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Maternal cardiac rhythm disorders in normal pregnancy
Heart,
Lung
and Circulation
48th Annual
2000; 9
MATERNAL CARDIAC RHYTHM DISORDERS IN ’ i PREGNANCY Niv Rotunda Hospital & Mater Misericordiae Hospital, Dublin, Ireland
NORMAL
Study Hypothesis: Healthy pregnant women, wthout apparent heart disease, who present with symptoms such as palpitations and presyncope, pose a clinical problem for the obstetrician, as not all can be offered cardiological referral. ‘Ihe exact incidence of cardiac arrhythmia in this population 1s unknownl. Theoretically, the haemodynamxc change and the altered autonomic responsiveness of pregnancy, m addition fo psychologxal stress can predispose to arrhythmia. This study tests the hypothws that the pregnant state facilitates arrhythmogenesis in women, without apparent heart disease, through inhibition of vagal cardiac modulation. Methods: An observational cohort study of 100 healthy, Caucasian women of mixed parity. Congenital arrhythnnas, thyroid dystimction and anemia were excluded prior to study en@. Subjects attended a designated research antenatal clinic and were monitored wth domicihary 24-hour ambulatory electmcardmgraphy at eight-week mtewals from 6 weeks gestation and in the postnatal period. The tapes were analysed with a Reynolds Medical Pathfinder 600 by a single observer (MNB). Outcome measnres were cardiac arrhythmias and time domain measwes of heart rate variability as per standard criteria. Microsoft Excel was used as the database and SPSS was used for statistical analysis. Results: 29 women were symptomatic during the monitoring periods and all 29 had cardiac arrhythmias on ambulatmy electrocardiography. The symptomatic episodes did not correlate with the rhythm disturbance. 64 of the 71 asymptomatic women also had rhythm disturbance on electrocardiography. The distribution of rhythm disturbance in both groups included sinus node, atria1 and ventricular arrhythmias. Only one patient reported symptoms during the post-natal period confuming a statistically significant reduction in symptoms (p
POLYUNSATURATED FATTY ACID THE N-3 EICOSAPENTANOIC ACID (EPA) STIMULATES THE NA-K PUMP IN RABBIT CARDIAC MYOCYTES. AD. Pitt*. C. mdes. H.H. Rasmussen and D.W. Whw Cardiology Dept. Royal North Shore Hospital, Sydney, NSW. Acute exposure of heart cells to fish oils, including EPA, has been shown to have antiarrhythmic effects including reduction of beating rate, hyperpolarisation of resting potential, and increase in threshold potential. Most studies have focused on the role of ion channels in mediating this effect. However, the influence of EPA on the Na-K pump has not been examined despite the importance of this enzyme in determining contractility and membrane potential. Methods: Whole cell patch clamping was conducted on cardiac myocytes isolated from rabbits. NdK+ pump current (I& was measured using pipette Na’ concentrations ([Na],,,) of 10 mM (near physiological intracellular levels) and 80 mM (to induce maximum I&. I, was defined as the shift in holding current upon exposure to 100 pM ouabain after 5-6 minutes superfusion with 5 PM EPA or control Tyrodes solution. To assess the involvement of Na+ influx into the cell we used a Na+-free superfusate. Results: (pA/pF, mean + SEM). EPA superfusion stimulated I, at [Na],,, of 10 mM (0.48 k 0.04 vs control 0.32 f 0.01, p
Scientific
Meeting
of CSANZ
A1.5’
SPECIFIC ACCUMULATION OF POLYMORPHONUCLEAR LEUKOCYTES ON ARTERIAL AND VENOUS THROMBI IN PLASMINOGEN KNOCK-OUT MICE BZene*.ce. J Kril. B Freedman and D Brie!=, Department of Cardiology, Concord
Hospital,
Sydney,
University
of Sydney
A number of studies demonstrate that alternative tibrinolytic mechanisms involvmg polymophonuclear leukocytes(PMNs) may contribute to clot lysis. However, substantial evidence for the role of these cells in nonplasmin mediated pathways of fibrinolysis has been obtained from in vitro studies and lacks firm biological confirmation. Plasminogen deficient mice provide the ideal tool for this study. To directly identify the PMNs incorporated into thrombi in vwo, simultaneous arterial and venous thrombl were induced by application of 20% ferric chloride to the left jugular vein and left common carotid artery m Plg+/+(n=ld) and Pig-i-(n=14) mice of either sex, aged 12 to 16 weeks. At 6, 24, 48 and 72 hours, Innnnnohistochemical staining with RB6-8C5 antibody (a specific cell surface marker for neutrophil) was utilised to characterise PMNs within the thmmbi. Viability was assumed if the cells retained their normal architecture by light microscopy and the total numbers of viable PMNs in both arterial and venous thrombi were quantitated (see table). --,Table: PMNs accumulation -tithin thmmbi in mice of different genotypes Venous thmmbi Arterial thrombi I Pig+/+ Pig-/Pig+/+ Plg-i584fll2 460f124 440f20 402+199 6 hours 1000+115 73lC157 453*44 361flOl 24 hours 350fl84 574f227 104*33 392f79 48 hours lOOf 252f50* 6lklO 255f41** 72 hours Data are mean + SEM. * P < 0.05; **P < 0.01 The number of viable PMNs in thrombi from P&i+ and Pig-i- mice was comparable 6 to 24 hours following thrombus formation. By 48 hours there was a greater retention of viable PMNs in arterial and venous thrombi of plasminogen knockout nnce than in control annnals. This suggests that PMN may be capable of contributing to sustained thrombolysis in response to significant thrombotic challenges m viva.
