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Biomedical subjects

William J Groh

Publications and source records attributed to William J Groh.

At least 19 recordsLinked to original sources

Characteristics of volunteers responding to emergencies in the Public Access Defibrillation Trial.

OBJECTIVES: To evaluate the characteristics of volunteers responding to emergencies in the North American Public Access Defibrillation (PAD) Trial. METHODS: The PAD Trial was a prospective evaluation of cardiac arrest survival in community facilities randomized to cardiopulmonary resuscitation (CPR) or to CPR with automated external defibrillators (AEDs). The PAD volunteers' characteristics were analyzed using Poisson regression clustered on the facility and offset by the number of emergency episodes to which volunteers were exposed. RESULTS: A total of 19,320 volunteers in 1260 facilities were trained to provide emergency care. Of these, 8169 volunteers were participating actively at their facility during a time when one or more emergency episodes occurred. There were 1971 emergency episodes responded to by 1245 volunteers. The treatment arm (CPR-only versus CPR+AED) was not associated with the likelihood of volunteer participation in an episode. Likewise, the volunteers' age or sex did not affect response. Volunteers more likely to respond were supervisory/management or security personnel, non-minority participants, volunteers with previous CPR training, volunteers with previous experience in emergency care and those who passed the PAD CPR skills follow-up test. Volunteers who had a formal education beyond a high school level were less likely to respond. CONCLUSIONS: Volunteers with previous emergency training and positions of responsibility in their facility had a greater likelihood of participation in medical emergencies in the PAD Trial.

Adult↗

Evaluation of [11C]hemicholinium-15 and [18F]hemicholinium-15 as new potential PET tracers for the high-affinity choline uptake system in the heart.

[(11)C]Hemicholinium-15 ([(11)C]HC-15) and [(18)F]hemicholinium-15 ([(18)F]HC-15) have been synthesized as new potential PET tracers for the heart high-affinity choline uptake (HACU) system. [(11)C]HC-15 was prepared by N-[(11)C]methylation of the appropriate precursor, 4-methyl-2-phenyl-morpholin-2-ol, using [(11)C]CH(3)OTf in 55-70% radiochemical yield decay corrected to end of bombardment (EOB) and 2-3Ci/mumol specific activity at end of synthesis (EOS). [(18)F]HC-15 was prepared by N-[(18)F]fluoromethylation of the precursor using [(18)F]FCH(2)OTf in 20-30% radiochemical yield decay corrected to EOB and >1.0Ci/mumol specific activity at EOS. The biodistribution of both compounds was determined in rats at 20min post-intravenous injection, and the results show the heart region uptakes 1.32+/-0.75%ID/g in R-ventricle for [(11)C]HC-15 and 1.28+/-0.81%ID/g in L-ventricle for [(18)F]HC-15, respectively. The dynamic PET imaging studies of [(11)C]HC-15 in rats were acquired 60min post-intravenous injection of the tracer using the IndyPET-II scanner. For the blocking experiments, the rats were intravenously pretreated with 3.0mg/kg of unlabeled HC-15 prior to [(11)C]HC-15 injection. [(11)C]HC-15 rat heart PET studies show rapid heart uptake to give clear heart images. The rat heart PET blocking studies found no significant blocking effect. The dynamic PET studies in normal and ablated dogs were performed using Siemens PET scanner with [(13)N]NH(3), [(11)C]HC-15, and [(18)F]HC-15. PET studies in dogs of both [(11)C]HC-15 and [(18)F]HC-15 also show significant heart uptake and give images of the heart. However, there is no significant change in [(11)C]HC-15 L-ventricle uptake following radiofrequency ablation in the dog. These results suggest that the localization of HC-15 tracers in the heart is mediated by non-specific processes, and the visualization of HC-15 tracers on the heart is related to non-specific binding of HACU.

Animals↗

ST-segment elevation myocardial infarction: recommendations on triage of patients to heart attack centers: is it time for a national policy for the treatment of ST-segment elevation myocardial infarction?

