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In its current application, off-pump coronary artery bypass grafting (OPCAB) requires clamping of the aorta to perform the proximal anastomosis. One of the important theoretical advantages of OPCAB is to avoid the undesirable effects of cross-clamping of the aorta. We report our early experience with a technique of no aortic clamping using the St. Jude aortic connector system in 11 patients.
BACKGROUND: We investigated the clinical outcome of elective and nonelective myocardial revascularization performed with intermittent aortic cross-clamping. METHODS: Prospective data on 800 consecutive patients (from May 1996 to July 2000), who underwent isolated myocardial revascularization with intermittent aortic cross-clamping, were analyzed. A subgroup analysis was performed on the elective (n = 520), urgent (n = 226), and emergency (n = 54) procedures. RESULTS: The elective group of patients had a mean age of 61.5 +/- 9.46 years, mean Parsonnet score of 5.23 +/- 5.1, and mean number of distal anastomoses of 3.22 +/- 1.04. The hospital mortality was 0.57%. The urgent group of patients had a mean age of 63.06 +/- 10.43 years, mean Parsonnet score of 6.73 +/- 6.22, and mean number of distal anastomoses of 3.21 +/- 1.04. The hospital mortality was 3.09%. The emergency group of patients had a mean age of 63.75 +/- 9.63 years, mean Parsonnet score of 11.24 +/- 11, and mean number of distal anastomoses of 2.87 +/- 0.86. Hospital mortality was 5.55%. Postoperative hospital stay was 7.11 +/- 5.47 days for the elective group, 7.59 +/- 5.07 days for the urgent group, and 7.40 +/- 4.01 days for the emergency group. CONCLUSIONS: Intermittent aortic cross-clamping is a safe technique both in elective and nonelective patients. The mortality and morbidity in the three subgroups analyzed reflects patients' distribution against Parsonnet score.
In two groups of animals (6 and 9 dogs), the aorta was cross-clamped 60 and 90 minutes, respectively, during hypothermic cardiopulmonary bypass. Immediately after cross-clamping, pharmacological cardiac arrest was induced by injecting 100 ml of a cold cardioplegic solution into the aortic root. Topical cardiac hypothermia was added. In hearts undergoing 90 minutes of ischemia, a repeat injection of the cardioplegic solution was done at 45 minutes. In 14 dogs (control group), only topical cardiac hypothermia was instituted for myocardial protection during 60 minutes of ischemia. Seven weeks after operation the surviving animals (6 in each group) were killed. Study of myocardial performance failed to demonstrate significant differences among the groups. Microscopic examination of transmural samples taken from anatomically defined sides of both ventricles, disclosed isolated, punctuate subendocardial scars in only 2 hearts of the control group. All the hearts having 90 minutes of pharmacological cardiac arrest and topical cardiac hypothermia exhibited diffuse fibrosis replacing 10 to 20% of the left ventricular myocardium. Extent and incidence of fibrosis were significantly higher in these hearts in comparison to those of the other groups. We conclude that pharmacological cardiac arrest plus topical cardiac hypothermia makes a safe and efficient method of myocardial protection during aortic cross-clamping only if the ischemic intervals is limited to 60 minutes. It cannot prevent permanent myocardial injury if the ischemic arrest is extended to 90 minutes.
The efficacy of cold blood potassium cardioplegia during periods of aortic cross-clamping (greater than 100 minutes) was assessed in 127 patients undergoing a variety of open-heart surgical procedures at New York University Medical Center from january, 1978, to April, 1979. Ischemic intervals ranged from 100 to 267 minutes (mean, 128 minutes). Cardiac-related deaths occurred in only 3 patients (2.4%), and overall operative mortality was 8.7% (11 patients). The rate of perioperative infarction was 10%. Fourteen patients (11%) required vasopressor support or balloon counterpulsation after cardiopulmonary bypass despite the lengthy cross-clamp intervals. Multivariate analysis revealed no significant relationship between the length of cross-clamp time and operative mortality (p = 0.29), incidence of perioperative infarction (p = 0.54), or the occurrence of low-output syndrome postoperatively (p = 0.68). These findings suggest that cold blood potassium cardioplegia provides adequate myocardial protection when periods of arrest as long as 3 to 4 hours are required for complex cardiac surgical procedures.
