Experience with spiral computed tomography as the sole diagnostic method for traumatic aortic rupture.

BACKGROUND: Spiral computed tomographic (CT) scan is an excellent screen for aortic trauma. Traditionally, aortography is performed when injury is suspected to confirm the diagnosis. We hypothesized that it is safe and expeditious to forgo aortography when the spiral CT demonstrates aortic injury. METHODS: Retrospective review of 54 patients undergoing aortic repair from July 1994 to December 1999. Spiral CT was the initial diagnostic study in 52 patients. Pseudoaneurysm or aortic wall defect in the presence of mediastinal hematoma was considered diagnostic. Angiography, initially routine, was later performed only when requested by the surgeon, and for all "nonnegative" studies (periaortic hematoma without detectable aortic injury). RESULTS: Twenty-six patients underwent angiography before operation (group 1). Nineteen group 1 spiral CTs were unequivocally diagnostic; 7 were nonnegative and angiography was required. Twenty-eight other patients underwent repair based on spiral CT alone (group 2). There was one false-positive result in both groups. There were no unexpected operative findings. Mean time from admission to diagnosis was 5.7+/-3.4 hours for group 1 and 1.7+/-1.7 hours for group 2 (p < 0.01). CONCLUSIONS: Operating on the basis of a diagnostic spiral CT is safe and expeditious. Aortography may be reserved for those with equivocal studies.

Heparinless partial cardiopulmonary bypass for the repair of aortic trauma.

OBJECTIVE: We hypothesized that partial cardiopulmonary bypass with a heparin-bonded system would be a technically simple, effective adjunct for reducing paraplegia during repair of traumatic aortic rupture. It avoids the risk of heparin, but, unlike left atrial-arterial bypass, it can heat, cool, oxygenate, and rapidly infuse volume if needed. METHODS: A retrospective review was conducted of patients admitted for aortic trauma from July 1994 to December 1999. Bypass consisted of femoral venous (right atrial) cannulation, a centrifugal pump, and an oxygenator-heater/cooler. Arterial return was to the femoral artery or distal aorta. The entire system was heparin-bonded and no systemic heparin was given. RESULTS: Heparin-bonded partial bypass was established in 50 patients (mean age 43 +/- 17 years). Crossclamp time was 32 +/- 11 minutes (range 14-70 minutes), mean flow 3.0 +/- 0.8 L/min, and bypass time 64 +/- 43 minutes. During repair, 58% of patients received volume through the system (mean 1.1 +/- 1.9 L). Core temperature rose slightly (35.9 degrees C +/- 0.7 degrees C to 36.3 degrees C +/- 0.8 degrees C). Three of the 15 patients who underwent percutaneous femoral arterial and venous cannulation concomitant with their angiograms had vessel injury, with one limb loss, and this procedure was discontinued. Thirty-five patients underwent percutaneous femoral vein and direct distal aortic cannulation without event. The mortality rate for patients supported by bypass was 10%, and all deaths were due to other injuries. There were no new cases of paraplegia and no worsening of intracranial or pulmonary injuries. CONCLUSIONS: Heparin-bonded bypass is technically simple to use and avoids the risk of anticoagulation. Paraplegia was avoided. The ability to correct hypothermia, oxygenate, and rapidly infuse volume may simplify management and improve outcomes.

The effect of angiotensin II on mitogen-activated protein kinase in human cardiomyocytes.

The role of angiotensin II (Ang II)-receptors on mitogen-activated protein kinase (MAPK) activation in cardiomyocytes remains controversial. Therefore, the current study was designed to investigate the actions of AT(1)- and AT(2)-receptors on Ang II-induced extracellular signal-regulated kinase (ERK), p38 and the c-Jun N-terminal kinase (JNK) MAPK activities in human cardiomyocytes. Human cardiac tissue was obtained from open-heart surgery (n=6). The cardiac tissue was minced and incubated in the special tissue culture system for 24 hours in the absence or presence of Ang II (10(-7) M). These studies were repeated with the AT(1)-receptor antagonist losartan (10(-6) M) or the AT(2)-receptor antagonist PD-123319 (10(-6) M). Immunohistochemical staining and Western blot analysis with phospho-antibodies were performed to determine ERK, JNK and p38 activities. Ang II increased ERK and p38 activities in human cardiomyocytes. The effects of Ang II were abolished by losartan and enhanced by PD-123319. Co-incubation with both losartan and PD-123319 resulted in a decrease of ERK and p38 activities in cardiomyocytes. The immunohistochemical staining of JNK showed no significant differences between Ang II alone, Ang II plus losartan and Ang II plus PD-123319 groups. In conclusion, Ang II has a potent effect on ERK and p38 MAPK activities in cardiomyocytes, by acting through AT(1)-receptors. This effect of Ang II is modified by AT(2)-receptors. Therefore, Ang II, via AT(1)- and AT(2)-receptor stimulation, has a distinct effect on MAPK activity in cardiomyocytes.

