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Sexually mature Yucatan micropigs are ovariectomized and fed a 4% cholesterol diet free of plant phytoestrogens with 40% of the calories from fat for 6 months.
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DeploymentPre-stent
CFX
ImmediatePost-stent
CFX
• COURTESY OF MICHAEL STUREK
• University of Indiana
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Coronary Artery Restenosis
• Stent implantation
• 2-6 weeks for lesion
• Occlusion may lead to infarction and aneurysm
Spontaneous Diseases
• CardiomyopathiesGenetic hypertrophic
• EndocarditisBeta Hemolytic Streptococcal
AORTA
AV VALVE ATRIUM
GENETIC MODELS
Left Hypoplastic Heart Syndrome (LHHS)
Ventricular Septal Defect (VSD)
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VSD - FTT Syndrome
Reduced stroke volume is due to failure ofend-diastolic volume to increase adequatelyinstead of reduced contractility, increasedafterload or reduced preload.
Corin WJ, Swindle MM, et al: J Clin Invest, 1988
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INDICATIONS FORFETAL INTERVENTION
Correct congenital defect
Fetal drug delivery
Antenatal therapy may prevent postnatal complications
FETAL HYDROPS
• Life threatening condition associated with increase in fluid, heart failure and fetal arrhythmias.
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Fetal / Maternal Blood Levels (Moricizine)
Swine Sheep
Maternal Level (mg/ml) 0.61 0.95
Fetal Level (mg/ml) 1.04 0.68
Fet / Mat Ratio 1.71 0.71
FETAL MODEL SUMMARY
• Antenatal therapy is indicated in life threatening conditions
• Fetal intervention may be performed in pigs and is valuable in the study of pharmacologic agents
• It is possible to treat human fetuses with antiarrhythmics administered to the mother
FUTURE DIRECTION IN RESEARCH
Tissue engineering with medicated gel delivered by catheter device
Intrauterine delivery of therapeutic agent to close the VSD
Gene therapy
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Induced Models
Neonatal Shunts - PDA, ASD, VSDAortopulmonary shuntsCoarctation of the aortaAneurysm modelsPressure & volume overload modelsGrowing heart modelMyocardial infarct/coronary arteryValvular replacement
Ventricular HypertrophyConcentric
Left Ventricular wall thickness
Systemic blood pressure
Pressure overload models induced by surgical banding
Eccentric
Left ventricular end diastolic diameter
Cardiac output
Volume overload models induced by arteriovenous fistulas or valvular regurgitation
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DILATEDCARDIOMYOPATHY
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Creation of the AAA in the Animal Model
AAA CreationPig # 3
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Pig Vs. Human ElectrophysiologyPaced and IntrinsicPulse Duration 0.5 msec
emptying time different, first pass metabolism• Renal—comparable anatomy and physiology• Dermal—transdermal absorption, wound healing• Hepatic—P4502D & 2C19 low, sulfation usually
absent, biotransformation both similar and different• Genetic—Pig genome project, ventricular septal