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BACKGROUND A better understanding of altered expression of myocardial beta-adrenoceptors can facilitate the diagnosis of early and late acute rejection of heart transplants. METHODS We submitted rats to heterotopic heart transplantation (iso- and allografts) of which one of each were treated with or without cyclosporin A for 4, 7, and 14 days (n=5, respectively). The cardiac sections were incubated in vitro with [3H]CGP 12177, or the hearts were labeled in vivo by intravenous injection of [3H]CGP 12177. Autoradiographic images of both were analyzed digitally and compared with histologic findings. RESULTS Beta-adrenoceptor distribution in native hearts and isografts was homogeneous, but highly differential distribution and density in allografts were observed in the left and right ventricular walls and in the interventricular septum despite treatment with cyclosporin A. High-density areas in the progressive course of acute rejection are commonly associated with up-regulation of beta-adrenoceptors in apparently viable myocytes, although histologic findings confirmed many infiltrating mononuclear cells. Low-density areas, which were identified in the right and left ventricular walls as early as 4 days after transplantation, correlated with derangement of myocytes, which was suggestive of early acute rejection. The images obtained by in vivo technique were comparable to in vitro images. CONCLUSIONS The alteration of beta-adrenoceptor expression in allografts showed a close relationship with the severity of acute rejection, and the techniques employed in this model were useful in our study of the rejection process and in detecting early and late acute rejection in the rat.

Background . We investigated the effects of cardiopulmonary bypass (CPB) on ileal homeostasis, and the influence of functional inhibition of complement C5a on CPB-induced mesenteric injury. Methods . Pigs were perfused on CPB for 1 hour and then perfused off CPB for an additional 2 hours. Antiporcine C5a monoclonal antibody (C5a MAb) was administered 20 minutes before onset of CPB to 6 pigs; 6 controls received saline vehicle. Total complement activity, ileal myeloperoxidase, and indices of ileal integrity were examined. Results. Treatment with C5a MAb ameliorated CPB-induced abnormalities in endothelium-dependent relaxation to ADP and substance P, and the hypercontractile response to phenylephrine of ileal microvessels (88 to 168 μm). Ileal myeloperoxidase activity [units/g protein] was 41 ± 11 in the C5a MAb group, compared to 83 ± 13 in the saline group (19 ± 10 base line). Total hemolytic complement activity was similar in the C5a MAb and saline groups (0.6 ± 0.2 and 0.7 ± 0.2 CH 50 units). During CPB, ileal mucosal blood flow and mucosal pH, edema formation, and epithelial permeability deteriorated similarly in saline and C5a MAb groups. Inducible nitric oxide synthase (iNOS) mRNA expression was similar before and after CPB. Conclusions. CPB is associated with significant physiologic alterations in mucosal perfusion, epithelial permeability, edema formation, and blood flow regulation. Inhibition of C5a limits neutrophil-mediated impairment of ileal microvascular regulation after bypass, but does not improve extravascular mesenteric dysfunction after CPB.

Background: The purpose of this study was to determine the influence of oxygenation of a hyperkalemic cardioplegic solution (K-CP) on endothelial modulation of vasomotor tone and to correlate these changes with the intracellular calcium concentration ([Ca++]i) in microvascular smooth muscle. Methods: Rat coronary arterioles were studied in a pressurized, no-flow normothermic state. Simultaneous monitoring of luminal diameter and [Ca++]i (fura-2) was performed with use of microscopic image analysis. Vessels were subjected to 60 minutes of oxygenated or hypoxic K-CP (K+ = 25.0 mmol/L) and were then reperfused with oxygenated Krebs–physiologic saline solution for 60 minutes. Results: In oxygenated K-CP, the K-CP–induced contraction and [Ca++]i accumulation were significantly increased in endothelium-denuded (ED) vessels compared with endothelium-intact vessels. The effect of ED in oxygenated K-CP was mimicked by administration of the nitric oxide synthase inhibitor NG-monomethyl-L -arginine. Conversely, in hypoxic K-CP the contraction was significantly attenuated in ED vessels compared with endothelium-intact vessels, although there was no significant difference in [Ca++]i. Indomethacin did not affect the endothelium-dependent contraction during hypoxic K-CP. Conclusions: Endothelium-derived nitric oxide modulates the vascular tone during K-CP by regulating the vascular smooth muscle [Ca++]i, whereas endothelium-derived contracting factor(s), which is not predominantly a product of cyclo-oxygenase, may play a prominent role under hypoxic K-CP by increasing vascular smooth muscle Ca++ sensitivity. (Surgery 1999;126:264-71.)