Traumatic aortic rupture: recent outcome with regard to neurologic deficit.

BACKGROUND: Traumatic aortic rupture is highly lethal, and its surgical treatment is complicated by a high rate of paraplegia. METHODS: The charts of 263 patients with traumatic aortic rupture from vehicular accidents treated between 1971 and 1998 were reviewed. Patients were grouped according to four periods: group 1, 1971 to 1975, (n = 31); group 2, 1976 to 1985, (n = 83); group 3, 1986 to 1994, (n = 82); and group 4, 1994 to 1998 (n = 67). Seventy-one patients died of exsanguination before definitive care. One hundred-ninety two patients had surgical repair with the following techniques: clamp and sew, 6 in group 1, 22 in group 2, 54 in group 3, none in group 4; shunt, 23 in group 1, 39 in group 2, 2 in group 3; cardiopulmonary bypass, 2 in group 1, 1 in group 3. Forty-three patients had partial bypass with the centrifugal pump and heparin-coated circuits in group 4. RESULTS: Operative mortality was 6 of 31 (19%) in group 1, 22 of 61 (36%) in group 2, 15 of 57 (26%) in group 3, and 7 of 43 (16%) in group 4. There was one case of paraplegia in group 1 (4%), ten in group 2 (18%), 11 in group 3 (26%), and none in group 4. This difference of paraplegia between the groups was significant (p<0.002). Significant factors for paraplegia were intraoperative hypotension (p<0.000002), cross-clamp time longer than 30 minutes (p<0.008), pump versus no pump (p<0.008), and younger age group (28+/-11 versus 39+/-17 years) (p<0.03). CONCLUSIONS: There were no statistically significant improvements in mortality rate over the four periods, although, the mortality rate was lowest in the last period when partial bypass with the centrifugal pump was used exclusively. Further, the use of the centrifugal pump with heparin-coated circuits, with femoral vein cannulation into the right atrium and distal aortic perfusion, reduced paraplegia significantly.

Magnetic resonance imaging provides evidence for remodeling of the right ventricle after single-lung transplantation for pulmonary hypertension.

BACKGROUND: In end-stage pulmonary hypertension (PH), the degree of right ventricular (RV) dysfunction has been considered so severe as to require combined heart-lung transplantation. Nevertheless, left ventricular (LV) and RV hemodynamics return to relatively normal levels after single-lung transplantation (SLT) alone. Accordingly, to test the hypothesis that LV and RV systolic function improves after SLT and that the dilated, thick-walled RV reverts to more normal geometry, we used cine MRI and finite-element (FE) analysis to study patients with end-stage PH. METHODS AND RESULTS: Seven patients with end-stage PH underwent cine MRI before and after SLT, and eight normal volunteers were also imaged with cine MRI. Short-axis images at the midventricular level were analyzed with customized image-processing software. The LV and RV ejection fractions, velocity of fiber shortening, RV end-diastolic (ED) and end-systolic (ES) chamber areas, and RV ES and ED wall thicknesses were calculated directly from the MRI images. Two-dimensional FE models of the heart were constructed from the MRI images at early diastole. LV and RV pressures were measured in the patients with a cardiac catheterization before and after SLT. Models were solved to yield diastolic LV, RV, and septal wall stresses. By use of a nonlinear optimization algorithm, LV and RV diastolic maternal properties were determined by minimization of the leastsquares difference between FE model-predicted and MRI-measured LV, RV, and epicardial chamber areas and circumferences. The results demonstrated a substantial reduction in RV wall stress after SLT (1.8 x 10(5) dynes/cm2 pre-SLT to 2 x 10(4) dynes/cm2 post-SLT; P < .001). The average RV diastolic elastic modulus was reduced significantly after SLT (1.5 x 10(6) dynes/cm2 pre-SLT to 1 x 10(5) dynes/cm2 post-SLT; P = .01), but there was no change in the LV elastic modulus. RV velocity of fractional shortening increased significantly after SLT (0.23 pre-SLT to 0.58 post-SLT, P = .02), and RV ED and ES wall thicknesses were reduced significantly (ED, 0.86 cm pre-SLT to 0.65 cm post-SLT, P = .03 and ES, 1.06 cm pre-SLT to 0.72 cm post-SLT, P = .005). CONCLUSIONS: These results provide evidence supporting the contention that LV and RV systolic function improved after SLT for end-stage PH and that the RV underwent significant remodeling within 3 to 6 months after lung transplantation.

