A dose-determining trial of heparinase-I (Neutralase) for heparin neutralization in coronary artery surgery.

UNLABELLED: Heparinase-I, a specific heparin-degrading enzyme, may represent an alternative to protamine. We explored the dose of heparinase-I for efficacy and safety in patients undergoing coronary artery surgery. At the conclusion of cardiopulmonary bypass, subjects received 5, 7, or 10 microg/kg of open-label heparinase-I instead of protamine. Activated clotting time (ACT) and its difference from a contemporaneous heparin-free sample (DeltaACT) at 3 min before and 3, 6, and 9 min after heparinase-I determined reversal efficacy. After surgery, we recorded hourly chest tube drainage. Systemic and pulmonary arterial blood pressure and cardiac output measurements before and immediately after heparinase-I were used to evaluate hemodynamic safety. Coagulation measurements included anti-factor Xa and anti-factor IIa activities. Forty-nine patients from seven institutions participated: 12 received 5 microg/kg, 21 received 7 microg/kg, 4 received two doses of 7 microg/kg, 8 received 10 microg/kg, and 4 received two doses of 10 microg/kg. Treatment groups did not differ demographically. Median DeltaACT 9 min later was 11, 7, and 4 s for the 5, 7, and 10 microg/kg groups, respectively. No adverse hemodynamic changes occurred with heparinase-I administration. The authors conclude that heparinase-I effectively restored the ACT after cardiopulmonary bypass. This effect appeared to be dose dependent. IMPLICATIONS: Heparinase-I (Neutralase(TM)) successfully restored activated coagulation time with no adverse hemodynamic events in patients undergoing coronary artery surgery with cardiopulmonary bypass in an open-label dose-determining trial.

Open versus endoscopic saphenous vein harvesting: wound complications and vein quality.

BACKGROUND: The saphenous vein is an important conduit for coronary artery bypass grafting. Wound complications from traditional open vein harvesting occur often. Minimally invasive endoscopic saphenous vein harvesting may decrease wound complications. Vein quality may be an issue with endoscopic harvesting. METHODS: We reviewed 568 patients who had bypass grafting and saphenous vein harvesting either endoscopic (group A, n = 180) versus open (group B, n = 388). Both groups were demographically similar and management identical. Wound complication was defined by the need for intervention and included lymphocele, hematoma, cellulitis, edema, eschar, and infection. Multiple vein segments were obtained from 8 patients, 4 from each group, and examined histologically. RESULTS: Wound complications were significantly less in group A (9/180, 5%) versus group B (55/388, 14.2%), p value equal to or less than 0.001. Open harvesting (p< or =0.001), diabetes (p< or =0.001), and obesity (p< or =0.02) were risk factors for wound complication by univariate analysis. By multiple logistic analysis, open harvesting (p< or = 0.0007) and diabetes (p< or =0.0001) were independent risk factors for wound infection. Histologic evaluation of vein samples showed that there was no difference between the groups and vascular structural integrity was maintained. CONCLUSIONS: Endoscopic saphenous vein harvesting was associated with fewer wound complications and infections. Vein quality was not adversely effected because of endoscopic harvesting.

Effects of cardioplegic arrest on left ventricular systolic and diastolic function of the intact neonatal heart.

The effects of cardiopulmonary bypass and cardioplegic arrest on left ventricular systolic and diastolic function were studied in 20 intact neonatal lambs instrumented with ultrasonic dimension transducers and micromanometers for collection of left ventricular pressure-dimension data. Group I lambs underwent 2 hours of hypothermic cardiopulmonary bypass (25 degrees C) alone; group II lambs underwent 2 hours of hypothermic cardiopulmonary bypass (25 degrees C) with 1 hour of multidose, cold, crystalloid cardioplegic arrest (St. Thomas' Hospital No. 2 solution). The control neonatal lamb left ventricle was found to be relatively stiff, with the limit of diastolic filling reached at physiologic left ventricular filling pressures, resulting in apparent descending limbs of left ventricular function. After cardiopulmonary bypass, identical results were obtained in groups I and II. A significant loss of left ventricular compliance limited left ventricular performance via two mechanisms. First, left ventricular preload was significantly decreased, with a concomitant diminution in left ventricular stroke work; afterload (pressure work) was maintained at the expense of volume work (flow), which declined significantly. Second, preload behaved as though fixed, resulting in a loss of impedance matching (afterload mismatch). Although contractility as assessed by the end-systolic pressure-dimension relationship was significantly increased (because of increased levels of circulating catecholamines), global systolic performance as quantified by the stroke work/end-diastolic length relationship remained unchanged, reflecting the afterload sensitivity of the latter parameter in the face of fixed preload. We conclude that cardiopulmonary bypass in the intact neonate results in a loss of compliance and impedance matching rather than a loss of contractility; however, the addition of 1 hour of cold, crystalloid cardioplegic arrest results in no dysfunction beyond that attributable to cardiopulmonary bypass alone.

