CPR for patients in a persistent vegetative state?
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Canada↗
Biomedical subjects
J Belik
Publications and source records attributed to J Belik.
Myosin light chain phosphatase and kinase abnormalities in fetal sheep pulmonary hypertension.
Inasmuch as smooth muscle contractile protein abnormalities may account for the maintenance of a high pulmonary vascular resistance, we evaluated the pulmonary arterial myosin light chain kinase (MLCK) and phosphatase (MLCP) in normal and pulmonary hypertensive (PH) fetal sheep. In addition, aorta and vena cava MLCP and MLCK activities were also measured. The MLCK activity (nanomoles/min/mg) was determined by the incorporation of [32P]PO4(-3) to the 20-kD smooth muscle myosin light chains and the MLCP activity by assaying for the dephosphorylation of the 20-kD myosin light chain (MLCP-light chain) and heavy meromyosin (MLCP-HMM). The MLCP content was determined by Western blot analysis. PH was characterized by a significant increase in the right-to-left ventricular wall weight ratio from 0.99 +/- 0.04 in the control to 1.52 +/- 0.12 in the experimental group (p < 0.01). The pulmonary MLCP-light chain and MLCP-HMM activities in the experimental group were 2.0 +/- 0.2 and 1.3 +/- 0.2 and significantly lower than in the control group values (3.8 +/- 0.5 and 2.5 +/- 0.3; p < 0.01). The MLCK activity was 9.6 +/- 1.2 in the control and 7.8 +/- 0.7 in the experimental fetal pulmonary artery (p = NS). The activities of both enzymes in the aorta and vena cava samples were not altered by PH. The MLCP content in experimental animals (0.50 +/- 0.09 OD x mm2) was significantly lower than that for the control pulmonary tissue (1.72 +/- 0.42; p < 0.01), suggesting that PH down-regulates pulmonary vascular MLCP expression. In conclusion, the maintenance of a high pulmonary vascular resistance in PH may be secondary to abnormalities in tissue content and/or activity of MLCP.
Animals↗
Use of tolazoline to counteract vasospasm in peripheral arterial catheters in neonates.
Arterial access for blood sampling and continuous blood pressure monitoring is the cornerstone of modern neonatal intensive care. Although umbilical arterial catheters have traditionally been utilized for arterial access, they are associated with potentially devastating complications. Consequently, there has been an increase in the use of peripheral arterial catheters. Unfortunately, these catheters have a limited useful lifespan secondary to vasospasm, intimal damage and/or thrombus formation. In this report, we describe the use of tolazoline (0.02 to 0.2 mg/kg/h) to counteract local arterial vasospasm in five critically ill neonates, where arterial access was vital for care but difficult to maintain.
Arteries↗
Susceptibility of exogenous surfactant to phospholipase A2 degradation.
The inhibition of surfactant biophysical activity in vivo is potentially mediated by many factors, including serum proteins, particularly enzymatic proteins such as phospholipases. In the present study, we investigated the susceptibility of the phosphatidylcholine component of two exogenous surfactants, Exosurf and Survanta, to secretory-type phospholipase A2 (PLA2) deacylation in vitro. Lyophilized Exosurf and Survanta preparations were incubated at 37 degrees C for 120 min in the presence of bovine pancreatic PLA2, and the production of lysophosphatidylcholine was determined as a measure of the magnitude of phosphatidylcholine deacylation. The phosphatidylcholine component of Survanta was readily deacylated by PLA2, whereas the dipalmitoylphosphatidycholine (DPPC) component of Exosurf was resistant over the entire duration of the assay. To further evaluate this observed resistance the individual and combined effects of tyloxapol and hexadecanol, components of Exosurf, upon PLA2 deacylation of Survanta and DPPC were investigated. In both Survanta and DPPC preparations, PLA2-mediated deacylation was significantly inhibited in the presence of tyloxapol. We conclude that the presence of tyloxapol in the Exosurf preparation inhibits secretory type PLA2 mediated DPPC deacylation. This unique feature of Exosurf may be of clinical significance when this preparation is utilized in the treatment of surfactant-deficient infants.
