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Biomedical subjects

C E Arentzen

Publications and source records attributed to C E Arentzen.

At least 19 recordsLinked to original sources

Hepatic and vena cava resection using cardiopulmonary bypass with hypothermic circulatory arrest.

When large hepatic or retroperitoneal tumors encroach upon hepatic veins or vena cava and make conventional resection hazardous, the most commonly used method of hepatic resection or vena cava reconstruction includes hepatic vascular exclusion, at times with venovenous bypass or aortic occlusion. These techniques result in warm liver ischemia, and may be accompanied by significant systemic hypotension, despite aggressive central venous preloading. Hepatic lobe (two patients) and retroperitoneal sarcoma (one patient) resections were done in a cold, bloodless field without significant complications. Standard cardiopulmonary bypass techniques with heparin and cardioplegia were used. Systemic circulatory arrest was done at 15 degrees C with isolated retrograde perfusion of the brain through the jugular veins. Hepatic vein and vena cava reconstructions were performed with arrest times of between 30 and 78 minutes. Blood loss was gradual and easily controlled, occurring during the rewarming phase when clot formation was inhibited by cold and heparin.

Adult↗

Characterization of inwardly rectifying K+ channel in human cardiac myocytes. Alterations in channel behavior in myocytes isolated from patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Little is known about the characteristics of the inwardly rectifying K+ channel (IK1) and the influence of preexisting heart disease on the channel properties in the human heart. METHODS AND RESULTS: We studied the characteristics of cardiac IK1 in freshly isolated adult human atrial and ventricular myocytes by using the patch-clamp technique. Specimens were obtained from the atria and ventricles of 48 patients undergoing cardiac surgery or transplantation and from four explanted donor hearts. The action potential in ventricular myocytes exhibited a longer duration (391.4 +/- 30.2 milliseconds at 90% repolarization, n = 10) than in atrium (289.4 +/- 23.0 milliseconds, n = 18, P < .001) and had a fast late repolarization phase (phase 3). The final phase of repolarization in ventricle was frequency independent. Whole-cell IK1 in ventricle exhibited greater slope conductance (84.0 +/- 7.9 nS at the reversal potential, EK; n = 27) than in atrium (9.7 +/- 1.2 nS at EK; n = 8, P < .001). The steady-state current-voltage (I-V) relation in ventricular IK1 demonstrated inward rectification with a region of negative slope. This negative slope region was not prominent in atrial IK1. The macroscopic currents were blocked by Ba2+ and Cs+. The channel characteristics in ventricular myocytes from patients with congestive heart failure after idiopathic dilated cardiomyopathy (DCM) exhibited distinct properties compared with those from patients with ischemic cardiomyopathy (ICM). The action potential in ventricular myocytes from patients with DCM had a longer duration (490.8 +/- 24.5 milliseconds, n = 11) compared with that for ICM (420.6 +/- 29.6 milliseconds, n = 11, P < .01) and had a slow repolarization phase (phase 3) with a low resting membrane potential. The whole-cell current slope conductance for DCM was smaller (41.2 +/- 9.0 nS at EK, n = 7) than that for ICM (80.7 +/- 17.0 nS, n = 6, P < .05). In single-channel recordings from cell-attached patches, ventricular IK1 channels had characteristics similar to those of atrial IK1; channel openings occurred in long-lasting bursts with similar conductance and gating kinetics. In contrast, the percent of patches in which IK1 channels were found was 34.7% (25 of 72) of patches in atrium and 88.6% (31 of 35) of patches in ventricle. Single IK1 channel activity for DCM exhibited frequent long-lasting bursts separated by brief interburst intervals at every holding voltage with the open probability displaying little voltage sensitivity (approximately 0.6). Channel activity was observed in 56.2% (18 of 32) of patches for DCM and 77.4% (24 of 31) of patches for ICM. Similar results were obtained from atrial IK1 channels for DCM. In addition, channel characteristics were not significantly different between ICM and explanted donor hearts (donors). IK1 channels in cat and guinea pig had characteristics virtually similar to those of humans, with the exception of lower open probability than that in humans. CONCLUSIONS: These results suggest that the electrophysiological characteristics of human atrial and ventricular IK1 channels were similar to those of other mammalian hearts, with the possible exception that the channel open probability in humans may be higher, that the whole-cell IK1 density is higher in human ventricle than in atrium, and that IK1 channels in patients with DCM exhibited electrophysiological properties distinct from IK1 channels found in patients with ICM and in donors.