15- to 30-year follow-up of patients undergoing repair of ruptured congenital aneurysms of the sinus of Valsalva.

Rupture of a congenital aneurysm of the sinus of Valsalva is a rare congenital cardiac malformation. Between 1956 and 1971, we operated on 14 patients aged 9 to 36 years (median, 20 years) for repair of a ruptured aneurysm of the sinus of Valsalva, and have followed each patient to the present. Two operative and 4 late deaths occurred, 3 following a second cardiac operation and the other from dysrhythmia. Late complications have included development of complete heart block in 2 patients (necessitating permanent pacemaker insertion 11 and 24 years after initial repair), progression of aortic regurgitation in 2 (necessitating valve replacement 9 and 13 years after initial repair), and endocarditis in 1 patient 20 years after repair. Four of the 8 remaining long-term survivors (followed for 15 to 30 years [mean, 23.6 years]) are in New York Heart Association (NYHA) Class I, and the other 4 are in NYHA Class II. Three of the 5 patients with suture closure (no pledgets or adjacent ventricular septal defect repair) of the ruptured aneurysm of the sinus of Valsalva sustained recurrent rupture and required repeat closure. Whether the lack of prosthetic material to bolster the repair or inadequate resection of redundant aneurysmal fibrous tissue was responsible for these recurrences cannot be stated. Operative management of patients with ruptured congenital aneurysms of the sinus of Valsalva is discussed.

The effects of verapamil on left ventricular function in the presence of beta-adrenergic blockade.

Supraventricular tachyarrhythmias frequently complicate myocardial revascularization. Intravenous administration of verapamil has been effective in terminating these arrhythmias. To determine the effects of verapamil on left ventricular systolic function, we implanted ultrasonic dimension transducers in dogs and, after they had recovered from the operation, studied them while they were awake and unsedated. Intravenous administration of verapamil (0.2 mg/kg) resulted in an elevation of cardiac output above baseline because of reflex-induced tachycardia. Contractility, as measured by the load-independent end-systolic pressure-volume relationship, remained unchanged. When the animals were pretreated with atropine and propranolol, verapamil resulted in a fall in cardiac output and contractility. The intact animal responded to the vasodilatory effect of verapamil by releasing catecholamines to maintain cardiac output and hemodynamic stability. Only when this compensatory mechanism was blocked by a beta-adrenergic blocker do the inherently negative inotropic and chronotropic effects of verapamil become apparent. The clinical ramifications of this finding are of greater importance to the surgeon as more patients receive beta-adrenergic blocking agents up to the time of the immediate preoperative period. We conclude that verapamil should be administered with caution to patients with supraventricular tachyarrhythmias who have been receiving beta-adrenergic blocking agents.

Effects of transplantation on atrioventricular nodal accommodation and hysteresis.