Despite substantial progress in the diagnosis and treatment of acute ST-segment elevation myocardial infarction (STEMI), implementation of this knowledge into routine clinical practice has been variable. It has become increasing clear that primary percutaneous coronary intervention (PCI) is the preferred method of reperfusion if it can be performed in a timely manner. Recent European data suggest that transfer for direct PCI may also be preferable to fibrinolytic therapy. We believe it is time to establish a national policy for treatment of patients with STEMI to develop a coordinated system of care similar to that of the level 1 trauma system.

Electrocardiography↗

Adverse events associated with lay emergency response programs: the public access defibrillation trial experience.

UNLABELLED: The adverse event (AE) profile of lay volunteer CPR and public access defibrillation (PAD) programs is unknown. We undertook to investigate the frequency, severity, and type of AE's occurring in widespread PAD implementation. DESIGN: A randomized-controlled clinical trial. SETTING: One thousand two hundred and sixty public and residential facilities in the US and Canada. PARTICIPANTS: On-site, volunteer, lay personnel trained in CPR only compared to CPR plus automated external defibrillators (AEDs). INTERVENTION: Persons experiencing possible cardiac arrest receiving lay volunteer first response with CPR+AED compared with CPR alone. MAIN OUTCOME MEASURE: An AE is defined as an event of significance that caused, or had the potential to cause, harm to a patient or volunteer, or a criminal act. AE data were collected prospectively. RESULTS: Twenty thousand three hundred and ninety six lay volunteers were trained in either CPR or CPR+AED. One thousand seven hundred and sixteen AEDs were placed in units randomized to the AED arm. There were 26,389 exposure months. Only 36 AE's were reported. There were two patient-related AEs: both patients experienced rib fractures. There were seven volunteer-related AE's: one had a muscle pull, four experienced significant emotional distress and two reported pressure by their employee to participate. There were 27 AED-related AEs: 17 episodes of theft involving 20 devices, three involved AEDs that were placed in locations inaccessible to the volunteer, four AEDs had mechanical problems not affecting patient safety, and three devices were improperly maintained by the facility. There were no inappropriate shocks and no failures to shock when indicated (95% upper bound for probability of inappropriate shock or failure to shock = 0.0012). CONCLUSIONS: AED use following widespread training of lay-persons in CPR and AED is generally safe for the volunteer and the patient. Lay volunteers may report significant, usually transient, emotional stress following response to a potential cardiac arrest. Within the context of this prospective, randomized multi-center study, AEDs have an exceptionally high safety profile when used by trained lay responders.

Canada↗

Facile synthesis and PET imaging of a novel potential heart acetylcholinesterase tracer N-[11C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2',2'-diphenylpropionoxymethyl)pyridinium.

A new AChE tracer N-[(11)C]methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2',2'-diphenylpropionoxymethyl)pyridinium ([(11)C]MDDP, [(11)C]1) has been synthesized in 40-65% radiochemical yield. Initial PET dynamic studies of [(11)C]MDDP in rat heart showed rapid heart uptake and blood pool clearance to give high-quality heart images. Blocking studies of [(11)C]MDDP with pretreatment drug neostigmine in rats found only minor reductions in rat heart [(11)C]MDDP retention. The results suggest that [(11)C]MDDP delineates the heart very clearly, and the uptakes of [(11)C]MDDP in rat heart might be related to non-specific binding.

Acetylcholinesterase↗

Thoracic spinal cord stimulation reduces the risk of ischemic ventricular arrhythmias in a postinfarction heart failure canine model.

