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Biomedical subjects

E Patterson

Publications and source records attributed to E Patterson.

At least 55 records · Page 3Linked to original sources
PubMed1995

Electrophysiological characterization of a novel class III antiarrhythmic agent, GLG-V-13 in the mammalian heart.

GLG-V-13, a novel 3,7-diheterabicyclo[3.3.1]nonane, was examined both in vivo and in vitro in order to characterize its electrophysiological, haemodynamic and inotropic properties. Left ventricular epicardial monophasic action potential (MAP), surface ECG and mean arterial blood pressure (MBP) were recorded in six pentobarbital-anaesthetized, artificially ventilated and thoracotomized guinea-pigs. When studied in an intravenous dose interval ranging between 0.5 micrograms/kg and 500 micrograms/kg, GLG-V-13 dose-dependently lengthened the MAP duration (p < 0.05 at doses above 5 micrograms/kg), the atrioventricular conduction time (p < 0.05 at doses above 1 microgram/kg) and the RR interval (p < 0.05 at doses above 25 micrograms/kg). At the highest dose (500 micrograms/kg) these variables were increased by 30%, 13% and 23%, respectively. Only minor effects were noted on intraventricular conduction time (QRS interval) and MBP. In rabbit atrial and papillary muscle preparations, GLG-V-13 (0.32 to 3.2 mg/l) did not exert negative inotropic action. In 10 intact anaesthetized mongrel dogs, left ventricular endocardial MAP at 90% repolarization (MAP90) was measured during atrial pacing before and after administration of GLG-V-13, 3 and 6 mg/kg i.v., respectively.

Action Potentials↗
PubMed1995

Atrial inputs as determinants of atrioventricular nodal conduction: re-evaluation and new concepts.

Radiofrequency ablation was combined with standard recording and pacing procedures to determine the role of the perinodal fast pathway (FP) and slow pathway (SP) in atrioventricular (A-V) conduction in normal dog hearts. In 16 anesthetized, open-chest dogs, we recorded atrial (A) electrograms from the high right atrium (HRA), His bundle (Hb) region and coronary sinus (CS) ostium. In 8 dogs, during HRA pacing at a cycle length of 400 ms, FP ablation induced a significant change in A-H interval (61 +/- 12 to 107 +/- 9 ms, p < 0.001) but no change in Wenckebach cycle length (185 +/- 14 to 190 +/- 12 ms, NS). During ventricular pacing (400 ms cycle length) there was a shift in retrograde atrial activation so that Hb (A) delayed more than CS (A). Subsequent SP ablation in this same group of 8 dogs, produced a significant prolongation of antegrade Wenckebach cycle length (190 +/- 10 to 277 +/- 36 ms, p < 0.002) but only one instance of complete A-V block even though both FP and SP were ablated in accordance with clinical criteria. In another group of 8 dogs, a specially designed ablation electrode was inserted into the right atrium and positioned at the level of the fossa ovalis, 10-12 mm superior to the perinodal area. A radiofrequency linear lesion across the interatrial system induced a marked PR interval prolongation due to an intra-atrial rather than A-V nodal delay. The A-H interval was unchanged, and there was no change in antegrade or retrograde Wenckebach cycle length. In contrast, to the findings in both these groups direct damage to the A-V node showed immediate change in the A-H interval and at the same time progression to second degree and complete heart block. Taken together these results suggest that the perinodal FP and SP are composed of transitional cells which possess distinct electrophysiological properties not shared by adjacent atrial tissues or the compact A-V node itself. We conclude that the persistence of A-V conduction, albeit modified, after FP and SP ablation, suggests the existence of multiple atrio A-V nodal inputs whereas retrograde conduction relies mainly on dual exits from the A-V node to the atria.

Animals↗
PubMed1994

Facilitation of reentry by lidocaine in canine myocardial infarction.

