TUESDAY MORNING, MAY 9, 1989

7:30 a.m. FORUM SESSION - HYNES BALLROOM

F1. Selective Annuloplasty of the Tricuspid Valve: Two-Year Experience

CARMINE MINALE*, HEINRICH LAMBERTZ*,

SIGRID NIKOL* and BRUNO JOSEF MESSMER

Aachen, West Germany

Between June 1986 and October 1988, 40 patients with multiple-valve disease underwent tricuspid valve repair by a new technique. This consists of three steps: separation of the anterior and posterior leaflets from the anulus over a length averaging 4.6 + /- 1.2 cm (2.5 - 8.0 cm) to allow coaptation of the three leaflets in the middle; exclusion of ²A of the isolated anulus (average: 3.4 + /- 1.0 cm) with a continuous 3-0 Tycron suture; repositioning of the leaflets to the shortened anulus by a 4-0 Prolene suture. Patients age averaged 60 yrs (29 - 73). Preoperatively 16 of them were class III and 24 class IV of the NYHA. 22 Pts had a previous valve operation. Three patients died in hospital because of respiratory failure (2.5%) and cardiac failure (5.0%), respectively. After a mean follow-up time of 12 months, there were neither late mortality nor valve related complications. Overall late survival was 92.5%. All Pts whose follow-up period lasted 6 or more months improved their functional status to class I or II (NYHA). Echocardiographic evaluation of the tricuspid valve in four chamber view showed a maximal anulus diameter averaging 26.5 +/- 6.0 mm/m^-2 BSA preoperatively and 19.6 + /- 1.7 mm/m"² BSA postoperatively (p = 0.005). Postoperatively the shortening fraction of tricuspid anulus during systole averaged 11 + / 5.0%; trivial (1/3) and moderate (2/3) regurgitation were evidenced in two and one patient, respectively. Eighteen patients underwent postoperative hemodynamic investigation. Over the tricuspid valve there was a median gradient of 1.3 +/- 1.0 mmHg. Mean right atrial pressure dropped from an average of 18 +/- 8.0 mmHg preoperatively to 12 +/- 8.0 mmHg postoperatively (p = 0.03). The medium-term results with the present method show a high survival rate compared with the current methods of tricuspid valve surgery. In addition clinical and hemodynamic improvements are striking in almost all patients. Further advantage of the present method is the simplicity of restoring normal anatomic relationship of the tricuspid ap-parate without using rigid and/or prosthetic materials.

*By Invitation

F2. Electrically Conditioned Skeletal Muscle for Augmentation of Cardiac Function

RACE L. KAO*, IGNACIO Y. CHRISTLIEB*,

GEORGE J. MAGOVERN, SANG B. PARK* and

GEORGE J. MAGOVERN, JR.*

Pittsburgh, Pennsylvania

Since skeletal muscle and heart muscle are composed mainly of contractile proteins, utilization of autogenous skeletal muscle to correct a myocardial defect and augment ventricular contraction are logical approaches. However, all the early attempts to replace or assist cardiac function with skeletal muscle have been plagued by rapid skeletal muscle fatigue. Recently, electric conditioning has made skeletal muscle capable of continuous repetitive contraction, and clinical application of dynamic cardiomyoplasty has become a reality. Skeletal muscle contracts mainly in the direction of its fiber orientation. How to utilize the skeletal muscle contractile force to maximize cardiac output in an ailing heart is the goal of this study.

Dogs were anesthetized and prepared for sterile surgical procedure. The left latissimus dorsi muscle was freed with intact neurovascular supply before being iternalized into the thoracic cavity and wrapped around the ventricles at different muscle fiber orientations with fixation stitches. After three weeks of recovery and revascularization, the muscle was conditioned over a six week period by a pulse generator. At 6, 12 and 24 weeks after the conditioning, hemodynamic evaluation after propranolol infusion (3mg/kg) was performed. Propranolol decreased the cardiac output, contractility, stroke work index, and blood pressure 40% to 60% for several hours, thus providing an ideal condition to study the improvement of cardiac function by synchronously stimulating the latissimus dorsi muscle to contract with the heart. When the muscle fibers were oriented in an ideal direction, a significant increase in cardiac output (44%), stroke work index (126%), and arterial systolic pressure (57%) were observed. These results clearly documented the augmentation of depressed ventricular function by stimulating a conditioned skeletal muscle with proper fiber orientation over the heart.