1,2-Dipalmitoylphosphatidylcholine↗
Effects of central apnea on cerebral blood flow velocity in healthy term infants.
We evaluated a new method of monitoring cerebral blood flow velocity (CBFV) and described changes in CBFV in relation to central apnea in 17 healthy term infants. The area under the velocity curve during apnea did not change, whereas area under the velocity curve per the waveform showed a significant difference, suggesting that stability is maintained through an increase in CBFV with each heartbeat. The maintenance of cerebral hemodynamics during isolated central apnea supports the assumption that these episodes are benign.
Blood Flow Velocity↗
The myogenic response of arterial vessels is increased in fetal pulmonary hypertension.
The stretch-induced myogenic response (MR) of large-capacitance pulmonary arteries were studied in normal and pulmonary hypertensive fetuses as well as normal newborn and adult sheep. Pulmonary hypertension in the fetus was induced by ligation of the ductus arteriosus for 12 d. The MR was obtained by stretching the vessel segments in vitro from their resting diameter (no load) to the diameter at which the muscle fibers were at optimal length (Lo), and the response was measured as a percentage of force obtained after supramaximal electrical stimulation (Po). In five control and four pulmonary hypertensive fetuses, the MR was also obtained after a stretch of 140% of Lo. The pulmonary hypertensive fetal arteries had a lower stress (1.3 +/- 0.4 versus 4.0 +/- 0.5 mN/mm2; p < 0.001) and shortening capacity compared with the fetal control (5.1 +/- 1.6 versus 9.9 +/- 0.8% of Lo; p < 0.01). The MR was observed in 21% of the control and 30% of the experimental fetuses, and it was of greater magnitude in the latter (14.8 +/- 1.9 of Po versus 34.3 +/- 2.5%, respectively; p < 0.01). When stretched to 140% of Lo, the MR was also greater in the experimental (514 +/- 148% of Po) than the control fetuses (142 +/- 68; p < 0.05). Postnatally, the MR was present in 67% of the newborn and 15% of the adult pulmonary artery segments, and the response was greatest in the newborn (23.1 +/- 4.2% of Po) compared with the adult (2.3 +/- 0.8; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Inhaled nitric oxide monitoring.
UNLABELLED: Recently, inhaled nitric oxide (NO) became clinically available for the treatment of persistent pulmonary hypertension of the newborn. Such use requires administration and continuous monitoring of a very low concentration of NO to prevent potential toxicity. Since limited data on the reliability of NO monitoring devices are available, we evaluated the performance of a chemiluminescent and electrochemical sensor NO analyzer in a patient ventilator circuit. RESULTS: The chemiluminescence analyzer readings were significantly altered by the oxygen concentration in the ventilator circuit. When the FiO2 was increased from 0.21 to 1, a 4.5% +/- 0.3 decrease in the NO readings was found (p < 0.01). Similarly, adding humidity to the circuit, reduced the NO readings by 4.8% +/- 0.9 (p < 0.01). The effect of gas pressure was proportional to its magnitude but independent of whether a pulsatile or continuous gas flow was provided. At a mean airway pressure of 15 cm H2O, the NO readings increased by 3.94% +/- 0.05 (NO = 10 parts per million) and 3.97% +/- 0.02 (40 parts per million) (p < 0.01). The electrochemical sensor NO readings were directly proportional to the ventilator circuit pressure but independent of whether a pulsatile or continuous gas flow was provided. At a mean airway pressure of 15 cm H2O, the NO reading was increased by 25.39% +/- 0.04 (NO = 40 parts per million) (p < 0.01) and 1.07% +/- 0.16 (NO = 10 parts per million) (p NS). The greatest difference with NO = 10 parts per million from baseline was found at a mean airway pressure of 6 cm H2O (6.67% +/- 0.23; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Inhalation↗
Large pulmonary arteries and the control of pulmonary vascular resistance in the newborn.