The authors studied the effects of lidocaine in 18 consecutive dogs with myocardial infarction 1 to 4 days after two-stage left anterior descending coronary artery ligation. Electrophysiologic testing was performed in anesthetized dogs after infarction with single-, double-, or triple-programmed extrastimuli or rapid bursts (3 beats at 240 to 420 beats/min) delivered to the right ventricular outflow tract. Inducibility of sustained monomorphic ventricular tachycardia after an intravenous bolus of lidocaine (3 to 6 mg/kg) was compared in the same animal to the premedicated state. In the control state, sustained monomorphic ventricular tachycardia was inducible in 6 of 18 dogs. After administration of lidocaine, electrically induced sustained monomorphic ventricular tachycardia was initiated in an additional nine dogs (which were previously noninducible; after lidocaine administration vs control p < 0.02). The antiarrhythmic agent induced further rate-dependent slowing of conduction in the periinfarction subepicardium, which at a critical value of rate and amount of conduction delay resulted in sustained reentrant monomorphic tachycardia. These results show that lidocaine has marked proarrhythmic action in this canine model of myocardial infarction, probably because of its depressant effect on injured cardiac tissue.

Animals↗
PubMed1994

Bacterial vaginosis is associated with prematurity and vaginal fluid mucinase and sialidase: results of a controlled trial of topical clindamycin cream.

OBJECTIVE: The pathogenesis of preterm birth and other adverse pregnancy outcomes linked with reproductive tract infection remains poorly understood. Mucolytic enzymes, including mucinases and sialidases (neuraminidase), are recognized virulence factors among enteropathogens and bacteria that cause periodontal infection. Perturbation of maternal cervicovaginal mucosa membrane host defenses by such enzyme-producing microorganisms may increase the risk of subclinical intrauterine infection during pregnancy and thus increase risks of preterm birth. STUDY DESIGN: We prospectively evaluated vaginal fluid mucinase and sialidase and selected cervicovaginal bacteria along with pregnancy outcomes in 271 women. Within this study, women with bacterial vaginosis (16 to 27 week' gestation) were treated with 2% clinadmycin vaginal cream or placebo. Enzyme, microbial findings, treatment effects, and pregnancy outcomes were compared among drug- and placebo-treated women and control women without bacterial vaginosis. RESULTS: Presence of bacterial vaginosis at intake was associated with increased risk of preterm birth (relative risk 3.3, 95% confidence interval 1.2 to 9.1, p = 0.02), premature rupture of membranes (relative risk 3.8, 95% confidence interval 1.6 to 9.0, p = 0.002), and preterm premature rupture of membranes. Mucinase and sialidase activities were more commonly identified, and they occurred in higher concentrations, if present, in women with bacterial vaginosis (mucinase: 44.3% with bacterial vaginosis vs 27.4% without, p = 0.007; sialidase: 45% with bacterial vaginosis vs 12% without p < 0.001). Sialidase activity was associated with bacterial vaginosis-linked organisms (Gardnerella vaginalis, Mobiluncus spp, and Mycoplasma hominis) and Chlamydia trachomatis and yeast species; mucinase activity was associated only with bacterial vaginosis-linked microorganisms. Clindamycin, 2% cream, was effective treatment for bacterial vaginosis and temporarily reduced mucinase and sialidase activities. Topical treatment of bacterial vaginosis did not reduce risks of perinatal morbidity. Women with persistent or recurrent sialidase 8 weeks after treatment were at increased risk of preterm birth (15.6% vs 7.4%) premature rupture of membranes (30% vs 15%), and low birth weight (20% vs 3%, relative risk 6.8, 95% confidence interval 1.6 to 28.1). CONCLUSIONS: Persistence of sialidase-producing vaginal microorganisms in numbers sufficient to increase vaginal fluid sialidase activity may be a risk factor for possibly preventable subclinical intrauterine infection and preterm birth. This study confirms and further informs our understanding of the association of bacterial vaginosis and preterm birth; studies to evaluate whether systemic treatment for bacterial vaginosis can effectively reduce vaginal mucolytic enzymes and risks of prematurity and other morbid outcomes are continuing.

Administration, Topical↗
PubMed1994

Facilitation of reentry by lidocaine in canine myocardial infarction.