BACKGROUND: Thoracic spinal cord stimulation (SCS) is a promising therapy in treating refractory angina. This study was designed to investigate SCS with regard to the risk of arrhythmias during myocardial ischemia and its cardiac electrophysiological effects. METHODS AND RESULTS: We studied 22 dogs with healed anterior myocardial infarction (MI) and superimposed heart failure (HF) induced by rapid ventricular pacing. SCS was applied at the dorsal T1-T2 segments of the spinal cord (at 50 Hz, 0.2 ms) for 15 minutes. Transient (2-minute) myocardial ischemia was induced on 2 separate occasions (no SCS and SCS) to provoke ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation; VT/VF). Ischemic episodes were separated by 90 minutes, and dogs were randomly assigned to receive SCS or no SCS before the first or second ischemic episode. SCS reduced the occurrence of VT/VF from 59% to 23% when SCS was applied during transient myocardial ischemia (odds ratio, 0.36; 95% confidence interval, 0.1626 to 0.5646; P=0.0009). SCS also decreased sinus rate by 7.5+/-14 bpm (P=0.048), increased the PR interval by 11.1+/-14.7 ms (P=0.009), and reduced systolic blood pressure by 9.8+/-13.6 mm Hg (P=0.02). CONCLUSIONS: Thoracic SCS appears to protect against ischemic VT/VF in a canine model of healed MI and HF. SCS reduced sinus rate and systolic blood pressure, changes consistent with the previously known antisympathetic effect of SCS, which may have contributed to the antiarrhythmic benefits.

Animals↗

Familial clustering of muscular and cardiac involvement in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is associated with both skeletal and cardiac muscle involvement. The aim of the present study was to determine whether familial clustering is observed in the severity of muscle involvement in DM1. We evaluated 51 sibling groups constituting 112 patients with genetically-verified DM1. The siblings were similar to each other in age, cytosine-thymine-guanine (CTG) repeat length, age at disease onset, muscular impairment rating score, and electrocardiographic markers of cardiac conduction disease. After adjusting for the similarities between siblings in age and CTG repeat length, the siblings remained similar to each other in measures of both skeletal and cardiac muscle involvement. These results suggest that factors other than CTG repeat length play a role in the severity and progression of the degenerative skeletal and cardiac muscle disease in DM1.

Adolescent↗

Factors associated with poor survival in women experiencing cardiac arrest in a rural setting.

OBJECTIVES: The purpose of this study was to determine whether gender differences exist in the characteristics and outcomes for out-of-hospital cardiac arrest (OHCA) occurring in a rural setting. BACKGROUND: In urban settings, women have a lower incidence of OHCA than men but otherwise a comparable survival for ventricular fibrillation (VF) OHCA. Whether OHCA gender differences exist in rural settings is not clear. METHODS: The study consisted of a prospective collection and analysis of nontraumatic, adult OHCA prompting a 911 call in six rural Indiana counties. RESULTS: Over an average period of 2.2 years, 138 women and 250 men experienced OHCA (annual incidence rate: 56.4 per 100,000 men and 29.3 per 100,000 women). Women were older, less likely to experience OHCA in a public setting, more likely to be in an extended care facility, and less likely to have a witnessed arrest than were men. Women were less likely to present with an initial rhythm of VF than men (33.3% vs 53.6%, P < .001). Women in VF had a longer time interval from 911 call to first shock compared with men. Women had poorer survival to hospital discharge for all OHCA (2.2% vs 7.2%, P = .04) and VF OHCA (2.2% vs 13.4%, P = .05) compared with men. After age adjustment, female gender remained associated with a poorer OHCA survival outcome. With adjustment for all significant arrest characteristics, female gender was no longer associated with survival. CONCLUSIONS: In a rural population, women suffering OHCA have a dismal survival rate likely because of multiple unfavorable arrest characteristics.

Age Factors↗

Ischemic ventricular arrhythmias during heart failure: a canine model to replicate clinical events.

