Results of the treatment of patent ductus arteriosus

Since the first effective surgical treatment of PAD, the indications for such a treatment have been more extensive and its results and methods have been changing. We present 123 patients who underwent surgery for PAD in the Clinic of Cardiosurgery, Institute of Cardiology, Medical Academy of Lód? within 1978-1987. In 101 cases PAD was dissected and both ends were sutured in two layers with continuous sutures, and in 22 cases PAD was ligated with 3 ligatures. In 30 patients PAD coincided with other congenital defects of the circulatory system. No cases of recanalization were observed in our patients. One death in the postoperative course was noted.     

Mathematical model of flow through the patent ductus arteriosus

The ductus arteriosus is one of several shunts in the cardiovascular system. It is a small vessel connecting the aortic arch and pulmonary artery that allows blood to bypass the pulmonary circulation. It is open during foetal development because the foetal lungs cannot function and oxygenation of the blood occurs by exchange with the maternal blood in the placenta. Normally it closes a few days after birth; however, in a small number of people closure does not occur, leading to a condition known as patent ductus arteriosus. In this paper our aim is to investigate the resulting cardiovascular effects. We develop a mathematical model of the haemodynamics in three different idealised geometries by assuming that the entry flow is irrotational and remains so in the core until at least the shunt position. We argue that separation or diffusion of vorticity into the core flow is delayed due to the high frequency associated with the pulsatile component of the flow profile. The analysis uses complex potential theory, Schwarz–Christoffel transformations, conformal mappings and Fourier series. The main results are based on the assumption that the flow in patients with patent ductus arteriosus is similar to the flow in healthy adults, and we apply this assumption using boundary conditions that are representative of physiological values in healthy adults. The model suggests that the pressures in the aorta and pulmonary artery are likely to equalise, that the shear stress increases near the edges of the shunt and that backflow of large volumes may occur from the pulmonary artery into the aorta or towards the ventricles due to the presence of the patent shunt. Our results strongly suggest that an abnormal compensatory physiology develops in patients with patent ductus arteriosus.     

Respiratory effects of a patent ductus arteriosus in premature newborn lambs

We examined the respiratory effects of a patent ductus arteriosus in 29 premature lambs (131-135 days gestational age) after infiltrating the ductal wall with formaldehyde solution (Formalin) and placing a snare around the ductus to regulate its patency. The lambs were given sheep surfactant, paralyzed, and mechanically ventilated at birth. We first compared 8 lambs with open ductus and 13 lambs with closed ductus during the 12 h after birth. Although lambs with open ductus had greater pulmonary blood flow (301 +/- 36 vs. 188 +/- 11 ml.min-1.kg-1, mean +/- SE, at 12 h of age) and mean pulmonary arterial (44 +/- 3 vs. 33 +/- 2 mmHg) and left ventricular end-diastolic (6 +/- 0.6 vs 4 +/- 0.7 mmHg) pressures, we found no differences in dynamic respiratory compliance (Cdyn = 0.55 +/- 0.07 vs. 0.55 +/- 0.03 ml.cmH2O-1.kg-1), midtidal volume resistance (62 +/- 5 X 10(-3) vs. 62 +/- 7 X 10(-3) cmH2O.ml-1.s), or functional residual capacity (FRC = 27 +/- 3 vs. 26 +/- 2 ml.kg-1). Alveolar-arterial PO2 difference was lower in the lambs with open ductus (238 +/- 65 vs. 362 +/- 37 Torr). Next, we challenged eight lambs with two separate saline infusions (50 ml.kg-1 over 3 min), each given with the ductus alternately closed or open. When the ductus was closed, FRC was unchanged, but Cdyn increased by 18% immediately after the infusion. When the ductus was open, FRC decreased by 16% and Cdyn decreased by 12%. We conclude that the premature lamb is surprisingly resistant to changes in respiratory function from ductal patency during the immediate neonatal period.     

Prostaglandin biosynthesis and catabolism in the lamb ductus arteriosus, aorta and pulmonary artery.

