Richard N. Edie

Prevalence of Heparin-Associated Antibodies Without Thrombosis in Patients Undergoing Cardiopulmonary Bypass Surgery

BACKGROUND Patients with cardiovascular disease almost invariably receive heparin before cardiopulmonary bypass surgery, which places them at risk of developing heparin-associated antibodies with a risk of thromboembolic complications. This study was designed to determine the prevalence of heparin-induced antibodies in patients before and after cardiopulmonary bypass surgery. METHODS AND RESULTS Plasma from 111 patients was tested before surgery and 5 days after surgery for heparin-dependent platelet-reactive antibodies with a 14C-serotonin-release assay (SRA) and for antibodies to heparin/platelet factor 4 complexes with an ELISA. Heparin exposure after surgery was minimized. Heparin-dependent antibodies were detected before surgery in 5% of patients with SRA and 19% of patients with ELISA. By the fifth postoperative day, there was a marked increase in patients positive on the SRA or ELISA (13% and 51%, respectively; P < .01 for each). Patients who had received heparin therapy earlier in their hospitalization were more likely to have a positive ELISA before surgery (35%; P = .017) and a positive ELISA (68%; P = .054) or SRA (30%; P = .002) after surgery. However, there was no difference in the prevalence of thrombocytopenia or thromboembolic events between the antibody-positive and-negative groups. CONCLUSIONS Approximately one fifth of patients undergoing cardiopulmonary bypass surgery have heparin-induced platelet antibodies detectable before the procedure as a result of prior heparin exposure, and many more develop antibodies after surgery. The absence of an association between these antibodies and thromboembolic complications in this study may be, in part, attributable to careful avoidance of heparin after surgery. The high prevalence of heparin-induced antibodies in this setting suggests that these patients may be at risk of developing thrombotic complications with additional heparin exposure.

Electrophysiologic properties and response to pharmacologic agents of fibers from diseased human atria.

SUMMARY We used standard nicroketrode to record action potentials of human right trial fibers obtained during cardiac surgery, and correlated these potential with dinical and preoperative ECG data. Human atrial fibers were classified as follows: Group A (ten patients) had a maximum diastolic potential (MDP) of −71.4 ± 5.1 mV (mea ± SD), and actin potentials that were primarily fast pe These atria were normal or sdghty dilated. In group B (12 patients) MDP was −50.3 ± 5.7 mV; action potentials were slow responses and the atria were moderately to markedly dilated. Atrial arrhythmias occued in four grop B and no group A patients. The ECG revealed a signfcant (P < 0.005) in P wave duration: group A, 89 ± 3.0 nec; B, 111 ± 6.0 msec. Verapamil, 0.1 mg/L, markedly depre roup B action potentials. Verapamil, 0.1–1.0 mg/L, de only the action potential plateau of group -A. Procanamlde 1–100 mg/L had equivalent effects on fibers of both groups A and B, effects whc were small at dosages of less than 40 mg/L. Procalnamide did ot depress slow response automaticity, but verapamil (0.1–1 mg/L) did.

The cellular electrophysiologic effects of digitalis on human atrial fibers.

We used microelectrode techniques to study the indirect and direct actions of ouabain on human atrial fibers (HAF) obtained from patients with congenital heart disease undergoing open heart surgery. At 15 min of superfusion ouabain, 2 × 10-7M, induced an increase in maximum diastolic potential (MDP), action potential (AP) amplitude and upstroke velocity of phase 0 depolarization (Vmax) and a decrease in AP duration. Spontaneously beating HAF showed a decrease in automaticity. Acetylcholine (3 × 10-6M) induced identical effects on AP characteristics and automaticity. Prior treatment with atropine (1 × 10-6M) blocked these effects of ouabain and acetylcholine. Superfusion with ouabain (2 × 10-7M) for 30 to 90 min resulted in decreased MDP, AP amplitude and Vma., and a further decrease in AP duration. Phase 4 depolarization and spontaneous rate increased and delayed afterdepolarization and tachyarrhythmia occurred. The ACh-like effects of digitalis decrease automaticity and increase MDP of HAF; the direct effects decrease MDP, increase automaticity, and induce tachyarrhythmia occurred. The ACh-like effects of digitalis decrease automaticity and increase MDP of HAF; the direct effects decrease MDP, increase automaticity, and induce tachyarrhythmias.

