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Biomedical subjects

J Y Kresh

Publications and source records attributed to J Y Kresh.

At least 19 recordsLinked to original sources
PubMed2000

Early detection of acute allograft rejection by linear and nonlinear analysis of heart rate variability.

OBJECTIVE: The first months after orthotopic heart transplantation are associated with the highest risk of acute allograft rejection. This study explores the utility and reliability of linear and novel nonlinear metrics of heart rate variability as predictors of graft rejection. The underlying hypothesis is that the transplanted heart, in response to inflammatory mediators, alters the dynamic properties of its rhythm-generating system. METHODS: In a cross-sectional study of 45 patients who had undergone heart transplantation, spanning a period of 4 months after the operation, heart rate variability was examined by time- and frequency-domain analysis. The nonlinear features of heart rate variability were studied by computing a pointwise correlation dimension of R-R interval time series. The results of heart rate variability analysis were compared with those of endomyocardial surveillance biopsy studies using the International Society for Heart and Lung Transplantation scoring system. RESULTS: Duration of heart transplantation itself exhibited a significant (P<.05) association with the onset of rejection. Specific predictors of acute rejection based on heart rate variability were identified, including shortening of the R-R interval (from 700 +/- 68 to 648 +/- 72 ms), an increase in the ratio of low-frequency (0.04-0.15 Hz) to high-frequency (0.15-0.40 Hz) spectral power (from 0.3 +/- 0.2 to 0.6 +/- 0.4), and a decrease in pointwise correlation dimension values (from 1.7 +/- 0.7 to 0.9 +/- 0.3 units). Multivariable logistic regression analysis (R (2) = 0.4) revealed that the only significant independent risk predictors were pointwise correlation dimension (odds ratio, 2.2 per 0.1 unit) and duration of heart transplantation (odds ratio, 1.7 per week). CONCLUSION: Nonlinear measures of heart rate variability provide noninvasive means for identifying patients undergoing cardiac transplantation with acute rejection, thereby enabling the assessment of the time-dependent adaptive response of the donor heart to its host.

Adult↗
PubMed1998

Evolution in functional complexity of heart rate dynamics: a measure of cardiac allograft adaptability.

The capacity of self-organized systems to adapt is embodied in the functional organization of intrinsic control mechanisms. Evolution in functional complexity of heart rate variability (HRV) was used as measure of the capacity of the transplanted heart to express newly emergent regulatory order. In a cross-sectional study of 100 patients after (0-10 yr) heart transplantation (HTX), heart rate dynamics were assessed using pointwise correlation dimension (PD2) analysis. A new observation is that, commencing with the acute event of allograft transplantation, the dynamics of rhythm formation proceed through complex phase transitions. At implantation, the donor heart manifested metronome-like chronotropic behavior (PD2 approximately 1.0). At 11-100 days, dimensional complexity of HRV reached a peak (PD2 approximately 2.0) associated with resurgence in the high-frequency component (0.15-0.5 Hz) of the power spectral density. Subsequent dimensional loss to PD2 approximately 1.0 at 20-30 mo after HTX was followed by a progressive near-linear gain in system complexity, reaching PD2 approximately 3.0 7-10 yr after HTX. The "dynamic reorganization" in the allograft rhythm-generating system, seen in the first 100 days, is a manifestation of the adaptive capacity of intrinsic control mechanisms. The loss of HRV 2 yr after HTX implies a withdrawal of intrinsic autonomic control and/or development of an entrained dynamic pattern characteristic of extrinsic sympathetic input. The subsequent long-term progressive rise in dimensional complexity of HRV can be attributed to the restoration of a functional order patterning parasympathetic control. The recognition that the decentralized heart can restitute the multidimensional state space of HR generator dynamics independent of external autonomic signaling may provide a new perspective on principles that constitute homeodynamic regulation.

Adaptation, Physiological↗
PubMed1997

Bradykinin modulation of isolated rabbit heart function is mediated by intrinsic cardiac neurons.