Aortic cross-clamping may produce ischemic damage due to a discrepancy between supply and demand. Supply is determined by noncoronary collateral flow and substrate stores, and demand by electromechanical activity, wall tension, and temperature. The effects of 60 minutes of conventional hypothermic ischemic arrest were compared to those of pharmacological arrest. Noncoronary collateral blood supply was comparable in both groups during cross-clamping. With ischemic arest, mechanical activity and endocardial electrical activity persisted and wall tension fell progressively. With pharmacological arrest, electromechanical activity stopped in less than 1 minute but returned (with increased wall tension) nearly 1 hour. Thirty minutes following reperfusion, coronary flow was redistributed away from subendocardium after ischemic arrest and toward endocardium after pharmacological arrest. Myocardial performance was depressed severely after conventional arrest and only mildy after pharmacological arrest. We conclude that aortic cross-clamping is safer with pharmacological arrest than with ischemic arrest. The cardioplegic solution modifies the supply/demand balance favorably, but it is washed out by noncoronary collateral blood supply.
A modification of the Kocher clamp used for wire closure of the sternum is described. With the clamp applied securely to the individual strands, the wire can be readily twisted; the shorter length of the clamp allows the surgeon a much firmer grip on the wire and saves considerable time during closure.
A soft vascular clamp was used for hemostasis and stabilization of the operative field during minimally invasive direct coronary artery bypass (MIDCAB). The instrument was gently applied so that it clamps the coronary artery by grasping the adjacent myocardium. The method offered dry and stable operative field without a special instrument or technique. The surgical results have been satisfactory. We found application of the vascular clamp to be very helpful for MIDCAB.
BACKGROUND: Monophosphoryl lipid-A (MLA) has a late window (24 hours) of cardioprotection against acute myocardial infarction. It is not known whether MLA, administered, 24 hours before surgery, attenuates intraoperative ventricular dysfunction "stunning" associated with aortic cross-clamping and reperfusion during elective cardiac surgery. We determined the dose-response relationship between MLA and ventricular function in a canine model of global myocardial stunning in the absence of necrosis. The role of expression of inducible heat shock protein 70 (HSP 70i) was also investigated. METHODS: Mongrel dogs (n = 32) were intravenously injected with either a vehicle solution or 3, 5, 10, 35 ug/kg MLA. Twenty four hours later, dogs were anesthetized and instrumented, in situ, to monitor the left ventricular performance (the slope of regression between stroke-work and end diastolic length). Tissue samples were obtained to determine HSP70i using immunoblot analysis. After a period of equilibration on cardiopulmonary bypass, the aortic cross-clamp was applied at normothermia for 30 minutes followed by 60 minutes of reperfusion. ATP and catabolites were determined in transmural myocardial biopsies. Triphenyl-tetrazolium chloride (TTC) staining was used to determine myocardial necrosis. RESULTS: MLA treatment did not alter myocardial contractility or ATP metabolism. Global ischemia resulted in about 50% depletion of ATP and remained depressed during reperfusion in all groups. MLA-treated hearts had improved functional recovery in a dose dependent-manner. Significant recovery was observed at the highest dose (35 ug/kg) compared to the control group. Immunoblot analysis demonstrated significant increase in HSP 70i in the MLA-treated hearts. CONCLUSIONS: MLA exhibits a delayed (24 hours) window of protection against myocardial stunning associated with aortic cross-clamping. HSP70i expression may play a role in MLA-mediated cardioprotection.