In the immediate neonatal period the pulmonary vascular resistance is higher than later in life. The role of maturational differences in the smooth muscle mechanical properties of large capacitance vessels in this response has not been previously studied. To this end, we studied the smooth muscle isometric and isotonic mechanical properties, as well as the myogenic response of large extralobar pulmonary arteries in newborn and adult guinea pigs. Compared with the adult, the newborn pulmonary vascular smooth muscle generates less force and has a similar shortening capacity but longer isometric and isotonic relaxation half times. The myogenic response could be elicited in 80% of the newborn and 70% of the adult vessels. A 20% increase in vessel diameter resulted in force generation equivalent to 46 +/- 5.1% of maximal isometric tension in the newborn. Such a response was significantly greater than observed for the adult vessels (14 +/- 2.8%; p < 0.001). Our results showed significant maturational differences in the mechanical properties of the large pulmonary artery smooth muscle in the newborn. We speculate that the presence of myogenic response in large pulmonary capacitance vessels and the observed greater magnitude of stretch-induced force generation in the newborn may play an important role in the maintenance of a higher pulmonary vascular resistance in the neonatal period.
Aging↗
Pulmonary hypertension and vascular remodeling in fetal sheep.
Vascular remodeling is commonly associated with pulmonary hypertension (PH) postnatally, but little is known about its presence in fetuses. In sixteen fetal sheep (126 wk gestation), the ductus arteriosus (DA) was ligated, and the animals were studied at 4, 8, and 14 days after surgery. The uninstrumented twins served as controls. Four days post-DA ligation PH resulted in an increase in the right and left ventricular free wall weight ratio (1.2 +/- 0.1 vs. 1.0 +/- 0.1 in the controls; P < 0.01), with a further progressive increase at 8 (1.4 +/- 0.1 vs. 1.0 +/- 0.1; P < 0.01) and 14 days (1.5 +/- 0.2 vs. 1.0 +/- 0.1; P < 0.01). An increase in vascular percent medial thickness was observed after 4 days of DA ligation and was restricted to small vessels. The large arteries collagen and elastin contents were 28.9 +/- 3.4 and 27.1 +/- 3.4 micrograms/micrograms of DNA, respectively, and were not significantly different from control values even after 14 days DA ligation. We further compared elastin synthesis in fetal and neonatal arteries in vitro. Synthesis in the fetus was greater than the newborn (10.6 +/- 1.4 vs. 4.6 +/- 0.7 cpm.mg wet wt-1.h-1; P < 0.01). Vessel endothelium denudation reduced synthesis to 60 +/- 8% of controls in the fetus, whereas no change was seen in the newborn. After an increase in wall stress, synthesis increased in the fetus (194 +/- 28% of control P < 0.01) and newborn (173 +/- 25%; P < 0.01). Removal of the endothelium abolished the response.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Myogenic response in large pulmonary arteries and its ontogenesis.
To evaluate the myogenic response and its ontogeny in large pulmonary arteries, we studied 45 newborn and 30 adult guinea pigs. Compared with the those of the adult, the newborn arterial vessels possessed a significantly (p < 0.01) smaller diameter (1153 +/- 34 versus 1656 +/- 65 microns), static compliance (2.2 +/- 0.3 versus 4.6 +/- 0.7 microns/mN), and active stress (3.4 +/- 0.4 versus 5.8 +/- 0.7 mN/mm2). Stretch-induced contraction was obtained by quick stretch of the vessel segments to 120, 140, 160, 180, or 200% of their optimal length, and the myogenic response was measured as the change in force after muscle relaxation with papaverine. A myogenic response was observed in 94% of the newborn and 93% of adult vessel segments, and significant age differences in the response were present. The magnitude of the active force generated for any stretch over 120% was significantly greater in the newborn (p < 0.01), and as a percentage of K+ (127 mM) stimulation, a 2-fold stretch of the vessels' optimal length resulted in a force of 1073 +/- 159% in the newborn compared with 51 +/- 16% in the adult (p < 0.01). The myogenic response in these large pulmonary vessels was completely suppressed by a calcium channel blocker (D-600) but unaltered by addition of a nitric oxide synthase inhibitor (NG-methyl-L-arginine) or indomethacin. We conclude that the large pulmonary arterial vessels of the guinea pig exhibit a powerful stretch-induced myogenic response that is greater in the newborn period.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Oxidoreductases↗
Developmental differences in vascular smooth muscle mechanics in pulmonary and systemic circulations.
