John G. Morgan
Royal Melbourne Hospital
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by John G. Morgan.
Circulation | 2003
Joseph B. Morton; Prashanthan Sanders; Jithendra K. Vohra; Paul B. Sparks; John G. Morgan; Steven J. Spence; Leeanne Grigg; Jonathan M. Kalman
Background—Adults with an atrial septal defect (ASD) frequently develop late atrial arrhythmias. We sought to characterize the pattern and persistence of atrial electrical remodeling caused by chronic right atrial (RA) stretch in this group. Methods and Results—Thirteen ASD patients without atrial arrhythmia (42±10 years old; RA volume, 65±16 mL) and 17 normal control subjects (44±11 years old; RA volume, 38±8 mL) had electrophysiological study to measure (1) atrial effective refractory period (AERP) from the low lateral/high lateral/high septal RA and distal coronary sinus (CS), (2) dispersion of AERP, (3) lateral-RA and CS conduction time during constant pacing, (4) conduction delay across the crista terminalis measuring the number of crista catheter bipoles (0–10) recording discrete double potentials during pacing, (5) corrected sinus node recovery time, and (6) P-wave duration. After ASD closure (8.3±5.6 months), follow-up echo studies (n=12) and electrophysiological study (n=4) were performed. The low-lateral AERP, P-wave duration, sinus node recovery time, and extent of conduction delay across the crista terminalis were significantly greater in ASD patients. No differences were found for other measured electrophysiological study parameters. At follow-up, there was incomplete resolution of RA volume (47±12 mL;P <0.01 versus before surgery), a trend toward shortening of the AERP at the lateral RA and an increase at the distal CS and high septal RA, but persisting extensive, widely split crista double potentials. Conclusions—Chronic RA stretch because of ASD causes electrical remodeling with modest increases in RA ERP, conduction delay at the crista terminalis, and sinus node dysfunction. Conduction delay at the crista terminalis persists beyond ASD closure and may contribute to the long-term atrial arrhythmia substrate in this condition.
Circulation | 2005
Igal A. Sebag; Mark D. Handschumacher; Fumito Ichinose; John G. Morgan; Ana Clara Tude Rodrigues; J. Luis Guerrero; Wolfgang Steudel; Michael J. Raher; Elkan F. Halpern; Geneviève Derumeaux; Kenneth D. Bloch; Michael H. Picard; Marielle Scherrer-Crosbie
Background—Tissue Doppler imaging (TDI) is a novel echocardiographic method to quantify regional myocardial function. The objective of this study was to assess whether myocardial velocities and strain rate (SR) could be obtained by TDI in mice and whether these indices accurately quantified alterations in left ventricular (LV) systolic function. Methods and Results—TDI was performed in 10 healthy mice to measure endocardial (vendo) and epicardial systolic velocities and SR. In further experiments, TDI indices were compared with dP/dtmax and with sonomicrometer-derived regional velocities, at rest and after administration of dobutamine or esmolol. TDI indices were also studied serially in 8 mice before and 4 and 7 hours after endotoxin challenge. Myocardial velocities and SR were obtained in all mice with low measurement variability. TDI indices increased with administration of dobutamine (vendo from 2.2±0.3 to 3.8±0.2 cm/s [P<0.01]; SR from 12±2 to 20±2 s−1 [P<0.05]) and decreased with administration of esmolol (vendo 1.4±0.2 cm/s [P<0.05]; SR 6±1 s−1 [P<0.01]). Both indices correlated strongly with dP/dtmax (r2=0.79 for SR and r2= 0.69 for vendo; both P<0.0001). SR and shortening fraction were predictors of dP/dtmax even after adjustment for the confounding effect of the other variables. Vendo correlated closely with sonomicrometer-measured velocity (r2=0.71, P<0.0005). After endotoxin challenge, decreases in both vendo and SR were detected before decreases in shortening fraction became manifest. Conclusions—Myocardial velocities and SR can be measured noninvasively in mice with the use of TDI. Both indices are sensitive markers for quantifying LV global and regional function in mice.