Myocardial material property determination in the in vivo heart using magnetic resonance imaging.

OBJECTIVES: To determine nonlinear material properties of passive, diastolic myocardium using magnetic resonance imaging (MRI) tissue-tagging, finite element analysis (FEA) and nonlinear optimization. BACKGROUND: Alterations in the diastolic material properties of myocardium may pre-date the onset of or exist exclusive of systolic ventricular dysfunction in disease states such as hypertrophy and heart failure. Accordingly, significant effort has been expended recently to characterize the material properties of myocardium in diastole. The present study defines a new technique for determining material properties of passive myocardium using finite element (FE) models of the heart, MRI tissue-tagging and nonlinear optimization. This material parameter estimation algorithm is employed to estimate nonlinear material parameter sin the in vivo canine heart and provides the necessary framework to study the full complexities of myocardial material behavior in health and disease. METHODS AND RESULTS: Material parameters for a proposed exponential strain energy function were determined by minimizing the least squares difference between FE model-predicted and MRI-measured diastolic strains. Six mongrel dogs underwent MRI imaging with radiofrequency (RF) tissue-tagging. Two-dimensional diastolic strains were measured from the deformations of the MRI tag lines. Finite element models were constructed from early diastolic images and were loaded with the mean early to late left ventricular and right ventricular diastolic change in pressure measured at the time of imaging. A nonlinear optimization algorithm was employed to solve the least squares objective function for hte material parameters. Average material parameters for the six dogs were E = 28,722 +/- 15984 dynes/cm2 and c = 0.00182 +/- 0.00232 cm2/dyne. CONCLUSION: This parameter estimation algorithm provides the necessary framework for estimating the nonlinear, anisotropic and non-homogeneous material properties of passive myocardium in health and disease in the in vivo beating heart.

Spline surface interpolation for calculating 3-D ventricular strains from MRI tissue tagging.

A method is developed and validated for approximating continuous smooth distributions of finite strains in the ventricles from the deformations of magnetic resonance imaging (MRI) tissue tagging "tag lines" or "tag surfaces." Tag lines and intersections of orthogonal tag lines are determined using a semiautomated algorithm. Three-dimensional (3-D) reconstruction of the displacement field on tag surfaces is performed using two orthogonal sets of MRI images and employing spline surface interpolation. The 3-D regional ventricular wall strains are computed from an initial reference image to a deformed image in diastole or systole by defining a mapping or transformation of space between the two states. The resultant mapping is termed the measurement analysis solution and is defined by determining a set of coefficients for the approximating functions that best fit the measured tag surface displacements. Validation of the method is performed by simulating tag line or surface deformations with a finite element (FE) elasticity solution of the heart and incorporating the measured root-mean-square (rms) errors of tag line detection into the simulations. The FE-computed strains are compared with strains calculated by the proposed procedure. The average difference between two-dimensional (2-D) FE-computed strains and strains calculated by the measurement analysis was 0.022 +/- 0.009 or 14.2 +/- 3.6% of the average FE elasticity strain solution. The 3-D displacement reconstruction errors averaged 0.087 +/- 0.002 mm or 2.4 +/- 0.1% of the average FE solution, and 3-D strain fitting errors averaged 0.024 +/- 0.011 or 15.9 +/- 2.8% of the average 3-D FE elasticity solution. When the rms errors in tag line detection were included in the 2-D simulations, the agreement between FE solution and fitted solution was 24.7% for the 2-D simulations and 19.2% for the 3-D simulations. We conclude that the 3-D displacements of MRI tag lines may be reconstructed accurately; however, the strain solution magnifies the small errors in locating tag lines and reconstructing 3-D displacements.

Mechanical dysfunction in the border zone of an ovine model of left ventricular aneurysm.