Action Potentials↗

An analysis of lidocaine block of sodium current in isolated human atrial and ventricular myocytes.

Lidocaine is a Na+ channel blocker that is highly effective for the treatment of ventricular tachyarrhythmias, but is largely ineffective against atrial arrhythmias. If is not known if this differential efficacy is the result of differences in lidocaine inhibition of atrial v ventricular Na+ channels. The purpose of the present study was to characterize lidocaine block of Na+ channels in human atrium and ventricle. We used the whole cell voltage clamp technique with low external and internal Na+ concentrations (5 mM) to study the Na+ current (INa) in single human atrial and ventricular cells isolated enzymatically from specimens obtained during surgery. We found that tonic block of peak INa by lidocaine (200 microM, holding potential = -140 mV, 0.1 Hz, at 17 degrees C) was not voltage dependent in either cell type. Reduction of maximal peak Na+ conductance in 41 atrial cells (19.8 +/- 2.7%) and nine ventricular cells (22.6 +/- 1.7%) was virtually identical. The rate of onset of block development was determined during depolarization to either -80 mV or -20 mV. The time course of onset of block was described by a single exponential at -80 mV and by a double exponential at -20 mV. When the rate of block onset during a single conditioning depolarization was compared to that which developed during conditioning by a train of brief pulses (3 ms, 30 Hz), onset was faster during the pulse train. The results were nearly identical for atrial and ventricular INa. The time constants of recovery from block following either single pulse or multiple-pulse conditioning did not differ. These data suggest that lidocaine binds to both the activated and inactivated states of the human cardiac Na+ channel. Using an analytical method based upon the Guarded Receptor Hypothesis, we calculated apparent rate constants describing lidocaine's interaction with the three primary states of the human Na+ channel (resting, activated and inactivated). Rate constants were similar to those reported for other mammalian species. Our results demonstrate that lidocaine block of INa is virtually identical for human atrial and ventricular cells; thus additional mechanisms must be invoked to explain the differential efficacy of lidocaine against ventricular as compared to atrial dysrhythmias.

Adolescent↗

Modulation of alloreactivity in transplant recipients by phenotypic manipulation of donor endothelium.

Phenotypic manipulation of allograft endothelium to reduce immunogenicity would have a significant impact on transplantation. In this study we have demonstrated that random seeding of a heart allograft with endothelium, of host origin, not only promotes long-term survival, but reduces the requirement for pharmacologic immunosuppression. We propose that this simple technology could easily be extrapolated to the clinical arena where hypothermia and preservation solutions have allowed allografts to remain ex vivo for extended periods.

Animals↗

A frequency domain analysis of spatial organization of epicardial maps.

Mapping of organized rhythms like sinus rhythm uses activation times from individual electrograms, and often assumes that the map for a single activation is similar to maps for subsequent activations. However, during fibrillation, activation times and electrograms are not easy to define, and maps change from activation to activation. Volume and complexity of data make analysis of more than a few seconds of fibrillation difficult. Magnitude Squared Coherence (MSC), a frequency domain measure of the phase consistency between two signals, can be used to help interpret longer data segments without defining activation times or electrograms. Sinus rhythm, flutter, and fibrillation in humans and swine were mapped with an array of unipolar electrodes (2.5 mm apart) at 240 sites on the atrial or ventricular epicardium. Four-second data segments were analyzed. One site near the center of the array was chosen ad hoc as a reference. MSC maps were made by measuring mean MSC from 0-50 Hz between every point in the array relative to the reference. Isocoherence contours were drawn. The effects of bias in the coherence estimate due to misalignment were investigated. Average MSC versus distance from the reference was measured for all rhythms. Results indicate that in a 4-s segment of fibrillation, there can exist some phase consistency between one site and the reference and little or none between a second site and the reference even when both sites are equidistant from the reference. In fibrillation, isocoherence contours are elongated and irregularly shaped, reflecting long-term, but nonuniform, spatial organization. That is, activation during fibrillation cannot be considered as random over a 4-s interval. Bias in the coherence estimate due to misalignment is significant for sinus rhythm and flutter, but can be corrected by manual realignment. Average MSC drops with distance for all rhythms, being most pronounced for fibrillation, MSC maps may provide insights into long-term spatial organization of rhythms that would otherwise be cumbersome and difficult to interpret with standard time domain analysis.