Perioperative coronary arterial spasm: Long-term follow-up☆

Six patients who survived episodes of coronary arterial spasm occurring immediately after coronary bypass grafting were followed up for 15 to 30 (mean 20) months after operation. In all patients coronary spasm occurred in an unobstructed dominant right coronary artery and caused inferior transmural ischemia. Sudden circulatory collapse occurred in five of the six patients as a consequence of acute coronary spasm. All patients were treated with nitroglycerin followed by nifedipine. No patient has had recurrent angina or other evidence of spontaneous coronary spasm since surgery. Cardiac catheterization studies, including ergonovine maleate testing, were repeated 3 to 12 months after surgery in five of the six patients. The right coronary artery and all bypass grafts were patent in all five. Four patients had new inferior wall motion abnormalities. Ergonovine provoked focal right coronary arterial spasm in one patient. It is concluded that manifestations of coronary spasm after myocardial revascularization range from asymptomatic S-T segment elevation to severe hypotension. These episodes of perioperative spasm may cause myocardial necrosis. Coronary spasm has not recurred in patients who survived perioperative spasm, but some patients may have a continued predisposition to development of coronary spasm late after surgery.

The role of preoperative radial artery ultrasound and digital plethysmography prior to coronary artery bypass grafting

OBJECTIVE Doppler ultrasound and digital plethysmography are used at our institution to determine the suitability of the radial artery for harvest prior to coronary artery bypass grafting (CABG). The purpose of this study is to determine the value of this preoperative evaluation. METHODS A retrospective analysis of non-invasive radial artery testing was performed on 187 CABG patients. Criteria used to exclude radial arteries from harvest were anatomic abnormalities (size<2 mm, diffuse calcifications), and perfusion deficits during radial artery occlusion (>40% reduction in digital pressure, non-reversal of radial artery flow, or minimal increase in ulnar velocity). A questionnaire was used to determine the incidence of postoperative hand ischemia or rehabilitation. RESULTS In 187 patients, 346 arms were evaluated. Ninety-four arms (27.1%) were excluded for harvesting. Anatomical abnormalities included size<2 mm (1.5%), diffuse calcifications (8.7%), congenital anomalies (2.3%), and radial artery occlusion (0.3%). Circulatory abnormalities included non-reversal of flow (7.2%), abnormal digital pressures (5.5%), and inappropriate increase in ulnar velocity (1.7%). A total of 116 radial arteries were harvested. There were no episodes of hand ischemia. No patient required hand rehabilitation. CONCLUSIONS Doppler ultrasound and digital plethysmography identifies both perfusion (14.5%) and anatomical (12.7%) abnormalities that may make the radial artery less suitable as a bypass conduit.

Heparin-induced thrombocytopenia: bovine versus porcine heparin in cardiopulmonary bypass surgery.

BACKGROUND Studies have demonstrated a high incidence of antibodies to heparin/platelet factor 4 complexes, the antigen in heparin-induced thrombocytopenia, in patients after cardiopulmonary bypass surgery. In many hospitals, beef lung heparin has been used historically for cardiopulmonary bypass, and there has been reluctance to change to porcine heparin despite concerns of an increased incidence of heparin-induced thrombocytopenia in patients receiving bovine heparin. METHODS A prospective randomized trial comparing bovine and porcine heparin in cardiopulmonary bypass surgery was conducted. Presurgery and postsurgery heparin antibody formation was studied using the serotonin release assay and a heparin/platelet factor 4 enzyme-linked immunosorbent assay. RESULTS Data available on 98 patients, randomized to receive either bovine or porcine heparin, revealed no significant difference in patient positivity by serotonin release assay (12% in both groups) or by the heparin/platelet factor 4 enzyme-linked immunosorbent assay (29% with porcine and 35% with bovine heparin) postoperatively. There were no significant differences between preoperative and postoperative platelet counts or thromboembolic complications. CONCLUSIONS Our study does not support the belief that bovine heparin is more likely than porcine heparin to induce the development of antibodies to heparin/platelet factor 4.