To evaluate the maturational changes in vascular muscle mechanics we studied and compared the isotonic half-time relaxation (t1/2P,CE) and maximal load-bearing capacity normalized to stress of pulmonary and systemic arterial muscle from perinatal and adult sheep. For the pulmonary and systemic vessels t1/2P,CE was significantly shorter in adult than in perinatal sheep (P < 0.01). In newborns t1/2P,CE of the pulmonary vessels was 185 +/- 31 (SE) s, longer than that of the systemic vessels (64 +/- 10 s; P < 0.01). In adults t1/2P,CE of the pulmonary vessels (101 +/- 14 s) was longer than that of the systemic vessels (37 +/- 5 s; P < 0.01). Maximal load-bearing capacities normalized to stress of pulmonary vessels of fetal and newborn sheep were twofold greater than those of adult sheep and of the systemic vessels of newborns and adults (P < 0.01). In conclusion, significant maturational changes in the isotonic and isometric mechanical properties of vascular pulmonary and systemic smooth muscle were observed in sheep.
Aging↗
Fetal ductus arteriosus ligation. Pulmonary vascular smooth muscle biochemical and mechanical changes.
To evaluate the smooth muscle mechanical and biochemical changes associated with persistent pulmonary hypertension syndrome of the newborn, we studied 31 fetal sheep in which the ductus arteriosus was ligated at 125 days of gestation. Sixty-one noninstrumented and six sham-operated fetuses served as controls. All animals were delivered by cesarean section at 137-140 days of gestation, and the experimental group had the ductus arteriosus ligated for 12 +/- 3 days. The ligated group demonstrated a higher mean (+/- SEM) pulmonary artery pressure (72.3 +/- 3.8 versus 54.1 +/- 2 mm Hg, p < 0.01) and right ventricular mean free wall weight (12.5 +/- 0.7 versus 6.8 +/- 0.3 g, p < 0.01) as compared with the sham-operated group. Significant changes in the pulmonary vascular smooth muscle of the ligated group were observed. The myosin content of vessels from the second through fifth generation demonstrated a significant increase in actin and myosin content (p < 0.01), but given their disproportional changes, the noninstrumented group demonstrated a lower actin/myosin ratio than the experimental group (p < 0.01). Changes in the myosin heavy chain isoform stoichiometry, characterized by an increase in both the mean high/low myosin heavy chain isoform ratio (1.8 +/- 0.3 versus 1.0 +/- 0.1, p < 0.05) and the nonmuscle isoform as a percentage of the total myosin heavy chain (12.4 +/- 0.7% versus 2.7 +/- 0.9%, p < 0.01), were also observed in the ligated as compared with the noninstrumented animals. In addition, the muscle Mg-ATPase activity was significantly (p < 0.05) reduced in the experimental group.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Intratracheal N-acetylcysteine use in infants with chronic lung disease.
To evaluate the effect of intratracheal administration of N-acetylcysteine (Mucomyst) on the clinical status, pulmonary function and gas exchange in premature infants with chronic lung disease, we conducted a randomized, placebo-controlled, crossover trial. Ten mechanically ventilated infants (gestational age 27 +/- 1 week; postnatal age 22 +/- 6 days) with clinical and radiological evidence of chronic lung disease and increased airway secretion were enrolled in the study. Each infant received tracheal administration of 5% N-acetylcysteine for one week and saline placebo every 4 h for another week. N-acetylcysteine was associated with a 59 +/- 26% increase in total airway resistance by the third day of treatment (p less than 0.01). A two-fold increase in airway resistance associated with an increased frequency of bradycardia and cyanosis spells was seen in two of the infants following three days of N-acetylcysteine administration, with a rapid improvement in their condition when subsequently switched to saline. Overall, N-acetylcysteine administration had no effect on the variables measured. We conclude that intratracheal administration of N-acetylcysteine to liquefy airway mucus neither improves the clinical condition nor hastens recovery in premature infants with chronic lung disease and its administration may lead to increased total airway resistance and cyanotic spells. The present data do not support the use of N-acetylcysteine as a mucolytic agent in premature infants with chronic lung disease.