Circulation Research | 2007
Fumito Ichinose; Emmanuel Buys; Tomas G. Neilan; Elissa Furutani; John G. Morgan; Davinder S. Jassal; Amanda R. Graveline; Robert J. Searles; Chee Chew Lim; Masao Kaneki; Michael H. Picard; Marielle Scherrer-Crosbie; Stefan Janssens; Ronglih Liao; Kenneth D. Bloch
Myocardial dysfunction contributes to the high mortality of patients with endotoxemia. Although nitric oxide (NO) has been implicated in the pathogenesis of septic cardiovascular dysfunction, the role of myocardial NO synthase 3 (NOS3) remains incompletely defined. Here we show that mice with cardiomyocyte-specific NOS3 overexpression (NOS3TG) are protected from myocardial dysfunction and death associated with endotoxemia. Endotoxin induced more marked impairment of Ca2+ transients and cellular contraction in wild-type than in NOS3TG cardiomyocytes, in part, because of greater total sarcoplasmic reticulum Ca2+ load and myofilament sensitivity to Ca2+ in the latter during endotoxemia. Endotoxin increased reactive oxygen species production in wild-type but not NOS3TG hearts, in part, because of increased xanthine oxidase activity. Inhibition of NOS by NG-nitro-l-arginine-methyl ester restored the ability of endotoxin to increase reactive oxygen species production and xanthine oxidase activity in NOS3TG hearts to the levels measured in endotoxin-challenged wild-type hearts. Allopurinol, a xanthine oxidase inhibitor, attenuated endotoxin-induced reactive oxygen species accumulation and myocardial dysfunction in wild-type mice. The protective effects of cardiomyocyte NOS3 on myocardial function and survival were further confirmed in a murine model of polymicrobial sepsis. These results suggest that increased myocardial NO levels attenuate endotoxin-induced reactive oxygen species production and increase total sarcoplasmic reticulum Ca2+ load and myofilament sensitivity to Ca2+, thereby reducing myocardial dysfunction and mortality in murine models of septic shock.
Circulation | 2011
Joseph Cheriyan; Andrew J. Webb; Lea Sarov-Blat; Maysoon Elkhawad; Sharon Wallace; Kaisa M. Mäki-Petäjä; David Collier; John G. Morgan; Zixing Fang; Robert N. Willette; John J. Lepore; John R. Cockcroft; Dennis L. Sprecher; Ian B. Wilkinson
Background— Oxidized low-density lipoprotein reduces endothelial nitric oxide production (an important mediator of vasoregulation) and activates p38 mitogen-activated protein kinase (MAPK), a mediator of vascular inflammation. Animal models of vascular stress have previously predicted improvements in vascular function after p38 MAPK inhibition. We hypothesized that a selective p38&agr;/&bgr; MAPK inhibitor (losmapimod; GW856553) would improve compromised nitric oxide–mediated vasoregulation in patients with hypercholesterolemia. Methods and Results— Untreated hypercholesterolemic patients (low-density lipoprotein cholesterol >4.1 mmol/L) were randomized to receive losmapimod 7.5 mg (n=27) or placebo (n=29) twice daily for 28 days. Patients with known vascular disorders (eg, diabetes mellitus, coronary heart disease) were excluded. Forearm blood flow was measured by venous occlusion plethysmography in response to serial intra-arterial infusion of acetylcholine, sodium nitroprusside, and NG-monomethyl-l-arginine (L-NMMA). Acetylcholine and L-NMMA responses were significantly impaired (P=0.01 and P=0.03) compared with responses in control subjects (n=12). In hypercholesterolemic patients treated with losmapimod, responses to acetylcholine were improved by 25% (95% confidence interval, 5 to 48; P=0.01), to sodium nitroprusside by 20% (95% confidence interval, 3 to 40; P=0.02), and to L-NMMA by 10% (95% confidence interval, −1 to 23; P=0.07) compared with placebo. C-reactive protein was reduced by 57% (95% confidence interval, −81 to −6%; P<0.05) in patients treated with losmapimod compared with placebo. Conclusions— Losmapimod improves nitric oxide–mediated vasodilatation in hypercholesterolemic patients, which is consistent with findings in previous translational animal models. These data support the hypothesis that attenuating the inflammatory milieu by inhibiting p38 MAPK activity improves NO activity. This suggests p38 MAPK as a novel target for patients with cardiovascular disease. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00474864.