*By Invitation

F3. Oxygen Utilization in Postischemic "Stunned" Myocardium

JOSEPH E. BAVARIA*, SATOSHI FURUKAWA*,

GERHARD KREINER*, MARK B. RATCLIFFE*,

DANIEL K. BOGEN* and L. HENRY EDMUNDS, JR.

Philadelphia, Pennsylvania

We tested the hypothesis that oxygen (0₂) consumption increases after reversible myocardial ischemia. Left ventricular (LV) 0₂ consumption (LV02) before and after 20 minutes of warm (37°C) ischemia was related to the integral of LV systolic wall stress (SSI) at different afterloads in 16 sheep. LV coronary blood flow (CBF) was measured by ultrasonic Doppler and coronary sinus 0₂ saturation by fiberoptic oximetry. LV pressure was measured directly by Millar catheter; LV volume and wall thickness was calculated from sonomicrometry measurements (4 axes) using an ellipsoid model. Afterload was varied by partial inflation of a descending thoracic aortic balloon. Animals were cannulated for cardiopulmonary bypass; preishemic measurements were obtained (n=129); bypass was started; the aorta was clamped 20 min. (CBF = 0); and 89 measurements were obtained 45-90 minutes after release of the aortic clamp. LV wall stress throughout systole (SSI) was calculated and integrated from continuous computer generated LV pressure and volume measurements (mmHg*sec). LV02 (ul/100gm/beat) was olotted as a function of SSI for ore- and DOstischemic hearts.

	Regression Equation	n	r-value
Preischemic:	LV02 = 1.15 (SS) + 18.3	129	0.78
Postischemic:	LV02 = 4.35 (SSI) + 5.6	89	0.65

LV02 is linearly related to SSI in both pre- and postischemic hearts. However, the 378% increase in slope (p = .005) indicates a massive increase in 0₂ consumption of postischemic "stunned" myocardium, severe impairment of 0₂ utilization efficiency and increased vulnerability to ischemic necrosis if coronary vessels are diseased.

*By Invitation

F4. Augmenting Intracellular Adenosine Improves Postischemic Myocardial Recovery

STEVEN F. BOLLING*, LARRY E. BIES*,

KIM P. GALLAGHER* and EDWARD L. BOVE

Ann Arbor, Michigan

The use of cardioplegia during surgically-induced ischemia greatly reduces myocardial metabolic requirements. However, adenosine triphosphate (ATP) depletion may occur, resulting in poor functional recovery after ischemia. This study investigated if augmenting intracellular adenosine by delivering exogenous adenosine or by inhibiting adenosine degradation with 2-deoxycoformycin (DCF, a non-competitive inhibitor of adenosine deaminase), during cardioplegic arrest, could enhance myocardial functional and metabolic recovery following ischemia. Isolated, perfused rabbit hearts were subjected to 120 minutes of hypothermic (34 °C) cardioplegic-induced ischemia. Controls received St. Thomas cardioplegia (CTL); remaining hearts received cardioplegia containing 200 mM adenosine (ADO), or 1 mM DCF or combined ADO/DCF. Functional results are 45 min after reperfu-sion, (mean ± SEM,*p < .05 vs CTL):

	N	(%DP)	ΔEDP/ΔEDV	CK-loss (IU/L)
CTL	23	38 ± 4	74 ± 10	424 ± 11
ADO	10	66 ± 7*	41 ± 6*	105 ± 11*
DCF	8	59 ± 2*	52 ± 4*	188 ± 10*
ADO/DCF	10	75 ± 2*	31 ± 1*	104 ± 9*

Following ischemia and reperfusion, recovery of developed pressure (%DP) and post ischemic diastolic stiffness (AEDP/AEDV, the slope of linear end-diastolic pressure-volume curves) was significantly better in treated hearts when compared with control. Creatine kinase (CK) loss, a reflection of ATP wastage, was less in all treated hearts. To determine if ADO or DCF minimized depletion of ATP during ischemia or accelerated repletion of ATP in the postischemic period, Nucleotide levels were obtained before, during and after ischemia. Metabolic results show myocardial adenosine (AD) and ATP as mM/mg protein, (mean ± SEM,*p<.05 vs. CTL).