BACKGROUND: Development of experimental animal models has played an invaluable role in understanding the mechanisms of ventricular arrhythmias. OBJECTIVES: The purpose of this study was to evaluate a new canine model of myocardial infarction (MI), heart failure, and ischemic ventricular arrhythmias in an attempt to replicate clinical conditions. METHODS: Thirty-six mongrel dogs underwent placement of a permanent ventricular pacemaker and induction of an anterior MI by percutaneous transcatheter embolization of polyvinyl foam particles into the left anterior descending coronary artery (just distal to the first septal branch). After a 2-week recovery period, heart failure was induced by continuous rapid ventricular pacing at 200 to 240 ppm for 3 weeks. Transient (4-minute) myocardial ischemia was induced via balloon occlusion of the proximal left circumflex coronary artery. Echocardiographic and electrophysiologic testing was performed before MI creation and repeated prior to acute ischemia induction. RESULTS: Seven dogs (19%) died within several hours of MI creation. All surviving dogs developed severe left ventricular systolic dysfunction. Significant increases in the intraatrial and intraventricular conduction intervals were observed following MI creation and heart failure induction compared with baseline values, as evidenced by increases in the duration of the P wave and QRS complex. Significant increases in corrected QT interval and ventricular refractoriness were observed. Acute transient ischemia induced sustained ventricular tachycardia or ventricular fibrillation in 21 of 29 dogs (72%). CONCLUSION: This canine model can serve as a useful tool for studying ventricular arrhythmias during the interactions of healed infarction, heart failure, increased sympathetic tone, and myocardial ischemia.

Animals↗

Intrathecal clonidine reduces the incidence of ischemia-provoked ventricular arrhythmias in a canine postinfarction heart failure model.

BACKGROUND: Intrathecal clonidine (ITC) is used clinically to manage neuropathic pain but frequently causes hypotension and bradycardia due to centrally mediated sympatholytic effects. OBJECTIVES: The purpose of this study was to evaluate the cardiac electrophysiologic effects of thoracic ITC and its effects on ischemia-provoked ventricular arrhythmias. METHODS: Twelve mongrel dogs with healed myocardial infarctions and heart failure were evaluated. ITC was delivered locally via catheter to the T2-T4 spinal segments and was dosed to reduce heart rate (HR) by >20% to 25%. Electrophysiologic testing was performed before and after ITC. Transient (4-minute) myocardial ischemia was induced via left circumflex coronary artery occlusion on two separate occasions to provoke ventricular arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]). Ischemic episodes were separated by 1 to 2 days, and dogs were randomly assigned to receive ITC or intrathecal saline flush (control) prior to the first or the second ischemic episode. RESULTS: ITC produced significant decrease in HR (31%) and increases in PR interval (22%), Wenckebach cycle length (122%), and atrial and ventricular effective refractory periods (19% and 9%, respectively) but had no significant effect on systemic blood pressure. The occurrence of VT/VF was reduced from 9 of 12 to 3 of 12 dogs when ITC was administered prior to transient myocardial ischemia (P = .04). ITC also blunted ischemia-induced HR increase by 74%. CONCLUSION: ITC reduced ischemia-induced VT/VF in a canine model of healed myocardial infarction with superimposed heart failure and acute ischemia. Results from electrophysiologic testing were consistent with a clonidine-induced reduction in cardiac sympathetic activity from the spinal cord. These data suggest that ITC administration may be a novel approach to treating ventricular arrhythmias.

Adrenergic alpha-Agonists↗

Implementation of community-based public access defibrillation in the PAD trial.

BACKGROUND: The Public Access Defibrillation (PAD) Trial was a randomized, controlled trial designed to measure survival to hospital discharge following out-of-hospital cardiac arrest (OOH-CA) in community facilities trained and equipped to provide PAD, compared with community facilities trained to provide cardiopulmonary resuscitation (CPR) without any capacity for defibrillation. OBJECTIVES: To report the implementation of community-based lay responder emergency response programs in 1,260 participating facilities recruited for the PAD Trial in the United States and Canada. METHODS: This was a descriptive study of the characteristics of participating facilities, volunteers, and automated external defibrillator (AED) placements compiled by the PAD Trial, and a qualitative study of factors that facilitated or impeded implementation of emergency lay responder programs using focus groups of PAD Trial site coordinators. RESULTS: The PAD Trial enrolled 1,260 community facilities (14.8% residential), with 20,400 lay volunteers (mean +/- standard deviation = 13.4 +/- 10.7 per facility) trained to respond to OOH-CA. The 598 locations randomized to receive AEDs required 2.7 +/- 1.8 AEDs per facility. Volunteer attrition was high, 36% after two years. Barriers to recruitment and implementation included identification of appropriate "at-risk" facilities, lack of interest or fear of litigation by a facility key decision maker, lack of motivated potential volunteer responders, training and retraining resource requirements, and lack of an existing communication/response infrastructure. CONCLUSIONS: These data indicate that implementation of community-based lay responder programs is feasible in many types of facilities, although these programs require substantial resources and commitment, and many barriers to implementation of effective PAD programs exist.