Despite continuing controversies regarding its antiarrhythmic and antifibrillatory efficacy lidocaine is frequently used for the treatment of ventricular arrhythmias occurring in the early phase of acute myocardial infarction (MI). The authors studied the effects of lidocaine in 18 consecutive MI dogs 1-4 days (2.8 +/- 0.3 day) after the two-stage left anterior descending coronary artery (LAD) ligation and in 11 dogs, in which the LAD and the distal branches of the left circumflex artery was ligated 12-75 (mean 35) days prior to study. Electrophysiologic testing was performed in anesthetized post-infarction dogs using single, double or triple programmed extrastimuli or rapid bursts (3 beats at 240-420/min) delivered to the right ventricular outflow tract. Inducibility of SMVT (uniform QRS morphology lasting > 30 sec at a rate of > 250 beat/min) after an i.v. bolus of lidocaine (3-6 mg/kg) was compared in the same animal to the pre-drug state. During the control state, SMVT was inducible in 6/18 dogs. After the administration of lidocaine, electrically induced SMVT was initiated in additionally 9 dogs (which were previously non-inducible; post-lidocaine vs control p < 0.02). Sustained reentry was induced by 3 mg/kg lidocaine in 5 dogs (310 +/- 62 beat/min) and by 6 mg/kg in 4 (261 +/- 52 beat/min). In the 8 survivors of the chronic MI group, SMVT was inducible before lidocaine administration in one, but in 7 after lidocaine. The antiarrhythmic agent induced further rate-dependent slowing of conduction in the peri-infarction subepicardium, which at a critical value of rate and amount of conduction delay resulted in sustained reentrant monomorphic tachycardia. These results show that lidocaine has arrhythmogenic/proarrhythmic actions in these canine models of MI probably due to its depressant effect on moderately sick cardiac tissue. The 'modification' of the functional properties of the arrhythmia substrate by lidocaine can promote the formation of new reentrant pathways leading to manifest sustained ventricular reentry under electrophysiologic study.

Acute Disease↗
PubMed1993

Electrophysiologic actions of BRB-I-28 in ischemically injured canine myocardium.

We examined the electrophysiologic actions of BRB-I-28 using two in vivo and two in vitro models of myocardial ischemic injury. In intact canine heart studied 4 days after anterior descending coronary artery occlusion, BRB-I-28 (3 and 6 mg/kg, i.v.) prolonged refractoriness in ischemically injured epicardium to an extent similar to that caused by lidocaine (3 and 6 mg/kg i.v.). BRB-I-28 produced less rate-dependent epicardial delay and, unlike lidocaine, failed to facilitate reentrant arrhythmia formation. Lidocaine and BRB-I-28 (3 and 6 mg/kg i.v.) produced similar rate-dependent prolongation of HV intervals in the normal His-Purkinje system, and produced both tonic and use-dependent conduction block in the ischemically injured His-Purkinje system studied 2 h after anteroseptal coronary artery ligation. In isolated superfused ventricular epicardium studied 1-4 days after anterior descending coronary artery ligation, BRB-I-28 reduced action potential amplitude (APA) and maximum phase 0 upstroke (Vmax) in normal (3.2 mg/L) and ischemically injured (1 and 3.2 mg/L) tissue, with marked tonic and use-dependent conduction block (3.2 mg/L). AP potential duration (APD) was unaltered. In isolated, superfused, ischemically injured canine endocardium studied 24 h after anterior descending coronary artery occlusion, BRB-I-28 (3.2 and 10 ml/L) reduced APA and Vmax and prolonged refractoriness and conduction times in ischemically injured tissue without altering APD. Tonic block was more prominent, and use-dependent block was observed at lower drug concentrations in ischemically injured tissue. The data demonstrate selective conduction depression and prolongation of refractoriness for BRB-I-28 in ischemically injured tissues. Both use-dependent and tonic conduction block contribute to the decrease in conduction observed with BRB-I-28 in ischemically injured myocardium, with more prominent tonic conduction block present in ischemically injured epicardium and His-Purkinje tissue at 2-24 h after coronary artery occlusion than in ischemically injured left ventricular (LV) epicardium studied 4 days after coronary artery occlusion.