We examined whether pulmonary endothelial dysfunction associated with cardiopulmonary bypass (CPB) may be mediated by complement C5a in pigs. Pigs were placed on normothermic CPB for 1 h with or without a previous administration of 1.6 mg/kg anti-C5a monoclonal antibody (MAb), then reperfused for 2 h. Pulmonary tissue myeloperoxidase activity was measured. Expression of nitric oxide synthase (NOS) was measured by reverse transcriptase polymerase chain reaction and Western blotting. Pulmonary arterioles approximately 100 m mi n diameter were preconstricted with the thromboxane analog U46619 1 mM, and relaxation responses to adenosine diphosphate 10 29 ‐10 24 M, substance P 10 212 ‐10 26 M, and sodium nitroprusside 10 29 ‐10 24 M were examined in vitro by videomicroscopy. Relaxation to the endothelium-dependent dilators adenosine diphosphate and substance P was attenuated after CPB; this attenuation was prevented by the previous administration of MAb. Relaxation to sodium nitroprusside was not affected by CPB. Neutrophil sequestration, as measured by MPO activity, increased after CPB, either with or without MAb. Transcription of NOS was unchanged by CPB, but translation of constitutive NOS was decreased after CPB, and this decrease was prevented by a previous administration of MAb. We conclude that pig pulmonary endothelial dysfunction associated with CPB may be mediated by C5a. The mechanism may involve changes in NOS translation. Implications: In pigs, pulmonary endothelial dysfunction may occur after cardiopulmonary bypass due to product(s) of complement activation.

Background. Although administration of the sialyl Lewis x oligosaccharide may reduce myocardial injury after ischemia‐reperfusion, its effect on coronary and cerebral microvascular regulation and its clinical application during cardiac operation have not been examined. Methods. Pigs were placed on normothermic cardiopulmonary bypass after 30 minutes of left anterior descending coronary artery occlusion. The hearts were then arrested with cold high potassium cardioplegia. After 1 hour the cross-clamp was removed and the pigs were weaned from cardiopulmonary bypass and perfused for an additional 1 hour. CY-1503 (a sodium salt of the sialyl Lewis X oligosaccharide, n 5 6) was administered before reperfusion. Six other pigs received saline vehicle. Endothelium-dependent relaxation of precontracted coronary and brain arterioles (70 to 180 mm) to adenosine 5*diphosphate and endothelium-independent relaxation to sodium nitroprusside were studied in vitro with videomicroscopy. Control values were obtained from uninstrumented pigs. Myeloperoxidase activity in the myocardium and brain was measured to quantify neutrophil infiltration. Cardiac function and perfusion were assessed by left ventricular systolic pressure, maximum rate of increase of left ventricular pressure, left anterior descending coronary artery blood flow and percent segmental shortening, and cerebral vascular resistance, internal carotid artery blood flow, and the constitutively expressed and inducible isoform of nitric oxide synthase mRNA were measured. Results. The impaired myocardial contractile function after ischemia and cardioplegia was not improved by administration of CY-1503. The reduced endotheliumdependent relaxation responses of coronary and brain arterioles during ischemia followed by cardioplegia and cardiopulmonary bypass were improved with CY-1503, but the altered pattern of organ perfusion was not improved. Myeloperoxidase activity was increased in the heart after ischemia‐ cardioplegia and in the brain after cardiopulmonary bypass. CY-1503 reduced myeloperoxidase activity in both the myocardium and in the brain. Expressions of myocardial inducible isoform or constitutively expressed nitric oxide synthase were not altered in the heart. Conclusions. Although the sialyl Lewis x oligosaccharide does reduce neutrophil infiltration and endothelial injury in the coronary and cerebral microcirculation after cardiopulmonary bypass, it does not have significant beneficial acute effects on organ perfusion or function in the myocardium or brain.

