicardial pressures. Subendocardial pressure markedly changes during inotropic stimulation or myocardial ischemia. In three canine allografts and in an isolated, perfused and vented beating heart similar responses were observed during pharmacologic and hemodynamic testing. The intramyocardial pressure measurement proved to be relatively insensitive to preload and afterload changes provided coronary perfusion remained unaltered. Ventricular fibrillation produced an elevated and oscillating intramyocardial pressure while cardioplegic arrest reduced it to near zero. Diastolic pressure measurements were most sensitive to detect myocardial contracture ("stone" heart) during which intramyocardial pressure increased significantly. The "stone" heart exhibited persistent mechanical activity despite no visible contraction. The edematous heart's response to inotropic stimulation was reduced. Ischemia induced by inadequate perfusion was detected by a rapid drop in systolic intramyocardial pressure, preferentially affecting the endocardial region. This study establishes that the change in diastolic intramyocardial pressures in response in inotropic stimulus is a reliable indicator of myocardial contractility and viability and could be used during the procurement and preservation of the heart for transplantation.

Animals

An interactive microcomputer-based graphics system for analysis of cardiodynamic function.

An on-line interactive, modular, menu-driven microcomputer-based data acquisition and analysis system was designed and implemented. This system includes a low-cost commercial desk-top graphics computer with a modular construction. All these operations are performed using extended BASIC "CALL" statements. The system is designed to be used in a cardiovascular research and laboratory environment where the assessment of hemodynamic and cardiodynamic function includes routine measurements of pressure and flow. In addition, the measurement of regional and global left ventricular chamber dimensions have been implemented. The modular design of the software system is "human-engineered" to enable a simple, cost effective computer system to perform physiological measurement and control. Extended BASIC language instructions provide the casual computer user with a simple yet effective means of implementing on-line data acquisition, analysis and graphic production and display.

Cardiovascular Physiological Phenomena