Age Distribution↗

Prevalence of structural cardiac abnormalities in patients with myotonic dystrophy type I.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a neurological disorder with known cardiac involvement, including conduction disturbances, arrhythmias, and ventricular dysfunction. We studied which clinical and electrocardiographic features are associated with structural cardiac abnormalities. METHODS: History, physical examination, electrocardiography, and genetic testing were performed on 382 patients with DM1, and cardiac imaging was performed on 100 of these patients. RESULTS: Clinical congestive heart failure was found in 7 of the 382 patients (1.8%). Structural cardiac abnormalities determined with cardiac imaging included left ventricular hypertrophy (19.8%), left ventricular dilatation (18.6%), left ventricular systolic dysfunction (14.0%), mitral valve prolapse (13.7%), regional wall motion abnormality (11.2%), and left atrial dilatation (6.3%). Left ventricular systolic dysfunction was associated with increasing age (relative risk [RR], 1.9 per decade; 95% CI, 1.1-3.2; P =.02), cytosine-thymine-guanine (CTG) repeat length (RR, 2.8 per 500 repeats; 95% CI, 1.3-6.3; P =.01), P-R >200 ms (RR, 14.7; 95% CI, 3.0-73.1; P =.001), and QRS >120 ms (RR, 5.7; 95% CI, 1.5-21.8; P =.01). P-R >200 ms was predictive of regional wall motion abnormalities. QRS >120 ms correlated with regional wall motion abnormalities and left atrial dilatation. CONCLUSIONS: Several clinical and electrocardiographic findings in patients with DM1 are significantly associated with structural heart abnormalities. These results suggest an underlying genetic and pathophysiologic correlate that may lead to cardiac disease in these patients.

Adolescent↗

Optical mapping of the functional reentrant circuit of ventricular tachycardia in acute myocardial infarction.

OBJECTIVES: We used optical mapping to characterize the reentrant circuit of ventricular tachycardia (VT) during acute myocardial infarction (MI) in isolated canine left ventricular preparations. BACKGROUND: The nature of the reentrant circuit that underlies VT during acute MI is not well understood. METHODS: Using optical mapping in isolated canine left ventricular preparations, we characterized the reentrant circuit of monomorphic VT (mean cycle length 245.3 +/- 15.6 ms, n = 7) induced by programmed stimulation during acute MI. RESULTS: Optical mapping during VT revealed a functional reentrant circuit consisting of four components: (1) a protected isthmus located between the infarction area and the functional line of block; (2) an entrance site located at one end of the isthmus; (3) an exit site located at the other end of the isthmus; and (4) an outer loop consisting of nonischemic normal tissue, connecting the exit and entrance sites. Rate-dependent slow conduction within the border zone was associated with significant changes (n = 6) in action potential amplitude (99.1 +/- 0.4 vs 71.4 +/- 0.6 mV, P < .01), maximal diastolic potential (-80.6 +/- 0.2 vs -65.4 +/- 0.6 mV, P < .05), action potential duration at 90% repolarization (APD(90); 188.4 +/- 1.0 vs 164.3 +/- 3.1 ms, P < .05), and dV/dt (302.4 +/- 7.9 vs 168.5 +/- 3.6 V/s, P < .05). Compared to preparations with no inducible VT (n = 7), formation of a functional line of block was the key mechanism for initiation of functional reentry in preparations with VT. When comparing preparations with sustained and nonsustained VT, preservation of slow conduction over the isthmus was the key component for maintenance of sustained VT. CONCLUSIONS: The reentrant circuit of monomorphic VT in the setting of acute MI involved both the infarction border zone and nonischemic normal tissue. The underlying mechanism is related to the presence of rate-dependent slow conduction and the development of a functional line of block in the border zone.

Acute Disease↗

Cardiac function tests in neuromuscular diseases.