Heart Rhythm | 2012
S. Kumar; F. Sutherland; Joseph B. Morton; Geoffrey Lee; John G. Morgan; James Wong; David E. Eccleston; John Voukelatos; Manohar L. Garg; Paul B. Sparks
BACKGROUND Persistent atrial fibrillation (AF) is associated with a high risk of recurrence after electrical cardioversion. OBJECTIVE We examined if long-term supplementation with omega-3 polyunsaturated fatty acids in fish oils commenced >1 month prior to electrical cardioversion and continued thereafter reduces recurrence of persistent AF. METHODS This was an open-label, randomized study of 178 patients with persistent AF >1-month duration. Participants were assigned to control group (n = 87) or omega-3 group (6 g/d fish oil; n = 91) and underwent cardioversion 1 month later. Concurrent antiarrhythmic use of sotalol or amiodarone was permitted. Fish oil was continued till return of persistent AF or a maximum of 1 year. Intention-to-treat analysis was performed for the primary end point defined as the recurrence of persistent AF. RESULTS Mean duration of fish oil intake was 56 days precardioversion and a total of 242 days in follow-up. Eicosapentaenoic acid and docosahexaenoic acid, the active components of fish oils, were 1.8-fold and 2.1-fold higher, respectively, in the omega-3 group compared with controls at the time of cardioversion (P <.001). At 90 days, 38.5% of the patients receiving omega-3 fatty acid supplement had AF recurrence compared with 77.5% of the controls (hazard ratio [omega-3 vs control] 0.38; 95% confidence interval 0.27-0.56; P <.001). Omega-3 intake was associated with a significant reduction in AF recurrence with or without concurrent antiarrhythmic drugs. CONCLUSIONS Omega-3 polyunsaturated fatty acid supplementation commenced >1 month prior to electrical cardioversion and continued thereafter reduces the recurrence of persistent AF. Randomized controlled trials on long-term fish oil supplementation are needed to confirm these findings.
Circulation | 2002
Prashanthan Sanders; Joseph B. Morton; John G. Morgan; Neil C. Davidson; Steven J. Spence; Jitendra K. Vohra; Jonathan M. Kalman; Paul B. Sparks
Background—Atrial mechanical stunning develops on termination of chronic atrial arrhythmias and is implicated in the genesis of thromboembolic complications after cardioversion. The mechanisms responsible for atrial mechanical stunning are unknown. The effects of atrial rate, isoproterenol, and calcium on atrial mechanical function in patients with atrial stunning have not been evaluated, and it is not known if atrial stunning can be reversed. Methods and Results—Thirty-five patients with chronic atrial flutter (AFL) undergoing radiofrequency ablation were studied. Fifteen patients in sinus rhythm undergoing ablation for paroxysmal AFL were studied as control for effects of the procedure. Left atrial appendage emptying velocities (LAAEVs) and spontaneous echocardiographic contrast (LASEC) were assessed by transesophageal echocardiography during AFL, after reversion to sinus rhythm, during atrial pacing at cycle lengths of 750 to 250 ms, after a postpacing pause, and with isoproterenol or calcium. With termination of AFL, LAAEV decreased from 59.0±3.7 cm/s to 18.8±1.4 cm/s (P <0.0001) and LASEC grade increased from 0.9±0.1 to 2.2±0.2 (P <0.0001). Pacing increased LAAEV to a maximum of 38.4±3.2 cm/s (P <0.0001) and reduced LASEC grade to 1.9±0.2 (P =0.005). Isoproterenol and calcium reversed atrial mechanical stunning with LAAEV increasing to 89.3±12.6 cm/s (P =0.0007) and 50.2±10.5 cm/s (P =0.005), respectively, and LASEC grade decreasing to 0.2±0.1 (P =0.001) and 1.4±0.2 (P =0.01), respectively. The postpacing pause increased LAAEV to 69.3±3.7 cm/s (P <0.0001). No change in LAAEV was observed in the paroxysmal AFL group. Conclusion—Atrial mechanical stunning can be reversed by pacing at increased rates and through the administration of isoproterenol or calcium. These findings suggest a functional contractile apparatus in the mechanically remodeled atrium as a result of chronic atrial flutter.
