WEDNESDAY MORNING, MAY 3, 1972

8:30 A.M. Scientific Session: THORACIC SURGERY FORUM

Los Angeles Ballroom

31. Normothermic Anoxic Arrest of the Heart: Is There a Means for Estimating the Safe Period?

DAVID C. MACGREGOR*, VIRENDRAMEHTA*, MILAN KRAJICEK*,

JAN KRYSPIN* and ALAN S. TRIMBLE, Toronto, Ontario, Canada

Normothermic anoxic arrest of the heart has been widely used in open-heart surgery. There is a considerable amount of concern that this technique has a deleterious effect on the myocardium. We have attempted to develop a method of predicting the "safe period" of such an arrest by applying a polarographic technique.

Fifty mongrel dogs were placed on total cardiopulmonary bypass and normothermic anoxic arrest was produced by cross-clamping the ascending aorta and venting the left ventricle. Using a unipolar platinum electrode inserted into the left ventricular myocardium, a biphasic constant current pulse was applied at one minute intervals and the resulting decay curves were recorded graphically. It was noted that a steady state was reached within 15 minutes. The maximum estimated tolerance time for 100% resuscitability of the heart was found to be a multiple of five times the period taken for the curves to reach a steady state. At a multiple of six times, only 50% of the hearts could be resuscitated and at eight times, none.

We feel that this technique may provide an estimate of the safe period of anoxic cardiac arrest clinically. Preliminary studies have shown that similar types of decay curves can be produced in the human heart.

*By Invitation

32. The Reversibility of Acute Myocardial Ischemic Injury by Restoration of Coronary Flow

CHARLES M. O'BRIEN*, MARY CARROLL*, P. T. O'ROURKE*,

E. L. RHODES*, OTTO GAGO*, JOE D. MORRIS and

HERBERT E. SLOAN, Ann Arbor, Michigan

The role of time in the reversibility of acute myocardial ischemic injury by restoration of coronary blood flow was studied in 20 dogs. The anterior descending coronary artery was occluded for one and two hours followed by release of the occlusion for two hours. Control animals were sacrificed after either one or two hours of occlusion. Rubidium⁸⁶ was injected into all animals prior to sacrifice, and specimens of left ventricular wall were examined to determine the uptake of Rb . Left ventricular specimens were examined histochemically to demonstrate various aerobic enzymes. None of the dogs with gross infarcts demonstrated by nitroblue tetrazohum (NET) stain revealed any significant histochemical changes when compared to non-ischemic myocardium. The metabolic injury responsible for the demonstration of infarction by NBT stain within two hours of coronary occlusion is not due to decreased activity of the enzymes studied. The metabolic injury produced by one hour of ischemia as determined by Rb⁸⁶ uptake is reversed by restoration of coronary flow for two hours. Although the metabolic injury produced by two hours of ischemia is not reversed by two hours of restored circulation, the lack of histochemically demonstrable enzyme changes leaves open the possibility of the reversibility of this ischemic damage with a longer period of restored coronary flow.

*By Invitation

33. Changes in Vein Grafts Following Aortocoronary Bypass Induced by Pressure and Ischemia

WILLIAM R. BRODY*, Stanford, California, WILLIAM W. ANGELL*

and JON C. KOSEK.*, Palo Alto, California

Sponsored by Norman E. Shumway

Several reports of histologic changes m saphenous vein grafts used for aortocoronary (A/C) bypass have described proliferative and fibrotic changes leading to graft sclerosis and eventual thrombosis. This study reports the influence of pressure and ischemia in producing similar changes in A/C grafts m dogs.

Thirty dogs underwent A/C bypass with autologous vein grafts, with specimens obtained from one to 360 days post-op and studied with light and electron microscopy. Serial changes in these grafts consisted of (1) necrosis of medial smooth muscle cells, (2) medial fibrosis, and (3) intimal proliferation.

To isolate the relative contributions of pressure and ischemia to these changes, twenty experimental vein grafts were interposed into the femoral artery or vein in one of four groups

Graft ischemia was produced by interruption of the vasa vasorum by complete dissection of the vein from its surrounding bed. Microscopic examination of graft specimens from Groups A and B (ischemic grafts) showed changes (1) and (2) described above, while Groups A and C (systemic pressure grafts) demonstrated intimal proliferation. Only Group A (both ischemia and systemic pressure) showed all three changes observed in the A/C grafts.