Myocardial involvement is a known complication of neuromuscular diseases and is a leading cause of morbidity and mortality in these disorders. Identifying patients early using cardiac function tests helps understand the mechanisms underlying cardiac involvement and may help limit the progression of cardiac disease before the onset of significant symptoms and limitation. This article outlines the tests available to assess cardiac involvement associated with neuromuscular diseases and offers guidelines for management once they are discovered.

Arrhythmias, Cardiac↗

Facile synthesis and initial PET imaging of novel potential heart acetylcholinesterase imaging agents [11C]pyridostigmine and its analogs.

A series of 11C-labeled analogs of the acetylcholinesterase (AChE) inhibitor pyridostigmine have been synthesized for evaluation as new potential positron emission tomography (PET) imaging agents for heart AChE. The appropriate precursors for radiolabeling were slightly modified from commercial reagents. The new tracers [11C]pyridostigmine (1), [11C]para-pyridostigmine (2) and [11C]ortho-pyridostigmine (3) were prepared by N-[11C]methylation of the precursors using [11C]methyl triflate. Pure target compounds were isolated by a solid-phase extraction (SPE) purification procedure with 60-85% radiochemical yields (decay corrected to end of bombardment), and a synthesis time of 10-15 min. The initial PET dynamic studies of compounds (1-3) in rat heart showed rapid heart uptake and blood pool clearance to give high quality heart images. These results suggest the new tracers delineate the heart very clearly and could be potential heart AChE imaging agents.

Acetylcholinesterase↗

Measuring survival rates from sudden cardiac arrest: the elusive definition.

BACKGROUND: Measuring survival from sudden out-of-hospital cardiac arrest (OOH-CA) is often used as a benchmark of the quality of a community's emergency medical service (EMS) system. The definition of OOH-CA survival rates depends both upon the numerator (surviving cases) and the denominator (all cases). PURPOSE: The purpose of the public access defibrillation (PAD) trial was to measure the impact on survival of adding an automated external defibrillator (AED) to a volunteer response system trained in CPR. This paper reports the definition of OOH-CA developed by the PAD trial investigators, and it evaluates alternative statistical methods used to assess differences in reported "survival." METHODS: Case surveillance was limited to the prospectively determined geographic boundaries of the participating trial units. The numerator in calculating a survival rate should include only those patients who survived an event but who otherwise would have died except for the application of some facet of emergency medical care-in this trial a defibrillatory shock. Among denominators considered were: total population of the study unit, all deaths within the study unit, and documented ventricular fibrillation cardiac arrests. The PAD classification focused upon cases that might have benefited from the early use of an AED, in addition to the likely benefit from early recognition of OOH-CA, early access of EMS, and early cardiopulmonary resuscitation (CPR). Results of this classification system were used to evaluate the impact of the PAD definition on the distribution of cardiac arrest case types between CPR only and CPR + AED units. RESULTS: Potential OOH-CA episodes were classified into one of four groups: definite, probable, uncertain, or not an OOH-CA. About half of cardiac arrests in the PAD units were judged to be definite OOH-CA events and therefore potentially treatable with an AED. However, events that occurred in CPR-only units were less likely to be classified as definite or probable OOH-CA events than those in CPR + AED units (43% versus 55%, odds ratio 0.78, 95% confidence interval 0.57-1.07). The study retained sufficient power to permit a statistical analysis of the alternative hypothesis that the CPR + AED method results in twice as many survivors as a CPR-only approach. The result is critically dependent on the denominator used for calculating survival rates; but the analysis does not require a denominator as the numerators will have identical Poisson distributions (counts for rare events) under the null hypothesis since randomization distributes the risk of cardiac arrest evenly between the two arms. CONCLUSION: Reported OOH-CA rates and survival rates vary widely, depending upon the definitions applied to events. Rigorous assessment of treatments applied to improve survival can be obscured by inappropriate definitions. Large-scale randomized interventions designed to improve survival from OOH-CA can be evaluated based upon the absolute numbers of patients surviving, rather than a change in the proportion surviving.

Cardiopulmonary Resuscitation↗