Objectives: The present study was designed to study the effects of a single intrapericardial injection of basic fibroblast growth factor on myocardial vascular resistance and endothelium-dependent microvascular dilatation in a porcine model of chronic myocardial ischemia and to investigate the mechanism of ischemia-induced impairment of endothelium-dependent vasodilatation. Methods : Yorkshire pigs underwent ameroid constrictor placement on the left circumflex coronary artery. At 3 weeks, animals were randomized to a single intrapericardial injection of saline solution (n = 10), 30 μg basic fibroblast growth factor (n = 10), or 2 mg basic fibroblast growth factor (n = 10). Myocardial vascular resistance in the normal (left anterior descending) and ischemic collateral-dependent (left circumflex artery) territories (using colored microspheres) and microvascular reactivity to adenosine diphosphate and sodium nitroprusside were measured before treatment and 4 weeks after treatment. The expression of inducible and endothelial nitric oxide synthase was determined in normal and ischemic myocardium by means of reverse transcriptase–polymerase chain reaction and Western analysis, and the effect of nitric oxide on endothelium-dependent vasodilatation was determined. Results : Compared with results in the control group, treatment with basic fibroblast growth factor resulted in significant improvement in left circumflex artery resistance and endothelium-dependent vasodilatation, reflecting increased collaterals. Myocardial ischemia was associated with increased expression of inducible nitric oxide synthase with no change in endothelial nitric oxide synthase. However, the nitric oxide donor sodium nitroprusside did not affect endothelium-dependent vasodilatation to adenosine diphosphate. Conclusions : A single intrapericardial bolus of basic fibroblast growth factor may be a useful therapeutic strategy for the treatment of myocardial ischemia in patients with coronary artery disease. Although chronic myocardial ischemia is associated with increased expression of inducible nitric oxide synthase, it does not appear to be the cause of altered endothelial function. (J Thorac Cardiovasc Surg 1998;116:1022-8)

Background Cardioplegia is known to affect coronary vascular reactivity. We examined the effects of intermittent cold and continuous warm blood cardioplegia on β-adrenoceptor–mediated, adenosine triphosphate–sensitive K + (K + ATP )–channel–mediated, and endothelium-dependent relaxation and on the myogenic tone of coronary arterioles. Methods Pigs were placed on cardiopulmonary bypass. Hearts were arrested for 1 hour with a cold blood cardioplegic solution administered intermittently (n=12; iCB-CP) or with a warm blood cardioplegic solution delivered continuously (n=12; cWB-CP). Selected hearts (n=6 in each group) were then reperfused for 1 hour. In vitro relaxation responses of precontracted microvessels (50 to 160μm) were studied in a pressurized no-flow state. Results Relaxation in response to isoproterenol (β-adrenergic agonist) was similar after iCB-CP and cWB-CP, whereas forskolin (adenylate cyclase activator)–induced relaxation was impaired more after iCB-CP than after cWB-CP. After reperfusion the respective responses were similar. Both iCB-CP and cWB-CP preserved receptor-mediated, endothelium-dependent relaxation in response to adenosine, 5 * -diphosphate; non–receptor-mediated endothelium-dependent relaxation in response to A23187; endothelium-independent cyclic guanosine monophosphate–mediated relaxation in response to sodium nitroprusside, and K + ATP -channel–mediated relaxation. Relaxations in response to 8-bromo-cyclic guanosine monophosphate (a cyclic guanosine monophosphate–dependent protein kinase activator) and to 8-bromo-cyclic adenosine monophosphate (a cyclic adenosine monophosphate–dependent protein kinase activator) were impaired after iCB-CP alone and after reperfusion, whereas the respective responses were not affected after cWB-CP. Myogenic tone was decreased similarly after iCB-CP and cWB-CP but was not further altered after reperfusion. Cardiac function was similar after iCB-CP and cWB-CP. Conclusions These results suggest that cWB-CP is similar to iCB-CP in its ability to preserve endothelium-dependent relaxation and K + ATP -channel function. The superior preservation of β-adrenergic-cyclic adenosine monophosphate–mediated coronary responses after cWB-CP is brief and associated with minimal improvement of myocardial function and myogenic tone.

