What is the clinical evidence from this study?

Study design: Other. Population: Left ventricular diastolic stiffness (n=10). Intervention: beta-aminopropionitrile (BAPN) vs. untreated controls. Primary outcome: Chamber stiffness (p=< 0.05).

September 1, 1995

Inhibition of collagen cross-linking: effects on fibrillar collagen and ventricular diastolic function

Q: What are the key findings of this study?

Inhibition of collagen cross-linking with BAPN significantly decreased chamber stiffness (0.06 vs 0.13, P<0.05) and myocardial stiffness (6.6 vs 10.4, P<0.05) in normal adult pigs.

Key Result

Inhibition of collagen cross-linking with BAPN significantly decreased chamber stiffness (0.06 vs 0.13, P<0.05) and myocardial stiffness (6.6 vs 10.4, P<0.05) in normal adult pigs.

Structured PICO

Does inhibition of collagen cross-linking with BAPN reduce ventricular diastolic stiffness in normal adult pigs?

Population

10 normal adult pigs treated with BAPN or serving as untreated controls for 6 weeks to assess ventricular diastolic function.

Intervention

beta-aminopropionitrile (BAPN) 10 g/day orally for 6 weeks

Comparator

Untreated controls

Outcome

Left ventricular chamber stiffness and myocardial stiffnesssurrogate

Inhibition of collagen cross-linking with BAPN reduces left ventricular diastolic stiffness in normal pigs, supporting the role of the fibrillar collagen network in determining diastolic stiffness.

Main Result

Absolute Event Rate: 0.06% vs 0.13%

p-value: p=< 0.05

Abstract

The fibrillar collagen network is postulated to be a primary determinant of left ventricular diastolic stiffness. This hypothesis was tested by examining the structural and physiological effects of a reduction in fibrillar collagen content and cross-linking in the intact left ventricle. Collagen cross-linking was inhibited by treating five normal adult pigs with beta-aminopropionitrile (BAPN; 10 g/day po) for 6 wk; five normal untreated pigs served as controls. Left ventricular volume, mass, and function were determined by simultaneous echocardiography and catheterization. Chamber stiffness, defined by pressure vs. volume data, and myocardial stiffness, defined by stress vs. dimension data, were determined from variably loaded beats during dextran infusion. Collagen distribution (% area) and integrity (% confluence) were determined by light microscopy. Collagen content was measured by hydroxyproline assay, and collagen cross-linking was measured by salt extraction. BAPN decreased collagen distribution (% area decreased from 12 +/- 1% in control to 7 +/- 1% in BAPN, P < 0.05), collagen integrity (% confluence decreased from 8 +/- 1% in control to 4 +/- 1% in BAPN, P < 0.05), collagen content (from 36 +/- 2 mg/g dry wt in control to 27 +/- 2 mg/g dry wt in BAPN, P < 0.05), and collagen cross-linking (extractable collagen increased from 21 +/- 2% in control to 28 +/- 2% in BAPN, P < 0.05). BAPN decreased chamber stiffness (0.13 +/- 0.02 in control to 0.06 +/- 0.01 in BAPN, P < 0.05) and myocardial stiffness (10.4 +/- 0.5 in control to 6.6 +/- 0.5 in BAPN, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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