The motility assay of K. Visscher, M. J. Schnitzer, and S. M. Block (Nature, 400:184-189, 1999) in which the movement of a bead powered by a single kinesin motor can be measured is a very useful tool in characterizing the force-dependent steps of the mechanochemical cycle of kinesin motors, because in this assay the external force applied to the bead can be controlled (clamped) arbitrarily. However, because the bead is elastically attached to the motor and the response of the clamp is not fast enough to compensate the Brownian motion of the bead, interpretation or analysis of the data obtained from the assay is not trivial. In a recent paper (Y. Chen and B. Yan, Biophys. Chem. 91:79-91, 2001), we showed how to evaluate the mean velocity of the bead and the motor in the motility assay for a given mechanochemical cycle. In this paper we extend the study to the evaluation of the fluctuation or the randomness of the velocity using a Monte Carlo simulation method. Similar to the mean, we found that the randomness of the velocity of the motor is also influenced by the parameters that affect the dynamic behavior of the bead, such as the viscosity of the medium, the size of the bead, the stiffness of the elastic element connecting the bead and the motor, etc. The method presented in this paper should be useful in modeling the kinetic mechanism of any processive motor (such as conventional kinesin and myosin V) based on measured force-clamp motility data.
Localized membrane current and potential measurements were made on the squid giant axon in voltage clamp experiments. Spatial control of potential was impaired by the use of axial current supplying electrodes with surface resistance greater than 20 ohms for a centimeter length of axon. No region of membrane which was indeed subjected to a potential step showed more than one inward current peak. Other patterns were results of space clamp failure. Membrane current and potential patterns during space clamp failure were approximately reproduced in computations on a model containing two membrane patches obeying the equations of Hodgkin and Huxley. Non-uniformities in the axon or electrodes are not necessary for non-uniform electrical behavior. An extension of the core conductor model which includes the axial wire and external solution has been analyzed. The space constant of electrotonic spread is less than 0.5 mm with a usable electrode. Errors of about 5 per cent are introduced by ignoring the external solution. Resistance between the membrane and the control electrodes reduces the control and a few ohm cm(2) could lead to serious errors in interpretation.
In this paper we extend the simulation of the voltage clamp of a single nerve fiber to a bundle of axons. These simulations included not only the description of the voltage clamp circuit and a single unidimensional cable to represent the preparation in the "node" region of a double sucrose gap used previously but also a series resistance and a shunt pathway. The output of the voltage control amplifier is applied across the membrane plus the series resistance, producing a voltage drop across the series resistance due to the current generated by the membrane in response to a depolarizing voltage step. Since the membrane current has an inward and an outward phase, voltage drops of opposite sign are produced across the series resistance. During the transient current and at all points along an axon, the potential deviation produced by the series resistance is opposite to the deviation produced by the longitudinal gradient. Only at a command potential equal to the sodium equilibrium potential, the membrane potential transiently matches the command potential. For the attempted voltage clamp of an axon, values of series resistance larger than 50 omega-cm2 allowed propagated action potentials in the membrane. In spite of the presence of propagated action potentials at the calbe membrane, the recorded current does not show "notches" and it has a phase of inward current and a phase of outward current. It is concluded that, in a multicellular preparation with series resistance, the recording of a square voltage pulse does not indicate voltage control of the transmembrane potential. The presence of a shunt pathway produces inaccurate values of current density. Neither series or shunt resistance produce "notches" in the current records.
Ketterer, et al. (1971) have suggested that a combination of electrostatic and chemical interactions may cause hydrophobic ions absorbed within a bilayer lipid membrane to reside in two potential wells, each close to a membrane surface. The resulting two planes of charges would define three regions of membrane dielectric: two identical outer regions each between a plane of absorbed charges and the plane of closest approach of ions in the aqueous phase; and the inner region between the two planes of adsorbed charges. The theory describing charge translocation across the inner region is based on a simple three-capacitor model. A significant theoretical conclusion is that the difference between the voltage across the inner region, V(i), and the voltage across the entire membrane, V(m), is directly proportional to the amount of charge that has flowed in a voltage clamp experiment. We demonstrate that we can construct an "inner voltage clamp" that can maintain, with positive feedback, a constant inner voltage, V(i). The manifestation of proper feedback is that the clamp current (after a voltage step) will exhibit pure (i.e., single time-constant) exponential decay, because the voltage dependent rate constants governing translocation will be independent of time. The "pureness" of the exponential is maximized when the standard deviation of the least-square fit of the appropriate exponential equation to the experimental data is minimized. The concomitant feedback is directly related to the capacitances of the inner and outer membrane regions, C(i) and C(o).Experimental results with tetraphenylborate ion adsorbed in bacterial phosphatidylethanolamine/n-decane bilayers indicate C(i) approximately 5 . 10(-7)F/cm(2) and C(o) approximately 5 . 10(-5)F/cm(2).