Animals↗
PubMed1993

Rapid inward current in ischemically-injured subepicardial myocytes bordering myocardial infarction.

INTRODUCTION: To determine if collagenase-dispersed epicardial myocytes overlying myocardial infarction reproduce the same altered electrophysiology observed in intact epicardium, multicellular tissue preparations and enzymatically-dispersed myocytes from ischemically-injured canine subepicardium were examined 1 and 4 days after myocardial infarction. METHODS AND RESULTS: The electrophysiologic changes observed with ischemic injury in enzymatically-dispersed myocytes were not different from changes observed in multicellular tissue preparations at 1 and 4 days postinfarction. Ischemically-injured myocytes were depolarized versus normal myocytes at [K0]+ (2.5 to 40 mM) with reduced membrane potentials also observed in injured subepicardial tissue preparations [K0]+ (4 to 24 mM). On day 1, the reduced Vmax and the prolonged recovery of Vmax from inactivation were consistent with the reduced membrane potentials observed at each [K0]+. The half-maximal Vmax, maximal Vmax, and Boltzmann constant (k) in injured myocytes were unchanged versus normal myocytes. On day 4 postinfarction, the half-maximal Vmax was shifted to a more negative membrane potential, the maximal Vmax was reduced, and k was increased in injured versus normal myocytes. Prolonged recovery from inactivation was observed with depressed membrane potentials in injured myocytes on day 4. CONCLUSION: Enzymatically-dispersed myocytes from ischemically-injured subepicardium closely reproduce altered cellular properties observed in multicellular tissue preparations. The data suggest that 1 day postinfarction, altered conduction and refractoriness largely result from a reduced membrane potential. At 4 days, a reduced maximal Vmax, a shift in the inactivation curve to more negative voltages, and prolonged recovery of Vmax from inactivation also contribute to slowed conduction and prolonged refractoriness.

Animals↗
PubMed1993

Detection of Trichomonas vaginalis in pregnant women with the InPouch TV culture system.

Trichomonas vaginalis causes a common genitourinary infection which is frequently asymptomatic. At present, pregnant women are not usually screened for the infection unless they are symptomatic. In the present study, we screened and obtained samples for culture from all pregnant women attending a prenatal clinic with the InPouch TV culture system and compared results with those of standard culture in Diamond's medium and slide wet mount examination. The InPouch TV culture system was as reliable as Diamond's medium in detecting T. vaginalis and may be useful and effective in a pregnancy clinic setting.

Animals↗
PubMed1993

The comparative antiarrhythmic and proarrhythmic activity of a 3,7-diheterobicyclo[3.3.1]nonane, BRB-I-28, and lidocaine in the 1-4-day-old infarcted dog heart.

We compared the electrophysiological effects and quantified the antiarrhythmic/proarrhythmic potential of the 3,7-diheterobicyclo[3.3.1]nonane-derivative, BRB-I-28 and lidocaine in 15 consecutive postinfarction dogs. Electrophysiologic studies were performed in anesthetized animals, 1-4 days (mean +/- SE = 2.47 +/- 0.36) after the two-stage ligation of the left anterior descending coronary artery. Inducibility of sustained monomorphic ventricular tachycardia (SMVT) was compared in the pre-drug state, and after i.v. lidocaine (3 and 6 mg/kg) and BRB-I-28 (3 and 6 mg/kg) administration. During the control state, SMVT was inducible in 6/15 dogs (40%). After the administration of lidocaine, the rate of the inducible SMVT slowed (353 +/- 91 to 272 +/- 96 beat/min; p < 0.01), but due to the proarrhythmic action of the drug, SMVT became inducible in 13/15 dogs (87%). Sustained reentry was induced after 3 mg/kg lidocaine in 3 dogs and after 6 mg/kg in 4. The mean aortic blood pressure in these SMVTs was 36 +/- 8 mm Hg. After administration of BRB-I-28 (6 mg/kg) SMVT was not inducible in 2/6 and in 4 the SMVT rate was slowed (380 +/- 104 to 208 +/- 105 beat/min; p < 0.005) before termination in 3. In 2 dogs SMVT was induced after BRB-I-28 was given whereas they were non-inducible in the control state (proarrhythmic effect: 13%). Furthermore the hemodynamic state during the SMVTs was more stable after BRB-I-28 (mean aortic blood pressure = 65 +/- 7 mm Hg; post-BRB-I-28 vs post-lidocaine, p < 0.001). During sinus rhythm, lidocaine caused a transient lowering of the MBP (105 +/- 17 to 84 +/- 18 mm Hg; p < 0.001), whereas, BRB-I-28, induced a consistent but short-lasting pressor response (98 +/- 18 to 120 +/- 29 mm Hg; p < 0.001) after its bolus injection. The low proarrhythmic activity and the lack of a cardiodepressant action makes this new chemical class of antiarrhythmics worthy of further development.