	Baseline		Ischemia		1 min p reflow		15 min p reflow
	AD	ATP	AD	ATP	AD	ATP	AD	ATP
CTL	2.2 ± .04	2. 3 ± .01	2.0 ± .12	0.8 ± .01	1 .9 ± .05	1.8.05	1 .5 ± .07	1.3 + .19
ADO	2.4 ± .06	2.6 ± .11	5.6 ± .17*	0.8 ± .04	5.9 ± .09*	5.9 ± .05*	4.0 ± .11*	6.9 ± .07*
DCF	2.0 ± .13	2.2 ± .09	2.9 ± .09*	0.8 ± .01	3.1 ± .06*	2.4 ± .06*	2.9 ± .06*	2. 7 ± .05*

During ischemia, ATP fell equally in all groups, indicating that ADO and DCF did not alter ischemia-induced depletion of ATP. However, intracellular adenosine was augmented in treated hearts. Consequently, during reperfusion ADO and DCF hearts had significantly enhanced ATP levels suggesting that augmenting myocardial adenosine accelerated repletion of ATP postischemia. In conclusion, adenosine and DCF augment intracellular adenosine and allow better metabolic ATP repletion following ischemia, improving post ischemic myocardial functional recovery.

*By Invitation

F5. Increased Tolerance of the Immature Myocardium to Hypoxia and Ischemia by Intravenous Metabolic Support

PIERRE L. JULIA*, EDWARD R. KOFSKY*,

GERALD D. BUCKBERG, HELAN I. BUGYI*

and HELEN YOUNG*

Los Angeles, California

Hypothesis: A substrate enriched intravenous solution increases tolerance of the immature myocardium to acute hypoxia and allows a better recovery after subsequent ischemia.

Methods: Thirteen neonatal puppies (2-4 kg) underwent one hour of acute hypoxia (pO₂ = 25 to 30 mmHg), followed by 45 minutes of normothermic global ischemia on total vented bypass and normal blood reperfusion. Ventricular function was assessed by inscribing Starling function curves and measuring stroke work indices (SWI) before hypoxia and after reperfusion. Seven puppies (control), received normal saline infusion at 4 cc/kg/hour. Six other puppies received a 4 cc/kg/hour intravenous infusion of Glutamate/ Aspartate, Glucose Insulin Potassium, Mercaptopropionylglycine (MFC), Carnitine and Catalase, during hypoxia and reperfusion.

Results: In control hearts, acute hypoxia depleted myocardial glutamate and Aspartate by 52%* and 48%* caused severe hemodynamic deterioration (55% decrease of SWI)*; three of seven (43%) required premature institution of bypass. Post-ischemic LV function recovered to only 40% of control levels*. In contrast, IV metabolic infusions maintained tissue Glutamate** and Aspartate** in treated hearts during hypoxia, and allowed cardiac index to raise 20%*; all treated hearts tolerated 1 hour of hypoxia, and stroke work recovered 70%** of SWI after subsequent ischemia.

Conclusions: Imparied tolerance of immature hearts to acute hypoxia and subsequent ischemia is due to substrate depletion. This impairment can be reduced by intravenous metabolic support during hypoxia and reperfusion and leads to improved recovery of post-ischemic function.

*p<0.05 vs pre-hypoxia,**p<0.05 vs control group

*By Invitation

F6. Leukocyte Depletion Ameliorates Free-Radical Mediated Lung Injury Following Cardiopulmonary Bypass