These findings suggest that ischemia, secondary to interruption of the vasa vasorum, is responsible for early necrosis and medial fibrosis observed m A/C grafts, while intimal proliferation appears to be induced by "artenalization" of the vein from systemic pressure.

*By Invitation

34. Graft Flow and Reactive Hyperemia in the Human Heart

NEVILLE BITTAR*, GEORGE G. ROWE*, WILLIAM P. YOUNG,

GEORGE M. KRONCKE*, JOHN D. FOLTS* and

DONALD R. KAHN, Madison, Wisconsin

Graft flow and myocardial reactive hyperemia (MRH) responses were measured in 27 patients following completion of coronary by-pass surgery. MRH was produced by temporary occlusions of the graft and, in several instances, the proximal coronary artery, for periods of 10 and 20 seconds. Fifty-two saphenous grafts were studied. Of 18 grafts to the right coronary artery (RCA), MRH occurred in 11. Average RCA flow was 63 cc/min. There were 23 grafts to the left anterior descending, MRH occurred in 11, and average flow was 88 cc/min. The circumflex graft flow averaged 80 cc/min. and 9 of the 11 grafts showed MRH response. MRH occurred in 18 patients where obstruction was judged on arteriograms to be greater than 90%. MRH was absent with obstruction less than 90%, suggesting this is the degree of critical stenosis at rest. However, there were 9 instances without MRH in spite of 90% obstruction which may be due to inability of resistance vessels to respond further to anoxia, distal obstruction, or errors in judging degree of stenosis. These preliminary studies suggest that MRH responses can be used to test the vasodilator capacity of the coronary beds and ‘may assist in determining the adequacy of revascularization procedures.

*By Invitation

35. Norepinephrine Induced Augmentation of Myocardial Contractility as a Means for Assessing the Immediate Efficacy of Aorta to Coronary Artery Bypass Grafts

ANDREW S. WECHSLER*, CARL GILL*, FRANKLIN ROSENFELDT*,

NEWLAND H. OLDHAM* and DAVID C. SABISTON, JR.,

Durham, North Carolina

In the non-stressed myocardium, it is difficult to demonstrate the immediate effects of an acute aorta to coronary artery bypass graft By studying the intrinsic contractile response of the myocardium to norepinephnne (NE) infusion with an acute bypass graft open and occluded, it was possible to discern salutary effects on the graft not evident in the control state.

Ten dogs were studied 3-5 weeks after placing an ameroid constrictor about the left circumflex coronary artery and ligating a branch of the left anterior descending artery. Myocardial contractility was assessed by the ratio of instantaneous rate of left ventricular pressure rise to a common developed left ventricular pressure (dp/dt / CDLVP) and by extrapolating the plot of contractile element velocity (dp/dt / 32.P) against left ventricular pressure to a point of zero load (V_max).

In each dog studied, contractility was unchanged with the graft open (mean flow 27 ± 2.6 cc/min) or dosed in the control state. However, when NE 0.3 Mg/kg/min was infused, there was a 68% (dp/dt / CDLVP) and 46% (V_max) greater increase in contractility (P < .01) with the graft open (mean flow 76 ± 4.3 cc/min) than with the graft closed, without other demonstrable hemodynanuc differences.

This highly sensitive test is currently being applied to intraoperative assessment of aorta to coronary artery bypass grafts in man.

*By Invitation

36. An Assessment of Intra-Aortic Balloon Pumping (IABP) in Hypovolemic and Ischemic Heart Preparations

KARL T. WEBER*, JOSEPH S. JANICKI*,

ALFRED A. WALKER*, Birmingham, Alabama

Sponsored by John W. Kirklin

IABP has been proposed in the treatment of cardiogemc shock following myocardial infarction. The balloon is positioned in the thoracic aorta and inflation-deflation, or timing, synchronized with the electrocardiogram. The effect of several variables on IABP were examined in seven dogs and fifteen calves and included mean arterial pressure (20-100 mmHg), heart rate (50-180 beats/nun), balloon volume (20, 30, and 40 cc) and timing. Inflation was initiated at the dicrotic notch and continued into early, middle or late isometric systole. Hypovolemia was accomplished with right heart bypass or phlebotomy and acute ischemia with coronary occlusion. IABP evaluation criteria included the augmentation of mean arterial diastolic or coronary perfusion pressure (MADP) and peripheral coronary pressure (PCP) distal to the occlusion, left ventricular stroke volume and mean ejection rate; the control or abolition of premature ventricular contractions, the reduction of tension time index, mean impedance to ejection, and left ventricular end diastolic pressure.