Animals↗
PubMed1993

Coronary vascular injury after transient coronary artery occlusion.

BACKGROUND: Microvascular function was examined in dog hearts subjected to transient coronary artery occlusion. EXPERIMENTAL DESIGN: Temporary coronary artery occlusion (15 or 30 minutes) followed by prolonged reperfusion (24 to 72 hours) was performed in dogs. Myocardial blood flow (radioactive microspheres), vascular permeability (human serum albumin uptake), and apparent vascular volume (radioactively labeled erythrocytes) were used as measures of vascular function. Myeloperoxidase was used as a measure of leukocyte uptake. Free radical formation was measured by electron spin resonance using a spin trapping agent (phenyl N-tert-butylnitrone). RESULTS: A 30-minute occlusion followed by reperfusion produced prolonged hyperemia, increased vascular permeability, increased apparent vascular volume, and increased leukocyte uptake. Extravasation of red blood cells and carbon black was present within the coronary artery distribution. The altered vascular function was temporally correlated with prolonged leukocyte uptake and free radical production, returning to control values only at 72 hours. A 15-minute occlusion increased vascular permeability at 24 hours, without altering myocardial blood flow or apparent vascular volume. Transmural myocardial leukocyte accumulation after a 15-minute occlusion was minimal in the absence of myocardial infarction or other histologic alterations. Active free radical formation was minimal at 24 hours, with a return of vascular permeability to control values at 48 hours. CONCLUSIONS: The data demonstrate prolonged dysfunction of the coronary microvasculature after a transient 30-minute occlusion of the left anterior descending coronary artery. The prolonged injury is associated temporally with leukocyte uptake and free radical formation in the presence of minimal infarction. A transient 15-minute occlusion produces a different pattern of vascular dysfunction with an abbreviated duration (24 hours), not associated with myocardial necrosis, extensive leukocyte uptake, nor prolonged free radical formation.

Animals↗
PubMed1993

Coronary vascular injury following transient coronary artery occlusion: prevention by pretreatment with deferoxamine, dimethylthiourea and N-2-mercaptoproprionyl glycine.

The role of oxygen-derived free radicals as initiators of vascular dysfunction observed 24 hr after transient coronary artery occlusion (15 or 30 min) was examined in the anesthetized dog. A 15-min occlusion increased human serum (HSA) albumin extravasation within anterior myocardium without producing myocardial necrosis or edema. Minimal leukocyte uptake and free radical formation were present at 24 hr. 2-Mercaptoproprionyl glycine (MPG) (a free radical scavenger), deferoxamine (a chelator of ferrous ions) and dimethylthiourea (a hydroxyl ion scavenger), administered 15 min before coronary artery occlusion and extending 1.5 hr into reperfusion, reduced HSA uptake within anterior myocardium. A different pattern of injury was present after a 30-min occlusion. Subendocardial necrosis (1.2 +/- 0.8 g), edema, HSA extravasation and leukocyte uptake were observed at 24 hr. MPG failed to reduce the extent of necrosis, HSA extravasation, edema, leukocyte uptake or free radical formation. HSA extravasation, leukocyte uptake, tissue edema and free radical formation present 24 hr after a 30-min occlusion were reduced by acute deferoxamine and dimethylthiourea, but not by acute MPG administration. The failure of MPG to reduce HSA extravasation observed 24 hr after a 30-min coronary artery occlusion was associated with both leukocyte uptake and continued free radical formation, whereas dimethylthiourea and deferoxamine reduced leukocyte uptake, free radical formation and HSA extravasation.