Acetylcysteine↗
Pulmonary and systemic vascular smooth muscle mechanical characteristics in newborn sheep.
To investigate the hypothesis that the higher pulmonary vascular resistance in newborn sheep is the result of developmental differences in the vascular muscle mechanical properties, we evaluated pulmonary arteries from newborn and adult sheep and compared them with their respective systemic counterparts (common carotid arteries). The newborn pulmonary artery mechanical stress (13.0 +/- 1.4 mN/mm2) and shortening capacity (11.4 +/- 1.1% of optimal length) were lower (P less than 0.01) than in the adult (20.4 +/- 2.5 and 15.6 +/- 1.3, respectively). The adult carotid artery muscle developed a greater stress (97.6 +/- 18.5 mN/mm2) than the newborn (40.7 +/- 5.0; P less than 0.01), whereas no age differences in shortening capacity were observed (newborn = 19.4 +/- 1.7; adult = 18.4 +/- 1.5% of optimal length). The contraction half-time was similar for the pulmonary and carotid arteries and was not affected by age, whereas the relaxation half-times of the newborn pulmonary (30.7 +/- 2.9 s) and carotid artery (23.3 +/- 1.5) were greater than in the adult (24.9 +/- 2.9 and 14.6 +/- 1.4, respectively; P less than 0.01). The myosin contents of the pulmonary and carotid arteries, as an indicator of the tissue muscle mass, were similar and did not change with age. In conclusion, while the lower stress and shortening capacity of the newborn pulmonary arteries limit their maximum capacity to vasoconstrict, the significantly greater relaxation time of their vascular muscle, a new observation, may account for the higher resistance to blood flow after birth.
Aging↗
Pulmonary vascular smooth muscle: biochemical and mechanical developmental changes.
To evaluate the developmental changes in pulmonary vascular smooth muscle contractile protein content, mechanical properties, and their contribution to the high resistance characteristic of the fetal and immediate neonatal period, we studied pulmonary vessels of fetal, newborn, and adult sheep, as well as newborn and adult pigs. Strips of the second- through fifth-generation vessels were dissected, and their content of tissue total smooth muscle cell protein, myosin, and actin-to-myosin ratio were measured; the mechanical properties of the second-generation vascular strips were also studied. For all ages the smooth muscle protein and myosin content of the second-generation vessels were significantly greater than for the lower pulmonary vascular orders (P less than 0.05). The myosin content in fetal sheep (0.77 +/- 0.03 micrograms/mg wet tissue) was similar to that of the newborn (0.79 +/- 0.04) and adult (0.86 +/- 0.05). However, the smooth muscle protein content (7.94 +/- 0.21 micrograms/mg wet tissue) and the actin-to-myosin ratio of the pulmonary vascular tissue of the fetus (1.00 +/- 0.04) were lower (P less than 0.01) in the fetal than in the newborn (9.16 +/- 0.26 and 1.60 +/- 0.12) and adult (9.38 +/- 0.3 and 1.60 +/- 0.11, respectively). No differences were observed for these parameters between the newborn and adult pig. Stress (16.5 +/- 1.7 mN/mm2) and the maximum shortening capacity (13.0 +/- 1.5% of optimal length) in the newborn pulmonary vascular strips were significantly greater than for the fetus (6.8 +/- 1.4 and 5.9 +/- 1.0, respectively) but similar to those of the adult sheep.(ABSTRACT TRUNCATED AT 250 WORDS)
Actins↗
The effect of repeated intermittent hypoxia on pulmonary vasoconstriction in the newborn.