Our findings indicate (1) maximum hemodynamic effectiveness (p < 0.01) occurred with inflation extending into middle to late isometric systole, (2) MADP augmentation was dependent on mean arterial pressure and balloon volume, (3) heart rate did not affect pump performance, and (4) in the acutely ischemic heart, PCP and arrhythmia control during IABP appeared dependent on the collateral bed and MADP.

*By Invitation

37. Hemodynamic and Angiocardiographic Evaluation Following Mustard Procedure for Transposition of the Great Arteries (TGA)

JOHN R. MORGAN*, B. LYNN MILLER*, GEORGE R. DAICOFF,

and E. JAMES ANDREWS*, Gainesville, Florida

Between August, 1967, and September, 1970, 24 patients ranging in age from six months to 18 years had correction of TGA by the Mustard procedure and the following associated lesions: nine ventricular septal defects (VSD), ten instances of valvar and subvalvar pulmonary stenosis (PS). The operative mortality rate was 29%.

Sixteen of the 17 survivors underwent postoperative cardiac catheterization and angiocardiography. Only one patient showed significant superior vena cava obstruction by catheterization study which was unsuspected clinically but which led to modification of the surgical technic. One patient had a moderate sized, Indirection shunt about the atrial baffle. No patient had pulmonary venous obstruction. Six of the 12 patients had modest elevation of the left atrial pressure. Mild tricuspid valve incompetence was demonstrated in only one of nine patients having right ventricular angiocardiography. Two of four patients with repaired VSD's had small residual shunts. The left ventricular pressure was reduced by surgical relief of the PS. Three patients had evidence of pulmonary vascular disease, two of which had uncomplicated TGA with Blalock-Hanlon procedures performed early in life.

An unexpected and previously undescribed finding was diminished blood flow to the left pulmonary artery in four patients, two of which had near total occlusion.

*By Invitation

38. Replacement of Portions of Canine Esophagus with Composite Prosthesis and Greater Omentum

WILLIAM A. BARNES* and SAVERIO F. REDO, New York, New York

A five centimeter segment of the esophagus was excised and replaced with a polyurethane tube encased in stainless steel mesh. Greater omentum as (1) a free graft and (2) in a vascularized, intact state was sutured completely around the composite prosthesis.

In five animals with free omental graft, the graft necrosed and dogs died in 6-10 days. Until time of death these animals had an apparently unremarkable post-operative course. Of the five animals with vascularized (intact) omentum two died 28 and 69 days after surgery as the result of hermation through the incision in the diaphragm used to bring the omentum into the chest. There was no evidence of leakage at the anastomoses. The composite tube was in place and the omental wrap was intact. Two animals who had been eating well were killed 38 and 75 days postoperatively. The omental wrap was firmly attached to the composite tube, healing was excellent and the esophagus patent throughout. The fifth animal continues to do well 120 days after surgery.

The results indicate that segments of the esophagus may be successfully replaced with the composite tube described, utilizing vascularized (intact) omentum as an omental wrap sutured about the prosthesis. Free omental grafts do not survive and should not be used.

*By Invitation

39. One-Stage Bilateral Allotransplantation of the Canine Lungs: Early Rejection and Prolonged Survival with Immunosuppression

YOSHIO KONDO*, EROL ISIN*, JOHN V. COCKREL*

and JAMES D. HARDY, Jackson, Mississippi

The technical and physiological feasibility of one-stage bilateral lung auto-transplantation has been proven recently in our laboratory. Five dogs are presently alive at 20-24 months postoperatively with only slightly depressed respiratory function (PO₂65-76, PCO₂25-31, pH 7.38-7.45). These experiences have encouraged us to expand the procedure to include allotransplantation. Of 45 dogs receiving bilateral lung allografts simultaneously from unrelated donors, 34 survived over 48 hours, eight received no immunosuppression (control group), and 26 received various combinations of immunosuppressants including azathioprme, methotrexate, predmsolone, methylpredmsolone and ALG (treatment group). In the control group, all dogs died between 3-6 days postoperatively with clinical signs and gross findings of lung edema. Histologic studies revealed extensive evidence of rejection reaction markedly different in grade from the rejection seen in unilateral allografts. In the treated group, onset of rejection was delayed with initial adequate ventilation, 12 of 26 survived 6-177 days, the longest survivor died of late acute rejection, and another is active at 5½ months. Beneficial effects and hazards of immunosuppression, specific for obligatory lung allografts, were demonstrated by functional studies (blood gases, spirometry, cardiac catheterization, EGG, perfusion scan), complications, and biopsy and autopsy studies.