Animals↗

beta-Adrenergic modulation of the inwardly rectifying potassium channel in isolated human ventricular myocytes. Alteration in channel response to beta-adrenergic stimulation in failing human hearts.

The beta-adrenergic modulation of the inwardly-rectifying K+ channel (IK1) was examined in isolated human ventricular myocytes using patch-clamp techniques. Isoproterenol (ISO) reversibly depolarized the resting membrane potential and prolonged the action potential duration. Under the whole-cell C1- -free condition, ISO applied via the bath solution reversibly inhibited macroscopic IdK1. The reversal potential of the ISO-sensitive current was shifted by approximately 60 mV per 10-fold change in the external K+ concentration and was sensitive to Ba2+. The ISO-induced inhibition of IK1 was mimicked by forskolin and dibutyrl cAMP, and was prevented by including a cAMP-dependent protein kinase (PKA) inhibitor (PKI) in the pipette solution. In single-channel recordings from cell-attached patches, bath applied ISO could suppress IK1 channels by decreasing open state probability. Bath application of the purified catalytic sub-unit of PKA to inside-out patches also inhibited IK1 and the inhibition could be antagonized by alkaline phosphatase. When beta-adrenergic modulation of IK1 was compared between ventricular myocytes isolated from the failing and the nonfailing heart, channel response to ISO and PKA was significantly reduced in myocytes from the failing heart. Although ISO inhibited IK1 in a concentration-dependent fashion in both groups, a half-maximal concentration was greater in failing (0.12 microM) than in nonfailing hearts (0.023 microM). These results suggest that IK1 in human ventricular myocytes can be inhibited by a PKA-mediated phosphorylation and the modulation is significantly reduced in ventricular myocytes from the failing heart compared to the nonfailing heart.

Adrenergic beta-Agonists↗

The haemostatic effectiveness of autologous platelet rich plasma sequestered after heparin administration and institution of cardiopulmonary bypass.

Preoperative harvesting and postoperative reinfusion of autologous platelet rich plasma (PRP) has been reported to decrease blood loss as well as the requirement for homologous blood transfusion following cardiopulmonary bypass (CPB). We have developed a technique of intraoperative PRP sequestration which occurs during the initial period of CPB after the patient's circulation is supported and heparin has been given (PRP+). This process does not require any additional hardware, personnel or expense and it is performed without difficulty or complication. To evaluate the effect of PRP+ sequestration and reinfusion on blood loss and homologous blood requirement after CPB, we randomly assigned 126 consecutive patients undergoing elective open heart surgery into the experimental group 1 (PRP+) (n = 64) or the control (no platelet pheresis) group 2 (n = 52). A third group (n = 10) were not included in the randomization. Patients in group 3 had PRP prepared by conventional techniques (PRPc) prior to heparin administration and given to the patient after protamine infusion. Aggregation and activation studies were performed on the PRP+, PRPc, and blood bank platelets (BBP). Per cent aggregation of PRP in response to ADP was superior to that of BBP. There were no significant differences in ADP induced aggregation between PRP+ and PEPc. There was no significant difference in platelet activation (CD62) or number between the three groups. Patients infused with PRP+ showed significantly increased aggregation to ADP when compared with untreated patients 120 minutes after return to the ICW. Furthermore, more homologous haemostatic components (platelets/fresh frozen plasma) were required in the control group. We have demonstrated that collection of autologous PRP+ after administration of heparin does not interfere with its haemostatic effectiveness compared with PRPc prepared before the initiation of bypass. Moreover, this can be performed universally in haemodynamically unstable patients without any additional costs.

Aged↗

The relationship between hospital charges and a modified Parsonnet risk score.