BACKGROUND: The pathophysiology of regional mechanical dysfunction in the border zone (BZ) region of left ventricular aneurysm was studied in an ovine model using magnetic resonance imaging tissue-tagging and regional deformation analysis. METHODS: Transmural infarcts were created in adult Dorsett sheep (n = 8) by ligation of the distal homonymous coronary artery and were allowed to mature into left ventricular aneurysms for 8 to 12 weeks. Animals were imaged subsequently using double oblique magnetic resonance imaging with radiofrequency tissue tagging. Short axis slices were selected for analysis that included predominantly the septal component of the aneurysm as well as adjacent BZ regions in the anterior and posterior ventricular walls. Dark grid patterns of magnetic presaturations were placed on the myocardium and tracked as they deformed during the diastolic, isovolumic systolic, and systolic ejection phases of the cardiac cycle. Regional ventricular wall strains were calculated in BZ regions and regions remote from the aneurysm and compared with strains measured in corresponding regions from normal control sheep (n = 6). RESULTS: Diastolic midwall circumferential strains (fiber extensions) were relatively preserved, but abnormal circumferential lengthening strains were observed in the BZ regions during isovolumic systole. Peak circumferential strains ranged from 0.04 to 0.07 in the BZ regions but averaged -0.05 in the normal hearts (p = 0.002 for the anterior BZ and p = 0.001 for the posterior BZ). Midwall end-systolic fiber strains were depressed in the anterior BZ (-0.03 to -0.09 for the BZ versus -0.11 for the normal heart, p < 0.0001) but not in the posterior BZ (p = 0.19). CONCLUSIONS: Our data support the theory that the stretching of BZ fibers during isovolumic systole contributed to a reduction in fiber shortening during systolic ejection and thus reduced the overall contribution of these fibers to forward ventricular output.

A multimedia-based histology laboratory course: elimination of the traditional microscope laboratory.

UNLABELLED: We have developed a multimedia-based laboratory course which has enabled us to eliminate the microscope and traditional microscope laboratory that have been mainstays of our histology course and histology courses at almost all institutions where histology is taught. The multimedia laboratory uses a library of histology images (approximately 24,000) stored on videodisc ( HISTOLOGY: A Photographic Atlas, by S. Downing) as its microscope slide collection and accesses those images through barcode and computer interfaces. The laboratory workstations consist of a videodisc player, videodisc monitor, computer, and computer monitor. One workstation is available for every 4-students, and our students are encouraged to work together in groups of four or five. In our current set-up, the students are introduced to and instructed in the basic principles of histology using a computer program that interfaces with the videodisc images. The computer program is divided into 19 chapters (the chapters are typical of the chapters found in a normal histology textbook) and has: (1) a laboratory component that covers the material traditionally covered in the microscope laboratory, and (2) a lecture component that enables the students to evaluate their understanding of the lecture material in a non-punishing way. The laboratory section of each chapter is divided into a "MicroLab" section, an "InFo Time" section, and a "Quiz Time" section. Each of these sections interfaces with histological images stored on the videodisc. The students are encouraged to work through the "MicroLab" section of each chapter before moving on to the "InFo Time" and "Quiz Time" sections. The "MicroLab" sections introduce the students to the various tissues and organs of the body and is interfaced with the videodisc player and the histology images stored on the videodisc. These sections describe the basic histological features of the various tissues and organs and give the students access to multiple examples of what they are studying. The "InFo Time" sections bring up specific images and ask the students to think about the images. Information about the images being observed is available if the students want it and the students can flag those images that they found difficult. The Quiz Time section of the program is also interfaced with the videodisc player and provides access to a large number of histology images stored on the videodisc. The "Quiz Time" sections provide non-punishing review questions that the students can study after she has worked her way through the "MicroLab" and "InFo Time" sections. In addition to the use of a computer program to access the histology images stored on videodisc, we use barcodes that address specific images on the histology videodisc in a variety of ways to augment the students' laboratory and lecture experience. The benefits of using multimedia in place of the traditional microscope and microscope slide collection are numerous and include the speed at which specific histological images can be accessed and reviewed (when compared to finding a structure on a glass slide), a significant reduction in the amount of laboratory time needed by the student to learn the same amount of information, the ease of tutoring on a large monitor screen (when compared to trying to discuss a histological structure with a student through the eyepiece of a microscope), the encouragement of group study (which is difficult to do when a student is working 1-on-with a microscope), and the reduction of the number of faculty necessary to cover a typical histology laboratory session. The use of barcodes that address specific videodisc histology images has greatly changed our examination procedures and has significantly expanded the usefulness of the traditional lecture note handouts given to our students.