Animals↗
PubMed1992

High-performance liquid chromatographic determination of BRB-I-28, a novel antiarrhythmic agent, in dog plasma and urine.

A sensitive reversed-phase high-performance liquid chromatographic (HPLC) technique with ultraviolet detection has been developed to determine the concentration of BRB-I-28 (I), a novel antiarrhythmic agent, in dog plasma and urine. The mobile phase was acetonitrile-methanol-37.5 mM phosphate buffer, pH 6.8-triethylamine (50:50:75:0.1, v/v). The compound was extracted from dog plasma and urine with chloroform after alkalinization with sodium hydroxide. The extraction recovery was 83% from plasma and 84% from urine. Good linearity (r > 0.996) was observed throughout the ranges 0.1-12.0 micrograms/ml (plasma) and 0.1-8.0 micrograms/ml (urine). Intra- and inter-assay variabilities were less than 4%. The lower limit of quantitation was 0.08 microgram/ml in either plasma or urine. HPLC analysis of plasma and urine samples from a dog treated with I has demonstrated that the method was accurate and reproducible.

Animals↗
PubMed1992

Association of cervicovaginal infections with increased vaginal fluid phospholipase A2 activity.

OBJECTIVE: The purpose of this study was to determine if phospholipase A2 was detectable within vaginal fluid and to correlate its presence with the presence of common lower genital tract infection or microbial conditions. STUDY DESIGN: Pregnant women were examined at the first prenatal visit with standard clinical evaluations and microbiologic cultures or tests. Vaginal fluid samples were evaluated for phospholipase A2 activity by means of a standardized enzyme fluorometric assay. Data were stratified to control for coexisting infections. RESULTS: Phospholipase A2 activity was detected among 29.8% of women and was independently associated with the presence of bacterial vaginosis (p < 0.001), Trichomonas. vaginalis (p < 0.04), and Chlamydia trachomatis (p < 0.02). The percentage of women with phospholipase A2 activity and the level of activity was increased in the presence of more than one infection. CONCLUSIONS: Elevated reproductive tract phospholipase A2 concentrations among pregnant women may play roles in the pathogenesis of preterm labor and birth. Identification of pregnant women with increased concentrations in vaginal fluid may allow for development of effective intervention strategies to reduce the risk of preterm birth.

Animals↗
PubMed1992

Mapping in the atrioventricular junction.

Ectopic conduction is defined as the premature exit of the cardiac impulse from the specialized conduction system across a damaged Purkinje-ventricular muscle interface. This anomalous form of atrioventricular (AV) conduction was induced in the dog heart by lidocaine injection of the His bundle-interventricular septum interface and by ischemic damage of the AV junction subsequent to anterior septal artery ligation in the dog heart. The electrocardiogram (ECG) manifestation of ectopic conduction is the loss of initial forces and replacement of the Q waves with delta waves. In order to verify these effects, the authors devised a multi-electrode, malleable plaque (63 electrode sites) that could be secured at the AV junction during venous occlusion in the open-chest, anesthetized dog. Preliminary maps indicated a dramatic change in activation that proceeded from apex to base of the heart in the control state and reversed after ischemic damage to the His bundle. In vitro, it was possible to induce ectopic conduction by lidocaine injection at the interface of the right bundle branch and septal muscle. Microelectrode studies demonstrated that foot potentials, for example, electrotonic, or subthreshold potentials mediated the connection from Purkinje to muscle in the damaged zone. In a recent set of experiments in vivo, subthreshold stimulation (STS) was delivered to simulate electrotonic potentials to the His bundle region, and right ventricular apex, using multipolar electrode catheters. In the normal heart, STS delivered as DC constant current or pulse trains (1000 Hz, 50 ms pulse duration) induced shortened P-R intervals and delta waves with or without bundle branch block patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The clinicopathological features of three babies with osteogenesis imperfecta resulting from the substitution of glycine by valine in the pro alpha 1 (I) chain of type I procollagen.