Vascular endothelial growth factor (VEGF) has been utilized to improve blood flow in the setting of myocardial or peripheral vascular ischemia. In this investigation we studied the hemodynamic effects of intracoronary VEGF administration. Hemodynamic parameters and Doppler flow wire recordings from the left anterior descending coronary artery were measured after intracoronary infusion of VEGF (1, 10, and 100 micrograms) in 28 intubated pigs. Additional studies were performed using an in vitro isolated microvessel preparation. VEGF produced a highly significant dose-dependent increase in coronary blood flow (maximal 3.51 +/- 0.85-fold) in the absence of significant changes in epicardial artery diameter, a decline in mean arterial pressure (maximal 43%), and a decrease in left ventricular end-diastolic pressure (maximal 52%), all of which could be inhibited by pretreatment with NG-nitro-L-arginine. The increase in coronary flow seen with 10 or 100 micrograms VEGF was significantly greater than the maximal vasodilation achieved with serotonin or nitroglycerin and was equivalent to a maximal adenosine response. In summary, VEGF stimulates nitric oxide (NO)-dependent dilation of coronary microvessels, and repeat administrations of VEGF resulted in rapid development of tachyphylaxis to VEGF as well as serotonin, but not to nitroglycerin or adenosine, which appeared to be secondary to impaired NO production.

We compared the effect of hypermagnesium and hyperkalemic crystalloid cardioplegia on beta-adrenoceptor-mediated and endothelium-dependent relaxation and myogenic responses of coronary arterioles. Pigs were placed on cardiopulmonary bypass. Hearts were arrested with cold hypermagnesium (25 mM Mg2+, hyper-Mg, n = 12) or hyperkalemic (25 mM K+, hyper-K, n = 12) crystalloid cardioplegia for 1 hr. Hearts of selected pigs (n = 6 in each group) were then reperfused for 1 hr. In vitro relaxation responses of acetylcholine-pre-contracted arterioles were studied in a pressurized no-flow state with video-microscopy. Relaxation of pre-contracted coronary microvessels (70-150 microns) to isoproterenol (beta-adrenergic agonist) and forskolin (adenylate cyclase activator) was preserved after cardioplegia using a hyper-Mg solution. In contrast, responses were impaired to isoproterenol [P0.01 (two-factor ANOVA) vs. controls, n = 6] and forskolin (P0.01) after hyper-K cardioplegia. After 1 hr of reperfusion, relaxation responses to isoproterenol and forskolin were partially recovered. Hyper-Mg cardioplegia and post-cardioplegic reperfusion did not affect receptor-mediated endothelium-dependent relaxation to ADP, non-receptor-mediated endothelium-dependent relaxation to A23187, and endothelium-independent relaxation to nitroprusside. However, responses to ADP (P0.01) and A23187 (P0.05) were selectively impaired after hyper-K cardioplegia. Myogenic contraction was impaired after either hyper-Mg or hyper-K cardioplegia. Left ventricular systolic pressure, coronary blood flow, and +dP/dt were similar after hyper-Mg or hyper-K cardioplegia. These results suggest that hyper-Mg cardioplegia is superior to hyper-K cardioplegia in terms of preserving beta-adrenoceptor-mediated and endothelium-dependent regulation of the coronary microcirculation, yet it has minimal if any additional beneficial effect on preserving myogenic responses or myocardial contractile function.