Ventricular interaction in the pathologic heart. A model based study.

The effects of direct ventricular interaction and interaction mediated by the pericardium on the diastolic left ventricle (LV) were quantified using idealized models of five pathologic conditions. Two-dimensional (2D) mathematical models were constructed in long and short axis views of four pathologic LV conditions and the normal heart (NL): dilated cardiomyopathy (DCM), concentric LV hypertrophy (HYP), chronic anterior-apical infarction in a normal shaped LV (CAINL), and CAI in a dilated LV (CAID). To assess the effects of RV pressure increase on the LV mechanical state, RV pressure was systematically increased for several LV pressures and changes in the LV diastolic pressure-area relationships, and LV free wall and septal principal stresses and strains were quantified. At higher RV pressures, with pericardial effects included in the models, the pressure-area relationship was similar for all models, indicating that, at these higher pressures, the effects of RV and pericardial pressures are more important than global LV shape, wall thickness, or material properties in determining the pressure-area relationship. There were significant differences among models in the changes in LV free wall and septal stress and strain after an increase in RV pressure. These models may be of use in predicting interaction in the corresponding clinical state.

Pathogenesis of ischemic mitral insufficiency.

We developed a new animal model of ischemic mitral insufficiency in sheep and used it to test the hypothesis that the combination of posterior papillary muscle infarction and left ventricular dilatation was required to produce mitral regurgitation after acute inferior myocardial infarction of moderate size. In 12 sheep, ligation of the first two circumflex marginal coronary arteries infarcted 23% of the left ventricular mass, increased left ventricular cavitary area from 13.2 +/- 1.2 cm2 to 20.0 +/- 2.7 cm2 by 8 weeks and did not produce ischemic mitral regurgitation. In 13 sheep, ligation of the second and third circumflex marginal arteries infarcted 21% of the left ventricular mass and, in 11 of these sheep, the posterior papillary muscular mass as well. When the papillary muscle was included, this infarction produced progressively severe mitral regurgitation over 8 weeks, as left ventricular cavitary area increased from 12.5 +/- 2.6 cm2 to 22.8 +/- 3.8 cm2. We conclude that neither posterior papillary muscle infarction nor left ventricular dilatation alone produces ischemic mitral regurgitation after moderate-sized inferior wall infarction, but that the combination does.

Myocardial electrical impedance mapping of ischemic sheep hearts and healing aneurysms.

BACKGROUND: This study was designed to examine the bulk electrical properties of myocardium and their variation with the evolution of infarction after coronary occlusion. These properties may be useful in distinguishing between normal, ischemic, and infarcted tissue on the basis of electrophysiological parameters. METHODS AND RESULTS: The electrical impedance of myocardial tissue was studied in a sheep model of infarction. The animal model involved a one-stage ligation of the left anterior descending and second diagonal arteries at a point 40% of the distance from the apex to the base. By use of a four-electrode probe, an epicardial mapping system was developed that allowed for cardiac cycle gated and signal-averaged measurements. Subthreshold current (15 microA) was injected through two of the electrodes at frequencies of 1, 5, and 15 kHz and the induced potential measured with the other two electrodes. Epicardial maps of the left ventricle were obtained during acute infarction and at 1-, 2-, and 6-week intervals after occlusion. Results showed the average specific impedance of the myocardium before infarction to be 158 +/- 26 omega-cm independent of location on the epicardium. By 60 minutes after coronary occlusion, the specific impedance had increased by 199% (p < 0.005, n = 9); it remained elevated for up to 4 hours. One week after infarction, the specific impedance decreased to 59% of the control value (p < 0.025, n = 8). Six weeks after occlusion, the specific impedance remained low at 57% of that of the noninfarcted tissue (p < 0.005, n = 9). The phase angle of the complex impedance was also measured and revealed similar changes. The hydroxyproline content of the tissue was assayed to assess infarct healing. CONCLUSIONS: In this animal model, impedance is a bulk electrical property of tissue that varies with the evolution of myocardial infarction. Impedance mapping revealed significantly different values for normal, ischemic, and infarcted tissue and may prove useful in better defining the electrophysiological characteristics of such tissue.

Adriamycin-induced inhibition of melanoma cell invasion is correlated with decreases in tumor cell motility and increases in focal contact formation.