The features of three babies with perinatal lethal osteogenesis imperfecta (OI II) resulting from substitutions of glycine by valine in the triple helical domain of the alpha 1(I) chain of type I collagen were studied. The babies were heterozygous for this substitution at residue 1006 in case 1 (OI35), 973 in case 2 (OI59), and 256 in case 3 (OI7B). OI35 had the most severe clinical form, OI IIC, with premature rupture of membranes, severe antepartum haemorrhage, stillbirth, severe short limbed dwarfism, and extreme osteoporosis. OI59 was a better formed baby but was also born prematurely as a result of premature rupture of membranes and severe antepartum haemorrhage. She had the radiographic features of OI IIA. OI7B was born at term and also had the radiographic features of OI IIA. Pathological examination of the skeletons of OI35 and OI59 showed grossly deficient intramembranous and endochondral ossification. Trabecular bone was sparse in the long bones and vertebrae. The trabeculae contained a cartilage core and an overlying layer of woven bone or osteoid. The diaphyses lacked cortical bone. The periosteal fibroblasts of OI35 contained grossly distended rough endoplasmic reticulum consistent with the 53% reduction in collagen secretion by cultured dermal fibroblasts. The aorta, skin, and lungs were hypoplastic in OI35 and OI59. The findings in this study show that glycine substitutions by valine in Gly-X-Y triplets, from glycine 256 to glycine 1006, of the triple helical domain of alpha 1(I) chains produce the OI II phenotype. The phenotype was most severe in the baby with the most carboxy-terminal substitution.

Adult↗
PubMed1992

Effects of BRB-I-28, a novel antiarrhythmic agent, and its derivatives on cardiac Na+,K(+)-ATPase, Mg(2+)-ATPase activities and contractile force.

The effects of BRB-I-28, SAZ-VII-22 and SAZ-VII-23, a novel class of antiarrhythmic agents and other 3,7-diheterobicyclo[3.3.1]nonane (DHBCN) derivatives on guinea pig myocardial Na+,K(+)-ATPase and Mg(2+)-activated ATPase activities were investigated in comparison with those of tedisamil, lidocaine and ouabain. BRB-I-28, SAZ-VII-22, SAZ-VII-23, tedisamil and their derivatives produced concentration-dependent inhibition on both Na+,K(+)-ATPase and Mg(2+)-activated ATPase. Ouabain had no effect on the Mg(2+)-activated ATPase activity and GLG-IV-44 had no significant inhibition on Na+,K(+)-ATPase. Molar refractivity, retention time in reverse-phase HPLC, and partition coefficients were determined and the influence of these three parameters on the inhibitory effects of DHBCN on ATPase was examined. It seems that inhibitory effects of DHBCN derivatives on Na+,K(+)-ATPase and Mg(2+)-activated ATPase increase with an increase in lipophilicity, while hydrophilic groups of the drugs may not be important for interaction between drugs and ATPases. The effects of BRB-I-28 on contractile force development in rabbit atrial and papillary muscles were studied. At paced rates of 0.5 and 1.0 Hz in atrial muscle, BRB-I-28 produced an apparent positive inotropic effect in isolated rabbit atrial muscle, which is consistent with its inhibitory effects on Na+,K(+)-ATPase and Mg(2+)-ATPase activities. Inhibitory effects on myocardial Na+,K(+)-ATPase and Mg(2+)-activated ATPase activities may be the basis of some electrophysiological effects of antiarrhythmic properties of BRB-I-28, SAZ-VII-22, SAZ-VII-23, and tedisamil.

Animals↗