Study objective Acute renal failure, which is a serious complication following open heart surgery, has a high mortality rate. Previous reports have shown that the calcium antagonist diltiazem is beneficial either as an adjunct to cardioplegic solution or perioperative treatment for preservation of postoperative cardiovascular function. We studied the effects of diltiazem on renal function, plasma atrial natriuretic peptide levels, and the renin-angiotensin-aldosterone system in patients who had undergone coronary artery bypass grafting. Patients and measurements Diltiazem was administered, 0.1 mg/kg, in a bolus injection followed by continuous infusion at a rate of 2 μg/kg/min during surgery, and 30 mg through a nasogastric tube at every 8 h. Hemodynamics, renal function, and plasma hormone levels were measured in the diltiazem-treated group (n=13) and the nontreated group (n=10). Results Heart rate, mean arterial pressure, and systemic vascular resistance index in the diltiazem-treated group were significantly lower than those in the nontreated group following cardiopulmonary bypass. Urine volume, creatinine clearance, and free water clearance were well preserved in the diltiazem-treated group. However, plasma renin activity and aldosterone levels were significantly higher in the diltiazem-treated group with the same changes in plasma atrial natriuretic peptide levels. Conclusion Perioperative treatment with diltiazem has a beneficial effect on postoperative renal function, and reflex sympathetic activation induced by peripheral vasodilation activated the renin-angiotensin-aldosterone system.

In canine right ventricular muscle, the influence of ICI 147,798, a slowly dissociable beta 1-adrenoceptor antagonist, on the positive inotropic effect and cyclic AMP production of T-0509, a selective beta 1-agonist, and isoproterenol, a nonselective beta-agonist, were examined to elucidate the properties of the high- and low-affinity states or subtypes of beta 1-adrenoceptor. ICI 147,798 (1 x 10(-8) - 1 x 10(-5) M) produced biphasic concentration-response curves for the positive inotropic effect of T-0509 that were due to its insurmountable antagonism against the lower concentrations of T-0509. The maximum of the biphasic curves were almost the same as Camax. Analysis of hemiequilibrium antagonism by ICI 147,798 against T-0509 showed the dissociation constant (pKB) of ICI 147,798 to be approximately 8. On the other hand, ICI 147,798 produced a parallel rightward shift of the curves of isoproterenol. Schild analysis showed pA2 to be 7.98 +/- 0.04, suggesting competitive antagonism. The concentration-response curve for the increase in cyclic AMP elicited by T-0509 in the presence of 1 x 10(-6) M ICI 147,798 was also biphasic, but slightly depressed as compared with that of control, whereas that elicited by isoproterenol was shifted to the right. The positive inotropy and increase in cyclic AMP produced by T-0509 and isoproterenol in the presence of ICI 147,798 may be mediated by the low-affinity state of beta 1-adrenoceptor, which mechanism may be different from that producing the positive inotropy through the high-affinity state of beta 1-adrenoceptor.

This study was designed to investigate the site of vascular endothelial growth factor (VEGF)-induced vasodilation in the systemic and coronary vasculature. Intracoronary infusion of VEGF in Yorkshire pigs resulted in a significant drop in the mean arterial blood pressure, with a decline in the left ventricular left end-diastolic pressure, and no change in the heart rate. Coronary blood flow increase after intracoronary infusion of 10 mg VEGF (2.63 +/- 0.49x) was comparable to that seen after 40 mg of intracoronary adenosine (2.5 +/- 0.53x, p = 0.67) and was significantly higher then after 200 mg of intracoronary nitroglycerine (1.9 +/- 0.12x, p = 0.0005). At the same time, intracoronary VEGF did not result in a significant increase in coronary cross-sectional area determined using intravascular ultrasound. In vitro, VEGF produced dose-dependent relaxation of myocardial and systemic arterioles and venules (arterioles: 60-100 mm and venules: 120-200 mm in internal diameter) that was partially inhibited by L-NNA, but had no effect on epicardial coronary arteries, systemic arteries, or veins. Both VEGF receptors (flt-1 and flk-1) were identified on endothelial cells of epicardial arteries and veins. We conclude that this spatial heterogeneity of VEGF vasomotor effects cannot be explained by the absence VEGF receptors and suggests differential patterns of signal transduction in the vascular tree.

