Functional consequences of acute collagen degradation studied in crystalloid perfused rat hearts

Objectives: 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, isovlumically 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.