POTENTIAL
ON
INFLAMMATION
MONOCYTE-DERIVED
S.Nakhla. University
EFFECTS
OF NITROGLYCERIN
MACROPHAGES
(GTN)
(MDMS).
A.K.Death?
K.C.Y.Cb S.Poon. D.S. Celex~&~, Department of Sydney, Heart Research Institute, Sydney, NSW
of Medicme,
GTN is one of the most frequently used therapeutic agents for the symptomatic relief of stable or unstable angina. Little is known, however, about the potential anti-atherogenic or anti-inflammatory effects of this me&cation. We now describe evidence that GTN has pro-inflammatory effects on metalloproteinase (MMP) gene expression and activities in MDMs. Monocytes were isolated from whole blood by elutriation and allowed to differentiate into macrophages over X-10 days. The MDMs were then treated for 4 hours with GTN (200pmol), G’I’N (2000pmol; approximate peak concentration after GTN administration in viva), SIN-l (2000pmol; another nitric oxide donor) or vehicle. MMP activity was measured by zymography, tissue inlnbitor of metalloproteinase-1 (TIMP-1) protein levels measured by ELISA and MMP/TIMP mRNA levels were quantified by competitive RTPCR.
The major MMP expressed
by MDMs
was the gelatinase,
MMP-9.
GTN
treatment stimulated a dose-dependent increase in MMP-9 mRNA levels (GTN 200:193&5, GTN 2000:372?4, p
MMP-2
and MMP-7
mRNA
levels, respectively,
compared
to control
cells.
MMP activity is tightly controlled by their specific inhibitor proteins, the TIMPs, and TIMP-1 mRNA and protein levels were decreased in GTN 2000treated MDMs compared to control cells (mRNA:62+20%, protein:52+15%, PCO.05). Therefore, GTN actwates MMP but represses TIMP expression in MDMs. The subsequent imbalance in MMPiTIMP expression associated wth GTN treahnent could lead to enhanced MDM degradation potential, thus increasing the vulnerability of a plaque to rupture.
Lung
and Circulation
48th Annual
2000; 9
MATERNAL CARDIAC RHYTHM DISORDERS IN ’ i PREGNANCY Niv Rotunda Hospital & Mater Misericordiae Hospital, Dublin, Ireland
NORMAL
Study Hypothesis: Healthy pregnant women, wthout apparent heart disease, who present with symptoms such as palpitations and presyncope, pose a clinical problem for the obstetrician, as not all can be offered cardiological referral. ‘Ihe exact incidence of cardiac arrhythmia in this population 1s unknownl. Theoretically, the haemodynamxc change and the altered autonomic responsiveness of pregnancy, m addition fo psychologxal stress can predispose to arrhythmia. This study tests the hypothws that the pregnant state facilitates arrhythmogenesis in women, without apparent heart disease, through inhibition of vagal cardiac modulation. Methods: An observational cohort study of 100 healthy, Caucasian women of mixed parity. Congenital arrhythnnas, thyroid dystimction and anemia were excluded prior to study en@. Subjects attended a designated research antenatal clinic and were monitored wth domicihary 24-hour ambulatory electmcardmgraphy at eight-week mtewals from 6 weeks gestation and in the postnatal period. The tapes were analysed with a Reynolds Medical Pathfinder 600 by a single observer (MNB). Outcome measnres were cardiac arrhythmias and time domain measwes of heart rate variability as per standard criteria. Microsoft Excel was used as the database and SPSS was used for statistical analysis. Results: 29 women were symptomatic during the monitoring periods and all 29 had cardiac arrhythmias on ambulatmy electrocardiography. The symptomatic episodes did not correlate with the rhythm disturbance. 64 of the 71 asymptomatic women also had rhythm disturbance on electrocardiography. The distribution of rhythm disturbance in both groups included sinus node, atria1 and ventricular arrhythmias. Only one patient reported symptoms during the post-natal period confuming a statistically significant reduction in symptoms (p
POLYUNSATURATED FATTY ACID THE N-3 EICOSAPENTANOIC ACID (EPA) STIMULATES THE NA-K PUMP IN RABBIT CARDIAC MYOCYTES. AD. Pitt*. C. mdes. H.H. Rasmussen and D.W. Whw Cardiology Dept. Royal North Shore Hospital, Sydney, NSW. Acute exposure of heart cells to fish oils, including EPA, has been shown to have antiarrhythmic effects including reduction of beating rate, hyperpolarisation of resting potential, and increase in threshold potential. Most studies have focused on the role of ion channels in mediating this effect. However, the influence of EPA on the Na-K pump has not been examined despite the importance of this enzyme in determining contractility and membrane potential. Methods: Whole cell patch clamping was conducted on cardiac myocytes isolated from rabbits. NdK+ pump current (I& was measured using pipette Na’ concentrations ([Na],,,) of 10 mM (near physiological intracellular levels) and 80 mM (to induce maximum I&. I, was defined as the shift in holding current upon exposure to 100 pM ouabain after 5-6 minutes superfusion with 5 PM EPA or control Tyrodes solution. To assess the involvement of Na+ influx into the cell we used a Na+-free superfusate. Results: (pA/pF, mean + SEM). EPA superfusion stimulated I, at [Na],,, of 10 mM (0.48 k 0.04 vs control 0.32 f 0.01, p
