Are Aging and Heart Failure Similar Syndromes of Sympathetic

Dysregulation?

Anthony Garcia

Pathophysiology of Heart FailurePathophysiology of Heart Failure

Heart failure (HF) is a syndrome that can be Heart failure (HF) is a syndrome that can be characterized by left ventricular dysfunction characterized by left ventricular dysfunction which leads to an ineffective pump and which leads to an ineffective pump and inadequate oxygen delivery.inadequate oxygen delivery.

4.8 million Americans have HF and 400,000 4.8 million Americans have HF and 400,000 new cases are diagnosed annually.new cases are diagnosed annually.

HF patients are less able to adapt to HF patients are less able to adapt to temperature changes, physical exercise and temperature changes, physical exercise and to perform normal daily activities.to perform normal daily activities.

(NHANES: 1999-2004). Source: NCHS and NHLBI.

Prevalence of Heart Failure Prevalence of Heart Failure By Age and GenderBy Age and Gender

The Aging Population:The Aging Population:Persons 65 Years or Older (Actual and Estimated)Persons 65 Years or Older (Actual and Estimated)

Kansas U.S.

0

10

20

30

Popu

latio

n 65

+ yr

s. (%

)

2000 2050

2000 2050 2000 2050

Kansas U.S.

US Census Bureau, Population Division, Interim State Population Projections. 2005.

HF EpidemicHF Epidemic

The combined impact of an aging The combined impact of an aging population and the age-related distribution population and the age-related distribution of HF have increased the incidence of this of HF have increased the incidence of this condition to epidemic proportions.condition to epidemic proportions.

Sympathetic Nervous SystemSympathetic Nervous System

The sympathetic nervous system (SNS) The sympathetic nervous system (SNS) plays a crucial role in regulating plays a crucial role in regulating homeostasis under basal conditions and homeostasis under basal conditions and in response to acute and chronic in response to acute and chronic stressors.stressors.

Sympathetic nerves are spontaneously Sympathetic nerves are spontaneously active and sympathetic nerve discharge active and sympathetic nerve discharge (SND) can be recorded using (SND) can be recorded using electrophysiological techniques. electrophysiological techniques.

Sympathetic Nervous SystemSympathetic Nervous System

Forebrain, brainstem, and spinal neural Forebrain, brainstem, and spinal neural circuits are critically involved in SNS circuits are critically involved in SNS regulation and direct recordings of activity regulation and direct recordings of activity in sympathetic nerves provide a measure in sympathetic nerves provide a measure of the output of central sympathetic of the output of central sympathetic circuits.circuits.

Representative SNS RecordingsRepresentative SNS Recordings

Lumbar SND

Adrenal SND

Renal SND

Splenic SND

PulsatilePressure

Renal SND

Adrenal SND

Splenic SND

PulsatilePressure

4 NerveSimultaneous

Recording

3 NerveSimultaneous

Recording

4 s

Sympathetic Nervous System Sympathetic Nervous System Control PathwaysControl Pathways

SNS Regulation in HF and AgingSNS Regulation in HF and Aging

Sympathetic dysregulation is considered a Sympathetic dysregulation is considered a hallmark of both HF and aging.hallmark of both HF and aging.

However, the regional pattern of basal However, the regional pattern of basal sympathetic activation differs in individuals sympathetic activation differs in individuals with healthy aging and individuals with HF.with healthy aging and individuals with HF.

These data suggest a diversity in These data suggest a diversity in mechanisms mediating SNS regulation in mechanisms mediating SNS regulation in aging and HF syndromes.aging and HF syndromes.

However, not a single study has determined However, not a single study has determined SNS responses to acute stress in young and SNS responses to acute stress in young and aged rats with HF.aged rats with HF.

Published Research Studies Measuring Published Research Studies Measuring SNS Activity in Young and Aged HF RatsSNS Activity in Young and Aged HF Rats

30

0

10

20

40

50

Published Research Studies Measuring Published Research Studies Measuring SNS Activity in Young and Aged HF RatsSNS Activity in Young and Aged HF Rats

In the absence of specific studies on aged HF In the absence of specific studies on aged HF rats, the majority of information aimed at rats, the majority of information aimed at determining mechanisms mediating sympathetic determining mechanisms mediating sympathetic dysregulation with HF has been extrapolated dysregulation with HF has been extrapolated from studies using young HF rats, a glaring from studies using young HF rats, a glaring omission based on the combined impact of the omission based on the combined impact of the aging population and the age-related distribution aging population and the age-related distribution of HF.of HF.

HypothesisHypothesis

Aging and HF are not similar syndromes Aging and HF are not similar syndromes of SNS dysregulation as evidenced by of SNS dysregulation as evidenced by differences in SND responses to acute differences in SND responses to acute heating in young-HF compared with aged-heating in young-HF compared with aged-HF rats, and in aged-HF compared with HF rats, and in aged-HF compared with aged sham-HF rats. aged sham-HF rats.

Experimental TechniquesExperimental Techniques

Anesthetized Fischer 344 ratsAnesthetized Fischer 344 rats HF-induced by myocardial infarctionHF-induced by myocardial infarction HF documented using transthoracic HF documented using transthoracic

echocardiography and histological echocardiography and histological techniquestechniques

Sympathetic nerve activity recorded using Sympathetic nerve activity recorded using electrophysiological techniqueselectrophysiological techniques

Environmental stressor: acute heat stressEnvironmental stressor: acute heat stress

Left Ventricle of a HF RatLeft Ventricle of a HF Rat

Preliminary ResultsPreliminary Results

Tc (ºC) Tc (ºC)

Summary and ConclusionSummary and Conclusion

Aged HF rats can be used in Aged HF rats can be used in neurophysiological experimental studies.neurophysiological experimental studies.

Echocardiographic techniques can be Echocardiographic techniques can be used to diagnose HF in aged rats. used to diagnose HF in aged rats.

Aged HF rats show similar SND Aged HF rats show similar SND responses to acute heating as young HF responses to acute heating as young HF rats.rats.

AcknowledgementsAcknowledgements

Developing Scholars ProgramDeveloping Scholars Program McNair Scholars ProgramMcNair Scholars Program Colleagues: Dr. Tim Musch, Dr. Mike Colleagues: Dr. Tim Musch, Dr. Mike

Kenney, Dr. Marco Margiocco, Kim Kenney, Dr. Marco Margiocco, Kim Hosking, Sue Hagemann, Rick FelsHosking, Sue Hagemann, Rick Fels

Funding: NIH-HLBIFunding: NIH-HLBI