Health care now consumes approximately 14 percent of the U.S. Gross National Product (GNP). The amount of money spent on health care in America per capita and as a percentage of GNP far exceeds that of any other industrialized country. Currently, the financial burden of health care is being shouldered by government and business. The expenditure of billions of dollars of corporate profits on health care progressively undermines the global competitiveness of American business. These economic realities have emerged as the dominant driving force in health care reform. Cost control efforts to date have focused on strategies to limit inpatient hospital expenditures. The DRG prospective payment system is designed to reimburse a fixed sum based on the diagnostic category of the patient. The DRG payment is essentially independent of underlying patient characteristics that can potentially drive up expenditures. The work reported in this article was done to develop a descriptive formula that could be used to predict resource consumption in the care of patients. The financial viability of a hospital depends on its ability to predict expenditures, allocate resources, and choose its service areas correctly. Errors in financial forecasting in the era of prospective payment will result in financial failures of entire institutions.

Age Factors↗

Alterations in muscarinic K+ channel response to acetylcholine and to G protein-mediated activation in atrial myocytes isolated from failing human hearts.

BACKGROUND: A variety of previous studies have demonstrated reduced diastolic potential and electrical activity in atrial specimens from patients with heart disease. Although K+ channels play a major role in determining resting membrane potential and repolarization of the action potential, little is known about the effects of preexisting heart disease on human atrial K+ channel activity. METHODS AND RESULTS: We characterized the inwardly rectifying K+ channel (IKI) and the muscarinic K+ channel [IK(ACh)] in atrial myocytes isolated from patients with heart failure (HF) and compared electrophysiological characteristics with those from donors (control) by the patch-clamp technique. Resting membrane potentials of isolated atrial myocytes from HF were more depolarized (-51.1 +/- 9.7 mV, mean +/- SD, n = 30 patients) than those from donors (-73.0 +/- 7.2 mV, n = 4 patients, P < .001). The action potential duration in HF was longer than that in donors. Although acetylcholine (ACh) shortened the action potential, reduced the overshoot, and hyperpolarized the atrial cell membrane in HF, these effects were attenuated compared with those observed in donors. The whole-cell membrane current slope conductance in HF was small, the reversal potential was more positive, and the sensitivity to ACh was less compared with donors. In single-channel recordings from cell-attached patches, IK1 channel conductance and gating characteristics were the same in HF and donor atria. When ACh was included in the pipette solution, IK(ACh) was activated in both groups. Single-channel slope conductance of IK(ACh) averaged 42 +/- 3 pS (n = 28) in HF and 44 +/- 2 pS (n = 4) in donors, and mean open lifetime was 1.3 +/- 0.3 milliseconds (n = 24) in HF and 1.5 +/- 0.4 milliseconds (n = 4) in donors. These values were virtually identical in the two groups (not significantly different, NS), although both single IK1 and IK(ACh) channel densities were less in HF. Channel open probability of IK(ACh) was also less in HF (4.0 +/- 1.2%, n = 24) than in donors (6.8 +/- 1.1%, n = 3, P < .01). The concentration of ACh at half-maximal activation was 0.11 mumol/L in HF and 0.03 mumol/L in donors. In excised inside-out patches, IK(ACh) from HF required higher concentrations of GTP and GTP gamma S to activate the channel compared with donors. These results suggest a reduced IK(ACh) channel sensitivity to M2 cholinergic receptor-linked G protein (Gi) in HF compared with donors. CONCLUSIONS: Atrial myocytes isolated from failing human hearts exhibited a lower resting membrane potential and reduced sensitivity to ACh compared with donor atria. Whole-cell and single-channel measurements suggest that these alterations are caused by reduced IK1 and IK(ACh) channel density and reduced IK(ACh) channel sensitivity to Gi-mediated channel activation in HF.

Acetylcholine↗

Intraoperative procurement of autologous fibrin glue.

A method of intraoperative procurement of autologous fibrin glue is described. The relative efficacy of our autologous preparation is compared with that of fibrin glue made with homologous cryoprecipitate. Experimentally, the fibrinogen content and the strength are less than those found in cryoprecipitate and appear related to the fibrinogen content of the autologous plasma used as substrate in the fibrin glue reaction. Clinically, no significant differences are noted in the performance of autologous fibrin glue. We believe the absence of the risk of blood-borne infection with the autologous product is a major advantage.