OBJECTIVE: Bradykinin (BK) is an endogenous peptide exerting a potent influence on the behavior of the heart. The local regulatory mechanisms responsible for BK modulation of cardiac automaticity and contractility remain poorly understood. The role of the intrinsic cardiac nervous system (ICNS) in mediating the BK-induced regulatory effect was investigated. METHODS: Heart rate (HR) and intramyocardial pressure (IMP) changes in response to BK (1.2-80 nmol) were studied in isolated rabbit hearts (n = 37). The intrinsic neural mechanisms underlying the cardiac effects of BK were characterized by use of atropine (ATR, 10(-6) M), timolol (TIM, 10(-5) M), hexamethonium (HEX, 10(-4) M), and tetrodotoxin (TTX, 10(-7) M). Modulation of beta-adrenergic tone by dobutamine (DOB, 1.6 x 10(-6) M) was used to expose the physiological importance of intrinsic cholinergic systems in mediating the cardiac action of BK. RESULTS: A single dose of BK induced an increase in IMP and a biphasic HR response. The negative chronotropic response to BK was correlated with negative HR change induced by nicotine activation of ICNS. BK-elicited 'bradycardia' was abolished by ATR and TTX, and attenuated (approximately 50%) by HEX. ATR and TTX potentiated the positive HR-response which was not affected by TIM. BK selectively antagonized [by 48.1(5.1)%] the DOB-induced tachycardia but did not modify the accompanied inotropic potentiation. CONCLUSIONS: These findings are the first demonstration that in the autonomically decentralized heart, the negative chronotropic action of BK is mediated by intrinsic cardiac cholinergic neurons. It would appear that the intrinsic neural network response, and not merely the BK-induced potentiation of cardiac postganglionic neural activity is involved in the local neuromodulatory action of BK. This intrinsic cardiac regulatory mechanism seems to play a major role in mitigating the adrenergically induced tachycardia, thus endowing this peptide with the capacity for cardioprotection.

Adrenergic beta-Agonists↗
PubMed1997

Differentiation of intramyocardial fluid pressure from fiber stress.

To characterize the complex force field generated in the ventricular myocardium, intramyocardial pressure (IMP) measurement is used as an indirect means of assessing the distribution of regional wall stress. To resolve the long term confusion associated with this measurement, IMP is divided into its two dominant components: intramyocardial fluid pressure (IFP) and intramyocardial fiber stress (IFS). The intramyocardial response to regional and global contractile function is examined in terms of changes in the magnitude and transmural gradient of IMP recording. The experimental results support the theoretical concept proposed where the hydraulic properties of the myocardium proved to have an influence on cardiac function. To gain a deeper understanding of myocardial function, cellular and subcellular components must be considered.

Animals↗
PubMed1997

The heart as a self-regulating system: integration of homeodynamic mechanisms.

In the past the study of mechanical and electrical properties of the heart has been disjointed with minimal overlap and unification. The fact remains that these features are tightly coupled and central to the functioning heart. The maintenance of adequate cardiac output relies upon the highly integrated autoregulatory mechanisms and modulation of cardiac myocyte function. Regional ventricular mechanics and energetics are dependent upon muscle fiber stress-strain rate, the passive properties of myocardial collagen matrix, adequate vascular perfusion, transcapillary transport and electrical activation pattern. Intramural hydraulic "loading" is regulated by coronary arterial and venous dynamics. All of these components are under the constant influence of intrinsic cardiac and extracardiac autonomic neurons, as well as circulating hormones. A brief overview of the putative regulation of these various components is presented in this paper.

Autonomic Pathways↗
PubMed1996

Internal thoracic artery for coronary artery grafting in octogenarians.

