Medical Pharmacology Chapter 46:  Congestive Heart Failure

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Receptor polymorphism


Comparative pathophysiology: diastolic vs. systolic heart failure



  • Diastolic heart failure may develop slowly and occur as a result those long-term consequences of compensatory physiological responses.  

    • Factors that may induce diastolic functional pathologies include increased heart rate, left ventricular hypertrophy, and myocardial ischemia.  Some of these factors may be associated with progressive myocardial "remodeling"

      • Recall that the key to rapid myocardial relaxation is the ability to re-sequester free Ca2+

        • Furthermore, this process requires ionic translocation against a significant concentration gradient (10,000: 1) and as such is coupled to ATP hydrolysis.The ratio is 1 ATP hydrolyzed for every two Ca2+  translocated by the calcium-ATPase pump.

      • Therefore, factors the decrease ATP availability will impair this translocation process. 

        •  Myocardial hypertrophy and ischemia reduce ATP availability and can be therefore readily identified as contributing  pathologic factors that impair myocardial relaxation.  Additionally, hypertrophic ventricular muscle tissue exhibits reduced compliance (increased stiffness)

  •  1Factors that impair ventricular contraction include:

    •  Hypertrophy, ischemia, hypertension, collagen deposition and fibrosis, regional asynchrony, increase preloaded and afterload, intrinsic abnormalities in calcium movement, and tachycardia

  • Factors that reduce ventricular compliance (increased stiffness) include:

    • Hypertrophy, hypertension, collagen deposition and fibrosis, pericardial constriction or restriction.

  • Aging is associated with increased likelihood of left ventricular hypertrophy and/or ischemia.  

    • Aging is also associated with increased collagen deposition which reduces ventricular compliance.  However other important causes those diastolic failure include coronary vascular disease, hypertension, diabetes, obesity, and aortic stenosis.

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