KO BANDO*, RAVI PILLAI*, DUKE E. CAMERON*,

JEFFREY D. BRAWN*, JERRY A. WINKELSTEIN*,

GROVER M. HUTCHINS*, BRUCE A. REITZ and

WILLIAM A. BAUMGARTNER

Baltimore, Maryland

Activated leukocytes and oxygen free radicals have been implicated in the pathogenesis of lung injury following Cardiopulmonary bypass (CPB). To determine whether leukocyte depletion could prevent this injury, a dog model simulating routine cardiac surgery was used. Mongrel dogs (11-17 kg) were placed on Cardiopulmonary bypass using a bubble oxygenator and cooled to 27°C. Following aortic cross-clamping and cardioplegic arrest for 90 min, animals were rewarmed, weaned from CPB, and stabilized for 90 min. Control animals (n = 5) were perfused on CPB with whole blood. Leukocyte-depleted (LD) animals (n = 5) had a leukocyte filter incorporated in the CPB circuit. Pre-CPB leukocyte counts (WBC) were similar in the groups. On CPB, WBC decreased by 64% in controls and by 97% in LD animals. After CPB, LD resulted in less intrapulmonary leukocyte sequestration, as determined by the difference in right and left atrial WBC counts. 90 min after CPB, WBC returned to pre-CPB levels in controls, but remained low in the LD group. Free radical activity was assayed by spectrophotometric measurement of plasma conjugated dienes and was significantly reduced by LD. Pulmonary function [paOj on Fi0₂=1, extravascular lung water (EVLW), pulmonary vascular resistance (PVR)] 90 minutes after CPB was better preserved in LD animals; only controls had histologic evidence of in-travascular leukocyte aggregation, perivascular hemorrhage, and focal alveolar injury.

WBC						Lung Function
	Pre-CPB	On CPB	Posl-CPB	RA-LA	Free Rad Act	PaO2	EVLW	PVR
Control	6753 ± 638	2432 ± 197	6048 ± 817	1320 ± 217	287 ± 16	13.2 ± 1.0	607 ± 80
LD	6534 ± 712	191 ± 76*	747 ± 160*	220 ± 45*	1.06 ± .06*	443 ± 23*	8.2 ± 0.5*	126 ± 33*

(Values are mean ± SEM;*p<0.05 compared to control; WBC in cells/mm³; Free Radical Activity in absorption units @ 233nm 30 minutes after CPB; paO₂ in torr; EVLW in cc/kg; PVR in dynes sec cm^-5)

These data suggest that circulating leukocytes contribute to lung injury during CPB and are associated with increased oxygen radical activity, pulmonary edema, and vasoconstriction. Leukocyte depletion substantially reduces the pulmonary injury seen after CPB.

*By Invitation

F7. Nuclear Scan Guided Rib Biopsy

DARROCH W.O. MOORES*, BRUCE LINE*,

STANLEY W. DZIUBAN* and MARTIN F. McKNEALLY

Albany, New York

The bone scan is a sensitive screening device which is frequently used to stage patients with known or suspected malignancy. An abnormal bone scan is associated with corresponding normal radiographs in approximately 50% of cases. Definitive tissue diagnosis of the bone lesion is often needed to determine optimal therapy, but localization of the lesion is imprecise unless it is palpable. Use of the nuclear scan to localize and mark the rib enhances the precision of the biopsy procedure.

Thirty-three consecutive cancer patients with suspicious rib abnormalities on bone scan underwent nuclear scan guided biopsy. Each patient had a repeat localizing scan with TC-99 MPD radionuclide on the day of the planned biopsy. The site of abnormality was marked with methylene blue injected into the skin overlying the lesion and down to the periosteum at the specific site. The patient was then taken to the operating room and underwent excision of the marked area, through a small incision.

Pathological abnormality was identified in all but one of the resected specimens, an accuracy of 97%. Despite a presumed or proven diagnosis of cancer in 33 patients, 16 specimens (48%) showed benign pathology. There were no complications associated with this technique which reduces the morbidity and increases the precision of rib biopsy.

*By Invitation

F8. Combination Immunotherapy Using Low Dose Interleukin-2 (IL-2) and Tumor Necrosis Factor-Alpha (TNF) for Non-Small Cell Lung Cancer