Objectives: Extensive aortic replacement, such as concomitant aortic root and arch replacement, thoracoabdominal aortic repair, and complete thoracic aorta replacement, remains controversial. We studied surgical morbidity and mortality in patients undergoing concomitant aortic root and arch replacement, and those undergoing secondary replacement of the thoracoabdominal aorta after this preceding procedure.Subjects and Methods: Between January, 1987 and March 1999, 21 patients (mean age: 52 years) underwent concomitant aortic root and arch replacement involving 3 surgical procedures—aortic root replacement with composite graft and arch (n=12), aortic root replacement with valve sparing and arch (n=4), or aortic root replacement with composite graft and arch and elephant trunk (n=5).Results: Overall hospital mortality was 4.8%. Six patients (mean age: 42 years) underwent secondary thoracoabdominal aorta replacement after the concomitant root and arch procedure. The mean time until secondary surgery was 9.5 months. There was 1 hospital death.Conclusion: Concomitant replacement of the aortic root and arch, or secondary replacement of the thoracoabdominal aorta after concomitant root and arch replacement can be conducted with low surgical morbidity and mortality.

Pacemaker implantation in premature infants presents technical problems because of the relatively larger size of the pulse generator compared with their bodies. A new technique with which successful generator implantation was performed in 2 premature infants less than 2,000 g of body weight is described. The generator is wrapped in a Gore-Tex surgical membrane. A piece of membrane overlying the electrical contact surface of the generator is removed, and the generator is fixed to the abdominal wall in the peritoneal cavity. The technique is simple to perform and would give relative ease in generator exchange.

The use of Mg2+-supplemented hyperkalemic cardioplegia preserves microvascular function. However, the mechanism of this beneficial action remains to be elucidated. We investigated the effects of Mg2+supplementation on the regulation of intracellular calcium concentration ([Ca2+]i) and vascular function using an in vitro microvascular model. Ferret coronary arterioles (80–150 μm in diameter) were studied in a pressurized (40 mmHg) no-flow, normothermic (37°C) state. Simultaneous monitoring of internal luminal diameter and [Ca2+]iusing fura 2 were made with microscopic image analysis. The microvessels ( n = 6 each group) were divided into four groups according to the content of MgCl2(nominally 0, 1.2, 5.0, and 25.0 mM) in a hyperkalemic cardioplegic solution ([K+] 25.0 mM). After baseline measurements, vessels were subjected to 60 min of hypoxia with hyperkalemic cardioplegia (equilibrated with 95% N2-5% CO2) containing each concentration of Mg2+([Mg2+]) and were then reoxygenated. During hyperkalemic cardioplegia, [Ca2+]iincreased in a time-dependent manner in all groups. In the lower [Mg2+] cardioplegia groups, [Ca2+]iwas significantly increased at the end of the 60-min cardioplegic period (247 ± 44 nM and 236 ± 49 nM in [Mg2+] 0 and 1.2 mM groups, respectively; both P < 0.05 vs. baseline) with 19.6–17.2% vascular contraction. Conversely, there was no significant [Ca2+]iincrease in the higher [Mg2+] cardioplegia groups and less vascular contraction (5.4–4.1%, both P < 0.05 vs. [Mg2+] 1.2 mM group). After reperfusion, agonist (U-46619, thromboxane A2analog)-induced vascular contraction was significantly enhanced in the lower [Mg2+] cardioplegia groups (both P < 0.05 vs. control) but was normalized in the higher [Mg2+] cardioplegia groups. Intrinsic myogenic contraction was significantly decreased in the lower [Mg2+] cardioplegia groups (both P < 0.05 vs. control) but was preserved in the higher [Mg2+] cardioplegia groups. These results suggest that supplementation of the solution with >5.0 mM [Mg2+] may prevent hyperkalemic cardioplegia-related intracellular Ca2+overloading and preserve vascular contractile function in coronary microvessels.