Tumor cell adhesion to the extracellular matrix (ECM) is closely linked with tumor cell invasion and metastasis. In this study, we demonstrate that low levels of adriamycin, a widely used anticancer drug, can inhibit the invasion of highly metastatic K1735-M2 mouse melanoma cells in vitro through a reconstituted basement membrane extract. Adriamycin-induced inhibition of melanoma cell invasion occurred at levels of the drug (i.e. 1 ng/ml) that did not inhibit tumor cell growth, suggesting that the observed inhibition in tumor cell invasion was not due to the well-documented ability of adriamycin to interfere with DNA and/or RNA synthesis. Rather, these studies indicated that adriamycin-induced inhibition of melanoma cell invasion was accompanied by a corresponding decrease in the ability of adriamycin-treated tumor cells to migrate in response to several isolated ECM components including fibronectin, laminin and basement membrane (type IV) collagen. The decreased migration of adriamycin-treated tumor cells was not accompanied by a decrease in the adhesion or spreading of the adriamycin-treated cells on substrata coated with these ECM components. Instead, adriamycin-treated cells actually exhibited a slightly increased propensity (compared to untreated control cells) to adhere on fibronectin-, laminin-, and type IV collagen-coated substrata. Additionally, adriamycin treatment caused a dramatic increase in focal contact formation by these melanoma cells, as assessed by fluorescent microscopy of actin and vinculin. In addition to providing a useful model for which to study the molecular and cellular basis for focal contact formation, these results further emphasize the results of several other investigators that have suggested an important role for focal contacts in modulating tumor cell motility, invasion and metastasis.

Release of vasoactive substances during cardiopulmonary bypass.

Cardiopulmonary bypass is associated with bleeding and thrombotic complications, massive fluid shifts, and cellular and hormonal defense reactions that are collectively termed "the whole body inflammatory response." A host of vasoactive substances are produced, released or altered during cardiopulmonary bypass. These hormones, autacoids, and cytokines react with specific receptor proteins distributed throughout the body, and mediate the vascular smooth muscle and endothelial cell contractions that are responsible for much of the morbidity associated with open heart operations. This essay briefly reviews the actions, sources, and perturbations of the approximately 25 vasoactive substances known or believed to be altered by cardiopulmonary bypass, and provides an introductory reference list.

Protection of platelets during long-term extracorporeal membrane oxygenation in sheep with a single dose of a disintegrin.

BACKGROUND: Both short- and long-term extracorporeal membrane oxygenation (ECMO) causes platelet loss and dysfunction. Bitistatin is a reversible inhibitor of the platelet glycoprotein IIb/IIIa receptor. This study tests the hypothesis that inhibition of platelets by bitistatin during initial contact with the perfusion circuit preserves platelet number and function during long-term ECMO in sheep. METHODS AND RESULTS: Bitistatin, purified from crude snake venom, was tested for its effect on platelet count, responsiveness to ADP, release of platelet factor 4, and prevention of surface-adsorbed glycoprotein IIIa in vitro and during 24 hours of ECMO in nine splenectomized sheep. During simulated extracorporeal circulation, 0.5-1.0 microgram/ml bitistatin significantly prevented platelet adhesion, attenuated release of sheep platelet factor 4, and preserved platelet responsiveness to ADP. During ECMO at 1.8 l/min for 24 hours, a single dose of bitistatin (200 micrograms/kg) (n = 4) produced higher platelet counts (p = 0.0002) and suppressed release of platelet factor 4 (p = 0.035) for 16 hours compared with five control animals. This dose of bitistatin caused an immediate inhibition of platelet aggregation; however, between 4 and 24 hours of perfusion, platelets of bitistatin-treated animals were more responsive to ADP (p < 0.0001) compared with platelets in control animals. The amount of glycoprotein IIIa antigen extracted by Triton X-100 from the perfusion circuits was reduced in bitistatin-treated sheep. CONCLUSIONS: A single dose of bitistatin given before blood contact with the ECMO circuit briefly inhibits platelet adhesion and aggregation but thereafter preserves platelet numbers and function and suppresses alpha-granule release for 12-16 hours of ECMO.

The stretched ventricle. Myocardial creep and contractile dysfunction after acute nonischemic ventricular distention.