STEPHEN C. YANG*, LAURIE OWEN-SCHAUB*,

JERE LICCARDELLO*, WAUN K. HONG*,

ELIZABETH A. GRIMM* and JACK A. ROTH*

Houston, Texas

Sponsored by: Clifton F. Mountain, Houston, Texas

The purpose of this study was to define alternative activation pathways for the induction of lymphokine-activated killer (LAK) activity against primary lung cancer cells. Single cell suspensions from 32 fresh surgical non-small cell lung cancer (NSCLC) specimens were tested for natural killer (NK) and LAK susceptibility in a 4-hr ^5lCr-release assay. All tumor samples were sensitive to LAK lysis induced with IL-2 alone. Using a combination of IL-2 and TNF, lytic activity was increased (p<0.01) a mean of 4-fold against 31 of the 32 specimens (range 0.7-16.3). All samples were resistant to lysis by NK cells and TNF alone. We initiated a clinical trial to test the toxicities, anti-tumor efficacy, and immunomodulatory effects of using combination low dose IL-2 and TNF in patients with Stage Illb and IV NSCLC. All patients received a continuous daily I.V. infusion of IL-2 at 1x10⁶ Cetus Units/m² on days 1-5. Seven patients were given a single daily I.M. dose of TNF at 25 /-ig/m² simultaneously with IL-2 on days 1-5 (Level I), with their TNF dose doubled after two cycles. Four patients were started at a TNF dose of 50 /-ig/m² with IL-2 (Level II). These doses of either agent alone were ineffective in previous studies. Treatment cycles were given every 3 weeks. All toxicities were reversible, and patients did not require ICU monitoring during therapy. Measurable tumor regression occurred in three patients (all at level I). In one patient, there was a major clinical response with complete resolution of pulmonary metastasis, which has lasted 7 months. Three patients had radiographic stabilization of disease (mean = 9 weeks) before progression. All patients had augmented LAK and NK activity while on therapy, assessed by in vitro cytolysis of Raji and K562 targets, respectively, with autologous lymphocytes. Phenotypic analysis of these lymphocytes revealed a predominance of CD3+ cells during therapy, with varying levels of CD4 + and CD8 + populations. We conclude that IL-2 and TNF have synergistic efficacy in the treatment of NSCLC.

*By Invitation

F9. Angiogenic Factor: A Possible Mechanism for Neovascularization Produced by Omental Pedicles

RAYMOND CARTIER*, ISABELLE BRUNETTE*,

KAZUHIRO HASHIMOTO*, WILLIAM M. BOURNE*

and HARTZELL V. SCHAFF Rochester, Minnesota

Recent success in single and double lung transplants may be credited to improved immunosuppressive regimens and bronchial omentopexy which reduces the incidence of early dehiscence and late stenosis. To determine a possible mechanism by which omental pedicles protect bronchial anastomoses from ischemia we studied the angiogenic potential of a lipid extract of omentum. A rabbit cornea model was used to quantify neovascularization produced by methanol-chloroform extract of homogenized autologous omentum (AO) or perirenal fat. In 22 anesthetized rabbits, 10 µlof omental lipid extract was injected in the cornea. In each animal the opposite eye was used as a control and was injected with a similar volume of extract prepared from perirenal fat. The side of injection of AO was randomized and was not known to the investigator assessing neovascularization on days 4, 7, 14, and 21 following injection. Neovascularization was measured by a point-counting method of microphotography and was expressed as the surface area (mm2), the relative density (point-count/mm2) and the absolute density (point-count/total surface) of new blood vessels. At day 4 after injection, neovascualrization in corneas injected with AO was significantly (p<.05) greater than control for all the parameters studied; absolute density of neovessel growth induced by AO was 3 times that of control. The angiogenic effect diminished with time, and by 21 days after injection corneal neovascularization was comparable for the two groups. Our results suggest that the lipid fraction of omentum has angiogenic activity which may stimulate neovascularization in ischemic tissues. Lack of sustained activity may be due to washout by neovessels or local tissue metabolism of angiogenic factor(s).

*By Invitation

FORUM ALTERNATE

Improved Myocardial Preservation During Cold Storage for Transplantation Using Substrate Enhancement

CONSTANCE HAAN*, HAROLD L. LAZAR*,

SAMUEL RIVERS*, CHERYL COADY* and

RICHARD J. SHEMIN

Boston, Massachusetts

Cold storage techniques used in cardiac transplantation may result in depressed ventricular function. Previous studies have shown that substrate enhancement with the amino acid L-Glutamate minimizes ischemic damage when added to cardioplegic solutions during ischemic arrest. This study was therefore undertaken to determine whether substrate enhancement with L-Glutamate during periods of cold storage would improve ventricular function in transplanted hearts.