BACKGROUND: Use of the left internal thoracic artery as a bypass graft has been shown to result in better long-term patency and improved survival. In elderly patients, the internal thoracic artery has been used less often for coronary artery bypass grafts because of the belief that greater morbidity and mortality are associated with this procedure. This study was undertaken to test this premise in the octogenarian population. METHODS: Over an 8-year period, 474 consecutive patients 80 years of age and greater had coronary artery bypass grafting. The left internal thoracic artery was used in 188 patients (39.7%) (group 1) and saphenous vein grafts only (group 2), in 286 (60.3%). The mean age was 82.6 years (range, 80 to 95 years). There were 312 men (65.8%) and 162 women (34.2%). RESULTS: Use of the internal thoracic artery as a graft has risen steadily each year, as has the number of patients who are octogenarians. The hospital mortality rate was 7.8%. Patients in group 1 had a mortality rate of 9.0% and patients in group 2, a mortality rate of 7.0%. The mortality rate among survivors at 1 year was 6.7%. Long-term survival was significantly greater in group 1. CONCLUSIONS: On the basis of this study, we conclude that the internal thoracic artery is the bypass graft of choice, especially in regard to long-term mortality, and should not be denied to this high-risk group.

Age Distribution↗
PubMed1996

Two-port analysis of microcirculation: an extension of windkessel.

We examined the suitability of the three-element windkessel as a reduced model of pulsatile pressure-flow relations at arteriolar and venular ends of a microcirculatory bed. Frequency domain (two-port) analysis of a distributed model of an idealized (single input, single output) microvascular network in skeletal muscle, consisting of 391 discrete vessel segments from a 20-microns-diameter arteriole to a 28-microns-diameter venule, demonstrated that the three-element windkessel is a good representation of arterial input impedance when pressure pulsations are absent at the venous end. The same model with different parameter values accounts well for venous pressure-flow relations if no pulsations occur at the arterial end. We showed that a five-element model (2 compliances, 3 resistors) provided a superior representation of pulsatile pressure-flow relations at both arterial and venous ends. Relating parameter values to known properties of the network revealed the physiological significance of the five elements. This model may prove a useful component in circulatory models incorporating both arteries and veins. While parameter values obtained herein were strictly valid for the particular microvascular network described, guidelines are provided based on physiological properties so that values may be estimated for different microvascular beds.

Animals↗
PubMed1994

Effects of venous pressure on coronary circulation and intramyocardial fluid mechanics.

This investigation examined the interaction between right heart pressure (RHP), coronary perfusion pressure (CPP), intramyocardial tissue pressure (IMP), and coronary flow mechanics, including partitioning of coronary effluent in the isolated Krebs-Henseleit perfused rabbit heart. The major new finding was a parallel shift in the IMP-inflow relationship to a higher tissue pressure level in response to an increase in RHP. Accompanying the rise in RHP from 0 to 15 and 25 mmHg, IMP at zero coronary inflow in the beating (and arrested) heart increased from 5.8 +/- 1.0 (7.7 +/- 1.2) to 16.3 +/- 1.2 (17.9 +/- 1.3) and 28.6 +/- 1.7 (26.4 +/- 2.0) mmHg, respectively. A concomitant parallel shift in the CPP-inflow relation to higher pressures was consistently observed. The fraction of total coronary flow drained by the right heart was not constant. A higher partition of coronary outflow to the left heart (7.8 +/- 3.8, 34.3 +/- 3.0, and 47.9 +/- 4.3%, respectively) accompanied the increase in RHP. Intramyocardial partitioning of coronary outflow pathways mediates the effects of venous pressure modulation on coronary circulation. The interaction between coronary venous pressure and the extravascular environment modifies the effective back pressure to arterial inflow.

Animals↗
PubMed1993

Intramyocardial mechanical states: vessel-interstitium-muscle interface.

The intramural blood vessels and fluid-filled interstitial space form a hydraulic continuum enmeshed by myocardial muscle layers and collagen matrix. Coronary circulation was found to be strongly influenced by passive and active properties of the muscle surrounding the coronary microvasculature. Selective remodeling of the extracellular collagen-matrix and partial uncoupling of the intramyocardial structure(s) cause profound functional alterations in the coronary circulation and interstitial compartment fluid-dynamics. Mechanical impediment to coronary inflow resides in the muscle fiber-interstitium-microvessel interface, functioning independently of the generated chamber pressure conditions.

Animals↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1987

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↗
PubMed1986

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↗