In the present study, atrioventricular nodal accommodation and hysteresis characteristics were evaluated in awake, unsedated dogs, before (n = 10) and after cardiac transplantation (n = 10). Chronically instrumented animals were atrially paced at a cycle length (CL) of 400 ms, followed by an abrupt decrease in pacing CL to 300 ms, followed by an abrupt return in pacing CL to 400 ms (with pacing sustained for 60 s at each CL). Atrioventricular nodal conduction characteristics (assessed by AH intervals) were simultaneously monitored. Under control conditions, AH intervals lengthened rapidly after an abrupt decrease in pacing CL [mean time for AH interval lengthening to stabilize (Tonset) = 2 +/- 1 s], whereas AH intervals lengthened more slowly (P less than 0.05) after transplantation (Tonset = 41 +/- 4 s). Similarly, after an abrupt increase in pacing CL, control AH intervals shortened rapidly [mean time for AH interval to return to base line (Tonset) = 5 +/- 1 s], whereas AH intervals shortened more slowly (P less than 0.05) after transplantation (Tonset = 42 +/- 5 s). Thus accommodation appears to be an intrinsic atrioventricular nodal response (present after cardiac denervation by transplantation) to abrupt, sustained atrial CL changes. Furthermore equivalence (P = NS) in atrioventricular nodal accommodation responses to symmetric CL decreases and increases after transplantation suggests that hysteresis [i.e., nonequivalence (P less than 0.05) in atrioventricular nodal accommodation responses], as seen under control conditions, results primarily from extrinsic (neural) modification of intrinsic atrioventricular nodal responses to symmetric CL changes.

Left ventricular dysfunction in a canine model of chronic cyanosis.

States of low cardiac output frequently complicate the postoperative course of patients undergoing repair of cyanotic congenital heart lesions. The relative contribution of chronic cyanosis alone to the postoperative deterioration in left ventricular function remains unknown. To study the effects of chronic cyanosis on left ventricular function, nine dogs underwent inferior vena cava-to-left atrial anastomosis, a model that minimizes abnormal left ventricular hemodynamic loads. After at least 6 months of chronic cyanosis (mean arterial pO2 of 44 mm Hg and mean hematocrit of 61%), the dogs were instrumented with ultrasonic dimension transducers and micromanometers for collection of left ventricular pressure-dimension data. Studies were performed 7 to 10 days after recovery from instrumentation while the dogs were awake and alert. Nine normal dogs were also instrumented and served as controls. Pressure and dimension data were collected during transient vena cava occlusions before and after the combined administration of propranolol and atropine to produce autonomic blockade. Contractile function as measured by dP/dt, ejection fraction, and the stroke work-end diastolic length relationship was decreased by autonomic blockade to a similar extent in both normal and cyanotic dogs. After autonomic blockade, normal dogs were able to maintain stroke volume and cardiac index by utilization of Frank-Starling reserves (increased left ventricular end diastolic volume). In contrast, dogs with cyanosis were unable to maintain stroke volume and cardiac index or to increase left ventricular end diastolic volume after autonomic blockade. Dogs with cyanosis had reduced ventricular diastolic compliance, and they more fully used Frank-Starling reserves to maintain normal stroke volume and cardiac index in the control state when compared with normal dogs. The diminished preload reserves of the cyanotic dogs limited systolic performance (stroke volume and cardiac index) only at reduced levels of contractility produced by autonomic blockade.

A review of the pharmacology and clinical uses of ivermectin.

The avermectins were introduced in 1981 and constitute a potent new class of anthelmintic agents. They are naturally-derived products of microbial action displaying an exceptionally wide range of antiparasitic efficacy against internal and external parasites of domestic animals. This paper reviews their isolation and chemistry, mechanism of action, chemical efficacy and safety in cattle, sheep, swine, horses and dogs.

Central aorta-pulmonary artery shunts in neonates with complex cyanotic congenital heart disease.

Methods of palliating critical pulmonary oligemia in neonates with complex cyanotic congenital heart disease continue to evolve. Pulmonary artery distortion and other complications of the use of native vessels to increase pulmonary blood flow has led to the more frequent use of polytetrafluoroethylene shunts either in a central position or as a modified Blalock-Taussig shunt. Central aorta-pulmonary artery shunts have largely fallen into disfavor because of previously reported unacceptably high incidences of complications such as shunt thrombosis, congestive heart failure, and pulmonary artery distortion. This report details our experience palliating 23 neonates with pulmonary atresia or severe pulmonary stenosis by placing central aorta-pulmonary artery shunts utilizing a short segment (less than 1 cm) of polytetrafluoroethylene. Although three of the 23 died postoperatively, none of the 23 patients had evidence of shunt thrombosis. Congestive heart failure, a potential complication of any pulmonary artery shunt, was present in eight of the 20 survivors but did not require shunt takedown and was readily controlled by digoxin. Repeat catheterization was performed in 12 patients; pulmonary angiography showed good growth of both pulmonary arteries and there was no evidence of pulmonary artery hypertension. Although minor pulmonary artery distortion was present in two patients, this distortion was centrally located and easily remedied at the time of total correction. Thus we have found the central aorta-pulmonary artery shunt to be an extremely effective and reliable means of palliating pulmonary artery hypoplasia as a result of pulmonary atresia or severe pulmonary stenosis in neonates.

