Functional consequences of acute collagen degradation studied in crystalloid perfused rat hearts.
OBJECTIVE
The impact of acute collagen disruption by the disulfide donor, 5,5'-dithio-2-nitrobenzoic acid (DTNB) on ventricular properties was tested in rat hearts.


METHODS
Collagen was degraded acutely in 13 isolated, isovolumically contracting rat hearts by perfusion with 1 mM DTNB added to Krebs-Henseleit solution for 1 hour followed by 2-hour perfusion with normal solution. Another 13 hearts were perfused with normal solution for 3 hours (Control).


RESULTS
Collagen content was 3.5 +/- 0.5% of ventricular dry weight in control group compared with 2.1 +/- 0.4% in DTNB group (decrease by 40%, p < 0.01). Scanning electron micrographs revealed loss of the delicate collagen network surrounding muscle fibers in DTNB treated hearts. Developed pressure at a fixed volume decreased to 86 +/- 17% of the baseline value after 3-hour perfusion in the control group, whereas in DTNB treated hearts developed pressure fell to 68 +/- 13% (p < 0.01). End-diastolic pressure was set at 5 mmHg at the beginning of the experiment and rose to 15 +/- 8 mmHg in control and 30 +/- 13 mmHg (p < 0.01) in the treated hearts. Concomitantly, wet-to-dry weight ratio increased from 5.63 +/- 0.26 in control to 6.07 +/- 0.11 (p < 0.05) in the DTNB treated hearts. A separate set of experiments on isolated myocytes excluded the possibility of a direct effect of DTNB on myocyte contractile function.


CONCLUSIONS
These data suggested that with 40% collagen disruption by DTNB there is a significant increase in tissue edema that results in a decrease in chamber capacitance; in addition, there is a significant decrease in systolic performance which reflects the combined effect of edema and loss of collagen.
Todaka
K
K
Department of Pharmacology, College of Physicians & Surgeons of Columbia University, New York, New York 10032, USA.
Jiang
T
T
Chapman
J T
JT
Gu
A
A
Zhu
S M
SM
Herzog
E
E
Hochman
J S
JS
Steinberg
S F
SF
Burkhoff
D
D
D000818:Animals; D001834:Body Water / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D000077324:Crystalloid Solutions; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D005109:Extracellular Matrix / Q000187:drug effects; D005260:Female; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007552:Isotonic Solutions; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010477:Perfusion; D010952:Plasma Substitutes; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000077324:Crystalloid Solutions; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D003094:Collagen; D004228:Dithionitrobenzoic Acid