Adhesiveness↗

Sodium current in isolated human ventricular myocytes.

Although fast sodium current (INa) plays a major role in the generation and conduction of the cardiac impulse, the electrophysiological characteristics of INa in isolated human ventricular myocytes have not yet been fully described. We characterized the human ventricular INa of enzymatically isolated myocytes using whole cell voltage-clamp techniques. Sixty myocytes were isolated from ventricular specimens obtained from 22 patients undergoing open-heart surgery. A low temperature (17 degrees C) and Na+ concentration in the external solution (5 or 10 mM) allowed good voltage control and facilitated the measurement of INa. Cs+ was substituted for K+ in both internal and external solutions to block K+ currents, and F- was added to the internal solution to block Ca2+ current. INa was activated at a voltage threshold of approximately -70 mV, and maximal inward current was obtained at approximately -30 mV (holding potential = -140 mV). The voltage dependence of steady-state INa availability (h infinity) was sigmoidal with half inactivation occurring at -97.3 +/- 1.1 mV and a slope factor of 5.77 +/- 0.10 mV (n = 60). We did not detect any significant differences in these parameters in cells from patients with a variety of disease states, with or without congestive heart failure. The overlap in voltage dependence of h infinity and Na+ conductance suggested the presence of a Na+ "window" current. An inactivation time course was voltage dependent and was fitted best by the sum of two exponentials. The rate of recovery from inactivation also was voltage dependent and fitted by the sum of two exponentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Characterization of the sodium current in single human atrial myocytes.

Patch-clamp recording techniques have permitted measurement of the fast Na+ current (INa) in isolated cardiac cells from a number of species in recent years. However, there is still only very little information concerning human cardiac INa. The purpose of this study was to describe the kinetics of INa in normal-appearing, Ca(2+)-tolerant, enzymatically isolated human atrial myocytes using whole-cell voltage-clamp techniques. Atrial specimens were obtained from 46 patients undergoing open heart surgery. Cs+ was substituted for K+ in both pipette and external solutions and F- was added to the former. The reversal potential of the rapid inward current varied approximately 57 mV at 17 +/- 1 degrees C with a 10-fold change in [Na+]o, and the current was completely blocked by 100 microM tetrodotoxin, findings typical of the fast cardiac Na+ current. The tetrodotoxin dose-response curve was best fitted by an equation describing binding to high- and low-affinity sites. INa was activated at a voltage threshold of -70 to -60 mV, and peak inward current was obtained at approximately -30 mV (holding potential, -140 mV). The inactivation time course was voltage dependent and was fitted best by the sum of two exponentials. The relation between voltage and steady-state availability (h infinity) was sigmoidal with the half-inactivation at -95.8 +/- 0.9 mV and a slope factor of 5.3 +/- 0.1 mV (n = 46), and we did not observe a significant difference with disease and age. The overlap of the h infinity and activation curves suggested the presence of a Na+ "window" current. Recovery from inactivation also was voltage dependent and best fitted by a model describing the sum of two exponentials. Recovery occurred after an initial delay at potentials positive to -140 mV, suggesting that inactivation of human atrial INa is a multistate process. We conclude that INa of normal-appearing, Ca(2+)-tolerant human atrial myocytes is similar to that of other mammalian cardiac cells with the possible exception of having two tetrodotoxin binding sites.

Adolescent↗

Acetylcholine-sensitive potassium channels in human atrial myocytes.

Single channel recording techniques were used to study acetylcholine (ACh)-sensitive K+ channel activity in human atrial myocytes isolated from specimens obtained during corrective cardiac surgery. Under conditions of cell-attached patch, the presence of ACh in the patch pipette activated K+ channels. Single channel activity occurred in periodic bursts. The channels exhibited a slope conductance of 46 +/- 2 pS inwardly (means +/- SD, n = 4). During a burst, both open and closed time histograms were fitted by a single exponential curve, suggesting the existence of one open and one closed state during a burst. Open probability increased directly with ACh concentration without affecting open time. The channel could be activated by GTP and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) (in the presence and absence of ACh in the pipette, respectively). Slope conductance, the response to GTP and GTP gamma S, and the independence of activation from Ca2+ were similar to those for other species. In contrast, sensitivity to ACh appeared diminished compared with frog atrial myocytes.