Original article: cardiovascularHeparin-induced thrombocytopenia: bovine versus porcine heparin in cardiopulmonary bypass surgery

BACKGROUND Studies have demonstrated a high incidence of antibodies to heparin/platelet factor 4 complexes, the antigen in heparin-induced thrombocytopenia, in patients after cardiopulmonary bypass surgery. In many hospitals, beef lung heparin has been used historically for cardiopulmonary bypass, and there has been reluctance to change to porcine heparin despite concerns of an increased incidence of heparin-induced thrombocytopenia in patients receiving bovine heparin. METHODS A prospective randomized trial comparing bovine and porcine heparin in cardiopulmonary bypass surgery was conducted. Presurgery and postsurgery heparin antibody formation was studied using the serotonin release assay and a heparin/platelet factor 4 enzyme-linked immunosorbent assay. RESULTS Data available on 98 patients, randomized to receive either bovine or porcine heparin, revealed no significant difference in patient positivity by serotonin release assay (12% in both groups) or by the heparin/platelet factor 4 enzyme-linked immunosorbent assay (29% with porcine and 35% with bovine heparin) postoperatively. There were no significant differences between preoperative and postoperative platelet counts or thromboembolic complications. CONCLUSIONS Our study does not support the belief that bovine heparin is more likely than porcine heparin to induce the development of antibodies to heparin/platelet factor 4.

Clostridial mycotic aneurysm of the thoracoabdominal aorta : A case report

Clostridial infection of the aorta is a rare and life-threatening condition. The management of a mycotic aneurysm involving the thoracoabdominal aorta due to Clostridium septicum infection is presented. Successful surgical management of the aortic infection involved arterial resection, wide debridement of the surrounding tissues, and in situ graft replacement. Sixteen additional cases of clostridial infection of the aortoiliac segment reported in the literature are also summarized. In ten of these 17 cases, an associated colonic adenocarcinoma was documented.

Basic Fibroblast Growth Factor Identified in Chronically Stimulated Cardiomyoplasties

In the presence of myocardial ischemia, chronic electrical stimulation of a latissimus dorsi (LD) cardiomyoplasty enhances extramyocardial collateral blood flow. We postulated that basic fibroblast growth factor (bFGF) may mediate extramyocardial collateral formation. To test this hypothesis, LDs from goats with cardiomyoplasties were probed for the presence of bFGF by Western blot analysis and immunohistochemistry. Three groups were studied: static LD cardiomyoplasty (group 1); LD cardiomyoplasty stimulated at a 2-Hz frequency for 6 weeks (group 2); and LD cardiomyoplasty electrically stimulated and given human recombinant bFGF (group 3). There was no evidence of bFGF in the left LDs of group 1 by Western blot. Basic fibroblast growth factor-like immunoreactive evidence was found in the left LDs of group 2 goats by both Western blot and immunohistochemistry. In the right LDs of group 2, bFGF-like material was found by immunohistochemistry but not by Western blot, which suggests that the tissue concentrations were low (near the limits of detection). The left LDs of group 3 were positive for bFGF by Western blot and immunohistochemistry. Group 3 right LDs were positive for bFGF by immunohistochemistry. Immunohistochemical findings in group 2 indicate that bFGF is present in goat skeletal muscle. Western blot data from groups 1 and 2 suggest that bFGF may be increased in chronically stimulated cardiomyoplasties. From findings in group 3, we conclude that exogenous bFGF does not downregulate, and may upregulate, endogenous production. These results support the possibility that skeletal muscle bFGF is an important factor in extramyocardial collateral formation.

Techniques to enhance extramyocardial collateral blood flow after a cardiomyoplasty.

ObjectiveChronic stimulation of a cardiomyoplasty was combined with low-dose infusion of heparin into the arterial supply of the cardiomyoplasty in order to determine if latissimus-derived collateral blood flow could be further enhanced. Summary Background DataAcute and chronic stimulation of a latissimus dorsi cardiomyoplasty increased extramyocardial collateral blood flow to 35 ± 9% and 27 ± 5%, respectively, of normal myocardial blood flow. MethodsA model of coronary artery disease was created with an ameroid constrictor in goats, and a cardiomyoplasty was performed. Heparin (15 to 50 U/h) was delivered into the left subclavian artery for a period of 4 weeks. Simultaneously, the latissimus dorsi was chronically stimulated at 2 Hz. ResultsChronic ischemic myocardium received a collateral flow per gram from the skeletal muscle equivalent to 11.8 ± 5.2% of the blood flow to normal myocardium. The extramyocardial collateral flow correlated with the latissimus muscle flow (r = 0.72). ConclusionsEnhancement of extramyocardial collateral flow was not found with heparin treatment. In view of the correlation of extra-coronary collateral flow with latissimus muscle flow, the lack of a heparin effect may have been due to low latissimus blood flow. These results suggest that extramyocardial collateral blood flow to the myocardium is highest if the blood flow to the latissimus dorsi muscle is maintained.