Sixteen rabbit hearts were rapidly excised and perfused with Krebs solution (37°C) on a Langendorff apparatus. Following control measurements of LV function and coronary blood flow, all hearts were arrested with hypothermic (4°C), crystalloid, potassium (28mEq/L) cardioplegia and stored at 3°C for 3 hours. They were then rewarmed and reperfused with Krebs solution for 60 minutes at which time final post-ischemic measurement were made. L-Glutamate (4mM) was added to both the cardioplegic and reperfusate solutions in 8 hearts while 8 others received no L-Glutamate. Results are Mean±SE;*p < .02; + LVEDV = .8 ml; + + MAP = 75 mmHg.

	Glutamate	Non-Glutamate
+dP/dt+ (% recovery)	87 ± 4*	64 ± 4
-dP/dt+ (% recovery)	94 ± 10*	73 ± 5
LVEDP + (mmHg) preischemia vs postischemia	34±3 vs 34 ±5	35 ± 4 vs 56 ± 5*
Coronary blood flow + + (ml/min)preischemia vs postischemia	53±4 vs 49±3	63 ± 2 vs 41 ± 2*

We conclude that the addition of L-Glutamate to hearts during periods of cold storage and subsequent reperfusion results in superior recovery of myocardial contractility, relaxation, compliance, and coronary blood flow. Substrate enhancement with L-Glutamate may become an important addition to cold storage techniques during cardiac transplantation.

*By Invitation

TUESDAY MORNING, May 9, 1989

9:00 a.m. SCIENTIFIC SESSION - HYNES BALLROOM

14. Phrenic Nerve Pacing of the Quadraplegic Patient

JOSEPH I. MILLER, JAMES A. FARMER*,

WILLIAM H. STUART* and DAVID F. APPLE*

Atlanta, Georgia

Phrenic nerve pacing (PNP) is a modality that can be utilized to free a quadraplegic patient (pt) from ventilatory dependency. During a 4 year period (1984-1988), 23 pts with an age range of 17 to 63 years (mean 31 years) underwent implantation of a phrenic nerve (PN) pacemaker because of ventilatory dependency secondary to quadraplegia. Fourteen pts had a unilateral PN implant, and 9 pts had a bilateral PN implant. The time of injury to implant was 12 to 16 weeks. The site of implant was the cervical PN in 13 pts, and thoracic PN in 10 pts. During the past 24 months, only a transthoracic approach has been utilized. Indication for pacing was failure to be weaned from ventilatory support in all pts. Failure to stimulate the PN at implant was noted in 3 pts, despite preoperative testing indicating an acceptable response. There were no deaths, and minor complications developed in 4 pts. Follow-up is available in 21 of 23 pts. Eight pts are completely off the ventilator; 9 pts are markedly improved, but on the ventilator at night; 3 pts are moderately improved; 3 pts showed no response at implant. Three pts required re-exploration for component failure from 6 weeks to 18 months after implant. A complete discussion of the surgical technique, PN testing, and PN training will be presented.

*By Invitation

15. Esophageal Reconstruction for Complex Benign Esophageal Disease

F. HENRY ELLIS, JR. and S. PETER GIBB*

Burlington, Massachusetts

Conservative operations on the esophagus are currently preferred to radical resective procedures for benign esophageal disorders. However, our results after reoperative fundoplication and myotomy procedures are less good than those that follow primary procedures and our results after gastroplasty-fundoplication are suboptimal suggesting that a more radical approach be adopted for selected complex esophageal problems. We have therefore reviewed our experience with such operations to determine whether such an approach is warranted and which operation has the best results.

From January 1970 to October 1988, 32 reconstructive procedures for complex benign esophageal disease were performed representing 6.7% of all operations done for benign disorders of the distal esophagus. The procedures employed were esophagogastrostomy (6), colon interposition (7), and esophagogastrostomy, antrectomy and Roux-Y diversion (19). These 32 patients had undergone a total of 62 prior operations, an average of nearly two per patient. Pertinent associated disorders were achalasia in 11 patients, Barrett's esophagus in 3, one of whom also had scleroderma, and one patient each with scleroderma, lye stricture, diffuse esophageal spasm, and giant leiomyoma. Reconstruction was required because of severe gastroesophageal reflux disease in 26 patients, 20 of whom had an esophageal stricture. Other indications for reconstruction included three patients with esophageal perforation and mediastinitis requiring esophageal defunctioning and one patient each with an infarcted gastroplasty tube, lye stricture, and giant leiomyoma. Esophageal resection was required in 24 patients and two underwent cardiopksty. There was one hospital death and 9 (29%) postoperative complications.