Scientific
Meeting
of CSANZ
A1.5’
SPECIFIC ACCUMULATION OF POLYMORPHONUCLEAR LEUKOCYTES ON ARTERIAL AND VENOUS THROMBI IN PLASMINOGEN KNOCK-OUT MICE BZene*.ce. J Kril. B Freedman and D Brie!=, Department of Cardiology, Concord
Hospital,
Sydney,
University
of Sydney
A number of studies demonstrate that alternative tibrinolytic mechanisms involvmg polymophonuclear leukocytes(PMNs) may contribute to clot lysis. However, substantial evidence for the role of these cells in nonplasmin mediated pathways of fibrinolysis has been obtained from in vitro studies and lacks firm biological confirmation. Plasminogen deficient mice provide the ideal tool for this study. To directly identify the PMNs incorporated into thrombi in vwo, simultaneous arterial and venous thrombl were induced by application of 20% ferric chloride to the left jugular vein and left common carotid artery m Plg+/+(n=ld) and Pig-i-(n=14) mice of either sex, aged 12 to 16 weeks. At 6, 24, 48 and 72 hours, Innnnnohistochemical staining with RB6-8C5 antibody (a specific cell surface marker for neutrophil) was utilised to characterise PMNs within the thmmbi. Viability was assumed if the cells retained their normal architecture by light microscopy and the total numbers of viable PMNs in both arterial and venous thrombi were quantitated (see table). --,Table: PMNs accumulation -tithin thmmbi in mice of different genotypes Venous thmmbi Arterial thrombi I Pig+/+ Pig-/Pig+/+ Plg-i584fll2 460f124 440f20 402+199 6 hours 1000+115 73lC157 453*44 361flOl 24 hours 350fl84 574f227 104*33 392f79 48 hours lOOf 252f50* 6lklO 255f41** 72 hours Data are mean + SEM. * P < 0.05; **P < 0.01 The number of viable PMNs in thrombi from P&i+ and Pig-i- mice was comparable 6 to 24 hours following thrombus formation. By 48 hours there was a greater retention of viable PMNs in arterial and venous thrombi of plasminogen knockout nnce than in control annnals. This suggests that PMN may be capable of contributing to sustained thrombolysis in response to significant thrombotic challenges m viva.
POTENTIAL
ON
INFLAMMATION
MONOCYTE-DERIVED
S.Nakhla. University
EFFECTS
OF NITROGLYCERIN
MACROPHAGES
(GTN)
(MDMS).
A.K.Death?
K.C.Y.Cb S.Poon. D.S. Celex~&~, Department of Sydney, Heart Research Institute, Sydney, NSW
of Medicme,
GTN is one of the most frequently used therapeutic agents for the symptomatic relief of stable or unstable angina. Little is known, however, about the potential anti-atherogenic or anti-inflammatory effects of this me&cation. We now describe evidence that GTN has pro-inflammatory effects on metalloproteinase (MMP) gene expression and activities in MDMs. Monocytes were isolated from whole blood by elutriation and allowed to differentiate into macrophages over X-10 days. The MDMs were then treated for 4 hours with GTN (200pmol), G’I’N (2000pmol; approximate peak concentration after GTN administration in viva), SIN-l (2000pmol; another nitric oxide donor) or vehicle. MMP activity was measured by zymography, tissue inlnbitor of metalloproteinase-1 (TIMP-1) protein levels measured by ELISA and MMP/TIMP mRNA levels were quantified by competitive RTPCR.
The major MMP expressed
by MDMs
was the gelatinase,
MMP-9.
GTN
treatment stimulated a dose-dependent increase in MMP-9 mRNA levels (GTN 200:193&5, GTN 2000:372?4, p
MMP-2
and MMP-7
mRNA
levels, respectively,
compared
to control
cells.
MMP activity is tightly controlled by their specific inhibitor proteins, the TIMPs, and TIMP-1 mRNA and protein levels were decreased in GTN 2000treated MDMs compared to control cells (mRNA:62+20%, protein:52+15%, PCO.05). Therefore, GTN actwates MMP but represses TIMP expression in MDMs. The subsequent imbalance in MMPiTIMP expression associated wth GTN treahnent could lead to enhanced MDM degradation potential, thus increasing the vulnerability of a plaque to rupture.