Microelectrode penetration of small cells leads to a sustained depolarization of the resting membrane potential due to a transmembrane shunt resistance (Rs) introduced by the microelectrode. This has led to underestimation of the resting membrane potential of various cell types. However, measurement of the fast potential transient occurring within the first few milliseconds after microelectrode penetration can provide information about pre-impalement membrane electrophysiological properties. We have analyzed an equivalent circuit of a microelectrode measurement to establish the conditions under which the peak of the impalement transients (Ep) approaches the pre-impalement resting membrane potential (Em) of small cells most closely. The simulation studies showed that this is the case when the capacitance of the microelectrode is low and the membrane capacitance of the cell high. In experiments performed to assess the reliability of Ep as a measure of Em, whole-cell patch clamp measurements were performed in the current clamp mode to monitor, free from the effects of Rs, Em in cultured human monocytes. Microelectrode impalement of such patch clamped cells and measurement of Ep made it possible to detect correlation between Ep and Em and showed that for small cells such as human monocytes Ep is on average 6 mV less negative than the resting membrane potential.
Study of the excitatory sodium current (INa) intact heart muscle has been hampered by the limitations of voltage clamp methods in multicellular preparations that result from the presence of large series resistance and from extracellular ion accumulation and depletion. To minimize these problems we voltage clamped and internally perfused freshly isolated canine cardiac Purkinje cells using a large bore (25-microns diam) double-barreled flow-through glass suction pipette. Control of [Na+]i was demonstrated by the agreement of measured INa reversal potentials with the predictions of the Nernst relation. Series resistance measured by an independent microelectrode was comparable to values obtained in voltage clamp studies of squid axons (less than 3.0 omega-cm2). The rapid capacity transient decays (tau c less than 15 microseconds) and small deviations of membrane potential (less than 4 mV at peak INa) achieved in these experiments represent good conditions for the study of INa. We studied INa in 26 cells (temperature range 13 degrees-24 degrees C) with 120 or 45 mM [Na+]o and 15 mM [Na+]i. Time to peak INa at 18 degrees C ranged from 1.0 ms (-40 mV) to less than 250 microseconds (+ 40 mV), and INa decayed with a time course best described by two time constants in the voltage range -60 to -10 mV. Normalized peak INa in eight cells at 18 degrees C was 2.0 +/- 0.2 mA/cm2 with [Na+]o 45 mM and 4.1 +/- 0.6 mA/cm2 with [Na+]o 120 mM. These large peak current measurements require a high density of Na+ channels. It is estimated that 67 +/- 6 channels/micron 2 are open at peak INa, and from integrated INa as many as 260 Na+ channels/micron2 are available for opening in canine cardiac Purkinje cells.