Potentiation of cardiac electrophysiologic effects of verapamil after autonomic blockade or cardiac transplantation.

Cardiac electrophysiologic effects of verapamil in vivo are the result of both direct and indirect actions on the heart (the latter due to augmentation of sympathetic neural tone, diminution of parasympathetic neural tone, and increased circulating catecholamines). In this study we assessed the interaction of verapamil's direct and indirect actions on electrophysiologic properties of the heart in awake, previously instrumented, unsedated dogs. After administration of intravenous verapamil (0.2 mg/kg), electrophysiologic effects were assessed serially over a 1 hr period in 10 awake dogs before (group 1 studies) and during pharmacologic autonomic blockade (group 2 studies), and in a subset of these dogs (n = 5) after orthotopic cardiac transplantation (group 3 studies). In group 1 dogs, sinus cycle length (SCL) initially shortened after verapamil (postverapamil 379 +/- 50 msec vs baseline of 494 +/- 72 msec, p less than .001) and subsequently gradually prolonged. In groups 2 and 3, transient SCL shortening was absent. SCL prolonged promptly after verapamil, and sinus arrest developed in two of 10 group 2 and two of five group 3 animals. Verapamil exerted a negative dromotropic effect on atrioventricular node conduction in all three experimental groups, as assessed by drug-induced changes in minimum cycle length with sustained 1:1 atrioventricular conduction and measurements of atrioventricular node effective and functional refractory period. However, compared with findings in group 1, this negative dromotropic effect occurred more rapidly and was markedly potentiated in groups 2 and 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Giant gastric ulcers. A review of 49 cases.

Traditional therapy for giant gastric ulcers (greater than 3 cm) has been gastric resection because of a presumed high risk of hemorrhage and recurrence. To determine the validity of this approach and decide whether the need for resection has been altered by the introduction of H2-blockers, the records of 10,054 gastroduodenal endoscopies performed between 1971 and 1984 were reviewed. Forty-nine patients with giant gastric ulcers were identified. Five patients had malignant ulcers. Ten patients underwent gastric resection as initial therapy. Thirty-four patients were initially treated without surgery and were divided into Group I (no H2-blockers; 9 patients) and Group II (H2-blockers; 25 patients). Medical therapy was successful in three of nine patients (33%) in Group I and in 20 of 25 patients (80%) in Group II. Of 11 patients who failed medical therapy (7 intractability, 3 recurrence, and 1 fatal hemorrhage), 10 underwent subsequent gastric resection. Of the 20 patients treated surgically (10 initial and 10 medical failures), none were readmitted for recurrent ulcer disease. These data suggest that medical therapy of benign giant gastric ulcers is often effective and not associated with an excessive incidence of complications, as believed. Successful healing of these ulcers is greatly enhanced when H2-blockers are employed. Thus, the presence of an uncomplicated benign giant gastric ulcer is not an absolute indication for gastric resection.

Pancreatic islet cell carcinoma with gastrin and vasoactive intestinal polypeptide production.

The case history of a patient with an islet cell carcinoma, which produced both gastrin and vasoactive intestinal polypeptide (VIP), is presented. Although several examples have been observed of the combined production of these hormones by pancreatic endocrine tumors, few reports have related the clinical details of such cases. Resolution of diarrhea occurred in our patient after institution of nasogastric suction and cimetidine therapy, suggesting that gastric hypersecretion, rather than VIP activity, accounted for this problem. Chemotherapy with streptozotocin and 5-fluorouracil was highly effective in ameliorating clinical symptoms, diminishing serum levels of gastrin and VIP, and greatly reducing the bulk of metastatic disease in this case.