Bone morphogenetic protein 2 (BMP2) in chromosomal region 20p12 belongs to a gene superfamily encoding TGF-β-signaling proteins involved in bone and cartilage biology. Monoallelic deletions of 20p12 ...are variably associated with cleft palate, short stature, and developmental delay. Here, we report a cranioskeletal phenotype due to monoallelic truncating and frameshift BMP2 variants and deletions in 12 individuals from eight unrelated families that share features of short stature, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. De novo occurrence and autosomal-dominant inheritance of variants, including paternal mosaicism in two affected sisters who inherited a BMP2 splice-altering variant, were observed across all reported families. Additionally, we observed similarity to the human phenotype of short stature and skeletal anomalies in a heterozygous Bmp2-knockout mouse model, suggesting that haploinsufficiency of BMP2 could be the primary phenotypic determinant in individuals with predicted truncating variants and deletions encompassing BMP2. These findings demonstrate the important role of BMP2 in human craniofacial, skeletal, and cardiac development and confirm that individuals heterozygous for BMP2 truncating sequence variants or deletions display a consistent distinct phenotype characterized by short stature and skeletal and cardiac anomalies without neurological deficits.
The radial artery has more smooth muscle in its wall than the other arterial conduits and is known to be vasospastic. Because it is frequently necessary to use vasoconstrictors early after coronary ...bypass surgery we investigated the effects of phenylephrine on conduit flow in this setting.
Thirty patients undergoing coronary artery bypass with all arterial conduits in which the radial artery was used as a T-graft were randomly assigned to receive intravenous infusions of normal saline (n = 10); nitroglycerin, 0.5 μg · kg · min (n = 11); or nicardipine, 0.5 μg · kg · min (n = 9), beginning early in the operation. After discontinuation of cardiopulmonary bypass and achievement of stable hemodynamics, control measurements were obtained, and this was followed by phenylephrine infusion to achieve a 20% increase in mean arterial pressure, after which the measurements were repeated.
Mean radial artery flow increased similarly in all groups: normal saline, 40% ± 25%; nicardipine, 37% ± 27%; nitroglycerin, 48% ± 36% (
P = .533). Comparable changes occurred in arterial pressure and systemic vascular resistance, whereas the cardiac index remained unchanged.
Radial artery blood flow increases when the mean arterial pressure is increased with phenylephrine. There was no evidence of a conduit vasoconstrictive effect, which could limit or reduce conduit flow. Vasocontriction with phenylephrine is appropriate to provide adequate perfusion pressure for radial artery grafts.
Anticoagulation with recombinant hirudin (r-hirudin) (Refludan) has been suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought ...to develop a modified activated coagulation time (ACT) that would allow quantification of the levels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB were enrolled in this IRB-approved study. R-hirudin was added to blood specimens obtained before heparin administration (before CPB) and 30 min after heparin neutralization with protamine (after CPB) to result in concentrations of 0, 2, 4, 6, 7, or 8 microg/mL. Kaolin/ACT and complete blood count measurements were assayed in native specimens (first 10 patients, Phase I) or in specimens mixed with equal volumes of commercial normal plasma (second 11 patients, Phase II). In Phase I, good (r(2) = 0.83) linear relationships between ACT values and r-hirudin concentrations (< or =4 microg/mL) were observed in specimens obtained before CPB. However, ACT values were markedly prolonged (P < 0.0001) by r-hirudin in specimens obtained after CPB, with ACT values generally exceeding the ACT's detection limit (>999 s) at hirudin concentrations >2 microg/mL. In patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values obtained with hirudin concentration < or =4 microg/mL) in the post-CPB period (0.022 +/- 0.004 microg. mL(-1). s(-1)) were similar (P = 0.47) to those (0.019 +/- 0.004 microg. mL(-1). s(-1)) obtained in the pre-CPB period. Accordingly, a significant relationship between normal plasma-supplemented ACT values and predilution hirudin concentration was obtained in the post-CPB (hirudin = 0.039ACT - 4.34, r(2) = 0.91) period. Although our data demonstrate that the ACT test cannot be used to monitor hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted blood specimens yields a consistent linear relationship between hirudin concentration and ACT values up to a predilution concentration of 8 microg/mL. Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB.
A modified activated clotting time test system that may be helpful in monitoring hirudin anticoagulation in patients with heparin-induced thrombocytopenia during cardiac surgery with cardiopulmonary bypass is described.