Patch-clamp performance can be improved without altering the normal headstage configuration described by (Hamill, O. P., A. Marty, E. Neher, B. Sakmann, and F. J. Sigworth, 1981, Pfluegers Arch. Eur. J. Physiol., 391:85-100). The "supercharging" method permits resolution of such fast events as calcium and sodium tail currents. Digital computer modeling and analog electronic simulation were used to identify appropriate shapes for the command voltage and the voltage applied to a capacitor tied to the input of the headstage. The voltage command pulse consists of a step with a brief (5-15 microseconds) rectangular spike on its leading edge. Spike amplitude is a function of the membrane capacitance and the access resistance. The spike drives current through the access resistance and speeds charging of the membrane capacitance, making it possible to complete a voltage step within 5-15 microseconds. Clamping speed is independent of the electrode and feedback resistance over a wide range. The second function of the patch clamp amplifier is current measurement, and good time resolution requires suppression of the capacity transient. This can be accomplished by applying an appropriately shaped voltage to the small capacitor tied to the input of the headstage. Series resistance compensation for ionic current transients does not interfere with supercharging. Although the focus of this paper is on whole cell recording, the supercharging concept may prove useful for single channel and bilayer recording techniques.
A method is described for the simultaneous measurement of changes in membrane current and unidirectional radiotracer flux in internally dialyzed voltage-clamped squid giant axons. The small currents that are produced by electrogenic transport processes or steady-state ionic currents can be resolved using this method. Because the use of grounded guard electrodes in the end pools is not, by itself, an adequate means of eliminating end-effects, two ancillary end pool clamp circuits are described to eliminate extraneous current flow from the ends of the axon. The end pool voltage-clamp circuits serve to minimize net current flow between the end pools and center pool, and employ stable, low-impedance calomel electrodes to monitor the potentials of the end and center pools. The adequacy of the method is demonstrated by experiments in which unidirectional 22Na efflux and current, flowing through tetrodotoxin (TTX)-sensitive Na channels into Na-free seawater, under K-free conditions, are shown to be equal. The equality of unidirectional TTX-sensitive flux and current is maintained over the entire range of membrane potentials examined (-60 to +20 mV). The method has been applied to a series of experiments in which the voltage dependence and stoichiometry of the Na/K pump have been measured (Rakowski et al., 1989), and can be applied in general to the simultaneous measurement of changes in current and flux of other electrogenic transport processes, and of currents through ionic channels that open under steady-state conditions.
The cardiac sodium current was studied in guinea pig ventricular myocytes using the cell-attached patch voltage clamp at 37 degrees C in the presence of 145 mM external sodium concentration. When using large patch pipettes (access resistance, 1-2 M omega), the capacity current transient duration was typically 70 microseconds for voltage clamp steps up to 150 mV. At 37 degrees C the maximum inward sodium current peaked in approximately 200 microseconds after the onset of a clamp step and at this strong depolarization, less than 10% of the sodium current developed during the capacity transient. The sodium current developed smoothly and the descending limb of the current-voltage relationship usually spanned a range of 40 mV. Moreover, currents reduced by inactivation of sodium channels could be scaled to superimpose on the maximum current. Current tails elicited by deactivation followed a monoexponential time course that was very similar for currents of different sizes. Data obtained over a range of temperatures (15 degrees-35 degrees C) showed that the steady-state inactivation and conductance-voltage curves were shifted to more negative voltages at lower temperatures. These results demonstrate the feasibility of investigating the sodium current of mammalian cardiac cells at 37 degrees C in normal physiological solutions.
Analytical solutions are derived for arbitrarily branching passive neurone models with a soma and somatic shunt, for synaptic inputs and somatic voltage commands, for both perfect and imperfect somatic voltage clamp. The solutions are infinite exponential series. Perfect clamp decouples different dendritic trees at the soma: each exponential component exists only in one tree; its time constant is independent of stimulating and recording position within the tree; its amplitude is the product of a factor constant over that entire tree and factors dependent on stimulating and recording positions. Imperfect clamp to zero is mathematically equivalent to voltage recording with a shunt. As the series resistance increases, different dendritic trees become more strongly coupled. A number of interesting response symmetries are evident. The solutions reveal parameter dependencies, including an insensitivity of the early parts of the responses to specific membrane resistivity and somatic shunt, and an approximately linear dependence of the slower time constants on series resistance, for small series resistances. The solutions are illustrated using a "cartoon" representation of a CA1 pyramidal cell and a two-cylinder + soma model.