Homogenates of tissues from fetal and neonatal lamb ductus arteriosus, aorta and pulmonary artery have the capacity to convert arachidonic acid as well as the intermediate prostaglandin endoperoxide, prostaglandin H2, into three products: prostaglandins E2, F2alpha and a major product 6-ketoprostaglandin F1alpha. The three tissues also displayed prostaglandin 15-hydroxydehydrogenase and 13-reductase catabolic activities. The catabolishing system showed considerable substrate specificity: prostaglandin E1 was a good substrate whereas prostaglandins F1alpha and F2alpha were completely devoid of catabolism. The complete system was observed in immature as well as mature arterial vessels, in the fetus as well as the neonate (up to 7 days old). These experiments demonstrate the presence of several components of the prostaglandin system in these tissues and offer biochemical evidence for the implication of prostaglandins E2 and I2 in the maintenance of the ductus and neighboring vessels in a relaxed state in the fetus.     

Loss of Notch2 and Notch3 in vascular smooth muscle causes patent ductus arteriosus

The overlapping roles of the predominant Notch receptors in vascular smooth muscle cells, Notch2 and Notch3, have not been clearly defined in vivo. In this study, we use a smooth muscle‐specific deletion of Notch2 together with a global Notch3 deletion to produce mice with combinations of mutant and wild‐type Notch2/3 alleles in vascular smooth muscle cells. Mice with complete loss of Notch3 and smooth muscle‐expressed Notch2 display late embryonic lethality and subcutaneous hemorrhage. Mice without smooth muscle‐Notch2 and only one wild‐type copy of Notch3 die within one day of birth and present with vascular defects, most notably patent ductus arteriosus (DA) and aortic dilation. These defects were associated with decreased expression of contractile markers in both the DA and aorta. These results demonstrate that Notch2 and Notch3 have overlapping roles in promoting development of vascular smooth muscle cells, and together contribute to functional closure of the DA. genesis 53:738–748, 2015. © 2015 Wiley Periodicals, Inc.     

Magnetic resonance tomography in the diagnosis of aneurysm and coarctation of the thoracic aorta]

MR-tomography (MRT) was performed in 25 patients with aneurysms and in 11 with coarctation of the thoracic aorta. For investigations a device with a resistive magnet (the force of a field--0.23 T) was used simultaneously with ECG. MRT revealed all cases of aortic dissection (10 patients) and one case with a false-positive result. Oblique sections in the direction of the thoracic aorta were used to assess the state of the aortic arch branches. Comparison of MRT and x-ray computerized tomography has shown that the diagnostic value of both methods was almost equal, however MRT was a safer method and easier to use. MRT was shown to be a method of choice for diagnosis of aneurysms and coarctations of the thoracic aorta but cannot be a substitution for aortography.     

Concentrations of prostaglandin E2 and F2 alpha in the cardiovascular system of infants with persisting patent ductus arteriosus

The distribution of prostaglandin E2 and F2 alpha was examined in the peripheral veins and in several positions of the cardiovascular system before and after the blood had passed through the lungs in 37 infants. Prostaglandin E2 varied from 0.25 +/- 0.09 ng/ml to 0.44 +/- 0.09 ng/ml when measured in the pulmonary artery, the ductus arteriosus, the right atrium, the right ventricle, the left atrium, the left ventricle, the inferior vena cava and the descending aorta. Prostaglandin F2 alpha was much higher in these positions of the cardiovascular system. The range was 0.99 +/- 0.36 ng/ml to greater than 2.0 ng/ml. The vascular tissues produced virtually identical high amounts of prostaglandin E2 and F2 alpha, but there were no significant differences in prostaglandin E2 and F2 alpha, concentrations, in venous blood as well as in systemic arterial blood. The results suggest that prostaglandin E2 is not responsible for the persisting patency of the ductus arteriosus in infants. There is no explanation for the increased prostaglandin F2 alpha concentrations in these patients.     