Comparison of the results in the three surgical groups is difficult because of the small sample size. Even so, certain trends are apparent. Persistent reflux constitutes a potential hazard of simple esophagogastrectomy even when combined with fundoplication. Results after colon interposition are somewhat better but may be compromised by anastomotic leakage and resultant stricture formation. Successful relief of reflux and dysphagia coupled with the paucity of postoperative complications characterize the results of resection coupled with antrectomy and Roux-Y diversion. We currently prefer its use in properly selected cases of complex benign esophageal disease.

*By Invitation

16. Maintenance of Hemostasis by Aprotinin During Cardiopulmonary Bypass. High Continuous Versus Low Single Dosage Aprotinin

CH. R.H. WILDEVUUR* L. EIJSMAN*,

K. J. ROOZENDAAL* and W. VAN OERVEREN*

Amsterdam and Groningen, Netherlands

Sponsored by: John W. Kirklin, Birmingham, Alabama

The efficacy of aprotinin to reduce postoperative bloodless after car-diopulmonary bypass (CPB) in routine coronary artery grafting and reopera-tions is well established. Aprotinin appears to preserve the platelet adhesive capacity and to inhibit the intrinsic clotting, kallikrein and fibrinolytic system. The capillary bleeding, which is the main cause of the increased postoperative bleeding after CPB is thought to be a platelet defect, which may be caused by blood-material contact and by proteolytic attack from activated plasmatic systems. These systems as well as platelet adhesive receptors alter mainly during the first 5 minutes of CPB. Therefore it seems of prime importance to overcome this period with protective measures. We studied the efficacy of aprotinin in three groups of patients. Group I received placebo, without aprotinin (n = 28). Group II received aprotinin during the whole operation (6.10⁶ KIU) (n = 28). Group III received aprotinin in the pump prime only (2.10⁶ KIU) (n = 12).

Perioperative bloodless, determined by the loss of hemoglobin (Hb) in gauzes and suction system was 93 g Hb in Group I (placebo) and reduced in the aprotinin treated Groups II and III to 68 and 46 g Hb. respectively (p<0.001). Postoperative bloodloss was dramatically reduced by aprotinin treatment from around 40 g Hb in Group I to 21 and 16 g Hb in Group II and III, respectively (p<0.001). The mean bleeding time increased by 220 seconds in Group I and by 170 and 160 seconds in Group II and III, resp. A consequence of the reduced bloodloss by aprotinin treatment was that the volume and percentage postoperative blood transfusions were reduced by two third. Despite this, the aprotinin treated patients left the intensive care unit with a similar Hb as the placebo patients (6.5 mmol versus 6.4 mmol).

Since administration of a single bolus aprotinin in the prime solution has the same clinical benefit as the continuous infusion of the high dosis, a practical routine application of aprotinin in clinical CPB is envisaged.

10:00 a.m. Intermission - Visit Exhibits

*By Invitation

10:45 a.m. SCIENTIFIC SESSION - HYNES BALLROOM

17. Surgery for Infarct Related Ventricular Septal Defects Improved Early Results Combined with Analysis of Late-Functional Status

PETER D. SKILLINGTON*, ROBERT H. DA VIES*,

KEITH D. DAWKINS*, NEVILLE CONWA Y*,

ROBERT K. LAMB*, DARRYL F. SHORE*,

JAMES L. MONRO*, KEITH ROSS and

ANDREW J. LUFF*

Southampton, England

Sponsored by: Gary W. A kins, Boston, Massachusetts

101 patients (mean age 64.9 years) underwent surgical correction of post infarction ventricular septal defect (VSD) at this institution over a 15 year period (1973-1988). The overall early mortality was 20.8%, although the most recent experience with 36 patients (January 1987 - October 1988) has seen this fall to 11.1%. Factors found to significantly influence early death were:

(1) Site of infarction: Anterior 12.1%, inferior 32.6% (p = .022);

(2) Time interval between infarction and surgery: Less than 1 week 34.1%, over 1 week 10.5% (p = .008);

(3) Cardiogenic shock: Present 38.1%, absent 8.5% (p = .001).