Acetylcholine↗

Contribution of atrioventricular synchrony to left ventricular systolic function in a closed-chest canine model of complete heart block: implications for single-chamber rate-variable cardiac pacing.

This study assessed the impact of atrioventricular (AV) synchrony on characteristics of left ventricular (LV) systolic function during ventricular pacing over a wide heart rate range in a conscious closed-chest canine model of complete AV block. Ten healthy adult dogs underwent thoracotomy during which complete AV block was created by formaldehyde injection, and paired ultrasonic sonomicrometers were positioned on the LV anterior-posterior minor axis. Following recovery from surgery, peak and end-diastolic LV transmural pressure, maximum dP/dt, stroke work, end-diastolic minor axis dimension, and maximum velocity of shortening, were quantitated at heart rates of 80, 100, 120, 140, and 160 beats per minute (bpm) during both ventricular pacing alone and AV sequential pacing with increasing AV intervals (0, 50, 100, 150, 200, 250, and 300 ms). Over the heart rate range tested, parameters of LV systolic function did not differ significantly during ventricular pacing with or without AV synchrony. For example, during ventricular pacing alone maximum LV dP/dt varied from 2110 +/- 70 mmHg/s to 2463 +/- 567 mmHg/s, a range essentially identical to that observed in the presence of AV synchrony. On the other hand, although the impact on LV performance of varying AV interval from 0 to 300 ms was small, differences tended to become more pronounced at higher pacing rates. At 80 bpm, neither stroke work nor maximum LV dP/dt were affected by change in AV interval, while at heart rates greater than or equal to 120 bpm both stroke work and LV dP/dt tended to maximize at AV intervals of 50 and 100 ms and thereafter declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of pressure-induced right ventricular hypertrophy on left ventricular diastolic properties and dynamic geometry in the conscious dog.

To determine whether chronic pressure overload and hypertrophy of the right ventricle alter the diastolic properties of the left ventricle, six adult dogs underwent banding of the pulmonary artery and were instrumented for studies 8 months later. Fourteen control dogs were also studied. Pressure and dimension data were collected from the dogs while they were awake and unsedated. The anterior-posterior, septal-free wall, and base-apex axis diameters of the left ventricle were measured with ultrasonic dimension transducers. Right and left ventricular pressures were measured with micromanometers. Pulmonary arterial banding resulted in increased right ventricular/body mass ratios (2.70 +/- 0.36 g/kg vs 1.52 +/- 0.15 g/kg control; p less than or equal to .05) and increased left ventricular/body mass ratios (4.84 +/- 0.64 g/kg vs 4.21 +/- 0.49 g/kg control; p less than or equal to .05). Right ventricular peak systolic and end-diastolic pressures were higher among the banded dogs (50 +/- 20/7 +/- 5 mm Hg vs 31 +/- 6/3 +/- 2 mm Hg control; p less than or equal to .05). A rearrangement in the three-dimensional geometry of diastolic filling occurred in the banded dogs. Extension from unstressed diastolic dimension (strain) in the base-apex axis was significantly larger in the banded dogs at left ventricular transmural pressures of 12, 8, and 4 mm Hg; strains in the septal-free wall axis were significantly smaller at transmural pressures of 12 and 8 mm Hg. Normalized diastolic left ventricular pressure-volume data and midwall circumferential stress-strain data were fit to the Kelvin viscoelastic equation. The normalized pressure-volume relationships of the banded dogs lay significantly to the left of those of the controls, indicating a loss of left ventricular chamber compliance. The midwall circumferential stress-strain relationships of the banded dogs were also shifted to the left, indicating a loss of intrinsic myocardial compliance. Thus, during the course of right ventricular hypertrophy caused by right ventricular pressure overload, alterations in the mass, geometry, and material properties of the left ventricle occur. At 8 months the chamber compliance of the left ventricle is compromised by these changes.

Animals↗

Effects of global ischemia on the diastolic properties of the left ventricle in the conscious dog.