Circulation-cardiovascular Imaging | 2008
Geneviève Derumeaux; Fumito Ichinose; Michael J. Raher; John G. Morgan; Tereza Coman; Candace Lee; Jose Maria Cuesta; Hélène Thibault; Kenneth D. Bloch; Michael H. Picard; Marielle Scherrer-Crosbie
Background—Aging is accompanied by an alteration in myocardial contractility. However, its noninvasive detection is difficult. The effect of chronic exercise on this decrease is unknown. Murine models of senescence are increasingly used to test therapies in aging. We tested whether strain rate imaging detected left ventricular (LV) systolic dysfunction in aging mice and was able to assess a potential improvement after exercise. Methods and Results—Young (3 weeks), adult (2 to 3 months), and old (6 to 18 months) C57BL6 male mice underwent echocardiograms with strain rate imaging, either in sedentary conditions or before, 2 weeks and 4 weeks after chronic swimming. Hemodynamic parameters of LV function including maximal and end-systolic elastance were obtained before euthanizing. LV fibrosis was measured using Sirius red staining. Conventional echocardiography was unable to detect LV systolic dysfunction in old mice, whereas both systolic strain rate and load-independent hemodynamic parameters such as preload recruitable stroke work and end-systolic elastance were significantly decreased. Both strain rate and load-independent hemodynamic parameters normalized after 4 weeks of exercise. Both endocardial and epicardial fibrosis were increased in the LV of aging mice. Endocardial fibrosis decreased in exercised aged mice. Conclusions—Strain rate noninvasively detects LV systolic dysfunction associated with aging in mice, whereas conventional echocardiography does not. Chronic exercise normalizes LV systolic function and decreases fibrosis in old mice. Strain rate imaging in mice may be a useful tool to monitor the effect of new therapeutic strategies preventing the myocardial dysfunction associated with aging.
Heart Rhythm | 2011
S. Kumar; F. Sutherland; Miriam Wheeler; Patrick M. Heck; Geoffrey Lee; A. Teh; Manohar L. Garg; John G. Morgan; Paul B. Sparks
BACKGROUND Atrial mechanical stunning is a form of tachycardia-mediated atrial cardiomyopathy that manifests after reversion of persistent atrial arrhythmias to sinus rhythm. OBJECTIVES This study sought to examine whether chronic omega-3 polyunsaturated fatty acid supplementation with fish oils can reverse atrial mechanical stunning. METHODS Patients undergoing reversion of persistent atrial fibrillation (AF) or atrial flutter (AFL) to sinus rhythm were randomized to a control group (n = 26) or an omega-3 group (n = 23). The latter were prescribed 6 g/day of fish oil for ≥1 month prior to the procedure. Parameters of left atrial appendage function were compared immediately before and immediately after reversion. RESULTS After fish oil intake for a mean of 70 days, the following were noted favoring the omega-3 group among both AF and AFL patients: (1) 2-fold higher serum omega-3 levels (P < .001), (2) less mean decrease in emptying velocity (e.g., AF: 8% vs. 32%, P = .02), (3) less mean decrease in appendage emptying fraction (e.g., AFL: 7% vs. 60%, P = .002), (4) lower incidence of new or increased spontaneous echocardiographic contrast (e.g., AF: 11% vs. 62.5%, P = .003), and (5) lower incidence of atrial mechanical stunning (e.g., AFL: 20% vs. 100%, P = .001). Omega-3 intake conferred protection against stunning in a multivariable analysis (odds ratio 0.18, P = .02). CONCLUSION Chronic fish oil ingestion in humans attenuates atrial mechanical stunning after reversion of atrial arrhythmias to sinus rhythm. This suggests that fish oils may target or even reverse underlying cellular and/or structural remodeling that occurs in response to persistent atrial arrhythmias.
European Heart Journal | 2015
Etienne Aliot; Axel Brandes; Lars Eckardt; A. Elvan; Michele Gulizia; Hein Heidbuchel; Josef Kautzner; Lluis Mont; John G. Morgan; André Ng; Lukasz Szumowski; Sakis Themistoclakis; Isabelle C. Van Gelder; Stephan Willems; Paulus Kirchhof
Atrial fibrillation is not only a common condition and increasingly so in ageing populations, it is also a common cause of stroke, cardiovascular death, and cardiovascular hospitalizations. Even on optimal anticoagulation and rate control therapy, AF patients are at an unacceptable risk for cardiovascular death, in particular sudden death and death from heart failure. Furthermore, many patients with AF are hospitalized because of AF, illustrating the unmet needs in the current evidence-based management of AF.
Journal of Cardiovascular Electrophysiology | 2015
S. Kumar; Gregor J. Brown; F. Sutherland; John G. Morgan; David T. Andrews; Liang-Han Ling; A. McLellan; Geoffrey Lee; Timothy Robinson; Patrick M. Heck; Karen Halloran; Joseph B. Morton; Peter M. Kistler; Jonathan M. Kalman; Paul B. Sparks
The transesophageal echo probe (TEE) is commonly used before and during atrial fibrillation (AF) ablation under general anesthesia (GA). We sought to determine the potential contribution of the TEE probe to esophageal injury after pulmonary vein isolation (PVI) alone for paroxysmal AF.