Non-significant variables included pre-operative renal function, age, and concomitant coronary artery bypass.

Of the 80 hospital survivors, eight (8) were subsequently found to have recurrence requiring re-operation with survival in seven (7). Late follow up is 99% complete and reveals an actuarial survival for all 101 patients of 70.3% at 5 years (95% confidence interval (60.6 - 80.0), and 40.0% at 10 years (95% confidence interval 21.7 - 58.4). The functional status of the surviving patients has been analyzed by a graded treadmill exercise protocol, whilst left ventricular functional assessment was by nuclear scan (ejection fraction calculated by M.U.G.A.), with additional information on miral and tricuspid valve function by echocardiogram. Colour Doppler has been used to determine the presence of residual V.S.D.

The findings are that most late survivors have limited exercise tolerance related to both cardiac and non-cadiac factors. Left ventricular function is moderately impaired (mean ejection fraction = 0.38). However, many patients are elderly and have adapted to their residual symptoms without significant changes to their lifestyle.

*By Invitation

18. Cardiogenic Shock: A Medical/Surgical Emergency

BRADLEY S. ALLEN*, ELIOT R. ROSENKRANZ*,

GERALD D. BVCKBERG, JAKOB DAVTYAN*,

HILLEL LAKS and DAVIS C. DRINK WATER*

Los Angeles, California

Five years ago we reported our initial encouraging experience using warm (37°C) amino acid enriched blood cardioplegia induction in patients undergoing emergency CABG for cardiogenic shock. The use of aspartate/ glutamate blood cardioplegia allows for resuscitation of the heart with reversal of the LV power failure unlike medical therapy where hospital mortality is > 90% without operation. This report a) confirms these results in a larger population (78 patients) with up to 6 years follow-up, b) emphasizes operative strategy, and c) identifies predictive clinical characteristics of early and late mortality to improve patient selection and timing of operation in this otherwise fatal disease.

Seventy-eight consecutive patients on maximum inotropic and intra-aortic balloon support underwent emergency CABG (3.4 ± 1* days) post-infarction for severe LV power failure (SWI < 25, LAP > 20 mmHg). All received 37°C glutamate and aspartate blood cardioplegia (BCP) induction, multidose cold (r °C) BCP replenishment and warm BCP reperfusate. Viable areas were grafted first to ensure cardioplegic distribution.

LV power failure was reversed in 94% of patients; 73 of 78 patients had discontinuation of inotropes and intra-aortic balloon. Early mortality (< 30 days) was only 7% (3/45) with early operation (< 18 hours), and rose to 33%** (11/33) if operation was delayed > 18 hours. Six of 14 early deaths were due to progression of pre-op organ failure despite reversal of shock. Thirteen of 64 early survivors died 11 ± 5 months post-operatively of end-stage heart failure (13/78), 17% late mortality. Late mortality after early operation (< 18 hr) was 9.5% (4/42) vs 41% (9/22) after late operation (> 18 hr).** Non-survivors (early and late) had a higher incidence of extending vs acute evolving infarction (12/63 vs 1/15)**, b) longer delay from shock to operation (7/45 vs 20/33)**, more pre-op organ failure (6/27 vs 2/51)** and d) greater incidence of previous infarction (19/41 vs 8/37)**. Thirty-two of 51 late survivors (63%) remain physically active.

We conclude that cardiogenic shock should be considered a medical/ surgical emergency as early operation can reverse LV power failure in most patients. In order to accomplish this, a defined operative strategy using warm induction aspartate glutamate blood cardioplegia is necessary to resuscitate the myocardium. Post-operative mortality (early and late) is due principally to delay of operation leading to progression of preoperative organ failure or progression of underlying cardiac disease if infarction becomes established, "mean ± S.E.,**p<0.05

11:30 a.m. ADDRESS BY HONORED SPEAKER

TRANSPLANTATION OF KNOWLEDGE

Francis M. Fontan, Bordeaux-Pessac, France

12:15 p.m. Adjourn for Lunch - Visit Exhibits

12:15 p.m. Cardiothoracic Residents' Luncheon† - Independence Room, Sheraton

†Admission will be ticket only. Residents will be the guest of the Association.

*By Invitation