Clotrimazole (CLT), used in the treatment of patients with sickle cell disease, directly blocks Ca2+-activated K+ (K+INF POS="STACK"Ca) channels in red cells and in portal vein smooth muscle cells by a cytochrome P450(cyt P450)-independent mechanism. Therefore, we examined the effects of CLT on vasomotor tone of coronary arterioles. Rat coronary arterioles (80-180 micro(m) in diameter) were studied in vitro in a pressurized no-flow state with a video microscopy. CLT (0.1 micromol/L) elicited in nonprecontracted vessels a small contraction (10% baseline diameter, P0.05 vs time control), consistent with blockade of a hyperpolarizing K+ channel. However, similar contraction was produced by the cyt P450 blocker 17-octadecynoic acid (17-ODYA, 100 micromol/L), suggesting possible involvement of arachidonate metabolites of cyt P450. In contrast, microvessels precontracted with the thromboxane A2 analog U46619 dilated in response to CLT [90% relaxation of the U46619-induced precontraction at 100 micromol/L (P0.01 vs time control)] and its structural analogs flutrimazole (FLT), UR-4055, UR4057, UR-4058, and UR-4059. This relaxation was cyt P450-independent, since the in vivo CLT metabolite (CLT-carbinol) was equipotent with CLT, and 17-ODYA did not promote relaxation. CLT-induced dilation was not inhibited by the nitric oxide synthase inhibitor NGnitro-l-arginine (100 micromol/L, P0.5) or affected by endothelial denudation (P0.5). Thus, CLT at concentrations1 micromol/L is a potent vasodilator of rat coronary arterioles. This dilation is likely mediated through a vascular smooth muscle mechanism independent of cyt P450 and is not modulated by nitric oxide or by the endothelium. This effect may arise from CLT's reported ability to inhibit voltage-gated Ca2+ channels or to inhibit, in some tissues, Ca2+ release from intracellular stores. The CLT- and FLT-induced relaxation may be a property common to this class of drugs and have clinical applicability.

An adult patient with a spontaneous aneurysm of a patent ductus arteriosus was successfully treated. The lumen of the aneurysm communicated with the distal aortic arch and the pulmonary artery. Closure of the pulmonary arterial orifice of the ductus arteriosus and replacement of the inferior wall of the distal aortic arch and proximal descending aorta with prosthetic graft were performed under partial cardiopulmonary bypass using a centrifugal pump. The postoperative recovery was uneventful.

We report a case of isolated congenital tricuspid regurgitation caused by a cleft in the anterior tricuspid leaflet associated with a patent foramen ovale. Preoperative echocardiography revealed severe tricuspid regurgitation resulting from anterior tricuspid leaflet prolapse. The patient underwent successful tricuspid valve repair with simple cleft suture and annuloplasty and direct closure of the patent foramen ovale.

Objective: Neutrophil adhesion to endothelium contributes to cardiopulmonary dysfunction after cardiac surgical procedures. Initial neutrophil-endothelial interactions involve selectins, which bind carbohydrate ligands, such as sialyl-Lewis X . Blockade of selectin-mediated neutrophil interactions with CY1503, a synthetic oligosaccharide analog of sialyl-Lewis X , could limit neutrophil-mediated injury after cardiopulmonary bypass. Methods: The efficacy of CY1503 treatment was tested in a lamb model of cardiopulmonary bypass with hypothermic circulatory arrest. Neonatal lambs received CY1503 (n = 6, CPB-CY1503) or saline solution vehicle (n = 7, CPB-saline) into the pump prime before bypass and as a continuous infusion throughout reperfusion. Five lambs served as control animals for in vitro microvessel studies. Indexes of myocardial function (preload recruitable stroke work index, and rate of pressure rise) and pulmonary function (compliance, airway resistance, and arterial PO 2 ) were measured before bypass and during reperfusion. The effect of CY1503 on endothelium-dependent vascular reactivity was assessed by means of in vitro pulmonary and coronary microvessel studies. Results: Myocardial function was depressed after circulatory arrest, but CY1503 preserved function near baseline (36% ± 25% vs 99% ± 19% of baseline at 3 hours of reperfusion). CY1503-treated animals also demonstrated improved pulmonary function during reperfusion. In vitro microvessel analysis of vascular reactivity revealed endothelial dysfunction after circulatory arrest compared with control lambs. CY1503-treated lambs (CPB-CY1503) had intact endothelial function, as demonstrated by normal vasodilatory responses to endothelium-dependent vasodilators. Conclusions: CY1503 preserves cardiopulmonary and endothelial function after cardiopulmonary bypass and hypothermic circulatory arrest in neonatal lambs. This suggests a role for selectin-mediated, neutrophil-endothelial interactions in the inflammatory response after cardiac operations. (J Thorac Cardiovasc Surg 2000;120:230-7)