The effect of repeated intermittent hypoxia upon the basal pulmonary vascular tone in the newborn period is unknown. We therefore studied the central hemodynamic response to seven repeated intermittent hypoxic challenges in acutely prepared piglets under 2 weeks of age. Catheters were placed in the aorta, pulmonary artery, and atria, and an electromagnetic flow probe was positioned around the main pulmonary artery. Each hypoxic challenge (Fio2 = 0.14) lasted 5 min, and was separated by an equal duration of ventilation with air. Nine control animals were ventilated with air for 90 min, a period of time equivalent to the seven challenges in the experimental group, and subjected to one hypoxic challenge at the end. Hypoxia uniformly induced pulmonary vasoconstriction. Repeated intermittent hypoxic challenges produced a progressive increase in pulmonary artery pressure and vascular resistance, both during air ventilation and hypoxia. For each challenge, the vascular resistance value achieved during hypoxia was directly related to the immediately preceding air ventilation one, and the magnitude of hypoxic pulmonary vasoconstriction, defined as the incremental change in resistance from air to hypoxia, was not different from the first to the last challenge in the experimental group. In the control group the pulmonary vascular tone did not change during the 90 min of air ventilation, and the single hypoxic challenge induced an increase in pulmonary vascular pressure and resistance similar in magnitude to the first challenge in the experimental group. Indomethacin administration to five experimental animals, after the last challenge, reversed the increase in air ventilation pulmonary artery pressure and vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
The effect of an increase in systemic arterial pressure in the newborn with right ventricular hypertension.
To evaluate the effect of an elevation in systemic arterial pressure upon pulmonary blood flow and arterial oxygenation during right ventricular hypertension (RVH), we acutely studied 13 1-d-old piglets. Catheters were positioned in the pulmonary artery, both atria, and the aorta for hemodynamic measurements. An electromagnetic probe was positioned in the main pulmonary artery for pulmonary blood flow measurement. Systemic and regional blood flow were measured with the radiolabeled microsphere technique. A balloon-mounted catheter was advanced in the aorta and maintained at the lower thoracic level. After induction of RVH (pulmonary artery banding), a significant decrease in arterial O2 pressure from 54.4 +/- 1.6 to 10.6 +/- 0.4 kPa (p less than 0.01), a 30% reduction in systemic arterial pressure, and a 44% decrease in pulmonary blood flow were observed. During RVH, partial inflation of the aortic balloon to restore the systemic arterial pressure to its initial value led to an increase in arterial O2 pressure to 23.5 +/- 3.1 kPa (p less than 0.01). Full inflation of the balloon further increased the arterial O2 pressure to 32.6 +/- 2.9 kPa (p less than 0.01). Aortic balloon inflation increased pulmonary blood flow in 11 and systemic O2 delivery in nine of the 13 animals. RVH was associated with a significant increase in cerebral and right ventricular myocardial free-wall blood flow and a decrease in renal and bowel blood flow and O2 delivery (p less than 0.01). Aortic balloon inflation during RVH did not change either the cerebral or myocardial free-wall blood flow, but further significantly decreased renal and bowel blood flow and O2 delivery.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Intralipid-induced decrease in oxygenation in neonates is related to changes in the respiratory quotient.
Intravenous lipid infusion has been previously reported to be associated with hypoxemia. Different mechanisms have been proposed, but none have explored the decrease in respiratory quotient (RQ) following lipid administration as a possible factor. Ten neonates without respiratory problems, breathing room air and on total parenteral nutrition were studied. Arterialized capillary blood gases, transcutaneous PO2 (TcPO2) measurements and expired gas concentrations were obtained, prior to and 1 g/kg of 10% lipid emulsion was infused over 6 h. Following lipid infusion, the TcPO2 decreased from 72 +/- 8 to 65 +/- 8 mm Hg and the RQ decreased from 0.94 +/- 0.08 to 0.86 +/- 0.5 (p less than 0.05), while the pH, PaCO2 and the alveolar-arterial oxygen tension difference did not change. The decrease in TcPO2 significantly correlated with the decrease in alveolar oxygen tension. Seven of the 10 infants had a significant decrease in TcPO2 with a significant decrease in RQ from 0.98 +/- 0.05 to 0.85 +/- 0.06 (p less than 0.01). In 3 patients with no significant change in TcPO2 following intralipid administration, the RQ was initially significantly lower than the rest of the group (0.85 +/- 0.04; p less than 0.05) and did not change at the end of the infusion (0.88 +/- 0.03). These data suggest that the changes in PaO2 following lipid infusion in neonates without lung disease and breathing room air, are related to the decrease in alveolar oxygen tension secondary to the change in RQ.
Blood Gas Monitoring, Transcutaneous↗