Background. We assessed the efficacy of a continuous infusion of nicardipine and nitroglycerin in reducing the incidence and severity of perioperative myocardial ischemia during elective coronary ...artery bypass grafting procedures in a prospective, randomized, controlled study.
Methods. Patients received either nicardipine infusion (0.7 to 1.4 μg · kg ·
−1 · min
−1; n = 30) or nitroglycerin (0.5 to 1 μg · kg
−1 · min
−1; n = 30) or neither medication (n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes (MIE) were considered to have occurred with ST-segment depressions or elevations of at least 1 mm and at least 2 mm (for both depressions or elevations), each at J + 60 ms and lasting at least 1 minute, using a two-channel Holter monitor.
Results. Only nicardipine significantly decreased the duration (
p = 0.02) of the 1-mm or greater minutes per hour (3.2 ± 1.2 minutes per hour) and eliminated the number (
p = 0.02) of the 2-mm or greater minutes per hour (zero minutes per hour) when compared with control patients (17.2 ± 5.6 minutes per hour and 0.17 minutes per hour, respectively) during the intraoperative postbypass period.
Conclusions. Our results suggest that nicardipine lessened the severity of myocardial ischemia shortly after coronary revascularization and could be considered as an alternative to standard antiischemic therapy.
Perioperative myocardial ischemic episodes are predictive of adverse cardiac outcomes after coronary artery bypass surgery. We compared the efficacy of continuous infusions of nicardipine (group NIC) ...and nitroglycerin (group NTG) in reducing the frequency and severity of myocardial ischemic episodes. Patients received either a nicardipine infusion, 0.7 to 1.4 microg/kg/min (n = 30), nitroglycerin infusion, 0.5 to 1 microg/kg/min (n = 30), or neither medication (group C; n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes were considered as ST segment depressions or elevations of 1 mm or greater from baseline, each at J + 60 milliseconds and lasting 1 minute or greater, using a two-channel Holter monitor. Only nicardipine significantly decreased the duration (3.2 +/- 1.2 min/h) and the area under the ST time curve (AUC; 5.7 +/- 15.7 AUC/h) of 1-mm or greater myocardial ischemic episodes compared with group C (17.2 +/- 5.6 min/h and 30.1 +/- 49 AUC/h, respectively) during the intraoperative postbypass period. A trend toward lower frequency, duration, and area under the ST time curve of myocardial ischemic episodes was observed in group NIC compared with group NTG. Cardiac indices and mixed venous oxygen saturations were significantly greater, whereas systemic pressures were less in group NIC compared with group NTG for the same period. These results suggest that nicardipine, but not nitroglycerin, decreased the duration and area under the ST time curve of myocardial ischemic episodes shortly after coronary revascularization. Larger studies are required to verify the efficacy of nicardipine in reducing the severity of myocardial ischemia during cardiac surgery.
The aim of this study is to characterize and compare the left ventricular (LV) diastolic filling patterns in patients with paroxysmal (PAF) versus chronic atrial fibrillation (CAF) undergoing the ...maze procedure and to examine their relation with the hemodynamic status. Fifty patients with PAF and 22 with CAF were studied. Hemodynamic measurements and transesophageal echocardiography (TEE) were performed after the induction of anesthesia but before surgical incision, at stable conditions. Transmitral (TMF) and pulmonary venous flow (PVF) velocities were recorded with the pulsed Doppler method. Statistical analysis between the two groups (PAF and CAF) was performed using Student's t-test and chi-squared test, with P less than .05 statistically significant. Compared with patients in the PAF group, those in the CAF group had: (1) higher pulmonary capillary wedge pressure (14 +/- 5 v 12 +/- 4 mm Hg; P < .05), (2) lower left ventricular fraction of area change (43% +/- 6% v 52% +/- 9%; P < .01), (3) slower PVF systolic wave velocity (23 +/- 10 v 35 +/- 15 cm/s; P < .05), and (4) lower ratio of PVF systolic to diastolic wave velocity (0.75 +/- 0.3 v 1.2 +/- 0.4; P < .05). In the present study, LV filling patterns of abnormal relaxation were found in all our patients who underwent the maze procedure for CAF or PAF. Although the cause of LV filling abnormalities is not apparent, the data suggest LV diastolic dysfunction is prevalent in these patients.
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