The alterations in regional diastolic mechanics that occur during regional myocardial ischemia (creep and increased myocardial stiffness) may be the result of interactions between the ischemic and surrounding nonischemic myocardium rather than the direct result of ischemia. Thus similar changes may not occur when the entire left ventricle is ischemic. Thus similar changes may not occur when the entire left ventricle is ischemic. To investigate this proposition, left ventricular diastolic mechanics were studied in seven chronically instrumented conscious dogs during global left ventricular ischemia. The anterior-posterior, septal-free wall, and base-apex axes of the left ventricle were measured with ultrasonic dimension transducers. Left and right ventricular pressures were measured with micromanometers. Myocardial blood flows were measured with left atrial injections of 15 microns radioactive microspheres. Global left ventricular ischemia was induced by hydraulic constriction of the left main coronary artery, which resulted in a 54% decrease in mean left ventricular subendocardial blood flow. Left ventricular volume, midwall circumference, and midwall circumferential stress were calculated from ellipsoidal shell theory. To construct pressure-strain and stress-strain relationships from diastolic data collected during vena caval occlusions, all measured and calculated dimensions were normalized to Lagrangian strains (fractional extension from unstressed dimension). During ischemia, creep (elongation of unstressed dimension) occurred in each of the three left ventricular axes. The mean unstressed dimension of the anterior-posterior axis increased from 5.39 +/- 0.53 to 5.85 +/- 0.50 cm ( p less than or equal to .05); the septal-free wall unstressed dimension increased from 5.11 +/- 0.53 to 5.72 +/- 0.80 cm (p less than or equal to .05); and the base-apex unstressed dimension increased from 7.04 +/- 0.61 to 7.25 +/- 0.65 cm (p less than or equal to .05). The relationship between diastolic midwall circumferential stress and strain shifted upward and to the left with ischemia, indicating that an increase in intrinsic myocardial stiffness had occurred. As a result of these mechanical alterations, there was a decrease in left ventricular chamber compliance that was manifested by a leftward shift of the diastolic pressure-volume strain relationship. Neither systolic bulging nor dysynchronous systolic shortening occurred in any of the three left ventricular spatial axes during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Improved immunosuppression for heart transplantation.

Since 1981, at the University of Minnesota, and more recently at Washington University in St. Louis, cyclosporine has been used as the main immunosuppressive agent for heart transplantation. It was initially combined with prednisone and given in a manner similar to that described at Stanford. In late 1983, concern regarding the nephrotoxic side effects of cyclosporine were heightened due to the fact that a potential recipient had chronic renal insufficiency secondary to renal damage suffered during previous heart surgery. In this patient it was decided to use lower doses of cyclosporine and to add azathioprine to maintain adequate immunosuppression. Initially, the same prednisone therapy was employed. This patient had an uncomplicated course following heart transplantation and was discharged with a normal renal function. This experience was the origin of a trial consisting of using cyclosporine, azathioprine, and prednisone as immunotherapy for heart transplantation. This report describes the results of this therapy in 17 patients.

Azathioprine↗

Abnormalities in myocardial perfusion during tachycardia in dogs with left ventricular hypertrophy: metabolic evidence for myocardial ischemia.

This study tested the hypothesis that in the chronically hypertrophied left ventricle pacing stress may cause abnormalities of perfusion that result in myocardial ischemia. Left ventricular hypertrophy (LVH) was produced by banding the ascending aorta of 10 dogs at 6 weeks of age, and studies were carried out after the animals had reached adulthood and when mean left ventricular/body weight ratio was 74% greater than in eight control dogs. Myocardial blood flow was measured with microspheres during pacing at 100, 200, and 250 beats/min, while aortic and coronary sinus blood samples were obtained for determination of concentrations of lactate and the adenosine metabolites inosine and hypoxanthine. In the control dogs, increasing heart rates were associated with an increase in mean myocardial blood flow while subendocardial flow was maintained at a level equal to or greater than subepicardial flow. Myocardial lactate uptake ranged from +60% to -5%, and adenosine metabolites were not detected in coronary sinus blood (less than 0.5 microM/l). In four dogs that underwent aortic banding no production of lactate or adenosine metabolites was observed at any heart rate; in these animals subendocardial flow was maintained at a level equal to or greater than subepicardial flow at all pacing rates. The remaining six dogs with LVH demonstrated net lactate production significantly greater than control during pacing at 250 beats/min; five of these six animals also produced adenosine metabolites.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