Comparison of renal effects of ibuprofen versus indomethacin during treatment of patent ductus arteriosus in contiguous historical cohorts

Background

The study aimed to investigate the pharmacokinetics of intravenous ciprofloxacin and the adequacy of 400 mg every 12 hours in critically ill Intensive Care Unit (ICU) patients on continuous veno-venous haemodiafiltration (CVVHDF) with particular reference to the effect of achieved flow rates on drug clearance.

Methods

This was an open prospective study conducted in the intensive care unit and research unit of a university teaching hospital. The study population was seven critically ill patients with sepsis requiring CVVHDF. Blood and ultrafiltrate samples were collected and assayed for ciprofloxacin by High Performance Liquid Chromatography (HPLC) to calculate the model independent pharmacokinetic parameters; total body clearance (TBC), half-life (t_1/2) and volume of distribution (Vd). CVVHDF was performed at prescribed dialysate rates of 1 or 2 L/hr and ultrafiltration rate of 2 L/hr. The blood flow rate was 200 ml/min, achieved using a Gambro blood pump and Hospal AN69HF haemofilter.

Results

Seventeen profiles were obtained. CVVHDF resulted in a median ciprofloxacin t_1/2 of 13.8 (range 5.15-39.4) hr, median TBC of 9.90 (range 3.10-13.2) L/hr, a median V_dss of 125 (range 79.5-554) L, a CVVHDF clearance of 2.47+/-0.29 L/hr and a clearance of creatinine (Cl_cr) of 2.66+/-0.25 L/hr. Thus CVVHDF, at an average flow rate of ~3.5 L/hr, was responsible for removing 26% of ciprofloxacin cleared. At the dose rate of 400 mg every 12 hr, the median estimated C_pmax/MIC and AUC_0-24/MIC ratios were 10.3 and 161 respectively (for a MIC of 0.5 mg/L) and exceed the proposed criteria of >10 for C_pmax/MIC and > 100 for AUC_0-24/MIC. There was a suggestion towards increased ciprofloxacin clearance by CVVHDF with increasing effluent flow rate.

Conclusions

Given the growing microbial resistance to ciprofloxacin our results suggest that a dose rate of 400 mg every 12 hr, may be necessary to achieve the desired pharmacokinetic - pharmacodynamic (PK-PD) goals in patients on CVVHDF, however an extended interval may be required if there is concomitant hepatic impairment. A correlation between ciprofloxacin clearance due to CVVHDF and creatinine clearance by the filter was observed (r² = 0.76), providing a useful clinical surrogate marker for ciprofloxacin clearance within the range studied.

Trial Registration

Current Controlled Trials ISRCTN52722850     

Morphologic changes in the coronary arteries in experimental coarctation of the aorta and following its correction

In 33 puppies 2-4 months of age the model of a congenital heart disease was made as coarctation of the aorta. In 6-12 months 18 animals were taken to study, and in 15 animals the coarctation was removed. The latter animals were observed for other 6-12 months. The hearts of both groups were separately weighed, and the vessels of the coronary system were studied by means of a complex of histological and morphometric methods. Simultaneously, the number of smooth muscle cells, as well as the area and volume of their nuclei in media of small coronary arteries were estimated. At the experimental coarctation of the aorta certain hypertrophic-hyperplastic changes in coronary arteries at all branching levels take place. They are of a compensatory-adaptive character and reflect certain reactions of the vascular wall to an increased coronary hemodynamics under conditions of hyperfunction and hypertrophy of the cardiac muscle. Surgical removal of the coarctation is accompanied with a reduce of the hemodynamic loading of the heart, diminished degree of hypertrophy of the organ and a marked decrease of the hypertrophic-hyperplastic changes in its vessels. At the same time, the cardiac vascular system is adapting to the new conditions of circulation: rearrangement of some coronary arteries and arterioles according to the closed type and reduction of circulation in the vascular branches which have lost their importance in feeding the myocardium.