*By Invitation

40. Serial Observations on Immunologically Matched Lung Homografts

JOHN R. BENFIELD, KOICHIRO SHIMADA*, MICHAEL E. PETER*,

BERNARD GONDOS* and GILDON BEALL*, Torrance, California

Differentiation of rejection from infection is a major banner to successful human lung transplantation. To facilitate this critical differentiation, we have adapted a multi-discipline approach to observing failing lung allografts.

Rejection was studied in 12 Immunologically matched immunosuppressed beagle recipients. Serial lung biopsies were examined by light and electron microscopy (EM) and searched for immunofluorescent antibodies. Endobronchial changes were followed by fiberoptic bronchophotography and pulmonary function studies included inhalation and perfusion scanning. An in vitro cytotoxicity assay was developed using donor cells labeled with Cr as targets for recipient effector cells.

Important changes in Type I and Type II alveolar cells were observed by EM. Progressive V/Q derangement with disproportionate deterioration of ventilation was noted as a physiological hallmark of failing transplants. Cytotoxicity assays have not yet reliably correlated with the microscopic cntena of rejection but seem likely to do so. Bronchophotography was helpful in identifying pneumonia and during rejection, characteristic terminal bronchial edema of the recipient's own lung was seen.

We shall show characteristic findings of failing lung transplants with in-halation-perfusion scanning, bronchophotography and lung biopsies. Currently available immunologic aids to identifying pulmonary homograft rejection will be reviewed.

*By Invitation

41. Usefulness of Echocardiography in Patients Undergoing Mitral Valve Surgery

MICHAEL L. JOHNSON*, JOSEPH H. HOLMES*, RICHARD D. SPANGLER*

and BRUCE C. PATON, Denver, Colorado

Echocardiography is of particular value in determining movement of the mitral valve leaflets. Its non-invasive, non-mjunous qualities lend itself to sequential observation in patients undergoing cardiac surgery. Preoperative determination of significant mitral insufficiency of non-rheumatic etiology is possible. Following attempted annuloplasty in one patient with anterior leaflet prolapse, echocardio-graphic tracings obtained within one hour post-surgery demonstrated persistent mitral insufficiency. Prosthetic replacement of the mitral valve was performed at which time dehiscence of the repair was noted. Echocardiography utilizing a gas sterilized transducer applied directly to the heart during mitral commissurotomy in two patients demonstrated a change from severe mitral stenosis to mild stenosis without evidence of prolapse of the anterior leaflet of the mitral valve. In addition, examination of the aortic and tricuspid valve, and the right and left ventricular chambers was obtained during surgery. Disc excursion, opening and dosing velocities were determined in 30 patients with normally functioning mitral valve prostheses. Dysfunction of two disc valves was detected by ultrasound and thrombus formation was confirmed at reoperation. Measuiement of disc movement is accurate to within 0.6 mm. to 1 mm.

*By Invitation

42. The Clinical Application of Low Output Pacemakers

SOL CENTER and PETER TARJAN*, Miami, Florida

A five milliampere demand pacemaker with a proven life expectancy of 30-33 months has been used clinically for the past three years in 112 patients. Sixteen patients received low output pacemakers at the time of initial pervenous implantation, 96 others at the time of reimplantation. Because of the confusion which persists regarding acute and chronic stimulation thresholds, 12 patients had stimulation thresholds measured for 12 days post initial implantation. Current thresholds below 4.0 milliamperes were measured in all. Thresholds 30 days postoperatively measured 1.3-2.6 milliamperes. Chronic stimulation thresholds were measured in 165 patients during a six year follow-up period. Thresholds of 4.0 milliamperes or less were found in 93% of patients at the time of first, second, and third reimplantations. Of 112 patients receiving low output pacemakers, only two required reimplantation of a 10 milliampere pacemaker because of rising thresholds.

Aside from the practicality of low output pacemaker implantation initially, 93% of patients now carrying standard 10 milliampere pacemakers could have low output pacemakers at reimplantation. The advantages are obvious: 1) Longer intervals between operations, 2) lower infection rates which are directly proportional to the number of reimplantations; and 3) decreasing costs.

*By Invitation