The hypothesis that nonischemic distention of the arrested, flaccid ventricle causes myocardial creep and reduces ventricular contractile force was tested in 16 sheep. Left ventricular volume was calculated from ultrasonic dimension transducers spanning left ventricular major and minor axes and left ventricular wall thickness. Changes in left ventricular volume were plotted against left ventricular pressure, with and without temporary occlusion of both venae cavae before and after nonischemic distention of the continuously perfused, flaccid nonbeating left ventricle arrested with oxygenated, normothermic blood-potassium perfusate. During 12 minutes of cardiac arrest, an apical balloon progressively distended the left ventricle to a peak pressure of 40 mm Hg in 11 sheep using a protocol designed to prevent subendocardial ischemia or mechanical injury. Coronary sinus lactate measurements and myocardial distribution of microspheres confirmed the absence of ischemia in 16 animals. In five control sheep the balloon was inserted but not inflated. Left ventricular volume at zero pressure increased from 5.9 +/- 3.5 to 9.5 +/- 4.4 ml (p < 0.05) after balloon inflation and did not change in the control animals. After maximum distention of the balloon, static left ventricular volumes at identical pressures were significantly greater. After passive distention, the slope of the end-systolic pressure-volume relationship, a measure of contractility, decreased significantly (p < 0.05) from 7.1 +/- 2.8 to 3.5 +/- 1.8 mm Hg/ml and did not change in the control group. Passive distention ("stretching") of the nonischemic flaccid left ventricle thus causes myocardial creep and reduces ventricular contractility.

Repair of left ventricular aneurysm. Changes in ventricular mechanics, hemodynamics, and oxygen consumption.

Anteroapical left ventricular aneurysms were produced in 23 sheep by coronary arterial ligation. Plication of the aneurysm does not change stroke volume or cardiac output and does not significantly change left ventricular oxygen consumption from the preoperative value of 5.1 +/- 2.6 ml/100 gm per minute. Plication, however, does increase left ventricular end-systolic elastance from 3.2 +/- 0.9 to 4.4 +/- 1.5 mm Hg/mm (p = 0.005). In nine of these sheep the midsagittal plane of the left ventricle was imaged by means of an array of sonomicrometry crystals before and after plication of the aneurysm. Regional wall stresses at end-systole and end-diastole and changes in diastolic function were calculated for anterior and posterior ventricular walls in the border zone adjacent to the aneurysm and in more basilar myocardium remote from the infarct. Plication significantly reduced end-systolic wall stresses and systolic stress integrals in the posterior border zone and remote myocardium, but it did not significantly change anterior wall systolic stresses or stress integrals. Plication also decreased diastolic stretching of border zone myocardium. Plication of anteroapical left ventricular aneurysm produced a shorter, more spherical ventricle and removed the dyskinetic segments but altered deformation (strain) in both circumferential and longitudinal directions. The changes in ventricular wall geometry and deformation provide an explanation for the increased ventricular end-systolic elastance and unchanged stroke volume observed after aneurysm plication.

Left ventricular assistance without thoracotomy: mediastinal and transseptal approaches to the left heart.

Two methods to cannulate the left atrium for initiating mechanical left ventricular circulatory assistance using a centrifugal pump were investigated in 25 sheep. A modified Dennis transatrial septal approach produced flow rates of 88.6 +/- 14 mL.kg-1.min-1 through 21F catheters inserted during fluoroscopy through the jugular vein. In 8 animals the septal perforation was plugged after decannulation with a modified Rashkind umbrella plug. Fibroendothelial tissue covered the plug by 4 week. In 7 other animals, the septal defect was not plugged. The septal defect reached pinpoint size by 2 weeks and was completely closed by 4 weeks. In 10 sheep, the left atrium was cannulated from the neck through the mediastinum. Left ventricular assistance flow averaged 71.6 +/- 14 mL.kg-1.min-1. Mean blood loss during 1 hour of left ventricular assistance was 47 mL. In 8 animals, the atrial perforation was plugged with a mean blood loss of 253 +/- 194 mL. In 2 animals, the perforation was intentionally not plugged; mean blood loss was 700 mL. All animals survived. The modified Dennis transatrial method is recommended as a safe, expeditious, cost-effective method to implement left ventricular assistance without thoracotomy. The mediastinal approach, which is technically possible in humans, is more difficult but feasible. Left ventricular assistance has been proven to be the most effective way to rest the failing, ejecting left ventricle. Implementation without thoracotomy potentially expands applications of left ventricular assistance for temporary support of patients with severe manifestations of ischemic heart disease.